Posttraumatic stress avoidance symptoms as mediators in the development of alcohol use disorders after exposure to childhood sexual abuse in a Swiss community sample.

This study examined the role of posttraumatic stress disorder (PTSD) symptoms of re-experience, avoidance, and hyperarousal in the relationship between different types of trauma and alcohol use disorders (AUD). We used data from 731 trauma-exposed individuals who participated in the first wave of the PsyCoLaus-study. Trauma characteristics were assessed relatively to the occurrence of lifetime PTSD symptoms and AUD. The results suggest that lifetime and childhood sexual abuse as well as overall childhood trauma were directly linked to AUD and PTSD symptoms, in particular to avoidance symptoms. From single symptom clusters PTSD avoidance was found to specifically mediate the trauma-AUD pathway. Both childhood and sexual trauma strongly contribute to the comorbidity of PTSD and AUD and avoidance-type symptoms appear to play a central role in maintaining this association. Hence, the alleviation of avoidance symptoms might be an important target for therapeutic intervention among victims of sexual abuse before specific addiction treatment is initiated.

Synergism between a foldase and an unfoldase: reciprocal dependence between the thioredoxin-like activity of DnaJ and the polypeptide-unfolding activity of DnaK.

The role of bacterial Hsp40, DnaJ, is to co-chaperone the binding of misfolded or alternatively folded proteins to bacterial Hsp70, DnaK, which is an ATP-fuelled unfolding chaperone. In addition to its DnaK targeting activity, DnaJ has a weak thiol-reductase activity. In between the substrate-binding domain and the J-domain anchor to DnaK, DnaJ has a unique domain with four conserved CXXC motives that bind two Zn(2+) and partly contribute to polypeptide binding. Here, we deleted in DnaJ this Zn-binding domain, which is characteristic to type I but not of type II or III J-proteins. This caused a loss of the thiol-reductase activity and strongly reduced the ability of DnaJ to mediate the ATP- and DnaK-dependent unfolding/refolding of mildly oxidized misfolded polypeptides, an inhibition that was alleviated in the presence of thioredoxin or DTT. We suggest that in addition to their general ability to target misfolded polypeptide substrates to the Hsp70/Hsp110 chaperone machinery, Type I J-proteins carry an ancillary protein dithiol-isomerase function that can synergize the unfolding action of the chaperone, in the particular case of substrates that are further stabilized by non-native disulfide bonds. Whereas the unfoldase can remain ineffective without the transient untying of disulfide bonds by the foldase, the foldase can remain ineffective without the transient ATP-fuelled unfolding of wrong local structures by the unfoldase.

Liberal alcohol legislation: does it amplify the effects among Swiss men of person-related risk factors on heavy alcohol use?

AIM: To estimate the statistical interactions between alcohol policy strength and the person-related risk factors of sensation-seeking, antisocial personality disorder and attention-deficit/hyperactivity disorder related to heavy alcohol use. DESIGN: Cross-sectional survey. SETTING: Young Swiss men living within 21 jurisdictions across Switzerland. PARTICIPANTS: A total of 5701 Swiss men (mean age 20 years) participating in the Cohort Study on Substance Use Risk Factors (C-SURF). MEASUREMENTS: Outcome measures were alcohol use disorder (AUD) as defined in the DSM-5 and risky single-occasion drinking (RSOD). Independent variables were sensation-seeking, antisocial personality disorder (ASPD), attention-deficit/hyperactivity disorder (ADHD) and an index of alcohol policy strength. FINDINGS: Alcohol policy strength was protective against RSOD [odds ratio (OR) = 0.91 (0.84-0.99)], while sensation-seeking and ASPD were risk factors for both RSOD [OR = 1.90 (1.77-2.04); OR = 1.69 (1.44-1.97)] and AUD [OR = 1.58 (1.47-1.71); OR = 2.69 (2.30-3.14)] and ADHD was a risk factor for AUD [OR = 1.08 (1.06-1.10)]. Significant interactions between alcohol policy strength and sensation-seeking were identified for RSOD [OR = 1.06 (1.01-1.12)] and AUD [OR = 1.06 (1.01-1.12)], as well as between alcohol policy strength and ASPD for both RSOD [OR = 1.17 (1.03-1.31)] and AUD [OR = 1.15 (1.02-1.29)]. These interactions indicated that the protective effects of alcohol policy strength on RSOD and AUD were lost in men with high levels of sensation-seeking or an ASPD. No interactions were detected between alcohol policy strength and ADHD. CONCLUSION: Stronger alcohol legislation protects against heavy alcohol use in young Swiss men, but this protective effect is lost in individuals with high levels of sensation-seeking or having an antisocial personality disorder.

