Perfluorinated alkyl acids and fecundity assessment in striped mullet (\u3ci\u3eMugil cephalus\u3c/i\u3e) at Merritt Island national wildlife refuge

This study investigated wild caught striped mullet (Mugil cephalus) at Merritt Island National Wildlife Refuge (MINWR) for levels of 15 perfluoroalkyl acids (PFAA) in tandem with individual fecundity measurements (Oocyte sub-stage 2 late, n=42) and oocyte reproductive stages (Stages 1–5, n=128). PFAAmeasurementswere quantified in stripedmullet liver (n=128),muscle (n=49), and gonad (n=10). No significant negative impacts of liver PFAA burden on wild-caught,mullet fecundity endpoints were observed in this study; however, changes in PFAAwere observed in the liver asmullet progressed through different sub-stages of oocyte development. Of the PFAA with significant changes by sub-stage of oocyte development, the carboxylic acids (perfluorooctanoic acid, perfluorononanoic acid, and perfluorotridecanoic acid) increased in the liver with increasing sub-stage while the sulfonic acid and its precursor (perfluorooctanesulfonic acid (PFOS) and perfluorooctanesulfonamide, respectively) decreased in the liver with increasing sub-stage of oocyte development. This is a unique find and suggests PFAA change location of compartmentalization as mullet progress towards spawning. Investigations also revealed higher than expected median muscle and gonad levels of PFOS in striped mullet collected at MINWR (9.01 ng/g and 80.2 ng/g, respectively)

Perfluorinated Alkyl Acids in Plasma of American Alligators (Alligator Mississippiensis) from Florida and South Carolina

This study aimed to quantitate fourteen perfluoroalkyl acids (PFAAs) in 125 adult American alligators at twelve sites across the southeastern US. Of those fourteen PFAAs, nine were detected in 65% - 100% of the samples: PFOA, PFNA, PFDA, PFUnA, PFDoA, PFTriA, PFTA, PFHxS, and PFOS. Males (across all sites) showed significantly higher concentrations of four PFAAs: PFOS (p = 0.01), PFDA (p = 0.0003), PFUnA (p = 0.021), and PFTriA (p = 0.021). Concentrations of PFOS, PFHxS, and PFDA in plasma were significantly different among the sites in each sex. Alligators at Merritt Island National Wildlife Refuge and Kiawah Nature Conservancy both exhibited some of the highest PFOS concentrations (medians 99.5 ng/g and 55.8 ng/g respectively) in plasma measured to date in a crocodilian species. A number of positive correlations between PFAAs and snout-vent length (SVL) were observed in both sexes suggesting PFAA body burdens increase with increasing size. In addition, several significant correlations among PFAAs in alligator plasma may suggest conserved sources of PFAAs at each site throughout the greater study area. This study is the first to report PFAAs in American alligators, reveals potential PFAA hot spots in Florida and South Carolina, and provides and additional contaminant of concern when assessing anthropogenic impacts on ecosystem health

Patient-reported GP health assessments rather than individual cardiovascular risk burden are associated with the engagement in lifestyle changes: Population-based survey in South Australia

