The relationship between different dimensions of alcohol use and the burden of disease-an update.

Alcohol use is a major contributor to injuries, mortality and the burden of disease. This review updates knowledge on risk relations between dimensions of alcohol use and health outcomes to be used in global and national Comparative Risk Assessments (CRAs). Systematic review of reviews and meta-analyses on alcohol consumption and health outcomes attributable to alcohol use. For dimensions of exposure: volume of alcohol use, blood alcohol concentration and patterns of drinking, in particular heavy drinking occasions were studied. For liver cirrhosis, quality of alcohol was additionally considered. For all outcomes (mortality and/or morbidity): cause of death and disease/injury categories based on International Classification of Diseases (ICD) codes used in global CRAs; harm to others. In total, 255 reviews and meta-analyses were identified. Alcohol use was found to be linked causally to many disease and injury categories, with more than 40 ICD-10 three-digit categories being fully attributable to alcohol. Most partially attributable disease categories showed monotonic relationships with volume of alcohol use: the more alcohol consumed, the higher the risk of disease or death. Exceptions were ischaemic diseases and diabetes, with curvilinear relationships, and with beneficial effects of light to moderate drinking in people without heavy irregular drinking occasions. Biological pathways suggest an impact of heavy drinking occasions on additional diseases; however, the lack of medical epidemiological studies measuring this dimension of alcohol use precluded an in-depth analysis. For injuries, except suicide, blood alcohol concentration was the most important dimension of alcohol use. Alcohol use caused marked harm to others, which has not yet been researched sufficiently. Research since 2010 confirms the importance of alcohol use as a risk factor for disease and injuries; for some health outcomes, more than one dimension of use needs to be considered. Epidemiological studies should include measurement of heavy drinking occasions in line with biological knowledge

A Sexual Shift Induced by Silencing of a Single Insulin-Like Gene in Crayfish: Ovarian Upregulation and Testicular Degeneration

In sequential hermaphrodites, intersexuality occurs naturally, usually as a transition state during sexual re-differentiation processes. In crustaceans, male sexual differentiation is controlled by the male-specific androgenic gland (AG). An AG-specific insulin-like gene, previously identified in the red-claw crayfish Cherax quadricarinatus (designated Cq-IAG), was found in this study to be the prominent transcript in an AG cDNA subtractive library. In C. quadricarinatus, sexual plasticity is exhibited by intersex individuals in the form of an active male reproductive system and male secondary sex characters, along with a constantly arrested ovary. This intersexuality was exploited to follow changes caused by single gene silencing, accomplished via dsRNA injection. Cq-IAG silencing induced dramatic sex-related alterations, including male feature feminization, a reduction in sperm production, extensive testicular degeneration, expression of the vitellogenin gene, and accumulation of yolk proteins in the developing oocytes. Upon silencing of the gene, AG cells hypertrophied, possibly to compensate for low hormone levels, as reflected in the poor production of the insulin-like hormone (and revealed by immunohistochemistry). These results demonstrate both the functionality of Cq-IAG as an androgenic hormone-encoding gene and the dependence of male gonad viability on the Cq-IAG product. This study is the first to provide evidence that silencing an insulin-like gene in intersex C. quadricarinatus feminizes male-related phenotypes. These findings, moreover, contribute to the understanding of the regulation of sexual shifts, whether naturally occurring in sequential hermaphrodites or abnormally induced by endocrine disruptors found in the environment, and offer insight into an unusual gender-related link to the evolution of insulins