A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis.

Alcohol misuse is the leading cause of cirrhosis and the second most common indication for liver transplantation in the Western world. We performed a genome-wide association study for alcohol-related cirrhosis in individuals of European descent (712 cases and 1,426 controls) with subsequent validation in two independent European cohorts (1,148 cases and 922 controls). We identified variants in the MBOAT7 (P = 1.03 × 10(-9)) and TM6SF2 (P = 7.89 × 10(-10)) genes as new risk loci and confirmed rs738409 in PNPLA3 as an important risk locus for alcohol-related cirrhosis (P = 1.54 × 10(-48)) at a genome-wide level of significance. These three loci have a role in lipid processing, suggesting that lipid turnover is important in the pathogenesis of alcohol-related cirrhosis.

Temporal Patterns of Alcohol Consumption and Alcohol-Related Road Accidents in Young Swiss Men: Seasonal, Weekday and Public Holiday Effects.

AIMS: To assess seasonal, weekday, and public holiday effects on alcohol-related road accidents and drinking diaries among young Swiss men. METHODS: Federal road accident data (35,485 accidents) from Switzerland and drinking diary data from a large cohort of young Swiss men (11,930 subjects) were analysed for temporal effects by calendar week, weekday and public holiday (Christmas, New Years, National Day). Alcohol-related accidents were analysed using rate ratios for observed versus expected numbers of accidents and proportions of alcohol-related accidents relative to the total number. Drinking diaries were analysed for the proportion of drinkers, median number of drinks consumed, and the 90th percentile's number of drinks consumed. RESULTS: Several parallel peaks were identified in alcohol-related accidents and drinking diaries. These included increases on Fridays and Saturdays, with Saturday drinking extending until early Sunday morning, an increase during the summer on workdays but not weekends, an increase at the end of the year, and increases on public holidays and the evening before. CONCLUSIONS: Our results suggest specific time-windows that are associated with increases in drinking and alcohol-related harm. Established prevention measures should be enforced during these time-windows to reduce associated peaks.

Intoxication alcoolique aux urgences : dilemmes de prise en charge. Deux situations cliniques fréquentes. [The dilemma of defining "adequate" ED care for acute alcohol intoxication. About two case reports]

L'intoxication éthylique aiguë (IEA) est un motif de recours fréquent en médecine d'urgence. Bien qu'évoluant de manière spontanément favorable dans la majorité des cas, un certain nombre de complications sont susceptibles de survenir dans ce contexte, entrainant des répercussions significatives sur le pronostic des patients. Or, les altérations neurocomportementales accompagnant classiquement ce type d'intoxication mettent régulièrement les cliniciens face à des dilemmes de prise en charge complexes à résoudre. D'autre part, si les propriétés de l'éthanol peuvent atténuer l'expression clinique de certaines pathologies, un certain nombre d'affection de nature métabolique ou neurologique sont susceptibles d'être interprétées à tort comme des IEA. La littérature médicale ne fournissant que peu d'outils d'aide à la décision dans ce domaine, il est souvent difficile de trouver un compromis acceptable entre recours excessif aux examens complémentaires et banalisation face aux patients alcoolisés. A partir de situations cliniques, le présent article propose une approche pragmatique de deux problématiques régulièrement associées à une IEA et sources d'erreur diagnostique, le traumatisme crânien et l'état d'agitation. Ainsi, une meilleure définition des conditions de recours au scanner cérébral en cas de traumatisme crânien et l'adoption d'un protocole de sédation précoce dans l'ivresse excito-motrice doivent permettre de contourner en partie les difficultés soulevées par ces patients.

