Ebola Virus Persistence in Semen of Male Survivors

We investigated the duration of Ebola virus (EBOV) RNA and infectious EBOV in semen specimens of 5 Ebola virus disease (EVD) survivors. EBOV RNA and infectious EBOV was detected by real-time RT-PCR and virus culture out to 290 days and 70 days, respectively, after EVD onset

MRI identifies plantar plate pathology in the forefoot of patients with rheumatoid arthritis

Previous cadaveric studies have suggested that forefoot deformities at the metatarsophalangeal (MTP) joints in patients with rheumatoid arthritis (RA) might result from the failure of the ligamentous system and displacement of the plantar plates. This study aimed to examine the relationship between plantar plate pathology and the rheumatoid arthritis magnetic resonance imaging score (RAMRIS) of the lesser (second to fifth) MTP joints in patients with RA using high-resolution 3 T magnetic resonance imaging (MRI). In 24 patients with RA, the forefoot was imaged using 3 T MRI. Proton density fat-suppressed, T2-weighted fat-suppressed and T1-weighted post gadolinium sequences were acquired through 96 lesser MTP joints. Images were scored for synovitis, bone marrow oedema and bone erosion using the RAMRIS system and the plantar plates were assessed for pathology. Seventeen females and 7 males with a mean age of 55.5 years (range 37–71) and disease duration of 10.6 years (range 0.6–36) took part in the study. Plantar plate pathology was most frequently demonstrated on MRI at the fifth MTP joint. An association was demonstrated between plantar plate pathology and RAMRIS-reported synovitis, bone marrow oedema and bone erosion at the fourth and fifth MTP joints. In patients with RA, 3 T MRI demonstrates that plantar plate pathology at the lesser MTP joints is associated with features of disease severity. Plantar plate pathology is more common at the fourth and fifth MTP joints in subjects with RA in contrast to the predilection for the second MTP reported previously in subjects without RA

Organotypic Culture of Physiologically Functional Adult Mammalian Retinas

BACKGROUND: The adult mammalian retina is an important model in research on the central nervous system. Many experiments require the combined use of genetic manipulation, imaging, and electrophysiological recording, which make it desirable to use an in vitro preparation. Unfortunately, the tissue culture of the adult mammalian retina is difficult, mainly because of the high energy consumption of photoreceptors. METHODS AND FINDINGS: We describe an interphase culture system for adult mammalian retina that allows for the expression of genes delivered to retinal neurons by particle-mediated transfer. The retinas retain their morphology and function for up to six days— long enough for the expression of many genes of interest—so that effects upon responses to light and receptive fields could be measured by patch recording or multielectrode array recording. We show that a variety of genes encoding pre- and post-synaptic marker proteins are localized correctly in ganglion and amacrine cells. CONCLUSIONS: In this system the effects on neuronal function of one or several introduced exogenous genes can be studied within intact neural circuitry of adult mammalian retina. This system is flexible enough to be compatible with genetic manipulation, imaging, cell transfection, pharmacological assay, and electrophysiological recordings

Cross-sectional analysis of baseline differences of candidates for rotator cuff surgery: a sex and gender perspective

