Survey of the Factors Associated with a Woman's Choice to Have an Epidural for Labor Analgesia

Objectives. The purpose of this study was to determine the factors associated with whether a woman received an epidural in labor and to determine the main source used to obtain information about labor epidurals. Methods. Over a one-month period, we surveyed all patients who labored, the day after their delivery. We used multiple logistic regression to identify potential predictive factors after initial univariate analysis. Results. 320 women who met enrollment criteria delivered during the study period and 94% completed the study. Of the 302 patients surveyed, 80% received an epidural for labor. Univariate analysis showed the following variables were associated with whether women received an epidural (P < .01): partner preference, prior epidural, language, education, type of insurance, age, duration, and pitocin use. Using computed multiple logistic regression only partner preference and prior epidural were associated with whether women received an epidural. Conclusion. It was not surprising that a previous epidural was predictive of a patient receiving an epidural. The strong association with partner preference and epidural use suggests this is an important factor when counseling pregnant women with regard to their decision to have a labor epidural

Coxsackievirus B3 Inhibits Antigen Presentation In Vivo, Exerting a Profound and Selective Effect on the MHC Class I Pathway

Many viruses encode proteins whose major function is to evade or disable the host T cell response. Nevertheless, most viruses are readily detected by host T cells, and induce relatively strong T cell responses. Herein, we employ transgenic CD4+ and CD8+ T cells as sensors to evaluate in vitro and in vivo antigen presentation by coxsackievirus B3 (CVB3), and we show that this virus almost completely inhibits antigen presentation via the MHC class I pathway, thereby evading CD8+ T cell immunity. In contrast, the presentation of CVB3-encoded MHC class II epitopes is relatively unencumbered, and CVB3 induces in vivo CD4+ T cell responses that are, by several criteria, phenotypically normal. The cells display an effector phenotype and mature into multi-functional CVB3-specific memory CD4+ T cells that expand dramatically following challenge infection and rapidly differentiate into secondary effector cells capable of secreting multiple cytokines. Our findings have implications for the efficiency of antigen cross-presentation during coxsackievirus infection

Functional analysis of the EsaB component of the<i> Staphylococcus aureus</i> Type VII secretion system

This study was supported by the Wellcome Trust (through Investigator Award 10183/Z/15/Z to TP and through Clinical PhD studentship support to CPH through grant 104241/z/14/z), the Biotechnology and Biological Sciences Research Council and the Medical Research Council (through grants BB/H007571/1 and MR/M011224/1, respectively).Type VII secretion systems (T7SS) are found in many bacteria and secrete proteins involved in virulence and bacterial competition. In Staphylococcus aureus the small ubiquitin-like EsaB protein has been previously implicated as having a regulatory role in the production of the EsxC substrate. Here we show that in the S. aureus RN6390 strain, EsaB does not genetically regulate production of any T7 substrates or components, but is indispensable for secretion activity. Consistent with EsaB being an essential component of the T7SS, loss of either EsaB or EssC are associated with upregulation of a common set of iron acquisition genes. However, a further subset of genes were dysregulated only in the absence of EsaB. Quantitative western blotting indicates that EsaB is present at very low levels in cells. Substitution of a highly conserved threonine for alanine or arginine resulted in a loss of EsaB activity and destabilisation of the protein. Taken together our findings show that EsaB is essential for T7SS activity in RN6390.Publisher PDFPeer reviewe

Determinants of low bone mineral density in people with multiple sclerosis: Role of physical activity

Background People with multiple sclerosis (PwMS) have reduced bone mineral density (BMD), but the causes are unclear. Some factors that may cause reduced BMD in PwMS have been understudied, including physical activity, inflammation, cortisol, symptomatic fatigue, and depression. The aim of this study was to investigate factors that may uniquely contribute to reduced BMD in PwMS as compared to people without MS. We hypothesized that physical activity would be the primary determinant of low BMD in PwMS, with additional contributions from inflammation and sympathetic nervous system activation. Methods We tested 23 PwMS (16 women; median EDSS: 2) and 22 control participants (16 women). BMD was measured from the femoral neck and lumbar spine with dual x-ray absorptiometry. Disability was measured with the Expanded Disability Status Scale, and functional capacity was measured with the Multiple Sclerosis Functional Composite. Questionnaires measured symptomatic fatigue and depression. A blood draw was used to measure calcium, phosphate, vitamin D, N-terminal telopeptide, osteopontin, and cytokine markers of inflammation. Physical activity was measured with accelerometry. Salivary cortisol and cardiac heart rate variability also were obtained. All outcome variables were compared between groups with independent samples t-tests. Variables that were different between groups and significantly correlated (Pearson product-moment) with femoral neck BMD, were included in a theoretical model to explain femoral neck BMD. The expected direction of relations in the theoretical model were developed based upon the results of previous research. A Bayesian path analysis was used to test the relations of predictive variables with femoral neck BMD and interrelations among predictive variables, as detailed in the theoretical model. Results PwMS had lower BMD at the femoral neck than controls (p = =0.04; mean difference: -0.09; 95% CI: -0.2, -0.004; Cohen\u27s d = =0.65), and there was a smaller, statistically non-significant difference in BMD at the lumbar spine (p = =0.07; mean difference: -0.08; 95% CI: -0.17, 0.007; Cohen\u27s d = =0.59). PwMS also had lower functional capacity (p ≤ 0.001; Cohen\u27s d = =1.50), greater fatigue (pd = =1.88), greater depression (pd = =1.31), and decreased physical activity (p = =0.03; Cohen\u27s d = =0.62). Using path analysis to test our theoretical model, we found that disability (standardized estimate= -0.17), physical activity (standardized estimate=0.39), symptomatic fatigue (standardized estimate= -0.36), depression (standardized estimate= -0.30), and inflammatory markers (standardized estimate=0.27) explained 51% of the variance in femoral neck BMD. Inflammatory markers were also predictive of disability (standardized estimate=0.44) and physical activity (standardized estimate= -0.40). Symptomatic fatigue and depression were correlated (r = =0.64). Conclusion Physical activity, symptomatic fatigue, depression, disability, and inflammation all contributed independently to decreased femoral neck BMD in PWMS. Bone metabolism in PwMS is complex. Efforts to increase physical activity and address symptomatic fatigue and depression may improve bone mineral density in PwMS. Future research should investigate the mechanisms through which symptomatic fatigue and depression contribute to reduced BMD in PwMS

