Identifying the determinants of premature mortality in Russia: overcoming a methodological challenge

Background  

It is thought that excessive alcohol consumption is related to the high mortality among working age men in Russia. Moreover it has been suggested that alcohol is a key proximate driver of the very sharp fluctuations in mortality seen in this group since the mid-1980s. Designing an individual-level study suitable to address the potential acute effects of alcohol consumption on mortality in Russia has posed a challenge to epidemiologists, especially because of the need to identify factors that could underlie the rapid changes up and down in mortality rates that have been such a distinctive feature of the Russian mortality crisis. In order to address this study question which focuses on exposures acting shortly before sudden death, a cohort would be unfeasibly large and would suffer from recruitment bias.     

Alcohol and Russian mortality: a continuing crisis

Background Russia remains in the grip of a mortality crisis in which alcohol plays a central role. In 2007, male life expectancy at birth was 61 years, while for females it was 74 years. Alcohol is implicated particularly in deaths among working‐age men. Aims To review the current state of knowledge about the contribution of alcohol to the continuing very high mortality seen among Russian adults Results Conservative estimates attribute 31–43% of deaths among working‐age men to alcohol. This latter estimate would imply a minimum of 170 000 excess deaths due to hazardous alcohol consumption in Russia per year. Men drink appreciably more than women in Russia. Hazardous drinking is most prevalent among people with low levels of education and those who are economically disadvantaged, partly because some of the available sources of ethanol are very cheap and easy to obtain. The best estimates available suggest that per capita consumption among adults is 15–18 litres of pure ethanol per year. However, reliable estimation of the total volume of alcohol consumed per capita in Russia is very difficult because of the diversity of sources of ethanol that are available, for many of which data do not exist. These include both illegal spirits, as well as legal non‐beverage alcohols (such as medicinal tinctures). In 2006 regulations were introduced aimed at reducing the production and sale of non‐beverage alcohols that are commonly drunk. These appear to have been only partially successful. Conclusion There is convincing evidence that alcohol plays an important role in explaining high mortality in Russia, in particular among working age men. However, there remain important uncertainties about the precise scale of the problem and about the health effects of the distinctive pattern of alcohol consumption that is prevalent in Russia today. While there is a need for further research, enough is known to justify the development of a comprehensive inter‐sectoral alcohol control strategy. The recent fall in life expectancy in Russia should give a renewed urgency to attempts to move the policy agenda forward.     

Anti-cancer activity of withaferin A in B-cell lymphoma

Withaferin A (WA), a withanolide from the plant, Ashwagandha (Withania somnifera) used in Ayurvedic medicine, has been found to be valuable in the treatment of several medical ailments. WA has been found to have anticancer activity against various solid tumors, but its effects on hematological malignancies have not been studied in detail. WA strongly inhibited the survival of several human and murine B cell lymphoma cell lines. Additionally, in vivo studies with syngeneic-graft lymphoma cells suggest that WA inhibits the growth of tumor but does not affect other proliferative tissues. We demonstrate that WA inhibits the efficiency of NF-κB nuclear translocation in diffuse large B cell lymphomas and found that WA treatment resulted in a significant decrease in protein levels involved in B cell receptor signaling and cell cycle regulation. WA inhibited the activity of heat shock protein (Hsp) 90 as reflected by a sharp increase in Hsp70 expression levels. Hence, we propose that the anti-cancer effects of WA in lymphomas are likely due to its ability to inhibit Hsp90 function and subsequent reduction of critical kinases and cell cycle regulators that are clients of Hsp90.