© 2019 The Author(s). Background: Little is known about whether a more comprehensive health assessment, performed by a general practitioner (GP) during a clinical encounter, could influence patients' lifestyle. We aimed to investigate whether health assessments, performed by GPs, are more important than the presence of cardiovascular disease (CVD) or cardiometabolic risk factors (obesity, diabetes, hypertension, dyslipidaemia) for engagement in lifestyle change. Methods: Cross-sectional, population-based survey conducted in South Australia (September-December 2017) using face-To-face interviews and self-reported data of 2977 individuals aged 15+ years. The main outcome was engagement in four lifestyle changes: 1) increasing fruit/vegetable intake, 2) increasing physical activity level, 3) reducing alcohol consumption, and 4) attempts to stop smoking. Health assessments performed by a GP in the last 12 months included clinical/laboratory investigations (weight/waist circumference, blood pressure, glucose levels, lipid levels) and questions about lifestyle/wellbeing (current diet, physical activity, smoking status, alcohol intake, mental health, sleeping problems). Results were restricted to individuals aged 35+ years because of the low prevalence of CVD or their risk factors among younger participants. Logistic regression was used in all associations, adjusted for sociodemographic, lifestyle, mental health, and clinical variables. Results: Of the 2384 investigated adults (mean age 57.3 ± 13.9 years; 51.9% females), 10.2% had CVD and 49.1% at least one cardiometabolic risk factor. Clinical/laboratory assessments performed by the GP were 2-3 times more frequent than assessments of lifestyle, mental health status, or sleeping problems, especially among those with CVD. Individuals with CVD or a cardiometabolic risk factor were no more likely to be increasing their fruit/vegetable consumption (33.6%), physical activity level (40.9%), reducing alcohol consumption (31.1%), or trying to quit smoking (34.0%) than 'healthy' participants. However, lifestyle changes were between 30 and 100% more likely when GPs performed three or more health assessments (either clinical/laboratory or questions about lifestyle/wellbeing) than when individuals did not visit the GP or when GPs performed no any assessment during these clinical encounters (p < 0.05 in all cases). Conclusion: More frequent and comprehensive CVD-related assessments by GPs were more important in promoting a healthier lifestyle than the presence of CVD or cardiometabolic risk factors by themselves

Measuring research impact: a large cancer research funding programme in Australia

Background: Measuring research impact is of critical interest to philanthropic and government funding agencies interested in ensuring that the research they fund is both scientifically excellent and has meaningful impact into health and other outcomes. The Beat Cancer Project (BCP) is a AUD $34 m cancer research funding scheme that commenced in 2011. It was initiated by an Australian charity (Cancer Council SA), and supported by the South Australian Government and the state’s major universities. Methods: This study applied Buxton and Hanney’s Payback Framework to assess research impact generated from the BCP after 3 years of funding. Data sources were an audit of peer-reviewed publications from January 2011 to September 2014 from Web of Knowledge and a self-report survey of investigators awarded BCP research funding during its first 3 years of implementation (2011–2013). Of the 104 surveys, 92 (88 Results: The BCP performed well across all five categories of the Payback Framework. In terms of knowledge production, 1257 peer-reviewed publications were generated and the mean impact factor of publishing journals increased annually. There were many benefits to future research with 21 respondents (23$1 that the cancer charity invested, the BCP gained an additional AUD $6.06. Five projects (5%) had informed policy and 5 (5%) informed product development, with an additional 31 (34%) and 35 (38%) projects, respectively, anticipating doing so. In terms of health and sector and broader economic benefits, 8 (9%) projects had influenced practice or behaviour of health staff and 32 (34%) would reportedly to do so in the future. Conclusions: Research impact was a priority of charity and government funders and led to a deliberate funding strategy. Emphasising research impact while maintaining rigorous, competitive processes can achieve the joint objectives of excellence in research, yielding good research impact and a high rate of leverage for philanthropic and public investment, as indicated by these early results

An ACACB variant implicated in diabetic nephropathy associates with body mass index and gene expression in obese subjects

Acetyl coenzyme A carboxylase B gene (ACACB) single nucleotide polymorphism (SNP) rs2268388 is reproducibly associated with type 2 diabetes (T2DM)-associated nephropathy (DN). ACACB knock-out mice are also protected from obesity. This study assessed relationships between rs2268388, body mass index (BMI) and gene expression in multiple populations, with and without T2DM. Among subjects without T2DM, rs2268388 DN risk allele (T) associated with higher BMI in Pima Indian children (n = 2021; p-additive = 0.029) and African Americans (AAs) (n = 177; p-additive = 0.05), with a trend in European Americans (EAs) (n = 512; p-additive = 0.09), but not Germans (n = 858; p-additive = 0.765). Association with BMI was seen in a meta-analysis including all non-T2DM subjects (n = 3568; p-additive = 0.02). Among subjects with T2DM, rs2268388 was not associated with BMI in Japanese (n = 2912) or EAs (n = 1149); however, the T allele associated with higher BMI in the subset with BMI≥30 kg/m(2) (n = 568 EAs; p-additive = 0.049, n = 196 Japanese; p-additive = 0.049). Association with BMI was strengthened in a T2DM meta-analysis that included an additional 756 AAs (p-additive = 0.080) and 48 Hong Kong Chinese (p-additive = 0.81) with BMI≥30 kg/m(2) (n = 1575; p-additive = 0.0033). The effect of rs2268388 on gene expression revealed that the T risk allele associated with higher ACACB messenger levels in adipose tissue (41 EAs and 20 AAs with BMI\u3e30 kg/m(2); p-additive = 0.018) and ACACB protein levels in the liver tissue (mixed model p-additive = 0.03, in 25 EA bariatric surgery patients with BMI\u3e30 kg/m(2) for 75 exams). The T allele also associated with higher hepatic triglyceride levels. These data support a role for ACACB in obesity and potential roles for altered lipid metabolism in susceptibility to DN

