Photoactivatable drugs for nicotinic optopharmacology

Photoactivatable pharmacological agents have revolutionized neuroscience, but the palette of available compounds is limited. We describe a general method for caging tertiary amines by using a stable quaternary ammonium linkage that elicits a red shift in the activation wavelength. We prepared a photoactivatable nicotine (PA-Nic), uncageable via one- or two-photon excitation, that is useful to study nicotinic acetylcholine receptors (nAChRs) in different experimental preparations and spatiotemporal scales

A reappraisal of the impact of dairy foods and milk fat on cardiovascular disease risk

Background This review provides a reappraisal of the potential effects of dairy foods, including dairy fats, on cardiovascular disease (CVD)/coronary heart disease (CHD) risk. Commodities and foods containing saturated fats are of particular focus as current public dietary recommendations are directed toward reducing the intake of saturated fats as a means to improve the overall health of the population. A conference of scientists from different perspectives of dietary fat and health was convened in order to consider the scientific basis for these recommendations. Aims This review and summary of the conference focus on four key areas related to the biology of dairy foods and fats and their potential impact on human health: (a) the effect of dairy foods on CVD in prospective cohort studies; (b) the impact of dairy fat on plasma lipid risk factors for CVD; (c) the effects of dairy fat on non-lipid risk factors for CVD; and (d) the role of dairy products as essential contributors of micronutrients in reference food patterns for the elderly. Conclusions Despite the contribution of dairy products to the saturated fatty acid composition of the diet, and given the diversity of dairy foods of widely differing composition, there is no clear evidence that dairy food consumption is consistently associated with a higher risk of CVD. Thus, recommendations to reduce dairy food consumption irrespective of the nature of the dairy product should be made with cautionJ. Bruce German, Robert A. Gibson, Ronald M. Krauss, Paul Nestel, Benoît Lamarche, Wija A. van Staveren, Jan M. Steijns, Lisette C. P. G. M. de Groot, Adam L. Lock and Frédéric Destaillat

Reasons for non-recruitment of eligible patients to a randomised controlled trial of secondary prevention after intracerebral haemorrhage: observational study.

Recruitment to randomised prevention trials is challenging, not least for intracerebral haemorrhage (ICH) associated with antithrombotic drug use. We investigated reasons for not recruiting apparently eligible patients at hospital sites that keep screening logs in the ongoing REstart or STop Antithrombotics Randomised Trial (RESTART), which seeks to determine whether to start antiplatelet drugs after ICH.EDGE project number 14013British Heart Foundation Special Project (SP/12/2/29422) & Project (PG/14/50/30891) fundin

Lifecourse social conditions and racial disparities in incidence of first stroke

Purpose Some previous studies found excess stroke rates among black subjects persisted after adjustment for socioeconomic status (SES), fueling speculation regarding racially patterned genetic predispositions to stroke. Previous research was hampered by incomplete SES assessments, without measures of childhood conditions or adult wealth. We assess the role of lifecourse SES in explaining stroke risk and stroke disparities. Methods Health and Retirement Study participants age 50+ (n = 20,661) were followed on average 9.9 years for self- or proxy-reported first stroke (2175 events). Childhood social conditions (southern state of birth, parental SES, self-reported fair/poor childhood health, and attained height), adult SES (education, income, wealth, and occupational status) and traditional cardiovascular risk factors were used to predict first stroke onset using Cox proportional hazards models. Results Black subjects had a 48% greater risk of first stroke incidence than whites (95% confidence interval, 1.33–1.65). Childhood conditions predicted stroke risk in both blacks and whites, independently of adult SES. Adjustment for both childhood social conditions and adult SES measures attenuated racial differences to marginal significance (hazard ratio, 1.13; 95% CI, 1.00–1.28). Conclusions Childhood social conditions predict stroke risk in black and White American adults. Additional adjustment for adult SES, in particular wealth, nearly eliminated the disparity in stroke risk between black and white subjects