27 March 2020 In General Health

The microbiota is known to modulate the host response to influenza infection through as-yet-unclear mechanisms. We hypothesized that components of the microbiota exert effects through type I interferon (IFN), a hypothesis supported by analysis of influenza in a gain-of-function genetic mouse model. Here we show that a microbially associated metabolite, desaminotyrosine (DAT), protects from influenza through augmentation of type I IFN signaling and diminution of lung immunopathology. A specific human-associated gut microbe, Clostridium orbiscindens, produced DAT and rescued antibiotic-treated influenza-infected mice. DAT protected the host by priming the amplification loop of type I IFN signaling. These findings show that specific components of the enteric microbiota have distal effects on responses to lethal infections through modulation of type I IFN.

27 March 2020 In General Health

Public health groups, researchers, the beverage alcohol industry, and other stakeholders have promoted and applied the concept of "responsible drinking" for the past 50 years. However, little is known about the state of the existing responsible drinking evaluation research and its application to policy and practice. This project provides a scoping review of studies evaluating responsible drinking interventions. Two primary research questions guided this investigation: (1) To what extent have authors attempted to define the concept of responsible drinking while evaluating responsible drinking interventions? and (2) What is the state of the responsible drinking intervention evaluation literature? We retrieved 49 peer-reviewed articles that evaluated interventions designed to promote "responsible drinking." Four articles provided, or attempted to provide, an explicit definition of responsible drinking; these four definitions lacked consensus. The existing responsible drinking interventions varied considerably in terms of the messages they attempted to convey (e.g., avoid binge drinking, use protective behavioral strategies, stick to relatively safe drinking limits), again suggesting lack of consensus. We observed greater consensus concerning the approach to evaluating responsible drinking interventions: studies typically recruited college students to complete brief, well-controlled experiments and measured potential predictors of drinking behavior (e.g., attitudes, expectancies, intentions) rather than actual drinking behavior. We discuss limitations of this methodological approach and the need for greater consensus regarding the concept of responsible drinking.

27 March 2020 In General Health

OBJECTIVE: We assessed the influence of sex on the effects of smoking and alcohol consumption on the risk of Parkinson's disease (PD).

METHODS: This population-based cohort study examined data of 6,795,816 Koreans aged >/=40 years from the Korean National Health Insurance Service database who completed a national program for general health check-up at 2009. For a maximum 9 years' observation period, incident PD was tracked, and hazard ratios and 95% confidence intervals (CIs) were computed using the Cox proportional hazard models, adjusted for potential confounding factors for each sex group. We tested interactions on the addictive scale by estimating the relative excess risk due to interaction (RERI).

RESULTS: 3,400,538 men and 3,395,278 women generated 24,365,694 and 24,754,154 person-years, respectively. A total of 13,223 men (0.39%) and 14,818 women (0.44%) developed PD during follow-up. Current smoking and alcohol independently reduced the risk of PD in both sexes. Current male smokers tended to have a lower risk of PD than current female smokers at equal smoking intensity (P < 0.0001 for interaction) and duration (P < 0.0001 for interaction). In contrast, at equal alcohol intakes, PD risk tended to be lower in female drinkers than in male drinkers (P < 0.0001 for interaction). A superadditive interaction between smoking and alcohol was found in current male smokers (RERI, 0.19; 95% CI, 0.04 to 0.34; P = 0.015) and female ex-smokers (RERI, 0.42; 95% CI, 0.09 to 0.76; P = 0.014).

CONCLUSION: Our data suggest sex-related differences in individual and joint impacts of smoking and alcohol intake on the risk of PD.

27 March 2020 In Dementia

INTRODUCTION: Observational studies have suggested that light-to-moderate alcohol consumption decreases the risk of Alzheimer's disease, but it is unclear if this association is causal.

METHODS: Two-sample Mendelian randomization (MR) analysis was used to examine whether alcohol consumption, alcohol dependence, or Alcohol Use Disorder Identification Test (AUDIT) scores were causally associated with the risk of Late-Onset Alzheimer's disease (LOAD) or Alzheimer's disease age of onset survival (AAOS). Additionally, gamma-glutamyltransferase levels were included as a positive control.

RESULTS: There was no evidence of a causal association between alcohol consumption, alcohol dependence, or AUDIT, and LOAD. Alcohol consumption was associated with an earlier AAOS and increased gamma-glutamyltransferase blood concentrations. Alcohol dependence was associated with a delayed AAOS.

DISCUSSION: MR found robust evidence of a causal association between alcohol consumption and an earlier AAOS, but not alcohol intake and LOAD risk. The protective effect of alcohol dependence is potentially due to survivor bias.

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