Cortactin overexpression results in sustained epidermal growth factor receptor signaling by preventing ligand-induced receptor degradation in human carcinoma cells

The chromosome 11q13 region is frequently amplified in human carcinomas and results in an increased expression of various genes including cortactin, and is also associated with an increased invasive potential. Cortactin acts as an important regulator of the actin cytoskeleton. It is therefore very tempting to speculate that cortactin is the crucial gene within the 11q13 amplicon that mediates the invasive potential of these carcinomas. Cortactin also participates in receptor-mediated endocytosis, and recent findings have shown that, during receptor internalization, cortactin overexpression inhibits the ubiquitylation-mediated degradation of the epidermal growth factor receptor, resulting in a sustained ligand-induced epidermal growth factor receptor activity

Predictors of chronic breathlessness: a large population study

<p>Abstract</p> <p>Background</p> <p>Breathlessness causes significant burden in our community but the underlying socio-demographic and lifestyle factors that may influence it are not well quantified. This study aims to define these predictors of chronic breathlessness at a population level.</p> <p>Methods</p> <p>Data were collected from adult South Australians in 2007 and 2008 (n = 5331) as part of a face-to-face, cross-sectional, whole-of-population, multi-stage, systematic area sampling population health survey. The main outcome variable was breathlessness in logistic regression models. Lifestyle factors examined included smoking history, smoke-free housing, level of physical activity and body mass index (obesity).</p> <p>Results</p> <p>The participation rate was 64.1%, and 11.1% of individuals (15.0% if aged ≥50 years) chronically had breathlessness that limited exertion. Significant bivariate associations with chronic breathlessness for the whole population and only those ≥50 included: increasing age; female gender; being separated/divorced/widowed; social disadvantage; smoking status; those without a smoke-free home; low levels of physical activity; and obesity. In multi-variate analyses adjusted for age, marital status (p < 0.001), physical activity (p < 0.001), obesity (p < 0.001), gender (p < 0.05) and social disadvantage (p < 0.05) remained significant factors. Smoking history was <it>not </it>a significant contributor to the model.</p> <p>Conclusions</p> <p>There is potential benefit in addressing reversible lifestyle causes of breathlessness including high body mass index (obesity) and low levels of physical activity in order to decrease the prevalence of chronic breathlessness. Clinical intervention studies for chronic breathlessness should consider stratification by body mass index.</p

Biological and clinical insights from genetics of insomnia symptoms

Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes. The underlying pathophysiological processes and causal relationships of insomnia with disease are poorly understood. Here we identified 57 loci for self-reported insomnia symptoms in the UK Biobank (n = 453,379) and confirmed their effects on self-reported insomnia symptoms in the HUNT Study (n = 14,923 cases and 47,610 controls), physician-diagnosed insomnia in the Partners Biobank (n = 2,217 cases and 14,240 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n = 83,726). Our results suggest enrichment of genes involved in ubiquitin-mediated proteolysis and of genes expressed in multiple brain regions, skeletal muscle, and adrenal glands. Evidence of shared genetic factors was found between frequent insomnia symptoms and restless legs syndrome, aging, and cardiometabolic, behavioral, psychiatric, and reproductive traits. Evidence was found for a possible causal link between insomnia symptoms and coronary artery disease, depressive symptoms, and subjective well-being

Genetic diversity fuels gene discovery for tobacco and alcohol use

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury(1-4). These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries(5). Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.Peer reviewe