Does familial risk for alcohol use disorder predict alcohol hangover?

Positive family history of alcohol use disorder (FHP), a variable associated with propensity for alcohol use disorder (AUD), has been linked with elevated hangover frequency and severity, after controlling for alcohol use. This implies that hangover experiences may be related to AUD. However, inadequate control of alcohol consumption levels, low alcohol dose and testing for hangover during the intoxication phase detract from these findings. Here, we present further data pertinent to understanding the relationship between family history and alcohol hangover. Study 1 compared past year hangover frequency in a survey of 24 FHP and 118 family history negative (FHN) individuals. Study 2 applied a quasi-experimental naturalistic approach assessing concurrent hangover severity in 17 FHP and 32 FHN individuals the morning after drinking alcohol. Both studies applied statistical control for alcohol consumption levels. In Study 1, both FHP status and estimated blood alcohol concentration on the heaviest drinking evening of the past month predicted the frequency of hangover symptoms experienced over the previous 12 months. In Study 2, estimated blood alcohol concentration the previous evening predicted hangover severity but FHP status did not. FHP, indicating familial risk for AUD, was not associated with concurrent hangover severity but was associated with increased estimates of hangover frequency the previous year

The effectiveness of a preferred intensity exercise programme on the mental health outcomes of young people with depression: a sequential mixed methods evaluation

<p>Abstract</p> <p>Background</p> <p>People with mental illness are more likely to suffer physical health problems than comparable populations who do not have mental illness. There is evidence to suggest that exercise, as well has having obvious physical benefits, also has positive effects on mental health. There is a distinct paucity of research testing its effects on young people seeking help for mental health issues. Additionally, it is generally found that compliance with prescribed exercise programmes is low. As such, encouraging young people to exercise at levels recommended by national guidelines may be unrealistic considering their struggle with mental health difficulties. It is proposed that an exercise intervention tailored to young people's preferred intensity may improve mental health outcomes, overall quality of life, and reduce exercise attrition rates.</p> <p>Methods/Design</p> <p>A sequential mixed methods design will be utilised to assess the effectiveness of an individually tailored exercise programme on the mental health outcomes of young people with depression. The mixed methods design incorporates a Randomised Controlled Trial (RCT), focus groups and interviews and an economic evaluation. <it>Participants: </it>158 young people (14-17 years) recruited from primary care and voluntary services randomly allocated to either the intervention group or control group. <it>Intervention group</it>: Participants will undertake a 12 week exercise programme of 12 × 60 minutes of preferred intensity aerobic exercise receiving motivational coaching and support throughout. Participants will also be invited to attend focus groups and 1-1 interviews following completion of the exercise programme to illicit potential barriers facilitators to participation. <it>Control group</it>: Participants will receive treatment as usual. <it>Primary Outcome measure</it>: Depression using the Children's Depression Inventory 2 (CDI-2). <it>Secondary Outcome measures</it>: Quality of Life (EQ-5D), physical fitness (Borg RPE scale, heart rate), incidents of self-harm, treatment received and compliance with treatment, and the cost effectiveness of the intervention. Outcome measures will be taken at baseline, post intervention and 6 month follow up.</p> <p>Discussion</p> <p>The results of this study will inform policy makers of the effectiveness of preferred intensity exercise on the mental health outcomes of young people with depression, the acceptability of such an intervention to this population and its cost effectiveness.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01474837">NCT01474837</a></p

Autoantibodies to BRAF, a new family of autoantibodies associated with rheumatoid arthritis

