Making Meaning of the Impact of Pre-Exposure Prophylaxis (PrEP) on Public Health and Sexual Culture: Narratives of Three Generations of Gay and Bisexual Men.

Pre-exposure prophylaxis (PrEP) with Truvada has emerged as an increasingly common approach to HIV prevention among gay, bisexual, and other men who have sex with men. This study examined generational differences and similarities in narrative accounts of PrEP among a diverse sample of 89 gay and bisexual men in the U.S. Over 50% of men in the older (52-59 years) and younger (18-25 years) generations endorsed positive views, compared with 32% of men in the middle (34-41 years) generation. Men in the middle cohort expressed the most negative (21%) and ambivalent (47%) views of PrEP. Thematic analysis of men's narratives revealed three central stories about the perceived impact of PrEP: (1) PrEP has a positive impact on public health by preventing HIV transmission (endorsed more frequently by men in the older and younger cohorts); (2) PrEP has a positive effect on gay and bisexual men's sexual culture by decreasing anxiety and making sex more enjoyable (endorsed more frequently by men in the middle and younger cohorts); and (3) PrEP has a negative impact on public health and sexual culture by increasing condomless, multi-partner sex (endorsed more frequently by men in the middle and younger cohorts). Results are discussed in terms of the significance of generation cohort in meanings of sexual health and culture and implications for public health approaches to PrEP promotion among gay and bisexual men.

Analyses of pig genomes provide insight into porcine demography and evolution.

For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars ∼1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.

A randomized, double-blind, placebo-controlled trial of a highly purified equine F(ab)2 antibody black widow spider antivenom.

STUDY OBJECTIVE: Black widow spider antivenom has never been tested in a randomized clinical trial, to our knowledge. We explore various efficacy measures for a novel F(ab)2 antivenom in patients with moderate to severe pain caused by black widow spider envenomation. METHODS: A randomized, placebo-controlled, double-blind, clinical trial was conducted in 12 academic emergency departments. We included patients at least 10 years old with moderate to severe latrodectism. Subjects received either a single intravenous infusion of antivenom or placebo. Pain was assessed with the visual analog scale. The primary efficacy outcome was the difference in pre- and posttreatment visual analog scale score. Prospectively defined secondary outcomes included treatment failures and time to clinically important decrease in pain. RESULTS: Twenty-four subjects were enrolled between October 2005 and October 2006; 13 were randomized to antivenom and 11 to placebo. The median change in visual analog scale at 150 minutes posttreatment was -50.0 mm (Interquartile Range [IQR] -67, -41 mm) in the antivenom treatment group and -46.0 mm (IQR -51, 0 mm) in the placebo treatment group (P=.14). There were 7 treatment failures (64%; 95% confidence interval 35% to 92%) in the placebo group and 3 (23%; 95% confidence interval 0.2% to 46%) in the antivenom group (P=.06). The median time to a clinically important decrease in pain after treatment was shorter in the antivenom group compared with the placebo group (30 minutes [IQR 30, 60 minutes] versus 90 minutes [IQR 30, 90 minutes]; P=.03). No serious adverse events or deaths were reported. CONCLUSION: Although the overall reduction in pain was similar for antivenom- and placebo-treated subjects, antivenom reduced pain more rapidly than placebo. No significant adverse events occurred in either group.

Functional connectivity reveals inefficient working memory systems in post-traumatic stress disorder.

We applied a covariance-based multivariate analysis to functional magnetic resonance imaging (fMRI) data to investigate abnormalities in working memory (WM) systems in patients with post-traumatic stress disorder (PTSD). Patients (n=13) and matched controls (n=12) were scanned with fMRI while updating or maintaining trauma-neutral verbal stimuli in WM. A multivariate statistical analysis was used to investigate large-scale brain networks associated with these experimental tasks. For the control group, the first network reflected brain activity associated with WM updating and principally involved bilateral prefrontal and bilateral parietal cortex. Controls' second network was associated with WM maintenance and involved regions typically activated during storage and rehearsal of verbal material, including lateral premotor and inferior parietal cortex. In contrast, PTSD patients appeared to activate a single fronto-parietal network for both updating and maintenance tasks. This is indicative of abnormally elevated activity during WM maintenance and suggests inefficient allocation of resources for differential task demands. A second network in PTSD, which was not activated in controls, showed regions differentially activated between WM tasks, including the anterior cingulate, medial prefrontal cortex, fusiform and supplementary motor area. These activations may be linked to hyperarousal and abnormal reactivity, which are characteristic of PTSD.

USE of CLINICAL TEST CLUSTERS VERSUS ADVANCED IMAGING STUDIES in the MANAGEMENT of PATIENTS with a SUSPECTED SLAP TEAR.