The Ess/Type VII secretion system of Staphylococcus aureus shows unexpected genetic diversity

We thank the core sequencing and informatics teams at the Sanger Institute for their assistance and The Wellcome Trust for its support of the Sanger Institute Pathogen Genomics and Biology groups. SRH, JP and MTGH were supported by Wellcome Trust grant 098051. Bioinformatics and Computational Biology analyses were supported by the University of St Andrews Bioinformatics Unit that is funded by a Wellcome Trust ISSF award (grant 105621/Z/14/Z). SP is funded by the UKCRC Translational Infection Research Initiative, and the NIHR Cambridge Biomedical Research Centre. CPH is supported by the Wellcome Trust (grant number 104241/z/14/z) TP is a Royal Society/Wolfson Merit Award Holder.BACKGROUND: Type VII protein secretion (T7SS) is a specialised system for excreting extracellular proteins across bacterial cell membranes and has been associated with virulence in Staphylococcus aureus. The genetic diversity of the ess locus, which encodes the T7SS, and the functions of proteins encoded within it are poorly understood. RESULTS: We used whole genome sequence data from 153 isolates representative of the diversity of the species to investigate the genetic variability of T7SS across S. aureus. The ess loci were found to comprise of four distinct modules based on gene content and relative conservation. Modules 1 and 4, comprising of the 5' and 3' modules of the ess locus, contained the most conserved clusters of genes across the species. Module 1 contained genes encoding the secreted protein EsxA, and the EsaAB and EssAB components of the T7SS machinery, and Module 4 contained two functionally uncharacterized conserved membrane proteins. Across the species four variants of Module 2 were identified containing the essC gene, each of which was associated with a specific group of downstream genes. The most diverse module of the ess locus was Module 3 comprising a highly variable arrangement of hypothetical proteins. RNA-Seq was performed on representatives of the four Module 2 variants and demonstrated strain-specific differences in the levels of transcription in the conserved Module 1 components and transcriptional linkage Module 2, and provided evidence of the expression of genes the variable regions of the ess loci. CONCLUSIONS: The ess locus of S. aureus exhibits modularity and organisational variation across the species and transcriptional variation. In silico analysis of ess loci encoded hypothetical proteins identified potential novel secreted substrates for the T7SS. The considerable variety in operon arrangement between otherwise closely related isolates provides strong evidence for recombination at this locus. Comparison of these recombination regions with each other, and with the genomes of other Staphylococcal species, failed to identify evidence of intra- and inter-species recombination, however the analysis identified a novel T7SS in another pathogenic staphylococci, Staphylococcus lugdunensis.Publisher PDFPeer reviewe

Biodesulfurization of dibenzothiophene and crude oil using electro-spray reactors

Biological removal of organic sulfur from petroleum feedstocks offers an attractive alternative to conventional thermochemical treatment due to the mild operating conditions afforded by the biocatalyst. In order for biodesulfurization to realize commercial success, reactors must be designed which allow for sufficient liquid / liquid and gas / liquid mass transfer while simultaneously reducing operating costs. In this study, the use of electric field contactors for the biodesulfurization of the model compound dibenzothiophene (DBT) as well as actual crude oil is investigated. The emulsion phase contactor (EPC) creates an emulsion of aqueous biocatalyst in the organic phase by concentrating forces at the liquid / liquid interface rather than imparting energy to the bulk solution as is done in impeller-based reactors. Characterization of emulsion quality and determination of rates of DBT oxidation to 2- hydroxybiphenyl (2-HBP) were performed for both batch stirred reactors (BSR) and the EPC. The EPC was capable of producing aqueous droplets of about 5 {micro}m in diameter using 3 W/L whereas the impeller-based reactor formed droplets between 100 and 200 {micro}m with comparable power consumption. The presence of electric fields was not found to adversely affect biocatalytic activity. Despite the greater surface area for reaction afforded by the EPC, rates of DBT oxidation in both reactors were similar, demonstrating that the biocatalyst used (Rhodococcus sp. IGTS8) was not active enough to be mass transport limited. The EPC is expected to have tremendous impact upon reactor operating costs and biocatalyst utilization once advances biocatalyst development provide systems that are mass transport limited