National Library of Energy BETA

Sample records for disease orthopedic maternity

  1. Bioactive glass coatings for orthopedic metallic implants

    SciTech Connect (OSTI)

    Lopez-Esteban, Sonia; Saiz, Eduardo; Fujino, Sigheru; Oku, Takeo; Suganuma, Katsuaki; Tomsia, Antoni P.

    2003-06-30

    The objective of this work is to develop bioactive glass coatings for metallic orthopedic implants. A new family of glasses in the SiO2-Na2O-K2O-CaO-MgO-P2O5 system has been synthesized and characterized. The glass properties (thermal expansion, softening and transformation temperatures, density and hardness) are in line with the predictions of established empirical models. The optimized firing conditions to fabricate coatings on Ti-based and Co-Cr alloys have been determined and related to the glass properties and the interfacial reactions. Excellent adhesion to alloys has been achieved through the formation of 100-200 nm thick interfacial layers (Ti5Si3 on Ti-based alloys and CrOx on Co-Cr). Finally, glass coatings, approximately 100 mu m thick, have been fabricated onto commercial Ti alloy-based dental implants.

  2. In-vivo orthopedic implant diagnostic device for sensing load, wear, and infection

    DOE Patents [OSTI]

    Evans, III, Boyd McCutchen; Thundat, Thomas G.; Komistek, Richard D.; Dennis, Douglas A.; Mahfouz, Mohamed

    2006-08-29

    A device for providing in vivo diagnostics of loads, wear, and infection in orthopedic implants having at least one load sensor associated with the implant, at least one temperature sensor associated with the implant, at least one vibration sensor associated with the implant, and at least one signal processing device operatively coupled with the sensors. The signal processing device is operable to receive the output signal from the sensors and transmit a signal corresponding with the output signal.

  3. Maternal blood metal levels and fetal markers of metabolic function

    SciTech Connect (OSTI)

    Ashley-Martin, Jillian; Dodds, Linda; Arbuckle, Tye E.; Ettinger, Adrienne S.; Shapiro, Gabriel D.; Fisher, Mandy; Taback, Shayne; Bouchard, Maryse F.; Monnier, Patricia; Dallaire, Renee; Fraser, William D.

    2015-01-15

    Exposure to metals commonly found in the environment has been hypothesized to be associated with measures of fetal growth but the epidemiological literature is limited. The Maternal–Infant Research on Environmental Chemicals (MIREC) study recruited 2001 women during the first trimester of pregnancy from 10 Canadian sites. Our objective was to assess the association between prenatal exposure to metals (lead, arsenic, cadmium, and mercury) and fetal metabolic function. Average maternal metal concentrations in 1st and 3rd trimester blood samples were used to represent prenatal metals exposure. Leptin and adiponectin were measured in 1363 cord blood samples and served as markers of fetal metabolic function. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between metals and both high (≥90%) and low (≤10%) fetal adiponectin and leptin levels. Leptin levels were significantly higher in female infants compared to males. A significant relationship between maternal blood cadmium and odds of high leptin was observed among males but not females in adjusted models. When adjusting for birth weight z-score, lead was associated with an increased odd of high leptin. No other significant associations were found at the top or bottom 10th percentile in either leptin or adiponectin models. This study supports the proposition that maternal levels of cadmium influence cord blood adipokine levels in a sex-dependent manner. Further investigation is required to confirm these findings and to determine how such findings at birth will translate into childhood anthropometric measures. - Highlights: • We determined relationships between maternal metal levels and cord blood adipokines. • Cord blood leptin levels were higher among female than male infants. • Maternal cadmium was associated with elevated leptin in male, not female infants. • No significant associations were observed between metals and

  4. SU-E-I-63: Quantitative Evaluation of the Effects of Orthopedic Metal Artifact Reduction (OMAR) Software On CT Images for Radiotherapy Simulation

    SciTech Connect (OSTI)

    Jani, S [Sharp Memorial Hospital, San Diego, CA (United States)

    2014-06-01

    Purpose: CT simulation for patients with metal implants can often be challenging due to artifacts that obscure tumor/target delineation and normal organ definition. Our objective was to evaluate the effectiveness of Orthopedic Metal Artifact Reduction (OMAR), a commercially available software, in reducing metal-induced artifacts and its effect on computed dose during treatment planning. Methods: CT images of water surrounding metallic cylindrical rods made of aluminum, copper and iron were studied in terms of Hounsfield Units (HU) spread. Metal-induced artifacts were characterized in terms of HU/Volume Histogram (HVH) using the Pinnacle treatment planning system. Effects of OMAR on enhancing our ability to delineate organs on CT and subsequent dose computation were examined in nine (9) patients with hip implants and two (2) patients with breast tissue expanders. Results: Our study characterized water at 1000 HU with a standard deviation (SD) of about 20 HU. The HVHs allowed us to evaluate how the presence of metal changed the HU spread. For example, introducing a 2.54 cm diameter copper rod in water increased the SD in HU of the surrounding water from 20 to 209, representing an increase in artifacts. Subsequent use of OMAR brought the SD down to 78. Aluminum produced least artifacts whereas Iron showed largest amount of artifacts. In general, an increase in kVp and mA during CT scanning showed better effectiveness of OMAR in reducing artifacts. Our dose analysis showed that some isodose contours shifted by several mm with OMAR but infrequently and were nonsignificant in planning process. Computed volumes of various dose levels showed <2% change. Conclusions: In our experience, OMAR software greatly reduced the metal-induced CT artifacts for the majority of patients with implants, thereby improving our ability to delineate tumor and surrounding organs. OMAR had a clinically negligible effect on computed dose within tissues. Partially funded by unrestricted

  5. SU-E-I-75: Evaluation of An Orthopedic Metal Artifact Reduction (O-MAR) Algorithm On Patients with Spinal Prostheses Near Spinal Tumors

    SciTech Connect (OSTI)

    Shen, Z; Xia, P; Djemil, T; Klahr, P

    2014-06-01

    Purpose: To evaluate the impact of a commercial orthopedic metal artifact reduction (O-MAR) algorithm on CT image quality and dose calculation for patients with spinal prostheses near spinal tumors. Methods: A CT electron density phantom was scanned twice: with tissue-simulating inserts only, and with a titanium insert replacing solid water. A patient plan was mapped to the phantom images in two ways: with the titanium inside or outside of the spinal tumor. Pinnacle and Eclipse were used to evaluate the dosimetric effects of O-MAR on 12-bit and 16-bit CT data, respectively. CT images from five patients with spinal prostheses were reconstructed with and without O-MAR. Two observers assessed the image quality improvement from O-MAR. Both pencil beam and Monte Carlo dose calculation in iPlan were used for the patient study. The percentage differences between non-OMAR and O-MAR datasets were calculated for PTV-min, PTV-max, PTV-mean, PTV-V100, PTV-D90, OAR-V10Gy, OAR-max, and OAR-D0.1cc. Results: O-MAR improved image quality but did not significantly affect the dose distributions and DVHs for both 12-bit and 16- bit CT phantom data. All five patient cases demonstrated some degree of image quality improvement from O-MAR, ranging from small to large metal artifact reduction. For pencil beam, the largest discrepancy was observed for OARV-10Gy at 5.4%, while the other seven parameters were ≤0.6%. For Monte Carlo, the differences between non-O-MAR and O-MAR datasets were ≤3.0%. Conclusion: Both phantom and patient studies indicated that O-MAR can substantially reduce metal artifacts on CT images, allowing better visualization of the anatomical structures and metal objects. The dosimetric impact of O-MAR was insignificant regardless of the metal location, image bit-depth, and dose calculation algorithm. O-MAR corrected images are recommended for radiation treatment planning on patients with spinal prostheses because of the improved image quality and no need to modify

  6. Preconception maternal polychlorinated biphenyl concentrations and the secondary sex ratio

    SciTech Connect (OSTI)

    Taylor, Kira C. [Division of Epidemiology, Statistics and Prevention Research, National Institutes of Child Health and Development (NICHD), NIH, DHHS, 6100 Executive Blvd, Room 7B03, Rockville, MD 20852 (United States); Department of Epidemiology, 1518 Clifton Road, NE Atlanta, GA 30322 (United States); Jackson, Leila W. [Department of Epidemiology and Biostatistics, WG37, Case Western Reserve University School of Medicine, 10900 Euclid Avenue Cleveland, OH 44106-4945 (United States); Lynch, Courtney D. [Division of Epidemiology, Statistics and Prevention Research, National Institutes of Child Health and Development (NICHD), NIH, DHHS, 6100 Executive Blvd, Room 7B03, Rockville, MD 20852 (United States); Kostyniak, Paul J. [Toxicology Research Center, 134 Cary Hall, University at Buffalo, State of New York, 3434 Main St., Buffalo, NY 14214-3000 (United States); Buck Louis, Germaine M. [Division of Epidemiology, Statistics and Prevention Research, National Institutes of Child Health and Development (NICHD), NIH, DHHS, 6100 Executive Blvd, Room 7B03, Rockville, MD 20852 (United States)]. E-mail: louisg@mail.nih.gov

    2007-01-15

    The secondary sex ratio is the ratio of male to female live births and historically has ranged from 102 to 106 males to 100 females. Temporal declines have been reported in many countries prompting authors to hypothesize an environmental etiology. Blood specimens were obtained from 99 women aged 24-34 prior to attempting pregnancy and quantified for 76 polychlorinated biphenyl (PCB) congeners using dual column gas chromatography with electron capture detection. Women were prospectively followed until pregnancy or 12 cycles of trying. The odds of a male birth for three PCB groupings (total, estrogenic, anti-estrogenic) controlling for maternal characteristics were estimated using logistic regression. Among the 50 women with live births and PCB data, 26 female and 24 male infants were born (ratio 0.92). After adjusting for age and body mass index, odds of a male birth were elevated among women in the second (OR=1.29) and third (OR=1.48) tertiles of estrogenic PCBs; odds (OR=0.70) were reduced among women in the highest tertile of anti-estrogenic PCBs. All confidence intervals included one. The direction of the odds ratios in this preliminary study varied by PCB groupings, supporting the need to study specific PCB patterns when assessing environmental influences on the secondary sex ratio.

  7. Maternal exposure to cadmium during gestation perturbs the vascular system of the adult rat offspring

    SciTech Connect (OSTI)

    Ronco, Ana Maria; Montenegro, Marcela; Castillo, Paula; Urrutia, Manuel; Saez, Daniel; Hirsch, Sandra; Zepeda, Ramiro; Llanos, Miguel N.

    2011-03-01

    Several cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30 ppm of cadmium during pregnancy. Echocardiographic examination shows altered heart morphology characterized by a concentric left ventricular hypertrophy. Also, we observed a reduced endothelium-dependent reactivity in isolated aortic rings of adult offspring, while endothelium-independent reactivity remained unaltered. These effects were associated with an increase of hem-oxygenase 1 (HO-1) expression in the aortas of adult offspring. The expression of HO-1 was higher in females than males, a finding likely related to the sex-dependent expression of the vascular cell adhesion molecule 1 (VCAM-1), which was lower in the adult female. All these long-term consequences were observed along with normal birth weights and absence of detectable levels of cadmium in fetal and adult tissues of the offspring. In placental tissues however, cadmium levels were detected and correlated with increased NF-{kappa}B expression - a transcription factor sensitive to inflammation and oxidative stress - suggesting a placentary mechanism that affect genes related to the development of the cardiovascular system. Our results provide, for the first time, direct experimental evidence supporting that exposure to cadmium during pregnancy reprograms cardiovascular development of the offspring which in turn may conduce to a long term increased risk of CVD.

  8. Gestational urinary bisphenol A and maternal and newborn thyroid hormone concentrations: The HOME Study

    SciTech Connect (OSTI)

    Romano, Megan E.; Webster, Glenys M.; Vuong, Ann M.; Thomas Zoeller, R.; Chen, Aimin; Hoofnagle, Andrew N.; Calafat, Antonia M.; Karagas, Margaret R.; Yolton, Kimberly; Lanphear, Bruce P.; Braun, Joseph M.

    2015-04-15

    Bisphenol A (BPA), an endocrine disruptor used in consumer products, may perturb thyroid function. Prenatal BPA exposure may have sex-specific effects on thyroid hormones (THs). Our objectives were to investigate whether maternal urinary BPA concentrations during pregnancy were associated with THs in maternal or cord serum, and whether these associations differed by newborn sex or maternal iodine status. We measured urinary BPA concentrations at 16 and 26 weeks gestation among pregnant women in the HOME Study (2003–2006, Cincinnati, Ohio). Thyroid stimulating hormone (TSH) and free and total thyroxine (T{sub 4}) and triiodothyronine (T{sub 3}) were measured in maternal serum at 16 weeks (n=181) and cord serum at delivery (n=249). Associations between BPA concentrations and maternal or cord serum TH levels were estimated by multivariable linear regression. Mean maternal urinary BPA was not associated with cord THs in all newborns, but a 10-fold increase in mean BPA was associated with lower cord TSH in girls (percent change=−36.0%; 95% confidence interval (CI): −58.4, −1.7%), but not boys (7.8%; 95% CI: −28.5, 62.7%; p-for-effect modification=0.09). We observed no significant associations between 16-week BPA and THs in maternal or cord serum, but 26-week maternal BPA was inversely associated with TSH in girls (−42.9%; 95% CI: −59.9, −18.5%), but not boys (7.6%; 95% CI: −17.3, 40.2%; p-for-effect modification=0.005) at birth. The inverse BPA–TSH relation among girls was stronger, but less precise, among iodine deficient versus sufficient mothers. Prenatal BPA exposure may reduce TSH among newborn girls, particularly when exposure occurs later in gestation. - Highlights: • Examined associations of BPA with thyroid hormones in pregnant women and newborns. • Assessed effect modification of BPA–thyroid hormone associations by newborn sex. • Greater BPA related to decreased thyroid stimulating hormone in girls' cord serum. • Results may

  9. Beryllium disease

    SciTech Connect (OSTI)

    Not Available

    1991-12-20

    After two workers at the nuclear weapons plant at Oak Ridge National Laboratory in Tennessee were diagnosed earlier this year with chronic beryllium disease (CBD), a rare and sometimes fatal scarring of the lungs, the Department of Energy ordered up a 4-year probe. Now, part of that probe has begun - tests conducted by the Oak Ridge Associated Universities' Center for Epidemiological Research measuring beryllium sensitivity in 3,000 people who've been exposed to the metal's dust since Manhattan Project managers opened the Y-12 plant at Oak Ridge in 1943. Currently, 119 Y-12 employees process beryllium, which has a number of industrial uses, including rocket heat shields and nuclear weapon and electrical components. The disease often takes 20 to 25 years to develop, and the stricken employees haven't worked with beryllium for years. There is no cure for CBD, estimated to strike 2% of people exposed to the metal. Anti-inflammatory steroids alleviate such symptoms as a dry cough, weight loss, and fatigue. Like other lung-fibrosis diseases that are linked to lung cancer, some people suspect CBD might cause some lung cancer. While difficult to diagnose, about 900 cases of CBD have been reported since a Beryllium Case Registry was established in 1952. The Department of Energy (DOE) estimates that about 10,000 DOE employees and 800,000 people in private industry have worked with beryllium.

  10. Effects of Love Canal soil extracts on maternal health and fetal development in rats

    SciTech Connect (OSTI)

    Silkworth, J.B.; Tumasonis, C.; Briggs, R.G.; Narang, A.S.; Narang, R.S.; Rej, R.; Stein, V.; McMartin, D.N.; Kaminsky, L.S.

    1986-10-01

    The effects of a solvent extract of the surface soil of the Love Canal chemical dump site, Niagara Falls, New York, and of a natural extract, or leachate, which is drained from the canal for treatment, on the maternal health and fetal development were determined in rats. The solvent extract, which was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (2, 3,7,8-TCDD) at 170 ppb and numerous other chlorinated organic compounds with the primary identified components being the isomers of benzenehexachloride (BHC), was dissolved in corn oil and administered by gavage to pregnant rats at 0,25,75, or 150 mg crude extract/kg/day on Days 6-15 of gestation. A 67% mortality was observed at the highest dose. The rats were sacrificed on Day 20. Dose-related increases in relative liver weight accompanied by hepatocyte hypertrophy were observed at all dose levels. Fetal birthweight was decreased at 75 and 150 mg extract/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. Based on literature values for BHC, all of the observed toxicity could be accounted for by the BHC contaminants of the extract. The crude organic phase of the leachate was administered to pregnant rats at 0,10,100, or 250 mg/kg/day as described above. Maternal weight gain decreased at 100 and 250 mg/kg/day, accompanied by 5 and 14% maternal mortality, and 1 and 3 dead fetuses, respectively. Early resorptions and the percentage of dead implants increased whereas fetal birthweights were decreased at 250 mg/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. The primary components of the complex leachate by mass were tetrachloroethanes; however, 2,3,7,8-TCDD, which was present at 3 ppm, probably accounted for all the observed toxicity.

  11. Concurrent determination of bisphenol A pharmacokinetics in maternal and fetal rhesus monkeys

    SciTech Connect (OSTI)

    Patterson, Tucker A.; Twaddle, Nathan C.; Roegge, Cindy S.; Callicott, Ralph J.; Fisher, Jeffrey W.; Doerge, Daniel R.

    2013-02-15

    Bisphenol A (BPA) is an important industrial chemical used as the monomer for polycarbonate plastic and in epoxy resins for food can liners. Worldwide biomonitoring studies consistently find a high prevalence of BPA conjugates in urine (> 90%) in amounts consistent with aggregate exposure at levels below 1 ?g/kg bw/d. The current study used LC/MS/MS to measure concurrently the pharmacokinetics of aglycone (active) and conjugated (inactive) deuterated BPA (d6) in maternal and fetal rhesus monkey serum, amniotic fluid, and placenta following intravenous injection in the dam (100 ?g/kg bw). Internal exposures of the fetus to aglycone d6-BPA (serum AUC) were attenuated by maternal, placental, and fetal Phase II metabolism to less than half that in the dam. Levels of aglycone and conjugated d6-BPA measured in whole placenta were consistent with a role in metabolic detoxification. The monotonic elimination of aglycone d6-BPA from the fetal compartment accompanied by persistent conjugate levels provides further evidence arguing against the hypothesis that BPA conjugates are selectively deconjugated by either the placenta or fetus. These results also provide benchmarks to guide the interpretation of human cord blood, amniotic fluid, and placenta sampling and measurement strategies as a basis for estimating fetal exposures to BPA. This study in a non-human primate model provides additional pharmacokinetic data for use in PBPK modeling of perinatal exposures to BPA from food contact, medical devices, and other environmental sources. - Highlights: ? Maternal, placental, and fetal Phase II metabolism attenuate fetal exposure to BPA. ? Serum AUC for aglycone BPA in fetal monkeys is less than half of that in the dam. ? BPA profiles in monkey fetus rule out selective deconjugation and accumulation. ? BPA levels in monkey placenta are similar to other metabolically active tissues. ? Some published human cord blood data for BPA are inconsistent with these measurements.

  12. Interim Chronic Beryllium Disease

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    1999-12-08

    Establishes Departmental expectations for addressing chronic beryllium disease throughout the Department until a Departmental rule on beryllium is promulgated. This Notice was replaced by final rule 10 CFR Part 850, Chronic Beryllium Disease Prevention Program, published December 8, 1999.

  13. Differential modulation of dibenzo[def,p]chrysene transplacental carcinogenesis: Maternal diets rich in indole-3-carbinol versus sulforaphane

    SciTech Connect (OSTI)

    Shorey, Lyndsey E.; Madeen, Erin P.; Atwell, Lauren L.; Ho, Emily; Lhr, Christiane V.; Pereira, Clifford B.; Dashwood, Roderick H.; Williams, David E.

    2013-07-01

    Cruciferous vegetable components have been documented to exhibit anticancer properties. Targets of action span multiple mechanisms deregulated during cancer progression, ranging from altered carcinogen metabolism to the restoration of epigenetic machinery. Furthermore, the developing fetus is highly susceptible to changes in nutritional status and to environmental toxicants. Thus, we have exploited a mouse model of transplacental carcinogenesis to assess the impact of maternal dietary supplementation on cancer risk in offspring. In this study, transplacental and lactational exposure to a maternal dose of 15 mg/Kg B.W. of dibenzo[def,p]chrysene (DBC) resulted in significant morbidity of offspring due to an aggressive T-cell lymphoblastic lymphoma. As in previous studies, indole-3-carbinol (I3C, feed to the dam at 100, 500 or 1000 ppm), derived from cruciferous vegetables, dose-dependently reduced lung tumor multiplicity and also increased offspring survival. Brussels sprout and broccoli sprout powders, selected for their relative abundance of I3C and the bioactive component sulforaphane (SFN), respectively, surprisingly enhanced DBC-induced morbidity and tumorigenesis when incorporated into the maternal diet at 10% wt/wt. Purified SFN, incorporated in the maternal diet at 400 ppm, also decreased the latency of DBC-dependent morbidity. Interestingly, I3C abrogated the effect of SFN when the two purified compounds were administered in equimolar combination (500 ppm I3C and 600 ppm SFN). SFN metabolites measured in the plasma of neonates positively correlated with exposure levels via the maternal diet but not with offspring mortality. These findings provide justification for further study of the safety and bioactivity of cruciferous vegetable phytochemicals at supplemental concentrations during the perinatal period. - Highlights: Dietary supplementation may modulate cancer risk in a mouse model of lymphoma. Cruciferous vegetables may not contain sufficient I3C for

  14. Toxicogenomic profiling in maternal and fetal rodent brains following gestational exposure to chlorpyrifos

    SciTech Connect (OSTI)

    Moreira, Estefania G.; Yu Xiaozhong; Robinson, Joshua F.; Griffith, Willian; Hong, Sung Woo; Beyer, Richard P.; Bammler, Theo K.; Faustman, Elaine M.

    2010-06-15

    Considering the wide variety of effects that have been reported to occur in the developmental neurotoxicity of chlorpyrifos (CP) and the lack of consensus on their dependence of brain acetylcholinesterase (AChE) activity inhibition, we applied microarray technology to explore dose-dependent alterations in transcriptional response in the fetal and maternal C57BL/6 mouse brain after daily gestational exposure (days 6 to 17) to CP (2, 4, 10, 12 or 15 mg/kg, sc). We identified significantly altered genes across doses and assessed for overrepresentation of Gene Ontology (GO) biological processes and KEGG pathways. We further clustered genes based on their expression profiles across doses and repeated the GO/pathways analysis for each cluster. The dose-effect relationship of CP on gene expression, both at the gene and pathway levels was non-monotonic and not necessarily related to brain AChE inhibition. The largest impact was observed in the 10 mg/kg dose group which was also the LOAEL for brain AChE inhibition. In the maternal brain, lower doses (4 mg/kg) influenced GO categories and pathways such as cell adhesion, behavior, lipid metabolism, long-term potentiation, nervous system development, neurogenesis, synaptic transmission. In the fetal brain, lower doses (2 and/or 4 mg/kg) significantly altered cell division, translation, transmission of nerve impulse, chromatin modification, long-term potentiation. In addition, some genes involved in nervous system development and signaling were shown to be specifically influenced by these lower CP doses. Our approach was sensitive and reflected the diversity of responses known to be disrupted by CP and highlighted possible additional consequences of CP neurotoxicity, such as disturbance of the ubiquitin proteasome system.

  15. Adventures in Infectious Diseases

    ScienceCinema (OSTI)

    Fisher-Hoch, Susan [University of Texas School of Public Health

    2014-06-25

    Dr. Susan Fisher-Hoch, Virologist and Epidemiologist, will discuss her research and travels associated with viral hemorrhagic fevers. From the Ebola outbreak in Reston, Virginia to outbreaks of Crimean Congo Hemorrhagic Fever in South Africa, Senegal, and Saudi Arabia, Dr. Fisher-Hoch has studied and tracked the pathophysiology of these viral diseases. These studies have led her from the Center for Disease Control in the United States, to Lyon, France where she was instrumental in designing, constructing, and rendering operational a laboratory capable of containing some of the world's most dangerous diseases.

  16. Gas bubble disease: introduction

    SciTech Connect (OSTI)

    Fickeisen, D.H.; Schneider, M.J.; Wedemeyer, G.A.

    1980-11-01

    In 1970, gas bubble disease was identified as a serious problem affecting salmonids in the Columbia and Snake river systems. The source of supersaturation was entrainment of air into water spilling over hydroelectric dams. Regional research projects focusing on tolerance bioassays were immediately implemented. Since then, the scope of gas bubble disease research has broadened to include problems in other aquatic systems, with other species. Emphasis has shifted from defining tolerance limits in bioassay systems to exploring behavioral and physiological aspects. Various methods of degasifying supersaturated water have been developed.

  17. Etiology of Early Lifestage Diseases, Project 84-44, 1985 Final Report.

    SciTech Connect (OSTI)

    Sauter, R.W.

    1986-10-01

    Each year hatcheries experience loss of eggs, fry and fingerlings due to a group of poorly defined diseases called White Spot and Coagulated Yolk. Samples of maternal blood and ovarian fluid (coelomic fluid), as well as unfertilized eggs, were collected at spawning and subsequently tested for the presence of bacteria. Our tests reveal that there is a wide range in mortality rates experienced by the progeny of different brood salmon. Microbiologic tests revealed that these eggs contained a variety of both Gram positive and Gram negative bacteria within their yolk and that the fluids from the females who produced these lots were contaminated with a variety of bacteria. In contrast the eggs and maternal fluids from the six egg lots which experienced the lowest mortalities did not contain high numbers of Gram positive bacteria and contributed only 5% of the total mortalities observed within the 30 egg lots tested. From the 60 egg lots tested over two brood years we have isolated 18 different bacterial genera containing 32 different species from within the yolk surface sterilized, unfertilized eggs. Our tests suggest that Aeromonas hydrophila, Pseudomonas (3 species) Staphylococcus aureus, Vibrio sp., Corynebacterium hoffmanii, Listeria sp. and Bacillus sp. when detected within the yolk of eggs sampled from egg lots prior to fertilization will be associated with higher than normal mortality rates when the remainder of the egg lots containing these bacteria are incubated and reared. 36 refs., 16 figs.

  18. Interactive effects of maternal and environmental exposure to coal combustion wastes decrease survival of larval southern toads (Bufo terrestris)

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Interactive effects of maternal and environmental exposure to coal combustion wastes decrease survival of larval southern toads (Bufo terrestris) Brian S. Metts a, * , Kurt A. Buhlmann a , David E. Scott a , Tracey D. Tuberville a , William A. Hopkins b a Savannah River Ecology Laboratory, Drawer E, Aiken, SC 29802, USA b Department of Fish and Wildlife Conservation, Virginia Tech, Blacksburg, VA 24061, USA a r t i c l e i n f o Article history: Received 16 August 2011 Received in revised form

  19. Using Wikipedia to forecast diseases

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Using Wikipedia to forecast diseases Using Wikipedia to forecast diseases Scientists can now monitor and forecast diseases around the globe more effectively by analyzing views of Wikipedia articles. November 13, 2014 Del Valle and her team observe findings from their research on disease patterns from analyzing Wikipedia articles. Del Valle and her team observe findings from their research on disease patterns from analyzing Wikipedia articles. Contact Nancy Ambrosiano Communications Office (505)

  20. Early detection of contagious diseases

    DOE Patents [OSTI]

    Colston, Jr., Billy W.; Milanovich, Fred P.; Estacio, Pedro; Chang, John

    2011-08-09

    This invention provides an electronic proximity apparatus and a surveillance method using such an apparatus for alerting individuals that are exposed to a contagious disease. When a person becomes symptomatic and is diagnosed as positive for a given contagious agent, individuals that have recently maintained a threshold proximity with respect to an infected individual are notified and advised to seek immediate medial care. Treatment of individuals in the very early phases of infection (pre-symptomatic) significantly reduces contagiousness of the infected population first exposed to the contagious disease, thus preventing spread of the disease throughout the general population.

  1. Meiotic interstrand DNA damage escapes paternal repair and causes chromosomal aberrations in the zygote by maternal misrepair

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Marchetti, Francesco; Bishop, Jack; Gingerich, John; Wyrobek, Andrew J.

    2015-01-08

    De novo point mutations and chromosomal structural aberrations (CSA) detected in offspring of unaffected parents show a preferential paternal origin with higher risk for older fathers. Studies in rodents suggest that heritable mutations transmitted from the father can arise from either paternal or maternal misrepair of damaged paternal DNA, and that the entire spermatogenic cycle can be at risk after mutagenic exposure. Understanding the susceptibility and mechanisms of transmission of paternal mutations is important in family planning after chemotherapy and donor selection for assisted reproduction. We report that treatment of male mice with melphalan (MLP), a bifunctional alkylating agent widelymore » used in chemotherapy, induces DNA lesions during male mouse meiosis that persist unrepaired as germ cells progress through DNA repair-competent phases of spermatogenic development. After fertilization, unrepaired sperm DNA lesions are mis-repaired into CSA by the egg's DNA repair machinery producing chromosomally abnormal offspring. In conclusion, these findings highlight the importance of both pre- and post-fertilization DNA repair in assuring the genomic integrity of the conceptus.« less

  2. Patching genes to fight disease

    SciTech Connect (OSTI)

    Holzman, D.

    1990-09-03

    The National Institutes of Health has approved the first gene therapy experiments, one of which will try to cure cancer by bolstering the immune system. The applications of such therapy are limited, but the potential aid to people with genetic diseases is great.

  3. Etiology of gas bubble disease

    SciTech Connect (OSTI)

    Bouck, G.R.

    1980-11-01

    Gas bubble disease is a noninfectious, physically induced process caused by uncompensated hyperbaric pressure of total dissolved gases. When pressure compensation is inadequate, dissolved gases may form emboli (in blood) and emphysema (in tissues). The resulting abnormal physical presence of gases can block blood vessels (hemostasis) or tear tissues, and may result in death. Population mortality is generally skewed, in that the median time to death occurs well before the average time to death. Judged from mortality curves, three stages occur in gas bubble disease: (1) a period of gas pressure equilibrium, nonlethal cavitation, and increasing morbidity; (2) a period of rapid and heavy mortality; and (3) a period of protracted survival, despite lesions, and dysfunction that eventually terminates in total mortality. Safe limits for gas supersaturation depend on species tolerance and on factors that differ among hatcheries and rivers, between continuous and intermittent exposures, and across ranges of temperature and salinity.

  4. New Clues in Predicting Alzheimer's Disease

    ScienceCinema (OSTI)

    Jagust, William

    2013-05-29

    Theres a new clue in the search to identify the harbingers of Alzheimers disease. More info: http://newscenter.lbl.gov/feature-stories/2008/12/16/predict-alzheimers-disease/

  5. RNA simulations boost understanding of retroviral diseases

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    RNA simulations boost understanding of retroviral diseases RNA simulations boost understanding of retroviral diseases New molecular dynamics research into how RNA folds into hairpin-shaped structures called tetraloops could provide important insights into new treatments for retroviral diseases. May 31, 2016 An example of RNA folded into a tetraloop, in this case the "Z-form duplex" under study that could provide medical treatment opportunities for retroviral diseases such as Zika and

  6. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Protein Instability and Lou Gehrig's Disease Protein Instability and Lou Gehrig's Disease Print Wednesday, 25 March 2015 00:00 A new study links protein instability with the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Using several biophysical techniques as well as small-angle x-ray scattering (SAXS) at the Advanced Light Source, researchers focused on the effects of mutations to a gene coding for a protein called

  7. Combined effects of perfluorooctane sulfonate (PFOS) and maternal restraint stress on hypothalamus adrenal axis (HPA) function in the offspring of mice

    SciTech Connect (OSTI)

    Ribes, Diana; Fuentes, Silvia; Torrente, Margarita; Colomina, M. Teresa [Department of Psychology and Research Center for Behavioral Assessment (CRAMC), 'Rovira i Virgili' University, Sescelades Campus, 43007 Tarragona, Catalonia (Spain); Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, 'Rovira i Virgili' University, Sant Llorenc 21, 43201 Reus, Catalonia (Spain); Domingo, Jose L., E-mail: joseluis.domingo@urv.ca [Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, 'Rovira i Virgili' University, Sant Llorenc 21, 43201 Reus, Catalonia (Spain)

    2010-02-15

    Although it is known that prenatal exposure to perfluorooctane sulfonate (PFOS) can cause developmental adverse effects in mammals, the disruptive effects of this compound on hormonal systems are still controversial. Information concerning the effects of PFOS on hypothalamus adrenal (HPA) axis response to stress and corticosterone levels is not currently available. On the other hand, it is well established that stress can enhance the developmental toxicity of some chemicals. In the present study, we assessed the combined effects of maternal restraint stress and PFOS on HPA axis function in the offspring of mice. Twenty plug-positive female mice were divided in two groups. Animals were given by gavage 0 and 6 mg PFOS/kg/day on gestation days 12-18. One half of the animals in each group were also subjected to restraint stress (30 min/session, 3 sessions/day) during the same period. Five plug-positive females were also included as non-manipulated controls. At 3 months of age, activity in an open-field and the stress response were evaluated in male and female mice by exposing them to 30 min of restraint stress. Male and female offspring were subsequently sacrificed and blood samples were collected to measure changes in corticosterone levels at four different moments related to stress exposure conditions: before stress exposure, immediately after 30 min of stress exposure, and recuperation levels at 60 and 90 min after stress exposure. Results indicate corticosterone levels were lower in mice prenatally exposed to restraint. In general terms, PFOS exposure decreased corticosterone levels, although this effect was only significant in females. The recuperation pattern of corticosterone was mainly affected by prenatal stress. Interactive effects between PFOS and maternal stress were sex dependent. The current results suggest that prenatal PFOS exposure induced long-lasting effects in mice.

  8. Therapeutic target for protozoal diseases

    DOE Patents [OSTI]

    Rathore, Dharmendar; Jani, Dewal; Nagarkatti, Rana

    2008-10-21

    A novel Fasciclin Related Adhesive Protein (FRAP) from Plasmodium and related parasites is provided as a target for therapeutic intervention in diseases caused by the parasites. FRAP has been shown to play a critical role in adhesion to, or invasion into, host cells by the parasite. Furthermore, FRAP catalyzes the neutralization of heme by the parasite, by promoting its polymerization into hemozoin. This invention provides methods and compositions for therapies based on the administration of protein, DNA or cell-based vaccines and/or antibodies based on FRAP, or antigenic epitopes of FRAP, either alone or in combination with other parasite antigens. Methods for the development of compounds that inhibit the catalytic activity of FRAP, and diagnostic and laboratory methods utilizing FRAP are also provided.

  9. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Protein Instability and Lou Gehrig's Disease Print A new study links protein instability with the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Using several biophysical techniques as well as small-angle x-ray scattering (SAXS) at the Advanced Light Source, researchers focused on the effects of mutations to a gene coding for a protein called superoxide dismutase (SOD). The study provides evidence that those proteins linked

  10. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Protein Instability and Lou Gehrig's Disease Print A new study links protein instability with the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Using several biophysical techniques as well as small-angle x-ray scattering (SAXS) at the Advanced Light Source, researchers focused on the effects of mutations to a gene coding for a protein called superoxide dismutase (SOD). The study provides evidence that those proteins linked

  11. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Protein Instability and Lou Gehrig's Disease Print A new study links protein instability with the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Using several biophysical techniques as well as small-angle x-ray scattering (SAXS) at the Advanced Light Source, researchers focused on the effects of mutations to a gene coding for a protein called superoxide dismutase (SOD). The study provides evidence that those proteins linked

  12. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Protein Instability and Lou Gehrig's Disease Print A new study links protein instability with the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Using several biophysical techniques as well as small-angle x-ray scattering (SAXS) at the Advanced Light Source, researchers focused on the effects of mutations to a gene coding for a protein called superoxide dismutase (SOD). The study provides evidence that those proteins linked

  13. Imaging of occupational and environmental lung diseases

    SciTech Connect (OSTI)

    Akira, M.

    2008-03-15

    The chest radiograph is the basic tool for identifying occupational and environmental lung diseases; however, its sensitivity and specificity for the diagnosis of occupational and environmental lung diseases are low. High-resolution CT is the optimal method of recognizing parenchymal abnormalities in occupational and environmental disease. With the exception of pleural plaques, the CT findings of occupational and environmental lung diseases are nonspecific. Therefore, correlation of imaging features with history of exposure, other clinical features, and sometimes pathology is needed for the diagnosis of pneumoconiosis.

  14. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    called superoxide dismutase (SOD). The study provides evidence that those proteins linked to more severe forms of the disease are less stable structurally and more prone to...

  15. Influence of metal(loid) bioaccumulation and maternal transfer on embryo-larval development in fish exposed to a major coal ash spill

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Greeley, Jr., Mark Stephen; Adams, S. Marshall; Elmore, Logan R.; McCracken, Mary Kitty

    2016-01-03

    In December 2008, an earthen retaining wall at the Tennessee Valley Authority (TVA) Kingston Fossil Fuel Plant failed and released 4.1 million m3 of coal ash to rivers flowing into Watts Bar Reservoir in east Tennessee, United States (U.S.). As part of a comprehensive effort to evaluate the risks to aquatic resources from this spill – the largest in U.S. history – we compared bioaccumulation and maternal transfer of selenium (Se), arsenic (As), and mercury (Hg) in adult redear sunfish (Lepomis macrolophus), collected two years after the spill from both coal-ash exposed and non-exposed areas of the Emory and Clinchmore » Rivers, with the success of embryo-larval development in their offspring. Whole body and ovary concentrations of Se in female sunfish at three study sites downstream of the spill were significantly elevated (site means = 4.9–5.3 and 6.7–9.0 mg/kg d.w. whole body and ovary concentrations, respectively) compared with concentrations in fish from reference sites upstream of the spill site (2.2–3.2 mg/kg d.w. for whole bodies and 3.6–4.8 mg/kg d.w. for ovaries). However, Se concentrations in coal ash-exposed areas remain below proposed U.S. Environmental Protection Agency (USEPA) criteria for the protection of aquatic life. Site-to-site variation in fish concentrations of As and Hg were not well-correlated with ash-exposure, reflecting the multiple sources of these metal(loid)s in the affected watersheds. In 7-day laboratory tests of embryos and larvae derived from in vitro crosses of eggs and sperm from these field-collected sunfish, fertilization success, hatching success, embryo-larval survival, and incidences of developmental abnormalities did not differ significantly between ash-exposed and non-exposed fish. Furthermore, these developmental endpoints were not correlated with whole body or ovary concentrations of Se, As, or Hg in the maternal fish, or with fish size, ovary weight, or gonadal-somatic indices. Furthermore, results from

  16. Disease Ontology 2015 update: An expanded and updated database of human diseases for linking biomedical knowledge through disease data

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Kibbe, Warren A.; Arze, Cesar; Felix, Victor; Mitraka, Elvira; Bolton, Evan; Fu, Gang; Mungall, Christopher J.; Binder, Janos X.; Malone, James; Vasant, Drashtti; et al

    2014-10-27

    The current version of the Human Disease Ontology (DO) (http://www.disease-ontology.org) database expands the utility of the ontology for the examination and comparison of genetic variation, phenotype, protein, drug and epitope data through the lens of human disease. DO is a biomedical resource of standardized common and rare disease concepts with stable identifiers organized by disease etiology. The content of DO has had 192 revisions since 2012, including the addition of 760 terms. Thirty-two percent of all terms now include definitions. DO has expanded the number and diversity of research communities and community members by 50+ during the past two years.more » These community members actively submit term requests, coordinate biomedical resource disease representation and provide expert curation guidance. Since the DO 2012 NAR paper, there have been hundreds of term requests and a steady increase in the number of DO listserv members, twitter followers and DO website usage. DO is moving to a multi-editor model utilizing Protégé to curate DO in web ontology language. In conclusion, this will enable closer collaboration with the Human Phenotype Ontology, EBI's Ontology Working Group, Mouse Genome Informatics and the Monarch Initiative among others, and enhance DO's current asserted view and multiple inferred views through reasoning.« less

  17. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    1941 at the age of only 38. Recently, an award-winning movie about the famous physicist, Stephen Hawking, depicted the disease's devastating physical toll. ALS kills by destroying...

  18. Zika Virus Disease and Prevention Presentation

    Broader source: Energy.gov [DOE]

    A “Zika Virus Disease and Prevention” presentation was made by Bonnie S. Richter, MPH, PhD, at the May 19 Office of Environment, Health, Safety and Security (EHSS) All Hands Meeting.

  19. Metabolomics reveals metabolic biomarkers of Crohn's disease

    SciTech Connect (OSTI)

    Jansson, J.K.; Willing, B.; Lucio, M.; Fekete, A.; Dicksved, J.; Halfvarson, J.; Tysk, C.; Schmitt-Kopplin, P.

    2009-06-01

    The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.

  20. Counting small RNA in disease-causing organisms

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    in disease-causing organisms Los Alamos researchers demonstrated improved technical methods capable of directly counting small RNA molecules in pathogenic (disease-causing)...

  1. Transgenic Mouse Model of Chronic Beryllium Disease

    SciTech Connect (OSTI)

    Gordon, Terry

    2009-05-26

    Animal models provide powerful tools for dissecting dose-response relationships and pathogenic mechanisms and for testing new treatment paradigms. Mechanistic research on beryllium exposure-disease relationships is severely limited by a general inability to develop a sufficient chronic beryllium disease animal model. Discovery of the Human Leukocyte Antigen (HLA) - DPB1Glu69 genetic susceptibility component of chronic beryllium disease permitted the addition of this human beryllium antigen presentation molecule to an animal genome which may permit development of a better animal model for chronic beryllium disease. Using FVB/N inbred mice, Drs. Rubin and Zhu, successfully produced three strains of HLA-DPB1 Glu 69 transgenic mice. Each mouse strain contains a haplotype of the HLA-DPB1 Glu 69 gene that confers a different magnitude of odds ratio (OR) of risk for chronic beryllium disease: HLA-DPB1*0401 (OR = 0.2), HLA-DPB1*0201 (OR = 15), HLA-DPB1*1701 (OR = 240). In addition, Drs. Rubin and Zhu developed transgenic mice with the human CD4 gene to permit better transmission of signals between T cells and antigen presenting cells. This project has maintained the colonies of these transgenic mice and tested the functionality of the human transgenes.

  2. Chronic beryllium disease: Diagnosis and management

    SciTech Connect (OSTI)

    Rossman, M.D.

    1996-10-01

    Chronic beryllium disease is predominantly a pulmonary granulomatosis that was originally described in 1946. Symptoms usually include dyspnea and cough. Fever, anorexia, and weight loss are common. Skin lesions are the most common extrathoracic manifestation. Granulomatous hepatitis, hypercalcemia, and kidney stones can also occur. Radiographic and physiologic abnormalities are similar to those in sarcoidosis. While traditionally the pathologic changes included granulomas and cellular interstitial changes, the hallmark of the disease today is the well-formed granuloma. Immunologic studies have demonstrated a cell-mediated response to beryllium that is due to an accumulation of CD4{sup +} T cells at the site of disease activity. Diagnosis depends on the demonstration of pathologic changes (i.e., granuloma) and evidence that the granuloma was caused by a hypersensitivity to beryllium (i.e., positive lung proliferative response to beryllium). Using these criteria, the diagnosis of chronic beryllium disease can now be made before the onset of clinical symptoms. Whether, with early diagnosis, the natural course of this condition will be the same as when it was traditionally diagnosed is not known. Currently, corticosteroids are used to treat patients with significant symptoms or evidence of progressive disease. 21 refs.

  3. Global disease monitoring and forecasting with Wikipedia

    SciTech Connect (OSTI)

    Generous, Nicholas; Fairchild, Geoffrey; Deshpande, Alina; Del Valle, Sara Y.; Priedhorsky, Reid; Salathé, Marcel

    2014-11-13

    Infectious disease is a leading threat to public health, economic stability, and other key social structures. Efforts to mitigate these impacts depend on accurate and timely monitoring to measure the risk and progress of disease. Traditional, biologically-focused monitoring techniques are accurate but costly and slow; in response, new techniques based on social internet data, such as social media and search queries, are emerging. These efforts are promising, but important challenges in the areas of scientific peer review, breadth of diseases and countries, and forecasting hamper their operational usefulness. We examine a freely available, open data source for this use: access logs from the online encyclopedia Wikipedia. Using linear models, language as a proxy for location, and a systematic yet simple article selection procedure, we tested 14 location-disease combinations and demonstrate that these data feasibly support an approach that overcomes these challenges. Specifically, our proof-of-concept yields models with up to 0.92, forecasting value up to the 28 days tested, and several pairs of models similar enough to suggest that transferring models from one location to another without re-training is feasible. Based on these preliminary results, we close with a research agenda designed to overcome these challenges and produce a disease monitoring and forecasting system that is significantly more effective, robust, and globally comprehensive than the current state of the art.

  4. Global disease monitoring and forecasting with Wikipedia

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Generous, Nicholas; Fairchild, Geoffrey; Deshpande, Alina; Del Valle, Sara Y.; Priedhorsky, Reid; Salathé, Marcel

    2014-11-13

    Infectious disease is a leading threat to public health, economic stability, and other key social structures. Efforts to mitigate these impacts depend on accurate and timely monitoring to measure the risk and progress of disease. Traditional, biologically-focused monitoring techniques are accurate but costly and slow; in response, new techniques based on social internet data, such as social media and search queries, are emerging. These efforts are promising, but important challenges in the areas of scientific peer review, breadth of diseases and countries, and forecasting hamper their operational usefulness. We examine a freely available, open data source for this use: accessmore » logs from the online encyclopedia Wikipedia. Using linear models, language as a proxy for location, and a systematic yet simple article selection procedure, we tested 14 location-disease combinations and demonstrate that these data feasibly support an approach that overcomes these challenges. Specifically, our proof-of-concept yields models with up to 0.92, forecasting value up to the 28 days tested, and several pairs of models similar enough to suggest that transferring models from one location to another without re-training is feasible. Based on these preliminary results, we close with a research agenda designed to overcome these challenges and produce a disease monitoring and forecasting system that is significantly more effective, robust, and globally comprehensive than the current state of the art.« less

  5. Treatment of Anthrax Disease Frequently Asked Questions

    SciTech Connect (OSTI)

    Judd, Kathleen S.; Young, Joan E.; Lesperance, Ann M.; Malone, John D.

    2010-05-14

    This document provides a summary of Frequently Asked Questions (FAQs) on the treatment of anthrax disease caused by a wide-area release of Bacillus anthracis spores as an act bioterrorism. These FAQs are intended to provide the public health and medical community, as well as others, with guidance and communications to support the response and long-term recovery from an anthrax event.

  6. Science On Tap - Understanding HIV and Infectious Diseases

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Science On Tap - Understanding HIV and Infectious Diseases Science On Tap - Understanding HIV and Infectious Diseases WHEN: Sep 17, 2015 5:30 PM - 7:00 PM WHERE: UnQuarked Wine...

  7. Software speeds detection of diseases and cancer-treatment targets

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Software speeds detection of diseases Software speeds detection of diseases and cancer-treatment targets The Lab has released an updated version of software that is now capable of ...

  8. NIOSH Alert-Preventing Sentization and Disease from Beryllium | Department

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    of Energy NIOSH Alert-Preventing Sentization and Disease from Beryllium NIOSH Alert-Preventing Sentization and Disease from Beryllium February 3, 2011 Preventing Sensitization and Disease from Beryllium Exposure The National Institute for Occupational Safety and Health (NIOSH) requests assistance in preventing beryllium sensitization and chronic beryllium disease. Development of these conditions requires exposure to beryllium and is affected by both job tasks and genetic factors. Some jobs

  9. Presentation, Zika Virus Disease and Prevention | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Presentation, Zika Virus Disease and Prevention Presentation, Zika Virus Disease and Prevention May 19, 2016 Dr. Richter presented information about the rapid evolution of the Zika virus, the regions reporting active mosquito transmission of the Zika virus, the disease symptoms and preventative steps. Presentation, Zika Virus Disease and Prevention (678.7 KB) More Documents & Publications Worker Health Summary, 1995-2004 CAIRS Direct Data Entry (CDDE) Online Training Package FAQS Reference

  10. A customizable model for chronic disease coordination: Lessons learned from the coordinated chronic disease program

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Voetsch, Karen; Sequeira, Sonia; Chavez, Amy Holmes

    2016-03-31

    In 2012, the Centers for Disease Control and Prevention provided funding and technical assistance to all states and territories to implement the Coordinated Chronic Disease Program, marking the first time that all state health departments had federal resources to coordinate chronic disease prevention and control programs. This article describes lessons learned from this initiative and identifies key elements of a coordinated approach. We analyzed 80 programmatic documents from 21 states and conducted semistructured interviews with 7 chronic disease directors. Six overarching themes emerged: 1) focused agenda, 2) identification of functions, 3) comprehensive planning, 4) collaborative leadership and expertise, 5) managedmore » resources, and 6) relationship building. Furthermore, these elements supported 4 essential activities: 1) evidence-based interventions, 2) strategic use of staff, 3) consistent communication, and 4) strong program infrastructure. On the basis of these elements and activities, we propose a conceptual model that frames overarching concepts, skills, and strategies needed to coordinate state chronic disease prevention and control programs.« less

  11. Visualizing Brain Metals in Health and Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Visualizing Brain Metals in Health and Disease figure 1 Fig. 1. Rapid-scanning x-ray fluorescence mapping ex perimental setup. Synchrotron x-rays at 11 keV passed through a 50 µm aperture (Ap). The beam intensity was monitored with a N2-filled ion chamber (I0). The brain slice was mounted vertically on a motorized stage (St) at 45° to the incident x-ray beam and raster scanned in the beam. A 13-element Ge detector (Ge) was positioned at a 90° angle to the beam. We all require iron, copper and

  12. Chronic Beryllium Disease Prevention Program Report

    SciTech Connect (OSTI)

    Lee, S

    2012-03-29

    This document describes how Lawrence Livermore National Laboratory (LLNL) meets the requirements and management practices of federal regulation 10 CFR 850, 'Chronic Beryllium Disease Prevention Program (CBDPP).' This revision of the LLNL CBDPP incorporates clarification and editorial changes based on lessons learned from employee discussions, observations and reviews of Department of Energy (DOE) Complex and commercial industry beryllium (Be) safety programs. The information is used to strengthen beryllium safety practices at LLNL, particularly in the areas of: (1) Management of small parts and components; and (2) Communication of program status to employees. Future changes to LLNL beryllium activities and on-going operating experience will be incorporated into the program as described in Section S, 'Performance Feedback.'

  13. Respiratory disease in Utah coal miners

    SciTech Connect (OSTI)

    Rom, W.N.; Kanner, R.E.; Renzetti, A.D. Jr.; Shigeoka, J.W.; Barkman, H.W.; Nichols, M.; Turner, W.A.; Coleman, M.; Wright, W.E.

    1981-04-01

    Two hundred forty-two Utah underground coal miners volunteered to participate in a respiratory disease study. They were an older group (mean, 56 years of age) and had spent a mean of 29 years in the coal-mining industry. The prevalence of chronic bronchitis was 57%, and that of coal worker's pneumoconiosis, 25%; only one worker had progressive massive fibrosis. Significant impairment of pulmonary function was found among those with a history of cigarette smoking. Chronic bronchitis or coal worker's penumoconiosis among nonsmokers did not impair pulmonary function. There was a significant association among the nonsmokers between increasing exposure to coal dust and coal worker's pneumoconiosis, but not for changes in pulmonary function. Coal mine dust had a significant influence in causing the symptom complex of chronic cough and sputum production, and coal worker's pneumoconiosis.

  14. Respiratory disease in Utah coal miners

    SciTech Connect (OSTI)

    Rom, W.N.; Kanner, R.E.; Renzetti, A.D. Jr.; Shigeoka, J.W.; Barkman, H.W.; Nichols, M.; Turner, W.A.; Coleman, M.; Wright, W.E.

    1981-04-01

    Two hundred forty-two Utah underground coal miners volunteered to participate in a respiratory disease study. They were an older group (mean, 56 years of age) and had spent a mean of 29 years in the coal-mining industry. The prevalence of chronic bronchitis was 57%, and that of coal worker's pneumoconiosis, 25%; only one worker had progressive massive fibrosis. Significant impairment of pulmonary function was found among those with a history of cigarette smoking. Chronic bronchitis or coal worker's pneumoconiosis among nonsmokers did not impair pulmonary function. There was a significant association among the nonsmokers between increasing exposure to coal dust and coal worker's pneumoconiosis, but not for changes in pulmonary function. Coal mine dust had a significant influence in causing the symptom complex of chronic cough and sputum production, and coal worker's pneumoconiosis.

  15. Optical detection dental disease using polarized light

    DOE Patents [OSTI]

    Everett, Matthew J.; Colston, Jr., Billy W.; Sathyam, Ujwal S.; Da Silva, Luiz B.; Fried, Daniel

    2003-01-01

    A polarization sensitive optical imaging system is used to detect changes in polarization in dental tissues to aid the diagnosis of dental disease such as caries. The degree of depolarization is measured by illuminating the dental tissue with polarized light and measuring the polarization state of the backscattered light. The polarization state of this reflected light is analyzed using optical polarimetric imaging techniques. A hand-held fiber optic dental probe is used in vivo to direct the incident beam to the dental tissue and collect the reflected light. To provide depth-resolved characterization of the dental tissue, the polarization diagnostics may be incorporated into optical coherence domain reflectometry and optical coherence tomography (OCDR/OCT) systems, which enables identification of subsurface depolarization sites associated with demineralization of enamel or bone.

  16. Automated diagnostic kiosk for diagnosing diseases

    SciTech Connect (OSTI)

    Regan, John Frederick; Birch, James Michael

    2014-02-11

    An automated and autonomous diagnostic apparatus that is capable of dispensing collection vials and collections kits to users interesting in collecting a biological sample and submitting their collected sample contained within a collection vial into the apparatus for automated diagnostic services. The user communicates with the apparatus through a touch-screen monitor. A user is able to enter personnel information into the apparatus including medical history, insurance information, co-payment, and answer a series of questions regarding their illness, which is used to determine the assay most likely to yield a positive result. Remotely-located physicians can communicate with users of the apparatus using video tele-medicine and request specific assays to be performed. The apparatus archives submitted samples for additional testing. Users may receive their assay results electronically. Users may allow the uploading of their diagnoses into a central databank for disease surveillance purposes.

