29 research outputs found

    Physical activity attenuates the influence of FTO variants on obesity risk: A meta-analysis of 218,166 adults and 19,268 children

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    Background: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268). Methods and Findings: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r2>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (pinteraction= 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. Concl

    Age at first birth in women is genetically associated with increased risk of schizophrenia

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    Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

    La conservazione preventiva del patrimonio librario come possibile alternativa al restauro tradizionale

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    The present paper focuses on the close relation between library collections and their preservation environment, aiming, in particular, at highlighting the importance of promoting and sustaining the monitoring. The paper proposes some simple and ready-to-use technologies – smart monitoring – to prevent future damages

    Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

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    Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

    Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

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    Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

    Potential Variation in Determination of Longissimus Muscle Area in Carcasses from Heifers Fed With or Without Zilpaterol Hydrochloride

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    This study was conducted to evaluate some sources of potential variation in determination of longissimus muscle area between the 12th and 13th ribs of carcasses from heifers fed with or without zilpaterol hydochloride. Cross sections of the rib-loin were taken cranial to the 11th rib and caudal to the 13th rib, about 3–4 millimeters thick at 90 degrees perpendicular to the long axis of the longissimus muscle. Potential variation of longissimus muscle area can arise from the natural variation of muscle size when cutting between the 12th and 13th ribs (up to 9%). Deviation in cutting perpendicular to the long axis of the muscle could contribute 6.9% error. There were no differences in the mean or range of longissimus muscle area among carcasses from heifers fed zilpaterol hydrochloride and controls. These data reinforce the written directions of the USDA to separate the longissimus muscle between the 12th and 13th ribs by a cut as close to 90 degrees as possible

    Climate science and famine early warning

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    Food security assessment in sub-Saharan Africa requires simultaneous consideration of multiple socio-economic and environmental variables. Early identification of populations at risk enables timely and appropriate action. Since large and widely dispersed populations depend on rainfed agriculture and pastoralism, climate monitoring and forecasting are important inputs to food security analysis. Satellite rainfall estimates (RFE) fill in gaps in station observations, and serve as input to drought index maps and crop water balance models. Gridded rainfall time-series give historical context, and provide a basis for quantitative interpretation of seasonal precipitation forecasts. RFE are also used to characterize flood hazards, in both simple indices and stream flow models. In the future, many African countries are likely to see negative impacts on subsistence agriculture due to the effects of global warming. Increased climate variability is forecast, with more frequent extreme events. Ethiopia requires special attention. Already facing a food security emergency, troubling persistent dryness has been observed in some areas, associated with a positive trend in Indian Ocean sea surface temperatures. Increased African capacity for rainfall observation, forecasting, data management and modelling applications is urgently needed. Managing climate change and increased climate variability require these fundamental technical capacities if creative coping strategies are to be devised
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