378 research outputs found

    Serum antibodies to Vibrio vulnificus biotype 3 lipopolysaccharide and susceptibility to disease caused by the homologous V. vulnificus biotype

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    In 1996 an outbreak of severe soft tissue infections caused by Vibrio vulnificus unexpectedly erupted in fish consumers in Israel with relatively little morbidity in fish farmers. To test the hypothesis that recurrent exposure of fishermen to the virulent strain may have provided protection against severe or symptomatic disease, we investigated the association between the immune response to V. vulnificus biotype 3 lipopolysaccharide (BT3 LPS) and disease susceptibility in fish farmers and fish consumers. Serum samples were tested for IgA and IgG of anti-BT3 LPS in fishermen and fish consumers who suffered from V. vulnificus BT3 infections and their matched controls. Pre-existing levels of IgG (IgG0) of anti-BT3 LPS were significantly lower in diseased fishermen who developed disease associated with the homologous biotype, compared to controls. In multivariate analysis, levels of IgG0 anti-BT3 LPS remained the only variable significantly associated with disease occurrence in fishermen. Higher levels of pre-existing IgG anti-BT 3 LPS antibodies may be associated with protection against severe or symptomatic disease with the homologous biotype in fishermen but not in subjects from the general public

    Natriuretic peptides and integrated risk assessment for cardiovascular disease. an individual-participant-data meta-analysis

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    BACKGROUND: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. METHODS: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. FINDINGS: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure. INTERPRETATION: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention

    Effect of partial portal vein ligation on hepatic regeneration

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    To evaluate the effect of portal hypertension and diminished portal venous blood flow to the liver on hepatic regeneration, male rats were subjected to partial portal vein ligation and subsequently to a two-thirds partial hepatectomy. The levels of ornithine decarboxylase activity at 6 h after partial hepatectomy were greater (p > 0.001) in the rats with prior partial portal vein ligation than in those without portal hypertension. The rats with prior partial portal vein ligation also had greater (p > 0.005) levels of thymidine kinase activity at 48 h after partial hepatectomy than did those without portal hypertension. Hepatic sex hormone receptor activity was not affected by prior partial portal vein ligation either before or after partial hepatectomy. The reductions in both estrogen and androgen receptor activity observed in the hepatic cytosol after partial hepatectomy were similar to those observed in control animals. These data indicate that animals with portal hypertension having a diminished hepatic portal blood flow have a normal capacity to regenerate hepatic mass following a hepatic resection © 1988 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

    Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci

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    Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: Rs13422522 (NYAP2; P = 8.87 × 10-11), rs12454712 (BCL2; P = 2.7 × 10-8), and rs10506418 (FAM19A2; P = 1.9 × 10-8). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci

    Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

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    Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loc

    Assessing spatial non-uniformities in lithium-ion battery state of charge using ultrasound immersion testing

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    Enhancing the performance, safety and reliability of battery management systems is crucial for advancing the state of the art in battery electric vehicles. Current research explores the potential of ultrasound to monitor state of charge (SoC) changes in individual cells. Understanding spatial variations in SoC is essential, as non-uniformities could lead to sub-optimal performance, premature ageing, and possible safety risks. This study uses ultrasound immersion C-scans to map wave speed and attenuation at different SoC levels during battery cycling. Results indicate non-uniform wave speed and attenuation suggestive of SoC spatial variations within single cells, emphasising the importance of addressing this issue. Acoustic measurements under various C-rates and relaxation periods are discussed, providing insights into lithium-ion rearrangement in graphite particles. Potential causes of structure and manufacturing variations of the cell are discussed, highlighting the need to address these issues to prevent overcharging or overdischarging in specific battery areas

    New genetic loci link adipose and insulin biology to body fat distribution.