  17. Chronic Beryllium Disease Prevention Program (10 CFR 850) | Department of

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Energy Chronic Beryllium Disease Prevention Program (10 CFR 850) Chronic Beryllium Disease Prevention Program (10 CFR 850) The DOE established a chronic beryllium disease prevention program (CBDPP) to reduce the number of workers currently exposed to beryllium in the course of their work at DOE facilities managed by DOE or its contractors, minimize the levels of, and potential for, exposure to beryllium, and establish medical surveillance requirements to ensure early detection of the

  18. Analyzing genetic tree sheds new light on disease outbreaks

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Analyzing genetic tree sheds new light on disease outbreaks Analyzing genetic tree sheds new light on disease outbreaks The team used computational phylogenetic analysis to examine how strains of HIV, both in computer modeling and compared with real-life case studies, would be transmitted. February 25, 2016 Using computational techniques, scientists at Los Alamos National Laboratory are working to more clearly understand how diseases such as HIV are spread. In this image, arrows indicate actual

  19. Recombinant herpes simplex virus useful for treating neoplastic disease

    DOE Patents [OSTI]

    Whitley, Richard J.; Roizman, Bernard

    2010-06-29

    Recombinant herpes simplex viruses comprising DNA encoding cytokines and methods for treating neoplastic diseases using the inventive recombinant viruses are disclosed.

  20. LANL spinoff receives NIH grant for respiratory disease diagnostic...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    LANL spinoff receives NIH grant LANL spinoff receives NIH grant for respiratory disease diagnostic device Mesa Tech has been awarded a grant to develop an inexpensive, ...

  1. Indoor air quality & airborne disease control in healthcare facilities...

    Office of Scientific and Technical Information (OSTI)

    Subject: 32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATION; MEDICAL ESTABLISHMENTS; INDOOR AIR POLLUTION; CONTROL SYSTEMS; DISEASES; THERMAL COMFORT; SPACE HVAC SYSTEMS Word ...

  2. AND NUCLEAR MEDICINE; DIAGNOSIS; DISEASES; GAMMA CAMERAS; GENETICS...

    Office of Scientific and Technical Information (OSTI)

    Converting energy to medical progress nuclear medicine NONE 62 RADIOLOGY AND NUCLEAR MEDICINE; DIAGNOSIS; DISEASES; GAMMA CAMERAS; GENETICS; NUCLEAR MEDICINE; PATIENTS; RADIATION...

  3. Update on the Hanford Site Chronic Beryllium Disease Prevention...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Chronic Beryllium Disease Prevention Program (CBDPP) Stan Branch Richland Operations Office Hanford Advisory Board Health, Safety and Environmental Protection Committee January 7,...

  4. Methods of treating parkinson's disease using viral vectors

    DOE Patents [OSTI]

    Bankiewicz, Krys; Cunningham, Janet

    2009-05-19

    Methods of delivering viral vectors, particularly recombinant AAV virions, to the CNS are provided. Also provided are methods of treating Parkinson's Disease.

  5. Structure of the Newcastle disease virus hemagglutinin-neuraminidase...

    Office of Scientific and Technical Information (OSTI)

    virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk Citation Details In-Document Search Title: Structure of the Newcastle disease virus ...

  6. Asbestos-related pulmonary disease in boilermakers

    SciTech Connect (OSTI)

    Demers, R.Y.; Neale, A.V.; Robins, T.; Herman, S.C. )

    1990-01-01

    Boilermakers are skilled building tradesmen who construct, repair, and dismantle boilers. The present study reports on the evaluation of members of a Michigan boilermaker's union for the presence of signs and symptoms of chronic pulmonary disease. Study variables included standardized evaluations of chest x-ray findings, pulmonary function testing, physical examination, and respiratory symptoms. An overall participation rate of 69% was achieved. A non-participant survey identified no significant differences between participants and non-participants in dyspnea, cough, age, or smoking history. Among participants with greater than 20 years experience in the trade, the mean FVC was 91% of predicted; the FEV1 was 86% of predicted; 25% showed at least a 1/0 profusion of interstitial markings on chest x-ray; 30% had bilateral pleural abnormalities; and 52% had audible inspiratory rales on physical examination. Forced vital capacity and forced expiratory volume at one second both decreased with years in the trade. Chest x-ray findings of interstitial fibrosis and pleural plaques were related to ten or more years in the trade, as were respiratory symptoms of pulmonary rales, wheeze, and dyspnea.

  7. Polymorphic microsatellites and Wilson disease (WD)

    SciTech Connect (OSTI)

    Stewart, E.A.; Cavalli-Sforza, L.L. ); White, A.; Tomfohrde, J.; Osborne-Lawrence, S.; Prestidge, L.; Bowcock, A.M. ); Bonne-Tamir, B.; Scheinberg, I.H.; George-Hyslop, P.; Giagheddu, M.; Kim, J.W.; Seo, J.K.; Lo, W.H.Y.; Ivanova-Smolenskaya, I.A.; Limborska, S.A.; Farrer, L.A.

    1993-10-01

    Wilson disease (WD), an autosomal recessive disorder of copper metabolism, has been previously mapped to chromosome 13q. Highly informative PCR-based polymorphic microsatellites closely linked to the WD locus (WND) at 13q14.3, as well as sequence-tagged sites for closely linked loci, are described. Two polymorphic microsatellite markers at D13S118 and D13S119 lie within 3 cM of WND. Two others (D13S227 and D13S228) were derived from a yeast artificial chromosome containing D13S31. These were placed on a genetic linkage map of chromosome 13 and were typed in 74 multiplex WD families from a variety of geographic origins (166 affected members). Multipoint analysis provides very high odds that the location of WND is between D13S31/D13S227/D13S228 and D13S59. Previous odds with RFLP-based markers were only 7:1 more likely than any other location. Current odds are 5,000:1. Preclinical testing of three cases of WD by using the highly informative polymorphic microsatellite markers is described. The markers described ensure that 95% of predictive tests using DNA from both parents and from at least one affected sib will have an accuracy >99%. 29 refs., 2 figs., 3 tabs.

  8. Reductions in (/sup 3/H)nicotinic acetylcholine binding in Alzheimer's disease and Parkinson's disease: an autoradiographic study

    SciTech Connect (OSTI)

    Whitehouse, P.J.; Martino, A.M.; Wagster, M.V.; Price, D.L.; Mayeux, R.; Atack, J.R.; Kellar, K.J.

    1988-05-01

    In Alzheimer's disease (AD) and Parkinson's disease (PD), dysfunction in the basal forebrain cholinergic system is accompanied by a consistent loss of presynaptic cholinergic markers in cortex, but changes in cholinergic receptor binding sites are poorly understood. In the present study, we used receptor autoradiography to map the distribution of nicotinic (/sup 3/H)acetylcholine binding sites in cortices of individuals with AD and PD and matched control subjects. In both diseases, a profound loss of nicotinic receptors occurs in all cortical layers, particularly the deepest layers.

  9. Timing of testing and treatment for asymptomatic diseases

    SciTech Connect (OSTI)

    K?rk?zlar, Eser; Faissol, Daniel M.; Griffin, Paul M.; Swann, Julie L.

    2010-07-01

    Many papers in the medical literature analyze the cost-effectiveness of screening for diseases by comparing a limited number of a priori testing policies under estimated problem parameters. However, this may be insufficient to determine the best timing of the tests or incorporate changes over time. In this paper, we develop and solve a Markov Decision Process (MDP) model for a simple class of asymptomatic diseases in order to provide the building blocks for analysis of a more general class of diseases. We provide a computationally efficient method for determining a cost-effective dynamic intervention strategy that takes into account (i) the results of the previous test for each individual and (ii) the change in the individuals behavior based on awareness of the disease. We demonstrate the usefulness of the approach by applying the results to screening decisions for Hepatitis C (HCV) using medical data, and compare our findings to current HCV screening recommendations.

  10. Update on the Hanford Site Chronic Beryllium Disease Prevention...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    by DOE- EM on March 13, 2013 2 Be CAP Status * Rev. 1 of the Hanford site wide Chronic Beryllium Disease Prevention Program (CBDPP) was approved by DOE March 7, 2012 * Rev....

  11. Array-based detection of genetic alterations associated with disease

    DOE Patents [OSTI]

    Pinkel, Daniel; Albertson, Donna G.; Gray, Joe W.

    2007-09-11

    The present invention relates to DNA sequences from regions of copy number change on chromosome 20. The sequences can be used in hybridization methods for the identification of chromosomal abnormalities associated with various diseases.

  12. Inexpensive handheld tests for diseases are in sight

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Cai has a passion: to use her expertise in biochemistry and genetics to create a non-invasive, point-of-care diagnostic device for disease detection. In following her passion, she...

  13. Science On Tap - Understanding HIV and Infectious Diseases

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Science On Tap - Understanding HIV and Infectious Diseases Science On Tap - Understanding HIV and Infectious Diseases WHEN: Sep 17, 2015 5:30 PM - 7:00 PM WHERE: UnQuarked Wine Room 145 Central Park Square, Los Alamos, New Mexico, 87544 USA SPEAKER: Ruy Ribeiro, Los Alamos National Laboratory CONTACT: Jessica Privette 505 667-0375 CATEGORY: Bradbury INTERNAL: Calendar Login Science On Tap - Every Third Thursday Event Description Science On Tap happens every third Thursday of the month, featuring

  14. Engineering disease resistance with pectate lyase-like genes

    DOE Patents [OSTI]

    Vogel, John; Somerville, Shauna

    2005-03-08

    A mutant gene coding for pectate lyase and homologs thereof is provided, which when incorporated in transgenic plants effect an increased level disease resistance in such plants. Also is provided the polypeptide sequence for the pectate lyase of the present invention. Methods of obtaining the mutant gene, producing transgenic plants which include the nucleotide sequence for the mutant gene and producing improved disease resistance in a crop of such transgenic plants are also provided.

  15. LANL spinoff receives NIH grant for respiratory disease diagnostic device

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    LANL spinoff receives NIH grant LANL spinoff receives NIH grant for respiratory disease diagnostic device Mesa Tech has been awarded a grant to develop an inexpensive, instrument-free, nucleic-acid testing device to diagnose various respiratory diseases in record time. October 19, 2011 Los Alamos National Laboratory sits on top of a once-remote mesa in northern New Mexico with the Jemez mountains as a backdrop to research and innovation covering multi-disciplines from bioscience, sustainable

  16. Software speeds detection of diseases and cancer-treatment targets

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Software speeds detection of diseases Software speeds detection of diseases and cancer-treatment targets The Lab has released an updated version of software that is now capable of identifying DNA from viruses and all parts of the Tree of Life. December 1, 2014 With Sequedex, a laptop computer can analyze DNA sequences faster than any current DNA sequencer can create them. With Sequedex, a laptop computer can analyze DNA sequences faster than any current DNA sequencer can create them. Contact

  17. Cerebrospinal Fluid Proteome of Patients with Acute Lyme Disease

    SciTech Connect (OSTI)

    Angel, Thomas E.; Jacobs, Jon M.; Smith, Robert P.; Pasternack, Mark S.; Elias, Susan; Gritsenko, Marina A.; Shukla, Anil K.; Gilmore, Edward C.; McCarthy, Carol; Camp, David G.; Smith, Richard D.

    2012-10-05

    Acute Lyme disease results from transmission of and infection by the bacterium Borrelia burgdorferi following a tick bite. During acute infection, bacteria can disseminate to the central nervous system (CNS) leading to the development of Lyme meningitis. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing for a deep view into the proteome for a cohort of patients with early-disseminated Lyme disease and CSF inflammation leading to the identification of proteins that reflect host responses, which are distinct for subjects with acute Lyme disease. Additionally, we analyzed individual patient samples and quantified changes in protein abundance employing label-free quantitative mass spectrometry based methods. The measured changes in protein abundances reflect the impact of acute Lyme disease on the CNS as presented in CSF. We have identified 89 proteins that differ significantly in abundance in patients with acute Lyme disease. A number of the differentially abundant proteins have been found to be localized to brain synapse and thus constitute important leads for better understanding of the neurological consequence of disseminated Lyme disease.

  18. Airborne spread of foot-and-mouth disease - model intercomparison

    SciTech Connect (OSTI)

    Gloster, J; Jones, A; Redington, A; Burgin, L; Sorensen, J H; Turner, R; Dillon, M; Hullinger, P; Simpson, M; Astrup, P; Garner, G; Stewart, P; D'Amours, R; Sellers, R; Paton, D

    2008-09-04

    Foot-and-mouth disease is a highly infectious vesicular disease of cloven-hoofed animals caused by foot-and-mouth disease virus. It spreads by direct contact between animals, by animal products (milk, meat and semen), by mechanical transfer on people or fomites and by the airborne route - with the relative importance of each mechanism depending on the particular outbreak characteristics. Over the years a number of workers have developed or adapted atmospheric dispersion models to assess the risk of foot-and-mouth disease virus spread through the air. Six of these models were compared at a workshop hosted by the Institute for Animal Health/Met Office during 2008. A number of key issues emerged from the workshop and subsequent modelling work: (1) in general all of the models predicted similar directions for 'at risk' livestock with much of the remaining differences strongly related to differences in the meteorological data used; (2) determination of an accurate sequence of events is highly important, especially if the meteorological conditions vary substantially during the virus emission period; and (3) differences in assumptions made about virus release, environmental fate, and subsequent infection can substantially modify the size and location of the downwind risk area. Close relationships have now been established between participants, which in the event of an outbreak of disease could be readily activated to supply advice or modelling support.

  19. Remote sensing, global warming, and vector-borne disease

    SciTech Connect (OSTI)

    Wood, B.; Beck, L.; Dister, S.; Lobitz, B.

    1997-12-31

    The relationship between climate change and the pattern of vector-borne disease can be viewed at a variety of spatial and temporal scales. At one extreme are changes such as global warming, which are continental in scale and occur over periods of years, decades, or longer. At the opposite extreme are changes associated with severe weather events, which can occur at local and regional scales over periods of days, weeks, or months. Key ecological factors affecting the distribution of vector-borne diseases include temperature, precipitation, and habitat availability, and their impact on vectors, pathogens, reservoirs, and hosts. Global warming can potentially alter these factors, thereby affecting the spatial and temporal patterns of disease.

  20. Investigation of saliva of patients with periodontal disease using NAA

    SciTech Connect (OSTI)

    Zamboni, C. B.; Metairon, S.; Medeiros, I. M. M. A.

    2013-05-06

    In this study the non-stimulated whole saliva of 26 healthy subjects (mean age 33.9 {+-} 11.0 years, range: 26 to 49 years) and 11 patients with periodontal disease (mean age 41.7 {+-} 11.5 years; range 29 to 55 years) was investigated using Neutron Activation Analysis (NAA) technique. The samples were obtained from donors at Sao Paulo city (Brazil). The analyses were performed in the nuclear reactor IEA-R1 (3.5-4.5MW, pool type) at IPEN/CNEN-SP (Brazil). Considerable changes in Ca and S saliva's level were identified in patients with periodontal disease suggesting they can be used as monitors of periodontal diseases.

  1. Association between environmental exposure to pesticides and neurodegenerative diseases

    SciTech Connect (OSTI)

    Parron, Tesifon; Requena, Mar; Hernandez, Antonio F.; Alarcon, Raquel

    2011-11-15

    Preliminary studies have shown associations between chronic pesticide exposure in occupational settings and neurological disorders. However, data on the effects of long-term non-occupational exposures are too sparse to allow any conclusions. This study examines the influence of environmental pesticide exposure on a number of neuropsychiatric conditions and discusses their underlying pathologic mechanisms. An ecological study was conducted using averaged prevalence rates of Alzheimer's disease, Parkinson's disease, multiple sclerosis, cerebral degeneration, polyneuropathies, affective psychosis and suicide attempts in selected Andalusian health districts categorized into areas of high and low environmental pesticide exposure based on the number of hectares devoted to intensive agriculture and pesticide sales per capita. A total of 17,429 cases were collected from computerized hospital records (minimum dataset) between 1998 and 2005. Prevalence rates and the risk of having Alzheimer's disease, Parkinson's disease, multiple sclerosis and suicide were significantly higher in districts with greater pesticide use as compared to those with lower pesticide use. The multivariate analyses showed that the population living in areas with high pesticide use had an increased risk for Alzheimer's disease and suicide attempts and that males living in these areas had increased risks for polyneuropathies, affective disorders and suicide attempts. In conclusion, this study supports and extends previous findings and provides an indication that environmental exposure to pesticides may affect the human health by increasing the incidence of certain neurological disorders at the level of the general population. -- Highlights: Black-Right-Pointing-Pointer Environmental exposure to pesticides and neurodegenerative-psychiatric disorders. Black-Right-Pointing-Pointer Increased risk for Alzheimer's disease and suicide attempts in high exposure areas. Black-Right-Pointing-Pointer Males from

  2. Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Xia, Jing; Rocke, David M.; Perry, George; Ray, Monika

    2014-01-01

    In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less

  3. Disease Diagnostics Research at Los Alamos National Laboratory

    SciTech Connect (OSTI)

    Mukundan, Harshini

    2015-04-10

    Human evolution and persistent diseases have existed side-by-side. A recent concern is the re-emergence of tuberculosis, one of the oldest and most challenging diseases known to man. Effective diagnosis can save lives and prevent its spread. This talk will cover how our immune system discriminates between itself and foreign entities and how a new laboratory and nature inspired strategy can detect tuberculosis equally well in human and animal populations. The approach is being extended to other applications such as the identification of strep throat and respiratory infections.

  4. Device, array, and methods for disease detection and analysis

    DOE Patents [OSTI]

    Rao, Rupa S.; Lane, Stephen M.; Matthews, Dennis L.; Coleman, Matthew A.

    2016-06-14

    A device and array coupled to capture molecules are provided. Specifically, the device and array can be used for detecting the presence and concentration of biomarkers in a sample from a subject. The device and array can also allow the use of a method for scoring a sample for, e.g., the purpose of diagnosing a disease. The method can also be advantageous to applications where there is a need to accurately determine the disease stage of a subject for the purpose of making therapeutic decisions.

  5. Compositions and Methods for the Treatment of Pierce's Disease

    DOE Patents [OSTI]

    Gupta, Goutam

    2008-10-07

    Chimeric anti-microbial proteins, compositions, and methods for the therapeutic and prophylactic treatment of plant diseases caused by the bacterial pathogen Xylella fastidiosa are provided. The anti-microbial proteins of the invention generally comprise a surface recognition domain polypeptide, capable of binding to a bacterial membrane component, fused to a bacterial lysis domain polypeptide, capable of affecting lysis or rupture of the bacterial membrane, typically via a fused polypeptide linker. In particular, methods and compositions for the treatment or prevention of Pierce's disease of grapevines are provided. Methods for the generation of transgenic Vitus vinefera plants expressing xylem-secreted anti-microbial chimeras are also provided.

  6. Azasugar inhibitors as pharmacological chaperones for Krabbe disease

    SciTech Connect (OSTI)

    Hill, Chris H.; Viuff, Agnete H.; Spratley, Samantha J.; Salamone, Stéphane; Christensen, Stig H.; Read, Randy J.; Moriarty, Nigel W.; Jensen, Henrik H.; Deane, Janet E.

    2015-03-23

    Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lipid component of myelin, and psychosine, a cytotoxic metabolite. Mutations of GALC that cause misfolding of the protein may be responsive to pharmacological chaperone therapy (PCT), whereby small molecules are used to stabilize these mutant proteins, thus correcting trafficking defects and increasing residual catabolic activity in cells. Here we describe a new approach for the synthesis of galacto-configured azasugars and the characterization of their interaction with GALC using biophysical, biochemical and crystallographic methods. We identify that the global stabilization of GALC conferred by azasugar derivatives, measured by fluorescence-based thermal shift assays, is directly related to their binding affinity, measured by enzyme inhibition. X-ray crystal structures of these molecules bound in the GALC active site reveal which residues participate in stabilizing interactions, show how potency is achieved and illustrate the penalties of aza/iminosugar ring distortion. The structure–activity relationships described here identify the key physical properties required of pharmacological chaperones for Krabbe disease and highlight the potential of azasugars as stabilizing agents for future enzyme replacement therapies. This work lays the foundation for new drug-based treatments of Krabbe disease.

  7. Ventilation assessment of an infectious disease ward housing TB patients

    SciTech Connect (OSTI)

    Crandall, M.S.; Hughes, R.T.

    1996-05-01

    The National Institute for Occupational Safety and Health (NIOSH) assisted the National Center for Infectious Diseases and the National Center for Prevention Services, Centers for Disease Control (CDC), in their investigation of nosocomial transmission of tuberculosis (TB) at a Veterans Administration Medical Center. NIOSH was asked to determine whether ventilation requirements expected of TB patient isolation facilities were being met. In the Infectious Disease ward (513), 24 staff were given a tuberculin skin test (TST) in the summer of 1991. Eleven (46%) were positive then, and 13 were negative. Ten of the 13 testing negative in 1991 were retested within a year, and 5 (50%) converted to a positive TST. NIOSH investigators made ventilation measurements on Ward 5B, an infectious diseases ward housing patients with acquired immune deficiency syndrome (AIDS), two of them with infectious TB, to determine the status of the systems serving the area. Airflow measurements showed that in all the single-patient rooms, exhaust airflow was essentially zero. The average supply airflow varied above and below the designed value. These rooms were all positively pressurized, which would be recommended for the isolation of infectious patients. Based on the measurements made during this evaluation, it was recommended that a separate isolation facility be constructed in the hospital to house infectious patients. Interim corrective measures for the systems in place were also recommended.

  8. Azasugar inhibitors as pharmacological chaperones for Krabbe disease

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Hill, Chris H.; Viuff, Agnete H.; Spratley, Samantha J.; Salamone, Stéphane; Christensen, Stig H.; Read, Randy J.; Moriarty, Nigel W.; Jensen, Henrik H.; Deane, Janet E.

    2015-03-23

    Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lipid component of myelin, and psychosine, a cytotoxic metabolite. Mutations of GALC that cause misfolding of the protein may be responsive to pharmacological chaperone therapy (PCT), whereby small molecules are used to stabilize these mutant proteins, thus correcting trafficking defects and increasing residual catabolic activity in cells. Here we describe amore » new approach for the synthesis of galacto-configured azasugars and the characterization of their interaction with GALC using biophysical, biochemical and crystallographic methods. We identify that the global stabilization of GALC conferred by azasugar derivatives, measured by fluorescence-based thermal shift assays, is directly related to their binding affinity, measured by enzyme inhibition. X-ray crystal structures of these molecules bound in the GALC active site reveal which residues participate in stabilizing interactions, show how potency is achieved and illustrate the penalties of aza/iminosugar ring distortion. The structure–activity relationships described here identify the key physical properties required of pharmacological chaperones for Krabbe disease and highlight the potential of azasugars as stabilizing agents for future enzyme replacement therapies. This work lays the foundation for new drug-based treatments of Krabbe disease.« less

  9. Possible mechanisms for arsenic-induced proliferative diseases

    SciTech Connect (OSTI)

    Wetterhahn, K.E.; Dudek, E.J.; Shumilla, J.A.

    1996-12-31

    Possible mechanisms for cardiovascular diseases and cancers which have been observed on chronic exposure to arsenic have been investigated. We tested the hypothesis that nonlethal levels of arsenic are mitogenic, cause oxidative stress, increase nuclear translocation of trans-acting factors, and increase expression of genes involved in proliferation. Cultured porcine vascular (from aorta) endothelial cells were used as a model cell system to study the effects of arsenic on the target cells for cardiovascular diseases. Treatment of postconfluent cell cultures with nonovertly toxic concentrations of arsenite increased DNA synthesis, similar to the mitogenic response observed with hydrogen peroxide. Within 1 hour of adding noncytotoxic concentrations of arsenite, cellular levels of oxidants increased relative to control levels, indicating that arsenite promotes cellular oxidations. Arsenite treatment increased nuclear translocation of NF-{kappa}B, an oxidative stress-responsive transcription factor, in a manner similar to that observed with hydrogen peroxide. Pretreatment of intact cells with the antioxidants N-acetylcysteine and dimethylfumarate prevented the arsenite-induced increases in cellular oxidant formation and NF-KB translocation. Arsenite had little or no effect on binding of NF-KB to its DNA recognition sequence in vitro, indicating that it is unlikely that arsenite directly affects NF-KB. The steady-state mRNA levels of intracellular adhesion molecule and urokinase-like plasminogen activator, genes associated with the active endothelial phenotype in arteriosclerosis and cancer metastasis, were increased by nontoxic concentrations of arsenite. These data suggest that arsenite promotes proliferative diseases like heart disease and cancer by activating oxidant-sensitive endothelial cell signaling and gene expression. It is possible that antioxidant therapy would be useful in preventing arsenic-induced cardiovascular disease and cancer.

  10. The Human Phenotype Ontology: Semantic Unification of Common and Rare Disease

    SciTech Connect (OSTI)

    Groza, Tudor; Khler, Sebastian; Moldenhauer, Dawid; Vasilevsky, Nicole; Baynam, Gareth; Zemojtel, Tomasz; Schriml, LynnMarie; Kibbe, WarrenAlden; Schofield, PaulN.; Beck, Tim; Vasant, Drashtti; Brookes, AnthonyJ.; Zankl, Andreas; Washington, NicoleL.; Mungall, ChristopherJ.; Lewis, SuzannaE.; Haendel, Melissa A.; Parkinson, Helen; Robinson, PeterN.

    2015-06-25

    The Human Phenotype Ontology (HPO) is widely used in the rare disease community for differential diagnostics, phenotype-driven analysis of next-generation sequence-variation data, and translational research, but a comparable resource has not been available for common disease. Here, we have developed a concept-recognition procedure that analyzes the frequencies of HPO disease annotations as identified in over five million PubMed abstracts by employing an iterative procedure to optimize precision and recall of the identified terms. We derived disease models for 3,145 common human diseases comprising a total of 132,006 HPO annotations. The HPO now comprises over 250,000 phenotypic annotations for over 10,000 rare and common diseases and can be used for examining the phenotypic overlap among common diseases that share risk alleles, as well as between Mendelian diseases and common diseases linked by genomic location. The annotations, as well as the HPO itself, are freely available.

  11. Using Genomics to Study Human Biology and Disease

    SciTech Connect (OSTI)

    Myers, Ricard M.

    2005-04-06

    The Human Genome Project culminated in April 2003 with the finished DNA sequence of all of the human chromosomes. This book of information, particularly in conjunction with the genome sequences of many other organisms, has already begun to revolutionize the way that biomedical scientists study our species. The identification of essentially all of our genes has provided a template upon which researchers can discover basic processes that govern cells, organs, and the whole organism, and to understand the fundamental causes of the diseases that occur when something goes wrong with a gene or a set of genes. The Genome Project has already made it possible to identify the genes that are defective in more than 1,000 rare inherited diseases, and these discoveries have helped to understand the mechanisms of the more common forms of these disorders. This understanding of primary defects in diseases - which is translated as mutations in genes that encode proteins that serve specific functions - is transforming the way that biotechnology and pharmaceutical companies identify drug targets, and a few notable cases have already had a striking impact on specific diseases. In addition, it has become clear that the differential response to drugs in human populations is heavily influenced by genes, and a whole field called pharmacogenetics has begun to identify these genetic factors. Such knowledge will allow physicians to prescribe drugs targeted to each individual, with the potential to increase efficacy and decrease side-effects. Determining the DNA sequence of the human genome and identifying the genes has been an exciting endeavor, but we are only just beginning to understand the treasures present in all of our DNA. My presentation will briefly describe the road we took to get the sequence, as well as the tools that we are developing to unlock its secrets.

  12. Modeling the Molecular Basis of Parkinson's Disease | Argonne Leadership

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Computing Facility Alpha-synuclein pentamer constructed with 4ns molecular dynamics (MD) conformers after equilibration on the membrane with MD. Alpha-synuclein pentamer constructed with 4ns molecular dynamics (MD) conformers after equilibration on the membrane with MD. Modeling the Molecular Basis of Parkinson's Disease PI Name: Igor Tsigelny PI Email: itsigeln@ucsd.edu Institution: University of California-San Diego/SDSC Allocation Program: INCITE Allocation Hours at ALCF: 1.2 Million

  13. Radiological approaches in the evaluation of joint disease in children

    SciTech Connect (OSTI)

    Poznanski, A.K.; Conway, J.J.; Shkolnik, A.; Pachman, L.M.

    1987-04-01

    In summary, the newer technologies in radiology have allowed us to visualize more clearly the manifestation of joint disease in children. The presence of small erosions and cartilage damage can be seen much better with magnetic resonance imaging than with any other modality short of arthrography, a much more invasive examination. Joint effusion, although sometimes visualized with conventional radiography, is probably best recognized with ultrasound or magnetic resonance imaging, although it can be detected with computed tomography as well. For the evaluation of avascular necrosis that can be associated with steroid use in joint disease, bone scintigraphy is a simple, sensitive method. Magnetic resonance may be as or more sensitive and gives additional information as well. In the detection of change with time, conventional radiography probably will remain the standard as it is still the simplest, least expensive examination; however, it has many limitations in specific cases. Bone scintigraphy may be of value in selected cases. Although we have still not had enough experience with magnetic resonance imaging to use it as a way of evaluating progress of joint disease, it promises to be the most sensitive radiologic measure of evaluating progress as small anatomical changes can be detected within the cartilage, which cannot be done easily with other means. 27 references.

  14. Vesicular Disease in 9-Week-Old Pigs Experimentally Infected with Senecavirus A

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Montiel, Nestor; Buckley, Alexandra; Guo, Baoqing; Kulshreshtha, Vikas; VanGeelen, Albert; Hoang, Hai; Rademacher, Christopher; Yoon, Kyoung-Jin; Lager, Kelly

    2016-07-01

    Senecavirus A has been infrequently associated with vesicular disease in swine since 1988. However, clinical disease has not been reproduced after experimental infection with this virus. Here we report vesicular disease in 9-week-old pigs after Sencavirus A infection by the intranasal route under experimental conditions.

  15. Advancements in Orthopedic Intervention: Retrograde Drilling and Bone Grafting of Osteochondral Lesions of the Knee Using Magnetic Resonance Imaging Guidance

    SciTech Connect (OSTI)

    Seebauer, Christian J.; Bail, Hermann J.; Rump, Jens C. Walter, Thula Teichgraeber, Ulf K. M.

    2010-12-15

    Computer-assisted surgery is currently a novel challenge for surgeons and interventional radiologists. Magnetic resonance imaging (MRI)-guided procedures are still evolving. In this experimental study, we describe and assess an innovative passive-navigation method for MRI-guided treatment of osteochondritis dissecans of the knee. A navigation principle using a passive-navigation device was evaluated in six cadaveric knee joint specimens for potential applicability in retrograde drilling and bone grafting of osteochondral lesions using MRI guidance. Feasibility and accuracy were evaluated in an open MRI scanner (1.0 T Philips Panorama HFO MRI System). Interactive MRI navigation allowed precise drilling and bone grafting of osteochondral lesions of the knee. All lesions were hit with an accuracy of 1.86 mm in the coronal plane and 1.4 mm the sagittal plane. Targeting of all lesions was possible with a single drilling. MRI allowed excellent assessment of correct positioning of the cancellous bone cylinder during bone grafting. The navigation device and anatomic structures could be clearly identified and distinguished throughout the entire drilling procedure. MRI-assisted navigation method using a passive navigation device is feasible for the treatment of osteochondral lesions of the knee under MRI guidance and allows precise and safe drilling without exposure to ionizing radiation. This method may be a viable alternative to other navigation principles, especially for pediatric and adolescent patients. This MRI-navigated method is also potentially applicable in many other MRI-guided interventions.

  16. Supratentorial Ependymoma: Disease Control, Complications, and Functional Outcomes After Irradiation

    SciTech Connect (OSTI)

    Landau, Efrat; Boop, Frederick A.; Conklin, Heather M.; Wu, Shengjie; Xiong, Xiaoping; Merchant, Thomas E.

    2013-03-15

    Purpose: Ependymoma is less commonly found in the supratentorial brain and has known clinical and molecular features that are unique. Our single-institution series provides valuable information about disease control for supratentorial ependymoma and the complications of supratentorial irradiation in children. Methods and Materials: A total of 50 children with newly diagnosed supratentorial ependymoma were treated with adjuvant radiation therapy (RT); conformal methods were used in 36 after 1996. The median age at RT was 6.5 years (range, 1-18.9 years). The entire group was characterized according to sex (girls 27), race (white 43), extent of resection (gross-total 46), and tumor grade (anaplastic 28). The conformal RT group was prospectively evaluated for neurologic, endocrine, and cognitive effects. Results: With a median follow-up time of 9.1 years from the start of RT for survivors (range, 0.2-23.2 years), the 10-year progression-free and overall survival were 73% + 7% and 76% + 6%, respectively. None of the evaluated factors was prognostic for disease control. Local and distant failures were evenly divided among the 16 patients who experienced progression. Eleven patients died of disease, and 1 of central nervous system necrosis. Seizure disorders were present in 17 patients, and 4 were considered to be clinically disabled. Clinically significant cognitive effects were limited to children with difficult-to-control seizures. The average values for intelligence quotient and academic achievement (reading, spelling, and math) were within the range of normal through 10 years of follow-up. Central hypothyroidism was the most commonly treated endocrinopathy. Conclusion: RT may be administered with acceptable risks for complications in children with supratentorial ependymoma. These results suggest that outcomes for these children are improving and that complications may be limited by use of focal irradiation methods.

  17. Development of Biomarkers for Chronic Beryllium Disease in Mice

    SciTech Connect (OSTI)

    Gordon, Terry

    2013-01-25

    Beryllium is a strategic metal, indispensable for national defense programs in aerospace, telecommunications, electronics, and weaponry. Exposure to beryllium is an extensively documented occupational hazard that causes irreversible, debilitating granulomatous lung disease in as much as 3 - 5% of exposed workers. Mechanistic research on beryllium exposure-disease relationships has been severely limited by a general lack of a sufficient CBD animal model. We have now developed and tested an animal model which can be used for dissecting dose-response relationships and pathogenic mechanisms and for testing new diagnostic and treatment paradigms. We have created 3 strains of transgenic mice in which the human antigen-presenting moiety, HLA-DP, was inserted into the mouse genome. Each mouse strain contains HLA-DPB1 alleles that confer different magnitude of risk for chronic beryllium disease (CBD): HLA-DPB1*0401 (odds ratio = 0.2), HLA-DPB1*0201 (odds ratio = 15), HLA-DPB1*1701 (odds ratio = 240). Our preliminary work has demonstrated that the *1701 allele, as predicted by human studies, results in the greatest degree of sensitization in a mouse ear swelling test. We have also completed dose-response experiments examining beryllium-induced lung granulomas and identified susceptible and resistant inbred strains of mice (without the human transgenes) as well as quantitative trait loci that may contain gene(s) that modify the immune response to beryllium. In this grant application, we propose to use the transgenic and normal inbred strains of mice to identify biomarkers for the progression of beryllium sensitization and CBD. To achieve this goal, we propose to compare the sensitivity and accuracy of the lymphocyte proliferation test (blood and bronchoalveolar lavage fluid) with the ELISPOT test in the three HLA-DP transgenic mice strains throughout a 6 month treatment with beryllium particles. Because of the availability of high-throughput proteomics, we will also identify

  18. Hanford Site Chronic Beryllium Disease Prevention Program (CBDPP) Contact List

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Chronic Beryllium Disease Prevention Program (CBDPP) Contact List Page 1 of 2 Updated 5/31/16 Primary and Alternate Membership Organization Primary Office Number Cell Number Alternate Office Number Cell Number BAG Fisher, Mark N/A 539-5588 Artzer, Josh 376-2463 430-5062 CHPRC/HAMTC Sherman, Larry 376-6436 438-2171 Spier, Tracy 373-1993 440-9118 CHPRC Bean, Tonya 376-6503 (303) 709-3047 Robinson, Roby Seydel, Scott (509) 699-9307 373-4860 (509) 699-9307 430-0184 CWB&CTC Park, Rick 372-9941

  19. Full-spectrum disease response : beyond just the flu.

    SciTech Connect (OSTI)

    Knazovich, Michael Ward; Cox, Warren B.; Henderson, Samuel Arthur

    2010-04-01

    Why plan beyond the flu: (1) the installation may be the target of bioterrorism - National Laboratory, military base collocated in large population center; and (2) International Airport - transport of infectious agents to the area - Sandia is a global enterprise and staff visit many foreign countries. In addition to the Pandemic Plan, Sandia has developed a separate Disease Response Plan (DRP). The DRP addresses Category A, B pathogens and Severe Acute Respiratory Syndrome (SARS). The DRP contains the Cities Readiness Initiative sub-plan for disbursement of Strategic National Stockpile assets.

  20. Osteogenic Sarcoma of the Maxilla: Neutron Therapy for Unresectable Disease

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Smoron, Geoffrey L.; Lennox, Arlene J.; Mcgee, James L.

    1999-01-01

    Purpose. To present a case study involving the use of fast neutron therapy to treat an extensive unresectable osteogenic sarcoma arising from the left maxilla. Patient. A 14-year-old male presented with a massive tumor producing severe distortion of his facial structures. He had already received six courses of chemotherapy, which had reduced his pain, but had not measurably reduced the tumor. Methods. The patient was treated with 66 MeV fast neutrons to a dose of 20.4 Gy in 13 fractions over 35 days. Results. CT assessments indicate gradually increasing calcification and noticeable reduction of soft-tissue disease in the frontalmore » sinus, orbit and maxillary antrum.There has been some recontouring of the facial structures.The boy conducts an active life, has no pain, and feels well. He was 17 years old at the last follow-up. Discussion. Fast neutrons have a greater biological effectiveness than conventional photon beams. Their use has been associated with improved chance for local control of unresectable disease.This case illustrates their effectiveness in controlling an unusual and aggressive osteogenic sarcoma of the facial bone and sinuses.« less

  1. Bead-based microfluidic immunoassay for diagnosis of Johne's disease

    SciTech Connect (OSTI)

    Wadhwa, Ashutosh [University of Tennessee, Center for Wildlife Health, Department of Forestry; Foote, Robert [ORNL; Shaw, Robert W [ORNL; Eda, Shigetoshi [ORNL

    2012-01-01

    Microfluidics technology offers a platform for development of point-of-care diagnostic devices for various infectious diseases. In this study, we examined whether serodiagnosis of Johne s disease (JD) can be conducted in a bead-based microfluidic assay system. Magnetic micro-beads were coated with antigens of the causative agent of JD, Mycobacterium avium subsp. paratuberculosis. The antigen-coated beads were incubated with serum samples of JD-positive or negative serum samples and then with a fluorescently-labeled secondary antibody (SAB). To confirm binding of serum antibodies to the antigen, the beads were subjected to flow cytometric analysis. Different conditions (dilutions of serum and SAB, types of SAB, and types of magnetic beads) were optimized for a great degree of differentiation between the JD-negative and JD-positive samples. Using the optimized conditions, we tested a well-classified set of 155 serum samples from JD negative and JD-positive cattle by using the bead-based flow cytometric assay. Of 105 JD-positive samples, 63 samples (60%) showed higher antibody binding levels than a cut-off value determined by using antibody binding levels of JD-negative samples. In contrast, only 43-49 JD-positive samples showed higher antibody binding levels than the cut-off value when the samples were tested by commercially-available immunoassays. Microfluidic assays were performed by magnetically immobilizing a number of beads within a microchannel of a glass microchip and detecting antibody on the collected beads by laser-induced fluorescence. Antigen-coated magnetic beads treated with bovine serum sample and fluorescently-labeled SAB were loaded into a microchannel to measure the fluorescence (reflecting level of antibody binding) on the beads in the microfluidic system. When the results of five bovine serum samples obtained with the system were compared to those obtained with the flow cytometer, a high level of correlation (linear regression, r2 = 0.994) was

  2. Ulcerative colitis and steroid-responsive, diffuse interstitial lung disease

    SciTech Connect (OSTI)

    Balestra, D.J.; Balestra, S.T.; Wasson, J.H.

    1988-07-01

    The authors describe a patient with ulcerative colitis and extracolonic manifestations in whom diffuse interstitial pulmonary disease developed that was responsive to glucocorticoid therapy one year after total proctocolectomy. The patient presented in December 1983 with a subacute course marked by cough and progressive exertional dyspnea, abnormal chest examination results, and a chest roentgenogram that revealed diffuse interstitital and alveolar infiltrates. A transbronchial biopsy specimen revealed a polymorphic interstitial infiltrate, mild interstitial fibrosis without apparent intraluminal fibrosis, and no vasculitis, granulomas, or significant eosinophilic infiltration. Within one week of the initiation of daily high-dose steroid therapy, the patient's symptoms dramatically improved; chest roentgenogram and forced vital capacity (60%) improved at a slower rate. All three measures deteriorated when alternate-day prednisone therapy was started but once again improved until the patient was totally asymptomatic, chest roentgenograms were normal, and forced vital capacity was 80% of the predicted value 2 1/2 years later.

  3. Resource Requirements Planning for Hospitals Treating Serious Infectious Disease Cases.

    SciTech Connect (OSTI)

    Vugrin, Eric D.; Verzi, Stephen Joseph; Finley, Patrick D.; Turnquist, Mark A.; Wyte-Lake, Tamar; Griffin, Ann R.; Ricci, Karen J.; Plotinsky, Rachel

    2015-02-01

    This report presents a mathematical model of the way in which a hospital uses a variety of resources, utilities and consumables to provide care to a set of in-patients, and how that hospital might adapt to provide treatment to a few patients with a serious infectious disease, like the Ebola virus. The intended purpose of the model is to support requirements planning studies, so that hospitals may be better prepared for situations that are likely to strain their available resources. The current model is a prototype designed to present the basic structural elements of a requirements planning analysis. Some simple illustrati ve experiments establish the mo del's general capabilities. With additional inve stment in model enhancement a nd calibration, this prototype could be developed into a useful planning tool for ho spital administrators and health care policy makers.

  4. OSTIblog Articles in the disease Topic | OSTI, US Dept of Energy Office of

    Office of Scientific and Technical Information (OSTI)

    Scientific and Technical Information disease Topic Sharing Data Leads to Progress by Nena Moss 19 Aug, 2010 in Personal Perspectives My mother died in March 2010 after a 15-year battle with Alzheimer's, so I pay particular attention to news about this dreadful disease. A recent New York Times article caught my eye: "Sharing of Data Leads to Progress on Alzheimer's." How did sharing data lead to progress on Alzheimer's? A collaborative effort, the Alzheimer's Disease Neuroimaging

  5. Edge effects, not connectivity, determine the incidence and development of a foliar fungal plant disease.

    SciTech Connect (OSTI)

    Johnson, Brenda, L.; Haddad, Nick, M.

    2011-08-01

    Using a model plant-pathogen system in a large-scale habitat corridor experiment, we found that corridors do not facilitate the movement of wind-dispersed plant pathogens, that connectivity of patches does not enhance levels of foliar fungal plant disease, and that edge effects are the key drivers of plant disease dynamics. Increased spread of infectious disease is often cited as a potential negative effect of habitat corridors used in conservation, but the impacts of corridors on pathogen movement have never been tested empirically. Using sweet corn (Zea mays) and southern corn leaf blight (Cochliobolus heterostrophus) as a model plant-pathogen system, we tested the impacts of connectivity and habitat fragmentation on pathogen movement and disease development at the Savannah River Site, South Carolina, USA. Over time, less edgy patches had higher proportions of diseased plants, and distance of host plants to habitat edges was the greatest determinant of disease development. Variation in average daytime temperatures provided a possible mechanism for these disease patterns. Our results show that worries over the potentially harmful effects of conservation corridors on disease dynamics are misplaced, and that, in a conservation context, many diseases can be better managed by mitigating edge effects.

  6. The Human Phenotype Ontology: Semantic Unification of Common and Rare Disease

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Groza, Tudor; Köhler, Sebastian; Moldenhauer, Dawid; Vasilevsky, Nicole; Baynam, Gareth; Zemojtel, Tomasz; Schriml, Lynn Marie; Kibbe, Warren Alden; Schofield, Paul N.; Beck, Tim; et al

    2015-06-25

    The Human Phenotype Ontology (HPO) is widely used in the rare disease community for differential diagnostics, phenotype-driven analysis of next-generation sequence-variation data, and translational research, but a comparable resource has not been available for common disease. Here, we have developed a concept-recognition procedure that analyzes the frequencies of HPO disease annotations as identified in over five million PubMed abstracts by employing an iterative procedure to optimize precision and recall of the identified terms. We derived disease models for 3,145 common human diseases comprising a total of 132,006 HPO annotations. The HPO now comprises over 250,000 phenotypic annotations for over 10,000more »rare and common diseases and can be used for examining the phenotypic overlap among common diseases that share risk alleles, as well as between Mendelian diseases and common diseases linked by genomic location. The annotations, as well as the HPO itself, are freely available.« less

  7. Toxicological and pharmacological concerns on oxidative stress and related diseases

    SciTech Connect (OSTI)

    Saeidnia, Soodabeh; Abdollahi, Mohammad

    2013-12-15

    Although reactive oxygen species (ROS) such as superoxide, hydrogen peroxide and hydroxyl radical are generated as the natural byproduct of normal oxygen metabolism, they can create oxidative damage via interaction with bio-molecules. The role of oxidative stress as a remarkable upstream part is frequently reported in the signaling cascade of inflammation as well as chemo attractant production. Even though hydrogen peroxide can control cell signaling and stimulate cell proliferation at low levels, in higher concentrations it can initiate apoptosis and in very high levels may create necrosis. So far, the role of ROS in cellular damage and death is well documented with implicating in a broad range of degenerative alterations e.g. carcinogenesis, aging and other oxidative stress related diseases (OSRDs). Reversely, it is cleared that antioxidants are potentially able to suppress (at least in part) the immune system and to enhance the normal cellular protective responses to tissue damage. In this review, we aimed to provide insights on diverse OSRDs, which are correlated with the concept of oxidative stress as well as its cellular effects that can be inhibited by antioxidants. Resveratrol, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statins, nebivolol and carvedilol, pentaerythritol tetranitrate, mitochondria-targeted antioxidants, and plant-derived drugs (alone or combined) are the potential medicines that can be used to control OSRD.

  8. Metabonomic Profiling of TASTPM Transgenic Alzheimer's Disease Mouse Model

    SciTech Connect (OSTI)

    Hu, Zeping; Browne, Edward R.; Liu, Tao; Angel, Thomas E.; Ho, Paul C.; Chun Yong Chan, Eric

    2012-12-07

    Identification of molecular mechanisms underlying early stage Alzheimer’s disease (AD) is important for the development of new therapies against and diagnosis of AD. In this study, non-targeted metabotyping of TASTPM transgenic AD mice was performed. The metabolic profiles of both brain and plasma of TASTPM mice were characterized using gas chromatography-mass spectrometry and compared to those of wild type C57BL/6J mice. TASTPM mice were metabolically distinct compared to wild type mice (Q28 Y = 0.587 and 0.766 for PLS-DA models derived from brain and plasma, respectively). A number of metabolites were found to be perturbed in TASTPM mice in both brain (D11 fructose, L-valine, L-serine, L-threonine, zymosterol) and plasma (D-glucose, D12 galactose, linoleic acid, arachidonic acid, palmitic acid and D-gluconic acid). In addition, enzyme immunoassay confirmed that selected endogenous steroids were significantly perturbed in brain (androstenedione and 17-OH-progesterone) and plasma (cortisol and testosterone) of TASTPM mice. Ingenuity pathway analysis revealed that perturbations related to amino acid metabolism (brain), steroid biosynthesis (brain), linoleic acid metabolism (plasma) and energy metabolism (plasma) accounted for the differentiation of TASTPM and wild-type

  9. The temporal patterns of disease severity and prevalence in schistosomiasis

    SciTech Connect (OSTI)

    Ciddio, Manuela; Gatto, Marino Casagrandi, Renato

    2015-03-15

    Schistosomiasis is one of the most widespread public health problems in the world. In this work, we introduce an eco-epidemiological model for its transmission and dynamics with the purpose of explaining both intra- and inter-annual fluctuations of disease severity and prevalence. The model takes the form of a system of nonlinear differential equations that incorporate biological complexity associated with schistosome's life cycle, including a prepatent period in snails (i.e., the time between initial infection and onset of infectiousness). Nonlinear analysis is used to explore the parametric conditions that produce different temporal patterns (stationary, endemic, periodic, and chaotic). For the time-invariant model, we identify a transcritical and a Hopf bifurcation in the space of the human and snail infection parameters. The first corresponds to the occurrence of an endemic equilibrium, while the latter marks the transition to interannual periodic oscillations. We then investigate a more realistic time-varying model in which fertility of the intermediate host population is assumed to seasonally vary. We show that seasonality can give rise to a cascade of period-doubling bifurcations leading to chaos for larger, though realistic, values of the amplitude of the seasonal variation of fertility.

  10. Multi-analyte analysis of saliva biomarkers as predictors of periodontal and pre-implant disease

    DOE Patents [OSTI]

    Braun, Thomas; Giannobile, William V; Herr, Amy E; Singh, Anup K; Shelburne, Charlie

    2015-04-07

    The present invention relates to methods of measuring biomarkers to determine the probability of a periodontal and/or peri-implant disease. More specifically, the invention provides a panel of biomarkers that, when used in combination, can allow determination of the probability of a periodontal and/or peri-implant disease state with extremely high accuracy.

  11. Milk production and distribution in low-dose counties for the Hanford Thyroid Disease Study

    SciTech Connect (OSTI)

    Schimmel, J.G. . Social and Economic Sciences Research Center); Beck, D.M. )

    1992-06-01

    This report identifies sources of milk consumed by residents of Ferry, Okanogan, and Stevens Counties. This information will be used by the Hanford thyroid Disease Study to determine whether thyroid disease has been increased among people exposed to past iodine--131 emissions from Hanford Site Facilities.

  12. Proceedings of the 2nd workshop on lyme disease in the Southeast

    SciTech Connect (OSTI)

    Apperson, C.S.; Levine, J.F.; Snoddy, E.L.

    1993-12-31

    This volume provides author prepared abstracts of oral presentation at the Second Workshop on Lyme Disease in the Southeast head in Raleigh, North Carolina September 7-9, 1993. The 33 presentations covered various aspects of the epidemic including geographical distribution of various species of ticks, transmission risks, Lyme Disease epidemiology, and taxonomic aspects.

  13. Delays in Reducing Waterborne and Water-related Infectious Diseases in China under Climate Change

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Hodges, Maggie; Belle, Jessica; Carlton, Elizabeth; Liang, Song; Li, Huazhong; Luo, Wei; Freeman, Matthew C.; Liu, Yang; Gao, Yang; Hess, Jeremy; et al

    2014-11-02

    Despite China’s rapid progress improving water, sanitation and hygiene (WSH) infrastructure and access, in 2011, 471 million people lacked access to improved sanitation, and 401 million people lacked access to household piped water. Infectious diseases are sensitive to changes in climate, particularly temperature, and WSH conditions. To explore possible impacts of climate change on these diseases in China in 2020 and 2030, we coupled estimates of the temperature sensitivity of diarrheal disease and three vector-borne diseases, temperature projections from global climate models using four emissions pathways, WSH-infrastructure development scenarios and projected demographic changes. By 2030, the projected impacts would delaymore » China’s historically rapid progress toward reducing the burden of WSH-attributable infectious disease by 8-85 months. This developmental delay provides a key summary measure of the impact of climate change in China, and in other societies undergoing rapid social, economic, and environmental change.« less

  14. Delays in Reducing Waterborne and Water-related Infectious Diseases in China under Climate Change

    SciTech Connect (OSTI)

    Hodges, Maggie; Belle, Jessica; Carlton, Elizabeth; Liang, Song; Li, Huazhong; Luo, Wei; Freeman, Matthew C.; Liu, Yang; Gao, Yang; Hess, Jeremy; Remais, Justin V.

    2014-11-02

    Despite China’s rapid progress improving water, sanitation and hygiene (WSH) infrastructure and access, in 2011, 471 million people lacked access to improved sanitation, and 401 million people lacked access to household piped water. Infectious diseases are sensitive to changes in climate, particularly temperature, and WSH conditions. To explore possible impacts of climate change on these diseases in China in 2020 and 2030, we coupled estimates of the temperature sensitivity of diarrheal disease and three vector-borne diseases, temperature projections from global climate models using four emissions pathways, WSH-infrastructure development scenarios and projected demographic changes. By 2030, the projected impacts would delay China’s historically rapid progress toward reducing the burden of WSH-attributable infectious disease by 8-85 months. This developmental delay provides a key summary measure of the impact of climate change in China, and in other societies undergoing rapid social, economic, and environmental change.

  15. Delays in Reducing Waterborne and Water-related Infectious Diseases in China under Climate Change

    SciTech Connect (OSTI)

    Hodges, Maggie; Belle, Jessica; Carlton, Elizabeth; Liang, Song; Li, Huazhong; Luo, Wei; Freeman, Matthew C.; Liu, Yang; Gao, Yang; Hess, Jeremy; Remais, Justin V.

    2014-12-01

    Despite China’s rapid progress improving water, sanitation and hygiene (WSH) infrastructure and access, in 2011, 471 million people lacked access to improved sanitation, and 401 million people lacked access to household piped water. Infectious diseases are sensitive to changes in climate, particularly temperature, and WSH conditions. To explore possible impacts of climate change on these diseases in China in 2020 and 2030, we coupled estimates of the temperature sensitivity of diarrheal disease and three vector-borne diseases, temperature projections from global climate models using four emissions pathways, WSH-infrastructure development scenarios and projected demographic changes. By 2030, the projected impacts would delay China’s historically rapid progress toward reducing the burden of WSH-attributable infectious disease by 8-85 months. This developmental delay provides a key summary measure of the impact of climate change in China, and in other societies undergoing rapid social, economic, and environmental change.

