Variation at the capsule locus, cps, of mistyped and non-typable Streptococcus pneumoniae isolates

The capsule polysaccharide locus (cps) is the site of the capsule biosynthesis gene cluster in encapsulated Streptococcus pneumoniae. A set of pneumococcal samples and non-pneumococcal streptococci from Denmark, the Gambia, the Netherlands, Thailand, the UK and the USA were sequenced at the cps locus to elucidate serologically mistyped or non-typable isolates. We identified a novel serotype 33B/33C mosaic capsule cluster and previously unseen serotype 22F capsule genes, disrupted and deleted cps clusters, the presence of aliB and nspA genes that are unrelated to capsule production, and similar genes in the non-pneumococcal samples. These data provide greater understanding of diversity at a locus which is crucial to the antigenic diversity of the pathogen and current vaccine strategies

New Fathers' Perinatal Depression and Anxiety-Treatment Options: An Integrative Review.

More than 10% of fathers experience depression and anxiety during the perinatal period, but paternal perinatal depression (PPND) and anxiety have received less attention than maternal perinatal mental health problems. Few mainstream treatment options are available for men with PPND and anxiety. The aim of this literature review was to summarize the current understanding of PPND and the treatment programs specifically designed for fathers with perinatal depression. Eight electronic databases were searched using a predefined strategy, and reference lists were also hand searched. PPND and anxiety were identified to have a negative impact on family relationships, as well as the health of mothers and children. Evidence suggests a lack of support and tailored treatment options for men having trouble adjusting to the transition to fatherhood. Of the limited options available, cognitive behavioral therapy, group work, and blended delivery programs, including e-support approaches appear to be most effective in helping fathers with perinatal depression and anxiety. The review findings have important implications for the understanding of PPND and anxiety. Future research is needed to address the adoption of father-inclusive and father-specific models of care to encourage fathers' help-seeking behavior. Inclusion of male-specific requirements into support and treatment options can improve the ability of services to engage new fathers. Psychotherapeutic intervention could assist to address the cognitive differences and dissonance for men adjusting to the role of father, including male identity and role expectations

An XMM-Newton observation of the extreme Narrow Line Seyfert 1 Galaxy, Mrk 359

We present XMM-Newton observations of Mrk 359, the first Narrow Line Seyfert 1 galaxy discovered. Even among NLS1s, Mrk 359 is an extreme case with extraordinarily narrow optical emission lines. The XMM-Newton data show that Mrk 359 has a significant soft X-ray excess which displays only weak absorption and emission features. The (2-10) keV continuum, including reflection, is flatter than the typical NLS1, with Gamma approximately 1.84. A strong emission line of equivalent width approximately 200 eV is also observed, centred near 6.4 keV. We fit this emission with two line components of approximately equal strength: a broad iron-line from an accretion disc and a narrow, unresolved core. The unresolved line core has an equivalent width of approximately 120 eV and is consistent with fluorescence from neutral iron in distant reprocessing gas, possibly in the form of a `molecular torus'. Comparison of the narrow-line strengths in Mrk 359 and other low-moderate luminosity Seyfert 1 galaxies with those in QSOs suggests that the solid angle subtended by the distant reprocessing gas decreases with increasing AGN luminosity.Comment: Accepted for publication in MNRA

Divergent trajectories of cellular bioenergetics, intermediary metabolism and systemic redox status in survivors and non-survivors of critical illness.

BACKGROUND: Numerous pathologies result in multiple-organ failure, which is thought to be a direct consequence of compromised cellular bioenergetic status. Neither the nature of this phenotype nor its relevance to survival are well understood, limiting the efficacy of modern life-support. METHODS: To explore the hypothesis that survival from critical illness relates to changes in cellular bioenergetics, we combined assessment of mitochondrial respiration with metabolomic, lipidomic and redox profiling in skeletal muscle and blood, at multiple timepoints, in 21 critically ill patients and 12 reference patients. RESULTS: We demonstrate an end-organ cellular phenotype in critical illness, characterized by preserved total energetic capacity, greater coupling efficiency and selectively lower capacity for complex I and fatty acid oxidation (FAO)-supported respiration in skeletal muscle, compared to health. In survivors, complex I capacity at 48 h was 27% lower than in non-survivors (p = 0.01), but tended to increase by day 7, with no such recovery observed in non-survivors. By day 7, survivors' FAO enzyme activity was double that of non-survivors (p = 0.048), in whom plasma triacylglycerol accumulated. Increases in both cellular oxidative stress and reductive drive were evident in early critical illness compared to health. Initially, non-survivors demonstrated greater plasma total antioxidant capacity but ultimately higher lipid peroxidation compared to survivors. These alterations were mirrored by greater levels of circulating total free thiol and nitrosated species, consistent with greater reductive stress and vascular inflammation, in non-survivors compared to survivors. In contrast, no clear differences in systemic inflammatory markers were observed between the two groups. CONCLUSION: Critical illness is associated with rapid, specific and coordinated alterations in the cellular respiratory machinery, intermediary metabolism and redox response, with different trajectories in survivors and non-survivors. Unravelling the cellular and molecular foundation of human resilience may enable the development of more effective life-support strategies