Are alcohol outlet densities strongly associated with alcohol-related outcomes? A critical review of recent evidence.

ISSUES: There have been reviews on the association between density of alcohol outlets and harm including studies published up to December 2008. Since then the number of publications has increased dramatically. The study reviews the more recent studies with regard to their utility to inform policy. APPROACH: A systematic review found more than 160 relevant studies (published between January 2009 and October 2014). The review focused on: (i) outlet density and assaultive or intimate partner violence; (ii) studies including individual level data; or (iii) 'natural experiments'. KEY FINDINGS: Despite overall evidence for an association between density and harm, there is little evidence on causal direction (i.e. whether demand leads to more supply or increased availability increases alcohol use and harm). When outlet types (e.g. bars, supermarkets) are analysed separately, studies are too methodologically diverse and partly contradictory to permit firm conclusions besides those pertaining to high outlet densities in areas such as entertainment districts. Outlet density commonly had little effect on individual-level alcohol use, and the few 'natural experiments' on restricting densities showed little or no effects. IMPLICATIONS AND CONCLUSIONS: Although outlet densities are likely to be positively related to alcohol use and harm, few policy recommendations can be given as effects vary across study areas, outlet types and outlet cluster size. Future studies should examine in detail outlet types, compare different outcomes associated with different strengths of association with alcohol, analyse non-linear effects and compare different methodologies. Purely aggregate-level studies examining total outlet density only should be abandoned. [Gmel G, Holmes J, Studer J. Are alcohol outlet densities strongly associated with alcohol-related outcomes? A critical review of recent evidence. Drug Alcohol Rev 2015].

Internet-Based Brief Intervention to Prevent Unhealthy Alcohol Use among Young Men: A Randomized Controlled Trial.

INTRODUCTION: Alcohol use is one of the leading modifiable morbidity and mortality risk factors among young adults. STUDY DESIGN: 2 parallel-group randomized controlled trial with follow-up at 1 and 6 months. SETTING/PARTICIPANTS: Internet based study in a general population sample of young men with low-risk drinking, recruited between June 2012 and February 2013. INTERVENTION: Internet-based brief alcohol primary prevention intervention (IBI). The IBI aims at preventing an increase in alcohol use: it consists of normative feedback, feedback on consequences, calorific value alcohol, computed blood alcohol concentration, indication that the reported alcohol use is associated with no or limited risks for health. INTERVENTION group participants received the IBI. Control group (CG) participants completed only an assessment. MAIN OUTCOME MEASURES: Alcohol use (number of drinks per week), binge drinking prevalence. Analyses were conducted in 2014-2015. RESULTS: Of 4365 men invited to participate, 1633 did so; 896 reported low-risk drinking and were randomized (IBI: n = 451; CG: n = 445). At baseline, 1 and 6 months, the mean (SD) number of drinks/week was 2.4(2.2), 2.3(2.6), 2.5(3.0) for IBI, and 2.4(2.3), 2.8(3.7), 2.7(3.9) for CG. Binge drinking, absent at baseline, was reported by 14.4% (IBI) and 19.0% (CG) at 1 month and by 13.3% (IBI) and 13.0% (CG) at 6 months. At 1 month, beneficial intervention effects were observed on the number of drinks/week (p = 0.05). No significant differences were observed at 6 months. CONCLUSION: We found protective short term effects of a primary prevention IBI. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN55991918.

Drinking locations and alcohol-related harm: Cross-sectional and longitudinal associations in a sample of young Swiss men.