  16. Health Detectives: Uncovering the Mysteries of Disease (LBNL Science at the Theater)

    ScienceCinema (OSTI)

    Bissell, Mina; Canaria, Christie; Celnicker, Susan; Karpen, Gary

    2014-05-06

    In this April 23, 2012 Science at the Theater event, Berkeley Lab scientists discuss how they uncover the mysteries of disease in unlikely places. Speakers and topics include: World-renowned cancer researcher Mina Bissell's pioneering research on the role of the cellular microenvironment in breast cancer has changed the conversation about the disease. How does DNA instability cause disease? To find out, Christie Canaria images neural networks to study disorders such as Huntington's disease. Fruit flies can tell us a lot about ourselves. Susan Celniker explores the fruit fly genome to learn how our genome works. DNA is not destiny. Gary Karpen explores how environmental factors shape genome function and disease through epigenetics.

  17. Mineral density volume gradients in normal and diseased human tissues

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Djomehri, Sabra I.; Candell, Susan; Case, Thomas; Browning, Alyssa; Marshall, Grayson W.; Yun, Wenbing; Lau, S. H.; Webb, Samuel; Ho, Sunita P.; Aikawa, Elena

    2015-04-09

    Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-raymore » fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.« less

  18. Mineral density volume gradients in normal and diseased human tissues

    SciTech Connect (OSTI)

    Djomehri, Sabra I.; Candell, Susan; Case, Thomas; Browning, Alyssa; Marshall, Grayson W.; Yun, Wenbing; Lau, S. H.; Webb, Samuel; Ho, Sunita P.; Aikawa, Elena

    2015-04-09

    Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.

  19. Disease mapping based on stochastic SIR-SI model for Dengue and Chikungunya in Malaysia

    SciTech Connect (OSTI)

    Samat, N. A.; Ma'arof, S. H. Mohd Imam

    2014-12-04

    This paper describes and demonstrates a method for relative risk estimation which is based on the stochastic SIR-SI vector-borne infectious disease transmission model specifically for Dengue and Chikungunya diseases in Malaysia. Firstly, the common compartmental model for vector-borne infectious disease transmission called the SIR-SI model (susceptible-infective-recovered for human populations; susceptible-infective for vector populations) is presented. This is followed by the explanations on the stochastic SIR-SI model which involve the Bayesian description. This stochastic model then is used in the relative risk formulation in order to obtain the posterior relative risk estimation. Then, this relative estimation model is demonstrated using Dengue and Chikungunya data of Malaysia. The viruses of these diseases are transmitted by the same type of female vector mosquito named Aedes Aegypti and Aedes Albopictus. Finally, the findings of the analysis of relative risk estimation for both Dengue and Chikungunya diseases are presented, compared and displayed in graphs and maps. The distribution from risk maps show the high and low risk area of Dengue and Chikungunya diseases occurrence. This map can be used as a tool for the prevention and control strategies for both diseases.

  20. Using social media for actionable disease surveillance and outbreak management. A systematic literature review

    SciTech Connect (OSTI)

    Charles-Smith, Lauren E.; Reynolds, Tera L.; Cameron, Mark A.; Conway, Mike; Lau, Eric H. Y.; Olsen, Jennifer M.; Pavlin, Julie A.; Shigematsu, Mika; Streichert, Laura C.; Suda, Katie J.; Corley, Courtney D.; Braunstein, Lidia Adriana

    2015-10-05

    Here, research studies show that social media may be valuable tools in the disease surveillance toolkit used for improving public health professionals’ ability to detect disease outbreaks faster than traditional methods and to enhance outbreak response. A social media work group, consisting of surveillance practitioners, academic researchers, and other subject matter experts convened by the International Society for Disease Surveillance, conducted a systematic primary literature review using the PRISMA framework to identify research, published through February 2013, answering either of the following questions: 1) Can social media be integrated into disease surveillance practice and outbreak management to support and improve public health? 2) Can social media be used to effectively target populations, specifically vulnerable populations, to test an intervention and interact with a community to improve health outcomes? Examples of social media included are Facebook, MySpace, microblogs (e.g., Twitter), blogs, and discussion forums. For Question 1, 33 manuscripts were identified, starting in 2009 with topics on Influenza-like Illnesses (n=15), Infectious Diseases (n = 6), Non-infectious Diseases (n=4), Medication and Vaccines (n=3), and Other (n=5). For Question 2, 32 manuscripts were identified, the first in 2000 with topics on Health Risk Behaviors (n=10), Infectious Diseases (n = 3), Non-infectious Diseases (n=9), and Other (n=10). The literature on the use of social media to support public health practice has identified many gaps and biases in current knowledge. Despite the potential for success identified in exploratory studies, there are limited studies on interventions and little use of social media in practice. However, information gleaned from the articles demonstrates the effectiveness of social media in supporting and improving public health and in identifying target populations for intervention. A primary recommendation resulting from the review is to

  1. Using social media for actionable disease surveillance and outbreak management. A systematic literature review

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Charles-Smith, Lauren E.; Reynolds, Tera L.; Cameron, Mark A.; Conway, Mike; Lau, Eric H. Y.; Olsen, Jennifer M.; Pavlin, Julie A.; Shigematsu, Mika; Streichert, Laura C.; Suda, Katie J.; et al

    2015-10-05

    Here, research studies show that social media may be valuable tools in the disease surveillance toolkit used for improving public health professionals’ ability to detect disease outbreaks faster than traditional methods and to enhance outbreak response. A social media work group, consisting of surveillance practitioners, academic researchers, and other subject matter experts convened by the International Society for Disease Surveillance, conducted a systematic primary literature review using the PRISMA framework to identify research, published through February 2013, answering either of the following questions: 1) Can social media be integrated into disease surveillance practice and outbreak management to support and improvemore » public health? 2) Can social media be used to effectively target populations, specifically vulnerable populations, to test an intervention and interact with a community to improve health outcomes? Examples of social media included are Facebook, MySpace, microblogs (e.g., Twitter), blogs, and discussion forums. For Question 1, 33 manuscripts were identified, starting in 2009 with topics on Influenza-like Illnesses (n=15), Infectious Diseases (n = 6), Non-infectious Diseases (n=4), Medication and Vaccines (n=3), and Other (n=5). For Question 2, 32 manuscripts were identified, the first in 2000 with topics on Health Risk Behaviors (n=10), Infectious Diseases (n = 3), Non-infectious Diseases (n=9), and Other (n=10). The literature on the use of social media to support public health practice has identified many gaps and biases in current knowledge. Despite the potential for success identified in exploratory studies, there are limited studies on interventions and little use of social media in practice. However, information gleaned from the articles demonstrates the effectiveness of social media in supporting and improving public health and in identifying target populations for intervention. A primary recommendation resulting from the review

  2. Using Social Media for Actionable Disease Surveillance and Outbreak Management: A Systematic Literature Review

    SciTech Connect (OSTI)

    Charles-Smith, Lauren E.; Reynolds, Tera; Cameron, Mark; Conway, Mike; Lau, Eric H.; Olsen, Jennifer; Pavlin, Julie A.; Shigematsu, Mika; Streichert, Laura; Suda, Katie; Corley, Courtney D.

    2015-10-05

    Research studies show that social media may be valuable tools in the disease surveillance toolkit used for improving public health professionals ability to detect disease outbreaks faster than traditional methods and to enhance outbreak response. A social media work group, consisting of surveillance practitioners, academic researchers, and other subject matter experts convened by the International Society for Disease Surveillance, conducted a systematic primary literature review using the PRISMA framework to identify research, published through February 2013, answering either of the following questions: 1) Can social media be integrated into disease surveillance practice and outbreak management to support and improve public health? 2) Can social media be used to effectively target populations, specifically vulnerable populations, to test an intervention and interact with a community to improve health outcomes? Examples of social media included are Facebook, MySpace, microblogs (e.g., Twitter), blogs, and discussion forums. For Question 1, 33 manuscripts were identified, starting in 2009 with topics on Influenza-like Illnesses (n=15), Infectious Diseases (n = 6), Non-infectious Diseases (n=4), Medication and Vaccines (n=3), and Other (n=5). For Question 2, 32 manuscripts were identified, the first in 2000 with topics on Health Risk Behaviors (n=10), Infectious Diseases (n = 3), Non-infectious Diseases (n=9), and Other (n=10). The literature on the use of social media to support public health practice has identified many gaps and biases in current knowledge. Despite the potential for success identified in exploratory studies, there are limited studies on interventions and little use of social media in practice. However, information gleaned from the articles demonstrates the effectiveness of social media in supporting and improving public health and in identifying target populations for intervention. A primary recommendation resulting from the review is to identify

  3. Whole-Genome Sequences of Two Borrelia afzelii and Two Borrelia garinii Lyme Disease Agent Isolates

    SciTech Connect (OSTI)

    Casjens, S.R.; Dunn, J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Fraser-Liggett, C. M.; Schutzer, S. E.

    2011-12-01

    Human Lyme disease is commonly caused by several species of spirochetes in the Borrelia genus. In Eurasia these species are largely Borrelia afzelii, B. garinii, B. burgdorferi, and B. bavariensis sp. nov. Whole-genome sequencing is an excellent tool for investigating and understanding the influence of bacterial diversity on the pathogenesis and etiology of Lyme disease. We report here the whole-genome sequences of four isolates from two of the Borrelia species that cause human Lyme disease, B. afzelii isolates ACA-1 and PKo and B. garinii isolates PBr and Far04.

  4. Integrating Heterogeneous Healthcare Datasets and Visual Analytics for Disease Bio-surveillance and Dynamics

    SciTech Connect (OSTI)

    Ramanathan, Arvind; Pullum, Laura L; Steed, Chad A; Quinn, Shannon; Chennubhotla, Chakra; Parker, Tara L

    2013-01-01

    n this paper, we present an overview of the big data chal- lenges in disease bio-surveillance and then discuss the use of visual analytics for integrating data and turning it into knowl- edge. We will explore two integration scenarios: (1) combining text and multimedia sources to improve situational awareness and (2) enhancing disease spread model data with real-time bio-surveillance data. Together, the proposed integration methodologies can improve awareness about when, where and how emerging diseases can affect wide geographic regions.

  5. Speaker for Nov. 1 Lecture to Discuss Deadliest Viral Diseases | Jefferson

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Lab Speaker for Nov. 1 Lecture to Discuss Deadliest Viral Diseases Speaker for Nov. 1 Lecture to Discuss Deadliest Viral Diseases NEWPORT NEWS, Va., Oct. 27, 2011 - A noted scientist will discuss some of the world's deadliest viruses as guest speaker at Jefferson Lab's Fall Science Series lecture to be held at the lab on Tuesday, Nov. 1. Susan Fisher-Hoch, a virologist and epidemiologist from the University of Texas School of Public Health will present: Studying Deadly Diseases. She will

  6. Global warming and the potential spread of vector-borne diseases

    SciTech Connect (OSTI)

    Patz, J.

    1996-12-31

    Climatic factors influence many vector-borne infectious diseases, in addition to demographic, biological, and ecological determinants. The United Nation`s Intergovernmental Panel on Climate Change (IPCC) estimates an unprecedented global rise of 2.0 C by the year 2100. Of major concern is that these changes can affect the spread of many serious infectious diseases, including malaria and dengue fever. Global warming would directly affect disease transmission by shifting the mosquito`s geographic range, increasing reproductive and biting rates, and shortening pathogen incubation period. Human migration and damage to health infrastructures from the projected increase in climate variability and sea level rise could indirectly contribute to disease transmission. A review of this literature, as well as preliminary data from ongoing studies will be presented.

  7. In utero and early life arsenic exposure in relation to long-term health and disease

    SciTech Connect (OSTI)

    Farzan, Shohreh F.; Karagas, Margaret R.; Chen, Yu

    2013-10-15

    Background: There is a growing body of evidence that prenatal and early childhood exposure to arsenic from drinking water can have serious long-term health implications. Objectives: Our goal was to understand the potential long-term health and disease risks associated with in utero and early life exposure to arsenic, as well as to examine parallels between findings from epidemiological studies with those from experimental animal models. Methods: We examined the current literature and identified relevant studies through PubMed by using combinations of the search terms “arsenic”, “in utero”, “transplacental”, “prenatal” and “fetal”. Discussion: Ecological studies have indicated associations between in utero and/or early life exposure to arsenic at high levels and increases in mortality from cancer, cardiovascular disease and respiratory disease. Additional data from epidemiologic studies suggest intermediate effects in early life that are related to risk of these and other outcomes in adulthood. Experimental animal studies largely support studies in humans, with strong evidence of transplacental carcinogenesis, atherosclerosis and respiratory disease, as well as insight into potential underlying mechanisms of arsenic's health effects. Conclusions: As millions worldwide are exposed to arsenic and evidence continues to support a role for in utero arsenic exposure in the development of a range of later life diseases, there is a need for more prospective studies examining arsenic's relation to early indicators of disease and at lower exposure levels. - Highlights: • We review in utero and early-life As exposure impacts on lifelong disease risks. • Evidence indicates that early-life As increases risks of lung disease, cancer and CVD. • Animal work largely parallels human studies and may lead to new research directions. • Prospective studies and individual exposure assessments with biomarkers are needed. • Assessing intermediary endpoints may

  8. Independent Oversight Inspection of the Hanford Site Chronic Beryllium Disease Prevention Program

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Independent Oversight Inspection of the Hanford Site Chronic Beryllium Disease Prevention Program June 2010 Office of Independent Oversight Office of Health, Safety and Security Office of Health, Safety and Security HSS x Hanford Site Chronic Beryllium Disease Prevention Program | i Abbreviations iii Executive Summary v 1 Introduction 1 2 Management and Oversight 3 3 Findings Requiring Corrective Action 14 4 Conclusions and Cross-Cutting Opportunities for Improvement 17 Appendix A - Supplemental

  9. Periostin differentially induces proliferation, contraction and apoptosis of primary Dupuytren's disease and adjacent palmar fascia cells

    SciTech Connect (OSTI)

    Vi, Linda; Feng, Lucy; Zhu, Rebecca D.; Wu, Yan; Lawson Health Research Institute, London, Ontario ; Satish, Latha; Gan, Bing Siang; Lawson Health Research Institute, London, Ontario; Department of Surgery, University of Western Ontario, London, Ontario; Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario; Department of Medical Biophysics, University of Western Ontario, London, Ontario ; O'Gorman, David B.

    2009-12-10

    Dupuytren's disease, (DD), is a fibroproliferative condition of the palmar fascia in the hand, typically resulting in permanent contracture of one or more fingers. This fibromatosis is similar to scarring and other fibroses in displaying excess collagen secretion and contractile myofibroblast differentiation. In this report we expand on previous data demonstrating that POSTN mRNA, which encodes the extra-cellular matrix protein periostin, is up-regulated in Dupuytren's disease cord tissue relative to phenotypically normal palmar fascia. We demonstrate that the protein product of POSTN, periostin, is abundant in Dupuytren's disease cord tissue while little or no periostin immunoreactivity is evident in patient-matched control tissues. The relevance of periostin up-regulation in DD was assessed in primary cultures of cells derived from diseased and phenotypically unaffected palmar fascia from the same patients. These cells were grown in type-1 collagen-enriched culture conditions with or without periostin addition to more closely replicate the in vivo environment. Periostin was found to differentially regulate the apoptosis, proliferation, {alpha} smooth muscle actin expression and stressed Fibroblast Populated Collagen Lattice contraction of these cell types. We hypothesize that periostin, secreted by disease cord myofibroblasts into the extra-cellular matrix, promotes the transition of resident fibroblasts in the palmar fascia toward a myofibroblast phenotype, thereby promoting disease progression.

  10. Percutaneous Cholangioscopy in the Management of Biliary Disease: Experience in 25 Patients

    SciTech Connect (OSTI)

    Hatzidakis, Adam A.; Alexandrakis, George; Kouroumalis, Helias; Gourtsoyiannis, Nicholas C.

    2000-11-15

    Purpose: To present our experience performing percutaneous cholangioscopy in the management of 25 patients with biliary disease.Methods: During the last 3 years, 26 percutaneous cholangioscopies were performed in 25 patients with common bile duct disease (n = 16), intrahepatic ducts disease (n = 6), and gallbladder disease (n = 4). Our patient population group included seven with common bile duct stones, three with intrahepatic lithiasis, and eight with benign strictures (six iatrogenic and two postinflammatory). In four patients malignancy was to be excluded, in two the tumor extent was to be evaluated, whereas in one case the correct placement of a metallic stent needed to be controlled. A 9.9 Fr flexible endoscope URF-P (Olympus, 1.2 mm working channel, 70-cm length) was used.Results: In total, percutaneous cholangioscopy answered 30 diagnostic questions, was technically helpful in 19 cases (performing lithotripsy or biopsy or guiding a wire), and of therapeutic help in 12 (performing stone retrieval). In 24 of 26 cases the therapeutic decision and the patient management changed because of the findings or because of the help of the method. In two cases biliary intervention failed to treat the cause of the disease. No major complication due to the use of the endoscopy was noted.Conclusions: Percutaneous cholangioscopy is a very useful tool in the management of patients with biliary disease. The method can help in diagnosis, in performing complex interventional procedures, and in making or changing therapeutic decisions.

  11. Role of paraoxonase 1 (PON1) in organophosphate metabolism: Implications in neurodegenerative diseases

    SciTech Connect (OSTI)

    Androutsopoulos, Vasilis P.; Kanavouras, Konstantinos; Tsatsakis, Aristidis M.

    2011-11-15

    Organophosphate pesticides are a class of compounds that are widely used in agricultural and rural areas. Paraoxonase 1 (PON1) is a phase-I enzyme that is involved in the hydrolysis of organophosphate esters. Environmental poisoning by organophosphate compounds has been the main driving force of previous research on PON1 enzymes. Recent discoveries in animal models have revealed the important role of the enzyme in lipid metabolism. However although PON1 function is well established in experimental models, the contribution of PON1 in neurodegenerative diseases remains unclear. In this minireview we summarize the involvement of PON1 genotypes in the occurrence of Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. A brief overview of latest epidemiological studies, regarding the two most important PON1 coding region polymorphisms PON1-L55M and PON1-Q192R is presented. Positive and negative associations of PON1 with disease occurrence are reported. Notably the MM and RR alleles contribute a risk enhancing effect for the development of some neurodegenerative diseases, which may be explained by the reduced lipoprotein free radical scavenging activity that may give rise to neuronal damage, through distinct mechanism. Conflicting findings that fail to support this postulate may represent the human population ethnic heterogeneity, different sample size and environmental parameters affecting PON1 status. We conclude that further epidemiological studies are required in order to address the exact contribution of PON1 genome in combination with organophosphate exposure in populations with neurodegenerative diseases.

  12. HepatoProteomics: Applying Proteomic Technologies to the Study of Liver Function and Disease

    SciTech Connect (OSTI)

    Diamond, Deborah L.; Proll, Sean; Jacobs, Jon M.; Chan, Eric Y.; Camp, David G.; Smith, Richard D.; Katze, Michael G.

    2006-08-01

    The wealth of human genome sequence information now available, coupled with technological advances in robotics, nanotechnology, mass spectrometry, and information systems, has given rise to a method of scientific inquiry known as functional genomics. By using these technologies to survey gene expression and protein production on a near global scale, the goal of functional genomics is to assign biological function to genes with currently unknown roles in physiology. This approach carries particular appeal in disease research, where it can uncover the function of previously unknown genes and molecular pathways that are directly involved in disease progression. With this knowledge may come improved diagnostic techniques, prognostic capabilities, and novel therapeutic approaches. In this regard, the continuing evolution of proteomic technologies has resulted in an increasingly greater impact of proteome studies in many areas of research and hepatology is no exception. Our laboratory has been extremely active in this area, applying both genomic and proteomic technologies to the analysis of virus-host interactions in several systems, including the study of hepatitis C virus (HCV) infection and HCV-associated liver disease. Since proteomic technologies are foreign to many hepatologists (and to almost everyone else), this article will provide an overview of proteomic methods and technologies and describe how they're being used to study liver function and disease. We use our studies of HCV infection and HCV-associated liver disease to present an operational framework for performing high throughput proteome analysis and extracting biologically meaningful information.

  13. The Biosurveillance Analytics Resource Directory (BARD): Facilitating the use of epidemiological models for infectious disease surveillance

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Margevicius, Kristen J.; Generous, Nicholas; Abeyta, Esteban; Althouse, Ben; Burkom, Howard; Castro, Lauren; Daughton, Ashlynn; Del Valle, Sara Y.; Fairchild, Geoffrey; Hyman, James M.; et al

    2016-01-28

    Epidemiological modeling for infectious disease is important for disease management and its routine implementation needs to be facilitated through better description of models in an operational context. A standardized model characterization process that allows selection or making manual comparisons of available models and their results is currently lacking. A key need is a universal framework to facilitate model description and understanding of its features. Los Alamos National Laboratory (LANL) has developed a comprehensive framework that can be used to characterize an infectious disease model in an operational context. The framework was developed through a consensus among a panel of subjectmore » matter experts. In this paper, we describe the framework, its application to model characterization, and the development of the Biosurveillance Analytics Resource Directory (BARD; http://brd.bsvgateway.org/brd/), to facilitate the rapid selection of operational models for specific infectious/communicable diseases. We offer this framework and associated database to stakeholders of the infectious disease modeling field as a tool for standardizing model description and facilitating the use of epidemiological models.« less

  14. Multiplexed Molecular Assays for Rapid Rule-Out of Foot-and-Mouth Disease

    SciTech Connect (OSTI)

    Lenhoff, R; Naraghi-Arani, P; Thissen, J; Olivas, J; Carillo, C; Chinn, C; Rasmussen, M; Messenger, S; Suer, L; Smith, S M; Tammero, L; Vitalis, E; Slezak, T R; Hullinger, P J; Hindson, B J; Hietala, S; Crossley, B; Mcbride, M

    2007-06-26

    A nucleic acid-based multiplexed assay was developed that combines detection of foot-and-mouth disease virus (FMDV) with rule-out assays for two other foreign animal diseases and four domestic animal diseases that cause vesicular or ulcerative lesions indistinguishable from FMDV infection in cattle, sheep and swine. The FMDV 'look-alike' diagnostic assay panel contains five PCR and twelve reverse transcriptase PCR (RT-PCR) signatures for a total of seventeen simultaneous PCR amplifications for seven diseases plus incorporating four internal assay controls. It was developed and optimized to amplify both DNA and RNA viruses simultaneously in a single tube and employs Luminex{trademark} liquid array technology. Assay development including selection of appropriate controls, a comparison of signature performance in single and multiplex testing against target nucleic acids, as well of limits of detection for each of the individual signatures is presented. While this assay is a prototype and by no means a comprehensive test for FMDV 'look-alike' viruses, an assay of this type is envisioned to have benefit to a laboratory network in routine surveillance and possibly for post-outbreak proof of freedom from foot-and-mouth disease.

  15. Respiratory diseases research at NIOSH: reviews of research programs of the National Institute for Occupational Safety and Health

    SciTech Connect (OSTI)

    2008-07-01

    Respiratory diseases caused by exposures to dangerous materials in the workplace have tremendous implications for worker health and, by extension, the national economy. The National Institute for Occupational Safety and Health (NIOSH) estimates that deaths from work-related respiratory diseases and cancers account for about 70% of all occupational disease deaths. NIOSH conducts research in order to detect and reduce work-related hazardous exposures, injuries, and diseases; its Respiratory Disease Research Program (RDRP) focuses on respiratory diseases. This National Research Council book reviews the RDRP to evaluate the 1) relevance of its work to improvements in occupational safety and health and 2) the impact of research in reducing workplace respiratory illnesses. The assessment reveals that the program has made essential contributions to preventing occupational respiratory disease. The National Research Council has rated the Program a 5 out of 5 for relevance, and a 4 out of 5 for impact. To further increase its effectiveness, the Respiratory Disease Research Program should continue and expand its current efforts, provide resources for occupational disease surveillance, and include exposure assessment scientists in its activities. There are numerous references to respiratory systems diseases caused by coal mining. 4 apps.

  16. Introduction to Focus Issue: Rhythms and Dynamic Transitions in Neurological Disease: Modeling, Computation, and Experiment

    SciTech Connect (OSTI)

    Kaper, Tasso J. Kramer, Mark A.; Rotstein, Horacio G.

    2013-12-15

    Rhythmic neuronal oscillations across a broad range of frequencies, as well as spatiotemporal phenomena, such as waves and bumps, have been observed in various areas of the brain and proposed as critical to brain function. While there is a long and distinguished history of studying rhythms in nerve cells and neuronal networks in healthy organisms, the association and analysis of rhythms to diseases are more recent developments. Indeed, it is now thought that certain aspects of diseases of the nervous system, such as epilepsy, schizophrenia, Parkinson's, and sleep disorders, are associated with transitions or disruptions of neurological rhythms. This focus issue brings together articles presenting modeling, computational, analytical, and experimental perspectives about rhythms and dynamic transitions between them that are associated to various diseases.

  17. A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm

    SciTech Connect (OSTI)

    Aderem, Alan; Adkins, Joshua N.; Ansong, Charles; Galagan, James; Kaiser, Shari; Korth, Marcus J.; Law, G. L.; McDermott, Jason E.; Proll, Sean; Rosenberger, Carrie; Schoolnik, Gary; Katze, Michael G.

    2011-02-01

    The 20th century was marked by extraordinary advances in our understanding of microbes and infectious disease, but pandemics remain, food and water borne illnesses are frequent, multi-drug resistant microbes are on the rise, and the needed drugs and vaccines have not been developed. The scientific approaches of the pastincluding the intense focus on individual genes and proteins typical of molecular biologyhave not been sufficient to address these challenges. The first decade of the 21st century has seen remarkable innovations in technology and computational methods. These new tools provide nearly comprehensive views of complex biological systems and can provide a correspondingly deeper understanding of pathogen-host interactions. To take full advantage of these innovations, the National Institute of Allergy and Infectious Diseases recently initiated the Systems Biology Program for Infectious Disease Research. As participants of the Systems Biology Program we think that the time is at hand to redefine the pathogen-host research paradigm.

  18. Severe gas bubble disease in a warmwater fishery in the midwestern united states

    SciTech Connect (OSTI)

    Crunkilton, R.L.; Czarnezki, J.M.; Trial, L.

    1980-11-01

    Supersaturation of the water of the Osage River below the Harry S. Truman Dam resulted in an epidemic of gas bubble disease that caused the largest fish kill in the history of Missouri. This is the first recorded evidence of serious supersaturation in the midwestern U.S. Total gas saturation levels up to 139% killed nearly 500,000 fish in the Osage River and the Lake of the Ozarks during April-May 1978. Nitrogen was the primary gas responsible for gas bubble disease mortalities. Instream cage bioassays defined the zone of lethal supersaturation. Significant mortality occurred in pelagic and near-shore species, deepwater species, and bottom-dwelling species. Susceptibility to disease was related to fish size.

  19. Severe gas bubble disease in a warmwater fishery in the midwestern United States

    SciTech Connect (OSTI)

    Crunkilton, R.L.; Czarnezki, J.M.; Trial, L.

    1980-11-01

    Gas bubble disease below Harry S. Truman Dam, sited on the upper Osage River and spilling into Lake of the Ozarks, caused the largest fish kill on record in Missouri. This is the first recorded evidence of serious supersaturation in the Midwest. Total gas saturation levels up to 139% killed nearly a half million fish in the upper 85 km of the Osage Arm, Lake of the Ozarks, during April to June, 1978 and 1979. Gas supersaturation occurred throughout the 150 km of this main-stem reservoir. Nitrogen was the primary gas responsible for gas bubble disease mortalities. Pelagic and near-shore species suffered the earliest and heaviest mortalities, but fish characteristic of deeper waters were increasingly killed as supersaturation persisted. Instream cage bioassays defined the zone of lethal supersaturation. Significant mortality occurred in bottom-dwelling fish of several species, due to long-term intermittent exposure. Susceptibility to gas bubble disease was related to fish size.

  20. Linkage disequilibrium in the region of the autosomal dominant polycystic kidney disease gene (PKD1)

    SciTech Connect (OSTI)

    Snarey, A. ); Thomas, S.; Harris, P.C. ); Schneider, M.C. ); Pound, S.E.; Wright, A.F. ); Barton, N.; Somlo, S.; Germino, G.G.; Reeders, S.T.

    1994-08-01

    The gene for autosomal dominant polycystic kidney disease (PKD1) is located on chromosome 16p, between the flanking markers D16S84 and D16S125 (26.6 prox). This region is 750 kb long and has been cloned. The authors have looked at the association of 10 polymorphic markers from the region, with the disease and with each other. This was done in a set of Scottish families that had previously shown association with D16S94, a marker proximal to the PKD1 region. They report significant association between two CA repeat markers and the disease but have not found evidence for a single founder haplotype in these families, indicating the presence of several mutations in this population. Their results favor a location of the PKD1 gene in the proximal part of the candidate region. 25 refs., 1 fig., 4 tabs.

  1. Serum Proteome Profiles in Stricturing Crohn’s Disease: A pilot study.

    SciTech Connect (OSTI)

    Townsend, Peter; Zhang, Qibin; Shapiro, Jason; Webb-Robertson, Bobbie-Jo M.; Bramer, Lisa M.; Schepmoes, Athena A.; Weitz, Karl K.; Mallette, Meaghan; Moniz, Heather; Bright, Renee; Merrick, Marjorie; Shah, Samir A.; Sands, Bruce E.; Leleiko, Neal

    2015-08-01

    Background: Crohn’s disease (CD) is a form of inflammatory bowel disease (IBD) with different described behaviors, including stricture. At present, there are no laboratory studies that can differentiate stricturing CD from other phenotypes of IBD. We performed a pilot study to examine differences in the proteome among patients with stricturing Crohn’s disease, non-stricturing Crohn’s disease, and ulcerative colitis (UC). Methods: Serum samples were selected from the Ocean State Crohn’s and Colitis Area Registry (OSCCAR), an established cohort of patients with IBD. Crohn’s disease patients with surgically-resected stricture were matched with similar patients with Crohn’s disease without known stricture, and with UC. Serum samples from each patient were digested and analyzed using liquid chromatography-mass spectrometry to characterize the proteome. Statistical analyses were performed to identify peptides and proteins that can differentiate CD with stricture. Results: Samples from 9 patients in each group (27 total patients) were analyzed. Baseline demographic characteristics were similar among the three groups. We quantified 7668 peptides and 897 proteins for analysis. ROC analysis identified a subset of peptides with an area under the curve greater than 0.9, indicating greater separation potential. Partial least squares discriminant analysis was able to distinguish among the three groups with up to 70% accuracy by peptides, and up to 80% accuracy by proteins. We identified the significantly different proteins and peptides, and determined their function based on previously published literature. Conclusions: The serum of patients with stricturing CD, non-stricturing CD, and UC are distinguishable via proteomic analysis. Some of the proteins that differentiate the stricturing phenotype have been implicated in complement activation, fibrinolytic pathways, and lymphocyte adhesion.

  2. Gas Bubble Disease Monitoring and Research of Juvenile Salmonids : Annual Report 1996.

    SciTech Connect (OSTI)

    Maule, Alec G.; Beeman, John W.; Hans, Karen M.; Mesa, M.G.; Haner, P.; Warren, J.J.

    1997-10-01

    This document describes the project activities 1996--1997 contract year. This report is composed of three chapters which contain data and analyses of the three main elements of the project: field research to determine the vertical distribution of migrating juvenile salmonids, monitoring of juvenile migrants at dams on the Snake and Columbia rivers, and laboratory experiments to describe the progression of gas bubble disease signs leading to mortality. The major findings described in this report are: A miniature pressure-sensitive radio transmitter was found to be accurate and precise and, after compensation for water temperature, can be used to determine the depth of tagged-fish to within 0.32 m of the true depth (Chapter 1). Preliminary data from very few fish suggest that depth protects migrating juvenile steelhead from total dissolved gas supersaturation (Chapter 1). As in 1995, few fish had any signs of gas bubble disease, but it appeared that prevalence and severity increased as fish migrated downstream and in response to changing gas supersaturation (Chapter 2). It appeared to gas bubble disease was not a threat to migrating juvenile salmonids when total dissolved gas supersaturation was < 120% (Chapter 2). Laboratory studies suggest that external examinations are appropriate for determining the severity of gas bubble disease in juvenile salmonids (Chapter 3). The authors developed a new method for examining gill arches for intravascular bubbles by clamping the ventral aorta to reduce bleeding when arches were removed (Chapter 3). Despite an outbreak of bacterial kidney disease in the experimental fish, the data indicate that gas bubble disease is a progressive trauma that can be monitored (Chapter 3).

  3. Geek-Up[04.01.2011]: A Discovery to Fight Cancer and Other Diseases |

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Department of Energy 4.01.2011]: A Discovery to Fight Cancer and Other Diseases Geek-Up[04.01.2011]: A Discovery to Fight Cancer and Other Diseases April 1, 2011 - 5:52pm Addthis Two structures of the Mre11-Rad50 complex were solved independently and overlaid, further revealing a flexible hinge in Rad50 near the Mre11 binding site | Courtesy of Lawrence Berkeley National Laboratory Two structures of the Mre11-Rad50 complex were solved independently and overlaid, further revealing a flexible

  4. Suppression of somatic expansion delays the onset of pathophysiology in a mouse model of Huntington’s Disease

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Budworth, Helen; Harris, Faye R.; Williams, Paul; Lee, Do Yup; Holt, Amy; Pahnke, Jens; Szczesny, Bartosz; Acevedo-Torres, Karina; Ayala-Peña, Sylvette; McMurray, Cynthia T.; et al

    2015-08-06

    Huntington’s Disease (HD) is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. The inherited disease allele expresses a toxic protein, and whether further somatic expansion adds to toxicity is unknown. We have created an HD mouse model that resolves the effects of the inherited and somatic expansions. We show here that suppressing somatic expansion substantially delays the onset of disease in littermates that inherit the same disease-length allele. Furthermore, a pharmacological inhibitor, XJB-5-131, inhibits the lengthening of the repeat tracks, and correlates with rescue of motormore » decline in these animals. The results provide evidence that pharmacological approaches to offset disease progression are possible.« less

  5. Suppression of somatic expansion delays the onset of pathophysiology in a mouse model of Huntington’s Disease

    SciTech Connect (OSTI)

    Budworth, Helen; Harris, Faye R.; Williams, Paul; Lee, Do Yup; Holt, Amy; Pahnke, Jens; Szczesny, Bartosz; Acevedo-Torres, Karina; Ayala-Peña, Sylvette; McMurray, Cynthia T.; McKinnon, Peter

    2015-08-06

    Huntington’s Disease (HD) is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. The inherited disease allele expresses a toxic protein, and whether further somatic expansion adds to toxicity is unknown. We have created an HD mouse model that resolves the effects of the inherited and somatic expansions. We show here that suppressing somatic expansion substantially delays the onset of disease in littermates that inherit the same disease-length allele. Furthermore, a pharmacological inhibitor, XJB-5-131, inhibits the lengthening of the repeat tracks, and correlates with rescue of motor decline in these animals. The results provide evidence that pharmacological approaches to offset disease progression are possible.

  6. Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease

    SciTech Connect (OSTI)

    Johnson, Reed F.; Hammoud, Dima A.; Lackemeyer, Matthew G.; Yellayi, Srikanth; Solomon, Jeffrey; Bohannon, Jordan K.; Janosko, Krisztina B.; Jett, Catherine; Cooper, Kurt; Blaney, Joseph E.; Jahrling, Peter B.

    2015-07-15

    Cowpox virus (CPXV) inoculation of nonhuman primates (NHPs) has been suggested as an alternate model for smallpox (Kramski et al., 2010, PLoS One, 5, e10412). Previously, we have demonstrated that intrabronchial inoculation of CPXV-Brighton Red (CPXV-BR) into cynomolgus monkeys resulted in a disease that shared many similarities to smallpox; however, severe respiratory tract disease was observed (Smith et al., 2011, J. Gen. Virol.). Here we describe the course of disease after small particle aerosol exposure of rhesus monkeys using computed tomography (CT) to monitor respiratory disease progression. Subjects developed a severe respiratory disease that was uniformly lethal at 5.7 log{sub 10} PFU of CPXV-BR. CT indicated changes in lung architecture that correlated with changes in peripheral blood monocytes and peripheral oxygen saturation. While the small particle aerosol inoculation route does not accurately mimic human smallpox, the data suggest that CT can be used as a tool to monitor real-time disease progression for evaluation of animal models for human diseases. - Highlights: • Small particle aerosol exposure of rhesus results in a severe respiratory disease. • CT findings correlated with peripheral oxygen saturation and monocyte increases. • Virus dissemination was limited and mainly confined to the respiratory tract. • CT provides insight into pathogenesis to aid development of animal models of disease.

  7. Higher coronary heart disease and heart attack morbidity in Appalachian coal mining regions

    SciTech Connect (OSTI)

    Hendryx, M.; Zullig, K.J.

    2009-11-15

    This study analyzes the U.S. 2006 Behavioral Risk Factor Surveillance System survey data (N = 235,783) to test whether self-reported cardiovascular disease rates are higher in Appalachian coal mining counties compared to other counties after control for other risks. Dependent variables include self-reported measures of ever (1) being diagnosed with cardiovascular disease (CVD) or with a specific form of CVD including (2) stroke, (3) heart attack, or (4) angina or coronary heart disease (CHD). Independent variables included coal mining, smoking, BMI, drinking, physician supply, diabetes co-morbidity, age, race/ethnicity, education, income, and others. SUDAAN Multilog models were estimated, and odds ratios tested for coal mining effects. After control for covariates, people in Appalachian coal mining areas reported significantly higher risk of CVD (OR = 1.22, 95% CI = 1.14-1.30), angina or CHO (OR = 1.29, 95% C1 = 1.19-1.39) and heart attack (OR = 1.19, 95% C1 = 1.10-1.30). Effects were present for both men and women. Cardiovascular diseases have been linked to both air and water contamination in ways consistent with toxicants found in coal and coal processing. Future research is indicated to assess air and water quality in coal mining communities in Appalachia, with corresponding environmental programs and standards established as indicated.

  8. Implementation Guide for use with 10 CFR Part 850, Chronic Beryllium Disease Prevention Program

    Broader source: Directives, Delegations, and Requirements [Office of Management (MA)]

    2001-01-04

    The Department of Energy (DOE) has established regulatory requirements for the Chronic Beryllium Disease Prevention Program (CBDPP) in Title 10 of the Code of Federal Regulations (CFR), Part 850 (10 CFR 850) [64 Federal Register (FR) 68854]. Supersedes DOE G 440.1-7. Certified 9-23-10.

  9. Genomics-enabled sensor platform for rapid detection of viruses related to disease outbreak.

    SciTech Connect (OSTI)

    Brozik, Susan Marie; Manginell, Ronald Paul; Moorman, Matthew Wallace; Xiao, Xiaoyin; Edwards, Thayne L.; Anderson, John Moses; Pfeifer, Kent Bryant; Branch, Darren W.; Wheeler, David Roger; Polsky, Ronen; Lopez, DeAnna M.; Ebel, Gregory D.; Prasad, Abhishek N.; Brozik, James A.; Rudolph, Angela R.; Wong, Lillian P.

    2013-09-01

    Bioweapons and emerging infectious diseases pose growing threats to our national security. Both natural disease outbreak and outbreaks due to a bioterrorist attack are a challenge to detect, taking days after the outbreak to identify since most outbreaks are only recognized through reportable diseases by health departments and reports of unusual diseases by clinicians. In recent decades, arthropod-borne viruses (arboviruses) have emerged as some of the most significant threats to human health. They emerge, often unexpectedly, from cryptic transmission foci causing localized outbreaks that can rapidly spread to multiple continents due to increased human travel and trade. Currently, diagnosis of acute infections requires amplification of viral nucleic acids, which can be costly, highly specific, technically challenging and time consuming. No diagnostic devices suitable for use at the bedside or in an outbreak setting currently exist. The original goals of this project were to 1) develop two highly sensitive and specific diagnostic assays for detecting RNA from a wide range of arboviruses; one based on an electrochemical approach and the other a fluorescent based assay and 2) develop prototype microfluidic diagnostic platforms for preclinical and field testing that utilize the assays developed in goal 1. We generated and characterized suitable primers for West Nile Virus RNA detection. Both optical and electrochemical transduction technologies were developed for DNA-RNA hybridization detection and were implemented in microfluidic diagnostic sensing platforms that were developed in this project.

  10. Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Canini, Laetitia; DebRoy, Swati; Mariño, Zoe; Conway, Jessica M.; Crespo, Gonzalo; Navasa, Miquel; D’Amato, Massimo; Ferenci, Peter; Cotler, Scott J.; Forns, Xavier; et al

    2014-06-10

    HCV kinetic analysis and modeling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to εmax) was fit to viral kinetic data. Our results show that baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001). Amore » biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, εmax, was significantly (p≤0.032) associated with increasing severity of liver disease (εmax[s.e.]=0.86[0.05], εmax=0.69[0.06] and εmax=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, SE=0.18/day]). HCV-infected cell loss rate (δ[SE]=0.62/day[0.05/day]) was high and similar among groups. We conclude that the high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.« less

  11. Milk production and distribution in low-dose counties for the Hanford Thyroid Disease Study. Hanford Environmental Dose Reconstruction Project

    SciTech Connect (OSTI)

    Schimmel, J.G.; Beck, D.M.

    1992-06-01

    This report identifies sources of milk consumed by residents of Ferry, Okanogan, and Stevens Counties. This information will be used by the Hanford thyroid Disease Study to determine whether thyroid disease has been increased among people exposed to past iodine--131 emissions from Hanford Site Facilities.

  12. SU-D-204-06: Dose and Image Quality Evaluation of a Low-Dose Slot-Scanning X-Ray System for Pediatric Orthopedic Studies

    SciTech Connect (OSTI)

    Liu, Z; Hoerner, M; Lamoureux, R; Rill, L; Arreola, M

    2015-06-15

    Purpose: Children in early teens with scoliosis require repeated radiographic exams over a number of years. The EOS (EOS imaging S.A., Paris, France) is a novel low-dose slot-scanning digital radiographic system designed to produce full-spine images of a free-standing patient. The radiation dose and image quality characteristics of the EOS were evaluated relative to those of a Computed Radiography (CR) system for scoliosis imaging. Methods: For dose evaluation, a full-torso anthropomorphic phantom was scanned five times using the default standard clinical protocols for both the EOS and a CR system, which include both posteroanterior and lateral full-spine views. Optically stimulated luminescent dosimeters (OSLDs), also known as nanoDots™ (Landauer, Inc., Glenwood, IL), were placed on the phantom’s surface to measure entrance skin dose. To assess image quality, MTF curves were generated from sampling the noise levels within the high-contrast regions of a line-pair phantom. Vertical and horizontal distortions were measured for the square line-pair phantom with the EOS system to evaluate the effects of geometric magnification and misalignment with the indicated imaging plane. Results: The entrance skin dose was measured to be 0.4 to 1.1 mGy for the EOS, and 0.7 to 3.6 mGy for the CR study. MTF comparison shows that CR greatly outperforms the EOS, despite both systems having a limiting resolution at 1.8 line-pairs per mm. Vertical distortion was unaffected by phantom positioning, because of the EOS slot-scanning geometry. Horizontal distortion increased linearly with miscentering distance. Conclusion: The EOS system resulted in approximately 70% lower radiation dose than CR for full-spine images. Image quality was found to be inferior to CR. Further investigation is required to see if EOS system is an acceptable modality for performing clinically diagnostic scoliosis examinations.

  13. Septal myocardial perfusion imaging with thallium-201 in the diagnosis of proximal left anterior descending coronary artery disease

    SciTech Connect (OSTI)

    Pichard, A.D.; Wiener, I.; Martinez, E.; Horowitz, S.; Patterson, R.; Meller, J.; Goldsmith, S.J.; Gorlin, R.; Herman, M.V.

    1981-07-01

    The use of myocardial perfusion imaging (MPI) to identify obstructive coronary disease of the left anterior descending coronary artery proximal to the first septal perforator (prox LAD) was studied in 60 patients. Perfusion of the septum and anteroapical areas with thallium-201 injected during exercise was compared to results of coronary arteriography. Septal MPI defect was found in 92.3% of patients with obstruction of the proximal LAD, 27.7% of patients with obstruction of LAD distal to first septal perforator, 0% in patients with obstructions involving right or circumflex arteries, and in 10.5% of patients without coronary disease. Anteroapical MPI defects were found with similar frequency in the three groups with obstructive coronary disease. Septal MPI defect had a sensitivity of 92.3% and specificity of 85.4% in the diagnosis of proximal LAD disease. Normal septal perfusion with thallium-201 virtually excluded proximal LAD disease.

  14. Portable microfluidic raman system for rapid, label-free early disease signature detection

    SciTech Connect (OSTI)

    Wu, Meiye; Davis, Ryan Wesley; Hatch, Anson

    2015-09-01

    In the early stages of infection, patients develop non-specific or no symptoms at all. While waiting for identification of the infectious agent, precious window of opportunity for early intervention is lost. The standard diagnostics require affinity reagents and sufficient pathogen titers to reach the limit of detection. In the event of a disease outbreak, triaging the at-risk population rapidly and reliably for quarantine and countermeasure is more important than the identification of the pathogen by name. To expand Sandia's portfolio of Biological threat management capabilities, we will utilize Raman spectrometry to analyze immune subsets in whole blood to rapidly distinguish infected from non-infected, and bacterial from viral infection, for the purpose of triage during an emergency outbreak. The goal of this one year LDRD is to determine whether Raman spectroscopy can provide label-free detection of early disease signatures, and define a miniaturized Raman detection system meeting requirements for low- resource settings.

  15. Occupational obstructive airway diseases in Germany: Frequency and causes in an international comparison

    SciTech Connect (OSTI)

    Latza, U.; Baur, X.

    2005-08-01

    Occupational inhalative exposures contribute to a significant proportion of obstructive airway diseases (OAD), namely chronic obstructive pulmonary disease (COPD) and asthma. The number of occupational OAD in the German industrial sector for the year 2003 are presented. Other analyses of surveillance data were retrieved from Medline. Most confirmed reports of OAD are cases of sensitizer induced occupational asthma (625 confirmed cases) followed by COPD in coal miners (414 cases), irritant induced occupational asthma (156 cases), and isocyanate asthma (54 cases). Main causes of occupational asthma in Germany comprise flour/flour constituents (35.9%), food/feed dust (9.0%), and isocyanates (6.5%). Flour and grain dust is a frequent cause of occupational asthma in most European countries and South Africa. Isocyanates are still a problem worldwide. Although wide differences in the estimated incidences between countries exist due to deficits in the coverage of occupational OAD, the high numbers necessitate improvement of preventive measures.

  16. Determining the risk of cardiovascular disease using ion mobility of lipoproteins

    DOE Patents [OSTI]

    Benner, W. Henry; Krauss, Ronald M.; Blanche, Patricia J.

    2010-05-11

    A medical diagnostic method and instrumentation system for analyzing noncovalently bonded agglomerated biological particles is described. The method and system comprises: a method of preparation for the biological particles; an electrospray generator; an alpha particle radiation source; a differential mobility analyzer; a particle counter; and data acquisition and analysis means. The medical device is useful for the assessment of human diseases, such as cardiac disease risk and hyperlipidemia, by rapid quantitative analysis of lipoprotein fraction densities. Initially, purification procedures are described to reduce an initial blood sample to an analytical input to the instrument. The measured sizes from the analytical sample are correlated with densities, resulting in a spectrum of lipoprotein densities. The lipoprotein density distribution can then be used to characterize cardiac and other lipid-related health risks.

  17. Mechanisms of disease: epithelial-mesenchymal transition and back again: does cellular plasticity fuel neoplastic progression?

    SciTech Connect (OSTI)

    Bissell, Mina J; Turley, Eva A.; Veiseh, Mandana; Radisky, Derek C.; Bissell, Mina J.

    2008-02-13

    Epithelial-mesenchymal transition (EMT) is a conversion that facilitates organ morphogenesis and tissue remodeling in physiological processes such as embryonic development and wound healing. A similar phenotypic conversion is also detected in fibrotic diseases and neoplasia, which is associated with disease progression. EMT in cancer epithelial cells often seems to be an incomplete and bi-directional process. In this Review, we discuss the phenomenon of EMT as it pertains to tumor development, focusing on exceptions to the commonly held rule that EMT promotes invasion and metastasis. We also highlight the role of the RAS-controlled signaling mediators, ERK1, ERK2 and PI3-kinase, as microenvironmental responsive regulators of EMT.

  18. Disease Mutations in Rab7 Result in Unregulated Nucleotide Exchange and Inappropriate Activation

    SciTech Connect (OSTI)

    B McCray; E Skordalakes; J Taylor

    2011-12-31

    Rab GTPases are molecular switches that orchestrate vesicular trafficking, maturation and fusion by cycling between an active, GTP-bound form, and an inactive, GDP-bound form. The activity cycle is coupled to GTP hydrolysis and is tightly controlled by regulatory proteins. Missense mutations of the GTPase Rab7 cause a dominantly inherited axonal degeneration known as Charcot-Marie-Tooth type 2B through an unknown mechanism. We present the 2.8 A crystal structure of GTP-bound L129F mutant Rab7 which reveals normal conformations of the effector binding regions and catalytic site, but an alteration to the nucleotide binding pocket that is predicted to alter GTP binding. Through extensive biochemical analysis, we demonstrate that disease-associated mutations in Rab7 do not lead to an intrinsic GTPase defect, but permit unregulated nucleotide exchange leading to both excessive activation and hydrolysis-independent inactivation. Consistent with augmented activity, mutant Rab7 shows significantly enhanced interaction with a subset of effector proteins. In addition, dynamic imaging demonstrates that mutant Rab7 is abnormally retained on target membranes. However, we show that the increased activation of mutant Rab7 is counterbalanced by unregulated, GTP hydrolysis-independent membrane cycling. Notably, disease mutations are able to rescue the membrane cycling of a GTPase-deficient mutant. Thus, we demonstrate that disease mutations uncouple Rab7 from the spatial and temporal control normally imposed by regulatory proteins and cause disease not by a gain of novel toxic function, but by misregulation of native Rab7 activity.

  19. "Artificial" brains, electrical grids, and disease modeling: Los Alamos

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    science discoveries unveiled September 15 Science discoveries unveiled "Artificial" brains, electrical grids, and disease modeling: Los Alamos science discoveries unveiled September 15 The event is an opportunity for business leaders and community members to learn about where science is heading, as well as for students to discover potential new career directions. September 8, 2009 Los Alamos National Laboratory sits on top of a once-remote mesa in northern New Mexico with the Jemez

  20. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    SciTech Connect (OSTI)

    Lake, April D.; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lu, Zhenqiang; Lehman-McKeeman, Lois D.; Cherrington, Nathan J.

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the classical (neutral) and alternative (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ? Altered hepatic bile acid composition is observed in progressive NAFLD. ? Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ? Increased levels of taurine and conjugated bile acids are observed in

  1. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

    SciTech Connect (OSTI)

    Wu, Weibin; Institutes of Biomedical Science, Fudan University, Shanghai 200032 ; Zhu, Bo; Peng, Xiaomin; Zhou, Meiling; Jia, Dongwei; Gu, Jianxin; Institutes of Biomedical Science, Fudan University, Shanghai 200032

    2014-01-03

    Highlights: FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR attenuated alcohol-induced liver injury and steatosis. Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients.

  2. A support vector machine classifier reduces interscanner variation in the HRCT classification of regional disease pattern in diffuse lung disease: Comparison to a Bayesian classifier

    SciTech Connect (OSTI)

    Chang, Yongjun; Lim, Jonghyuck; Kim, Namkug; Seo, Joon Beom; Lynch, David A.

    2013-05-15

    Purpose: To investigate the effect of using different computed tomography (CT) scanners on the accuracy of high-resolution CT (HRCT) images in classifying regional disease patterns in patients with diffuse lung disease, support vector machine (SVM) and Bayesian classifiers were applied to multicenter data. Methods: Two experienced radiologists marked sets of 600 rectangular 20 Multiplication-Sign 20 pixel regions of interest (ROIs) on HRCT images obtained from two scanners (GE and Siemens), including 100 ROIs for each of local patterns of lungs-normal lung and five of regional pulmonary disease patterns (ground-glass opacity, reticular opacity, honeycombing, emphysema, and consolidation). Each ROI was assessed using 22 quantitative features belonging to one of the following descriptors: histogram, gradient, run-length, gray level co-occurrence matrix, low-attenuation area cluster, and top-hat transform. For automatic classification, a Bayesian classifier and a SVM classifier were compared under three different conditions. First, classification accuracies were estimated using data from each scanner. Next, data from the GE and Siemens scanners were used for training and testing, respectively, and vice versa. Finally, all ROI data were integrated regardless of the scanner type and were then trained and tested together. All experiments were performed based on forward feature selection and fivefold cross-validation with 20 repetitions. Results: For each scanner, better classification accuracies were achieved with the SVM classifier than the Bayesian classifier (92% and 82%, respectively, for the GE scanner; and 92% and 86%, respectively, for the Siemens scanner). The classification accuracies were 82%/72% for training with GE data and testing with Siemens data, and 79%/72% for the reverse. The use of training and test data obtained from the HRCT images of different scanners lowered the classification accuracy compared to the use of HRCT images from the same scanner. For

  3. Changes in Gas Bubble Disease Signs for Migrating Juvenile Salmonids Experimentally Exposed to Supersaturated Gasses, 1996-1997 Progress Report.

    SciTech Connect (OSTI)

    Absolon, Randall F.

    1999-03-01

    This study was designed to answer the question of whether gas bubble disease (GBD) signs change as a result of the hydrostatic conditions juvenile salmonids encounter when they enter the turbine intake of hydroelectric projects during their downstream migration.