<p>Abstract</p> <p>Background</p> <p>The word "sex" refers to biological differences between men and women. Gender refers to roles, behaviors, activities, and attributes that a given society considers appropriate for men and women. Traditionally, treatment decisions have been based on patient's sex without including the gender. Assessment of disability secondary to musculoskeletal problems would not be complete or accurate unless potentially relevant biological and non-biological aspects of being a man or woman are taken into consideration. The purposes of this study were to: 1) investigate the difference in pre-operative characteristics between men and women who were candidates for rotator cuff surgery; and, 2) assess the relationship between level of disability and factors that represent sex and factors that signify gender.</p> <p>Method</p> <p>This was a cross-sectional study. The primary outcome measure of disability was a disease-specific outcome measure, the Western Ontario Rotator Cuff (WORC) index, and independent variables were sex, age, hand dominance, shoulder side involvement, BMI, co-morbidity, medication use, work status, smoking habits, strength, range of motion, level of pathology, concurrent osteoarthritis, expectations for recovery, and participation restriction. Parametric, non-parametric, univariable, subgroup, and multivariable analyses were conducted.</p> <p>Results</p> <p>One hundred and seventy patients were included in the study. The mean age was 57 ± 11, 85 were females. Women reported higher levels of disability despite similar or lower levels of pathology. Scores of the WORC were strongly influenced by factors that represented "gender" such as participation restriction (F = 28.91, p < 0.0001) and expectations for improved activities of daily living (F = 5.80, p = 0.004). Painfree combined range of motion, which represented an interaction between "sex" and "gender" was also associated with disability after being adjusted for all other relevant baseline factors (F = 25.82, p < 0.0001).</p> <p>Conclusion</p> <p>Gender-related factors such as expectations and participation limitations have an independent impact on disability in men and women undergoing rotator cuff related surgery.</p

A Combination of Independent Transcriptional Regulators Shapes Bacterial Virulence Gene Expression during Infection

Transcriptional regulatory networks are fundamental to how microbes alter gene expression in response to environmental stimuli, thereby playing a critical role in bacterial pathogenesis. However, understanding how bacterial transcriptional regulatory networks function during host-pathogen interaction is limited. Recent studies in group A Streptococcus (GAS) suggested that the transcriptional regulator catabolite control protein A (CcpA) influences many of the same genes as the control of virulence (CovRS) two-component gene regulatory system. To provide new information about the CcpA and CovRS networks, we compared the CcpA and CovR transcriptomes in a serotype M1 GAS strain. The transcript levels of several of the same genes encoding virulence factors and proteins involved in basic metabolic processes were affected in both ΔccpA and ΔcovR isogenic mutant strains. Recombinant CcpA and CovR bound with high-affinity to the promoter regions of several co-regulated genes, including those encoding proteins involved in carbohydrate and amino acid metabolism. Compared to the wild-type parental strain, ΔccpA and ΔcovRΔccpA isogenic mutant strains were significantly less virulent in a mouse myositis model. Inactivation of CcpA and CovR alone and in combination led to significant alterations in the transcript levels of several key GAS virulence factor encoding genes during infection. Importantly, the transcript level alterations in the ΔccpA and ΔcovRΔccpA isogenic mutant strains observed during infection were distinct from those occurring during growth in laboratory medium. These data provide new knowledge regarding the molecular mechanisms by which pathogenic bacteria respond to environmental signals to regulate virulence factor production and basic metabolic processes during infection

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury

Three Years after Legalization of Nonprescription Pharmacy Syringe Sales in California: Where Are We Now?

In January 2005, passage of California Senate Bill 1159 enabled California’s county or city governments to establish disease prevention demonstration projects (DPDPs) through which pharmacies could subsequently register to legally sell up to 10 syringes to adults without a prescription. California’s 61 local health jurisdictions (LHJs) were surveyed annually in 2005–2007 to monitor the progress of DPDP implementation and assess program coverage, facilitators, and barriers. Completed surveys were returned by mail, fax, e-mail, phone, or internet. We analyzed 2007 survey data to describe current DPDP status; data from all years were analyzed for trends in approval and implementation status. By 2007, 17 (27.9%) LHJs approved DPDPs, of which 14 (82.4%) had registered 532 (17.8%) of the 2,987 pharmacies in these 14 LHJs. Although only three LHJs added DPDPs since 2006, the number of registered pharmacies increased 102% from 263 previously reported. Among the LHJs without approved DPDPs in 2007, one (2.3%) was in the approval process, seven (16.3%) planned to seek approval, and 35 (81.4%) reported no plans to seek approval. Of 35 LHJs not planning to seek approval, the top four reasons were: limited health department time (40%) or interest (34%), pharmacy disinterest (31%), and law enforcement opposition (26%). Among eight LHJs pursuing approval, the main barriers were “time management” (13%), educating stakeholders (13%), and enlisting pharmacy participation (13%). The17 LHJs with DPDP represent 52% of California’s residents; they included 62% of persons living with HIV and 59% of IDU-related HIV cases, suggesting that many LHJs with significant numbers of HIV cases have approved DPDPs. Outcome studies are needed to determine whether SB 1159 had the desired impact on increasing syringe access and reducing blood-borne viral infection risk among California IDUs

