131 research outputs found
Evaluation of the Dental Health Aide Therapist Workforce Model in Alaska (Final Report)
In January 2008, the W.K. Kellogg Foundation, in collaboration with ANTHC, the Rasmuson Foundation, and the Bethel Community Services Foundation, requested that an experienced organization provide an independent, detailed, and objective evaluation of the initial implementation of the Dental Health Aide Therapist (DHAT) program
Distributing game instances in a hybrid client-server/P2P system to support MMORPG playability
Ethnic differences in the association between blood pressure components and chronic kidney disease in middle aged and older Asian adults
10.1186/1471-2369-14-86BMC Nephrology141
Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations
All authors: Olga Y. Gorlova ,
Yafang Li,
Ivan Gorlov,
Jun Ying,
Wei V. Chen,
Shervin Assassi,
John D. Reveille,
Frank C. Arnett,
Xiaodong Zhou,
Lara Bossini-Castillo,
Elena Lopez-Isac,
Marialbert Acosta-Herrera,
Peter K. Gregersen,
Annette T. Lee,
Virginia D. Steen,
Barri J. Fessler,
Dinesh Khanna,
Elena Schiopu,
Richard M. Silver,
Jerry A. Molitor,
Daniel E. Furst,
Suzanne Kafaja,
Robert W. Simms,
Robert A. Lafyatis,
Patricia Carreira,
Carmen Pilar Simeon,
Ivan Castellvi,
Emma Beltran,
Norberto Ortego,
Christopher I. Amos,
Javier Martin,
Maureen D. Mayes.Data Availability Statement: Genetic data is
available from dbGaP repository (https://www.ncbi.
nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_
id=phs000357.v1.p1).Gene-level analysis of ImmunoChip or genome-wide association studies (GWAS) data has not been previously reported for systemic sclerosis (SSc, scleroderma). The objective of this study was to analyze genetic susceptibility loci in SSc at the gene level and to determine if the detected associations were shared in African-American and White populations, using data from ImmunoChip and GWAS genotyping studies. The White sample included 1833 cases and 3466 controls (956 cases and 2741 controls from the US and 877 cases and 725 controls from Spain) and the African American sample, 291 cases and 260 controls. In both Whites and African Americans, we performed a gene-level analysis that integrates association statistics in a gene possibly harboring multiple SNPs with weak effect on disease risk, using Versatile Gene-based Association Study (VEGAS) software. The SNP-level analysis was performed using PLINK v.1.07. We identified 4 novel candidate genes (STAT1, FCGR2C, NIPSNAP3B, and SCT) significantly associated and 4 genes (SERBP1, PINX1, TMEM175 and EXOC2) suggestively associated with SSc in the gene level analysis in White patients. As an exploratory analysis we compared the results on Whites with those from African Americans. Of previously established susceptibility genes identified in Whites, only TNFAIP3 was significant at the nominal level (p = 6.13x10-3) in African Americans in the gene-level analysis of the ImmunoChip data. Among the top suggestive novel genes identified in Whites based on the ImmunoChip data, FCGR2C and PINX1 were only nominally significant in African Americans (p = 0.016 and p = 0.028, respectively), while among the top novel genes identified in the gene-level analysis in African Americans, UNC5C (p = 5.57x10-4) and CLEC16A (p = 0.0463) were also nominally significant in Whites. We also present the gene-level analysis of SSc clinical and autoantibody phenotypes among Whites. Our findings need to be validated by independent studies, particularly due to the limited sample size of African Americans.Funding was provided to MDM by the National Institutes of Health (NIH) the National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS https://www.niams.nih.gov/) Centers of Research Translation (CORT) P50-AR054144, NIH grant N01-AR-02251 and R01-AR-055258, and the Department of Defense (DD) Congressionally Directed Medical Research Program (http://cdmrp.army.mil/) W81XWH-07-1-011 and WX81XWH-13-1-0452 for the collection, analysis and interpretation of the data
The Osteopontin Level in Liver, Adipose Tissue and Serum Is Correlated with Fibrosis in Patients with Alcoholic Liver Disease
<div><h3>Background</h3><p>Osteopontin (OPN) plays an important role in the progression of chronic liver diseases. We aimed to quantify the liver, adipose tissue and serum levels of OPN in heavy alcohol drinkers and to compare them with the histological severity of hepatic inflammation and fibrosis.</p> <h3>Methodology/Principal Findings</h3><p>OPN was evaluated in the serum of a retrospective and prospective group of 109 and 95 heavy alcohol drinkers, respectively, in the liver of 34 patients from the retrospective group, and in the liver and adipose tissue from an additional group of 38 heavy alcohol drinkers. Serum levels of OPN increased slightly with hepatic inflammation and progressively with the severity of hepatic fibrosis. Hepatic OPN expression correlated with hepatic inflammation, fibrosis, TGFβ expression, neutrophils accumulation and with the serum OPN level. Interestingly, adipose tissue OPN expression also correlated with hepatic fibrosis even after 7 days of alcohol abstinence. The elevated serum OPN level was an independent risk factor in estimating significant (F≥2) fibrosis in a model combining alkaline phosphatase, albumin, hemoglobin, OPN and FibroMeter® levels. OPN had an area under the receiving operator curve that estimated significant fibrosis of 0.89 and 0.88 in the retrospective and prospective groups, respectively. OPN, Hyaluronate (AUROC: 0.88), total Cytokeratin 18 (AUROC: 0.83) and FibroMeter® (AUROC: 0.90) estimated significance to the same extent in the retrospective group. Finally, the serum OPN levels also correlated with hepatic fibrosis and estimated significant (F≥2) fibrosis in 86 patients with chronic hepatitis C, which suggested that its elevated level could be a general response to chronic liver injury.</p> <h3>Conclusion/Significance</h3><p>OPN increased in the liver, adipose tissue and serum with liver fibrosis in alcoholic patients. Further, OPN is a new relevant biomarker for significant liver fibrosis. OPN could thus be an important actor in the pathogenesis of this chronic liver disease.</p> </div
