Frontoparietal connectivity in substance-naïve youth with and without a family history of alcoholism

Frontoparietal connections underlie key executive cognitive functions. Abnormalities in the frontoparietal network have been observed in chronic alcoholics and associated with alcohol-related cognitive deficits. It remains unclear whether neurobiological differences in frontoparietal circuitry exist in substance-naïve youth who are at-risk for alcohol use disorders. This study used functional connectivity magnetic resonance imaging and diffusion tensor imaging to examine frontoparietal connectivity and underlying white matter microstructure in 20 substance-naïve youth with a family history of alcohol dependence and 20 well-matched controls without familial substance use disorders. Youth with a family history of alcohol dependence showed significantly less functional connectivity between posterior parietal and dorsolateral prefrontal seed regions (ps < .05), as compared to family history negative controls; however, they did not show differences in white matter architecture within tracts subserving frontoparietal circuitry (ps > .34). Substance-naïve youth with a family history of alcohol dependence show less frontoparietal functional connectivity in the absence of white matter microstructural abnormalities as compared to youth with no familial risk. This may suggest a potential neurobiological marker for the development of substance use disorders.     

Alcohol Use Behaviors Among Pharmacy Students

Objective. To identify reasons for drinking, determine the patterns of alcohol abuse, and explore relationships between drinking motives and alcohol abuse patterns in pharmacy students.Methods. A cross-sectional anonymous, voluntary, self-administered paper survey instrument was administered to first-year (P1) through third-year (P3) pharmacy students as part of a professional seminar.Results. Survey instruments were completed by 349 pharmacy students (95.9% cooperation rate). Using the Alcohol Use Disorders Identification Test criteria, 23.2% of students reported hazardous or harmful use and 67.2% of students reported consuming alcohol at hazardous levels during the past year. Students who were male (37.0%), single (25.3%), and attended the main campus (26.2%) were more likely than their counterparts to report hazardous or harmful alcohol use. Pharmacy students reported social motives as the most common reason for drinking; however, coping and enhancement motives were more predictive of harmful or hazardous alcohol use.Conclusion. Approximately 1 in 4 pharmacy students (23%) reported hazardous or harmful alcohol use. Education about the dangers of alcohol abuse and intervention programs from colleges and schools of pharmacy are recommended to help address this issue.     

Discovery of an Anion-Dependent Farnesyltransferase Inhibitor from a Phenotypic Screen

By employing a phenotypic screen, a set of compounds, exemplified by 1, were identified which potentiate the ability of histone deacetylase inhibitor vorinostat to reverse HIV latency. Proteome enrichment followed by quantitative mass spectrometric analysis employing a modified analogue of 1 as affinity bait identified farnesyl transferase (FTase) as the primary interacting protein in cell lysates. This ligand-FTase binding interaction was confirmed via X-ray crystallography and temperature dependent fluorescence studies, despite 1 lacking structural and binding similarity to known FTase inhibitors. Although multiple lines of evidence established the binding interaction, these ligands exhibited minimal inhibitory activity in a cell-free biochemical FTase inhibition assay. Subsequent modification of the biochemical assay by increasing anion concentration demonstrated FTase inhibitory activity in this novel class. We propose 1 binds together with the anion in the active site to inhibit farnesyl transferase. Implications for phenotypic screening deconvolution and HIV reactivation are discussed.     

Atypical Femur Fractures: A Review

Bisphosphonates are one of the most commonly prescribed medications for the treatment of osteoporosis. Their use has greatly decreased the number of osteoporosis-related vertebral and nonvertebral fractures. Recently, however, a relationship between long-term bisphosphonate use and subtrochanteric and femoral shaft fractures has been elucidated. These low-energy fractures, termed atypical femur fractures, exhibit unique characteristics in their pathophysiology, presentation, and radiographic appearance compared with more traditional high-energy femur fractures. Here we provide a review based on the most recent literature of the pathophysiology, presentation, evaluation, and management of these fractures. Despite an abundance of literature, atypical femur fractures remain difficult to treat, and surgeons must be aware of the tricks and complications associated with their management.