Context and culture associated with alcohol use amongst youth in major urban cities: A cross-country population based survey

Background: Alcohol consumption patterns are dependent upon culture and context. The aim of this study was to interview people aged 18–34 year old living in four cities in different regions of the world to explore differences in a range of alcohol measures to assist in determining culturally appropriate alcohol initiatives for this age group. Method: Multistage random sampling was consistent across the four cities (Ilorin (Nigeria), Wuhan (China), Montevideo (Uruguay) and Moscow (Russia)). The questionnaire was forward and back translated into relevant languages and face-to-face interviewing undertaken. The data were weighted to the population of each city. Uni-variable analysis (ever consumed, first time consumed, age when drunk for first time, number of days consumed, type consumed) and logistic regression modeling were undertaken. The final model for each city was adjusted for age, sex, marital status, highest education and employment status. In total 6235 interviews were undertaken (1391 in Ilorin, 1600 in Montevideo, 1604 in Moscow and 1640 in Wuhan). Results: Alcohol was consumed by 96.4% in Montevideo, 86.1% in Moscow, 53.4% in Wuhan and 33.3% in Ilorin. There was very little difference by gender except Ilorin males were more likely to consume alcohol than females. Alcohol was consumed on more days for Ilorin males; Wuhan females consumed alcohol on the least number of days; Ilorin had the most abstainers; Montevideo and Moscow the highest proportion of light drinkers; Ilorin and Montevideo the highest proportion of heavy drinkers. Differences by type of alcohol were also apparent. The final logistic regression model provided different models including higher alcohol consumption rates for males, 25–34 years of age, divorced/separated marital status and employed part time for Ilorin respondents; males and higher educated for Montevideo; males, 25 to 29 years of age and higher educated for Moscow; and 25–29 years of age, non-married and vocationally trained for those in Wuhan. Conclusion: Alcohol consumption in these four cities does not increase with age as found in most high income countries. The alcohol consumption patterns during this stage of the life cycle are important to assess so that high level, as well as country-specific, planning and interventions can be implemented

Present state and future perspectives of using pluripotent stem cells in toxicology research

The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, and discusses the potential of pluripotent stem cells for safety pharmacology and toxicology. Special attention is directed to the potential application of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) for the assessment of developmental toxicology as well as cardio- and hepatotoxicology. With respect to embryotoxicology, recent achievements of the embryonic stem cell test (EST) are described and current limitations as well as prospects of embryotoxicity studies using pluripotent stem cells are discussed. Furthermore, recent efforts to establish hPSC-based cell models for testing cardio- and hepatotoxicity are presented. In this context, methods for differentiation and selection of cardiac and hepatic cells from hPSCs are summarized, requirements and implications with respect to the use of these cells in safety pharmacology and toxicology are presented, and future challenges and perspectives of using hPSCs are discussed

Structural evidence for the critical role of the prion protein hydrophobic region in forming an infectious prion

Prion or PrPSc is the proteinaceous infectious agent causing prion diseases in various mammalian species. Despite decades of research, the structural basis for PrPSc formation and prion infectivity remains elusive. To understand the role of the hydrophobic region in forming infectious prion at the molecular level, we report X-ray crystal structures of mouse (Mo) prion protein (PrP) (residues 89-230) in complex with a nanobody (Nb484). Using the recombinant prion propagation system, we show that the binding of Nb484 to the hydrophobic region of MoPrP efficiently inhibits the propagation of proteinase K resistant PrPSc and prion infectivity. In addition, when added to cultured mouse brain slices in high concentrations, Nb484 exhibits no neurotoxicity, which is drastically different from other neurotoxic anti-PrP antibodies, suggesting that the Nb484 can be a potential therapeutic agent against prion disease. In summary, our data provides the first structure-function evidence supporting a crucial role of the hydrophobic region of PrP in forming an infectious prion