Delivery of chlamydia screening to young women requesting emergency hormonal contraception at pharmacies in Manchester, UK: a prospective study

<p>Abstract</p> <p>Background</p> <p>More women are requesting Emergency Hormonal Contraception (EHC) at pharmacies where screening for <it>Chlamydia trachomatis </it>is not routinely offered. The objective of this study was to assess the uptake of free postal chlamydia screening by women under 25 years who requested EHC at pharmacies in Manchester, UK.</p> <p>Methods</p> <p>Six Primary Care Trusts (PCTs) that had contracted with pharmacies to provide free EHC, requested the largest EHC providers (≥ 40 doses annually) to also offer these clients a coded chlamydia home testing kit. Pharmacies kept records of the ages and numbers of women who accepted or refused chlamydia kits. Women sent urine samples directly to the laboratory for testing and positive cases were notified. Audit data on EHC coverage was obtained from PCTs to assess the proportion of clients eligible for screening and to verify the uptake rate.</p> <p>Results</p> <p>33 pharmacies participated. Audit data for 131 pharmacy months indicated that only 24.8% (675/2718) of women provided EHC were also offered chlamydia screening. Based on tracking forms provided by pharmacies for the whole of the study, 1348/2904 EHC clients (46.4%) who had been offered screening accepted a screening kit. 264 (17.6%) of those who accepted a kit returned a sample, of whom 24 (9.1%) were chlamydia-positive. There was an increase in chlamydia positivity with age (OR: 1.2 per year; 1.04 to 1.44; p = 0.015).</p> <p>Conclusion</p> <p>Chlamydia screening for EHC pharmacy clients is warranted but failure of pharmacists to target all EHC clients represented a missed opportunity for treating a well defined high-risk group.</p

Capturing the essence of folding and functions of biomolecules using Coarse-Grained Models

The distances over which biological molecules and their complexes can function range from a few nanometres, in the case of folded structures, to millimetres, for example during chromosome organization. Describing phenomena that cover such diverse length, and also time scales, requires models that capture the underlying physics for the particular length scale of interest. Theoretical ideas, in particular, concepts from polymer physics, have guided the development of coarse-grained models to study folding of DNA, RNA, and proteins. More recently, such models and their variants have been applied to the functions of biological nanomachines. Simulations using coarse-grained models are now poised to address a wide range of problems in biology.Comment: 37 pages, 8 figure

Pneumococcal carriage in sub-Saharan Africa--a systematic review.

BACKGROUND: Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era. METHODS: A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region. RESULTS: Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6-70.8) in children less than 5 years, 42.6% (95% CI: 29.9-55.4) in children 5-15 years and 28.0% (95% CI: 19.0-37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9-24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes. CONCLUSION: Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination

MDCK Cystogenesis Driven by Cell Stabilization within Computational Analogues

The study of epithelial morphogenesis is fundamental to increasing our understanding of organ function and disease. Great progress has been made through study of culture systems such as Madin-Darby canine kidney (MDCK) cells, but many aspects of even simple morphogenesis remain unclear. For example, are specific cell actions tightly coupled to the characteristics of the cell's environment or are they more often cell state dependent? How does the single lumen, single cell layer cyst consistently emerge from a variety of cell actions? To improve insight, we instantiated in silico analogues that used hypothesized cell behavior mechanisms to mimic MDCK cystogenesis. We tested them through in vitro experimentation and quantitative validation. We observed novel growth patterns, including a cell behavior shift that began around day five of growth. We created agent-oriented analogues that used the cellular Potts model along with an Iterative Refinement protocol. Following several refinements, we achieved a degree of validation for two separate mechanisms. Both survived falsification and achieved prespecified measures of similarity to cell culture properties. In silico components and mechanisms mapped to in vitro counterparts. In silico, the axis of cell division significantly affects lumen number without changing cell number or cyst size. Reducing the amount of in silico luminal cell death had limited effect on cystogenesis. Simulations provide an observable theory for cystogenesis based on hypothesized, cell-level operating principles

Understanding psychiatric institutionalization: a conceptual review

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