International audienceBRAF (v raf murine sarcoma viral oncogene homologue B1) is a serine-threonine kinase involved in the mitogen-activated protein kinase (MAPK) signalling pathway, known to be implicated in the production of pro-inflammatory cytokines.We have observed that sera from rheumatoid arthritis (RA) patients recognize the BRAF's catalytic domain, which encompasses amino acids 416 to 766. Here, we identify peptide targets of anti-BRAF autoantibodies and test whether anti-BRAF autoantibodies may interfere with BRAF kinase activity.METHODS:Anti-BRAF autoantibodies were detected by ELISA (enzyme-linked immunosorbent assay) in the serum of RA patients and controls, using 40 overlapping 20mer peptides encompassing the catalytic domain of BRAF as immunosorbents. To test whether autoantibodies to BRAF influence BRAF kinase activity, we developed an in vitro phosphorylation assay of MEK1 (mitogen extracellular regulated kinase), a major BRAF substrate. MEK1 phosphorylation by BRAF was tested in the presence of purified anti-BRAF autoantibodies from RA patients or control antibody.RESULTS:We found that one BRAF peptide, P25 (656 to 675), is specifically recognized by autoantibodies from RA patients. Of interest, anti-P25 autoantibodies are detected in 21% of anti-CCP (cyclic citrullinated peptides) negative RA patients. Anti-BRAF autoantibodies activate the in vitro phosphorylation of MEK1 mediated by BRAF.CONCLUSIONS:Anti-BRAF autoantibodies from RA patients preferentially recognize one BRAF peptide: P25. Autoantibody responses to P25 are detected in 21% of anti-CCP negative RA patients. Most anti-BRAF autoantibodies activate BRAF kinase activity

Why do physicians prescribe dialysis? A prospective questionnaire study

Funding Information: This study was supported by an unrestricted grant 14CECPDEU1001 from Baxter Healthcare International. Baxter Novum is the result of a grant from Baxter Healthcare Corporation to Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, to support research activities at Karolinska Institutet to promote the understanding and treatment of renal disease. Bengt Lindholm is employed by Baxter Healthcare Corporation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Publisher Copyright: © 2017 Heaf et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.Introduction.The incidence of unplanned dialysis initiation (DI) with consequent increased comorbidity, mortality and reduced modality choice remains high, but the optimal timing of dialysis initiation (DI) remains controversial, and there is a lack of studies of specific reasons for DI. We investigated why and when physicians prescribe dialysis and hypothesized that physician motivation for DI is an independent factor which may have clinical consequences. Methods In the Peridialysis study, an ongoing multicenter prospective study assessing the causes and timing of DI and consequences of unplanned dialysis, physicians in 11 hospitals were asked to describe their primary, secondary and further reasons for prescribing DI. The stated reasons for DI were analyzed in relation to clinical and biochemical data at DI, and characteristics of physicians. Results In 446 patients (median age 67 years; 38% females; diabetes 25.6%), DI was prescribed by 84 doctors who stated 23 different primary reasons for DI. The primary indication was clinical in 63% and biochemical in 37%; 23% started for life-threatening conditions. Reduced renal function accounted for only 19% of primary reasons for DI but was a primary or contributing reason in 69%. The eGFR at DI was 7.2 ±3.4 ml/min/1.73 m2, but varied according to comorbidity and cause of DI. Patients with cachexia, anorexia and pulmonary stasis (34% with heart failure) had the highest eGFR (8.2–9.8 ml/min/1.73 m2), and those with edema, “low GFR”, and acidosis, the lowest (4.6–6.1 ml/min/1.73 m2). Patients with multiple comorbidity including diabetes started at a high eGFR (8.7 ml/min/1.73 m2). Physician experience played a role in dialysis prescription. Non-specialists were more likely to prescribe dialysis for life-threatening conditions, while older and more experienced physicians were more likely to start dialysis for clinical reasons, and at a lower eGFR. Female doctors started dialysis at a higher eGFR than males (8.0 vs. 7.1 ml/min/1.73 m2). Conclusions DI was prescribed mainly based on clinical reasons in accordance with current recommendations while low renal function accounted for only 19% of primary reasons for DI. There are considerable differences in physicians´ stated motivations for DI, related to their age, clinical experience and interpretation of biochemical variables. These differences may be an independent factor in the clinical treatment of patients, with consequences for the risk of unplanned DI.publishersversionPeer reviewe