  4. Cadmium exposure and cardiovascular disease in the 2005 Korea National Health and Nutrition Examination Survey

    SciTech Connect (OSTI)

    Lee, Mi-Sun; Park, Sung Kyun; Hu, Howard; Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI ; Lee, Sundong; Department of Preventive Medicine, School of Oriental Medicine, Sangji University, Wonju, Kangwon

    2011-01-15

    Background: Limited epidemiologic data are available concerning the cardiovascular effects of cadmium exposure, although recent studies suggest associations with myocardial infarction and peripheral arterial disease. We examined the associations of cadmium exposure with cardiovascular disease in nationally representative general Korean adults. Methods: We used cross-sectional data on blood cadmium and self-reported diagnoses of ischemic heart disease (IHD), stroke, and hypertension in a sub-sample of 1908 adults, aged 20 years and older, who participated in the 2005 Korea National Health and Nutrition Examination Survey (KNHANES). We used survey logistic regression models accounting for the complex sampling design to estimate the odds ratios (OR), adjusting for age, education, income, alcohol, smoking, body mass index, waist circumference, family history of hypertension, blood pressure, and blood lead. Results: The geometric mean of blood cadmium was 1.53 {mu}g/L. After adjusting for potential confounders, an interquartile range (IQR) increase in blood cadmium (0.91 {mu}g/L) was found to be associated with an increased risk for IHD (OR 2.1, 95% confidence interval (CI) 1.3-3.4). An IQR increase in blood cadmium was found to be associated with an elevated risk for hypertension only among men (OR 1.4, 95% CI 1.1-1.8) but not among women. No association was observed with stroke in both genders. Conclusions: These findings suggest that cadmium in blood may be associated with an increased risk for IHD and hypertension in the general Korean adult population.

  5. Rapid Disease Progression With Delay in Treatment of Non-Small-Cell Lung Cancer

    SciTech Connect (OSTI)

    Mohammed, Nasiruddin [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Kestin, Larry Llyn, E-mail: lkestin@beaumont.ed [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Grills, Inga Siiner; Battu, Madhu; Fitch, Dwight Lamar [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Wong, Ching-yee Oliver [Department of Nuclear Medicine, William Beaumont Hospital, Royal Oak, MI (United States); Margolis, Jeffrey Harold [Department of Medical Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Chmielewski, Gary William; Welsh, Robert James [Department of Thoracic Surgery, William Beaumont Hospital, Royal Oak, MI (United States)

    2011-02-01

    Purpose: To assess rate of disease progression from diagnosis to initiation of treatment for Stage I-IIIB non-small-cell lung cancer (NSCLC). Methods and Materials: Forty patients with NSCLC underwent at least two sets of computed tomography (CT) and 18-fluorodeoxyglucose positron emission tomography (PET) scans at various time intervals before treatment. Progression was defined as development of any new lymph node involvement, site of disease, or stage change. Results: Median time interval between first and second CT scans was 13.4 weeks, and between first and second PET scans was 9.0 weeks. Median initial primary maximum tumor dimension (MTD) was 3.5 cm (0.6-8.5 cm) with a median standardized uptake value (SUV) of 13.0 (1.7-38.5). The median MTD increased by a median of 1.0 cm (mean, 1.6 cm) between scans for a median relative MTD increase of 35% (mean, 59%). Nineteen patients (48%) progressed between scans. Rate of any progression was 13%, 31%, and 46% at 4, 8, and 16 weeks, respectively. Upstaging occurred in 3%, 13%, and 21% at these intervals. Distant metastasis became evident in 3%, 13%, and 13% after 4, 8, and 16 weeks, respectively. T and N stage were associated with progression, whereas histology, grade, sex, age, and maximum SUV were not. At 3 years, overall survival for Stage III patients with vs. without progression was 18% vs. 67%, p = 0.05. Conclusions: With NSCLC, treatment delay can lead to disease progression. Diagnosis, staging, and treatment initiation should be expedited. After 4-8 weeks of delay, complete restaging should be strongly considered.

  6. Discovery of Disease Co-occurrence Patterns from Electronic Healthcare Reimbursement Claims Data

    SciTech Connect (OSTI)

    Ramanathan, Arvind; Pullum, Laura L; Hobson, Tanner C; Quinn, Shannon; Chennubhotla, Chakra; Valkova, Silvia

    2014-01-01

    Effective public health surveillance is important for national secu- rity. With novel emerging infectious diseases being reported across different parts of the world, there is a need to build effective bio- surveillance systems that can track, monitor and report such events in a timely manner. Additionally, there is a need to identify sus- ceptible geographic regions/populations where these diseases may have a significant impact and design preemptive strategies to tackle them. With the digitization of health related information through electronic health records (EHR) and electronic healthcare claim re- imbursements (eHCR), there is a tremendous opportunity to ex- ploit these datasets for public health surveillance. In this paper, we present our analysis on the use of eHCR data for bio-surveillance by studying the 2009-2010 H1N1 pandemic flu season. We present a novel approach to extract spatial and temporal patterns of flu in- cidence across the United States (US) from eHCRs and find that a small, but distinct set of break-out patterns govern the flu and asthma incidence rates across the entire country. Further, we ob- serve a distinct temporal lag in the onset of flu when compared to asthma across geographic regions in the US. The patterns extracted from the data collectively indicate how these break-out patterns are coupled, even though the flu represents an infectious disease whereas asthma represents a typical chronic condition. Taken to- gether, our approach demonstrates how mining eHCRs can provide novel insights in tackling public health concerns.

  7. Tracers for monitoring the activity of sodium/glucose cotransporters in health and disease

    DOE Patents [OSTI]

    Wright, Ernest M; Barrio, Jorge R; Hirayama, Bruce A; Kepe, Vladimir

    2014-09-30

    Radiolabeled tracers for sodium/glucose cotransporters (SGLTs), their synthesis, and their use are provided. The tracers are methyl or ethyl pyranosides having an equatorial hydroxyl group at carbon-2 and a C 1 preferred conformation, radiolabeled with .sup.18F, .sup.123I, or .sup.124I, or free hexoses radiolabeled with .sup.18F, .sup.123I, or .sup.124. Also provided are in vivo and in vitro techniques for using these and other tracers as analytical and diagnostic tools to study glucose transport, in health and disease, and to evaluate therapeutic interventions.

  8. Epidemiology and Control of Infectious Diseases of Salmonids in the Columbia River Basin, 1987 Annual Report.

    SciTech Connect (OSTI)

    Fryer, John L.

    1989-01-01

    The Department of Microbiology at Oregon State University with funding from the Bonneville Power Administration has been conducting a study concerning the epidemiology and control of three fish pathogens which cause major disease problems in salmonids of the Columbia River basin. The pathogens studied include Cera to myxa Shasta, the myxosporean parasite which causes ceratomyxosis; Renibacterium salmoninarum, the bacterium which is the etiological agent of bacterial kidney disease; and the rhabdovirus which causes infectious hematopoietic necrosis (IHN). During this project, the host and geographic range of C. Shasta have been more precisely determined and the known geographic range has been significantly expanded. The effects of the parasite on fish migrating through the Columbia River and on their introduction into salt water have been examined. Similar studies have been conducted with R. salmoninarum and it has been shown that bacterial kidney disease occurs at all life stages of salmonids and is responsible for mortality in both fresh and salt water. It has also been demonstrated that different isolates of R. salmoninarum have different antigenic composition. Results of demonstration projects designed to control IHN by using UV treated water for early rearing of salmonid fry were equivocal. The scope of the project was considerably narrowed and focused during the past two years The project has concentrated on a study concerning the biology of C. Shasta and the identification of potential chemotherapeutants for control of bacterial kidney disease. The emphasis of work on C. Shasta has been its pathogenesis. This aspect of the parasite has been investigated using histopathologic and immunologic methodology. Mode of transmission, the nature of the infectious stage, and potential intermediate hosts of the parasite have also been areas of active research. Classes of chemotherapeutants with the highest potential for efficacy against R. salmoninarum have been

  9. Gas bubble disease in smallmouth bass and northern squawfish from the Snake and Columbia Rivers

    SciTech Connect (OSTI)

    Montgomery, J.C.; Becker, C.D.

    1980-11-01

    Supersaturation of the Columbia and Snake River systems was caused by entrainment of air into water spilling over hydroelectric dams. Total gas saturations of 100% or more have occurred during the spring in each river system. External signs of gas bubble diseases were noted in adult Smallmouth bass and northern squawfish collected from the lower Snake and mid-Columbia rivers during 1975-76. Emboli occurred beneath membranes of the opercula body, and fins of 72% of the smallmouth bass and 84% of the northern squawfish. Hemorrhage was also noted on the caudal, anal, and pectoral fins of several fish.

  10. Root Diseases and Exotic Ecosystems: Implications for Long-Term Site Productivity

    SciTech Connect (OSTI)

    Otrosina, W. J.; Garbelotto, M.

    1997-09-01

    Management activities and various land uses have taken place recently that have dramatically altered edaphic and environmental conditions under which forest tree species and ecosystems have evolved. Sequoia giganteum stands, fire suppression in this fire dependent ecosystem has resulted in increased mortality due to Heterobasidion annosum. On hypothesis is that fire suppression results in increased encroachment of true firs, easily infected by S-group Heterobasidion annosum, thereby transferring the disease via root contacts with S. giganteum. Existence of a hybrid with S and P ISG's of H. annosum may be evidence for anthropogenic influences on evolutionary pathways in this pathogen.

  11. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease

    SciTech Connect (OSTI)

    Willing, B.; Halfvarson, J.; Dicksved, J.; Rosenquist, M.; Jarnerot, G.; Engstrand, L.; Tysk, C.; Jansson, J. K

    2008-08-15

    Large inter-individual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease. To reduce variations in exposure during establishment of the gut flora and influence of genotype, we studied the mucosaassociated microbiota of monozygotic twin pairs that were discordant (n=6) or concordant (n=4) for Crohn's disease. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing and quantitative real-time PCR. The microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal Crohn's had a dramatically lower abundance (P<0.001) of Faecalibacterium prausnitzii and increased abundance (P<0.03) of Escherichia coli compared to healthy co-twins and those with Crohn's localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype. The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal Crohn's disease phenotype, distinct from colonic Crohn's disease and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of Crohn's and eventually customized treatment.

  12. Evolution of a genetic disease in an ethnic isolate:. beta. -Thalassemia in the Jews of Kurdistan

    SciTech Connect (OSTI)

    Rund, D.; Cohen, T.; Filon, D.; Rachmilewitz, E.; Oppenheim, A. ); Dowling, C.E.; Warren T.C.; Kazazian, H.H. Jr. ); Barak, I. )

    1991-01-01

    {beta}-Thalassemia is a hereditary disease caused by any of 90 different point mutations in the {beta}-globin gene. Specific populations generally carry a small number of mutations, the most common of which are those that are widely distributed regionally. The present study constitutes an extensive molecular characterization of this disease in a small, highly inbred ethnic group with a high incidence of {beta}-thalassemia-the Jews of Kurdistan. An unusual mutational diversity was observed. In 42 sibships 13 different mutations were identified, of which 3 are newly discovered. Four of the mutations are unique to Kurdish Jews and have not been discovered in any other population. A fifth was found outside Kurdish Jews only in an Iranian from Khuzistan, a region bordering Kurdistan. Two-thirds of the mutant chromosomes carry the mutations unique to Kurdish Jews. The authors traced the origin of the mutations to specific geographic regions within Kurdistan. This information, supported by haplotype analysis, suggests that thalassemia in central Kurdistan (northern Iraq) has evolved primarily from multiple mutational events. They conclude that several evolutionary mechanisms contributed to the evolution of {beta}-thalassemia in this small ethnic isolate.

  13. Proteomic Analysis of Lyme Disease: Global Protein Comparison of Three Strains of Borrelia burgdorferi

    SciTech Connect (OSTI)

    Jacobs, Jon M.; Yang, Xiaohua; Luft, Benjamin J.; Dunn, John J.; Camp, David G.; Smith, Richard D.

    2005-04-01

    The Borrelia burgdorferi spirochete is the causative agent of Lyme disease, the most common tick-borne disease in the United States. It has been studied extensively to help understand its pathogenicity of infection and how it can persist in different mammalian hosts. We report the proteomic analysis of the archetype B. burgdorferi B31 strain and two other strains (ND40, and JD-1) having different Borrelia pathotypes using strong cation exchange fractionation of proteolytic peptides followed by high-resolution, reversed phase capillary liquid chromatography coupled with ion trap tandem mass spectrometric (LC-MS/MS) analysis. Protein identification was facilitated by the availability of the complete B31 genome sequence. A total of 665 Borrelia proteins were identified representing ~38 % coverage of the theoretical B31 proteome. A significant overlap was observed between the identified proteins in direct comparisons between any two strains (>72%), but distinct differences were observed among identified hypothetical and outer membrane proteins of the three strains. Such a concurrent proteomic overview of three Borrelia strains based upon only the B31 genome sequence is shown to provide significant insights into the presence or absence of specific proteins and a broad overall comparison among strains.

  14. Iron and aluminum interaction with amyloid-beta peptides associated with Alzheimer’s disease

    SciTech Connect (OSTI)

    Drochioiu, Gabi; Ion, Laura; Murariu, Manuela; Habasescu, Laura

    2014-10-06

    An elevation in the concentration of heavy metal ions in Alzheimer’s disease (AD) brain has been demonstrated in many studies. Aβ precipitation and toxicity in AD brains seem to be caused by abnormal interactions with neocortical metal ions, especially iron, copper, zinc, and aluminum [1–3]. There is increasing evidence that iron and aluminum ions are involved in the mechanisms that underlie the neurodegenerative diseases [4,5]. However, evidence was brought to demonstrate that some Aβ fragments, at physiological pH, are not able to form binary complexes with Fe(III) ions of sufficient stability to compete with metal hydroxide precipitation [6]. On the contrary, multiple metal ions are known to interact with Aβ peptides [7]. Consequently, we investigated here the interaction of Fe(II/III) and Al(III) ions with some amyloid-β peptides and fragments that results in peptide aggregation and fibrillation [8,9]. Infrared spectroscopy, atomic force microscopy, scanning electron microscopy, electrophoresis and mass spectrometry demonstrated conformational changes of peptides in the presence of such metals.

  15. Evidence for increased recombination near the human insulin gene: implication for disease association studies

    SciTech Connect (OSTI)

    Chakravarti, A.; Elbein, S.C.; Permutt, M.A.

    1986-02-01

    Haplotypes for four new restriction site polymorphisms (detected by Rsa I, Taq I, HincII, and Sac I) and a previously identified DNA length polymorphism (5'FP), all at the insulin locus, have been studied in US Blacks, African Blacks, Caucasians, and Pima Indians. Black populations are polymorphic for all five markers, whereas the other groups are polymorphic for Rsa I, Taq I, and 5'FP only. The data suggest that approx. = 1 in 550 base pairs is variant in this region. The polymorphisms, even though located within 20 kilobases, display low levels of nonrandom association. Population genetic analysis suggests that recombination within this 20-kilobase segment occurs 24 times more frequently than expected if crossing-over occurred uniformly throughout the human genome. These findings suggest that population association between DNA polymorphisms and disease susceptibility genes near the insulin gene or structural mutations in the insulin gene will be weak. Thus, population studies would probably require large sample sizes to detect association. However, the low levels of nonrandom association increase the information content of the locus for linkage studies, which is the best alternative for discovering disease susceptibility genes.

  16. A Semiautomated Framework for Integrating Expert Knowledge into Disease Marker Identification

    SciTech Connect (OSTI)

    Wang, Jing; Webb-Robertson, Bobbie-Jo M.; Matzke, Melissa M.; Varnum, Susan M.; Brown, Joseph N.; Riensche, Roderick M.; Adkins, Joshua N.; Jacobs, Jon M.; Hoidal, John R.; Scholand, Mary Beth; Pounds, Joel G.; Blackburn, Michael R.; Rodland, Karin D.; McDermott, Jason E.

    2013-10-01

    Background. The availability of large complex data sets generated by high throughput technologies has enabled the recent proliferation of disease biomarker studies. However, a recurring problem in deriving biological information from large data sets is how to best incorporate expert knowledge into the biomarker selection process. Objective. To develop a generalizable framework that can incorporate expert knowledge into data-driven processes in a semiautomated way while providing a metric for optimization in a biomarker selection scheme. Methods. The framework was implemented as a pipeline consisting of five components for the identification of signatures from integrated clustering (ISIC). Expert knowledge was integrated into the biomarker identification process using the combination of two distinct approaches; a distance-based clustering approach and an expert knowledge-driven functional selection. Results. The utility of the developed framework ISIC was demonstrated on proteomics data from a study of chronic obstructive pulmonary disease (COPD). Biomarker candidates were identified in a mouse model using ISIC and validated in a study of a human cohort. Conclusions. Expert knowledge can be introduced into a biomarker discovery process in different ways to enhance the robustness of selected marker candidates. Developing strategies for extracting orthogonal and robust features from large data sets increases the chances of success in biomarker identification.

  17. Climate, Environmental, and Socioeconomic Change Weighing up the Balance in Vector-Borne Disease Transmission

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Parham, Paul; Waldock, Johanna; Christophides, George; Hemming, Deborah; Agusto, Folashade; Evans, Katherine J; Fefferman, Nina; Gaff, Holly; Gumel, Abba; LaDeau, Shannon; et al

    2015-01-01

    Arguably one of the most important effects of climate change is the potential impact on human health. While this is likely to take many forms, the implications for future transmission of vector-borne diseases (VBDs), given their ongoing contribution to global disease burden, are both extremely important and highly uncertain. In part, this is due not only to data limitations and methodological challenges when integrating climate-driven VBD models and climate change projections, but, perhaps most crucially, the multitude of epidemiological, ecological, and socioeconomic factors that drive VBD transmission, and this complexity has generated considerable debate over the last 10-15 years. Inmore » this article, and Theme Issue, we seek to elucidate current knowledge around this topic, identify key themes and uncertainties, evaluate ongoing challenges and open research questions, and, crucially, offer some solutions for the field moving forwards. Although many of these challenges are ubiquitous across multiple VBDs, more specific issues also arise in different vector-pathogen systems. This Theme Issue seeks to cover both, reflected in the breadth and depth of the topics and VBD-systems considered, itself strongly indicative of the challenging, but necessary, multidisciplinary nature of this research field.« less

  18. Climate, Environmental, and Socioeconomic Change Weighing up the Balance in Vector-Borne Disease Transmission

    SciTech Connect (OSTI)

    Parham, Paul; Waldock, Johanna; Christophides, George; Hemming, Deborah; Agusto, Folashade; Evans, Katherine J; Fefferman, Nina; Gaff, Holly; Gumel, Abba; LaDeau, Shannon; Lenhart, Suzanne; Mickens, Ronald; Naumova, Elena; Ostfeld, Richard; Ready, Paul; Thomas, Matthew; Velasco-Hernandez, Jorge; Edwin, Michael

    2015-01-01

    Arguably one of the most important effects of climate change is the potential impact on human health. While this is likely to take many forms, the implications for future transmission of vector-borne diseases (VBDs), given their ongoing contribution to global disease burden, are both extremely important and highly uncertain. In part, this is due not only to data limitations and methodological challenges when integrating climate-driven VBD models and climate change projections, but, perhaps most crucially, the multitude of epidemiological, ecological, and socioeconomic factors that drive VBD transmission, and this complexity has generated considerable debate over the last 10-15 years. In this article, and Theme Issue, we seek to elucidate current knowledge around this topic, identify key themes and uncertainties, evaluate ongoing challenges and open research questions, and, crucially, offer some solutions for the field moving forwards. Although many of these challenges are ubiquitous across multiple VBDs, more specific issues also arise in different vector-pathogen systems. This Theme Issue seeks to cover both, reflected in the breadth and depth of the topics and VBD-systems considered, itself strongly indicative of the challenging, but necessary, multidisciplinary nature of this research field.

  19. Hydrogen peroxide impairs autophagic flux in a cell model of nonalcoholic fatty liver disease

    SciTech Connect (OSTI)

    Jiang, Pengtao; University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan District, Beijing 100049 ; Huang, Zhen; Zhao, Hong; Wei, Taotao

    2013-04-19

    Highlights: Free fatty acids exposure induces elevated autophagy. H{sub 2}O{sub 2} inhibits autophagic flux through impairing the fusion between autophagosomes and lysosomes. Inhibition of autophagy potentiates H{sub 2}O{sub 2}-induced cell death. -- Abstract: Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease, but the pathogenesis of NAFLD is not fully clear. The aim of this study was to determine whether autophagy plays a role in the pathogenesis of NAFLD. We found that the levels of autophagy were elevated in hepatoma cells upon exposure to free fatty acids, as confirmed by the increase in the number of autophagosomes. However, exposure of hepatoma cells to H{sub 2}O{sub 2} and TNF-?, two typical second hit factors, increased the initiation of autophagy but inhibited the autophagic flux. The inhibition of autophagy sensitized cells to pro-apoptotic stimuli. Taken together, our results suggest that autophagy acts as a protective mechanism in the pathogenesis of NAFLD and that impairment of autophagy might induce more severe lesions of the liver. These findings will be a benefit to the understanding of the pathogenesis of NAFLD and might suggest a strategy for the prevention and cure of NAFLD.

  20. A Semiautomated Framework for Integrating Expert Knowledge into Disease Marker Identification

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Wang, Jing; Webb-Robertson, Bobbie-Jo M.; Matzke, Melissa M.; Varnum, Susan M.; Brown, Joseph N.; Riensche, Roderick M.; Adkins, Joshua N.; Jacobs, Jon M.; Hoidal, John R.; Scholand, Mary Beth; et al

    2013-01-01

    Background . The availability of large complex data sets generated by high throughput technologies has enabled the recent proliferation of disease biomarker studies. However, a recurring problem in deriving biological information from large data sets is how to best incorporate expert knowledge into the biomarker selection process. Objective . To develop a generalizable framework that can incorporate expert knowledge into data-driven processes in a semiautomated way while providing a metric for optimization in a biomarker selection scheme. Methods . The framework was implemented as a pipeline consisting of five components for the identification of signatures from integrated clustering (ISIC).more » Expert knowledge was integrated into the biomarker identification process using the combination of two distinct approaches; a distance-based clustering approach and an expert knowledge-driven functional selection. Results . The utility of the developed framework ISIC was demonstrated on proteomics data from a study of chronic obstructive pulmonary disease (COPD). Biomarker candidates were identified in a mouse model using ISIC and validated in a study of a human cohort. Conclusions . Expert knowledge can be introduced into a biomarker discovery process in different ways to enhance the robustness of selected marker candidates. Developing strategies for extracting orthogonal and robust features from large data sets increases the chances of success in biomarker identification.« less

  1. Method for detection of dental caries and periodontal disease using optical imaging

    DOE Patents [OSTI]

    Nathel, H.; Kinney, J.H.; Otis, L.L.

    1996-10-29

    A method is disclosed for detecting the presence of active and inactive caries in teeth and diagnosing periodontal disease uses non-ionizing radiation with techniques for reducing interference from scattered light. A beam of non-ionizing radiation is divided into sample and reference beams. The region to be examined is illuminated by the sample beam, and reflected or transmitted radiation from the sample is recombined with the reference beam to form an interference pattern on a detector. The length of the reference beam path is adjustable, allowing the operator to select the reflected or transmitted sample photons that recombine with the reference photons. Thus radiation scattered by the dental or periodontal tissue can be prevented from obscuring the interference pattern. A series of interference patterns may be generated and interpreted to locate dental caries and periodontal tissue interfaces. 7 figs.

  2. Method for detection of dental caries and periodontal disease using optical imaging

    DOE Patents [OSTI]

    Nathel, Howard; Kinney, John H.; Otis, Linda L.

    1996-01-01

    A method for detecting the presence of active and inactive caries in teeth and diagnosing periodontal disease uses non-ionizing radiation with techniques for reducing interference from scattered light. A beam of non-ionizing radiation is divided into sample and reference beams. The region to be examined is illuminated by the sample beam, and reflected or transmitted radiation from the sample is recombined with the reference beam to form an interference pattern on a detector. The length of the reference beam path is adjustable, allowing the operator to select the reflected or transmitted sample photons that recombine with the reference photons. Thus radiation scattered by the dental or periodontal tissue can be prevented from obscuring the interference pattern. A series of interference patterns may be generated and interpreted to locate dental caries and periodontal tissue interfaces.

  3. Low Prevalence of Chronic Beryllium Disease among Workers at a Nuclear Weapons Research and Development Facility

    SciTech Connect (OSTI)

    Arjomandi, M; Seward, J P; Gotway, M B; Nishimura, S; Fulton, G P; Thundiyil, J; King, T E; Harber, P; Balmes, J R

    2010-01-11

    To study the prevalence of beryllium sensitization (BeS) and chronic beryllium disease (CBD) in a cohort of workers from a nuclear weapons research and development facility. We evaluated 50 workers with BeS with medical and occupational histories, physical examination, chest imaging with HRCT (N=49), and pulmonary function testing. Forty of these workers also underwent bronchoscopy for bronchoalveolar lavage (BAL) and transbronchial biopsies. The mean duration of employment at the facility was 18 yrs and the mean latency (from first possible exposure) to time of evaluation was 32 yrs. Five of the workers had CBD at the time of evaluation (based on histology or HRCT); three others had evidence of probable CBD. These workers with BeS, characterized by a long duration of potential Be exposure and a long latency, had a low prevalence of CBD.

  4. Method and system for the diagnosis of disease using retinal image content and an archive of diagnosed human patient data

    DOE Patents [OSTI]

    Tobin, Kenneth W; Karnowski, Thomas P; Chaum, Edward

    2013-08-06

    A method for diagnosing diseases having retinal manifestations including retinal pathologies includes the steps of providing a CBIR system including an archive of stored digital retinal photography images and diagnosed patient data corresponding to the retinal photography images, the stored images each indexed in a CBIR database using a plurality of feature vectors, the feature vectors corresponding to distinct descriptive characteristics of the stored images. A query image of the retina of a patient is obtained. Using image processing, regions or structures in the query image are identified. The regions or structures are then described using the plurality of feature vectors. At least one relevant stored image from the archive based on similarity to the regions or structures is retrieved, and an eye disease or a disease having retinal manifestations in the patient is diagnosed based on the diagnosed patient data associated with the relevant stored image(s).

  5. DEVELOPMENT OF AUTOMATED SOFTWARE PROGRAM FOR THE ANALYSIS OF ALZHEIMER'S DISEASE BETA-AMYLOID SCANS

    SciTech Connect (OSTI)

    Mariotti, Jack; Zubal, George

    2013-12-18

    Study goal: A Phase 1 evaluation of the kinetics, clearance and cerebral distribution of one novel peripheral benzodiazepine receptors(PBR)positron emission tomography (PET) imaging agent, 18F-PBR-111 following intravenous administration in healthy volunteers and Alzheimer's disease (AD) patients. Short title: Evaluation of PET imaging with PBR-111 in HV and AD subjects Proof of Mechanism. Primary Objective: To evaluate the cerebral distribution of PBR-111 positron emission tomography (PET) for detection/exclusion of microglial activation in patients with Alzheimer's disease subjects compared to healthy volunteers. Secondary objectives: - To assess the dynamic uptake and washout of [18F]PBR-111, a potential imaging bio-marker for inflammatory changes in brain, using positron emission tomography in subjects with Alzheimer's disease (AD) and healthy volunteers (HV). - To perform blood metabolite characterization of [18F]PBR-111 in subjects with AD and HV to determine the nature of metabolites in assessment of [18F]-PBR-111 as a PET brain imaging agent. Name of radioactive drug substance: PBR-111 Dose(s): The applied PBR-111 radioactive dose will be up to 5.0 mCi, diluted in a maximum of 10 ml of saline. The radioligand will be administered as a slow intravenous bolus injection (i.e., 6 sec/ml) into a large vein (e.g., antecubital vein). Route of administration: Intravenous injection Duration of treatment: Single administration of a diagnostic agent Indication: PBR-111 positron emission tomography (PET) imaging has the potential to detect microglial activation. In the presence of PBR-111 uptake (representative of microglial activation), inflammation in the brain can be detected. Diagnosis and main criteria for inclusion: Study participants will be HVs and patients diagnosed with probable AD. HVs must be 18 years of age (at least four subjects 50 years of age) and have no evidence of cognitive impairment or other neurologic disease by medical history. The lack of

  6. Disease Control After Reduced Volume Conformal and Intensity Modulated Radiation Therapy for Childhood Craniopharyngioma

    SciTech Connect (OSTI)

    Merchant, Thomas E.; Kun, Larry E.; Hua, Chia-Ho; Wu, Shengjie; Xiong, Xiaoping; Sanford, Robert A.; Boop, Frederick A.

    2013-03-15

    Purpose: To estimate the rate of disease control after conformal radiation therapy using reduced clinical target volume (CTV) margins and to determine factors that predict for tumor progression. Methods and Materials: Eighty-eight children (median age, 8.5 years; range, 3.2-17.6 years) received conformal or intensity modulated radiation therapy between 1998 and 2009. The study group included those prospectively treated from 1998 to 2003, using a 10-mm CTV, defined as the margin surrounding the solid and cystic tumor targeted to receive the prescription dose of 54 Gy. The CTV margin was subsequently reduced after 2003, yielding 2 groups of patients: those treated with a CTV margin greater than 5 mm (n=26) and those treated with a CTV margin less than or equal to 5 mm (n=62). Disease progression was estimated on the basis of additional variables including sex, race, extent of resection, tumor interventions, target volume margins, and frequency of weekly surveillance magnetic resonance (MR) imaging during radiation therapy. Median follow-up was 5 years. Results: There was no difference between progression-free survival rates based on CTV margins (>5 mm vs ≤5 mm) at 5 years (88.1% ± 6.3% vs 96.2% ± 4.4% [P=.6386]). There were no differences based on planning target volume (PTV) margins (or combined CTV plus PTV margins). The PTV was systematically reduced from 5 to 3 mm during the time period of the study. Factors predictive of superior progression-free survival included Caucasian race (P=.0175), no requirement for cerebrospinal fluid shunting (P=.0066), and number of surveillance imaging studies during treatment (P=.0216). Patients whose treatment protocol included a higher number of weekly surveillance MR imaging evaluations had a lower rate of tumor progression. Conclusions: These results suggest that targeted volume reductions for radiation therapy using smaller margins are feasible and safe but require careful monitoring. We are currently investigating

  7. Key residues for the oligomerization of A{beta}42 protein in Alzheimer's disease

    SciTech Connect (OSTI)

    Ngo, Sam; Guo, Zhefeng

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer A{beta} oligomers are neurotoxins and likely the causing agents for Alzheimer's disease. Black-Right-Pointing-Pointer A{beta}42 fusion protein form globular oligomers. Black-Right-Pointing-Pointer A{beta}42 fusion protein oligomers contain SDS-resistant tetramers and hexamers. Black-Right-Pointing-Pointer Cysteine substitutions at residues 31, 32, 34, 39-41 disrupt A{beta}42 oligomerization. -- Abstract: Deposition of amyloid fibrils consisting of amyloid {beta} (A{beta}) protein as senile plaques in the brain is a pathological hallmark of Alzheimer's disease. However, a growing body of evidence shows that soluble A{beta} oligomers correlate better with dementia than fibrils, suggesting that A{beta} oligomers may be the primary toxic species. The structure and oligomerization mechanism of these A{beta} oligomers are crucial for developing effective therapeutics. Here we investigated the oligomerization of A{beta}42 in the context of a fusion protein containing GroES and ubiquitin fused to the N-terminus of A{beta} sequence. The presence of fusion protein partners, in combination with a denaturing buffer containing 8 M urea at pH 10, is unfavorable for A{beta}42 aggregation, thus allowing only the most stable structures to be observed. Transmission electron microscopy showed that A{beta}42 fusion protein formed globular oligomers, which bound weakly to thioflavin T and Congo red. SDS-PAGE shows that A{beta}42 fusion protein formed SDS-resistant hexamers and tetramers. In contrast, A{beta}40 fusion protein remained as monomers on SDS gel, suggesting that the oligomerization of A{beta}42 fusion protein is not due to the fusion protein partners. Cysteine scanning mutagenesis at 22 residue positions further revealed that single cysteine substitutions of the C-terminal hydrophobic residues (I31, I32, L34, V39, V40, and I41) led to disruption of hexamer and tetramer formation, suggesting that hydrophobic interactions between these

  8. The plant decapeptide OSIP108 prevents copper-induced toxicity in various models for Wilson disease

    SciTech Connect (OSTI)

    Spincemaille, Pieter; Pham, Duc-Hung; Chandhok, Gursimran; Verbeek, Jef; Zibert, Andree; Libbrecht, Louis; Schmidt, Hartmut; Esguerra, Camila V.; Witte, Peter A.M. de; Cammue, Bruno P.A.; Cassiman, David; Thevissen, Karin

    2014-10-15

    Background: Wilson disease (WD) is caused by accumulation of excess copper (Cu) due to a mutation in the gene encoding the liver Cu transporter ATP7B, and is characterized by acute liver failure or cirrhosis and neuronal cell death. We investigated the effect of OSIP108, a plant derived decapeptide that prevents Cu-induced apoptosis in yeast and human cells, on Cu-induced toxicity in various mammalian in vitro models relevant for WD and in a Cu-toxicity zebrafish larvae model applicable to WD. Methods: The effect of OSIP108 was evaluated on viability of various cell lines in the presence of excess Cu, on liver morphology of a Cu-treated zebrafish larvae strain that expresses a fluorescent reporter in hepatocytes, and on oxidative stress levels in wild type AB zebrafish larvae. Results: OSIP108 increased not only viability of Cu-treated CHO cells transgenically expressing ATP7B and the common WD-causing mutant ATP7B{sup H1069Q}, but also viability of Cu-treated human glioblastoma U87 cells. Aberrancies in liver morphology of Cu-treated zebrafish larvae were observed, which were further confirmed as Cu-induced hepatotoxicity by liver histology. Injections of OSIP108 into Cu-treated zebrafish larvae significantly increased the amount of larvae with normal liver morphology and decreased Cu-induced production of reactive oxygen species. Conclusions: OSIP108 prevents Cu-induced toxicity in in vitro models and in a Cu-toxicity zebrafish larvae model applicable to WD. General significance: All the above data indicate the potential of OSIP108 as a drug lead for further development as a novel WD treatment. - Highlights: • Wilson disease (WD) is characterized by accumulation of toxic copper (Cu). • OSIP108 increases viability of Cu-treated cellular models applicable to WD. • OSIP108 injections preserve liver morphology of Cu-treated zebrafish larvae. • OSIP108 injections into zebrafish larvae abrogates Cu-induced oxidative stress.

  9. Modeling oscillatory dynamics in brain microcircuits as a way to help uncover neurological disease mechanisms: A proposal

    SciTech Connect (OSTI)

    Skinner, F. K.; Department of Medicine , University of Toronto, 200 Elizabeth Street, Toronto, Ontario M5G 2C4; Department of Physiology, University of Toronto Medical Sciences Building, 3rd Floor, 1 King's College Circle, Toronto, Ontario M5S 1A8 ; Ferguson, K. A.; Department of Physiology, University of Toronto Medical Sciences Building, 3rd Floor, 1 King's College Circle, Toronto, Ontario M5S 1A8

    2013-12-15

    There is an undisputed need and requirement for theoretical and computational studies in Neuroscience today. Furthermore, it is clear that oscillatory dynamical output from brain networks is representative of various behavioural states, and it is becoming clear that one could consider these outputs as measures of normal and pathological brain states. Although mathematical modeling of oscillatory dynamics in the context of neurological disease exists, it is a highly challenging endeavour because of the many levels of organization in the nervous system. This challenge is coupled with the increasing knowledge of cellular specificity and network dysfunction that is associated with disease. Recently, whole hippocampus in vitro preparations from control animals have been shown to spontaneously express oscillatory activities. In addition, when using preparations derived from animal models of disease, these activities show particular alterations. These preparations present an opportunity to address challenges involved with using models to gain insight because of easier access to simultaneous cellular and network measurements, and pharmacological modulations. We propose that by developing and using models with direct links to experiment at multiple levels, which at least include cellular and microcircuit, a cycling can be set up and used to help us determine critical mechanisms underlying neurological disease. We illustrate our proposal using our previously developed inhibitory network models in the context of these whole hippocampus preparations and show the importance of having direct links at multiple levels.

  10. Nanoimaging to Prevent and Treat Alzheimers and Parkinsons Diseases. Scientific/Technical report

    SciTech Connect (OSTI)

    Yuri L. Lyubchenko, PhD, DSc

    2012-12-20

    This project will develop innovative approaches to characterization of the very early stages of protein aggregation that eventually can be translated to the development of early diagnostic tools and efficient treatments for Alzheimers, Parkinsons and Huntingtons diseases. Funding will be used to acquire nanoimaging technology for nanoscale imaging, manipulation and analysis of biomedical materials to develop treatments that will repair disabled proteins and cure diseases that result from protein malfunction, specifically Alzheimers and Parkinsons diseases. Expected outcomes include tests for early diagnosis and therapeutic treatments for these devastating neurological diseases. To elucidate the mechanisms of protein misfolding, we will establish an extensive program of experimental studies using a broad arsenal of advanced nanoscale and traditional techniques that will be integrated with molecular-scale modeling of protein misfolding and the nucleation of aggregate structures. To identify intracellular machinery or/and multicomponent complexes critically involved in protein misfolding, we will characterize interactions between targeted proteins and specific intracellular components or metabolites that impact on protein conformational pathways leading to protein misfolding accompanied by formation of toxic aggregated morphologies. To design innovative nanotechnology tools for the control of intracellular protein misfolding and aggregation processes, we will develop a predictive molecular scale model for intracellular protein misfolding and the formation of toxic aggregates. Verified through experimental studies, the objective is to establish an enabling foundation for the engineering of novel molecular diagnostics and therapeutics for various cellular pathologies.

  11. Analyzing and modeling the kinetics of amyloid beta pores associated with Alzheimer’s disease pathology

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Ullah, Ghanim; Demuro, Angelo; Parker, Ian; Pearson, John E.; Xu, Shang -Zhong

    2015-09-08

    Amyloid beta (Aβ) oligomers associated with Alzheimer’s disease (AD) form Ca2+-permeable plasma membrane pores, leading to a disruption of the otherwise well-controlled intracellular calcium (Ca2+) homeostasis. The resultant up-regulation of intracellular Ca2+ concentration has detrimental implications for memory formation and cell survival. The gating kinetics and Ca2+ permeability of Aβ pores are not well understood. We have used computational modeling in conjunction with the ability of optical patch-clamping for massively parallel imaging of Ca2+ flux through thousands of pores in the cell membrane of Xenopus oocytes to elucidate the kinetic properties of Aβ pores. The fluorescence time-series data from individualmore » pores were idealized and used to develop data-driven Markov chain models for the kinetics of the Aβ pore at different stages of its evolution. Our study provides the first demonstration of developing Markov chain models for ion channel gating that are driven by optical-patch clamp data with the advantage of experiments being performed under close to physiological conditions. As a result, we demonstrate the up-regulation of gating of various Ca2+ release channels due to Aβ pores and show that the extent and spatial range of such up-regulation increases as Aβ pores with low open probability and Ca2+ permeability transition into those with high open probability and Ca2+ permeability.« less

  12. Cardiovascular and Interventional Radiological Society of Europe Guidelines on Endovascular Treatment in Aortoiliac Arterial Disease

    SciTech Connect (OSTI)

    Rossi, Michele; Iezzi, Roberto

    2013-11-06

    PurposeThese guidelines are intended for use in assessing the standard for technical success and safety in aorto-iliac percutaneous endovascular interventions.MethodsAny recommendation contained in the text comes from the highest level and extension of literature review available to date.ResultsThe success of endovascular procedures is strictly related to an accurate planning based mainly on CT- or MR-angiography. TASC II A through C lesions have an endovascular-first option Pre-procedure ASA antiplatelet therapy is advisable in all cases. The application of stents improves the immediate hemodynamic and most likely long-term clinical results. Cumulative mean complication rate is 7.51% according to the most relevant literature. Most of the complications can be managed by means of percutaneous techniques.ConclusionThe design and quality of devices, as well as the easy and accuracy of performing these procedures, have improved over the last decades, leading to the preferential treatment of aorto-iliac steno-obstructive disease via endovascular means, often as first-line therapy, with high technical success rate and low morbidity. This is mirrored by the decreasing number of patients undergoing surgical grafts over the last years with patency, limb salvage, and survival rates equivalent to open reconstruction.

  13. Thermodynamics imprinting reveals differential binding of metals to {alpha}-synuclein: Relevance to parkinson's disease

    SciTech Connect (OSTI)

    Bharathi; Rao, K.S.J. . E-mail: kjr5n@yahoo.co.in

    2007-07-20

    The aggregation of {alpha}-synuclein is a hallmark feature of Parkinson's disease (PD) and other synucleinopathies. Metals are the significant etiological factors in PD, and their interaction with {alpha}-synuclein affect dramatically the kinetics of fibrillation in vitro and are proposed to play an important and potential neurodegenerative role in vivo. In the present study, we investigated the stoichiometry of binding of copper [Cu (II)] and iron [Fe (III)] with {alpha}-synuclein (wild recombinant type and A30P, A53T, E46K mutant forms) using isothermal titration calorimetry (ITC). {alpha}-Synuclein monomer (wild and mutant forms) titrated by Cu (II), showed two binding sites, with an apparent K {sub B} of 10{sup 5} M and 10{sup 4} M, respectively. But, {alpha}-synuclein (wild type and mutant forms) titrated with Fe (III) revealed a K {sub B} of 10{sup 5} M with single binding site. The present investigation uncovers the detailed binding propensities between metals and {alpha}-synuclein and has biological implications in PD.

  14. Analysis of HLA-DP association with beryllium disease susceptibility in pooled exposed populations

    SciTech Connect (OSTI)

    Cesare Saltini, Massimo Amicosante

    2009-12-19

    Berylliosis or Chronic Beryllium Disease is a chronic granulomatous disorder primarily involving the lung associated with the exposition to low doses of Beryllium (Be) in the workplace. Berylliosis risk has been associated with the presence of a glutamate at position 69 of the HLA-DP beta chain (HLA-DPbetaGlu69) that is expressed in about 97% of disease cases and in 27% of the unaffected Be-exposed controls (p<0.0001) (Richeldi et al. Science 1993; 262: 242-244.12). Since this first observation of an immunogenetic association between berylliosis and HLA-DPbetaGlu69 a number of studies have confirmed the role of this marker as the primary gene of susceptibility of berylliosis (Richeldi et al Am J Ind Med. 1997; 32:337-40; Wang et al J. Immunol. 1999; 163: 1647-53; Saltini et al Eur Respir J. 2001 18:677-84; Rossman et al Am J Respir Crit Care Med. 2002 165:788-94). Moreover, a structure/function interaction between HLA-DP molecules carrying Glu69 and beryllium in driving and developing the immune response against beryllium itself has been observed as: (1) Be-specific T-cells clones obtained from berylliosis patients recognize beryllium as antigen only when presented in the context of the HLA-DP{beta}Glu69 molecules but not in the context of HLA-DP allelic variants carrying Lys69 (Lombardi G et al. J Immunol 2001; 166: 3549-3555), and (2) beryllium presents an affinity for the HLA-DP2, carrying the berylliosis marker of susceptibility HLA-DPGlu69, from 40 to 100 times higher that the HLA-DP molecule carrying Lys69 (Amicosante M. et al Hum. Immunol. 2001; 62: 686-93). However, although the immunogenetic studies performed have been addressed a number of different questions about the genetic association between berylliosis and/or beryllium sensitization, exposure levels to beryllium and HLA markers, a number of questions are still open in the field mainly due to the limitation imposed by the low number of subjects carrying berylliosis or beryllium sensitization enrolled

  15. Structure of the Newcastle disease virus F protein in the post-fusion conformation

    SciTech Connect (OSTI)

    Swanson, Kurt; Wen, Xiaolin; Leser, George P.; Paterson, Reay G.; Lamb, Robert A.; Jardetzky, Theodore S. (Stanford-MED); (NWU); (HHMI)

    2010-11-17

    The paramyxovirus F protein is a class I viral membrane fusion protein which undergoes a significant refolding transition during virus entry. Previous studies of the Newcastle disease virus, human parainfluenza virus 3 and parainfluenza virus 5 F proteins revealed differences in the pre- and post-fusion structures. The NDV Queensland (Q) F structure lacked structural elements observed in the other two structures, which are key to the refolding and fusogenic activity of F. Here we present the NDV Australia-Victoria (AV) F protein post-fusion structure and provide EM evidence for its folding to a pre-fusion form. The NDV AV F structure contains heptad repeat elements missing in the previous NDV Q F structure, forming a post-fusion six-helix bundle (6HB) similar to the post-fusion hPIV3 F structure. Electrostatic and temperature factor analysis of the F structures points to regions of these proteins that may be functionally important in their membrane fusion activity.

  16. Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells

    SciTech Connect (OSTI)

    Liu, Xia; Zhao, Libo; Yang, Yongtao; Bode, Liv; Huang, Hua; Liu, Chengyu; Huang, Rongzhong; Zhang, Liang; and others

    2014-09-15

    Background: Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. Methods: Proteome and histone lysine acetylation were profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. Results: Post BDV infection, 4383 quantifiable differential proteins were identified and functionally annotated to metabolism pathways, immune response, DNA replication, DNA repair, and transcriptional regulation. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. Conclusions: BDV infection using a human strain impacted the whole proteome and histone lysine acetylation in OL cells. - Highlights: • A human strain of BDV (BDV Hu-H1) was used to infect human oligodendroglial cells (OL cells). • This study is the first to reveal the host proteomic and histone Kac profiles in BDV-infected OL cells. • BDV infection affected the expression of many transcription factors and several HATs and HDACs.

  17. Similarities of host defense mechanisms against pulmonary infectious disease in animals and man

    SciTech Connect (OSTI)

    Green, G.M.

    1984-01-01

    Evidence linking exposure to air pollutants with increased susceptibility to infectious diseases in humans comes from epidemiological, clinical, and experimental laboratory studies. The data suggest that the most common, and perhaps the most sensitive, index of the pulmonary effect of air pollutant exposure is on post upper respiratory infection, prolonged cough, phlegm, and purulent sputum. Experimental models of these relationships for extrapolation to humans should be able to measure such minor changes in symptomatology and physiology rather than require major lethal events. The bacterial aerosol model for quantifying nonspecific defense mechanisms of the bronchopulmonary tree utilizing nonpathogenic organisms fulfills this criterion. The function of the six major components of pulmonary antimicrobial defense mechanisms - including aerodynamic filtration, secretory respiratory tract fluid, fluid transport at the alveolar and bronchial levels, the phagocytic function of alveolar macrophages, the augmenting mechanisms of blood-derived inflammatory cells, and the secretory and cellular-specific immune mechanisms and their mediator products - can all be quantified by this experimental animal model system. The defensive functions are remarkably similar across animal species, and available human data suggest that findings obtained using the model may be extrapolatred to humans.

  18. Memorandum, Clarification of Title 10 of the Code of Federal Regulations, Part 850 (10 CPR 850), Chronic Beryllium Disease Prevention Program, Paragraph 850.34(g)

    Broader source: Energy.gov [DOE]

    The purpose of this memorandum is to clarification regarding the reporting of beryllium sensitization (BeS) and chronic beryllium disease (CBD) as required by paragraph 850.34(g) of the Chronic Beryllium Disease Prevention Program rule (10 CFR 850).

  19. The Impact of Preradiation Residual Disease Volume on Time to Locoregional Failure in Cutaneous Merkel Cell CarcinomaA TROG Substudy

    SciTech Connect (OSTI)

    Finnigan, Renee; Hruby, George; Wratten, Chris; Keller, Jacqui; Tripcony, Lee; Dickie, Graeme; Rischin, Danny; Poulsen, Michael

    2013-05-01

    Purpose: This study evaluated the impact of margin status and gross residual disease in patients treated with chemoradiation therapy for high-risk stage I and II Merkel cell cancer (MCC). Methods and Materials: Data were pooled from 3 prospective trials in which patients were treated with 50 Gy in 25 fractions to the primary lesion and draining lymph nodes and 2 schedules of carboplatin based chemotherapy. Time to locoregional failure was analyzed according to the burden of disease at the time of radiation therapy, comparing patients with negative margins, involved margins, or macroscopic disease. Results: Analysis was performed on 88 patients, of whom 9 had microscopically positive resection margins and 26 had macroscopic residual disease. The majority of gross disease was confined to nodal regions. The 5-year time to locoregional failure, time to distant failure, time to progression, and disease-specific survival rates for the whole group were 73%, 69%, 62%, and 66% respectively. The hazard ratio for macroscopic disease at the primary site or the nodes was 1.25 (95% confidence interval 0.57-2.77), P=.58. Conclusions: No statistically significant differences in time to locoregional failure were identified between patients with negative margins and those with microscopic or gross residual disease. These results must, however, be interpreted with caution because of the limited sample size.

  20. Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids

    SciTech Connect (OSTI)

    Casjens S. R.; Dunn J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Schutzer, S. E.; Gilcrease, E. B.; Huang, W. M.; Vujadinovic, M.; Aron, J. K.; Vargas, L. C.; Freeman, S.; Radune, D.; Weidman, J. F.; Dimitrov, G. I.; Khouri, H. M.; Sosa, J. E.; Halpin, R. A.; Fraser, C. M.

    2012-03-14

    Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33-40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi {approx}900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short {le}20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant.

  1. Analyzing and modeling the kinetics of amyloid beta pores associated with Alzheimer’s disease pathology

    SciTech Connect (OSTI)

    Ullah, Ghanim; Demuro, Angelo; Parker, Ian; Pearson, John E.; Xu, Shang -Zhong

    2015-09-08

    Amyloid beta (Aβ) oligomers associated with Alzheimer’s disease (AD) form Ca2+-permeable plasma membrane pores, leading to a disruption of the otherwise well-controlled intracellular calcium (Ca2+) homeostasis. The resultant up-regulation of intracellular Ca2+ concentration has detrimental implications for memory formation and cell survival. The gating kinetics and Ca2+ permeability of Aβ pores are not well understood. We have used computational modeling in conjunction with the ability of optical patch-clamping for massively parallel imaging of Ca2+ flux through thousands of pores in the cell membrane of Xenopus oocytes to elucidate the kinetic properties of Aβ pores. The fluorescence time-series data from individual pores were idealized and used to develop data-driven Markov chain models for the kinetics of the Aβ pore at different stages of its evolution. Our study provides the first demonstration of developing Markov chain models for ion channel gating that are driven by optical-patch clamp data with the advantage of experiments being performed under close to physiological conditions. As a result, we demonstrate the up-regulation of gating of various Ca2+ release channels due to Aβ pores and show that the extent and spatial range of such up-regulation increases as Aβ pores with low open probability and Ca2+ permeability transition into those with high open probability and Ca2+ permeability.

  2. Fourier Transform Infrared Imaging Showing Reduced Unsaturated Lipid Content in the Hippocampus of a mouse Model of Alzheimer's Disease

    SciTech Connect (OSTI)

    Leskovjan, A.C.; Kretlow, A.; Miller, L.M.

    2010-04-01

    Polyunsaturated fatty acids are essential to brain functions such as membrane fluidity, signal transduction, and cell survival. It is also thought that low levels of unsaturated lipid in the brain may contribute to Alzheimer's disease (AD) risk or severity. However, it is not known how accumulation of unsaturated lipids is affected in different regions of the hippocampus, which is a central target of AD plaque pathology, during aging. In this study, we used Fourier transform infrared imaging (FTIRI) to visualize the unsaturated lipid content in specific regions of the hippocampus in the PSAPP mouse model of AD as a function of plaque formation. Specifically, the unsaturated lipid content was imaged using the olefinic {double_bond}CH stretching mode at 3012 cm{sup -1}. The axonal, dendritic, and somatic layers of the hippocampus were examined in the mice at 13, 24, 40, and 56 weeks old. Results showed that lipid unsaturation in the axonal layer was significantly increased with normal aging in control (CNT) mice (p < 0.01) but remained low and relatively constant in PSAPP mice. Thus, these findings indicate that unsaturated lipid content is reduced in hippocampal white matter during amyloid pathogenesis and that maintaining unsaturated lipid content early in the disease may be critical in avoiding progression of the disease.

  3. Risk of death from cardiovascular disease associated with low-level arsenic exposure among long-term smokers in a US population-based study

    SciTech Connect (OSTI)

    Farzan, Shohreh F.; Chen, Yu; Rees, Judy R.; Zens, M. Scot; Karagas, Margaret R.

    2015-09-01

    High levels of arsenic exposure have been associated with increases in cardiovascular disease risk. However, studies of arsenic's effects at lower exposure levels are limited and few prospective studies exist in the United States using long-term arsenic exposure biomarkers. We conducted a prospective analysis of the association between toenail arsenic and cardiovascular disease mortality using longitudinal data collected on 3939 participants in the New Hampshire Skin Cancer Study. Using Cox proportional hazard models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals associated with the risk of death from any cardiovascular disease, ischemic heart disease, and stroke, in relation to natural-log transformed toenail arsenic concentrations. In this US population, although we observed no overall association, arsenic exposure measured from toenail clipping samples was related to an increased risk of ischemic heart disease mortality among long-term smokers (as reported at baseline), with increased hazard ratios among individuals with ≥ 31 total smoking years (HR: 1.52, 95% CI: 1.02, 2.27), ≥ 30 pack-years (HR: 1.66, 95% CI: 1.12, 2.45), and among current smokers (HR: 1.69, 95% CI: 1.04, 2.75). These results are consistent with evidence from more highly exposed populations suggesting a synergistic relationship between arsenic exposure and smoking on health outcomes and support a role for lower-level arsenic exposure in ischemic heart disease mortality. - Highlights: • Arsenic (As) has been associated with increased cardiovascular disease (CVD) risk. • Little is known about CVD effects at lower levels of As exposure common in the US. • Few have investigated the joint effects of As and smoking on CVD in US adults. • We examine chronic low-level As exposure and smoking in relation to CVD mortality. • Arsenic exposure may increase ischemic heart disease mortality among smokers in US.