Identifying and prioritizing strategies for comprehensive liver cancer control in Asia
<p>Abstract</p> <p>Background</p> <p>Liver cancer is both common and burdensome in Asia. Effective liver cancer control, however, is hindered by a complex etiology and a lack of coordination across clinical disciplines. We sought to identify strategies for inclusion in a comprehensive liver cancer control for Asia and to compare qualitative and quantitative methods for prioritization.</p> <p>Methods</p> <p>Qualitative interviews (N = 20) with international liver cancer experts were used to identify strategies using Interpretative Phenomenological Analysis and to formulate an initial prioritization through frequency analysis. Conjoint analysis, a quantitative stated-preference method, was then applied among Asian liver cancer experts (N = 20) who completed 12 choice tasks that divided these strategies into two mutually exclusive and exhaustive subsets. Respondents' preferred plan was the primary outcome in a choice model, estimated using ordinary least squares (OLS) and logistic regression. Priorities were then compared using Spearman's Rho.</p> <p>Results</p> <p>Eleven strategies were identified: <it>Access to treatments; Centers of excellence; Clinical education; Measuring social burden; Monitoring of at-risk populations; Multidisciplinary management; National guidelines; Public awareness; Research infrastructure; Risk-assessment and referral</it>; and <it>Transplantation infrastructure</it>. Qualitative frequency analysis indicated that <it>Risk-assessment and referral </it>(85%), <it>National guidelines </it>(80%) and <it>Monitoring of at-risk populations </it>(80%) received the highest priority, while conjoint analysis pointed to <it>Monitoring of at-risk populations </it>(p < 0.001), <it>Centers of excellence </it>(p = 0.002), and <it>Access to treatments </it>(p = 0.004) as priorities, while <it>Risk-assessment and referral </it>was the lowest priority (p = 0.645). We find moderate concordance between the qualitative and quantitative methods (rho = 0.20), albeit insignificant (p = 0.554), and a strong concordance between the OLS and logistic regressions (rho = 0.979; p < 0.0001).</p> <p>Conclusions</p> <p>Identified strategies can be conceptualized as the ABCs of comprehensive liver cancer control as they focus on <it>Antecedents</it>, <it>Better care </it>and <it>Connections </it>within a national strategy. Some concordance was found between the qualitative and quantitative methods (e.g. <it>Monitoring of at-risk populations</it>), but substantial differences were also identified (e.g. qualitative methods gave highest priority to risk-assessment and referral, but it was the lowest for the quantitative methods), which may be attributed to differences between the methods and study populations, and potential framing effects in choice tasks. Continued research will provide more generalizable estimates of priorities and account for variation across stakeholders and countries.</p
Are we ready to track climate-driven shifts in marine species across international boundaries? - A global survey of scientific bottom trawl data
A LC-MS metabolomics approach to investigate the effect of raw apple intake in the rat plasma metabolome
Fruit and vegetable consumption has been associated with several health benefits; however the mechanisms are largely unknown at the biochemical level. Our research aims to investigate whether plasma metabolome profiling can reflect biological effects after feeding rats with raw apple by using an untargeted UPLC-ESI-TOF-MS based metabolomics approach in both positive and negative mode. Eighty young male rats were randomised into groups receiving daily 0, 5 or 10 g fresh apple slices, respectively, for 13 weeks. During weeks 3-6 some of the animals were receiving 4 mg/ml 1,2-dimethylhydrazine dihydrochloride (DMH) once a week. Plasma samples were taken at the end of the intervention and among all groups, about half the animals were 12 h fasted. An initial ANOVA-simultaneous component analysis with a three-factor or two-factor design was employed in order to isolate potential metabolic variations related to the consumption of fresh apples. Partial least squares-discriminant analysis was then applied in order to select discriminative features between plasma metabolites in control versus apple fed rats and partial least squares modelling to reveal possible dose response. The findings indicate that in laboratory rats apple feeding may alter the microbial amino acid fermentation, lowering toxic metabolites from amino acids metabolism and increasing metabolism into more protective products. It may also delay lipid and amino acid catabolism, gluconeogenesis, affect other features of the transition from the postprandial to the fasting state and affect steroid metabolism by suppressing the plasma level of stress corticosteroids, certain mineralocorticoids and oxidised bile acid metabolites. Several new hypotheses regarding the cause of health effects from apple intake can be generated from this study for further testing in humans. © 2013 Springer Science+Business Media New York
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