Risk factors for alcohol and other drug use by healthcare professionals

<p>Abstract</p> <p>Background</p> <p>Given the increasingly stressful environment due to manpower shortages in the healthcare system in general, substance induced impairment among some healthcare professions is anticipated to grow. Though recent studies suggest that the prevalence of substance abuse is no higher in healthcare professionals (HPs) than the general population, given the responsibility to the public, any impairment could place the public at increased risk for errors. Few studies have ever reported predictors or risk factors for alcohol and other drug use (AOD) across a sample of HPs.</p> <p>Methods</p> <p>The study used a cross-sectional, descriptive self-report survey in a small northeastern state. A 7-page survey was mailed to a stratified random sample of 697 dentists, nurses, pharmacists and physicians registered in a northeastern state. The main outcome measures were demographic characteristics, lifetime, past year and past month prevalence of AOD use, the frequency of use, drug related dysfunctions, drug misuse and abuse potential. Six contacts during the summer of 2002 resulted in a 68.7% response rate (479/697).</p> <p>Results</p> <p>Risk factors contributing to any reported past year AOD use, as well as significant (defined as the amount of AOD use by the top 25% of respondents) past year AOD use by HPs were examined using logistic regression. Risk factors of any self-reported past year AOD use included moderate or more frequency of alcohol use, being in situations when offered AODs, feeling immune to the addictive effects of drugs (pharmaceutical invincibility) and socializing with substance abusers. Risk factors of significant past year AOD use were HPs with younger licensees, a moderate pattern of alcohol use and not socializing with substance abusers.</p> <p>Conclusion</p> <p>National and state organizations need to develop policies that focus on prevention, treatment, and rehabilitation of alcohol and other drug-using healthcare professionals. The results of this study may help to delineate the characteristics of HPs abusing drugs, leading to the development of more effective policies designed to protect the public, and move toward more tailored and effective intervention strategies for HPs.</p

Alien Invasive Slider Turtle in Unpredicted Habitat: A Matter of Niche Shift or of Predictors Studied?

BACKGROUND: Species Distribution Models (SDMs) aim on the characterization of a species' ecological niche and project it into geographic space. The result is a map of the species' potential distribution, which is, for instance, helpful to predict the capability of alien invasive species. With regard to alien invasive species, recently several authors observed a mismatch between potential distributions of native and invasive ranges derived from SDMs and, as an explanation, ecological niche shift during biological invasion has been suggested. We studied the physiologically well known Slider turtle from North America which today is widely distributed over the globe and address the issue of ecological niche shift versus choice of ecological predictors used for model building, i.e., by deriving SDMs using multiple sets of climatic predictor. PRINCIPAL FINDINGS: In one SDM, predictors were used aiming to mirror the physiological limits of the Slider turtle. It was compared to numerous other models based on various sets of ecological predictors or predictors aiming at comprehensiveness. The SDM focusing on the study species' physiological limits depicts the target species' worldwide potential distribution better than any of the other approaches. CONCLUSION: These results suggest that a natural history-driven understanding is crucial in developing statistical models of ecological niches (as SDMs) while "comprehensive" or "standard" sets of ecological predictors may be of limited use

Parental breeding age effects on descendants' longevity interact over 2 generations in matrilines and patrilines

Individuals within populations vary enormously in mortality risk and longevity, but the causes of this variation remain poorly understood. A potentially important and phylogenetically widespread source of such variation is maternal age at breeding, which typically has negative effects on offspring longevity. Here, we show that paternal age can affect offspring longevity as strongly as maternal age does and that breeding age effects can interact over 2 generations in both matrilines and patrilines. We manipulated maternal and paternal ages at breeding over 2 generations in the neriid fly Telostylinus angusticollis. To determine whether breeding age effects can be modulated by the environment, we also manipulated larval diet and male competitive environment in the first generation. We found separate and interactive effects of parental and grand-parental ages at breeding on descendants' mortality rate and life span in both matrilines and patrilines. These breeding age effects were not modulated by grand-parental larval diet quality or competitive environment. Our findings suggest that variation in maternal and paternal ages at breeding could contribute substantially to intrapopulation variation in mortality and longevity