BACKGROUND AND PURPOSE: The Magnetic Resonance Arthrogram (MRA) has served as the gold standard for identifying patients with possible Superior Labrum Anterior-Posterior (SLAP) lesions and are often required by orthopaedic surgeons prior to clinical evaluation. However, as the literature shows MRA sensitivity as 0.65-0.98, and specificity between 0.80-1.00, there is still room for misinterpretation of the imaging study, and potential mismanagement of a patient who may or may not exhibit a true SLAP lesion. It is proposed that by grouping a series of clinical special tests it may be possible to develop greater sensitivity in identifying a SLAP lesion, resulting in the ability to better manage this patient population, thus avoiding unnecessary and costly imaging studies and decreased referrals to surgical specialists. The purpose of this study is to examine specific combinations of SLAP lesion special tests and identify which clusters of tests have the highest sensitivity and specificities. This may allow therapists to improve the management of their patients by reliably diagnosing a SLAP lesion and referring only those who may need surgery to a physician. STUDY DESIGN: Literature review, diagnostic sensitivity/specificity outcomes. METHODS: A retrospective search of the current peer-reviewed literature was performed in an effort to identify the clinical special tests with the greatest sensitivity and specificity in identifying SLAP lesions. Based upon that search, the study was limited to five special tests: Biceps Load I, Biceps Load II, Speed's, Passive Compression, and O'Brien's tests. A multiple regression analysis was performed that looked at grouping of the tests to determine the diagnostic sensitivity/specificity when grouped. RESULTS: Obtaining positive results on three of the five special tests resulted in a sensitivity of 0.992-0.999 and a specificity of 0.992-0.999. The combination of the Biceps Load I/II and O'Brien's showed the highest sensitivity and specificity. CONCLUSION: The results indicate that a combination of at least three positive SLAP lesion tests may be clinically useful in diagnosing a shoulder SLAP lesion with greater diagnostic accuracy than those reported for MRI/MRA, thus improving patient management by referring only those who may require surgical intervention to a physician. LEVEL OF EVIDENCE: 2c, "Outcomes" Research.

The influence of primary care prescribing rates for new drugs on spontaneous reporting of adverse drug reactions.

INTRODUCTION: Adverse drug reaction (ADR) reporting makes a vital contribution to pharmacovigilance, although the factors that influence the reporting rate remain unclear. The aim of this study was to investigate whether the variation in the rate of reporting of suspected ADRs in different regions of Scotland was explained by differences in local prescribing practice and to quantify the extent of this influence. METHODS: Population and primary care prescribing data were obtained for ten geographical areas based on the 15 administrative regions of the National Health Service in Scotland. All reports of suspected ADRs received from within Scotland for 2000 and 2001 were available from the regional monitoring centre (Committee on Safety of Medicines, Scotland). The primary analysis was based on 14 medications that appeared in the 'top ten' list for the frequency of reported ADRs for either year. Reporting rates for each area were expressed both in terms of population (reports per million people) and in terms of estimated exposure to those medications in primary care (reports per 1000 prescriptions). For each analysis, the Pearson correlation coefficient between reporting and prescribing data was calculated using SPSS software. RESULTS: The 'top ten' medications accounted for 1715 of 2817 (60.9%, 95% CI 59.1, 62.7) ADR reports but only 2.2 million out of a total of 128 million primary care prescriptions (1.7%). Although there was a 3-fold geographical variation in the per-population ADR reporting rate, there was a close correlation between local reporting of ADRs and prescribing of the index medications (p = 0.66, p = 0.04, respectively). This implies that 44% of the observed variation in reporting rate can be attributed to variation in prescribing within the same population. DISCUSSION: Spontaneous ADR reporting in Scotland over the 2 years studied was highly concentrated on a small number of medications that were under intensive surveillance. Although there was a 3-fold variation in reporting rates from individual geographic areas when corrected for the size of the population, primary care prescribing data showed nearly half of this local variation in reporting rates could be explained by differences in prescribing. This study highlights the importance of considering prescribing practice when interpreting spontaneous ADR reporting data.

Influence of carrying a backpack on pelvic tilt, rotation, and obliquity in female college students.

The purpose of this investigation was to examine the influence of different methods of backpack carriage on pelvic tilt, obliquity and rotation of college-age females. Thirty subjects (mean age 22.4 years) participated in three conditions: walking without a backpack, carrying a backpack unilaterally, and carrying a backpack over both shoulders. The backpack was loaded with material that comprised 15% of the subject's body weight. Gait was analyzed using the Oxford Metrics VICON Clinical Manager system while the subject walked with no backpack, with a backpack unilaterally and bilaterally. Repeated measures analysis of variance was used to determine differences in angular motion and range of motion in pelvic tilt, rotation, and obliquity in three complete trials during the three walking conditions. Angular pelvic tilt was greatest with bilateral backpack carriage compared to unilateral carriage or walking without a backpack. Angles of pelvic obliquity and rotation were not changed across the three walking conditions. Range of motion for pelvic obliquity and rotation was significantly decreased when walking with a backpack. These results suggest that backpack carriage could cause permanent posture deviations in young female college students. More study is required to evaluate compressive forces during various walking conditions.