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    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

    Biomarker-predicted sugars intake compared with self-reported measures in US Hispanics/Latinos: results from the HCHS/SOL SOLNAS study

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    Abstract Objective Measurement error in self-reported total sugars intake may obscure associations between sugars consumption and health outcomes, and the sum of 24 h urinary sucrose and fructose may serve as a predictive biomarker of total sugars intake. Design The Study of Latinos: Nutrition &amp; Physical Activity Assessment Study (SOLNAS) was an ancillary study to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) cohort. Doubly labelled water and 24 h urinary sucrose and fructose were used as biomarkers of energy and sugars intake, respectively. Participants’ diets were assessed by up to three 24 h recalls (88 % had two or more recalls). Procedures were repeated approximately 6 months after the initial visit among a subset of ninety-six participants. Setting Four centres (Bronx, NY; Chicago, IL; Miami, FL; San Diego, CA) across the USA. Subjects Men and women ( n 477) aged 18–74 years. Results The geometric mean of total sugars was 167·5 (95 % CI 154·4, 181·7) g/d for the biomarker-predicted and 90·6 (95 % CI 87·6, 93·6) g/d for the self-reported total sugars intake. Self-reported total sugars intake was not correlated with biomarker-predicted sugars intake ( r =−0·06, P =0·20, n 450). Among the reliability sample ( n 90), the reproducibility coefficient was 0·59 for biomarker-predicted and 0·20 for self-reported total sugars intake. Conclusions Possible explanations for the lack of association between biomarker-predicted and self-reported sugars intake include measurement error in self-reported diet, high intra-individual variability in sugars intake, and/or urinary sucrose and fructose may not be a suitable proxy for total sugars intake in this study population

    Exploring the Relationship Between Sleep Apnea, Myocardial Infarct Size, and Coronary Collaterals in Acute Myocardial Infarction: A Multidisciplinary Study

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    Vaishnavi Kundel,1 Kavya Devarakonda,1 Samira Khan,1 Mayte Suarez-Farinas,1 Oren Cohen,1 Carlos Santos-Gallego,1 Mark A Menegus,2 Annapoorna Kini,1 Yuliya Vengrenyuk,1 Naotaka Okamoto,1 Hiroshi Ueda,1 Umesh Gidwani,1 Jorge R Kizer,3 Susan Redline,4 Robert Kaplan,2,5 Neomi Shah1 1Icahn School of Medicine at Mount Sinai, New York, NY, USA; 2Albert Einstein College of Medicine, Bronx, NY, USA; 3Cardiology Section, San Francisco Veterans Affairs Health Care System and Departments of Medicine, Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA; 4Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 5Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USACorrespondence: Vaishnavi Kundel, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1232, New York, NY, 10029, USA, Tel +1-212-241-1967, Email [email protected]: We designed a study investigating the cardioprotective role of sleep apnea (SA) in patients with acute myocardial infarction (AMI), focusing on its association with infarct size and coronary collateral circulation.Methods: We recruited adults with AMI, who underwent Level-III SA testing during hospitalization. Delayed-enhancement cardiac magnetic resonance (CMR) imaging was performed to quantify AMI size (percent-infarcted myocardium). Rentrop Score quantified coronary collateralization (scores 0– 3, higher scores indicating augmented collaterals). Group differences in Rentrop grade and infarct size were compared using the Wilcoxon Rank-Sum test and Fisher’s Exact test as appropriate, with a significance threshold set at p 0, with a trend toward significance (moderate SA versus other groups: 62.5% versus 28%, p=0.08).Conclusion: Our study did not find statistically significant differences in cardiac infarct size and the presence of coronary collaterals by sleep apnea severity among patients with AMI. However, our results are hypothesis-generating, and suggest that moderate SA may potentially offer cardioprotective benefits through enhanced coronary collaterals. These insights call for future research to explore the heterogeneity in ischemic preconditioning by SA severity and hypoxic burden to guide tailored clinical strategies for SA management in patients with AMI.Keywords: sleep apnea, MI, myocardial infarction, cardiac MRI, Rentrop, ischemic preconditionin

    Nursing Home Revenue Source and Information Availability During the Emergency Department Evaluation of Nursing Home Residents

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    Lack of access to medical information for nursing home residents during Emergency Department (ED) evaluation is a barrier to quality care. We hypothesized that the quantity of information available in the ED differs based on the funding source of the resident’s nursing home
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