Analysis of Microsatellite Variation in Drosophila melanogaster with Population-Scale Genome Sequencing

Genome sequencing technologies promise to revolutionize our understanding of genetics, evolution, and disease by making it feasible to survey a broad spectrum of sequence variation on a population scale. However, this potential can only be realized to the extent that methods for extracting and interpreting distinct forms of variation can be established. The error profiles and read length limitations of early versions of next-generation sequencing technologies rendered them ineffective for some sequence variant types, particularly microsatellites and other tandem repeats, and fostered the general misconception that such variants are inherently inaccessible to these platforms. At the same time, tandem repeats have emerged as important sources of functional variation. Tandem repeats are often located in and around genes, and frequent mutations in their lengths exert quantitative effects on gene function and phenotype, rapidly degrading linkage disequilibrium between markers and traits. Sensitive identification of these variants in large-scale next-gen sequencing efforts will enable more comprehensive association studies capable of revealing previously invisible associations. We present a population-scale analysis of microsatellite repeats using whole-genome data from 158 inbred isolates from the Drosophila Genetics Reference Panel, a collection of over 200 extensively phenotypically characterized isolates from a single natural population, to uncover processes underlying repeat mutation and to enable associations with behavioral, morphological, and life-history traits. Analysis of repeat variation from next-generation sequence data will also enhance studies of genome stability and neurodegenerative diseases

Blood pressure self-monitoring in pregnancy: examining feasibility in a prospective cohort study

Background: Raised blood pressure (BP) affects approximately 10% of pregnancies worldwide, and a high proportion of affected women develop pre-eclampsia. This study aimed to evaluate the feasibility of self-monitoring of BP in pregnancy in women at higher risk of pre-eclampsia. Methods: This prospective cohort study of self-monitoring BP in pregnancy was carried out in two hospital trusts in Birmingham and Oxford and thirteen primary care practices in Oxfordshire. Eligible women were those defined by the UK National Institute for Health and Care Excellence (NICE) guidelines as at higher risk of pre-eclampsia. A total of 201 participants were recruited between 12 and 16 weeks of pregnancy and were asked to take two BP readings twice daily three times a week through their pregnancy. Primary outcomes were recruitment, retention and persistence of self-monitoring. Study recruitment and retention were analysed with descriptive statistics. Survival analysis was used to evaluate the persistence of self-monitoring and the performance of self-monitoring in the early detection of gestational hypertension, compared to clinic BP monitoring. Secondary outcomes were the mean clinic and self-monitored BP readings and the performance of self-monitoring in the detection of gestational hypertension and pre-eclampsia compared to clinic BP. Results: Of 201 women recruited, 161 (80%) remained in the study at 36 weeks or to the end of their pregnancy, 162 (81%) provided any home readings suitable for analysis, 148 (74%) continued to self-monitor at 20 weeks and 107 (66%) at 36 weeks. Self-monitored readings were similar in value to contemporaneous matched clinic readings for both systolic and diastolic BP. Of the 23 who developed gestational hypertension or pre-eclampsia and self-monitored, 9(39%) had a raised home BP prior to a raised clinic BP. Conclusions: Self-monitoring of BP in pregnancy is feasible and has potential to be useful in the early detection of gestational hypertensive disorders but maintaining self-monitoring throughout pregnancy requires support and probably enhanced training