  4. Percutaneous Transsplenic Access to the Portal Vein for Management of Vascular Complication in Patients with Chronic Liver Disease

    SciTech Connect (OSTI)

    Chu, Hee Ho; Kim, Hyo-Cheol Jae, Hwan Jun; Yi, Nam-Joon; Lee, Kwang-Woong; Suh, Kyung-Suk; Chung, Jin Wook; Park, Jae Hyung

    2012-12-15

    Purpose: To evaluate the safety and feasibility of percutaneous transsplenic access to the portal vein for management of vascular complication in patients with chronic liver diseases. Methods: Between Sept 2009 and April 2011, percutaneous transsplenic access to the portal vein was attempted in nine patients with chronic liver disease. Splenic vein puncture was performed under ultrasonographic guidance with a Chiba needle, followed by introduction of a 4 to 9F sheath. Four patients with hematemesis or hematochezia underwent variceal embolization. Another two patients underwent portosystemic shunt embolization in order to improve portal venous blood flow. Portal vein recanalization was attempted in three patients with a transplanted liver. The percutaneous transsplenic access site was closed using coils and glue. Results: Percutaneous transsplenic splenic vein catheterization was performed successfully in all patients. Gastric or jejunal varix embolization with glue and lipiodol mixture was performed successfully in four patients. In two patients with a massive portosystemic shunt, embolization of the shunting vessel with a vascular plug, microcoils, glue, and lipiodol mixture was achieved successfully. Portal vein recanalization was attempted in three patients with a transplanted liver; however, only one patient was treated successfully. Complete closure of the percutaneous transsplenic tract was achieved using coils and glue without bleeding complication in all patients. Conclusion: Percutaneous transsplenic access to the portal vein can be an alternative route for portography and further endovascular management in patients for whom conventional approaches are difficult or impossible.

  5. Understanding the chemical properties of macerals and minerals in coal and its potential application for occupational lung disease prevention

    SciTech Connect (OSTI)

    Huang, X.; Finkelman, R.B.

    2008-07-01

    The objective of this review was to assess whether some chemical parameters in coal play a role in producing environmental health problems. Basic properties of coal - such as chemical forms of the organic materials, structure, compositions of minerals - vary from one coal mine region to another as well as from coals of different ranks. Most importantly, changes in chemical properties of coals due to exposure to air and humidity after mining - a dynamic process - significantly affect toxicity attributed to coal and environmental fate. Although coal is an extremely complex and heterogeneous material, the fundamental properties of coal responsible for environmental and adverse health problems are probably related to the same inducing components of coal. For instance, oxidation of pyrite (FeS{sub 2}) in the coal forms iron sulfate and sulfuric acid, which produces occupational lung diseases (e.g., pneumoconiosis) and other environmental problems (e.g., acid mine drainage and acid rain). Calcite (CaCO{sub 3}) contained in certain coals alters the end products of pyrite oxidation, which may make these coals less toxic to human inhalation and less hazardous to environmental pollution. Finally, knowledge gained on understanding of the chemical properties of coals is illustrated to apply for prediction of toxicity due to coal possibly before large-scale mining and prevention of occupational lung disease during mining.

  6. Structural determination of importin alpha in complex with beak and feather disease virus capsid nuclear localization signal

    SciTech Connect (OSTI)

    Patterson, Edward I.; Dombrovski, Andrew K.; Swarbrick, Crystall M.D.; Raidal, Shane R.; Forwood, Jade K.

    2013-09-06

    Highlights: •Circovirus capsid proteins contain large nuclear localization signals (NLS). •A method of nuclear import has not been elucidated. •Beak and feather disease virus (BFDV) capsid NLS was crystallized with importin α. •The structure showed BFDV NLS binding to the major site of importin α. •Result shows implications for mechanism of nuclear transport for all circoviruses. -- Abstract: Circoviruses represent a rapidly increasing genus of viruses that infect a variety of vertebrates. Replication requires shuttling viral molecules into the host cell nucleus, a process facilitated by capsid-associated protein (Cap). Whilst a nuclear localization signal (NLS) has been shown to mediate nuclear translocation, the mode of nuclear transport remains to be elucidated. To better understand this process, beak and feather disease virus (BFDV) Cap NLS was crystallized with nuclear import receptor importin-α (Impα). Diffraction yielded structural data to 2.9 Å resolution, and the binding site on both Impα and BFDV Cap NLS were well resolved. The binding mechanism for the major site is likely conserved across circoviruses as supported by the similarity of NLSs in circovirus Caps. This finding illuminates a crucial step for infection of host cells by this viral family, and provides a platform for rational drug design against the binding interface.

  7. Effects of didecyldimethylammonium chloride on the biochemistry, swimming performance, gill histology and disease resistance of juvenile rainbow trout (Oncorhynchus mykiss)

    SciTech Connect (OSTI)

    Johnston, B.D.; Wood, A.W.; Farrell, A.P.; Kennedy, C.J.

    1995-12-31

    The acute lethal and sublethal toxicity of the antisapstain didecyldimethylammonium chloride (DDAC) to juvenile rainbow trout (Oncorhynchus mykiss) was investigated. The 96-h LC{sub 50} value in a flow-through exposure system was 0.4 mg-1{sup {minus}1}. Plasma cortisol, glucose and lactate levels were significantly elevated after an acute 24-h exposure to 0.4 mg-1{sup {minus}1}. Values for hepato-somatic index (HSI), haematocit, leucocrit, plasma haemoglobin, and liver glycogen remained unchanged. Swimming performance decreased significantly after exposure to 0.2 mg-1{sup {minus}1} for exposure durations of 12-h and 24-h and to 0.4 mg{sup {minus}1} for exposure durations of 12-h, 24-h, and 48-h. Scanning electron microscopic analysis revealed no gross lesions in gill epithelia as a result of toxicant exposure. In disease challenge experiments, exposure to sublethal concentrations of DDAC for 24-h did not effect the susceptibility of rainbow trout to the pathogen Vibrio anguilarum. Of a suite of toxicity tests, specific biochemical markers were unsatisfactory in revealing sublethal toxic effects. These were best revealed by an integrative measure of performance, namely swimming performance, but not disease resistance.

  8. Optimized Volumetric Modulated Arc Therapy Versus 3D-CRT for Early Stage Mediastinal Hodgkin Lymphoma Without Axillary Involvement: A Comparison of Second Cancers and Heart Disease Risk

    SciTech Connect (OSTI)

    Filippi, Andrea Riccardo; Ragona, Riccardo; Piva, Cristina; Scafa, Davide; Fiandra, Christian; Fusella, Marco; Giglioli, Francesca Romana; Lohr, Frank; Ricardi, Umberto

    2015-05-01

    Purpose: The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). Methods and Materials: Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LAR{sub VMAT}-to-LAR{sub 3D-CRT}) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). Results: The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P=.02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P=.038) and valvular diseases (P<.0001) was observed for VMAT regardless of disease extent. Conclusions: In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly influenced by

  9. SU-E-QI-14: Quantitative Variogram Detection of Mild, Unilateral Disease in Elastase-Treated Rats

    SciTech Connect (OSTI)

    Jacob, R; Carson, J

    2014-06-15

    Purpose: Determining the presence of mild or early disease in the lungs can be challenging and subjective. We present a rapid and objective method for evaluating lung damage in a rat model of unilateral mild emphysema based on a new approach to heterogeneity assessment. We combined octree decomposition (used in three-dimensional (3D) computer graphics) with variograms (used in geostatistics to assess spatial relationships) to evaluate 3D computed tomography (CT) lung images for disease. Methods: Male, Sprague-Dawley rats (232 ± 7 g) were intratracheally dosed with 50 U/kg of elastase dissolved in 200 μL of saline to a single lobe (n=6) or with saline only (n=5). After four weeks, 3D micro-CT images were acquired at end expiration on mechanically ventilated rats using prospective gating. Images were masked, and lungs were decomposed to homogeneous blocks of 2×2×2, 4×4×4, and 8×8×8 voxels using octree decomposition. The spatial variance – the square of the difference of signal intensity – between all pairs of the 8×8×8 blocks was calculated. Variograms – graphs of distance vs. variance - were made, and data were fit to a power law and the exponent determined. The mean HU values, coefficient of variation (CoV), and the emphysema index (EI) were calculated and compared to the variograms. Results: The variogram analysis showed that significant differences between groups existed (p<0.01), whereas the mean HU (p=0.07), CoV (p=0.24), and EI (p=0.08) did not. Calculation time for the variogram for a typical 1000 block decomposition was ∼6 seconds, and octree decomposition took ∼2 minutes. Decomposing the images prior to variogram calculation resulted in a ∼700x decrease in time as compared to other published approaches. Conclusions: Our results suggest that the approach combining octree decomposition and variogram analysis may be a rapid, non-subjective, and sensitive imaging-based biomarker for quantitative characterization of lung disease.

  10. Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: Linking systems biology with vaccine development

    SciTech Connect (OSTI)

    Adams, Leslie G.; Khare, Sangeeta; Lawhon, Sara D.; Rossetti, Carlos A.; Lewin, Harris A.; Lipton, Mary S.; Turse, Joshua E.; Wylie, Dennis C.; Bai, Yu; Drake, Kenneth L.

    2011-09-22

    The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhanced approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic *sipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host's biosignatures

  11. Prevalence of respiratory symptoms and diseases in schoolchildren living in a polluted and in a low polluted area in Israel

    SciTech Connect (OSTI)

    Goren, A.I.; Hellmann, S.

    1988-02-01

    Second and fifth grade schoolchildren living in two communities with different levels of air pollution were studied. The parents of these children filled out ATS-NHLI health questionnaires. The prevalence of reported respiratory symptoms and pulmonary diseases was found to be significantly higher among children growing up in the polluted community (Ashdod) as compared with the low-pollution area (Hadera). Logistic models fitted for the respiratory conditions which differed significantly between both areas of residence also included background variables that could be responsible for these differences. Relative risk values, which were calculated from the logistic models, were in the range of 1.47 for cough without cold to 2.66 for asthma for children from Ashdod, as compared with 1.00 for children from Hadera.

  12. Is Primary Prostate Cancer Treatment Influenced by Likelihood of Extraprostatic Disease? A Surveillance, Epidemiology and End Results Patterns of Care Study

    SciTech Connect (OSTI)

    Holmes, Jordan A.; Wang, Andrew Z.; University of North Carolina-Lineberger Comprehensive Cancer Center, Chapel Hill, NC ; Hoffman, Karen E.; Hendrix, Laura H.; Rosenman, Julian G.; University of North Carolina-Lineberger Comprehensive Cancer Center, Chapel Hill, NC ; Carpenter, William R.; Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, NC; Department of Health Policy and Management, University of North Carolina School of Public Health, Chapel Hill, NC ; Godley, Paul A.; Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, NC; Division of Hematology-Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC ; Chen, Ronald C.

    2012-09-01

    Purpose: To examine the patterns of primary treatment in a recent population-based cohort of prostate cancer patients, stratified by the likelihood of extraprostatic cancer as predicted by disease characteristics available at diagnosis. Methods and Materials: A total of 157,371 patients diagnosed from 2004 to 2008 with clinically localized and potentially curable (node-negative, nonmetastatic) prostate cancer, who have complete information on prostate-specific antigen, Gleason score, and clinical stage, were included. Patients with clinical T1/T2 disease were grouped into categories of <25%, 25%-50%, and >50% likelihood of having extraprostatic disease using the Partin nomogram. Clinical T3/T4 patients were examined separately as the highest-risk group. Logistic regression was used to examine the association between patient group and receipt of each primary treatment, adjusting for age, race, year of diagnosis, marital status, Surveillance, Epidemiology and End Results database region, and county-level education. Separate models were constructed for primary surgery, external-beam radiotherapy (RT), and conservative management. Results: On multivariable analysis, increasing likelihood of extraprostatic disease was significantly associated with increasing use of RT and decreased conservative management. Use of surgery also increased. Patients with >50% likelihood of extraprostatic cancer had almost twice the odds of receiving prostatectomy as those with <25% likelihood, and T3-T4 patients had 18% higher odds. Prostatectomy use increased in recent years. Patients aged 76-80 years were likely to be managed conservatively, even those with a >50% likelihood of extraprostatic cancer (34%) and clinical T3-T4 disease (24%). The proportion of patients who received prostatectomy or conservative management was approximately 50% or slightly higher in all groups. Conclusions: There may be underutilization of RT in older prostate cancer patients and those with likely

  13. The effects of total dissolved gas on chum salmon fry survival, growth, gas bubble disease, and seawater tolerance

    SciTech Connect (OSTI)

    Geist, David R.; Linley, Timothy J.; Cullinan, Valerie I.; Deng, Zhiqun

    2013-02-01

    Chum salmon Oncorhynchus keta alevin developing in gravel habitats downstream of Bonneville Dam on the Columbia River are exposed to elevated levels of total dissolved gas (TDG) when water is spilled at the dam to move migrating salmon smolts downstream to the Pacific Ocean. Current water quality criteria for the management of dissolved gas in dam tailwaters were developed primarily to protect salmonid smolts and are assumed to be protective of alevin if adequate depth compensation is provided. We studied whether chum salmon alevin exposed to six levels of dissolved gas ranging from 100% to 130% TDG at three development periods between hatch and emergence (hereafter early, middle, and late stage) suffered differential mortality, growth, gas bubble disease, or seawater tolerance. Each life stage was exposed for 50 d (early stage), 29 d (middle stage), or 16 d (late stage) beginning at 13, 34, and 37 d post-hatch, respectively, through 50% emergence. The mortality for all stages from exposure to emergence was estimated to be 8% (95% confidence interval (CI) of 4% to 12%) when dissolved gas levels were between 100% and 117% TDG. Mortality significantly increased as dissolved gas levels rose above 117% TDG,; with the lethal concentration that produced 50% mortality (LC50 ) was estimated to be 128.7% TDG (95% CI of 127.2% to 130.2% TDG) in the early and middle stages. By contrast, there was no evidence that dissolved gas level significantly affected growth in any life stage except that the mean wet weight at emergence of early stage fish exposed to 130% TDG was significantly less than the modeled growth of unexposed fish. The proportion of fish afflicted with gas bubble disease increased with increasing gas concentrations and occurred most commonly in the nares and gastrointestinal tract. Early stage fish exhibited higher ratios of filament to lamellar gill chloride cells than late stage fish, and these ratios increased and decreased for early and late stage fish

  14. The tale of a modern animal plague: Tracing the evolutionary history and determining the time-scale for foot and mouth disease virus

    SciTech Connect (OSTI)

    Tully, Damien C. Fares, Mario A.

    2008-12-20

    Despite significant advances made in the understanding of its epidemiology, foot and mouth disease virus (FMDV) is among the most unexpected agricultural devastating plagues. While the disease manifests itself as seven immunologically distinct strains their origin, population dynamics, migration patterns and divergence times remain unknown. Herein we have assembled a comprehensive data set of gene sequences representing the global diversity of the disease and inferred the time-scale and evolutionary history for FMDV. Serotype-specific rates of evolution and divergence times were estimated using a Bayesian coalescent framework. We report that an ancient precursor FMDV gave rise to two major diversification events spanning a relatively short interval of time. This radiation event is estimated to have taken place towards the end of the 17th and the beginning of the 18th century giving us the present circulating Euro-Asiatic and South African viral strains. Furthermore our results hint that Europe acted as a possible hub for the disease from where it successfully dispersed elsewhere via exploration and trading routes.

  15. Elastic Deformation Properties of Implanted Endobronchial Wire Stents in Benign and Malignant Bronchial Disease: A Radiographic In Vivo Evaluation

    SciTech Connect (OSTI)

    Hautmann, Hubert; Rieger, Johannes; Huber, Rudolf M.; Pfeifer, Klaus J.

    1999-03-15

    Purpose: To evaluate the long-term mechanical behavior in vivo of expandable endobronchial wire stents, we imaged three different prostheses in the treatment of tracheobronchial disease. Methods: Six patients with bronchial stenoses (three benign, three malignant) underwent insertion of metallic stents. Two self-expandable Wallstents, two balloon-expandable tantalum Strecker stents and two self-expandable nitinol Accuflex stents were used. Measurements of deformation properties were performed during voluntary cough by means of fluoroscopy, at 1 month and 7-10 months after implantation. The procedures were videotaped, their images digitized and the narrowing of stent diameters calculated at intervals of 20 msec. Results: After stent implantation all patients improved with respect to ventilatory function. Radial stent narrowing during cough reached 53% (Wallstent), 59% (tantalum Strecker stent), and 52% (nitinol Accuflex stent) of the relaxed post-implantation diameter. Stent compression was more marked in benign compared with malignant stenoses. In the long term permanent deformation occurred with the tantalum Strecker stents; the other stents were unchanged. Conclusion: Endobronchial wire stents can be helpful in the treatment of major airway collapse and obstructing bronchial lesions. However, evidence of material fatigue as a possible effect of exposure to recurrent mechanical stress on the flexible mesh tube may limit their long-term use. This seems to be predominantly important in benign bronchial collapse.

  16. Review of Monitoring Plans for Gas Bubble Disease Signs and Gas Supersaturation Levels on the Columbia and Snake Rivers.

    SciTech Connect (OSTI)

    Fidler, Larry; Elston, Ralph; Colt, John

    1994-07-01

    Montgomery Watson was retained by the Bonneville Power Administration to evaluate the monitoring program for gas bubble disease signs and dissolved gas supersaturation levels on the Columbia and Snake rivers. The results of this evaluation will provide the basis for improving protocols and procedures for future monitoring efforts. Key study team members were Dr. John Colt, Dr. Larry Fidler, and Dr. Ralph Elston. On the week of June 6 through 10, 1994 the study team visited eight monitoring sites (smolt, adult, and resident fish) on the Columbia and Snake rivers. Additional protocol evaluations were conducted at the Willard Field Station (National Biological Survey) and Pacific Northwest Laboratories at Richland (Battelle). On June 13 and 14, 1994, the study team visited the North Pacific Division office of the U.S. Corps of Engineers and the Fish Passage Center to collect additional information and data on the monitoring programs. Considering the speed at which the Gas Bubble Trauma Monitoring Program was implemented this year, the Fish Passage Center and cooperating Federal, State, and Tribal Agencies have been doing an incredible job. Thirty-one specific recommendations are presented in this report and are summarized in Section 14.

  17. CFD modeling and image analysis of exhaled aerosols due to a growing bronchial tumor: Towards non-invasive diagnosis and treatment of respiratory obstructive diseases

    SciTech Connect (OSTI)

    Xi, Jinxiang [Central Michigan Univ., Mount Pleasant, MI (United States); Kim, JongWon [Central Michigan Univ., Mount Pleasant, MI (United States); Si, Xiuhua A. [California Baptist Univ., Riverside, CA (United States); Corley, Richard A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Kabilan, Senthil [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Wang, Shengyu [First Affiliated Hospital of Xi'an Medical Univ., Shaanxi (China); Mayo Clinic, Rochester, MN (United States)

    2015-01-01

    Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure variations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treat the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagrangian tracking approach were used to model respiratory airflows and aerosol dynamics. Respirations of tracer aerosols of 1 ?m at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug delivery protocol.

  18. CFD modeling and image analysis of exhaled aerosols due to a growing bronchial tumor: Towards non-invasive diagnosis and treatment of respiratory obstructive diseases

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Xi, Jinxiang; Kim, JongWon; Si, Xiuhua A.; Corley, Richard A.; Kabilan, Senthil; Wang, Shengyu

    2015-01-01

    Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure variations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treatmore » the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagrangian tracking approach were used to model respiratory airflows and aerosol dynamics. Respirations of tracer aerosols of 1 μm at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug delivery protocol.« less

  19. CFD modeling and image analysis of exhaled aerosols due to a growing bronchial tumor: Towards non-invasive diagnosis and treatment of respiratory obstructive diseases

    SciTech Connect (OSTI)

    Xi, Jinxiang; Kim, JongWon; Si, Xiuhua A.; Corley, Richard A.; Kabilan, Senthil; Wang, Shengyu

    2015-01-01

    Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure variations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treat the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagrangian tracking approach were used to model respiratory airflows and aerosol dynamics. Respirations of tracer aerosols of 1 μm at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug delivery protocol.

  20. CFD Modeling and Image Analysis of Exhaled Aerosols due to a Growing Bronchial Tumor: towards Non-Invasive Diagnosis and Treatment of Respiratory Obstructive Diseases

    SciTech Connect (OSTI)

    Xi, Jinxiang; Kim, JongWon; Si, Xiuhua A.; Corley, Richard A.; Kabilan, Senthil; Wang, Shengyu

    2015-02-06

    Diagnosis and prognosis of tumorigenesis are generally performed with CT, PET, or biopsy. Such methods are accurate, but have the limitations of high cost and posing additional health risks to patients. In this study, we introduce an alternative computer aided diagnostic tool that can locate malignant sites caused by tumorigenesis in a non-invasive and low-cost way. Our hypothesis is that exhaled aerosol distribution is unique to lung structure and is sensitive to airway structure vari-ations. With appropriate approaches, it is possible to locate the disease site, determine the disease severity, and subsequently formulate a targeted drug delivery plan to treat the disease. This study numerically evaluated the feasibility of the proposed breath test in an image-based lung model with varying pathological stages of a bronchial squamous tumor. Large eddy simulations and a Lagran-gian tracking approach were used to model respiratory airflows and aerosol dynamics. Respira-tions of tracer aerosols of 1 m at a flow rate of 20 L/min were simulated, with the distributions of exhaled aerosols recorded on a filter at the mouth exit. Aerosol patterns were quantified with multiple analytical techniques such as concentration disparity, spatial scanning and fractal analysis. We demonstrated that a growing bronchial tumor induced notable variations in both the airflow and exhaled aerosol distribution. These variations became more apparent with increasing tumor severity. The exhaled aerosols exhibited distinctive pattern parameters such as spatial probability, fractal dimension, and multifractal spectrum. Results of this study show that morphometric measures of the exhaled aerosol pattern can be used to detect and monitor the pathological states of respiratory diseases in the upper airway. The proposed breath test also has the potential to locate the site of the disease, which is critical in developing a personalized, site-specific drug de-livery protocol.

  1. Metal-sulfide mineral ores, Fenton chemistry and disease. Particle induced inflammatory stress response in lung cells

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Harrington, Andrea D.; Smirnov, Alexander; Tsirka, Stella E.; Schoonen, Martin A. A.

    2014-07-10

    The inhalation of mineral particulates and other earth materials, such as coal, can initiate or enhance disease in humans. Workers in occupations with high particulate exposure, such as mining, are particularly at risk. The ability of a material to generate an inflammatory stress response (ISR), a measure of particle toxicity, is a useful tool in evaluating said exposure risk. ISR is defined as the upregulation of cellular reactive oxygen species (ROS) normalized to cell viability. This study compares the ISR of A549 human lung epithelial cells after exposure to well-characterized common metal-sulfide ore mineral separates. The evaluation of the deleteriousmore » nature of ore minerals is based on a range of particle loadings (serial dilutions of 0.002 m2/mL stock) and exposure periods (beginning at 30 min and measured systematically for up to 24 h). There is a wide range in ISR values generated by the ore minerals. The ISR values produced by the sphalerite samples are within the range of inert materials. Arsenopyrite generated a small ISR that was largely driven by cell death. Galena showed a similar, but more pronounced response. Copper-bearing ore minerals generated the greatest ISR, both by upregulating cellular ROS and generating substantial and sustained cell death. Chalcopyrite and bornite, both containing ferrous iron, generated the greatest ISR overall. Particles containing Fenton metals as major constituents produce the highest ISR, while other heavy metals mainly generate cell death. Furthermore, this study highlights the importance of evaluating the chemistry, oxidation states and structure of a material when assessing risk management.« less

  2. Metal-sulfide mineral ores, Fenton chemistry and disease. Particle induced inflammatory stress response in lung cells

    SciTech Connect (OSTI)

    Harrington, Andrea D.; Smirnov, Alexander; Tsirka, Stella E.; Schoonen, Martin A. A.

    2014-07-10

    The inhalation of mineral particulates and other earth materials, such as coal, can initiate or enhance disease in humans. Workers in occupations with high particulate exposure, such as mining, are particularly at risk. The ability of a material to generate an inflammatory stress response (ISR), a measure of particle toxicity, is a useful tool in evaluating said exposure risk. ISR is defined as the upregulation of cellular reactive oxygen species (ROS) normalized to cell viability. This study compares the ISR of A549 human lung epithelial cells after exposure to well-characterized common metal-sulfide ore mineral separates. The evaluation of the deleterious nature of ore minerals is based on a range of particle loadings (serial dilutions of 0.002 m2/mL stock) and exposure periods (beginning at 30 min and measured systematically for up to 24 h). There is a wide range in ISR values generated by the ore minerals. The ISR values produced by the sphalerite samples are within the range of inert materials. Arsenopyrite generated a small ISR that was largely driven by cell death. Galena showed a similar, but more pronounced response. Copper-bearing ore minerals generated the greatest ISR, both by upregulating cellular ROS and generating substantial and sustained cell death. Chalcopyrite and bornite, both containing ferrous iron, generated the greatest ISR overall. Particles containing Fenton metals as major constituents produce the highest ISR, while other heavy metals mainly generate cell death. Furthermore, this study highlights the importance of evaluating the chemistry, oxidation states and structure of a material when assessing risk management.

  3. Risk of Leptomeningeal Disease in Patients Treated With Stereotactic Radiosurgery Targeting the Postoperative Resection Cavity for Brain Metastases

    SciTech Connect (OSTI)

    Atalar, Banu; Modlin, Leslie A.; Choi, Clara Y.H.; Adler, John R.; Gibbs, Iris C.; Chang, Steven D.; Harsh, Griffith R.; Li, Gordon; Nagpal, Seema; Hanlon, Alexandra; Soltys, Scott G.

    2013-11-15

    Purpose: We sought to determine the risk of leptomeningeal disease (LMD) in patients treated with stereotactic radiosurgery (SRS) targeting the postsurgical resection cavity of a brain metastasis, deferring whole-brain radiation therapy (WBRT) in all patients. Methods and Materials: We retrospectively reviewed 175 brain metastasis resection cavities in 165 patients treated from 1998 to 2011 with postoperative SRS. The cumulative incidence rates, with death as a competing risk, of LMD, local failure (LF), and distant brain parenchymal failure (DF) were estimated. Variables associated with LMD were evaluated, including LF, DF, posterior fossa location, resection type (en-bloc vs piecemeal or unknown), and histology (lung, colon, breast, melanoma, gynecologic, other). Results: With a median follow-up of 12 months (range, 1-157 months), median overall survival was 17 months. Twenty-one of 165 patients (13%) developed LMD at a median of 5 months (range, 2-33 months) following SRS. The 1-year cumulative incidence rates, with death as a competing risk, were 10% (95% confidence interval [CI], 6%-15%) for developing LF, 54% (95% CI, 46%-61%) for DF, and 11% (95% CI, 7%-17%) for LMD. On univariate analysis, only breast cancer histology (hazard ratio, 2.96) was associated with an increased risk of LMD. The 1-year cumulative incidence of LMD was 24% (95% CI, 9%-41%) for breast cancer compared to 9% (95% CI, 5%-14%) for non-breast histology (P=.004). Conclusions: In patients treated with SRS targeting the postoperative cavity following resection, those with breast cancer histology were at higher risk of LMD. It is unknown whether the inclusion of whole-brain irradiation or novel strategies such as preresection SRS would improve this risk or if the rate of LMD is inherently higher with breast histology.

  4. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    SciTech Connect (OSTI)

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  5. Arrested rearrangement of TCR V[beta] genes in thymocytes from children with x-linked severe combined immunodeficiency disease

    SciTech Connect (OSTI)

    Sleasman, J.W.; Harville, T.O.; White, G.B.; Barrett, D.J. ); George, J.F. ); Goodenow, M.M. Univ. of Alabama, Birmingham, AL )

    1994-07-01

    Human X-linked severe combined immunodeficiency disease (SCID) is an immunodeficiency disorder in which T cell development is arrested in the thymic cortex. B lymphocytes in children with X-linked SCID seem to differentiate normally. X-linked SCID is associated with a mutation in the gene that encodes the IL-2R [gamma]-chain. Because TCR-[beta] gene recombination is a pivotal initial event in T lymphocyte onteogeny within the thymus, the authors hypothesized that a failure to express normal IL-2R[gamma] could lead to impaired TCR-[beta] gene recombination in early thymic development. PCR was used to determine the status of TCR-[beta] gene-segment rearrangements in thymic DNA that had been obtained from children with X-linked SCID. The initial step in TCR-[beta] gene rearrangement, that of D[beta] to J[beta] recombination, was readily detected in all thymus samples from children with X-linked SCID; in contrast, V[beta] to DJ[beta] gene rearrangements were undetectable in the same samples. Both D[beta] to J[beta] and V[beta] to DJ[beta] TCR genes were rearranged in the thymic tissues obtained from immunologically normal children. The authors conclude that TCR[beta]-chain gene rearrangement is arrested in children with X-linked SCID. The results suggest a causative relationship between the failure of TCR [beta]-chain gene arrangements to proceed beyond DJ[beta] rearrangements and the production of a nonfunctional IL-2R [gamma]-chain. 45 refs., 3 figs.

  6. Novel mutations in the connexin 32 gene associated with X-linked Charcot-Marie-Tooth disease

    SciTech Connect (OSTI)

    Tan, C.; Ainsworth, P. |

    1994-09-01

    Charcot-Marie-Tooth disease is a pathologically and genetically hetergenous group of disorders that cause a progressive neuropathy, defined pathologically by degeneration of the myelin (CMT 1) of the axon (CMT 2) of the peripheral nerves. An X-linked type of the demyelinating form of this disorder (CMT X) has recently been linked to mutations in the connexin 32 (Cx32) gene, which codes for a 284 amino acid gap junction protein found in myelinated peripheral nerve. To date some 7 different mutations in this gene have been identified as being responsible for CMT X. The majority of these predict nonconservative amino acid substitutions, while one is a frameshift mutation which predicts a premature stop at codon 21. We report the results of molecular studies on three further local CMT X kindreds. The Cx32 gene was amplified by PCR in three overlapping fragments 300-450 bp in length using leukocyte-derived DNA as template. These were either sequenced directly using a deaza dGTP sequencing protocol, or were cloned and sequenced using a TA vector. In two of the kindreds the affected members carried a point mutation which was predicted to effect a non-conservative amino acid change within the first transmembrane domain. Both of these mutations caused a restriction site alteration (the loss of an Nla III and the creation of a Pvu II, respectively), and the former mutation was observed to segregate with the clinicial phenotype in affected family members. Affected members of the third kindred, which was a very large multigenerational family that had been extensively studied previously, were shown to carry a point mutation predicted to cause a premature truncation of the Cx32 gene product in the intracellular carboxy terminus. This mutation obliterated an Rsa I site which allowed a rapid screen of several other family members.

  7. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    SciTech Connect (OSTI)

    Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I.; Barrios, Roberto; Moorthy, Bhagavatula

    2013-10-15

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.

  8. Soluble FGFR4 extracellular domain inhibits FGF19-induced activation of FGFR4 signaling and prevents nonalcoholic fatty liver disease

    SciTech Connect (OSTI)

    Chen, Qiang; The First Affiliated Hospital of Xiamen University, Xiamen ; Jiang, Yuan; An, Yuan; Zhao, Na; Zhao, Yang; Yu, Chundong

    2011-06-17

    Highlights: {yields} Soluble FGFR4 extracellular domain (FGFR4-ECD) was effectively expressed. {yields} FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling. {yields} FGFR4-ECD reduced palmitic acid-induced steatosis of HepG2 cells. {yields} FGFR4-ECD reduced tetracycline-induced fatty liver in mice. {yields} FGFR4-ECD partially restored tetracycline-repressed PPAR{alpha} expression. -- Abstract: Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane tyrosine kinase receptor that plays a crucial role in the regulation of hepatic bile acid and lipid metabolism. FGFR4 underlies high-fat diet-induced hepatic steatosis, suggesting that inhibition of FGFR4 activation may be an effective way to prevent or treat nonalcoholic fatty liver disease (NAFLD). To determine whether neutralization of FGFR4 ligands by soluble FGFR4 extracellular domain (FGFR4-ECD) can inhibit the activation of FGFR4, we constructed FGFR4-ECD expression vector and showed that FGFR4-ECD was effectively expressed in cells and secreted into culture medium. FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling and reduced steatosis of HepG2 induced by palmitic acid in vitro. Furthermore, in a tetracycline-induced fatty liver model, expression of FGFR4-ECD in mouse liver reduced the accumulation of hepatic lipids and partially restored the expression of peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}), which promotes the mitochondrial fatty acid beta-oxidation but is repressed by tetracycline. Taken together, these results demonstrate that FGFR4-ECD can block FGFR4 signaling and prevent hepatic steatosis, highlighting the potential value of inhibition of FGFR4 signaling as a method for therapeutic intervention against NAFLD.

  9. Methods for assisting recovery of damaged brain and spinal cord and treating various diseases using arrays of x-ray microplanar beams

    DOE Patents [OSTI]

    Dilmanian, F. Avraham; Anchel, David J.; Gaudette, Glenn; Romanelli, Pantaleo; Hainfeld, James

    2010-06-29

    A method of assisting recovery of an injury site of the central nervous system (CNS) or treating a disease includes providing a therapeutic dose of X-ray radiation to a target volume through an array of parallel microplanar beams. The dose to treat CNS injury temporarily removes regeneration inhibitors from the irradiated site. Substantially unirradiated cells surviving between beams migrate to the in-beam portion and assist recovery. The dose may be staggered in fractions over sessions using angle-variable intersecting microbeam arrays (AVIMA). Additional doses are administered by varying the orientation of the beams. The method is enhanced by injecting stem cells into the injury site. One array or the AVIMA method is applied to ablate selected cells in a target volume associated with disease for palliative or curative effect. Atrial fibrillation is treated by irradiating the atrial wall to destroy myocardial cells while continuously rotating the subject.

  10. Development and Characterization of A Multiplexed RT-PCR Species Specific Assay for Bovine and one for Porcine Foot-and-Mouth Disease Virus Rule-Out

    SciTech Connect (OSTI)

    Smith, S M; Danganan, L; Tammero, L; Vitalis, B; Lenhoff, R; Naraghi-arani, P; Hindson, B

    2007-08-06

    Lawrence Livermore National Laboratory (LLNL), in collaboration with the Department of Homeland Security (DHS) and the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS) has developed candidate multiplexed assays that may potentially be used within the National Animal Health Laboratory Network (NAHLN), the National Veterinary Services Laboratory (Ames, Iowa) and the Plum Island Animal Disease Center (PIADC). This effort has the ability to improve our nation's capability to discriminate between foreign animal diseases and those that are endemic using a single assay, thereby increasing our ability to protect food and agricultural resources with a diagnostic test which could enhance the nation's capabilities for early detection of a foreign animal disease. In FY2005 with funding from the DHS, LLNL developed the first version (Version 1.0) of a multiplexed (MUX) nucleic-acid-based RT-PCR assay that included signatures for foot-and-mouth disease virus (FMDV) detection with rule-out tests for two other foreign animal diseases (FADs) of swine, Vesicular Exanthema of Swine (VESV) and Swine Vesicular Disease Virus (SVDV), and four other domestic viral diseases Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus 1 (BHV-1), Bluetongue virus (BTV) and Parapox virus complex (which includes Bovine Papular Stomatitis Virus [BPSV], Orf of sheep, and Pseudocowpox). In FY06, LLNL has developed Bovine and Porcine species-specific panel which included existing signatures from Version 1.0 panel as well as new signatures. The MUX RT-PCR porcine assay for detection of FMDV includes the FADs, VESV and SVD in addition to vesicular stomatitis virus (VSV) and porcine reproductive and respiratory syndrome (PRRS). LLNL has also developed a MUX RT-PCR bovine assay for detection of FMDV with rule out tests for the two bovine FADs malignant catarrhal fever (MCF), rinderpest virus (RPV) and the domestic diseases vesicular stomatitis virus (VSV

  11. Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation

    SciTech Connect (OSTI)

    Lenarczyk, Marek; Su, Jidong; Haworth, Steven T.; Komorowski, Richard; Fish, Brian L.; Migrino, Raymond Q.; Harmann, Leanne; Hopewell, John W.; Kronenberg, Amy; Patel, Shailendra; Moulder, John E.; Baker, John E.

    2015-06-01

    The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9 days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20–120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.

  12. Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Lenarczyk, Marek; Su, Jidong; Haworth, Steven T.; Komorowski, Richard; Fish, Brian L.; Migrino, Raymond Q.; Harmann, Leanne; Hopewell, John W.; Kronenberg, Amy; Patel, Shailendra; et al

    2015-06-01

    The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9more » days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20–120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.« less

  13. Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

    SciTech Connect (OSTI)

    Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian; Wang Ping

    2013-01-01

    Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

  14. Stereotactic Body Radiation Therapy Can Be Used Safely to Boost Residual Disease in Locally Advanced Non-Small Cell Lung Cancer: A Prospective Study

    SciTech Connect (OSTI)

    Feddock, Jonathan; Arnold, Susanne M.; Department of Medical Oncology, University of Kentucky, Lexington, Kentucky ; Shelton, Brent J.; Sinha, Partha; Conrad, Gary; Chen, Li; Rinehart, John; McGarry, Ronald C.

    2013-04-01

    Purpose: To report the results of a prospective, single-institution study evaluating the feasibility of conventional chemoradiation (CRT) followed by stereotactic body radiation therapy (SBRT) as a means of dose escalation for patients with stage II-III non-small cell lung cancer (NSCLC) with residual disease. Methods and Materials: Patients without metastatic disease and with radiologic evidence of limited residual disease (?5 cm) within the site of the primary tumor and good or complete nodal responses after standard CRT to a target dose of 60 Gy were considered eligible. The SBRT boost was done to achieve a total combined dose biological equivalent dose >100 Gy to the residual primary tumor, consisting of 10 Gy 2 fractions (20 Gy total) for peripheral tumors, and 6.5 Gy 3 fractions (19.5 Gy total) for medial tumors using the Radiation Therapy Oncology Group protocol 0813 definitions. The primary endpoint was the development of grade ?3 radiation pneumonitis (RP). Results: After a median follow-up of 13 months, 4 patients developed acute grade 3 RP, and 1 (2.9%) developed late and persistent grade 3 RP. No patients developed grade 4 or 5 RP. Mean lung dose, V2.5, V5, V10, and V20 values were calculated for the SBRT boost, and none were found to significantly predict for RP. Only advancing age (P=.0147), previous smoking status (P=.0505), and high CRT mean lung dose (P=.0295) were significantly associated with RP development. At the time of analysis, the actuarial local control rate at the primary tumor site was 82.9%, with only 6 patients demonstrating recurrence. Conclusions: Linear accelerator-based SBRT for dose escalation of limited residual NSCLC after definitive CRT was feasible and did not increase the risk for toxicity above that for standard radiation therapy.

  15. IL-2R{gamma} gene microdeletion demonstrates that canine X-linked severe combined immunodeficiency is a homologue of the human disease

    SciTech Connect (OSTI)

    Henthorn, P.S.; Fimiani, V.M.; Patterson, D.F.

    1994-09-01

    X-linked severe combined immunodeficiency (SCID) is characterized by profound defects in cellular and humoral immunity and, in humans, is associated with mutations in the gene for the {gamma} chain of the IL-2 receptor (IL-2R{gamma}). We have examined this gene in a colony of dogs established from a single X-linked SCID carrier female. Affected dogs have a 4-bp deletion in the first exon of the IL-2R{gamma} gene, which precludes the production of a functional protein, demonstrating that the canine disease is a true homologue of human X-linked SCID. 37 refs., 3 figs.

  16. Enhanced vector borne disease surveillance of California Culex mosquito populations reveals spatial and species-specific barriers of infection.

    SciTech Connect (OSTI)

    VanderNoot, Victoria A.; Curtis, Deanna Joy; Koh, Chung-Yan; Brodsky, Benjamin H; Lane, Todd

    2014-08-01

    Monitor i ng in f ectio n s in v ect o rs su c h as m osquit o es, s a nd fl i es, tsetse fl i es, a nd ticks to i denti f y hu m a n path o gens m a y s e r v e as a n ear l y w arn i ng det e ction system t o dir e ct loc a l g o v er n ment dise a se pr e v en t i v e m easu r e s . One major hurdle i n de t ection is the abi l i t y to scre e n l arge n u mbers of v e c t ors for h uman patho g ens w i thout t h e u s e of ge n o t y pe - s p ecific m o lecu l ar tec h nique s . N e x t genera t ion s equ e nc i ng (NG S ) pr o v i des a n unbi a sed p latfo r m capab l e of identi f y i ng k n o w n a n d unk n o w n p ath o ge n s circula t ing w i thin a v e ctor p opul a tion, but utili z ing t h is te c h nolo g y i s tim e - con s u ming a n d cos t l y for v ecto r -b o rne disease su r v e illan c e pr o gra m s. T o addr e s s this w e d e v e lop e d cos t -eff e ct i v e Ilumina(r) R NA- S eq l i bra r y p r epara t ion m e thodol o gies i n con j u n ction w i t h an automa t ed c ompu t at i onal a n a l y sis pipel i n e to ch a racter i ze t h e microbial popula t ions c ircula t i n g in Cu l e x m o squit o e s (Cul e x qui n quef a s c iatu s , C ul e x quinq u efasc i atus / pip i ens co m pl e x h y bri d s, and C u l e x ta r salis ) t hroug h out Californ i a. W e assembled 2 0 n o vel a n d w e l l -do c ume n ted a r b o v i ruses repres e nting mem b e rs of B u n y a v ir i da e , F l a v i virid a e, If a virida e , Meson i v i rida e , Nid o v iri d ae, O rtho m y x o virid a e, Pa r v o v iri d ae, Re o virid a e, R h a b d o v i rid a e, T y m o v iri d ae, a s w ell as s e v e r al u n assi g n e d v irus e s . In addit i o n, w e m app e d mRNA s pecies to d i vergent s peci e s of t r y panos o ma a nd pl a s modium eu k a r yotic parasit e s and cha r a c terized t he p r oka r yot i c microb i al c o mposit i on to i d enti f y bacteri a l tran s c r ipts der i v ed from wolba c hia, clo s tridi u m, m y c oplas m a, fusoba c

  17. A modified inflammatory bowel disease questionnaire and the Vaizey Incontinence questionnaire are more sensitive measures of acute gastrointestinal toxicity during pelvic radiotherapy than RTOG grading

    SciTech Connect (OSTI)

    Khalid, Usman; McGough, Camilla; Hackett, Claire; Blake, Peter; Harrington, Kevin J.; Khoo, Vincent S.; Tait, Diana; Norman, Andrew R.; Andreyev, H. Jervoise N. . E-mail: j@andreyev.demon.co.uk

    2006-04-01

    Purpose: Simple scales with greater sensitivity than Radiation Therapy Oncology Group (RTOG) grading to detect acute gastrointestinal toxicity during pelvic radiotherapy, could be clinically useful. Methods and Materials: Do questionnaires used in benign gastrointestinal diseases detect toxicity in patients undergoing radiotherapy? The patient-completed Inflammatory Bowel Disease (IBDQ) and Vaizey Incontinence questionnaires were compared prospectively at baseline and at Week 5 to physician-completed RTOG grading. Results: A total of 107 patients, median age 63 years, were recruited. After 5 weeks of treatment, patients with gynecologic and gastrointestinal cancer were more symptomatic than urologic patients (p 0.012; p = 0.014). Overall, 94% had altered bowel habits, 80% loose stool, 74% frequency, 65% difficult gas, 60% pain, >48% distress, 44% tenesmus, >40% restrictions in daily activity, 39% urgency, 37% fecal incontinence, and 40% required antidiarrheal medication. The median RTOG score was 1 (range, 0-2), median IBDQ score 204.5 (range, 74-224), and median Vaizey score 5 (range, 0-20). Chemotherapy preceding radiotherapy increased fecal incontinence (p 0.002). RTOG scores stabilized after 3 weeks, IBDQ scores peaked at Week 4, and Vaizey scores worsened throughout treatment. IBDQ and Vaizey scores distinguished between groups with different RTOG scores. Conclusion: The IBDQ and Vaizey questionnaires are reliable and sensitive, offering greater insight into the severity and range of symptoms compared with RTOG grading.

  18. A radiation hybrid map of the distal short arm of human chromosome II, containing the Beckwith-Weidemann and associated embroyonal tumor disease loci

    SciTech Connect (OSTI)

    Richard, C.W. III; Berg, D.J.; Meeker, T.C.; Myers, R.M.; Cox, D.R. ); Boehnke, M.; Hauser, E. ); Lichy, J.H. )

    1993-05-01

    The authors describe a high-resolution radiation hybrid (RH) map of the distal short arm of human chromosome 11 containing the Beckwith-Weidemann gene and the associated embryonal tumor disease loci. Thirteen human 11p15 genes and 17 new anonymous probes were mapped by a statistical analysis of the cosegregation of markers in 102 rodent-human radiation hybrids retaining fragments of human chromosome 11. The 17 anonymous probes were generated from lambda phage containing human 11p15.5 inserts, by using ALU-PCR. A comprehensive map of all 30 loci and a framework map of nine clusters of loci ordered at odds of 1,000:1 were constructed by a multipoint maximum-likelihood approach by using the computer program RHMAP. This RH map localizes one new gene to chromosome 11p15 (WEE1), provides more precise order information for several 11p15 genes (CTSD, H19, HPX,.ST5, RNH, and SMPD1), confirms previous map orders for other 11p15 genes (CALCA, PTH, HBBC, TH, HRAS, and DRD4), and maps 17 new anonymous probes within the 11p15.5 region. This RH map should prove useful in better defining the positions of the Beckwith-Weidemann and associated embryonal tumor disease-gene loci. 41 refs., 1 fig., 2 tabs.

  19. Enter filename

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    sources, prenatal radiation exposure, maternal or child medications, pesticides, second-hand cigarette smoke, factors associated with maternal pregnancy history (maternal age...

  20. Update to agency for toxic substances and disease registry 2012 report on assessment of biota exposure to mercury originating from Savannah River Site.

    SciTech Connect (OSTI)

    Kuhne, W.

    2015-08-10

    The purpose of this report is to 1) update previous Savannah River National Laboratory (SRNL) assessment reports (Kvartek et al. 1994 and Halverson et al. 2008) on the fate of mercury in the Savannah River Site (SRS) environment and 2) address comments and recommendations from the review of SRS by the Agency for Toxic Substances and Disease Registry (ATSDR) concerning the evaluation of exposures to contaminants in biota originating from the SRS. The ATSDR reviewed and evaluated data from SRS, South Carolina Department of Health & Environmental Control (SCDHEC) and the Georgia Department of Natural Resources (GDNR) concerning the non-radioactive contaminant mercury. This report will provide a response and update to conclusions and recommendations made by the ATSDR.

  1. Enhanced sensitivity and specificity of thallium-201 imaging for the detection of regional ischemic coronary disease by combining SPECT with bull's eye analysis

    SciTech Connect (OSTI)

    Kasabali, B.; Woodard, M.L.; Bekerman, C.; Pinsky, S.; Blend, M.J. (Michael Reese Hospital and Medical Center, Chicago, IL (USA))

    1989-07-01

    Previous studies have indicated that the combination of single photon emission computed tomography (SPECT) and quantitative bull's eye analysis (QBA) TI-201 cardiac stress imaging may improve the detection of myocardial ischemia over that achieved with planar (PLN) imaging. This study will evaluate the sensitivity and specificity of SPECT and QBA in the detection of disease in the left anterior descending (LAD), left circumflex (LCX), and right coronary artery. Ninety-nine patients who underwent both TI-201 stress imaging and coronary arteriography were evaluated retrospectively. Of the 99, 62 had PLN imaging and 37 were evaluated with SPECT; 23 of these 37 had QBA. The overall sensitivity and specificity were as follows: PLN, 94% and 50%; SPECT, 90% and 67%; QBA, 100% and 20%; and SPECT with QBA, 92% and 72%, respectively. The regional sensitivity and specificity of PLN for individual coronary arteries were as follows: RCA, 78% and 74%; LAD, 89% and 60%; LCX, 50% and 89%, respectively. For SPECT, the results were: RCA, 86% and 93%; LAD, 85% and 88%; and LCX, 60% and 88%. For QBA alone, the results were: RCA, 100% and 75%; LAD, 88% and 53%; and LCX, 100% and 89%. The results for QBA with SPECT were: RCA, 100% and 94%; LAD, 88% and 80%; and LCX, 67% and 95%. Thus, SPECT interpreted on conjunction with QBA showed higher sensitivity for evaluation of ischemia in the RCA and LCX arteries and higher specificity in the detection of LAD and RCA disease than did PLN TI-201 imaging. Because of the low specificity of QBA (20%), caution is advised in the interpretation of QBA alone without reviewing SPECT images.

  2. Impact of 18F-Fluoro-2-Deoxyglucose Positron Emission Tomography on Treatment Strategy and Radiotherapy Planning for Stage I-II Hodgkin Disease: A Prospective Multicenter Study

    SciTech Connect (OSTI)

    Pommier, Pascal; Dussart, Sophie; Girinsky, Theodore; Chabaud, Sylvie; Lagrange, Jean Leon; Nguyen, Tan Dat; Beckendorff, Veronique; D'Hombres, Anne; Artignan, Xavier; Bondiau, Pierre Yves; Carrie, Christian; Giammarile, Francesco

    2011-03-01

    Purpose: To quantify the impact of preradiotherapy 18F-fluoro-2-deoxyglucose positron-emission tomography (FDG-PET) on treatment strategy and radiotherapy planning for patients with Stage I/II Hodgkin disease included in a large prospective multicenter study. Patients and Methods: Conventional computed tomography and FDG-PET were performed just before the planned radiotherapy. The radiotherapy plan was first elaborated under blinded conditions for FDG-PET data. Then, the medical staff was asked to confirm or not confirm the treatment strategy and, if appropriate, to modify the radiotherapy plan based on additional information from FDG-PET. Results: Between January 2004 and January 2006, 137 patients were included (124 were available for analysis) in 11 centers (108 adults, 16 children). All but 1 patient had received chemotherapy before inclusion. Prechemotherapy work-up included FDG-PET for 61 patients, and data were available for elaboration of the first radiotherapy plan. Based on preradiotherapy FDG-PET data, the radiotherapy was cancelled in 6 patients (4.8%), and treatment plan modifications occurred in 16 patients (12.9%): total dose (11 patients), CTV volume (5 patients), number of beam incidences (6 patients), and number of CTV (6 patients). The concordance between the treatment strategies with or without preradiotherapy FDG-PET was 82.3%. Concordance results were not significantly different when prechemotherapy PET-CT information was available. Conclusion: Preradiotherapy FDG-PET for treatment planning in Hodgkin lymphoma may lead to significant modification of the treatment strategy and the radiotherapy planning in patients with Stage I or II Hodgkin disease, even in those who have undergone FDG-PET as part of the prechemotherapy work-up.

  3. A Multicenter Retrospective Analysis of Survival Outcome Following Postoperative Chemoradiotherapy in Non-Small-Cell Lung Cancer Patients With N2 Nodal Disease

    SciTech Connect (OSTI)

    Zou Bingwen; Xu Yong; Li Tao; Li Wenhui; Tang Bangxian; Zhou Lin; Li Lu; Liu Yongmei; Zhu Jiang; Huang Meijuan; Wang Jin; Ren Li; Gong Youlin; Che Guowei; Liu Lunxu; Hou Mei; Lu You

    2010-06-01

    Purpose: To retrospectively evaluate the role of postoperative chemoradiotherapy (POCRT) in patients with completely resected non-small-cell lung cancer (NSCLC) with N2 lymph node involvement. Methods and Materials: This study included 183 patients from four centers in southwest China who underwent radical section of Stage III-N2 NSCLC without any preoperative therapy. One hundred and four were treated with POCRT and 79 with postoperative chemotherapy (POCT) alone. The median radiation dose to clinical target volume (CTV) was 50 Gy (varying between 48 and 54 Gy), whereas the cycles of platinum-based chemotherapy ranged from two to six with a median of four. Results: The median duration of follow-up was 72 months. The 5-year overall survival rate (OS) was 30.5% in the POCRT group, and 14.4% in the POCT group (p = 0.007). The 5-year disease-free survival rate (DFS) was 22.2% in POCRT group and 9.3% in POCT group (p = 0.003). In a multivariate analysis, N1 nodal involvement (N1+/N2+) was associated with significantly worse OS (HR = 1.454, 95% CI, 1.012-2.087, p = 0.043) and DFS (HR = 1.685, 95% CI, 1.196-2.372, p = 0.003). Absence of radiotherapy and treatment with fewer than three cycles of chemotherapy both were poor prognostic factors for both OS and DFS. Conclusions: As compared with chemotherapy alone, adjuvant treatment with both radiotherapy and chemotherapy improves survival in patients with completely resected Stage III-N2 nodal disease in NSCLC. Future study of treatment modality with radiotherapy and chemotherapy is warranted, especially focusing on both N1 and N2 nodal status.

  4. Impact of Preoperative Radiotherapy on General and Disease-Specific Health Status of Rectal Cancer Survivors: A Population-Based Study

    SciTech Connect (OSTI)

    Thong, Melissa S.Y.; Mols, Floortje; Lemmens, Valery E.P.P.; Rutten, Harm J.T.; Roukema, Jan A.; Martijn, Hendrik; Poll-Franse, Lonneke V. van de

    2011-11-01

    Purpose: To date, few studies have evaluated the impact of preoperative radiotherapy (pRT) on long-term health status of rectal cancer survivors. Using a population-based sample, we assessed the impact of pRT on general and disease-specific health status of rectal cancer survivors up to 10 years postdiagnosis. The health status of older ({>=}75 years old at diagnosis) pRT survivors was also compared with that of younger survivors. Methods and Materials: Survivors identified from the Eindhoven Cancer Registry treated with surgery only (SU) or with pRT between 1998 and 2007 were included. Survivors completed the Short Form-36 (SF-36) health survey questionnaire and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 38 (EORTC QLQ-CR38) questionnaire. The SF-36 and EORTC QLQ-CR38 (sexuality subscale) scores of the survivors were compared to an age- and sex-matched Dutch normal population. Results: A total of 340 survivors (response, 85%; pRT survivors, 71%) were analyzed. Overall, survivors had similar general health status. Both short-term (<5 years) and long-term ({>=}5 years) pRT survivors had significantly poorer body image and more problems with gastrointestinal function, male sexual dysfunction, and defecation than SU survivors. Survivors had comparable general health status but greater sexual dysfunction than the normal population. Older pRT survivors had general and disease-specific health status comparable to that of younger pRT survivors. Conclusions: For better survivorship care, rectal cancer survivors could benefit from increased clinical and psychological focus on the possible long-term morbidity of treatment and its effects on health status.