BACKGROUND: Alcohol consumption--in particular drinking volume (DV) and risky single occasion drinking (RSOD)--has been related to a wide range of negative consequences and health problems. Previous studies also suggested that drinking in certain locations may be more strongly associated with the occurrence of alcohol-related harm than drinking in others. However, they were conducted in countries culturally and legally different from European countries and were limited to cross-sectional designs. This study investigates the cross-sectional and longitudinal associations of alcohol-related harm with DVs in different locations in a sample of young Swiss men. METHODS: A representative sample of 4536 young Swiss male drinkers completed baseline and 15-month follow-up questionnaires. These assessed DVs in 11 locations, alcohol-related harm (i.e. number of alcohol-related consequences and alcohol use disorder criteria) and frequency of RSOD. Cross-sectional and longitudinal associations of alcohol-related harm with DVs in each location were tested using regression models, with and without adjustment for frequency of RSOD. RESULTS: Both cross-sectional and longitudinal analyses showed significant positive associations between alcohol-related harm and DVs at friends' homes, in discos/nightclubs and in outdoor public places, when controlling for frequency of RSOD. In contrast, the contribution of DVs at one's own home and in restaurants was consistently not significant when adjusted for frequency of RSOD. When controlling for RSOD, associations between alcohol-related harm and DVs in bars/pubs, when playing sports, during other leisure activities, at cinemas/theatres, during sporting events, and during special events were not consistent between cross-sectional and longitudinal analyses. CONCLUSION: Results suggest that prevention interventions should not only target reducing the overall volume of alcohol consumed and the frequency of RSOD in general, but they should additionally focus on limiting alcohol consumption in outdoor public places, discos/nightclubs, and in friends' homes in particular, or at least on preventing harm occurring in these occasions.

Validation of French and German versions of a Perceived Neighborhood Social Cohesion questionnaire among young Swiss males, and its relationship with substance use

This study main purpose was the validation of both French and German versions of a Perceived Neighborhood Social Cohesion Questionnaire. The sample group comprised 5065 Swiss men from the "Cohort Study on Substance Use Risk Factors." Multigroup Confirmatory factor analysis showed that a three-factor model fits the data well, which substantiates the generalizability of Perceived Neighborhood Social Cohesion Questionnaire factor structure, regardless of the language. The Perceived Neighborhood Social Cohesion Questionnaire demonstrated excellent homogeneity (α = 95) and split-half reliability (r = .96). The Perceived Neighborhood Social Cohesion Questionnaire was sensitive to community size and participants' financial situation, confirming that it also measures real social conditions. Finally, weak but frequent correlations between Perceived Neighborhood Social Cohesion Questionnaire and alcohol, cigarette, and cannabis dependence were measured.

Condition-dependence, pleiotropy and the handicap principle of sexual selection in melanin-based colouration.

The signalling function of melanin-based colouration is debated. Sexual selection theory states that ornaments should be costly to produce, maintain, wear or display to signal quality honestly to potential mates or competitors. An increasing number of studies supports the hypothesis that the degree of melanism covaries with aspects of body condition (e.g. body mass or immunity), which has contributed to change the initial perception that melanin-based colour ornaments entail no costs. Indeed, the expression of many (but not all) melanin-based colour traits is weakly sensitive to the environment but strongly heritable suggesting that these colour traits are relatively cheap to produce and maintain, thus raising the question of how such colour traits could signal quality honestly. Here I review the production, maintenance and wearing/displaying costs that can generate a correlation between melanin-based colouration and body condition, and consider other evolutionary mechanisms that can also lead to covariation between colour and body condition. Because genes controlling melanic traits can affect numerous phenotypic traits, pleiotropy could also explain a linkage between body condition and colouration. Pleiotropy may result in differently coloured individuals signalling different aspects of quality that are maintained by frequency-dependent selection or local adaptation. Colouration may therefore not signal absolute quality to potential mates or competitors (e.g. dark males may not achieve a higher fitness than pale males); otherwise genetic variation would be rapidly depleted by directional selection. As a consequence, selection on heritable melanin-based colouration may not always be directional, but mate choice may be conditional to environmental conditions (i.e. context-dependent sexual selection). Despite the interest of evolutionary biologists in the adaptive value of melanin-based colouration, its actual role in sexual selection is still poorly understood.