Surveillance of congenital Zika syndrome in England and Wales: methods and results of laboratory, obstetric and paediatric surveillance.

The spread of the Zika virus (ZIKV) in the Americas led to large outbreaks across the region and most of the Southern hemisphere. Of greatest concern were complications following acute infection during pregnancy. At the beginning of the outbreak, the risk to unborn babies and their clinical presentation was unclear. This report describes the methods and results of the UK surveillance response to assess the risk of ZIKV to children born to returning travellers. Established surveillance systems operating within the UK - the paediatric and obstetric surveillance units for rare diseases, and national laboratory monitoring - enabled rapid assessment of this emerging public health threat. A combined total of 11 women experiencing adverse pregnancy outcomes after possible ZIKV exposure were reported by the three surveillance systems; five miscarriages, two intrauterine deaths and four children with clinical presentations potentially associated with ZIKV infection. Sixteen women were diagnosed with ZIKV during pregnancy in the UK. Amongst the offspring of these women, there was unequivocal laboratory evidence of infection in only one child. In the UK, the number and risk of congenital ZIKV infection for travellers returning from ZIKV-affected countries is very small

How Does Cryotherapy Effect Ankle Proprioception in Healthy Individuals?

Objectives: To investigate how a 15 minute Cryotherapy intervention effects proprioception by measuring Joint positional Sense (JPS) and static single legged balance. Design: Repeated measures design. Setting: Laboratory. Participants: Eighteen healthy university sports team students (11 males, 7 females) aged between 20-21 years. Main Outcome Measures: Participants were treated with 15 minutes Aircast Cryo-cuff. The subject’s skin temperature was measured before and immediately after 15 minutes Cryotherapy treatment. Ankle active joint positional sense (A-JPS) and passive joint positional sense (P-JPS) was measured at pre-test, immediately post-test and 5 minutes post-test. Static balance was measured by Centre of Pressure (CoP) mean path length, medial-lateral (ML) CoP mean Deviation and anterior-posterior (AP) CoP mean Deviation and mean time-to-boundary (TtB) Minima for AP and ML directions. Results: No significant differences found for the variables of JPS and static single balance testing after 15 minutes Cryotherapy treatment. However, mean differences for CoP mean path length and ML mean deviation were shown to improve following Cryotherapy treatment, results not previously found in the literature. Conclusion: Results suggest that 15 minute Cryo-cuff treatment doesn’t significantly affect proprioception. Although the effect of Cryotherapy on proprioception depends on cooling modality used, time frame applied and joint applied to

Lipid-soluble Vitamins A, D, and E in HIV-Infected Pregnant women in Tanzania.

There is limited published research examining lipid-soluble vitamins in human immunodeficiency virus (HIV)-infected pregnant women, particularly in resource-limited settings. This is an observational analysis of 1078 HIV-infected pregnant women enrolled in a trial of vitamin supplementation in Tanzania. Baseline data on sociodemographic and anthropometric characteristics, clinical signs and symptoms, and laboratory parameters were used to identify correlates of low plasma vitamin A (<0.7 micromol/l), vitamin D (<80 nmol/l) and vitamin E (<9.7 micromol/l) status. Binomial regression was used to estimate risk ratios and 95% confidence intervals. Approximately 35, 39 and 51% of the women had low levels of vitamins A, D and E, respectively. Severe anemia (hemoglobin <85 g/l; P<0.01), plasma vitamin E (P=0.02), selenium (P=0.01) and vitamin D (P=0.02) concentrations were significant correlates of low vitamin A status in multivariate models. Erythrocyte Sedimentation Rate (ESR) was independently related to low vitamin A status in a nonlinear manner (P=0.01). The correlates of low vitamin D status were CD8 cell count (P=0.01), high ESR (ESR >81 mm/h; P<0.01), gestational age at enrollment (nonlinear; P=0.03) and plasma vitamins A (P=0.02) and E (P=0.01). For low vitamin E status, the correlates were money spent on food per household per day (P<0.01), plasma vitamin A concentration (nonlinear; P<0.01) and a gestational age <16 weeks at enrollment (P<0.01). Low concentrations of lipid-soluble vitamins are widely prevalent among HIV-infected women in Tanzania and are correlated with other nutritional insufficiencies. Identifying HIV-infected persons at greater risk of poor nutritional status and infections may help inform design and implementation of appropriate interventions