  5. Whole Abdominopelvic Radiotherapy Using Intensity-Modulated Arc Therapy in the Palliative Treatment of Chemotherapy-Resistant Ovarian Cancer With Bulky Peritoneal Disease: A Single-Institution Experience

    SciTech Connect (OSTI)

    De Meerleer, Gert; Vandecasteele, Katrien; Ost, Piet; Delrue, Louke; Denys, Hannelore; Makar, Amin; Speleers, Bruno; Van Belle, Simon; Van den Broecke, Rudy; Fonteyne, Valerie; De Neve, Wilfried

    2011-03-01

    Purpose: To retrospectively review our experience with whole abdominopelvic radiotherapy (WAPRT) using intensity-modulated arc therapy in the palliative treatment of chemotherapy-resistant ovarian cancer with bulky peritoneal disease. Methods and Materials: Between April 2002 and April 2008, 13 patients were treated with WAPRT using intensity-modulated arc therapy. We prescribed a dose of 33 Gy to be delivered in 22 fractions of 1.5 Gy to the abdomen and pelvis. All patients had International Federation of Gynecology and Obstetrics Stage III or IV ovarian cancer at the initial diagnosis. At referral, the median age was 61 years, and the patients had been heavily pretreated with surgery and chemotherapy. All patients had symptoms from their disease, including gastrointestinal obstruction or subobstruction in 6, minor gastrointestinal symptoms in 2, pain in 4, ascites in 1, and vaginal bleeding in 2. A complete symptom or biochemical response required complete resolution of the patient's symptoms or cancer antigen-125 level. A partial response required {>=}50% resolution of these parameters. The actuarial survival was calculated from the start of radiotherapy. Results: The median overall survival was 21 weeks, with a 6-month overall survival rate of 45%. The 9 patients who completed treatment obtained a complete symptom response, except for ascites (partial response). The median and mean response duration (all symptoms grouped) was 24 and 37 weeks, respectively. Of the 6 patients presenting with obstruction or subobstruction, 4 obtained a complete symptom response (median duration, 16 weeks). Conclusion: WAPRT delivered using intensity-modulated arc therapy offers important palliation in the case of peritoneal metastatic ovarian cancer. WAPRT resolved intestinal obstruction for a substantial period.

  6. AAV-mediated delivery of the transcription factor XBP1s into the striatum reduces mutant Huntingtin aggregation in a mouse model of Huntington's disease

    SciTech Connect (OSTI)

    Zuleta, Amparo [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile) [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile); Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, University of Chile, Santiago (Chile); Vidal, Rene L. [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile) [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile); Neurounion Biomedical Foundation, Santiago (Chile); Armentano, Donna; Parsons, Geoffrey [Department of Molecular Biology, Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States)] [Department of Molecular Biology, Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States); Hetz, Claudio, E-mail: chetz@med.uchile.cl [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile) [Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago (Chile); Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, University of Chile, Santiago (Chile); Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Av., Boston, MA 02446 (United States); Neurounion Biomedical Foundation, Santiago (Chile)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer The contribution of ER stress to HD has not been directly addressed. Black-Right-Pointing-Pointer Expression of XBP1s using AAVs decreases Huntingtin aggregation in vivo. Black-Right-Pointing-Pointer We describe a new in vivo model of HD based on the expression of a large fragment of mHtt-RFP. -- Abstract: Huntington's disease (HD) is caused by mutations that expand a polyglutamine region in the amino-terminal domain of Huntingtin (Htt), leading to the accumulation of intracellular inclusions and progressive neurodegeneration. Recent reports indicate the engagement of endoplasmic reticulum (ER) stress responses in human HD post mortem samples and animal models of the disease. Adaptation to ER stress is mediated by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that attenuates protein folding stress by controlling the expression of distinct transcription factors including X-Box binding protein 1 (XBP1). Here we targeted the expression of XBP1 on a novel viral-based model of HD. We delivered an active form of XBP1 locally into the striatum of adult mice using adeno-associated vectors (AAVs) and co-expressed this factor with a large fragment of mutant Htt as a fusion protein with RFP (Htt588{sup Q95}-mRFP) to directly visualize the accumulation of Htt inclusions in the brain. Using this approach, we observed a significant reduction in the accumulation of Htt588{sup Q95}-mRFP intracellular inclusion when XBP1 was co-expressed in the striatum. These results contrast with recent findings indicating a protective effect of XBP1 deficiency in neurodegeneration using knockout mice, and suggest a potential use of gene therapy strategies to manipulate the UPR in the context of HD.

  7. Prognostic Importance of Gleason 7 Disease Among Patients Treated With External Beam Radiation Therapy for Prostate Cancer: Results of a Detailed Biopsy Core Analysis

    SciTech Connect (OSTI)

    Spratt, Daniel E.; Zumsteg, Zach; Ghadjar, Pirus; Pangasa, Misha; Pei, Xin; Fine, Samson W.; Yamada, Yoshiya; Kollmeier, Marisa; Zelefsky, Michael J.

    2013-04-01

    Purpose: To analyze the effect of primary Gleason (pG) grade among a large cohort of Gleason 7 prostate cancer patients treated with external beam radiation therapy (EBRT). Methods and Materials: From May 1989 to January 2011, 1190 Gleason 7 patients with localized prostate cancer were treated with EBRT at a single institution. Of these patients, 613 had a Gleason 7 with a minimum of a sextant biopsy with nonfragmented cores and full biopsy core details available, including number of cores of cancer involved, percentage individual core involvement, location of disease, bilaterality, and presence of perineural invasion. Median follow-up was 6 years (range, 1-16 years). The prognostic implication for the following outcomes was analyzed: biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM). Results: The 8-year bRFS rate for pG3 versus pG4 was 77.6% versus 61.3% (P<.0001), DMFS was 96.8% versus 84.3% (P<.0001), and PCSM was 3.7% versus 8.1% (P=.002). On multivariate analysis, pG4 predicted for significantly worse outcome in all parameters. Location of disease (apex, base, mid-gland), perineural involvement, maximum individual core involvement, and the number of Gleason 3+3, 3+4, or 4+3 cores did not predict for distant metastases. Conclusions: Primary Gleason grade 4 independently predicts for worse bRFS, DMFS, and PCSM among Gleason 7 patients. Using complete core information can allow clinicians to utilize pG grade as a prognostic factor, despite not having the full pathologic details from a prostatectomy specimen. Future staging and risk grouping should investigate the incorporation of primary Gleason grade when complete biopsy core information is used.

  8. Long none coding RNA HOTTIP/HOXA13 act as synergistic role by decreasing cell migration and proliferation in Hirschsprung disease

    SciTech Connect (OSTI)

    Xie, Hua; Zhu, Dongmei; Xu, Cao; Zhu, Hairong; Chen, Pingfa; Li, Hongxing; Liu, Xiang; Xia, Yankai; Tang, Weibing

    2015-08-07

    Long noncoding RNAs (lncRNAs) have been confirmed to be associated with various human diseases. However, whether they are associated with Hirschsprung disease (HSCR) progression remains unclear. In this study, we designed the experiment to explore the relationship between lncRNA HOTTIP and HOXA13, and their pathogenicity to HSCR. Quantitative real-time PCR and Western blot were performed to detect the levels of lncRNA, mRNAs, and proteins in colon tissues from 79 patients with HSCR and 79 controls. Small RNA interference transfection was used to study the function experiments in human 293T and SK-N-BE cell lines. The cell viability and activities were detected by the transwell assays, CCK8 assay, and flow cytometry, respectively. LncRNA HOTTIP and HOXA13 were significantly down-regulated in HSCR compared to the controls. Meanwhile, the declined extent of their expression levels makes sense between two main phenotype of HSCR. SiRNA-mediated knock-down of HOTTIP or HOXA13 correlated with decreased levels of each other and both reduced the cell migration and proliferation without affecting cell apoptosis or cell cycle. Our study demonstrates that aberrant reduction of HOTTIP and HOXA13, which have a bidirectional regulatory loop, may play an important role in the pathogenesis of HSCR. - Highlights: • LncRNA HOTTIP and HOXA13 are both down-regulated in HSCR. • HOTTIP and HOXA13 can regulate each other in 293T and SK-N-BE(2) cell lines. • Both HOTTIP and HOXA13 can decrease cell migration and proliferation.

  9. Development and Characterization of a Multiplexed RT-PCR Species Specific Assay for Bovine and one for Porcine Foot-and-Mouth Disease Virus Rule-Out Supplemental Materials

    SciTech Connect (OSTI)

    Smith, S; Danganan, L; Tammero, L; Lenhoff, R; Naraghi-arani, P; Hindson, B

    2007-08-06

    Lawrence Livermore National Laboratory (LLNL), in collaboration with the Department of Homeland Security (DHS) and the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS) has developed advanced rapid diagnostics that may be used within the National Animal Health Laboratory Network (NAHLN), the National Veterinary Services Laboratory (Ames, Iowa) and the Plum Island Animal Disease Center (PIADC). This effort has the potential to improve our nation's ability to discriminate between foreign animal diseases and those that are endemic using a single assay, thereby increasing our ability to protect animal populations of high economic importance in the United States. Under 2005 DHS funding we have developed multiplexed (MUX) nucleic-acid-based PCR assays that combine foot-and-mouth disease virus (FMDV) detection with rule-out tests for two other foreign animal diseases Vesicular Exanthema of Swine (VESV) and Swine Vesicular Disease (SVD) and four other domestic viral diseases Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus 1 (BHV-1 or Infectious Bovine Rhinotracheitus IBR), Bluetongue virus (BTV) and Parapox virus complex (which includes Bovine Papular Stomatitis Virus BPSV, Orf of sheep, and Pseudocowpox). Under 2006 funding we have developed a Multiplexed PCR [MUX] porcine assay for detection of FMDV with rule out tests for VESV and SVD foreign animal diseases in addition to one other domestic vesicular animal disease vesicular stomatitis virus (VSV) and one domestic animal disease of swine porcine reproductive and respiratory syndrome (PRRS). We have also developed a MUX bovine assay for detection of FMDV with rule out tests for the two bovine foreign animal diseases malignant catarrhal fever (MCF), rinderpest virus (RPV) and the domestic diseases vesicular stomatitis virus (VSV), bovine viral diarrhea virus (BVDV), infectious bovine rhinotracheitus virus (BHV-1), bluetongue virus (BTV), and the Parapox viruses

  10. BRCA1 loss pre-existing in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood

    SciTech Connect (OSTI)

    Bednarz, Natalia; Eltze, Elke; Semjonow, Axel; Rink, Michael; Andreas, Antje; Mulder, Lennart; Hannemann, Juliane; Fisch, Margit; Pantel, Klaus; Weier, Heinz-Ulrich G.; Bielawski, Krzysztof P.; Brandt, Burkhard

    2010-03-19

    A recent study concluded that serum prostate specific antigen (PSA)-based screening is beneficial for reducing the lethality of PCa, but was also associated with a high risk of 'overdiagnosis'. Nevertheless, also PCa patients who suffered from organ confined tumors and had negative bone scans succumb to distant metastases after complete tumor resection. It is reasonable to assume that those tumors spread to other organs long before the overt manifestation of metastases. Our current results confirm that prostate tumors are highly heterogeneous. Even a small subpopulation of cells bearing BRCA1 losses can initiate PCa cell regional and distant dissemination indicating those patients which might be at high risk of metastasis. A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances (AI) among circulating tumor cells (CTCs). The present analysis was aimed to elucidate the biological and clinical role of BRCA1 losses on metastatic spread and tumor progression in prostate cancer patients. Experimental Design: To map molecular progression in PCa outgrowth we used FISH analysis of tissue microarrays (TMA), lymph node sections and CTC from peripheral blood. We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by AI of the tumor suppressor gene PTEN and lack of the BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (p < 0.05), invasion to pelvic lymph nodes (LN, p < 0.05) as well as BR (p < 0.01). Their prevalence was twice as high within 62 LN metastases (LNMs) as in primary tumors (27%, p < 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between those two sites. In 4 of 7 patients with metastatic disease, BRCA1 losses

  11. Effect of Intravascular Iodinated Contrast Media on Natural Course of End-Stage Renal Disease Progression in Hemodialysis Patients: A Prospective Study

    SciTech Connect (OSTI)

    Janousek, Radim; Krajina, Antonin; Peregrin, Jan H.; Dusilova-Sulkova, Sylvie; Renc, Ondrej; Hajek, Jan; Dvorak, Kamil; Fixa, Petr; Cermakova, Eva

    2010-02-15

    We evaluated the impact of intravascular iodinated contrast medium on residual diuresis in hemodialyzed patients. Two groups of clinically stable hemodialyzed patients with residual diuresis minimally 500 ml of urine per day were studied. The patients from the first group were given iso-osmolal contrast agent iodixanol (Visipaque, GE Healthcare, United Kingdom) in concentration of iodine 320 mg/ml with osmolality 290 mOsm/kg of water during the endovascular procedure. The second control group was followed without contrast medium administered. Residual diuresis and residual renal excretory capacity expressed as 24-h calculated creatinine clearance were evaluated in the both groups after 6 months. The evaluated group included 42 patients who were given 99.3 ml of iodixanol in average (range, 60-180 ml). The control group included 45 patients. There was no statistically significant difference found between both groups in daily volume of urine (P = 0.855) and calculated clearance of creatinine (P = 0.573). We can conclude that residual diuresis is not significantly influenced by intravascular administration of iso-osmolal iodinated contrast agent (iodixanol) in range of volume from 60 to 180 ml in comparison to natural course of urinary output and residual renal function during end-stage renal disease. This result can help the nephrologist to decide which imaging method/contrast medium to use in dialyzed patients in current practice.

  12. Using Wikipedia to forecast diseases

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    the same way we check the weather each morning, individuals ... Brazil and Thailand, and tuberculosis in China and Thailand. ... public health data in one location and use it in another. ...

  13. Zika Virus Disease and Prevention

    Broader source: Energy.gov (indexed) [DOE]

    Most common symptoms of Zika are fever, rash, joint pain, or conjunctivitis (red eyes). ... they develop a fever, rash, joint pain, or red eyes during their trip or within 2 weeks ...

  14. Using Wikipedia to forecast disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    to plan for future outbreaks. The LANL team was able to successfully monitor influenza in the United States, dengue fever in Brazil and Thailand, and tuberculosis in China...

  15. Fridges to fight childhood disease

    SciTech Connect (OSTI)

    Lerner, T.

    1983-04-01

    A solar-powered refrigerator/freezer has been installed in a medical center in Bhoorbaral, India. The installation and performance of the refrigerator/freezer are described.

  16. Improved medical implants comes from nanostructuring

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    However, cobalt-chromium superalloys, stainless steels, and titanium alloys-the most commonly used materials in today's orthopedic devices- have the potential to present serious ...

  17. Comparative mapping of DNA markers from the familial Alzheimer disease and Down syndrome regions of human chromosome 21 to mouse chromosomes 16 and 17

    SciTech Connect (OSTI)

    Cheng, S.V.; Nadeau, J.H.; Tanzi, R.E.; Watkins, P.C.; Jagadesh, J.; Taylor, B.A.; Haines, J.L.; Sacchi, N.; Gusella, J.F. )

    1988-08-01

    Mouse trisomy 16 has been proposed as an animal model of Down syndrome (DS), since this chromosome contains homologues of several loci from the q22 band of human chromosome 21. The recent mapping of the defect causing familial Alzheimer disease (FAD) and the locus encoding the Alzheimer amyloid {beta} precursor protein (APP) to human chromosome 21 has prompted a more detailed examination of the extent of conservation of this linkage group between the two species. Using anonymous DNA probes and cloned genes from human chromosome 21 in a combination of recombinant inbred and interspecific mouse backcross analyses, the authors have established that the linkage group shared by mouse chromosome 16 includes not only the critical DS region of human chromosome 21 but also the APP gene and FAD-linked markers. Extending from the anonymous DNA locus D21S52 to ETS2, the linkage map of six loci spans 39% recombination in man but only 6.4% recombination in the mouse. A break in synteny occurs distal to ETS2, with the homologue of the human marker D21S56 mapping to mouse chromosome 17. Conservation of the linkage relationships of markers in the FAD region suggests that the murine homologue of the FAD locus probably maps to chromosome 16 and that detailed comparison of the corresponding region in both species could facilitate identification of the primary defect in this disorder. The break in synteny between the terminal portion of human chromosome 21 and mouse chromosome 16 indicates, however, that mouse trisomy 16 may not represent a complete model of DS.

  18. Prospective Study Evaluating Postoperative Radiotherapy Plus 2-Year Androgen Suppression for Post-Radical Prostatectomy Patients With Pathologic T3 Disease and/or Positive Surgical Margins

    SciTech Connect (OSTI)

    Choo, Richard [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States)], E-mail: choo.c@mayo.edu; Danjoux, Cyril; Gardner, Sandra; Morton, Gerard; Szumacher, Ewa; Loblaw, D. Andrew; Cheung, Patrick [Department of Radiation Oncology, Odette Cancer Centre, University of Toronto, Toronto, ON (Canada); Pearse, Maria [Department of Radiation Oncology, Auckland Hospital, Auckland (New Zealand)

    2009-10-01

    Purpose: To determine the efficacy of a combined approach of postoperative radiotherapy (RT) plus 2-year androgen suppression (AS) for patients with pathologic T3 disease (pT3) and/or positive surgical margins (PSM) after radical prostatectomy (RP). Methods and Materials: A total of 78 patients with pT3 and/or PSM after RP were treated with RT plus 2-year AS, as per a pilot, prospective study. Androgen suppression started within 1 month after the completion of RT and consisted of nilutamide for 4 weeks and buserelin acetate depot subcutaneously every 2 months for 2 years. Relapse-free rate, including freedom from prostate-specific antigen (PSA) relapse, was estimated using the Kaplan-Meier method. A Cox regression analysis was performed to evaluate prognostic factors for relapse. Prostate-specific antigen relapse was defined as a PSA rise above 0.2 ng/mL, with two consecutive increases over a minimum of 3 months. Results: The median age was 61 years at the time of RP. The median interval between RP and postoperative RT was 4.2 months. Forty-nine patients had undetectable PSA (<0.2 ng/mL), and 29 had persistently detectable postoperative PSA at the time of the protocol treatment. Median follow-up from RT was 6.4 years. Relapse-free rates at 5 and 7 years were 94.4% and 86.3%, respectively. Survival rates were 96% at 5 years and 93.1% at 7 years. On Cox regression analysis, persistently detectable postoperative PSA and pT3b-T4 were significant predictors for relapse. Conclusion: The combined treatment of postoperative RT plus 2-year AS yielded encouraging results for patients with pT3 and/or PSM and warrants a confirmatory study.

  19. Efficacy and Safety of a Novel Vascular Closure Device (Glubran 2 Seal) After Diagnostic and Interventional Angiography in Patients with Peripheral Arterial Occlusive Disease

    SciTech Connect (OSTI)

    Del Corso, Andrea; Bargellini, Irene Cicorelli, Antonio; Perrone, Orsola; Leo, Michele; Lunardi, Alessandro; Alberti, Aldo; Tomei, Francesca; Cioni, Roberto; Ferrari, Mauro; Bartolozzi, Carlo

    2013-04-15

    To prospectively evaluate safety and efficacy of a novel vascular closure device (Glubran 2 Seal) after peripheral angiography in patients with peripheral arterial occlusive disease (PAOD). From December 2010 to June 2011, all consecutive patients with PAOD undergoing peripheral angiography were prospectively enrolled onto the study after percutaneous antegrade or retrograde puncture of the common femoral artery. After angiography, the Glubran 2 Seal device was used to achieve hemostasis. The following data were registered: technical success and manual compression duration, patients' discomfort (scale 0-5), operators' technical difficulty (scale 0-5), and vascular complications. The site of hemostasis was evaluated by clinical inspection and color-coded Duplex ultrasound performed 1 day and 1 month after the procedure. One hundred seventy-eight patients were enrolled (112 male, mean age 70.8 years) with a total of 206 puncture sites, including 104 (50.5 %) antegrade accesses. The device was successful in 198(96.1 %) of 206 procedures, with 8 cases of manual compression lasting longer than 5 min (maximum 20 min). No major vascular complications were observed, resulting in 100 % procedural success. Minor complications occurred in seven procedures (3.4 %), including two cases of pseudoaneurysms, successfully treated by ultrasound-guided glue injection. The mean {+-} standard deviation score for patients' discomfort was 0.9 {+-} 0.7, whereas the mean score for operators' difficulty was 1.2 {+-} 0.9. In patients with PAOD, the Glubran 2 Seal represents a simple, painless, and efficient vascular closure device, able to achieve hemostasis both in antegrade and retrograde accesses.

  20. TU-C-12A-12: Differentiating Bone Lesions and Degenerative Joint Disease in NaF PET/CT Scans Using Machine Learning

    SciTech Connect (OSTI)

    Perk, T; Bradshaw, T; Muzahir, S; Jeraj, R; Meyer, E

    2014-06-15

    Purpose: [F-18]NaF PET can be used to image bone metastases; however, tracer uptake in degenerative joint disease (DJD) often appears similar to metastases. This study aims to develop and compare different machine learning algorithms to automatically identify regions of [F-18]NaF scans that correspond to DJD. Methods: 10 metastatic prostate cancer patients received whole body [F-18]NaF PET/CT scans prior to treatment. Image segmentation resulted in 852 ROIs, 69 of which were identified by a nuclear medicine physician as DJD. For all ROIs, various PET and CT textural features were computed. ROIs were divided into training and testing sets used to train eight different machine learning classifiers. Classifiers were evaluated based on receiver operating characteristics area under the curve (AUC), sensitivity, specificity, and positive predictive value (PPV). We also assessed the added value of including CT features in addition to PET features for training classifiers. Results: The training set consisted of 37 DJD ROIs with 475 non-DJD ROIs, and the testing set consisted of 32 DJD ROIs with 308 non-DJD ROIs. Of all classifiers, generalized linear models (GLM), decision forests (DF), and support vector machines (SVM) had the best performance. AUCs of GLM (0.929), DF (0.921), and SVM (0.889) were significantly higher than the other models (p<0.001). GLM and DF, overall, had the best sensitivity, specificity, and PPV, and gave a significantly better performance (p<0.01) than all other models. PET/CT GLM classifiers had higher AUC than just PET or just CT. GLMs built using PET/CT information had superior or comparable sensitivities, specificities and PPVs to just PET or just CT. Conclusion: Machine learning algorithms trained with PET/CT features were able to identify some cases of DJD. GLM outperformed the other classification algorithms. Using PET and CT information together was shown to be superior to using PET or CT features alone. Research supported by the Prostate

  1. Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease

    SciTech Connect (OSTI)

    Wahlang, Banrida; Song, Ming; Beier, Juliane I.; Cameron Falkner, K.; Al-Eryani, Laila; Clair, Heather B.; Prough, Russell A.; Osborne, Tanasa S.; Malarkey, David E.; Christopher States, J.; Cave, Matthew C.

    2014-09-15

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20 mg/kg or 200 mg/kg in corn oil) for 12 weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposure was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260 + HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20 mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200 mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200 mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant “second hit” in the transformation of steatosis to steatohepatitis. - Highlights: • Aroclor 1260 exposure decreased adiposity in mice fed with high fat diet • Aroclor 1260 exposure induced steatohepatitis in diet-induced obese mice • Aroclor 1260 (20 and 200 mg/kg) induced

  2. A case report of motor neuron disease in a patient showing significant level of DDTs, HCHs and organophosphate metabolites in hair as well as levels of hexane and toluene in blood

    SciTech Connect (OSTI)

    Kanavouras, Konstantinos; Tzatzarakis, Manolis N.; Mastorodemos, Vasileios; Plaitakis, Andreas; Tsatsakis, Aristidis M.

    2011-11-15

    Motor neuron disease is a devastating neurodegenerative condition, with the majority of sporadic, non-familial cases being of unknown etiology. Several epidemiological studies have suggested that occupational exposure to chemicals may be associated with disease pathogenesis. We report the case of a patient developing progressive motor neuron disease, who was chronically exposed to pesticides and organic solvents. The patient presented with leg spasticity and developed gradually clinical signs suggestive of amyotrophic lateral sclerosis, which was supported by the neurophysiologic and radiological findings. Our report is an evidence based case of combined exposure to organochlorine (DDTs), organophosphate pesticides (OPs) and organic solvents as confirmed by laboratory analysis in samples of blood and hair confirming systematic exposure. The concentration of non-specific dialkylphosphates metabolites (DAPs) of OPs in hair (dimethyphopshate (DMP) 1289.4 pg/mg and diethylphosphate (DEP) 709.4 pg/mg) and of DDTs (opDDE 484.0 pg/mg, ppDDE 526.6 pg/mg, opDDD 448.4 pg/mg, ppDDD + opDDT 259.9 pg/mg and ppDDT 573.7 pg/mg) were considerably significant. Toluene and n-hexane were also detected in blood on admission at hospital and quantified (1.23 and 0.87 {mu}g/l, respectively), while 3 months after hospitalization blood testing was found negative for toluene and n-hexane and hair analysis was provided decrease levels of HCHs, DDTs and DAPs. -- Highlights: Black-Right-Pointing-Pointer Exposure to pesticides and organic solvents might be a risk factor for sporadic MND. Black-Right-Pointing-Pointer We report a patient who developed progressive upper and lower motor neuron disease. Black-Right-Pointing-Pointer The patient had a history of occupational exposure to pesticides and solvents. Black-Right-Pointing-Pointer High DDTs' levels and increased levels of DMP and DEP were measured in his hair. Black-Right-Pointing-Pointer The patients' exposure to chemicals might have played

  3. PhyloChip Tackles Coral Disease

    ScienceCinema (OSTI)

    DeSantis, Todd

    2013-05-29

    Scientists at Berkeley Lab and the University of California, Merced are using an innovative DNA array developed at Berkeley Lab to catalog the microbes that live among coral in the tropical waters off the coast of Puerto Rico. More info: http://newscenter.lbl.gov/feature-stories/2009/02/02/coral-reefs/

  4. "Artificial" brains, electrical grids, and disease modeling:...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Deputy Principal Associate Director Duncan McBranch will discuss LDRD impacts on border security and the nation's energy grid at 1 p.m. The event is an ideal opportunity...

  5. PhyloChip Tackles Coral Disease

    SciTech Connect (OSTI)

    DeSantis, Todd

    2009-01-01

    Scientists at Berkeley Lab and the University of California, Merced are using an innovative DNA array developed at Berkeley Lab to catalog the microbes that live among coral in the tropical waters off the coast of Puerto Rico. More info: http://newscenter.lbl.gov/feature-stories/2009/02/02/coral-reefs/

  6. PhyloChip Tackles Coral Disease

    SciTech Connect (OSTI)

    Todd DeSantis

    2009-01-30

    Scientists at Berkeley Lab and the University of California, Merced are using an innovative DNA array developed at Berkeley Lab to catalog the microbes that live among coral in the tropical waters off the coast of Puerto Rico.

  7. PhyloChip Tackles Coral Disease

    ScienceCinema (OSTI)

    Todd DeSantis

    2010-01-08

    Scientists at Berkeley Lab and the University of California, Merced are using an innovative DNA array developed at Berkeley Lab to catalog the microbes that live among coral in the tropical waters off the coast of Puerto Rico.

  8. OCT for diagnosis of periodontal disease

    SciTech Connect (OSTI)

    Colston, B.W., LLNL

    1998-01-01

    We have developed a hand-held in vivo scanning device for use in the oral cavity. We produced, using this scanning device, in vivo OCT images of dental tissues in human volunteers. All the OCT images were analyzed for the presence of clinically relevant anatomical structures. The gingival margin, periodontal sulcus, and dento-enamel junction were visible in all the images. The cemento-enamel junction was discernible in 64% of the images and the alveolar bone presumptively identified for 71% of the images. These images represent, to our knowledge, the first in vivo OCT images of human dental tissue.

  9. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    more prone to form clusters or aggregates, suggesting that strategies for stabilizing SOD proteins could be useful in treating or preventing SOD-linked ALS. The Other ALS...

  10. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Light Source, researchers focused on the effects of mutations to a gene coding for a protein called superoxide dismutase (SOD). The study provides evidence that those proteins...

  11. Automated diagnostic kiosk for diagnosing diseases (Patent) ...

    Office of Scientific and Technical Information (OSTI)

    contained within a collection vial into the apparatus for automated diagnostic services. ... Save Share this Record Citation Formats MLA APA Chicago Bibtex Export Metadata Endnote ...

  12. Metabolic Prosthesis for Treating Ischemic Diseases - Energy...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    procedures (e.g., laser treatments andor vitrectomy in diabetic retinopathy) Safer than hyperbaric oxygen treatment regimes Reduces the potential for damage following ...

  13. Protein Instability and Lou Gehrig's Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Amyotrophic lateral sclerosis is notorious for its ability to strike down people in the prime of life. It first leapt into public consciousness when it afflicted baseball star...

  14. Chronic Beryllium Disease Prevention Program What's New

    Broader source: Energy.gov [DOE]

    For additional information Contact: David Weitzman, Office of Worker Safety and Health Policy at (301) 903-5401 or: David.Weitzman@hq.doe.gov.

  15. Noggin and BMP4 co-modulate adult hippocampal neurogenesis in the APP{sub swe}/PS1{sub {Delta}E9} transgenic mouse model of Alzheimer's disease

    SciTech Connect (OSTI)

    Tang, Jun; Song, Min; Wang, Yanyan; Fan, Xiaotang; Xu, Haiwei; Bai, Yun

    2009-07-31

    In addition to the subventricular zone, the dentate gyrus of the hippocampus is one of the few brain regions in which neurogenesis continues into adulthood. Perturbation of neurogenesis can alter hippocampal function, and previous studies have shown that neurogenesis is dysregulated in Alzheimer disease (AD) brain. Bone morphogenetic protein-4 (BMP4) and its antagonist Noggin have been shown to play important roles both in embryonic development and in the adult nervous system, and may regulate hippocampal neurogenesis. Previous data indicated that increased expression of BMP4 mRNA within the dentate gyrus might contribute to decreased hippocampal cell proliferation in the APP{sub swe}/PS1{sub {Delta}E9} mouse AD model. However, it is not known whether the BMP antagonist Noggin contributes to the regulation of neurogenesis. We therefore studied the relative expression levels and localization of BMP4 and its antagonist Noggin in the dentate gyrus and whether these correlated with changes in neurogenesis in 6-12 mo old APP{sub swe}/PS1{sub {Delta}E9} transgenic mice. Bromodeoxyuridine (BrdU) was used to label proliferative cells. We report that decreased neurogenesis in the APP/PS1 transgenic mice was accompanied by increased expression of BMP4 and decreased expression of Noggin at both the mRNA and protein levels; statistical analysis showed that the number of proliferative cells at different ages correlated positively with Noggin expression and negatively with BMP4 expression. Intraventricular administration of a chimeric Noggin/Fc protein was used to block the action of endogenous BMP4; this resulted in a significant increase in the number of BrdU-labeled cells in dentate gyrus subgranular zone and hilus in APP/PS1 mice. These results suggest that BMP4 and Noggin co-modulate neurogenesis.

  16. Poster — Thur Eve — 03: Application of the non-negative matrix factorization technique to [{sup 11}C]-DTBZ dynamic PET data for the early detection of Parkinson's disease

    SciTech Connect (OSTI)

    Lee, Dong-Chang; Jans, Hans; McEwan, Sandy; Riauka, Terence; Martin, Wayne; Wieler, Marguerite

    2014-08-15

    In this work, a class of non-negative matrix factorization (NMF) technique known as alternating non-negative least squares, combined with the projected gradient method, is used to analyze twenty-five [{sup 11}C]-DTBZ dynamic PET/CT brain data. For each subject, a two-factor model is assumed and two factors representing the striatum (factor 1) and the non-striatum (factor 2) tissues are extracted using the proposed NMF technique and commercially available factor analysis software “Pixies”. The extracted factor 1 and 2 curves represent the binding site of the radiotracer and describe the uptake and clearance of the radiotracer by soft tissues in the brain, respectively. The proposed NMF technique uses prior information about the dynamic data to obtain sample time-activity curves representing the striatum and the non-striatum tissues. These curves are then used for “warm” starting the optimization. Factor solutions from the two methods are compared graphically and quantitatively. In healthy subjects, radiotracer uptake by factors 1 and 2 are approximately 35–40% and 60–65%, respectively. The solutions are also used to develop a factor-based metric for the detection of early, untreated Parkinson's disease. The metric stratifies healthy subjects from suspected Parkinson's patients (based on the graphical method). The analysis shows that both techniques produce comparable results with similar computational time. The “semi-automatic” approach used by the NMF technique allows clinicians to manually set a starting condition for “warm” starting the optimization in order to facilitate control and efficient interaction with the data.

  17. Volume-Based Parameters of {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Improve Disease Recurrence Prediction in Postmastectomy Breast Cancer Patients With 1 to 3 Positive Axillary Lymph Nodes

    SciTech Connect (OSTI)

    Nakajima, Naomi; Kataoka, Masaaki; Sugawara, Yoshifumi; Ochi, Takashi; Kiyoto, Sachiko; Ohsumi, Shozo; Mochizuki, Teruhito

    2013-11-15

    Purpose: To determine whether volume-based parameters on pretreatment {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography in breast cancer patients treated with mastectomy without adjuvant radiation therapy are predictive of recurrence. Methods and Materials: We retrospectively analyzed 93 patients with 1 to 3 positive axillary nodes after surgery, who were studied with {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography for initial staging. We evaluated the relationship between positron emission tomography parameters, including the maximum standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG), and clinical outcomes. Results: The median follow-up duration was 45 months. Recurrence was observed in 11 patients. Metabolic tumor volume and TLG were significantly related to tumor size, number of involved nodes, nodal ratio, nuclear grade, estrogen receptor (ER) status, and triple negativity (TN) (all P values were <.05). In receiver operating characteristic curve analysis, MTV and TLG showed better predictive performance than tumor size, ER status, or TN (area under the curve: 0.85, 0.86, 0.79, 0.74, and 0.74, respectively). On multivariate analysis, MTV was an independent prognostic factor of locoregional recurrence-free survival (hazard ratio 34.42, 95% confidence interval 3.94-882.71, P=.0008) and disease-free survival (DFS) (hazard ratio 13.92, 95% confidence interval 2.65-103.78, P=.0018). The 3-year DFS rate was 93.8% for the lower MTV group (<53.1; n=85) and 25.0% for the higher MTV group (?53.1; n=8; P<.0001, logrank test). The 3-year DFS rate for patients with both ER-positive status and MTV <53.1 was 98.2%; and for those with ER-negative status and MTV ?53.1 it was 25.0% (P<.0001). Conclusions: Volume-based parameters improve recurrence prediction in postmastectomy breast cancer patients with 1 to 3 positive nodes. The addition of MTV to ER status or TN has potential

  18. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    medical implants comes from nanostructuring April 3, 2012 Quality of treatment for those with medical implants improves as science and medicine unite once more Metals have provided the strength, durability, and other characteristics that have been needed in bone implants since the inception of orthopedics. However, cobalt-chromium superalloys, stainless steels, and titanium alloys-the most commonly used materials in today's orthopedic devices- have the potential to present serious side effects.

  19. A New Approach to a Lyme Disease Vaccine

    SciTech Connect (OSTI)

    Livey, I.; Dunn, J.; O'Rourke, M.; Traweger, A.; Savidis-Dacho, H.; Crowe, B. A.; Barrett, P. N.; Yang, X.; Luft, B. J.

    2011-02-01

    A single recombinant outer surface protein A (OspA) antigen designed to contain protective elements from 2 different OspA serotypes (1 and 2) is able to induce antibody responses that protect mice against infection with either Borrelia burgdorferi sensu stricto (OspA serotype-1) or Borrelia afzelii (OspA serotype-2). Protection against infection with B burgdorferi ss strain ZS7 was demonstrated in a needle-challenge model. Protection against B. afzelii species was shown in a tick-challenge model using feral ticks. In both models, as little as .03 {micro}g of antigen, when administered in a 2-dose immunization schedule with aluminum hydroxide as adjuvant, was sufficient to provide complete protection against the species targeted. This proof of principle study proves that knowledge of protective epitopes can be used for the rational design of effective, genetically modified vaccines requiring fewer OspA antigens and suggests that this approach may facilitate the development of an OspA vaccine for global use.

  20. Title 10 CFR Part 850, Chronic Beryllium Disease Prevention Program

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... Any radiological implications of the two radioisotopic forms of beryllium would be addressed under the provisions of 10 CFR part 835, Occupational Radiation Protection. III. ...

  1. Low density lipoprotein fraction assay for cardiac disease risk

    DOE Patents [OSTI]

    Krauss, Ronald M.; Blanche, Patricia J.; Orr, Joseph

    1999-01-01

    A variable rate density gradient electrophoric gel is described which separate LDL subfractions with the precision of ultracentrifugation techniques. Also, an innovative bottom inlet mixing chamber particularly useful for producing these gels is described.

  2. A State-Wide Research Network for Alzheimer's Disease

    SciTech Connect (OSTI)

    Mintzer, Jacobo E.; Bachman, D. L.; Stuckey, M.; Ebeling, M.; Wagner, M. T.; Evans, W. J.; Hirth, V.; Walker, A.; Joglekar, R.; Faison, W.

    2014-03-13

    The Specific Aim of the proposal was to develop an administrative structure that will facilitate the development of AD research across the state of SC by providing key services such as (but not limited to) seeking funding research opportunities, financial tracking, regulatory management, central recruitment, training for investigators and coordinators, data collection, data storing, and data processing to researchers across the state.

  3. Statistical Mechanics of Prion Diseases (Journal Article) | SciTech...

    Office of Scientific and Technical Information (OSTI)

    Publication Date: 2001-07-30 OSTI Identifier: 40277303 Resource Type: Journal Article Resource Relation: Journal Name: Physical Review Letters; Journal Volume: 87; Journal Issue: ...

  4. Methods of treating Parkinson's disease using viral vectors

    DOE Patents [OSTI]

    Bankiewicz, Krys; Cunningham, Janet

    2012-11-13

    Methods of delivering viral vectors, particularly recombinant AAV virions, to the central nervous system (CNS) are provided for the treatment of CNS disorders, particularly those disorders which involve the neurotransmitter dopamine. The methods entail providing rAAV virions that comprise a transgene encoding aromatic amino acid decarboxylase (AADC) and administering the virions to the brain of a mammal using a non-manual pump.

  5. Low density lipoprotein fraction assay for cardiac disease risk

    DOE Patents [OSTI]

    Krauss, R.M.; Blanche, P.J.; Orr, J.

    1999-07-20

    A variable rate density gradient electrophoric gel is described which separates LDL subfractions with the precision of ultracentrifugation techniques. Also, an innovative bottom inlet mixing chamber particularly useful for producing these gels is described. 8 figs.

  6. A State-Wide Research Network for Alzheimer's Disease (Technical...

    Office of Scientific and Technical Information (OSTI)

    Contributing Orgs: MUSC & Ralph H. Johnson VAMC, Charleston, SC Senior Primary Care, Columbia, SC Comprehensive Neurological Services, Florence, SC Hospital Medicine Consultants, ...

  7. disease outbreak. Brozik, Susan Marie; Manginell, Ronald Paul...

    Office of Scientific and Technical Information (OSTI)

    developed in goal 1. We generated and characterized suitable primers for West Nile Virus RNA detection. Both optical and electrochemical transduction technologies were...

  8. Diseases of the kidney. Fourth edition. Volume 1

    SciTech Connect (OSTI)

    Schrier, R.W.; Gottschalk, C.W.

    1988-01-01

    This book contains over 100 chapters. Some of the chapter titles are: Intravenous Urography, Ultrasonography, and Radionuclide Studies; Computed Tomography and Magnetic Resonance Imaging; Diagnostic and Therapeutic Imaging of the Renal Circulation: Film-Screen Arteriography, Digital Subtraction Angiography, and Percutaneous Angioplasty and Embolization; Alport Syndrome; and Medullary Sponge Kidney.

  9. Bush Administration to Expand Beryllium Disease Screening Program...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    harmful, but small particles of beryllium-containing materials produced as by-products of machining or other processes can spread through the air and be breathed into the lungs. ...

  10. ORISE Research Participation Programs at the Centers for Disease...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Dr. Feng Liu Research Profile - Dr. Feng Liu Dr. Feng Liu performed research on influenza vaccines with the Pandemic Preparedness Team in the National Center for Immunization...

  11. Title 10 CFR Part 850, Chronic Beryllium Disease Prevention Program

    Office of Environmental Management (EM)

    Department of Energy Thousands of Students Prepare to Compete in the National Science Bowl Thousands of Students Prepare to Compete in the National Science Bowl January 29, 2013 - 5:00pm Addthis Members of the Los Alamos High School team, Los Alamos, New Mexico, concentrates on the answer to a question at the 2012 National Science Bowl in Washington D.C. on April 29, 2012. | Photograph by Dennis Brack, Office of Science Members of the Los Alamos High School team, Los Alamos, New Mexico,

  12. HOPM1 mediated disease resistance to Pseudomonas syringae in Arabidopsis

    DOE Patents [OSTI]

    He, Sheng Yang; Nomura, Kinya

    2011-11-15

    The present invention relates to compositions and methods for enhancing plant defenses against pathogens. More particularly, the invention relates to enhancing plant immunity against bacterial pathogens, wherein HopM1.sub.1-300 mediated protection is enhanced, such as increased protection to Pseudomonas syringae pv. tomato DC3000 HopM1 and/or there is an increase in activity of an ATMIN associated plant protection protein, such as ATMIN7. Reagents of the present invention further provide a means of studying cellular trafficking while formulations of the present inventions provide increased pathogen resistance in plants.

  13. Update on the Hanford Site Chronic Beryllium Disease Prevention...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Training and Implementation Medical Clearance and Restriction Language- Communication ... as follows: *Medical Referrals *Medical Clearance & Restriction *Beryllium Work Permit ...

  14. Platform for Pre-Symptomatic Detection of Citrus Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... non-exclusive right to practice any LANS-owned patents andor copyrighted software. ... Preferred Partner Attributes Demonstrated knowledge of product marketing, sales, and ...

  15. Platform for Pre-Symptomatic Detection of Citrus Disease

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    non-exclusive right to practice any LANS-owned patents andor copyrighted software. ... Preferred Partner Attributes * Demonstrated knowledge of product marketing, sales, and ...

  16. Collaborative Initiative in Biomedical Imaging to Study Complex Diseases

    SciTech Connect (OSTI)

    Lin, Weili; Fiddy, Michael A.

    2012-03-31

    The work reported addressed these topics: Fluorescence imaging; Optical coherence tomography; X-ray interferometer/phase imaging system; Quantitative imaging from scattered fields, Terahertz imaging and spectroscopy; and Multiphoton and Raman microscopy.

  17. Hanford Site Chronic Beryllium Disease Prevention Program (CBDPP...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    (406) 544-4502 Cowley, Dana Phillips MD, Karen 372-0015 376-4716 (509) 961-5609 NA MSA... Cell Number WHL (WAI Hanford Laboratory) Leonard, Bill 373-1820 554-7522 Temple, Ley ...

  18. Proteins' Amazing Origami Powers: Insight for Potential Disease...

    Broader source: Energy.gov (indexed) [DOE]

    that instead of creating a crane or a cat, you actually produce a working machine. ... be critical in determining the final form (whether a bat or a hat or a crane or a cat). ...

  19. Diagnosis and assessment of skeletal related disease using calcium 41

    DOE Patents [OSTI]

    Hillegonds, Darren J.; Vogel, John S.; Fitzgerald, Robert L.; Deftos, Leonard J.; Herold, David; Burton, Douglas W.

    2013-03-05

    A method of determining calcium metabolism in a patient comprises the steps of administering radioactive calcium isotope .sup.41Ca to the patient, allowing a period of time to elapse sufficient for dissemination and reaction of the radioactive calcium isotope .sup.41Ca by the patient, obtaining a sample of the radioactive calcium isotope .sup.41Ca from the patient, isolating the calcium content of the sample in a form suitable for precise measurement of isotopic calcium concentrations, and measuring the calcium content to determine parameters of calcium metabolism in the patient.

  20. Diagnosis and assessment of skeletal related disease using calcium 41

    DOE Patents [OSTI]

    Hillegonds, Darren J.; Vogel, John S.; Fitzgerald, Robert L.; Deftos, Leonard J.; Herold, David; Burton, Douglas W.

    2012-05-15

    A method of determining calcium metabolism in a patient comprises the steps of administering radioactive calcium isotope .sup.41Ca to the patient, allowing a period of time to elapse sufficient for dissemination and reaction of the radioactive calcium isotope .sup.41Ca by the patient, obtaining a sample of the radioactive calcium isotope .sup.41Ca from the patient, isolating the calcium content of the sample in a form suitable for precise measurement of isotopic calcium concentrations, and measuring the calcium content to determine parameters of calcium metabolism in the patient.

  1. Software speeds detection of diseases and cancer-treatment targets

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Software Tools Software Tools AMO's tools help manufacturers increase industrial energy efficiency at the plant-level and in specific systems. Learn step-by-step ways to identify opportunities, monitor progress, and improve efficiency in any facility. Some tools help facilities implement an energy management system and prepare to become ISO 50001 and Superior Energy Performance certified. Managing Your Plant's Energy Use The following tools help manufacturers track energy, identify areas of

  2. Counting small RNA in disease-causing organisms

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Counterterrorism A snapshot of NNSA's counterterrorism mission NNSA's mission of counterterrorism and counterproliferation is supported through innovative science and technology. Recently, Associate Administrator and Deputy Undersecretary for Counterterrorism and Counterproliferation Jay Tilden visited Oak Ridge National Laboratory (ORNL) and met with... Tilden appointed as Associate Administrator of Counterterrorism and Counterproliferation We are delighted to announce two key personnel

  3. Network Science: From the Web to Human Diseases

    SciTech Connect (OSTI)

    Barabasi, Albert-Laszlo

    2008-06-09

    Systems as diverse as the world wide web, Internet or the cell are described by highly interconnected networks with amazingly complex topology. Recent studies indicate that the evolution of these complex networks is governed by simple but generic laws, resulting in apparently universal architectural features. I will discuss this amazing order characterizing our interconnected work, and its implications to how we perceive the impact on communications and medicine, as well as touch upon the next challenge of network research, going beyond the structure and quantifying the dynamics of interconnected systems.

  4. BlueChoice

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Surgeon (including maternity services that are not part of OBGyn global delivery fee and complications of pregnancy) 10% after deductible 5 10% after deductible 10% after...

  5. SREL Reprint #3208

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Previous maternal exposure to coal combustion wastes (CCW) reduced larval survival to metamorphosis up to 57% compared to larvae of unexposed females. Larvae reared on CCW ...

  6. Microsoft Word - Scott-CV2013Sept.docx

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... TD, Scott DE, and Hopkins WA. Maternal transfer of contaminants and reduced reproductive success of southern toads (Bufo Anaxyrus terrestris) exposed to coal combustion waste. ...

  7. SREL Reprint #3245

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Maternal transfer of contaminants and reduced reproductive success of southern toads (Bufo Anaxyrus terrestris) exposed to coal combustion waste Brian S. Metts1, Kurt A. ...

  8. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    rhic (2) catalysis (homogeneous), solar (photovoltaic), bio-inspired, charge ... In addition, maternal Cd exposure markedly repressed cell proliferation and increased ...

  9. Method for detecting and diagnosing disease caused by pathological protein aggregation

    DOE Patents [OSTI]

    Stevens, Fred J.; Myatt, Elizabeth A.; Solomon, Alan

    2000-01-01

    A method is provided for detecting pathological macromolecules in a patient, comprising obtaining body fluid from the patient, pretreating the body fluid, subjecting the pretreated body fluid to size-exclusion chromatography to create an excluded fluid, and analyzing the excluded fluid to detect macromolecules having a predetermined molecular weight. The method also allows for comparing elution spectra with reference spectra of suspect pathologic proteins.

  10. Surface-enhanced Raman medical probes and system for disease diagnosis and drug testing

    DOE Patents [OSTI]

    Vo-Dinh, T.

    1999-01-26

    A probe for a surface-enhanced Raman scattering spectrometer includes a member of optically transmissive material for receiving the excitation radiation from a laser and for carrying the radiation emitted from a specimen to a detector. An end of the member for placing against the specimen has a coating that produces surface enhancement of the specimen during Raman scattering spectroscopic analysis. Specifically the coating is formed by a first layer of microparticles on the member and a metal layer over the first layer. The first layer may form a microstructure surface over which a metal layer is applied. Alternatively the coating may be a material containing microparticles of a metal. An optional layer of a material may be applied to the metal layer to concentrate onto the probe compounds of analytical interest onto the probe. 39 figs.

  11. Gene by Disease Interaction on Orbitofrontal Gray Matter in Cocaine Addiction

    SciTech Connect (OSTI)

    Alia-Klein, N.; Alia-Klein, N.; Parvaz, M.A.; Woicik, P.A.; Konova, A.; Maloney, T.; Shumay, E.; Wang, R.; Telang, F.; Biegon, A.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.; Volkow, N.D.; Goldstein, R.Z.

    2010-12-05

    Chronic cocaine use has been associated with structural deficits in brain regions having dopamine receptive neurons. However, the concomitant use of other drugs and common genetic variability in monoamine regulation present additional structural variability. We therefore examined variations in gray matter volume (GMV) as a function of lifetime drug use and the monoamine oxidase A (MAOA) genotype in cocaine use disorders (CUD) and healthy controls.

  12. Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Ounzain, Samir; Pezzuto, Iole; Micheletti, Rudi; Burdet, Frédéric; Sheta, Razan; Nemir, Mohamed; Gonzales, Christine; Sarre, Alexandre; Alexanian, Michael; Blow, Matthew J.; et al

    2014-08-19

    We report here that the key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Throughmore » a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.« less

  13. Surface-enhanced raman medical probes and system for disease diagnosis and drug testing

    DOE Patents [OSTI]

    Vo-Dinh, Tuan

    1999-01-01

    A probe for a surface-enhanced Raman scattering spectrometer includes a member of optically transmissive material for receiving the excitation radiation from a laser and for carrying the radiation emitted from a specimen to a detector. An end of the member for placing against the specimen has a coating that produces surface enhancement of the specimen during Raman scattering spectroscopic analysis. Specifically the coating is formed by a first layer of microparticles on the member and a metal layer over the first layer. The first layer may form a microstructure surface over which a metal layer is applied. Alternatively the coating may be a material containing microparticles of a metal. An optional layer of a material may be applied to the metal layer to concentrate onto the probe compounds of analytical interest onto the probe.

  14. Using Corticosteroids to Reshape the Gut Microbiome: Implications for Inflammatory Bowel Diseases

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Huang, Edmond Y.; Inoue, Takuya; Leone, Vanessa A.; Dalal, Sushila; Touw, Ketrija; Wang, Yunwei; Musch, Mark W.; Theriault, Betty; Higuchi, Kazuhide; Donovan, Sharon; et al

    2015-05-01

    Introduction—Commensal gut microbiota play an important role in regulating metabolic and inflammatory conditions. Reshaping intestinal microbiota through pharmacologic means may be a viable treatment option. Here we sought to delineate the functional characteristics of glucocorticoid-mediated alterations on gut microbiota and their subsequent repercussions on host mucin regulation and colonic inflammation. Methods—Adult male C57Bl/6 mice, germ-free (GF), Muc2-heterozygote (±), or Muc2-knockout (-/-) were injected with dexamethasone, a synthetic glucocorticoid, for four weeks. Fecal samples were collected for gut microbiota analysis via 16S rRNA T-RFLP and amplicon sequencing. Intestinal mucosa was collected for mucin gene expression studies. GF mice were conventionalized withmore » gut microbes from treated- and non-treated groups to determine their functional capacities in recipient hosts. Results—Exposure to DEX in WT mice led to substantial shifts in gut microbiota over a four-week period. Furthermore, a significant down-regulation of colonic Muc2 gene expression was observed after treatment. Muc2-knockout mice harbored a pro-inflammatory environment of gut microbes, characterized by the increase or decrease in prevalence of specific microbiota populations such as Clostridiales and Lactobacillaceae, respectively. This colitogenic phenotype was transmissible to IL10-knockout (IL10-KO) mice, a genetically susceptible model of colonic inflammatory disorders. Microbiota from donors pre-treated with DEX, however, ameliorated symptoms of inflammation. We conclude that commensal gut bacteria may be a key mediator of the anti-inflammatory effects observed in the large intestine after GC exposure. These findings underscore the notion that intestinal microbes comprise a “microbial organ” essential for host physiology that can be targeted by therapeutic approaches to restore intestinal homeostasis.« less

  15. Disease Control and Ototoxicity Using Intensity-Modulated Radiation Therapy Tumor-Bed Boost for Medulloblastoma

    SciTech Connect (OSTI)

    Polkinghorn, William R.; Dunkel, Ira J.; Souweidane, Mark M.; Khakoo, Yasmin; Lyden, David C.; Gilheeney, Stephen W.; Becher, Oren J.; Budnick, Amy S.; Wolden, Suzanne L.