A systematically improved high quality genome and transcriptome of the human blood fluke Schistosoma mansoni.

Schistosomiasis is one of the most prevalent parasitic diseases, affecting millions of people in developing countries. Amongst the human-infective species, Schistosoma mansoni is also the most commonly used in the laboratory and here we present the systematic improvement of its draft genome. We used Sanger capillary and deep-coverage Illumina sequencing from clonal worms to upgrade the highly fragmented draft 380 Mb genome to one with only 885 scaffolds and more than 81% of the bases organised into chromosomes. We have also used transcriptome sequencing (RNA-seq) from four time points in the parasite's life cycle to refine gene predictions and profile their expression. More than 45% of predicted genes have been extensively modified and the total number has been reduced from 11,807 to 10,852. Using the new version of the genome, we identified trans-splicing events occurring in at least 11% of genes and identified clear cases where it is used to resolve polycistronic transcripts. We have produced a high-resolution map of temporal changes in expression for 9,535 genes, covering an unprecedented dynamic range for this organism. All of these data have been consolidated into a searchable format within the GeneDB (www.genedb.org) and SchistoDB (www.schistodb.net) databases. With further transcriptional profiling and genome sequencing increasingly accessible, the upgraded genome will form a fundamental dataset to underpin further advances in schistosome research.

Associations between three clinical assessment tools for postural stability.

STUDY DESIGN: Clinical Measurement, Correlation, Reliability OBJECTIVES: To assess the relationship between the Single Leg Balance (SLB), modified Balance Error Scoring System (mBESS), and modified Star Excursion Balance (mSEBT) tests and secondarily to assess inter-rater and test-retest reliability of these tests. BACKGROUND: Ankle sprains often result in chronic instability and dysfunction. Several clinical tests assess postural deficits as a potential cause of this dysfunction; however, limited information exists pertaining to the relationship that these tests have with one another. METHODS: Two independent examiners measured the performance of 34 healthy participants completing the SLB Test, mBESS test, and mSEBT at two different time periods. The relationship between tests was assessed using the Pearson Correlation and Fisher's Exact Tests. Inter-rater and test-retest reliability were assessed using the intraclass correlation coefficient (ICC) and Kappa statistics. RESULTS: A significant correlation (r = -0.35) was observed between the mSEBT and the mBESS. Fisher's Exact Test showed a significant association between the SLB Test and mBESS (P = .048), but no association between the SLB and mSEBT (P = 1.000). Inter-rater reliability was excellent for the mSEBT and fair for the mBESS (ICCs of .91 and .61 respectively). Excellent agreement was observed between raters for the SLB test (k = 1.00). Test-retest reliability was excellent for the mSEBT (ICC = 0.98) and fair for the mBESS (ICC = 0.74). There was poor test-retest agreement for the SLB test (k = .211). CONCLUSION: THERE WAS A SIGNIFICANT RELATIONSHIP OBSERVED BETWEEN THE SLB TEST, MBESS TEST, AND MSEBT: however; strength of association measures showed limited overlap between these tests. This suggests that these tests are interrelated but may not assess equal components of postural stability.

Chronic cigarette smoking and the microstructural integrity of white matter in healthy adults: a diffusion tensor imaging study.

Results from recent studies suggest that chronic cigarette smoking is associated with increased white matter volume in the brain as determined by in vivo neuroimaging. We used diffusion tensor imaging to examine the microstructural integrity of the white matter in 10 chronic smokers and 10 nonsmokers. All individuals were healthy, without histories of medical or psychiatric illness. Fractional anisotropy (FA) and trace were measured in the genu, body, and splenium of the corpus callosum. FA provides a measure of directional versus nondirectional water diffusion, whereas trace provides a measure of nondirectional water diffusion. Lower FA and higher trace values are considered to reflect less brain integrity. Voxel-based morphometry was used to define volumes in each of these regions of the corpus callosum. Chronic smokers exhibited significantly higher FA in the body and whole corpus callosum and a strong trend for higher FA in the splenium compared with nonsmokers. FA did not differ between groups in the genu, and neither trace nor white matter volumes differed between groups in any of the regions of interest. When subdivided by Fagerström score (low vs. high), the low Fagerström group exhibited significantly higher FA in the body of the corpus callosum compared with the high Fagerström group and the nonsmokers. These results suggest that, among healthy adults, lower exposure to cigarette smoking is associated with increased microstructural integrity of the white matter compared with either no exposure or higher exposure. Additional studies are needed to further explore differences in white matter integrity between smokers and nonsmokers.