Multiple Genetic Mutations Associated with Polymyxin Resistance in Acinetobacter baumannii

We studied polymyxin B resistance in 10 pairs of clinical Acinetobacter baumannii isolates, two of which had developed polymyxin B resistance in vivo. All polymyxin B-resistant isolates had lower growth rates than and substitution mutations in the lpx or pmrB gene compared to their parent isolates. There were significant differences in terms of antibiotic susceptibility and genetic determinants of resistance in A. baumannii isolates that had developed polymyxin B resistance in vivo compared to isolates that had developed polymyxin B resistance in vitro.     

Chaotic mixing deep in the lung

Our current understanding of the transport and deposition of aerosols (viruses, bacteria, air pollutants, aerosolized drugs) deep in the lung has been grounded in dispersive theories based on untested assumptions about the nature of acinar airflow fields. Traditionally, these have been taken to be simple and kinematically reversible. In this article, we apply the recently discovered fluid mechanical phenomenon of irreversible low-Reynolds number flow to the lung. We demonstrate, through flow visualization studies in rhythmically ventilated rat lungs, that such a foundation is false, and that chaotic mixing may be key to aerosol transport. We found substantial alveolar flow irreversibility with stretched and folded fractal patterns, which lead to a sudden increase in mixing. These findings support our theory that chaotic alveolar flow--characterized by stagnation saddle points associated with alveolar vortices--governs gas kinematics in the lung periphery, and hence the transport, mixing, and ultimately the deposition of fine aerosols. This mechanism calls for a rethinking of the relationship of exposure and deposition of fine inhaled particles.     

Evidence of a Syndemic Among Young Canadian Gay and Bisexual Men: Uncovering the Associations Between Anti-gay Experiences,Psychosocial Issues,and HIV Risk

Syndemic has become an important theoretical model toward understanding how psychosocial issues may interact to increase HIV acquisition among gay and bisexual men. We measured the extent to which anti-gay experiences are associated with psychosocial issues, which in turn were hypothesized to have an additive effect on HIV risk, in a sample of Canadian young gay and bisexual men. Sixty-eight percent of men reported at least one form of anti-gay experience. For each additional form of anti-gay experience, our data demonstrated increased likelihood of psychosocial issues. Psychosocial issues had an additive effect, increasing the risk of unprotected intercourse in the last 12 months (doubling the risk for those with 3+ issues OR 1.95 [1.39–2.75]). Overall, our findings suggest that a syndemic is occurring among young Canadian gay and bisexual men, highlighting the need to expand HIV prevention efforts beyond sexual risk, to address stigma and gay men’s broader health concerns.     

Simple Sequence Repeats in the National Longitudinal Study of Adolescent Health: An Ethnically Diverse Resource for Genetic Analysis of Health and Behavior

Simple sequence repeats (SSRs) are one of the earliest available forms of genetic variation available for analysis and have been utilized in studies of neurological, behavioral, and health phenotypes. Although findings from these studies have been suggestive, their interpretation has been complicated by a variety of factors including, among others, limited power due to small sample sizes. The current report details the availability, diversity, and allele and genotype frequencies of six commonly examined SSRs in the ethnically diverse, population-based National Longitudinal Study of Adolescent Health. A total of 106,743 genotypes were generated across 15,140 participants that included four microsatellites and two di-nucleotide repeats in three dopamine genes (DAT1, DRD4, DRD5), the serotonin transporter, and monoamine oxidase A. Allele and genotype frequencies showed a complex pattern and differed significantly between populations. For both di-nucleotide repeats we observed a greater allelic diversity than previously reported. The availability of these six SSRs in a large, ethnically diverse sample with extensive environmental measures assessed longitudinally offers a unique resource for researchers interested in health and behavior.     

Identification of the designer steroid Androsta‐3,5‐diene‐7,17‐dione in a dietary supplement

A liquid chromatography‐mass spectrometry (LC–MS) screen for known anabolic‐androgenic steroids in a dietary supplement product marketed for “performance enhancement” detected an unknown compound having steroid‐like spectral characteristics. The compound was isolated using high performance liquid chromatography with ultraviolet detection (HPLC–UV) coupled with an analytical scale fraction collector. After the compound was isolated, it was then characterized using gas chromatography with simultaneous Fourier Transform infrared detection and mass spectrometry (GC–FT–IR–MS), liquid chromatography–high resolution accurate mass–mass spectrometry (LC–HRAM–MS) and nuclear magnetic resonance (NMR). The steroid had an accurate mass of m/z 285.1847 (error?0.57 ppm) for the protonated species [M + H]⁺, corresponding to a molecular formula of C₁₉H₂₄O₂. Based on the GC–FT–IR–MS data, NMR data, and accurate mass, the compound was identified as androsta‐3,5‐diene‐7,17‐dione. Although this is not the first reported identification of this designer steroid in a dietary supplement, the data provided adds information for identification of this compound not previously reported. This compound was subsequently detected in another dietary supplement product, which contained three additional active ingredients.     

All Men with Vasculogenic Erectile Dysfunction Require a Cardiovascular Workup

An association between erectile dysfunction and cardiovascular disease has long been recognized, and studies suggest that erectile dysfunction is an independent marker of cardiovascular disease risk. Therefore, assessment and management of erectile dysfunction may help identify and reduce the risk of future cardiovascular events, particularly in younger men. The initial erectile dysfunction evaluation should distinguish between predominantly vasculogenic erectile dysfunction and erectile dysfunction of other etiologies. For men believed to have predominantly vasculogenic erectile dysfunction, we recommend that initial cardiovascular risk stratification be based on the Framingham Risk Score. Management of men with erectile dysfunction who are at low risk for cardiovascular disease should focus on risk-factor control; men at high risk, including those with cardiovascular symptoms, should be referred to a cardiologist. Intermediate-risk men should undergo noninvasive evaluation for subclinical atherosclerosis. A growing body of evidence supports the use of emerging prognostic markers to further understand cardiovascular risk in men with erectile dysfunction, but few markers have been prospectively evaluated in this population. In conclusion, we support cardiovascular risk stratification and risk-factor management in all men with vasculogenic erectile dysfunction.