    2011-11-01

    Purpose: We previously reported excellent local control for treating medulloblastoma with a limited boost to the tumor bed. In order to decrease ototoxicity, we subsequently implemented a tumor-bed boost using intensity-modulated radiation therapy (IMRT), the clinical results of which we report here. Patients and Methods: A total of 33 patients with newly diagnosed medulloblastoma, 25 with standard risk, and 8 with high risk, were treated on an IMRT tumor-bed boost following craniospinal irradiation (CSI). Six standard-risk patients were treated with an institutional protocol with 18 Gy CSI in conjunction with intrathecal iodine-131-labeled monoclonal antibody. The majority of patients received concurrent vincristine and standard adjuvant chemotherapy. Pure-tone audiograms were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: Median age was 9 years old (range, 4-46 years old). Median follow-up was 63 months. Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) rates for standard-risk patients who received 23.4 or 36 Gy CSI (not including those who received 18 Gy CSI with radioimmunotherapy) were 81.4% and 88.4%, respectively, at 5 years; 5-year PFS and OS rates for high-risk patients were both 87.5%. There were no isolated posterior fossa failures outside of the boost volume. Posttreatment audiograms were available for 31 patients, of whom 6%, at a median follow-up of 19 months, had developed Grade 3 hearing loss. Conclusion: An IMRT tumor-bed boost results in excellent local control while delivering a low mean dose to the cochlea, resulting in a low rate of ototoxicity.

  16. Indoor Measurements of Environmental Tobacco Smoke Final Report to the Tobacco Related Disease Research Program

    SciTech Connect (OSTI)

    Apte, Michael G.; Gundel, Lara A.; Dod, Raymond L.; Russell, Marion L.; Singer, Brett C.; Sohn, Michael D.; Sullivan, Douglas P.; Chang, Gee-Minn; Sextro, Richard G.

    2004-03-02

    The objective of this research project was to improve the basis for estimating environmental tobacco smoke (ETS) exposures in a variety of indoor environments. The research utilized experiments conducted in both laboratory and ''real-world'' buildings to (1) study the transport of ETS species from room to room, (2) examine the viability of using various chemical markers as tracers for ETS, and (3) to evaluate to what extent re-emission of ETS components from indoor surfaces might add to the ETS exposure estimates. A three-room environmental chamber was used to examine multi-zone transport and behavior of ETS and its tracers. One room (simulating a smoker's living room) was extensively conditioned with ETS, while a corridor and a second room (simulating a child's bedroom) remained smoking-free. A series of 5 sets of replicate experiments were conducted under different door opening and flow configurations: sealed, leaky, slightly ajar, wide open, and under forced air-flow conditions. When the doors between the rooms were slightly ajar the particles dispersed into the other rooms, eventually reaching the same concentration. The particle size distribution took the same form in each room, although the total numbers of particles in each room depended on the door configurations. The particle number size distribution moved towards somewhat larger particles as the ETS aged. We also successfully modeled the inter-room transport of ETS particles from first principles--using size fractionated particle emission factors, predicted deposition rates, and thermal temperature gradient driven inter-room flows, This validation improved our understanding of bulk inter-room ETS particle transport. Four chemical tracers were examined: ultraviolet-absorbing particulate matter (UVPM), fluorescent particulate matter (FPM), nicotine and solanesol. Both (UVPM) and (FPM) traced the transport of ETS particles into the non-smoking areas. Nicotine, on the other hand, quickly adsorbed on unconditioned surfaces so that nicotine concentrations in these rooms remained very low, even during smoking episodes. These findings suggest that using nicotine as a tracer of ETS particle concentrations may yield misleading concentration and/or exposure estimates. The results of the solanesol analyses were compromised, apparently by exposure to light during collection (lights in the chambers were always on during the experiments). This may mean that the use of solanesol as a tracer is impractical in ''real-world'' conditions. In the final phase of the project we conducted measurements of ETS particles and tracers in three residences occupied by smokers who had joined a smoking cessation program. As a pilot study, its objective was to improve our understanding of how ETS aerosols are transported in a small number of homes (and thus, whether limiting smoking to certain areas has an effect on ETS exposures in other parts of the building). As with the chamber studies, we examined whether measurements of various chemical tracers, such as nicotine, solanesol, FPM and UVPM, could be used to accurately predict ETS concentrations and potential exposures in ''real-world'' settings, as has been suggested by several authors. The ultimate goal of these efforts, and a future larger multiple house study, is to improve the basis for estimating ETS exposures to the general public. Because we only studied three houses no firm conclusions can be developed from our data. However, the results for the ETS tracers are essentially the same as those for the chamber experiments. The use of nicotine was problematic as a marker for ETS exposure. In the smoking areas of the homes, nicotine appeared to be a suitable indicator; however in the non-smoking regions, nicotine behavior was very inconsistent. The other tracers, UVPM and FPM, provided a better basis for estimating ETS exposures in the ''real world''. The use of solanesol was compromised--as it had been in the chamber experiments.

  17. Chronic disease and early exposure to air-borne mixtures. 2. Exposure assessment

    SciTech Connect (OSTI)

    James Argo

    2007-10-15

    This work is part of a larger study of the impact of early exposure to releases from industry on the etiology of cancer. Releases from all kraft and sulfite mills, coke ovens, oil refineries, copper, nickel, and lead/zinc smelters operating in Canada during the exposure period of 1967-1970 have been determined. All plumes have been expressed in g BaP eq/d using the RASH methodology. The releases have been divided into process, boiler fuel, dioxin, and SO{sub 2} emissions. Combustion sources have been defined with FIREv6.23. Dioxin congenors are expected in all source types when the boiler fuel is heavy fuel oil, wood or wood bark, or coal. All about 90 communities examined have an inverted sex ratio. 53 refs., 2 figs., 4 tabs.

  18. Update on the Hanford Site Chronic Beryllium Disease Prevention Program (CBDPP)

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    June 18, 2015 Be Corrective Action Plan (CAP) * Be CAP was approved by DOE-HQ in September 2010 * CAP supplement addressing new consensus process and high-priority Phase 1 products was approved by DOE Office of Environmental Management (DOE-EM) in September 2011 * CAP supplement addressing lower priority Phase 2 and Phase 3 products was approved by DOE-EM on March 13, 2012 Be CAP Status * DOE HQ Enterprise Assessment review March 2015, awaiting final report, no findings, 3 Opportunities for

  19. Structure of an aprataxin?DNA complex with insights into AOA1 neurodegenerative disease

    SciTech Connect (OSTI)

    Tumbale, Percy; Appel, C. Denise; Kraehenbuehl, Rolf; Robertson, Patrick D.; Williams, Jessica S.; Krahn, Joe; Ahel, Ivan; Williams, R. Scott (NIEHS); (Manchester)

    2012-09-17

    DNA ligases finalize DNA replication and repair through DNA nick-sealing reactions that can abort to generate cytotoxic 5'-adenylation DNA damage. Aprataxin (Aptx) catalyzes direct reversal of 5'-adenylate adducts to protect genome integrity. Here the structure of a Schizosaccharomyces pombe Aptx-DNA-AMP-Zn{sup 2+} complex reveals active site and DNA interaction clefts formed by fusing a histidine triad (HIT) nucleotide hydrolase with a DNA minor groove-binding C{sub 2}HE zinc finger (Znf). An Aptx helical 'wedge' interrogates the base stack for sensing DNA ends or DNA nicks. The HIT-Znf, the wedge and an '[F/Y]PK' pivot motif cooperate to distort terminal DNA base-pairing and direct 5'-adenylate into the active site pocket. Structural and mutational data support a wedge-pivot-cut HIT-Znf catalytic mechanism for 5'-adenylate adduct recognition and removal and suggest that mutations affecting protein folding, the active site pocket and the pivot motif underlie Aptx dysfunction in the neurodegenerative disorder ataxia with oculomotor apraxia 1 (AOA1).

  20. Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease

    SciTech Connect (OSTI)

    Ounzain, Samir; Pezzuto, Iole; Micheletti, Rudi; Burdet, Frédéric; Sheta, Razan; Nemir, Mohamed; Gonzales, Christine; Sarre, Alexandre; Alexanian, Michael; Blow, Matthew J.; May, Dalit; Johnson, Rory; Dauvillier, Jérôme; Pennacchio, Len A.; Pedrazzini, Thierry

    2014-08-19

    We report here that the key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Through a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.

  1. AtMIN7 mediated disease resistance to Pseudomonas syringae in Arabidopsis

    DOE Patents [OSTI]

    He, Sheng Yang; Nomura, Kinya

    2011-07-26

    The present invention relates to compositions and methods for enhancing plant defenses against pathogens. More particularly, the invention relates to enhancing plant immunity against bacterial pathogens, wherein AtMIN7 mediated protection is enhanced and/or there is a decrease in activity of an AtMIN7 associated virulence protein such as a Pseudomonas syringae pv. tomato DC3000 HopM1. Reagents of the present invention provide a means of studying cellular trafficking while formulations of the present inventions provide increased pathogen resistance in plants.

  2. Method of treating inflammatory diseases using a radiolabeled ferric hydroxide calloid

    DOE Patents [OSTI]

    Atcher, Robert W.; Hines, John J.

    1992-01-01

    A ferric hydroxide colloid having an alpha-emitting radionuclide essentially on the outer surfaces and a method of forming same. The method includes oxidizing a ferrous hydroxide to ferric hydroxide in the presence of a preselected radionuclide to form a colloid having the radionuclide on the outer surface thereof, and thereafter washing the colloid, and suspending the washed colloid in a suitable solution. The labelled colloid is useful in cancer therapy and for the treatment of inflamed joints.

  3. OSTIblog Articles in the disease Topic | OSTI, US Dept of Energy...

    Office of Scientific and Technical Information (OSTI)

    John Q. Trojanowski, an Alzheimer's researcher at the University of Pennsylvania, "It's not science the way most of us have practiced it in our careers. But we all realized that we ...

  4. Premier Tools of Energy Research Also Probe Secrets of Viral Disease

    DOE R&D Accomplishments [OSTI]

    Chui, Glennda

    2011-03-28

    Advanced light sources peer into matter at the atomic and molecular scales, with applications ranging from physics, chemistry, materials science, and advanced energy research, to biology and medicine.

  5. Using Corticosteroids to Reshape the Gut Microbiome: Implications for Inflammatory Bowel Diseases

    SciTech Connect (OSTI)

    Huang, Edmond Y.; Inoue, Takuya; Leone, Vanessa A.; Dalal, Sushila; Touw, Ketrija; Wang, Yunwei; Musch, Mark W.; Theriault, Betty; Higuchi, Kazuhide; Donovan, Sharon; Gilbert, Jack; Chang, Eugene B.

    2015-05-01

    Introduction—Commensal gut microbiota play an important role in regulating metabolic and inflammatory conditions. Reshaping intestinal microbiota through pharmacologic means may be a viable treatment option. Here we sought to delineate the functional characteristics of glucocorticoid-mediated alterations on gut microbiota and their subsequent repercussions on host mucin regulation and colonic inflammation. Methods—Adult male C57Bl/6 mice, germ-free (GF), Muc2-heterozygote (±), or Muc2-knockout (-/-) were injected with dexamethasone, a synthetic glucocorticoid, for four weeks. Fecal samples were collected for gut microbiota analysis via 16S rRNA T-RFLP and amplicon sequencing. Intestinal mucosa was collected for mucin gene expression studies. GF mice were conventionalized with gut microbes from treated- and non-treated groups to determine their functional capacities in recipient hosts. Results—Exposure to DEX in WT mice led to substantial shifts in gut microbiota over a four-week period. Furthermore, a significant down-regulation of colonic Muc2 gene expression was observed after treatment. Muc2-knockout mice harbored a pro-inflammatory environment of gut microbes, characterized by the increase or decrease in prevalence of specific microbiota populations such as Clostridiales and Lactobacillaceae, respectively. This colitogenic phenotype was transmissible to IL10-knockout (IL10-KO) mice, a genetically susceptible model of colonic inflammatory disorders. Microbiota from donors pre-treated with DEX, however, ameliorated symptoms of inflammation. We conclude that commensal gut bacteria may be a key mediator of the anti-inflammatory effects observed in the large intestine after GC exposure. These findings underscore the notion that intestinal microbes comprise a “microbial organ” essential for host physiology that can be targeted by therapeutic approaches to restore intestinal homeostasis.

  6. Gas bubble disease in smallmouth bass and northern squawfish from the Snake and Columbia Rivers

    SciTech Connect (OSTI)

    Montgomery, J.C.; Becker, C.D.

    1980-11-01

    In 1975 and 1976, 179 smallmouth bass (Micropterus dolomieui) and 85 northern squawfish (Ptychocheilus oregonensis) were collected by angling from the lower Snake and mid-Columbia rivers, southeastern Washington. All fish were examined externally for gas bubble syndrome. Emboli were found beneath membranes of the opercula, body, and fins of 72% of the smallmouth bass and 84% of the northern squawfish. Hemorrhage was also noted on the caudal, anal, and pectoral fins of several smallmouth bass. Presence of gas bubble syndrome corresponded to the spring runoff when total dissolved gas supersaturations in river water exceeded 115%.

  7. Evaluation of Novel Design Strategies for Developing Zinc Finger Nucleases Tools for Treating Human Diseases

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Bach, Christian; Sherman, William; Pallis, Jani; Patra, Prabir; Bajwa, Hassan

    2014-01-01

    Zinc finger nucleases (ZFNs) are associated with cell death and apoptosis by binding at countless undesired locations. This cytotoxicity is associated with the binding ability of engineered zinc finger domains to bind dissimilar DNA sequences with high affinity. In general, binding preferences of transcription factors are associated with significant degenerated diversity and complexity which convolutes the design and engineering of precise DNA binding domains. Evolutionary success of natural zinc finger proteins, however, evinces that nature created specific evolutionary traits and strategies, such as modularity and rank-specific recognition to cope with binding complexity that are critical for creating clinical viable toolsmore » to precisely modify the human genome. Our findings indicate preservation of general modularity and significant alteration of the rank-specific binding preferences of the three-finger binding domain of transcription factor SP1 when exchanging amino acids in the 2nd finger.« less

  8. Asymptomatic and late-onset ornithine transcarbamylase deficiency caused by a A208T mutation: Clinical, biochemical and DNA analyses in a four-generation family

    SciTech Connect (OSTI)

    Ausems, M.G.E.M.; Bakker, E.; Kneppers, A.L.J.

    1997-01-20

    We describe a 4-generation family in which a previously healthy 10-year-old boy died of late-onset ornithine transcarbamylase (OTC) deficiency. Pedigree analysis and allopurinol loading tests in female relatives were not informative. A missense mutation (A208T) in the OTC gene was detected in the deceased patient and in several clinically healthy male and female relatives, the oldest male being 97 years old. OTC deficiency was established in autopsy liver tissue of the propositus and liver biopsy samples of his sister, mother, and a maternal uncle. The males had 4% and 6% residual activity, respectively, the females 58% and 67%, respectively. The observed relation between the mutation and the decreased OTC activity in liver tissue of these subjects suggests that the mutation is a deleterious one. Late-onset, {open_quotes}mild{close_quotes} OTC deficiency can have a fatal or a favorable outcome. The disease can segregate undetected in families. 16 refs., 1 fig., 1 tab.

  9. Methods And Compositions For Chromosome-Specific Staining

    DOE Patents [OSTI]

    Gray, Joe W.; Pinkel, Daniel

    2003-08-19

    Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyses. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods are provided to disable the hybridization capacity of shared, high copy repetitive sequences and/or remove such sequences to provide for useful contrast. Still further methods are provided to produce chromosome-specific staining reagents which are made specific to the targeted chromosomal material, which can be one or more whole chromosomes, one or more regions on one or more chromosomes, subsets of chromosomes and/or the entire genome. Probes and test kits are provided for use in tumor cytogenetics, in the detection of disease related loci, in analysis of structural abnormalities, such as translocations, and for biological dosimetry. Further, methods and prenatal test kits are provided to stain targeted chromosomal material of fetal cells, including fetal cells obtained from maternal blood. Still further, the invention provides for automated means to detect and analyse chromosomal abnormalities.

  10. Methods of biological dosimetry employing chromosome-specific staining

    DOE Patents [OSTI]

    Gray, Joe W.; Pinkel, Daniel

    2000-01-01

    Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyses. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods are provided to disable the hybridization capacity of shared, high copy repetitive sequences and/or remove such sequences to provide for useful contrast. Still further methods are provided to produce chromosome-specific staining reagents which are made specific to the targeted chromosomal material, which can be one or more whole chromosomes, one or more regions on one or more chromosomes, subsets of chromosomes and/or the entire genome. Probes and test kits are provided for use in tumor cytogenetics, in the detection of disease related loci, in analysis of structural abnormalities, such as translocations, and for biological dosimetry. Further, methods and prenatal test kits are provided to stain targeted chromosomal material of fetal cells, including fetal cells obtained from maternal blood. Still further, the invention provides for automated means to detect and analyse chromosomal abnormalities.

  11. Compositions for chromosome-specific staining

    DOE Patents [OSTI]

    Gray, J.W.; Pinkel, D.

    1998-05-26

    Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. The methods produce staining patterns that can be tailored for specific cytogenetic analyses. The probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods are provided to disable the hybridization capacity of shared, high copy repetitive sequences and/or remove such sequences to provide for useful contrast. Still further methods are provided to produce chromosome-specific staining reagents which are made specific to the targeted chromosomal material, which can be one or more whole chromosomes, one or more regions on one or more chromosomes, subsets of chromosomes and/or the entire genome. Probes and test kits are provided for use in tumor cytogenetics, in the detection of disease related loci, in analysis of structural abnormalities, such as translocations, and for biological dosimetry. Methods and prenatal test kits are provided to stain targeted chromosomal material of fetal cells, including fetal cells obtained from maternal blood. The invention provides for automated means to detect and analyze chromosomal abnormalities. 17 figs.

  12. Compositions for chromosome-specific staining

    DOE Patents [OSTI]

    Gray, Joe W.; Pinkel, Daniel

    1998-01-01

    Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyses. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods are provided to disable the hybridization capacity of shared, high copy repetitive sequences and/or remove such sequences to provide for useful contrast. Still further methods are provided to produce chromosome-specific staining reagents which are made specific to the targeted chromosomal material, which can be one or more whole chromosomes, one or more regions on one or more chromosomes, subsets of chromosomes and/or the entire genome. Probes and test kits are provided for use in tumor cytogenetics, in the detection of disease related loci, in analysis of structural abnormalities, such as translocations, and for biological dosimetry. Further, methods and prenatal test kits are provided to stain targeted chromosomal material of fetal cells, including fetal cells obtained from maternal blood. Still further, the invention provides for automated means to detect and analyse chromosomal abnormalities.

  13. United States

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... Ellis (1993) collected fecal pellets from the roost of a maternity colony in North ... In summer, little brown bats roost under rocks, in piles of wood, and in trees (Fenton and ...

  14. Organ-on-a-chip | The Ames Laboratory

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    a "placenta-on-a-chip" in order to mimic the nutrientwaste transfer between maternal blood and fetal blood that occurs in the cotyledon section of the placenta, and to test and...

  15. SU-E-T-309: Tangential Modulated Arc Therapy: A Novel Technique for the Treatment of Superficial Disease

    SciTech Connect (OSTI)

    Hadsell, M; Chin, E; Li, R; Xing, L; Bush, K

    2014-06-01

    Purpose: We propose a new type of treatment that employs a modulated and sliding tangential photon field to provide superior coverage of superficial targets when compared to other commonly employed methods while drastically reducing dose to the underlying sensitive structures often present in these cases. Methods: Modulated treatment plans were formulated for a set of three representative cases. The first was a revised treatment of a scalp sarcoma, while the second was a treatment of a right posterior chest wall sarcoma. For these cases, asymmetric jaw placement, angular limitations, and central isocenter placements were used to force the optimization algorithm into finding solutions with beamlines that were not perpendicular to the body surface. The final case targeted the chest wall of a breast cancer patient, in which standard treatments were compared to the use of modulated fields with multiple isocenters along the chest wall. Results: When compared with unrestricted modulated arcs, the tangential arc scalp treatment reduced the max and mean doses delivered to the brain by 33Gy (from 55 to 22Gy) and 6Gy (from 14Gy to 8Gy), respectively. In the right posterior chest wall case, the V10 in the ipsilateral lung was kept below 5% while retaining a Rx dose (45Gy) target coverage of over 97%. For the breast case, the modulated plan achieved reductions in high dose to the ipsilateral lung and heart by a factor of 23 when compared to classic laterally opposed tangents and reduced the V5 by 40% when compared to standard modulated arcs. Conclusion: Tangential modulated arc therapy has outperformed the conventional modalities of treatment for superficial lesions used in our clinic. We hope that with the advent of digitally controlled linear accelerators, we can uncover further benefits of this new technique and extend its applicability to a wider section of the patient population.

  16. Adjuvant Brachytherapy Removes Survival Disadvantage of Local Disease Extension in Stage IIIC Endometrial Cancer: A SEER Registry Analysis

    SciTech Connect (OSTI)

    Rossi, Peter J. Jani, Ashesh B.; Horowitz, Ira R.; Johnstone, Peter A.S.

    2008-01-01

    Purpose: To assess the role of radiotherapy (RT) in women with Stage IIIC endometrial cancer. Methods and Materials: The 17-registry Survival, Epidemiology, and End Results (SEER) database was searched for patients with lymph node-positive non-Stage IV epithelial endometrial cancer diagnosed and treated between 1988 and 1998. Two subgroups were identified: those with organ-confined Stage IIIC endometrial cancer and those with Stage IIIC endometrial cancer with direct extension of the primary tumor. RT was coded as external beam RT (EBRT) or brachytherapy (BT). Observed survival (OS) was reported with a minimum of 5 years of follow-up; the survival curves were compared using the log-rank test. Results: The therapy data revealed 611 women with Stage IIIC endometrial cancer during this period. Of these women, 51% were treated with adjuvant EBRT, 21% with EBRT and BT, and 28% with no additional RT (NAT). Of the 611 patients, 293 had organ-confined Stage IIIC endometrial cancer and 318 patients had Stage IIIC endometrial cancer with direct extension of the primary tumor. The 5-year OS rate for all patients was 40% with NAT, 56% after EBRT, and 64% after EBRT/BT. Adjuvant RT improved survival compared with NAT (p <0.001). In patients with organ-confined Stage IIIC endometrial cancer, the 5-year OS rate was 50% for NAT, 64% for EBRT, and 67% for EBRT/BT. Again, adjuvant RT contributed to improved survival compared with NAT (p = 0.02). In patients with Stage IIIC endometrial cancer and direct tumor extension, the 5-year OS rate was 34% for NAT, 47% for EBRT, and 63% for EBRT/BT. RT improved OS compared with NAT (p <0.001). Also, in this high-risk subgroup, adding BT to EBRT was superior to EBRT alone (p = 0.002). Conclusion: Women with Stage IIIC endometrial cancer receiving adjuvant EBRT and EBRT/BT had improved OS compared with patients receiving NAT. When direct extension of the primary tumor was present, the addition of BT to EBRT was even more beneficial.

  17. Effects of Adenovirus-Mediated Delivery of the Human Hepatocyte Growth Factor Gene in Experimental Radiation-Induced Heart Disease

    SciTech Connect (OSTI)

    Hu Shunying; Chen Yundai; Li Libing; Chen Jinlong; Wu Bin; Zhou, Xiao; Zhi Guang; Li Qingfang; Wang Rongliang; Duan Haifeng; Guo Zikuan; Yang Yuefeng; Xiao Fengjun; Wang Hua; Wang Lisheng

    2009-12-01

    Purpose: Irradiation to the heart may lead to late cardiovascular complications. The purpose of this study was to investigate whether adenovirus-mediated delivery of the human hepatocyte growth factor gene could reduce post-irradiation damage of the rat heart and improve heart function. Methods and Materials: Twenty rats received single-dose irradiation of 20 Gy gamma ray locally to the heart and were randomized into two groups. Two weeks after irradiation, these two groups of rats received Ad-HGF or mock adenovirus vector intramyocardial injection, respectively. Another 10 rats served as sham-irradiated controls. At post-irradiation Day 120, myocardial perfusion was tested by myocardial contrast echocardiography with contrast agent injected intravenously. At post-irradiation Day 180, cardiac function was assessed using the Langendorff technique with an isolated working heart model, after which heart samples were collected for histological evaluation. Results: Myocardial blood flow was significantly improved in HGF-treated animals as measured by myocardial contrast echocardiography at post-irradiation Day 120 . At post-irradiation Day 180, cardiac function was significantly improved in the HGF group compared with mock vector group, as measured by left ventricular peak systolic pressure (58.80 +- 9.01 vs. 41.94 +- 6.65 mm Hg, p < 0.05), the maximum dP/dt (5634 +- 1303 vs. 1667 +- 304 mm Hg/s, p < 0.01), and the minimum dP/dt (3477 +- 1084 vs. 1566 +- 499 mm Hg/s, p < 0.05). Picrosirius red staining analysis also revealed a significant reduction of fibrosis in the HGF group. Conclusion: Based on the study findings, hepatocyte growth factor gene transfer can attenuate radiation-induced cardiac injury and can preserve cardiac function.

  18. Early life ethanol exposure causes long-lasting disturbances in rat mesenchymal stem cells via epigenetic modifications

    SciTech Connect (OSTI)

    Leu, Yu-Wei; Chu, Pei-Yi; Chen, Chien-Min; Yeh, Kun-Tu; Liu, Yu Ming; Lee, Yen-Hui; Kuo, Shan-Tsu; Hsiao, Shu-Huei

    2014-10-24

    Highlights: • Ethanol exposure alters proliferation and differentiation of MSCs. • Ethanol exposure suppresses osteogenesis and adipogenesis of MSCs. • H3K27me3-associated genes/pathways are affected in ethanol-exposed MSCs. • Expression of lineage-specific genes is dysregulated in ethanol-exposed MSCs. - Abstract: Fetal alcohol syndrome (FAS) is a birth defect due to maternal alcohol consumption during pregnancy. Because mesenchymal stem cells (MSCs) are the main somatic stem cells in adults and may contribute to tissue homeostasis and repair in adulthood, we investigated whether early life ethanol exposure affects MSCs and contributes to the propensity for disease onset in later life. Using a rodent model of FAS, we found that ethanol exposure (5.25 g/kg/day) from postnatal days 4 to 9 in rat pups (mimic of human third trimester) caused long-term anomalies in bone marrow-derived MSCs. MSCs isolated from ethanol-exposed animals were prone to neural induction but resistant to osteogenic and adipogenic inductions compared to their age-matched controls. The altered differentiation may contribute to the severe trabecular bone loss seen in ethanol-exposed animals at 3 months of age as well as overt growth retardation. Expression of alkaline phosphatase, osteocalcin, aP2, and PPARγ were substantially inhibited, but BDNF was up-regulated in MSCs isolated from ethanol-exposed 3 month-old animals. Several signaling pathways were distorted in ethanol-exposed MSCs via altered trimethylation at histone 3 lysine 27. These results demonstrate that early life ethanol exposure can have long-term impacts in rat MSCs by both genetic and epigenetic mechanisms.

  19. Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

    SciTech Connect (OSTI)

    Ma, Noelle; Nicholson, Catherine J.; Wong, Michael; Holloway, Alison C.; Hardy, Daniel B.

    2014-02-15

    While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXR?), we measured LXR? expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXR? protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. It is due to nicotine-induced augmented expression of hepatic FAS and LXR? activity. Moreover, this involves nicotine-induced enhanced acetylation of

  20. Improving the osteointegration of Ti6Al4V by zeolite MFI coating

    SciTech Connect (OSTI)

    Li, Yong; Jiao, Yilai; Li, Xiaokang; Guo, Zheng

    2015-05-01

    Osteointegration is crucial for success in orthopedic implantation. In recent decades, there have been numerous studies aiming to modify titanium alloys, which are the most widely used materials in orthopedics. Zeolites are solid aluminosilicates whose application in the biomedical field has recently been explored. To this end, MFI zeolites have been developed as titanium alloy coatings and tested in vitro. Nevertheless, the effect of the MFI coating of biomaterials in vivo has not yet been addressed. The aim of the present work is to evaluate the effects of MFI-coated Ti6Al4V implants in vitro and in vivo. After surface modification, the surface was investigated using field emission scanning electron microscopy (FE-SEM) and energy dispersive spectroscopy (EDS). No difference was observed regarding the proliferation of MC3T3-E1 cells on the Ti6Al4V (Ti) and MFI-coated Ti6Al4V (M−Ti) (p > 0.05). However, the attachment of MC3T3-E1 cells was found to be better in the M−Ti group. Additionally, ALP staining and activity assays and quantitative real-time RT-PCR indicated that MC3T3-E1 cells grown on the M−Ti displayed high levels of osteogenic differentiation markers. Moreover, Van-Gieson staining of histological sections demonstrated that the MFI coating on Ti6Al4V scaffolds significantly enhanced osteointegration and promoted bone regeneration after implantation in rabbit femoral condylar defects at 4 and 12 weeks. Therefore, this study provides a method for modifying Ti6Al4V to achieve improved osteointegration and osteogenesis. - Highlights: • Osteointegration is a crucial factor for orthopedic implants. • We coated MFI zeolite on Ti6Al4V substrates and investigated the effects in vitro and in vivo. • The MFI coating displayed good biocompatibility and promoted osteogenic differentiation in vitro. • The MFI coating promoted osteointegration and osteogenesis peri-implant in vivo.

  1. SREL Reprint #3335

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    5 Consequences of maternal effects on offspring size, growth and survival in the desert tortoise M. G. Nafus1,2, B. D. Todd1, K. A. Buhlmann3, and T. D. Tuberville3 1Department of Wildlife, Fish and Conservation Biology, University of California, Davis, CA, USA 2San Diego Zoological Global, San Diego Zoo Institute for Conservation Research, Escondido, CA, USA 3University of Georgia’s Savannah River Ecology Laboratory, Aiken, SC, USA Abstract: Maternal body size can have notable consequences on

  2. Performance of a Nomogram Predicting Disease-Specific Survival After an R0 Resection for Gastric Cancer in Patients Receiving Postoperative Chemoradiation Therapy

    SciTech Connect (OSTI)

    Dikken, Johan L.; Coit, Daniel G.; Baser, Raymond E.; Gönen, Mithat; Goodman, Karyn A.; Brennan, Murray F.; Jansen, Edwin P.M.; Boot, Henk; Velde, Cornelis J.H. van de; Cats, Annemieke; Verheij, Marcel

    2014-03-01

    Purpose: The internationally validated Memorial Sloan-Kettering Cancer Center (MSKCC) gastric carcinoma nomogram was based on patients who underwent curative (R0) gastrectomy, without any other therapy. The purpose of the current study was to assess the performance of this gastric cancer nomogram in patients who received chemoradiation therapy after an R0 resection for gastric cancer. Methods and Materials: In a combined dataset of 76 patients from the Netherlands Cancer Institute (NKI), and 63 patients from MSKCC, who received postoperative chemoradiation therapy (CRT) after an R0 gastrectomy, the nomogram was validated by means of the concordance index (CI) and a calibration plot. Results: The concordance index for the nomogram was 0.64, which was lower than the CI of the nomogram for patients who received no adjuvant therapy (0.80). In the calibration plot, observed survival was approximately 20% higher than the nomogram-predicted survival for patients receiving postoperative CRT. Conclusions: The MSKCC gastric carcinoma nomogram significantly underpredicted survival for patients in the current study, suggesting an impact of postoperative CRT on survival in patients who underwent an R0 resection for gastric cancer, which has been demonstrated by randomized controlled trials. This analysis stresses the need for updating nomograms with the incorporation of multimodal strategies.

  3. Chemically induced Parkinson's disease: intermediates in the oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to the 1-methyl-4-phenyl-pyridinium ion

    SciTech Connect (OSTI)

    Chacon, J.N.; Chedekel, M.R.; Land, E.J.; Truscott, T.G.

    1987-04-29

    Various unstable intermediate oxidation states have been postulated in the metabolic activation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to the 1-methyl-4-phenyl pyridinium ion. We now report the first direct observation of these free radical intermediates by pulse radiolysis and flash photolysis. Studies are described of various reactions of such species, in particular with dopamine whose autoxidation to dopamine quinone is reported to be potentiated by 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine.

  4. Major prime contractors have developed a plan to address Hanford Beryllium exposure and are continuing to improve the Chronic Beryllium Disease Prevention Plan (CBDPP)

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    OMC-CS-532H Rev. 2 Published 05/05/16 Beryllium Information Booklet Beryllium Information Provided By: HPMC Occupational Medical Services http://www.hanford.gov/health/ Physical Address: MSIN G3-70 1979 Snyder Street, Suite 150 Richland, WA 99354 Mailing Address: P.O. Box 150 Richland, WA 99352 HPMC Occupational Medical Services - Beryllium Information Booklet OMC-CS-532H Rev. 2 Published 05/05/16 1 Table of Contents Disclaimer

  5. Treatment approach, delivery, and follow-up evaluation for cardiac rhythm disease management patients receiving radiation therapy: Retrospective physician surveys including chart reviews at numerous centers

    SciTech Connect (OSTI)

    Gossman, Michael S.; Wilkinson, Jeffrey D.; Mallick, Avishek

    2014-01-01

    In a 2-part study, we first examined the results of 71 surveyed physicians who provided responses on how they address the management of patients who maintained either a pacemaker or a defibrillator during radiation treatment. Second, a case review study is presented involving 112 medical records reviewed at 18 institutions to determine whether there was a change in the radiation prescription for the treatment of the target cancer, the method of radiation delivery, or the method of radiation image acquisition. Statistics are provided to illustrate the level of administrative policy; the level of communication between radiation oncologists and heart specialists; American Joint Committee on Cancer (AJCC) staging and classification; National Comprehensive Cancer Network (NCCN) guidelines; tumor site; patient's sex; patient's age; device type; manufacturer; live monitoring; and the reported decisions for planning, delivery, and imaging. This survey revealed that 37% of patient treatments were considered for some sort of change in this regard, whereas 59% of patients were treated without regard to these alternatives when available. Only 3% of all patients were identified with an observable change in the functionality of the device or patient status in comparison with 96% of patients with normal behavior and operating devices. Documented changes in the patient's medical record included 1 device exhibiting failure at 0.3-Gy dose, 1 device exhibiting increased sensor rate during dose delivery, 1 patient having an irregular heartbeat leading to device reprogramming, and 1 patient complained of twinging in the chest wall that resulted in a respiratory arrest. Although policies and procedures should directly involve the qualified medical physicist for technical supervision, their sufficient involvement was typically not requested by most respondents. No treatment options were denied to any patient based on AJCC staging, classification, or NCCN practice standards.

  6. Developing microbe-plant interactions for applications in plant-growth promotion and disease control, production of useful compounds, remediation, and carbon sequestration

    SciTech Connect (OSTI)

    Wu, C.H.; Bernard, S.; Andersen, G.L.; Chen, W.

    2009-03-01

    Interactions between plants and microbes are an integral part of our terrestrial ecosystem. Microbe-plant interactions are being applied in many areas. In this review, we present recent reports of applications in the areas of plant-growth promotion, biocontrol, bioactive compound and biomaterial production, remediation and carbon sequestration. Challenges, limitations and future outlook for each field are discussed.

  7. A Reanalysis of Curvature in the Dose Response for Cancer and Modifications by Age at Exposure Following Radiation Therapy for Benign Disease

    SciTech Connect (OSTI)

    Little, Mark P.; Stovall, Marilyn; Smith, Susan A.; Kleinerman, Ruth A.

    2013-02-01

    Purpose: To assess the shape of the dose response for various cancer endpoints and modifiers by age and time. Methods and Materials: Reanalysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by cancer endpoint (stomach, pancreas, lung, leukemia, all other). Results: There are statistically significant (P<.05) excess risks for all cancer and for lung cancer and borderline statistically significant risks for stomach cancer (P=.07), and leukemia (P=.06), with excess relative risks Gy{sup -1} of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI -0.002, 0.119), and 1.087 (95% CI -0.018, 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers. Conclusions: There are excess risks for various malignancies in this data set. Generally there is a marked downward curvature in the dose response and significant reduction in relative risk with increasing age at exposure. The consistency of risks with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

  8. Changes in Gas Bubble Disease Signs and Survival of Migrating Juvenile Salmonids Experimentally Exposed to Supersaturated Gasses, 1995-1996 Progress Report.

    SciTech Connect (OSTI)

    Absolon, Randall F.

    1997-11-01

    Research conducted in 1996 to evaluate (1) changes in GBD signs in juvenile salmonids resulting from passage through turbine intakes and bypass systems, and (2) relative survival during migration through the lower Snake River for juvenile salmonids experimentally exposed to supersaturation of dissolved gas.

  9. Method and product for phosphosilicate slurry for use in dentistry and related bone cements

    DOE Patents [OSTI]

    Wagh, Arun S.; Primus, Carolyn

    2006-08-01

    The present invention is directed to magnesium phosphate ceramics and their methods of manufacture. The composition of the invention is produced by combining a mixture of a substantially dry powder component with a liquid component. The substantially dry powder component comprises a sparsely soluble oxide powder, an alkali metal phosphate powder, a sparsely soluble silicate powder, with the balance of the substantially dry powder component comprising at least one powder selected from the group consisting of bioactive powders, biocompatible powders, fluorescent powders, fluoride releasing powders, and radiopaque powders. The liquid component comprises a pH modifying agent, a monovalent alkali metal phosphate in aqueous solution, the balance of the liquid component being water. The use of calcined magnesium oxide as the oxide powder and hydroxylapatite as the bioactive powder produces a self-setting ceramic that is particularly suited for use in dental and orthopedic applications.

  10. Imprinted genes and transpositions: epigenomic targets for low dose radiation effects. Final report

    SciTech Connect (OSTI)

    Jirtle, Randy L.

    2012-10-11

    The overall hypothesis of this grant application is that low dose ionizing radiation (LDIR) elicits adaptive responses in part by causing heritable DNA methylation changes in the epigenome. This novel postulate was tested by determining if the level of DNA methylation at the Agouti viable yellow (A{sup vy}) metastable locus is altered, in a dose-dependent manner, by low dose radiation exposure (<10 cGy) during early gestation. This information is particularly important to ascertain given the increased use of CT scans in disease diagnosis, increased number of people predicted to live and work in space, and the present concern about radiological terrorism. We showed for the first time that LDIR significantly increased DNA methylation at the A{sup vy} locus in a sex-specific manner (p=0.004). Average DNA methylation was significantly increased in male offspring exposed to doses between 0.7 cGy and 7.6 cGy with maximum effects at 1.4 cGy and 3.0 cGy (p<0.01). Offspring coat color was concomitantly shifted towards pseudoagouti (p<0.01). Maternal dietary antioxidant supplementation mitigated both the DNA methylation changes and coat color shift in the irradiated offspring (p<0.05). Thus, LDIR exposure during gestation elicits epigenetic alterations that lead to positive adaptive phenotypic changes that are negated with antioxidants, indicating they are mediated in part by oxidative stress. These findings provide evidence that in the isogenic Avy mouse model epigenetic alterations resulting from LDIR play a role in radiation hormesis, bringing into question the assumption that every dose of radiation is harmful. Our findings not only have significant implications concerning the mechanism of hormesis, but they also emphasize the potential importance of this phenomenon in determining human risk at low radiation doses. Since the epigenetic regulation of genes varies markedly between species, the effect of LDIR on other epigenetically labile genes (e.g. imprinted genes) in

  11. A cohort study of developmental polychlorinated biphenyl (PCB) exposure in relation to post-vaccination antibody response at 6-months of age

    SciTech Connect (OSTI)

    Jusko, Todd A.; De Roos, Anneclaire J.; Schwartz, Stephen M.; Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA ; Paige Lawrence, B.; Palkovicova, Lubica; Nemessanyi, Tomas; Drobna, Beata; Fabisikova, Anna; Kocan, Anton; Sonneborn, Dean; Jahnova, Eva; Kavanagh, Terrance J.; Trnovec, Tomas; Hertz-Picciotto, Irva

    2010-05-15

    Background: Extensive experimental data in animals indicate that exposure to polychlorinated biphenyls (PCBs) during pregnancy leads to changes in offspring immune function during the postnatal period. Whether developmental PCB exposure influences immunologic development in humans has received little study. Methods: The study population was 384 mother-infant pairs recruited from two districts of eastern Slovakia for whom prospectively collected maternal, cord, and 6-month infant blood specimens were available. Several PCB congeners were measured in maternal, cord, and 6-month infant sera by high-resolution gas chromatography with electron capture detection. Concentrations of IgG-specific anti-haemophilus influenzae type b, tetanus toxoid, and diphtheria toxoid were assayed in 6-month infant sera using ELISA methods. Multiple linear regression was used to estimate the relation between maternal, cord, and 6-month infant PCB concentrations and the antibody concentrations evaluated at 6-months of age. Results: Overall, there was little evidence of an association between infant antibody concentrations and PCB measures during the pre- and early postnatal period. In addition, our results did not show specificity in terms of associations limited to a particular developmental period (e.g. pre- vs. postnatal), a particular antibody, or a particular PCB congener. Conclusions: At the PCB concentrations measured in this cohort, which are high relative to most human populations today, we did not detect an association between maternal or early postnatal PCB exposure and specific antibody responses at 6-months of age.

  12. Identification and Protection of a Bat Colony in the 183-F Clearwell: Mitigation of Bat Habitat on the Hanford Site

    SciTech Connect (OSTI)

    K. A. Gano, J. G. Lucas, C. T. Lindsey

    2009-01-06

    An ecological investigation was conducted to evaluate mitigation options for demolition of a retired facility that contained a maternity roost of approximately 2,000 Myotis yumanensis bats. The recommendation from the study was to leave the non-contaminated structure intact and fence the area.

  13. Energy Systems and Population Health

    SciTech Connect (OSTI)

    Ezzati, Majid; Bailis, Rob; Kammen, Daniel M.; Holloway, Tracey; Price, Lynn; Cifuentes, Luis A.; Barnes, Brendon; Chaurey, Akanksha; Dhanapala, Kiran N.

    2004-04-12

    It is well-documented that energy and energy systems have a central role in social and economic development and human welfare at all scales, from household and community to regional and national (41). Among its various welfare effects, energy is closely linked with people s health. Some of the effects of energy on health and welfare are direct. With abundant energy, more food or more frequent meals can be prepared; food can be refrigerated, increasing the types of food items that are consumed and reducing food contamination; water pumps can provide more water and eliminate the need for water storage leading to contamination or increased exposure to disease vectors such as mosquitoes or snails; water can be disinfected by boiling or using other technologies such as radiation. Other effects of energy on public health are mediated through more proximal determinants of health and disease. Abundant energy can lead to increased irrigation, agricultural productivity, and access to food and nutrition; access to energy can also increase small-scale income generation such as processing of agricultural commodities (e.g., producing refined oil from oil seeds, roasting coffee, drying and preserving fruits and meats) and production of crafts; ability to control lighting and heating allows education or economic activities to be shielded from daily or seasonal environmental constraints such as light, temperature, rainfall, or wind; time and other economic resources spent on collecting and/or transporting fuels can be used for other household needs if access to energy is facilitated; energy availability for transportation increases access to health and education facilities and allow increased economic activity by facilitating the transportation of goods and services to and from markets; energy for telecommunication technology (radio, television, telephone, or internet) provides increased access to information useful for health, education, or economic purposes; provision of energy

  14. Low-dose radiation from 18F-FDG PET does not increase cancer frequency or shorten latency but reduces kidney disease in cancer-prone Trp53+/- mice

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    Taylor, Kristina; Lemon, Jennifer A.; Phan, Nghi; Boreham, Douglas R.

    2014-05-28

    There is considerable interest in the health effects associated with low-level radiation exposure from medical imaging procedures. Concerns in the medical community that increased radiation exposure from imaging procedures may increase cancer risk among patients are confounded by research showing that low-dose radiation exposure can extend lifespan by increasing the latency period of some types of cancer. The most commonly used radiopharmaceutical for positron emission tomography (PET) scans is 2-[18F] fluoro-2-deoxy-d-glucose (18F-FDG), which exposes tissue to a low-dose, mixed radiation quality: 634 keV β+ and 511 keV γ-rays. The goal of this research was to investigate how modification of cancermore » risk associated with exposure to low-dose ionising radiation in cancer-prone Trp53+/- mice is influenced by radiation quality from PET. At 7-8 weeks of age, Trp53+/- female mice were exposed to one of five treatments: 0 Gy, 10 mGy γ-rays, 10 mGy 18F-FDG, 4 Gy γ-rays, 10 mGy 18F-FDG + 4 Gy γ-rays (n > 185 per group). The large 4-Gy radiation dose significantly reduced the lifespan by shortening the latency period of cancer and significantly increasing the number of mice with malignancies, compared with unirradiated controls. The 10 mGy γ-rays and 10 mGy PET doses did not significantly modify the frequency or latency period of cancer relative to unirradiated mice. Similarly, the PET scan administered prior to a large 4-Gy dose did not significantly modify the latency or frequency of cancer relative to mice receiving a dose of only 4 Gy. The relative biological effectiveness of radiation quality from 18F-FDG, with respect to malignancy, is approximately 1. Furthermore, when non-cancer endpoints were studied, it was found that the 10-mGy PET group had a significant reduction in kidney lesions (P < 0.021), indicating that a higher absorbed dose (20 ± 0.13 mGy), relative to the whole-body average, which occurs in specific tissues, may not be detrimental.« less

  15. Tuberville Lab Personnel | Savannah River Ecology Laboratory

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Lab Personnel RESEARCH STAFF Kimberly wih pine snake Kimberly Price is a new research technician in the Tuberville lab. Kimberly graduated in 2015 with her B.S. in Ecology from Augusta University in Augusta, Georgia. While a student working with Dr. Brandon R. Cromer, she focused her undergraduate research on contamination and maternal transfer of mercury in southeastern aquatic turtles using the yellow-bellied slider (Trachemys scripta scripta) and the eastern river cooter (Pseudemys concinna

  16. DNA repair efficiency in germ cells and early mouse embryos and consequences for radiation-induced transgenerational genomic damage

    SciTech Connect (OSTI)

    Marchetti, Francesco; Wyrobek, Andrew J.

    2009-01-18

    Exposure to ionizing radiation and other environmental agents can affect the genomic integrity of germ cells and induce adverse health effects in the progeny. Efficient DNA repair during gametogenesis and the early embryonic cycles after fertilization is critical for preventing transmission of DNA damage to the progeny and relies on maternal factors stored in the egg before fertilization. The ability of the maternal repair machinery to repair DNA damage in both parental genomes in the fertilizing egg is especially crucial for the fertilizing male genome that has not experienced a DNA repair-competent cellular environment for several weeks prior to fertilization. During the DNA repair-deficient period of spermatogenesis, DNA lesions may accumulate in sperm and be carried into the egg where, if not properly repaired, could result in the formation of heritable chromosomal aberrations or mutations and associated birth defects. Studies with female mice deficient in specific DNA repair genes have shown that: (i) cell cycle checkpoints are activated in the fertilized egg by DNA damage carried by the sperm; and (ii) the maternal genotype plays a major role in determining the efficiency of repairing genomic lesions in the fertilizing sperm and directly affect the risk for abnormal reproductive outcomes. There is also growing evidence that implicates DNA damage carried by the fertilizing gamete as a mediator of postfertilization processes that contribute to genomic instability in subsequent generations. Transgenerational genomic instability most likely involves epigenetic mechanisms or error-prone DNA repair processes in the early embryo. Maternal and embryonic DNA repair processes during the early phases of mammalian embryonic development can have far reaching consequences for the genomic integrity and health of subsequent generations.

  17. ATOMIC LAYER DEPOSITION OF TITANIUM OXIDE THIN FILMS ONNANOPOROUS ALUMINA TEMPLATES FOR MEDICAL APPLICATIONS

    SciTech Connect (OSTI)

    Brigmon, R.

    2009-05-05

    Nanostructured materials may play a significant role in controlled release of pharmacologic agents for treatment of cancer. Many nanoporous polymer materials are inadequate for use in drug delivery. Nanoporous alumina provides several advantages over other materials for use in controlled drug delivery and other medical applications. Atomic layer deposition was used to coat all the surfaces of the nanoporous alumina membrane in order to reduce the pore size in a controlled manner. Both the 20 nm and 100 nm titanium oxide-coated nanoporous alumina membranes did not exhibit statistically lower viability compared to the uncoated nanoporous alumina membrane control materials. In addition, 20 nm pore size titanium oxide-coated nanoporous alumina membranes exposed to ultraviolet light demonstrated activity against Escherichia coli and Staphylococcus aureus bacteria. Nanostructured materials prepared using atomic layer deposition may be useful for delivering a pharmacologic agent at a precise rate to a specific location in the body. These materials may serve as the basis for 'smart' drug delivery devices, orthopedic implants, or self-sterilizing medical devices.

  18. ORISE: ORAU-managed beryllium lab marks outstanding year in 2013

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    higher risk of developing Chronic Beryllium Disease, a chronic disease that scars the lungs making it more difficult for oxygen to transfer into the bloodstream. The test...

  19. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... measures and health monitoring to prevent the development of acute or chronic beryllium disease, two pulmonary diseases created by an allergic reaction to beryllium in the lungs. ...

  20. Tracking Living Cells as They Differentiate in Real Time

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Alzheimer's disease, macular degeneration of the retina in diabetes, and mitochondrial diseases in children. In addition, specific processes like protein glycation can also be...

  1. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain ... Mutations of the Newcastle disease virus HN stalk region have been shown to affect both F ...

  2. ORISE: Recent Graduate Research Experiences - Lindsay Gabbert

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Control and Prevention concentrated on human disease. "Previously, I was focused on dengue hemorrhagic fever-a potentially life-threatening mosquito-borne tropical disease which...

  3. Genome Engineering with TAL Effector Nucleases

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    sequences in patients suffering from genetic diseases, the modification or insertion of genes in plants, and the generation of unique cell lines for treatment of diseases such as...

  4. Tracking Living Cells as They Differentiate in Real Time

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    these projects will target Alzheimer's disease, macular degeneration of the retina in diabetes, and mitochondrial diseases in children. In addition, specific processes like protein...

  5. New insights into regulating the gut's microbial community |...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    of microbiota-associated pathologies such as inflammatory bowel disease, obesity, diabetes, and celiac disease. Study: "Innate and Adaptive Humoral Responses Coat Distinct...

  6. Former Workers Medical Facilities with Experience Evaluating...

    Energy Savers [EERE]

    Former Workers Medical Facilities with Experience Evaluating Chronic Beryllium Disease Former Workers Medical Facilities with Experience Evaluating Chronic Beryllium Disease April...

  7. Enterprise Assessments Follow-up Review of the Hanford Site Chronic...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Review of the Hanford Site Chronic Beryllium Disease Prevention Program - June 2015 Enterprise Assessments Follow-up Review of the Hanford Site Chronic Beryllium Disease Prevention...

  8. Audit Report: IG-0726 | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    of beryllium disease, two of the objectives of the Chronic Beryllium Disease Prevention Program (Prevention Program). PDF icon Audit Report: IG-0726 More Documents &...

  9. EA-0896: Finding of No Significant Impact

    Broader source: Energy.gov [DOE]

    Center for Nuclear Medicine Research in Alzheimer's Disease Health Sciences Center- West Virginia University

  10. EA-0896: Final Environmental Assessment

    Broader source: Energy.gov [DOE]

    Center for Nuclear Medicine Research in Alzheimer's Disease Health Sciences Center- West Virginia University

  11. ORISE: Recent Graduate Research Experiences - Lindsay Gabbert

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Lindsay Gabbert Animal disease research opportunity proves to be rewarding assignment for graduate student Lindsay Gabbert Lindsay Gabbert performs research at the Plum Island Animal Disease Center, where she is helping to improve the vaccination for foot-and-mouth disease. Prior to Plum Island, she completed a fellowship at the Centers for Disease Control and Prevention, where she concentrated on human diseases. For Lindsay Gabbert, her current position as a research participant is a different

  12. Characterization of aerosols produced by surgical procedures

    SciTech Connect (OSTI)

    Yeh, H.C.; Muggenburg, B.A.; Lundgren, D.L.; Guilmette, R.A.; Snipes, M.B.; Jones, R.K.; Turner, R.S.

    1994-07-01

    In many surgeries, especially orthopedic procedures, power tools such as saws and drills are used. These tools may produce aerosolized blood and other biological material from bone and soft tissues. Surgical lasers and electrocautery tools can also produce aerosols when tissues are vaporized and condensed. Studies have been reported in the literature concerning production of aerosols during surgery, and some of these aerosols may contain infectious material. Garden et al. (1988) reported the presence of papilloma virus DNA in the fumes produced from laser surgery, but the infectivity of the aerosol was not assessed. Moon and Nininger (1989) measured the size distribution and production rate of emissions from laser surgery and found that particles were generally less than 0.5 {mu}m diameter. More recently there has been concern expressed over the production of aerosolized blood during surgical procedures that require power tools. In an in vitro study, the production of an aerosol containing the human immunodeficiency virus (HIV) was reported when power tools were used to cut tissues with blood infected with HIV. Another study measured the size distribution of blood aerosols produced by surgical power tools and found blood-containing particles in a number of size ranges. Health care workers are anxious and concerned about whether surgically produced aerosols are inspirable and can contain viable pathogens such as HIV. Other pathogens such as hepatitis B virus (HBV) are also of concern. The Occupational Safety and Health funded a project at the National Institute for Inhalation Toxicology Research Institute to assess the extent of aerosolization of blood and other tissues during surgical procedures. This document reports details of the experimental and sampling approach, methods, analyses, and results on potential production of blood-associated aerosols from surgical procedures in the laboratory and in the hospital surgical suite.

