Is There a Recent Epidemic of Women's Drinking? A Critical Review of National Studies

Alcohol consumption is increasing in the United States, as is alcohol‐attributable mortality. Historically, men have had higher rates of alcohol consumption than women, though evidence for birth cohort effects on gender differences in alcohol consumption and alcohol‐related harm suggests that gender differences may be diminishing. We review studies using U.S. national data that examined time trends in alcohol consumption and alcohol‐related harm since 2008. Utilizing a historical–developmental perspective, here we synthesize and integrate the literature on birth cohort effects from varying developmental periods (i.e., adolescence, young adulthood, middle adulthood, and late adulthood), with a focus on gender differences in alcohol consumption. Findings suggest that recent trends in gender differences in alcohol outcomes are heterogeneous by developmental stage. Among adolescents and young adults, both males and females are rapidly decreasing alcohol consumption, binge and high‐intensity drinking, and alcohol‐related outcomes, with gender rates converging because males are decreasing consumption faster than females. This pattern does not hold among adults, however. In middle adulthood, consumption, binge drinking, and alcohol‐related harms are increasing, driven largely by increases among women in their 30s and 40s. The trend of increases in consumption that are faster for women than for men appears to continue into older adult years (60 and older) across several studies. We conclude by addressing remaining gaps in the literature and offering directions for future research.     

Prediction of Early Adverse Events in Emergency Department Patients With Acute Heart Failure: A Systematic Review

Background

Acute heart failure (AHF) accounts for a substantial proportion of Emergency Department (ED) visits and hospitalizations. Previous studies have shown that emergency physicians' clinical gestalt is not sufficient to stratify patients with AHF into severe and requiring hospitalization vs nonsevere and safe to be discharged. Various prognostic algorithms have been developed to risk-stratify patients with AHF, however there is no consensus as to the best-performing risk assessment tool in the ED.

Structural approaches to HIV prevention

Recognition that social, economic, political, and environmental factors directly affect HIV risk and vulnerability has stimulated interest in structural approaches to HIV prevention. Progress in the use of structural approaches has been limited for several reasons: absence of a clear definition; lack of operational guidance; and limited data on the effectiveness of structural approaches to the reduction of HIV incidence. In this paper we build on evidence and experience to address these gaps. We begin by defining structural factors and approaches. We describe the available evidence on their effectiveness and discuss methodological challenges to the assessment of these often complex efforts to reduce HIV risk and vulnerability. We identify core principles for implementing this kind of work. We also provide recommendations for ensuring the integration of structural approaches as part of combined prevention strategies.     

Percutaneous cardiac recirculation-mediated gene transfer of an inhibitory phospholamban peptide reverses advanced heart failure in large animals.

OBJECTIVES: The purpose of this study was to develop a clinically applicable high-efficiency percutaneous means of therapeutic gene delivery to the failing heart. BACKGROUND: Substantial advances in the understanding of the cellular and molecular basis of heart failure (HF) have recently fostered interest in the potential utility of gene and cell therapy as novel therapeutic approaches. However, successful clinical translation is currently limited by the lack of safe, efficient, and selective delivery systems. METHODS: We developed a novel percutaneous closed-loop recirculatory system that provides homogeneous myocardial delivery for gene transfer in the failing large animal heart. After 4 weeks' rapid pacing in adult sheep to induce HF, the animals were randomly allocated to receive either adenovirus expressing a pseudophosphorylated mutant (AdS16E) of phospholamban (PLN) or Ad-beta-galactosidase (AdLacZ). RESULTS: Two weeks after gene delivery, in the presence of continued pacing, left ventricular (LV) ejection fraction had significantly improved in the AdS16E-treated animals (27 +/- 3% to 50 +/- 4%; p < 0.001), whereas a further decline occurred in the AdLacZ group (34 +/- 4% to 27 +/- 3%; p < 0.05). In conjunction, AdS16E delivery resulted in significant reductions in LV filling pressures and end-diastolic diameter (both p < 0.05). In conjunction, AdS16E-treated animals showed significant improvement in the expression of PLN and Ca2+-adenosine triphosphatase activity. In separate animals, recirculating AdLacZ delivery was shown to achieve superior myocardial gene expression in contrast to intracoronary delivery and was associated with lower systemic expression. CONCLUSIONS: We report the development of a novel closed-loop system for cardiac gene therapy. Using this approach delivery of AdS16E reversed HF progression in a large animal HF model.     

Identification of a fibrin-independent platelet contractile mechanism regulating primary hemostasis and thrombus growth

A fundamental property of platelets is their ability to transmit cytoskeletal contractile forces to extracellular matrices. While the importance of the platelet contractile mechanism in regulating fibrin clot retraction is well established, its role in regulating the primary hemostatic response, independent of blood coagulation, remains ill defined. Real-time analysis of platelet adhesion and aggregation on a collagen substrate revealed a prominent contractile phase during thrombus development, associated with a 30% to 40% reduction in thrombus volume. Thrombus contraction developed independent of thrombin and fibrin and resulted in the tight packing of aggregated platelets. Inhibition of the platelet contractile mechanism, with the myosin IIA inhibitor blebbistatin or through Rho kinase antagonism, markedly inhibited thrombus contraction, preventing the tight packing of aggregated platelets and undermining thrombus stability in vitro. Using a new intravital hemostatic model, we demonstrate that the platelet contractile mechanism is critical for maintaining the integrity of the primary hemostatic plug, independent of thrombin and fibrin generation. These studies demonstrate an important role for the platelet contractile mechanism in regulating primary hemostasis and thrombus growth. Furthermore, they provide new insight into the underlying bleeding diathesis associated with platelet contractility defects.     

Amino acid polymorphisms in Arabidopsis phytochrome B cause differential responses to light

Plants have a sophisticated system for sensing and responding to their light environment. The light responses of populations and species native to different habitats show adaptive variation; understanding the mechanisms underlying photomorphogenic variation is therefore of significant interest. In Arabidopsis thaliana, phytochrome B (PHYB) is the dominant photoreceptor for red light and plays a major role in white light. Because PHYB has been proposed as a candidate gene for several quantitative trait loci (QTLs) affecting light response, we have investigated sequence and functional variation in Arabidopsis PHYB. We examined PHYB sequences in 33 A. thaliana individuals and in the close relative Arabidopsis lyrata. From 14 nonsynonymous polymorphisms, we chose 5 for further study based on previous QTL studies. In a larger collection of A. thaliana accessions, one of these five polymorphisms, I143L, was associated with variation in red light response. We used transgenic analysis to test this association and confirmed experimentally that natural PHYB polymorphisms cause differential plant responses to light. Furthermore, our results show that allelic variation of PHYB activity is due to amino acid rather than regulatory changes. Together with earlier studies linking variation in light sensitivity to photoreceptor genes, our work suggests that photoreceptors may be a common target of natural selection.