  13. Fibroblast growth factor 2 inhibits up-regulation of bone morphogenic proteins and their receptors during osteoblastic differentiation of human mesenchymal stem cells

    SciTech Connect (OSTI)

    Biver, Emmanuel; Soubrier, Anne-Sophie; Thouverey, Cyril; Cortet, Bernard; Broux, Odile; Caverzasio, Joseph; Hardouin, Pierre

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer FGF modulates BMPs pathway in HMSCs by down-regulating BMP/BMPR expression. Black-Right-Pointing-Pointer This effect is mediated by ERK and JNK MAPKs pathways. Black-Right-Pointing-Pointer Crosstalk between FGF and BMPs must be taken into account in skeletal bioengineering. Black-Right-Pointing-Pointer It must also be considered in the use of recombinant BMPs in orthopedic and spine surgeries. -- Abstract: Understanding the interactions between growth factors and bone morphogenic proteins (BMPs) signaling remains a crucial issue to optimize the use of human mesenchymal stem cells (HMSCs) and BMPs in therapeutic perspectives and bone tissue engineering. BMPs are potent inducers of osteoblastic differentiation. They exert their actions via BMP receptors (BMPR), including BMPR1A, BMPR1B and BMPR2. Fibroblast growth factor 2 (FGF2) is expressed by cells of the osteoblastic lineage, increases their proliferation and is secreted during the healing process of fractures or in surgery bone sites. We hypothesized that FGF2 might influence HMSC osteoblastic differentiation by modulating expressions of BMPs and their receptors. BMP2, BMP4, BMPR1A and mainly BMPR1B expressions were up-regulated during this differentiation. FGF2 inhibited HMSCs osteoblastic differentiation and the up-regulation of BMPs and BMPR. This effect was prevented by inhibiting the ERK or JNK mitogen-activated protein kinases which are known to be activated by FGF2. These data provide a mechanism explaining the inhibitory effect of FGF2 on osteoblastic differentiation of HMSCs. These crosstalks between growth and osteogenic factors should be considered in the use of recombinant BMPs in therapeutic purpose of fracture repair or skeletal bioengineering.

  14. Microstructural characterization of as-cast biocompatible Co-Cr-Mo alloys

    SciTech Connect (OSTI)

    Giacchi, J.V.; Morando, C.N.; Fornaro, O.; Palacio, H.A.

    2011-01-15

    The microstructure of a cobalt-base alloy (Co-Cr-Mo) obtained by the investment casting process was studied. This alloy complies with the ASTM F75 standard and is widely used in the manufacturing of orthopedic implants because of its high strength, good corrosion resistance and excellent biocompatibility properties. This work focuses on the resulting microstructures arising from samples poured under industrial environment conditions, of three different Co-Cr-Mo alloys. For this purpose, we used: 1) an alloy built up from commercial purity constituents, 2) a remelted alloy and 3) a certified alloy for comparison. The characterization of the samples was achieved by using optical microscopy (OM) with a colorant etchant to identify the present phases and scanning electron microscopy (SE-SEM) and energy dispersion spectrometry (EDS) techniques for a better identification. In general the as-cast microstructure is a Co-fcc dendritic matrix with the presence of a secondary phase, such as the M{sub 23}C{sub 6} carbides precipitated at grain boundaries and interdendritic zones. These precipitates are the main strengthening mechanism in this type of alloys. Other minority phases were also reported and their presence could be linked to the cooling rate and the manufacturing process variables and environment. - Research Highlights: {yields}The solidification microstructure of an ASTM-F75 type alloy were studied. {yields}The alloys were poured under an industrial environment. {yields}Carbides and sigma phase identified by color metallography and scanning microscopy (SEM and EDS). {yields}Two carbide morphologies were detected 'blocky type' and 'pearlite type'. {yields}Minority phases were also detected.

  15. Selenium Preferentially Accumulates in the Eye Lens Following Embryonic Exposure: A Confocal X-ray Fluorescence Imaging Study

    SciTech Connect (OSTI)

    Choudhury, Sanjukta; Thomas, Jith; Sylvain, Nicole J.; Ponomarenko, Olena; Gordon, Robert A.; Heald, Steve M.; Janz, David M.; Krone, Patrick H.; Coulthard, Ian; George, Graham N.; Pickering, Ingrid J.

    2015-02-17

    Maternal transfer of elevated selenium (Se) to offspring is an important route of Se exposure for fish in the natural environment. However, there is a lack of information on the tissue specific spatial distribution and speciation of Se in the early developmental stages of fish, which provide important information about Se toxicokinetics. The effect of maternal transfer of Se was studied by feeding adult zebrafish a Se-elevated or a control diet followed by collection of larvae from both groups. Novel confocal synchrotron-based techniques were used to investigate Se within intact preserved larvae. Confocal X-ray fluorescence imaging was used to compare Se distributions within specific planes of an intact larva from each of the two groups. The elevated Se treatment showed substantially higher Se levels than the control; Se preferentially accumulated to highest levels in the eye lens, with lower levels in the retina, yolk and other tissues. Confocal X-ray absorption spectroscopy was used to determine that the speciation of Se within the eye lens of the intact larva was a selenomethionine-like species. Preferential accumulation of Se in the eye lens may suggest a direct cause-and-effect relationship between exposure to elevated Se and Se-induced ocular impairments reported previously. This study illustrates the effectiveness of confocal X-ray fluorescence methods for investigating trace element distribution and speciation in intact biological specimens

  16. Glomerular-specific imprinting of the mouse Gs{alpha} gene: How does this relate to hormone resistance in Albright hereditary osteodystrophy?

    SciTech Connect (OSTI)

    Williamson, C.M.; Dutton, E.R.; Seymour, A.

    1996-09-01

    The gene for alpha-stimulating guanine-nucleotide binding polypeptide, Gnas, has been considered as a candidate for the imprinting effects ascribed to distal mouse Chromosome (Chr) 2. Its human homologue (GNAS1) appears, from clinical and biochemical studies of patients with Albright hereditary ostodystrophy, to be paternally imprinted. GNAS1 maps to 20q13, a region that shows linkage conservation with distal mouse Chr 2. We have mapped Gnas within the imprinting region on distal Chr 2 by linkage analysis. To establish if Gnas is imprinted, we have looked for expression differences in tissues taken from mice carrying maternal duplication/paternal deficiency for distal Chr 2 (MatDp2) and its reciprocal (PatDp2). RNA in situ hybridization revealed high levels of Gnas mRNA in glomeruli of PatDp2 embryos at late gestation and lower levels in glomeruli of MatDp2 embryos. These results strongly suggest that Gnas is maternally imprinted and suggest that the mouse gene may be imprinted in a manner opposite the predicted in human. 42 refs., 4 figs.

  17. Inhalation developmental toxicology studies: Developmental toxicity of chloroprene vapors in New Zealand white rabbits. Final report

    SciTech Connect (OSTI)

    Mast, T.J.; Evanoff, J.J.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.

    1994-04-01

    Chloroprene, 2-chloro-1,3-butadiene, is a colorless liquid with a pungent ethereal odor that is primarily used as an intermediate in the manufacture of neoprene rubber, and has been used as such since about 1930. This study addressed the potential for chloroprene to cause developmental toxicity in New Zealand white rabbits following gestational exposure to 0, 10, 40, or 175 ppm chloroprene vapors, 6h/dy, 7dy/wk. Each treatment group consisted of 15 artificially inseminated females exposed on 6 through 28 days of gestation (dg). Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice on 29 dg. Implants were enumerated and their status recorded and live fetuses were examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. There were no overt signs of maternal toxicity and the change in maternal body weight over the course of the study was not affected. Exposure of pregnant rabbits to chloroprene vapors on 6-28 dg had no effect on the number of implantation, the mean percent of live pups per litter, or on the incidence of resorptions per litter. The incidence of fetal malformations was not increased by exposure to chloroprene. Results of this study indicate that gestational exposure of New Zealand white rabbits to 10, 40, or 175 ppm chloroprene did not result in observable toxicity to either the dam or the offspring.

  18. Inhalation developmental toxicology studies: Acetonitrile in rats. Final report

    SciTech Connect (OSTI)

    Mast, T.J.; Weigel, R.J.; Westerberg, R.B.; Boyd, P.J.; Hayden, B.K.; Evanoff, J.J.; Rommereim, R.L.

    1994-02-01

    The potential for acetonitrile to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 100, 400, or 1200 ppM acetonitrile, 6 hours/day, 7 days/week. Exposure of rats to these concentrations of acetonitrile resulted in mortality in the 1200 ppM group (2/33 pregnant females; 1/10 non-pregnant females). However, there were no treatment-related effects upon body weights or reproduction indices at any exposure level, nor was there a significant increase in the incidence of fetal malformations or variations. The only effect observed in the fetuses was a slight, but not statiscally significant, exposure-correlated increase in the incidence of supernumerary ribs. Determination of acetonitrile and cyanide concentrations in maternal rat blood showed that acetonitrile concentration in the blood increased with exposure concentration for all exposed maternal rats. Detectable amounts of cyanide in the blood were found only in the rats exposed to 1200 ppM acetonitrile ({approximately}2 {mu}g cyanide/g of blood).

  19. The production, purification and crystallization of a soluble form of the nonclassical MHC HLA-G: the essential role of cobalt

    SciTech Connect (OSTI)

    Clements, Craig S.; Kjer-Nielsen, Lars; Kostenko, Lyudmila; McCluskey, James; Rossjohn, Jamie

    2006-01-01

    X-ray diffraction data were collected to 1.9 from crystals of HLA-G. Cobalt ions were found to be essential for the production of diffracting crystals. HLA-G is a nonclassical class I major histocompatibility complex (MHC) molecule that is primarily expressed at the foetalmaternal interface. Although the role of HLA-G has not been fully elucidated, current evidence suggests it protects the foetus from the maternal immune response. In this report, HLA-G (44 kDa) is characterized by expression in Escherichia coli. The inclusion bodies were refolded in complex with a peptide derived from histone H2A (RIIPRHLQL), purified and subsequently crystallized. Correct refolding was determined using two conformation-dependent antibodies. Cobalt ions were shown to be an essential ingredient for obtaining diffraction-quality crystals. The crystals, which diffracted to 1.9 resolution, belonged to space group P3{sub 2}2{sub 1}, with unit-cell parameters a = b = 77.15, c = 151.72 .

  20. Final report on the developmental toxicity of ethylenediamine (CAS No. 107-15-3) in New Zealand white rabbits. Report for November-February 1992

    SciTech Connect (OSTI)

    Not Available

    1993-03-01

    Ethylenediamine (EDA) is a major industrial chemical with an estimated U.S. production of 64 million pounds in 1985. EDA is used as a chemical intermediate or solvent in manufacturing, as a paint thinner, and as a constituent of certain cosmetic, pharmaceutical and veterinary products. Based upon its widespread applications and the potential for exposure in pregnant women, EDA was evaluated for maternal and developmental toxicity using a laboratory animal model. Artificially-inseminated New Zealand White rabbits (26/group) were administered ethylenediamine (0, 10, 40 or 80 mg/kg/day) by gavage on gestational days (gd) 6 through 19. The doses administered were equivalent to 0, 22, 89 or 178 of EDA.2HC1. Maternal clinical signs, body weight, and food consumption were monitored at regular intervals throughout gestation. At termination (gd 30), the uterus was removed and examined to determine pregnancy status and to evaluate the number of resorptions, and dead or live fetuses. Dead or live fetuses were weighed, and live fetuses examined for external, visceral and skeletal defects.

  1. US Department of Energy - Office of FreedomCar and Vehicle Technologies and US Centers for Disease Control and Prevention - National Institute for Occupational Safety and Health Inter-Agency Agreement Research on "The Analysis of Genotoxic Activities of Exhaust Emissions from Mobile Natural Gas, Diesel, and Spark-Ignition Engines"

    SciTech Connect (OSTI)

    William E. Wallace

    2006-09-30

    The US Department of Energy-Office of Heavy Vehicle Technologies (now the DOE-Office of FreedomCar and Vehicle Technologies) signed an Interagency Agreement (IAA) with National Institute for Occupational Safety and Health (NIOSH), No.01-15 DOE, 9/4/01, for 'The analysis of genotoxic activities of exhaust emissions from mobile natural gas, diesel, and spark-ignition engines'; subsequently modified on 3/27/02 (DOE IAG No.01-15-02M1); subsequently modified 9/02/03 (IAA Mod No. 01-15-03M1), as 'The analysis of genotoxic activities of exhaust emissions from mobile internal combustion engines: identification of engine design and operational parameters controlling exhaust genotoxicity'. The DOE Award/Contract number was DE-AI26-01CH11089. The IAA ended 9/30/06. This is the final summary technical report of National Institute for Occupational Safety and Health research performed with the US Department of Energy-Office of FreedomCar and Vehicle Technologies under that IAA: (A) NIOSH participation was requested by the DOE to provide in vitro genotoxicity assays of the organic solvent extracts of exhaust emissions from a suite of in-use diesel or spark-ignition vehicles; (B) research also was directed to develop and apply genotoxicity assays to the particulate phase of diesel exhaust, exploiting the NIOSH finding of genotoxicity expression by diesel exhaust particulate matter dispersed into the primary components of the surfactant coating the surface of the deep lung; (C) from the surfactant-dispersed DPM genotoxicity findings, the need for direct collection of DPM aerosols into surfactant for bioassay was recognized, and design and developmental testing of such samplers was initiated.

  2. C:\\Forms\\OLD FORMS\\Dp5484-3.cdr

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Code 7a(21) - Skin disease or disorders Code 7b(22) - Dust diseases of lungs Code 7c(23) - Resp. due to toxic agents Code 7d(24) - Poisoning Code 7e(25) - Disorders-Physical agents ...

  3. Three Los Alamos scientists named 'Most Influential Scientific...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    disease only comes when the work has an impact on treating diseases such as HIV, influenza and hepatitis and ultimately in saving lives." Perelson is part of a multinational...

  4. 'Most Influential Scientific Minds'

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    disease only comes when the work has an impact on treating diseases such as HIV, influenza and hepatitis and ultimately in saving lives." Perelson is part of a multinational...

  5. Is Primary Prostate Cancer Treatment Influenced by Likelihood...

    Office of Scientific and Technical Information (OSTI)

    Patients with clinical T1T2 disease were grouped into categories of <25%, 25%-50%, and >50% likelihood of having extraprostatic disease using the Partin nomogram. Clinical T3T4 ...

  6. Infant sex-specific placental cadmium and DNA methylation associations

    SciTech Connect (OSTI)

    Mohanty, April F.; Farin, Fred M.; Bammler, Theo K.; MacDonald, James W.; Afsharinejad, Zahra; Burbacher, Thomas M.; Siscovick, David S.; and others

    2015-04-15

    Background: Recent evidence suggests that maternal cadmium (Cd) burden and fetal growth associations may vary by fetal sex. However, mechanisms contributing to these differences are unknown. Objectives: Among 24 maternal-infant pairs, we investigated infant sex-specific associations between placental Cd and placental genome-wide DNA methylation. Methods: We used ANOVA models to examine sex-stratified associations of placental Cd (dichotomized into high/low Cd using sex-specific Cd median cutoffs) with DNA methylation at each cytosine-phosphate-guanine site or region. Statistical significance was defined using a false discovery rate cutoff (<0.10). Results: Medians of placental Cd among females and males were 5 and 2 ng/g, respectively. Among females, three sites (near ADP-ribosylation factor-like 9 (ARL9), siah E3 ubiquitin protein ligase family member 3 (SIAH3), and heparin sulfate (glucosamine) 3-O-sulfotransferase 4 (HS3ST4) and one region on chromosome 7 (including carnitine O-octanoyltransferase (CROT) and TP5S target 1 (TP53TG1)) were hypomethylated in high Cd placentas. Among males, high placental Cd was associated with methylation of three sites, two (hypomethylated) near MDS1 and EVI1 complex locus (MECOM) and one (hypermethylated) near spalt-like transcription factor 1 (SALL1), and two regions (both hypomethylated, one on chromosome 3 including MECOM and another on chromosome 8 including rho guanine nucleotide exchange factor (GEF) 10 (ARHGEF10). Differentially methylated sites were at or close to transcription start sites of genes involved in cell damage response (SIAH3, HS3ST4, TP53TG1) in females and cell differentiation, angiogenesis and organ development (MECOM, SALL1) in males. Conclusions: Our preliminary study supports infant sex-specific placental Cd-DNA methylation associations, possibly accounting for previously reported differences in Cd-fetal growth associations across fetal sex. Larger studies are needed to replicate and extend these

  7. Enterprise Assessments Follow-up Review of the Hanford Site Chronic

    Energy Savers [EERE]

    Beryllium Disease Prevention Program - June 2015 | Department of Energy Assessments Follow-up Review of the Hanford Site Chronic Beryllium Disease Prevention Program - June 2015 Enterprise Assessments Follow-up Review of the Hanford Site Chronic Beryllium Disease Prevention Program - June 2015 June 2015 Follow-up Review of the Hanford Site Chronic Beryllium Disease Prevention Program The Office of Worker Safety and Health Assessments, within the U.S. Department of Energy's (DOE) independent

  8. The proposed revision to the NAAQS for carbon monoxide and its...

    Office of Scientific and Technical Information (OSTI)

    STANDARDS; CARBON MONOXIDE; BIOLOGICAL EFFECTS; NEW JERSEY; POLLUTION REGULATIONS; AIR POLLUTION; CARDIOVASCULAR DISEASES; HEALTH HAZARDS; PUBLIC HEALTH; SENSITIVITY; CARBON ...

  9. ORISE: Recent Graduate Research Experiences - Camila Dias Colberg

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Camila Dias Colberg Animal disease research opportunity proves to be rewarding assignment for graduate student Camila Dias Colberg Camila Dias Colberg is supporting research at the Plum Island Animal Disease Center to find a more effective treatment for foot-and-mouth disease. A Brazilian veterinarian, she hopes one day to be a licensed veterinarian in the United States. Click image to enlarge. The impact of foot-and-mouth disease hit home for Camila Dias Colberg in 2005 while working on her

  10. NMED_NNMCAB_Presentation_Final(5-18-16).pdf

    Office of Environmental Management (EM)

    of Energy NIOSH Alert-Preventing Sentization and Disease from Beryllium NIOSH Alert-Preventing Sentization and Disease from Beryllium February 3, 2011 Preventing Sensitization and Disease from Beryllium Exposure The National Institute for Occupational Safety and Health (NIOSH) requests assistance in preventing beryllium sensitization and chronic beryllium disease. Development of these conditions requires exposure to beryllium and is affected by both job tasks and genetic factors. Some jobs

  11. "Title","Creator/Author","Publication Date","OSTI Identifier...

    Office of Scientific and Technical Information (OSTI)

    ACIDS; CALIFORNIA; CHAINS; CHEMISTRY; DISEASES; FIBROSIS; FORECASTING; GENETICS; OPTIMIZATION; PROTEIN STRUCTURE; PROTEINS; QUEUES; SHAPE; SIMULATION PROTEIN STRUCTURE...

  12. Manipulating and Visualizing Proteins Simon, Horst D. 59 BASIC...

    Office of Scientific and Technical Information (OSTI)

    ACIDS; CALIFORNIA; CHAINS; CHEMISTRY; DISEASES; FIBROSIS; FORECASTING; GENETICS; OPTIMIZATION; PROTEIN STRUCTURE; PROTEINS; QUEUES; SHAPE; SIMULATION PROTEIN STRUCTURE...

  13. TITLE AUTHORS SUBJECT SUBJECT RELATED DESCRIPTION PUBLISHER AVAILABILI...

    Office of Scientific and Technical Information (OSTI)

    AMINO ACIDS CALIFORNIA CHAINS CHEMISTRY DISEASES FIBROSIS FORECASTING GENETICS OPTIMIZATION PROTEIN STRUCTURE PROTEINS QUEUES SHAPE SIMULATION PROTEIN STRUCTURE PREDICTION...

  14. ORISE: Consumer Health Resource Information Service (CHRIS) ...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    that disproportionately affect minorities, including: HIVAIDS Cardiovascular disease Diabetes Immunization Cancer Infant mortality ORISE provides health information training for...

  15. Former Workers Medical Facilities with Experience Evaluating Chronic

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Beryllium Disease | Department of Energy Workers Medical Facilities with Experience Evaluating Chronic Beryllium Disease Former Workers Medical Facilities with Experience Evaluating Chronic Beryllium Disease April 2011 This document provides a listing of medical facilities within the United States with experience in evaluating Chronic Beryllium Disease (CBD). Because the medical community at large is not experienced in the evaluation and treatment of individuals with CBD, this list is

  16. Enterprise Assessments Review of the East Tennessee Technology Park

    Office of Environmental Management (EM)

    Beryllium Disease Prevention Program - June 2015 | Department of Energy Review of the Hanford Site Chronic Beryllium Disease Prevention Program - June 2015 Enterprise Assessments Follow-up Review of the Hanford Site Chronic Beryllium Disease Prevention Program - June 2015 June 2015 Follow-up Review of the Hanford Site Chronic Beryllium Disease Prevention Program The Office of Worker Safety and Health Assessments, within the U.S. Department of Energy's (DOE) independent Office of Enterprise

  17. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Las Vegas, Nevada (United States) Yucca Mountain Project... contributing to death during maintenance therapy. ... disease control rate warrants additional ...

  18. CRAD, Assessment of the Site- February 17, 2010

    Broader source: Energy.gov [DOE]

    Assessment of the Site Chronic Beryllium Disease Prevention Plan (CBDPP) Implementation (HSS CRAD 64-37, Rev 0)

  19. Economic Assessment for the Notice of Proposed Rule Making for 10 CFR 850

    Office of Energy Efficiency and Renewable Energy (EERE)

    10 CFR 850, Chronic Beryllium Disease Prevention Program, Notice of Proposed Rulemaking and the accompanying Economic Assessment.

  20. antagonist Haga, Kazuko; Kruse, Andrew C.; Asada, Hidetsugu;

    Office of Scientific and Technical Information (OSTI)

    BIOLOGY; CENTRAL NERVOUS SYSTEM; DISEASES; DISSOCIATION; NERVES; ORGANS; POTASSIUM; PROTEINS; REGULATIONS; RESIDUES; TARGETS; TYROSINE The parasympathetic branch of the autonomic...

  1. TITLE AUTHORS SUBJECT SUBJECT RELATED DESCRIPTION PUBLISHER AVAILABILI...

    Office of Scientific and Technical Information (OSTI)

    BIOLOGY CENTRAL NERVOUS SYSTEM DISEASES DISSOCIATION NERVES ORGANS POTASSIUM PROTEINS REGULATIONS RESIDUES TARGETS TYROSINE The parasympathetic branch of the autonomic...

  2. "Title","Creator/Author","Publication Date","OSTI Identifier...

    Office of Scientific and Technical Information (OSTI)

    BIOLOGY; CENTRAL NERVOUS SYSTEM; DISEASES; DISSOCIATION; NERVES; ORGANS; POTASSIUM; PROTEINS; REGULATIONS; RESIDUES; TARGETS; TYROSINE",,"The parasympathetic branch of the...

  3. Search for: All records | DOE PAGES

    Office of Scientific and Technical Information (OSTI)

    Name: Subject: Identifier Numbers: Research Org: Sponsoring Org: Publication Date: ... implicated in several neurodegenerative diseases and other disorders, including cancer. ...

  4. Picture of the Week: Hot cells for medical isotopes

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    2 Hot cells for medical isotopes Isotopes from Los Alamos are used for the diagnosis of cardiac disease, calibration of PET scanners which in turn diagnose cancer, neurological disease, inflammatory diseases, trauma, and other circulatory diseases, and are increasingly being investigated for their potential to treat a variety of localized pathologies. June 7, 2015 Hot cells for medical isotopes x View extra-large image on Flickr » Every year, over 1,000,000 cardiac, cancer and other patients

  5. BeryllFactShts12-7-01

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Beryllium and Chronic Beryllium Disease Chronic Beryllium Disease will probably have little effect on your life. Even so, you should see a doctor regularly to monitor the disease. * Treatment with a group of drugs called corticoster- oids ("steroids"), such as prednisone, may be advised for those with symptoms of, or breathing tests that show Chronic Beryllium Disease. (These "steroids" are not the same as the ones you hear about athletes using.) These steroids reduce

  6. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Kjaergaard ; Amtorp, Ole ; Jonassen, Thomas ; Loft, Steffen Background: Particulate air pollution can aggravate cardiovascular disease by mechanisms suggested to involve ...

  7. Profile for Sara Y. Del Valle

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Biosciences Biosecurity Modeling of viral disease dynamics Epidemiology modeling Computational Physics and Applied Mathematics Mathematics Monte Carlo methods Discrete event ...

  8. Genes from the 20Q13 amplicon and their uses

    DOE Patents [OSTI]

    Gray, Joe; Collins, Colin; Hwang, Soo-in; Godfrey, Tony; Kowbel, David; Rommens, Johanna

    1999-01-01

    The present invention relates to cDNA sequences from a region of amplification on chromosome 20 associated with disease. The sequences can be used in hybridization methods for the identification of chromosomal abnormalities associated with various diseases. The sequences can also be used for treatment of diseases.

  9. Assessment of methods and results of reproductive occupational epidemiology: spontaneous abortions and malformations in the offspring of working women

    SciTech Connect (OSTI)

    Hemminki, K.; Axelson, O.; Niemi, M.L.; Ahlborg, G.

    1983-01-01

    Epidemiological studies relating occupational exposures of working women to spontaneous abortions and malformation are reviewed and some methodological considerations are presented. The reproductive epidemiology is less developed than epidemiology in general and seems to involve some specific problems. The exposures may be reported differently by the women depending on the outcome of the pregnancy; thus confirmation of exposure from an independent data source would be an asset. The types of occupational exposures of the women, suggested to carry a risk of spontaneous abortions, include anesthetic agents, laboratory work, copper smelting, soldering, and chemical sterilization using ethylene oxide and glutaraldehyde. Maternal employment in laboratories and exposure to solvents has been linked to a risk of congenital malformations in the offspring in five studies. Data on the teratogenic effects of anesthetic gases has been conflicting. In one study, employment in copper smelting was associated with malformations in the offspring.

  10. Repeated in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure affects male gonads in offspring, leading to sex ratio changes in F{sub 2} progeny

    SciTech Connect (OSTI)

    Ikeda, Masahiko . E-mail: ikedam@ys2.u-shizuoka-ken.ac.jp; Tamura, Masashi; Yamashita, Junko; Suzuki, Chinatsu; Tomita, Takako

    2005-08-15

    The effects of in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the reproductive system of male rat offspring (F{sub 1}) and the sex ratio of the subsequent generation (F{sub 2}) were examined. Female Holtzman rats were gavaged with an initial loading dose of 400 ng/kg TCDD prior to mating, followed by weekly maintenance doses of 80 ng/kg during mating, pregnancy, and the lactation period. Maternal exposure to TCDD had no significant effects on fetus/pup (F{sub 1}) mortality, litter size, or sex ratio on gestation day (GD) 20 or postnatal day (PND) 2. The TCDD concentration in maternal livers and adipose tissue on GD20 was 1.21 and 1.81 ng/kg, respectively, and decreased at weaning to 0.72 in the liver and 0.84 in the adipose tissue. In contrast, the TCDD concentration in pup livers was 1.32 ng/kg on PND2 and increased to 1.80 ng/kg at weaning. Ventral prostate weight of male offspring was significantly decreased by TCDD exposure on PND28 and 120 compared with that of controls. Weight of the testes, cauda epididymides, and seminal vesicle, and sperm number in the cauda epididymis were not changed by TCDD exposure at PND120. TCDD- or vehicle-exposed male offspring were mated with unexposed females. The sex ratio (percentage of male pups) of F{sub 2} offspring was significantly reduced in the TCDD-exposed group compared with controls. These results suggest that in utero and lactational TCDD exposures affect the development of male gonads in offspring (F{sub 1}), leading to changes in the sex ratio of the subsequent generation (F{sub 2})

  11. Placental concentrations of heavy metals in a mother-child cohort

    SciTech Connect (OSTI)

    Amaya, E.; Gil, F.; Freire, C.; National School of Public Health, Oswaldo Cruz Foundation , 21041-210 Rio de Janeiro ; Olmedo, P.; Fernandez-Rodriguez, M.; Fernandez, M.F.; Olea, N.; CIBER de Epidemiologia y Salud Publica

    2013-01-15

    Heavy metals are environmental contaminants with properties known to be toxic for wildlife and humans. Despite strong concerns about their harmful effects, little information is available on intrauterine exposure in humans. The aim of this study was to evaluate prenatal exposure to As, Cd, Cr, Hg, Mn, and Pb and its association with maternal factors in a population-based mother-child cohort in Southern Spain. Between 2000 and 2002, 700 pregnant women were recruited and 137 placentas from the cohort were randomly selected and analyzed for the selected metals by atomic absorption. Maternal sociodemographic and lifestyle factors were obtained by questionnaire after delivery. Bivariate analysis and multivariate linear regression were performed. Cd and Mn concentrations were detected in all placentas, while Cr, Pb, and Hg were found in 98.5%, 35.0%, and 30.7% of samples, respectively. The highest concentrations were observed for Pb (mean: 94.80 ng/g wet weight of placenta), followed by Mn (63.80 ng/g), Cr (63.70 ng/g), Cd (3.45 ng/g), and Hg (0.024 ng/g). Arsenic was not detected in any sample. Gestational age and smoking during pregnancy were associated with placental Cd concentrations, while no factor appeared to influence concentrations of Cr, Hg, Mn, or Pb. In comparison to results of European studies, these concentrations are in a low-intermediate position. Studies are required to investigate the factors contributing to early exposure to heavy metals and to determine how placental transfer of these toxic compounds may affect children's health.

  12. Laminated root rot in western North America. Forest Service general technical report

    SciTech Connect (OSTI)

    Thies, W.G.; Sturrock, R.N.

    1995-04-01

    Laminated root rot, caused by Phellinus weirii (Murr.) Gib., is a serious root disease affecting Douglas-fir and other commercially important species of conifers in northwestern North America. This report gives an overview of the disease as it occurs in the Pacific Northwest in Canada and the United States. Information on recognizing crown symptoms and signs of the disease is presented. The disease cycle of laminated root rot, from initiation to intensification and distribution within infected stands, is described. Finally, disease management strategies during stand development and at stand regeneration are discussed. Features on mechanical approaches also are included. The report is intended as a general reference for a wide audience.

  13. Risk Group and Biosafety Level Definitions

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Group and Biosafety Level Definitions European Economic Community (DIRECTIVE 93/88/EEC, Oct. 1993) (1) Group 1 biological agent means one that is unlikely to cause human disease; (2) Group 2 biological agent means one that can cause human disease and might be a hazard to workers; it is unlikely to spread to the community; there is usually effective prophylaxis or treatment available; (3) Group 3 biological agent means one that can cause severe human disease and present a serious hazard to

  14. ORISE: Recent Graduate Research Experiences - Krystina Addorisio

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Krystina Addorisio Researcher works to protect nation's food agriculture Krystina Assorisio Forensic scientist Krystina Addorisio, pictured right, has spent the last three years researching a vaccine for animal diseases such as foot-and-mouth-a contagious disease that affects cows, pigs and sheep-at the U.S. Department of Homeland Security's Plum Island Animal Disease Center. Click image to enlarge. Each morning, Krystina Addorisio commutes by ferry to work on a small island-the subject of some

  15. PHYSICS ASSEMBLY LABORATORY HAER NO. SC-43

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Department of Energy 0 Years, 10 Breakthroughs at Argonne's Fastest Supercomputer PHOTOS: 10 Years, 10 Breakthroughs at Argonne's Fastest Supercomputer February 24, 2016 - 12:46pm Addthis Understanding the molecular basis of Parkinson&#039;s disease 1 of 10 Understanding the molecular basis of Parkinson's disease Researchers ran simulations to understand how several proteins connected with Parkinson's disease interact to cause the degenerative neurological disorder. The findings provide

  16. Proton CCQE data release page

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    | Department of Energy Proteins' Amazing Origami Powers: Insight for Potential Disease Treatments Proteins' Amazing Origami Powers: Insight for Potential Disease Treatments October 4, 2011 - 12:46pm Addthis This is a visualization of drug molecules ("parade day-like balloons") in a simulated attack of the ribbon-like protein fibrils that are believed to be the cause of Alzheimer’s disease. <a

  17. General Counsel Legal Interpretation Regarding Medical Removal Protection

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Benefits Pursuant to 10 CFR Part 850, Chronic Beryllium Disease Prevention Program | Department of Energy Counsel Legal Interpretation Regarding Medical Removal Protection Benefits Pursuant to 10 CFR Part 850, Chronic Beryllium Disease Prevention Program General Counsel Legal Interpretation Regarding Medical Removal Protection Benefits Pursuant to 10 CFR Part 850, Chronic Beryllium Disease Prevention Program The following document is the Office of the General Counsel (GC) interpretation

  18. ALSNews Vol. 362

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    2 Print Protein Instability and Lou Gehrig's Disease 309 thumb A new study uses small-angle x-ray scattering as well as several advanced biophysical techniques to link protein instability to the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Read more... Contact: Elizabeth Getzoff and John Tainer Molecular Structure of Water at Gold Electrodes Revealed ALS researchers have now made a first-ever observation of the molecular

  19. ALSNews Vol. 362

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Spectroscopy ALSNews Vol. 362 Print Protein Instability and Lou Gehrig's Disease 309 thumb A new study uses small-angle x-ray scattering as well as several advanced biophysical techniques to link protein instability to the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Read more... Contact: Elizabeth Getzoff and John Tainer Molecular Structure of Water at Gold Electrodes Revealed ALS researchers have now made a first-ever

  20. ALSNews Vol. 362

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ALSNews Vol. 362 Print Protein Instability and Lou Gehrig's Disease 309 thumb A new study uses small-angle x-ray scattering as well as several advanced biophysical techniques to link protein instability to the progression of a lethal degenerative disease: amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Read more... Contact: Elizabeth Getzoff and John Tainer Molecular Structure of Water at Gold Electrodes Revealed ALS researchers have now made a first-ever observation of

  1. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Inexpensive handheld tests for diseases are in sight April 3, 2012 Diagnosing diseases will be easier than ever through the technology and initiative of Los Alamos scientists Los Alamos scientist Dr. Hong Cai has a passion: to use her expertise in biochemistry and genetics to create a non-invasive, point-of-care diagnostic device for disease detection. In following her passion, she and her colleague, Dr. Robert Cary at Bioscience Division, invented a suite of technologies for this application,

  2. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Alina Deshpande-Strengthening the fight against pandemics March 10, 2014 Strengthening the fight against pandemics Hailing from the world's second most populated country, microbiologist Alina Deshpande understands how our highly mobile and connected world may be susceptible to pandemics. Always fascinated by infectious diseases, Deshpande leads a global disease surveillance project at the Lab, a multi-million dollar effort that explores the most critical aspects of international disease

  3. labnews04-15-16.qxp_la02_02-20-04

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    up disease-carrying mosquitoes RED MEANS A DISEASE is present to Sandia researchers Cameron Ball and Robert Meagher as they test their QUASR, quenching of unincorporated amplification signal reporters, a technique to detect the presence of malaria and viruses like West Nile. Simple enough for field labs and handheld devices, QUASR's positive signal is 10 times brighter than a negative signal. (Photo by Dino Vournas) M osquitoes are deadly efficient at spreading disease. Despite vaccines and

  4. Isotopes for cancer and cardiac care

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Isotopes for cancer Isotopes for cancer and cardiac care Eva Birnbaum is interviewed on KSFR radio on the Lab's Isotope Program February 4, 2016 hot cell facility A worker uses remote manipulator arms to handle a highly radioactive target inside the Lab's radiochemistry hot cell facility. Isotopes from Los Alamos are used for the diagnosis of cardiac disease, for the calibration of PET scanners which in turn diagnose cancer, neurological disease, inflammatory diseases, trauma, and other

  5. Alumni: Zoltán Toroczkai, University of Notre Dame

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Zoltán Toroczkai, University of Notre Dame Alumni Link: Opportunities, News and Resources for Former Employees Latest Issue:September 2015 all issues All Issues » submit Alumni: Zoltán Toroczkai, University of Notre Dame Tracking disease spread through complex network modeling July 1, 2015 Tracking disease spread through complex network modeling Tracking disease spread through complex network modeling Contact Linda Anderman Email Zoltan Toroczkai Zoltan Toroczkai now at the University of

  6. Multiscale Blood Flow Simulations | Argonne Leadership Computing Facility

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    1 Research Domain: Biological Sciences Cerebral aneurysms (CAs) occur in up to 5% of the general population, leading to strokes for over 40,000 Americans each year. Sickle cell (SS) anemia - a chronic inflammatory disease - is the most common genetic diseases among African American, with an 8% incidence of the trait among this population; 50,000 individuals are suffering from sickle cell anemia in USA every year. Celebral malaria (CM) is a related red blood cell (RBC) disease, with significant

  7. Jefferson Lab Weekly Briefs November 25, 2015 | Jefferson Lab

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    and Shutdown Days, Jefferson Lab closed Environment, Safety, Health & Quality Safe Turkey Tips from the CDC The Centers for Disease Control and Prevention offer food safety...

  8. Stafford L. Warren, 1971 | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    of a biomedical research program which has resulted in many substantial applications of ionizing radiation to diagnosis and treatment of disease and to the general welfare

  9. Shields Warren, 1971 | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    research program which has resulted in many substantial applications of ionizing radiation to diagnosis and treatment of disease and to the general welfare. Back to 1970's ...

  10. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... I for suppressing bladder cancer proliferation Wang, Xiangbo ; Zhang, Lu ; ... of genes plays a critical role in many important human diseases, especially in cancer. ...

  11. Information Sciences and Technology

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    file systems Bioinformatics Infectious disease surveillance Climate change and energy security Smart grids Learn more about our Information Science and Technology capabilities

  12. Cardiovascular and Interventional Radiological Society of Europe...

    Office of Scientific and Technical Information (OSTI)

    Cardiovascular and Interventional Radiological Society of Europe Guidelines on Endovascular Treatment in Aortoiliac Arterial Disease Citation Details In-Document Search Title: ...

  13. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    changes (1) crystal structure (1) diseases (1) functionals (1) gtp-ases (1) hormones (1) materials science (1) proteins (1) regulations (1) spectroscopy (1)...

  14. Studying Amyotrophic Lateral Sclerosis at the APS

    ScienceCinema (OSTI)

    Gelfand, Paul; Miller, Lisa

    2014-06-05

    Researchers from Brookhaven National Lab come to Argonne's Advanced Photon Source to study Amyotrophic Lateral Sclerosis, commonly known as Lou Gehrig's disease.

  15. Understanding Radioactive Waste Raymond L. Murray, Professor...

    Office of Scientific and Technical Information (OSTI)

    ... disease Cancer Stroke Accidents, total Motor vehicle 52,411 Others 53,150 Influenza ... A, "Mortality 1978" in press) Motor vehicle Falls Fires Drowning Industrial Poisoning ...

  16. DOE/EH-0467 Interview with Dr. ...

    Office of Scientific and Technical Information (OSTI)

    ... relationship of human chromosomes to cancer, * the biological and medical effects o f ionizing radiation, with particular reference to cancer, leukemia, and genetic diseases, and ...

  17. Cynthia Phillips, ground-breaking expert in plasma waves &...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    type of neuroendocrine tumor that eventually spread to her liver and then her lungs. She fought hard against the disease - researching the latest treatments and even...

  18. Microsoft Word - WIPP Update 3_15_14

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    counts, which indicates they have no detectable radioactive contamination deep in their lungs. These results were confirmed by the Centers for Disease Control. Q. What indicated...

  19. Search for: All records | SciTech Connect

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    ... (IE) (United States) USDOE Office of Intelligence and Counterintelligence (IN) (United ... Although exercise exerts anti-inflammatory actions in multiple chronic diseases associated ...

  20. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    (2) crystallography (2) diseases (2) gtp-ases (2) hormones (2) morphine (2) particle accelerators (2) receptors (2) Filter by Author Weis, William I. (39) Kobilka, Brian K. ...

  1. Microsoft Word - SF30_M010.doc

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... of Civil Penalties for Classified Information 10 CFR824 Security Violations 10 CFR 835 Occupational Radiation Protection 10 CFR 850 Chronic Beryllium Disease Prevention ...

  2. Safeguards and Security General Technical Base Qualification...

    Energy Savers [EERE]

    ... Radiation Protection" * 10 CFR 850, "Chronic Beryllium Disease Prevention Program" * 10 CFR 851, "Worker Safety and Health Program" * 29 CFR 1910.120, "Hazardous Waste Operations ...

  3. Facility Maintenance Management Functional Area Qualification...

    Broader source: Energy.gov (indexed) [DOE]

    ... and Execution 3. 10 CFR 835, Occupational Radiation Protection 4. 10 CFR 850, Chronic Beryllium Disease Prevention Program 5. 10 CFR 851, Worker Safety and Health Program b. ...

  4. DNA-Binding Mechanism in Prokaryotic Partition Complex Formation

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    other invaders from outside our bodies can be deadly foes that bring disease and death. In either case, understanding how bacteria multiply and grow not only increases our...

  5. Brain Receptor Structures Key to Future Therapeutics

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    Brain Receptor Structures Key to Future Therapeutics Print With an aging population in ... diseases affecting the brain and its ability to make new connections and recall memories. ...

  6. 14655 Section J

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    for the Assessment of Civil Penalties for Classified Information Security Violations 10 CFR 835 Occupational Radiation Protection 10 CFR 850 Chronic Beryllium Disease Prevention ...

  7. 10 CFR 850 Notice of Proposed Rulemaking Public Hearing Transcript, Richland, Washington – June 28-30, 2016

    Broader source: Energy.gov [DOE]

    Transcript of the Richland, WA public hearings to received comments on the proposed amendments to 10 CFR 850, Chronic Beryllium Disease Prevention Program.

  8. OSTI, US Dept of Energy Office of Scientific and Technical Information...

    Office of Scientific and Technical Information (OSTI)

    ... Centers for Disease Control Environmental Protection Agency U.S. Geological Survey U.S. Fish & Wildlife Service Department of Homeland Security Department of Education Department ...

  9. Microsoft PowerPoint - Briefings_Galan

    Office of Environmental Management (EM)

    performed daily in the United States, including diagnosis of heart disease, treating cancer, and studying organ structure and function. - 1 in 13 residents will receive nuclear...

  10. Today's tuberculosis

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    part of a larger effort to diagnose a range of diseases, including influenza and breast cancer, and relies on the participation of biologists, chemists, engineers and materials...

  11. BlueChoice

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    4 Ambulance: Nonemergency Air Transfer (between facilities) 10% after deductible 4 CancerCongenital Heart Disease Care (Blue distinction programs only include a lodging per...

  12. BlueChoice

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    and Lodging: Benefits are available when these services are related to case-managed Cancer Services or Congenital Heart Disease if patient is receiving treatment from a Blue...

  13. BlueChoice

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Physician and Other Professional Provider Charges ) 10% after In-Network deductible 3 CancerCongenital Heart Disease Care (Blue distinction programs only include a lodging per...

  14. Fellows

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    recognition, sensors inspired by nature, and new approaches for the diagnosis of cancer and infectious disease. Swanson has authored over 260 articles in peer-reviewed...

  15. Genomics-enabled sensor platform for rapid detection of viruses...

    Office of Scientific and Technical Information (OSTI)

    recognized through reportable diseases by health departments and reports of unusual ... (arboviruses) have emerged as some of the most significant threats to human health. ...

  16. A Fullerene that Breaks the Rules

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    vehicle for delivering radiotracers for imaging or radiopharmaceuticals for treatment of diseases. Fullerenes also have a high electron affinity, and show great promise as...

  17. Structure of GDNF Family Ligand Artemin Complexed with Its GFRa3...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    motor neurons has stimulated interest in their use for the treatment of neurodegenerative diseases such as Parkinson's. These structurally related neurotrophic factors signal by...

  18. Aurora

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    that benefit humanity the most. From finding alternative energy sources to treating diseases to developing high-tech materials-the research done on leadership-class machines...

  19. ORISE Undergraduate Student Research Experiences: Christopher...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    research. It is mostly used in human genome research, which includes the study of genetics and DNA. The genomic information is essential to understanding diseases. It is also...

  20. Medical Screening Protocol for the Former Worker Medical Screening...

    Broader source: Energy.gov (indexed) [DOE]

    recommendations; repeat CT scan offered on an annual basis after initial baseline Welding Lung Asthma Chronic obstructive lung disease Respiratory symptoms...

  1. Steap3

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    or overexpression of Steap proteins is associated with a range of diseases, from anemia to prostate cancer. In the current study, the team solved the structure of the...

  2. Decision Models for Integrating Energy/Water

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ... This tension must be resolved because all three uses are essential for our survival. Drought, famine, poverty, terrorism, disease, conflict, social unrest and overall state failure ...

  3. SEQUEDEX

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    diseases (whether arising from bacteria, parasites, or viruses; characterizing gut, oral and skin microbiomes of humans, livestock, and pets; metagenomics of soils, rivers,...

  4. Los Alamos National Laboratory

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    such as proteins produced in response to trauma or disease. While existing biomarker measurement systems rely on occasional "snapshots" and expensive and time-consuming...

  5. Science On Tap

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    "The unnecessary and uncontrolled use of antibiotics and the use of antibiotics in food animals to prevent, control and treat disease and for promoting growth are only some...

  6. Forensic analysis of the microbiome of phones and shoes (Journal...

    Office of Scientific and Technical Information (OSTI)

    are shared between individuals inhabiting the same space may be relevant to human health and disease transmission. In this study, two participants sampled the front and back...

  7. Substrate Recognition Strategy for Botulinum Neurotoxin

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Substrate Recognition Strategy for Botulinum Neurotoxin Print Clostridal neurotoxins (CNTs) are the causative agents of the neuroparalytic diseases botulism and tetanus. By...

  8. ORISE: ORISE to develop needs assessment plan to support CDC...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    and Education (ORISE) will design and carry out a needs assessment plan for the Center for Disease Control and Prevention's (CDC) Advanced Molecular Detection and Response to ...

  9. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Structural Mechanism of Laforin Function in Glycogen Dephosphorylation and Lafora Disease Raththagala, Madushi ; Brewer, M. Kathryn ; Parker, Matthew W. ; Sherwood, Amanda R. ; ...

  10. OSTI, US Dept of Energy, Office of Scientific and Technical Informatio...

    Office of Scientific and Technical Information (OSTI)

    ... Aeronautics and Space Administration Department of Veterans Affairs Department of Commerce Department of Agriculture Centers for Disease Control Environmental Protection Agency ...

  11. Worker Safety and Health Enforcement Letter issued to Los Alamos...

    Office of Environmental Management (EM)

    National Laboratory (LANL) Technical Area 3, Building 141, Beryllium Technology ... and Health Program rule (10 C.F.R. Part 851) and Chronic Beryllium Disease Prevention ...

  12. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Software speeds detection of diseases and cancer-treatment targets December 1, 2014 New ... powerful, award-winning bioinformatics software that is now capable of identifying DNA ...

  13. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Filter Results Filter by Subject diseases (1) forecasting (1) glands (1) hazards (1) health hazards (1) inorganic, organic, physical, and analytical chemistry (1) lymph nodes (1) ...

  14. Structural Studies of Nitric Oxide Synthase Inhibitor Complexes...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    can cause inflammation, rheumatoid arthritis, inflammatory bowel disease, immune-type diabetes, stroke, and cancer. The three NOS isozymes are structurally similar and share...

  15. Stanford Synchrotron Radiation Lightsource

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    melanoma, and degenerative diseases like multiple sclerosis, Alzheimer's and Type 2 diabetes. Understanding of how Wnt proteins bind and activate Frizzled receptors is important...

  16. SREL Reprint #3151

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    has now shown to represent an important animal model for studies of obesity and diabetes, two diseases which have now become epidemic in many human populations worldwide...

  17. ORISE: Health Disparity Interventions

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    issues that disproportionately affect them, such as HIVAIDS, cardiovascular disease, diabetes, immunization, cancer and infant mortality. Equally important is improving access to...

  18. Gut microbes affect circadian rhythms in mice, study says | Argonne...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    was supported by the National Institute of Health's (NIH) National Institute of Diabetes and Digestive and Kidney Diseases; the Peter and Carol Goldman Family Research Fund;...

  19. Accident Investigation of the June 1, 2013 Stairway Fall Resulting...

    Broader source: Energy.gov (indexed) [DOE]

    show that examinations were conducted for employees with various illnesses, such as diabetes and Alzheimer's disease, which occurred off the job 9 . The Board believes that if a...

  20. Inhibition of Sirt1 promotes neural progenitors toward motoneuron...

    Office of Scientific and Technical Information (OSTI)

    Sirt1, to promote neural precursor cell (NPC) development during differentiation ... in the development of hESC-based cell therapy in motoneuron disease. less ...

  1. TITLE AUTHORS SUBJECT SUBJECT RELATED DESCRIPTION PUBLISHER AVAILABILI...

    Office of Scientific and Technical Information (OSTI)

    Converting energy to medical progress nuclear medicine NONE RADIOLOGY AND NUCLEAR MEDICINE DIAGNOSIS DISEASES GAMMA CAMERAS GENETICS NUCLEAR MEDICINE PATIENTS RADIATION DETECTION...

  2. Office of Environmental Management's Hanford Site Awards $99M...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    the Chronic Beryllium Disease Prevention Program, the Energy Employees Occupational Injury Compensation Program Act, and the medical records of current and former Hanford workers. ...

  3. Improvement of the quality of life through safe drinking water & poverty alleviation

    SciTech Connect (OSTI)

    Susheela, A.K.

    1997-12-31

    Fluorosis, a crippling disease caused by ingesting excess fluoride in drinking water, is a public health problem, affecting people in 20 nations in the world. One of the worst public health problems in the history of mankind known to have occurred and reported about 6 decades ago strangely enough the disease continue to be afflicting millions of people in India, Africa and China with all its severity even during the turn of the century. The present report describes the disease characteristics and the devastating manner in which the disease affects children and adults. The need to bring this to the attention of policy, makers, has been attempted.

  4. Relations between health indicators and residential proximity to coal mining in West Virginia

    SciTech Connect (OSTI)

    Hendryx, M.; Ahern, M.M.

    2008-04-15

    We used data from a survey of 16493 West Virginians merged with county-level coal production and other covariates to investigate the relations between health indicators and residential proximity to coal mining. Results of hierarchical analyses indicated that high levels of coal production were associated with worse adjusted health status and with higher rates of cardiopulmonary disease, chronic obstructive pulmonary disease, hypertension, lung disease, and kidney disease. Research is recommended to ascertain the mechanisms, magnitude, and consequences of a community coal-mining exposure effect.

  5. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    spread of disease August 15, 2011 LOS ALAMOS, New Mexico, August 15, 2011-Connecting social media and epidemiological research, a new study by Los Alamos National Laboratory...

  6. OSTI, US Dept of Energy Office of Scientific and Technical Information...

    Office of Scientific and Technical Information (OSTI)

    They help us absorb nutrients and contribute genes responsible for disease prevention, ... Thankfully, microbiome research is gaining momentum. Strategic investments by the ...

  7. OSTI, US Dept of Energy, Office of Scientific and Technical Informatio...

    Office of Scientific and Technical Information (OSTI)

    ... Centers for Disease Control Environmental Protection Agency U.S. Geological Survey U.S. Fish & Wildlife Service Department of Homeland Security Department of Education Department ...

  8. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Genetic barcodes Weier, Heinz -Ulrich G Herein are described multicolor FISH probe sets termed "genetic barcodes" targeting several cancer or disease-related loci to assess gene ...

  9. Heat Transfer Salts for Nuclear Reactor Systems - Chemistry Control...

    Office of Scientific and Technical Information (OSTI)

    and health monitoring to prevent the development of acute or chronic beryllium disease, two pulmonary diseasesmore created by an allergic reaction to beryllium in the lungs. ...

  10. Simultaneous cryo x-ray ptychographic and fluorescence microscopy...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    attached therapeutic or diagnostic agents, help elucidate the roles of trace metals in cell development, and further the study of diseases where trace metal misregulation is...

  11. Spontaneous Liver Rupture After Treatment With Drug-Eluting Beads...

    Office of Scientific and Technical Information (OSTI)

    Country of Publication: United States Language: English Subject: 62 RADIOLOGY AND NUCLEAR ... DRUGS; BODY; CARCINOMAS; DIGESTIVE SYSTEM; DISEASES; DRUGS; FAILURES; GLANDS; ...

  12. DEFINING THE EFFECTIVENESS OF UV LAMPS

    Office of Scientific and Technical Information (OSTI)

    ... Most reports have focused on the control of infectious diseases, such as tuberculosis ... for Preventing the Transmission of Mycobacterium Tuberculosis in Health-Care Facilities. ...

  13. Office of Scientific and Technical Information DOE PAGES (Beta...

    Office of Scientific and Technical Information (OSTI)

    ... Centers for Disease Control Environmental Protection Agency U.S. Geological Survey U.S. Fish & Wildlife Service Department of Homeland Security Department of Education Department ...

  14. Public Access to DOE Scientific Publications | OSTI, US Dept...

    Office of Scientific and Technical Information (OSTI)

    ... Centers for Disease Control Environmental Protection Agency U.S. Geological Survey U.S. Fish & Wildlife Service Department of Homeland Security Department of Education Department ...

  15. One Vaccine Leads to Another

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    One Vaccine Leads to Another Print Diphtheria is a potentially lethal respiratory disease that is fairly well controlled by vaccines discovered early last century. These vaccines...

  16. Frontiers in Science talks to explore new strategies for diagnosing...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    for diagnosing challenging diseases Harshini Mukundan discusses the re-emergence of tuberculosis in a series of lectures called "The Microbe Strikes Back: The Return of...

  17. Beryllium Information | The Ames Laboratory

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Beryllium Report 2001 Beryllium Report 2008 Beryllium Report 2010 Beryllium Report 2011 Beryllium News Release 6-5-09 Beryllium Fact Sheet Chronic Beryllium Disease Prevention Plan...

  18. Hanford Blog Archive - Hanford Site

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    has posted on its website a report on its independent inspection of the Hanford Site Chronic Beryllium Disease Prevention Program (Released June 2, 2010) June 02, 2010 Inspection...

  19. DE-AC06-04RL14383

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    during Fiscal Year (FY) 2012 to resolve corrective actions related to the Hanford Site Chronic Beryllium Disease Prevention Program (CBDPP). The contractor is hereby provided an...

  20. ORISE: Worker Health Studies - Beryllium Testing Laboratory

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    or manufacturing activities can cause sensitivity in some persons that may lead to chronic beryllium disease. The Oak Ridge Institute for Science and Education (ORISE)...