Protein and lipid kinase inhibitors as targeted anticancer agents of the Ras/Raf/MEK and PI3K/PKB pathways

The identification and characterization of the components of individual signal transduction cascades, and advances in our understanding on how these biological signals are integrated in cancer initiation and progression, have provided new strategies for therapeutic intervention in solid tumors and hematological malignancies. To this end, pharmaceutical efforts have been directed to target different components of the Ras/Raf/MEK and PI3K/PKB pathways. This review article covers recent salient achievements in the identification and development of Raf, MEK, and PI3K inhibitors

A new framework for designing programmes of assessment

Research on assessment in medical education has strongly focused on individual measurement instruments and their psychometric quality. Without detracting from the value of this research, such an approach is not sufficient to high quality assessment of competence as a whole. A programmatic approach is advocated which presupposes criteria for designing comprehensive assessment programmes and for assuring their quality. The paucity of research with relevance to programmatic assessment, and especially its development, prompted us to embark on a research project to develop design principles for programmes of assessment. We conducted focus group interviews to explore the experiences and views of nine assessment experts concerning good practices and new ideas about theoretical and practical issues in programmes of assessment. The discussion was analysed, mapping all aspects relevant for design onto a framework, which was iteratively adjusted to fit the data until saturation was reached. The overarching framework for designing programmes of assessment consists of six assessment programme dimensions: Goals, Programme in Action, Support, Documenting, Improving and Accounting. The model described in this paper can help to frame programmes of assessment; it not only provides a common language, but also a comprehensive picture of the dimensions to be covered when formulating design principles. It helps identifying areas concerning assessment in which ample research and development has been done. But, more importantly, it also helps to detect underserved areas. A guiding principle in design of assessment programmes is fitness for purpose. High quality assessment can only be defined in terms of its goals

IL-4 Amplifies the Pro-Inflammatory Effect of Adenosine in Human Mast Cells by Changing Expression Levels of Adenosine Receptors

Adenosine inhalation produces immediate bronchoconstriction in asthmatics but not in normal subjects. The bronchospastic effect of adenosine is largely mediated through adenosine-induced mast cell activation, the mechanism of which is poorly understood due to limitations in culturing human primary mast cells. Here, we show that human umbilical cord blood -derived mast cells incubated with the Th2 cytokine IL-4 develop increased sensitivity to adenosine. Potentiation of anti-IgE- induced and calcium ionophore/PMA-induced degranulation was augmented in mast cells cultured with IL-4, and this effect was reduced or abolished by pre-treatment with A2BsiRNA and selective A2B receptor antagonists, respectively. IL-4 incubation resulted in the increased expression of A2B and reduced expression of A2A adenosine receptors on human mast cells. These results suggest that Th2 cytokines in the asthmatic lung may alter adenosine receptor expression on airway mast cells to promote increased responsiveness to adenosine

Membrane Docking Geometry of GRP1 PH Domain Bound to a Target Lipid Bilayer: An EPR Site-Directed Spin-Labeling and Relaxation Study

The second messenger lipid PIP3 (phosphatidylinositol-3,4,5-trisphosphate) is generated by the lipid kinase PI3K (phosphoinositide-3-kinase) in the inner leaflet of the plasma membrane, where it regulates a broad array of cell processes by recruiting multiple signaling proteins containing PIP3-specific pleckstrin homology (PH) domains to the membrane surface. Despite the broad importance of PIP3-specific PH domains, the membrane docking geometry of a PH domain bound to its target PIP3 lipid on a bilayer surface has not yet been experimentally determined. The present study employs EPR site-directed spin labeling and relaxation methods to elucidate the membrane docking geometry of GRP1 PH domain bound to bilayer-embedded PIP3. The model target bilayer contains the neutral background lipid PC and both essential targeting lipids: (i) PIP3 target lipid that provides specificity and affinity, and (ii) PS facilitator lipid that enhances the PIP3 on-rate via an electrostatic search mechanism. The EPR approach measures membrane depth parameters for 18 function-retaining spin labels coupled to the PH domain, and for calibration spin labels coupled to phospholipids. The resulting depth parameters, together with the known high resolution structure of the co-complex between GRP1 PH domain and the PIP3 headgroup, provide sufficient constraints to define an optimized, self-consistent membrane docking geometry. In this optimized geometry the PH domain engulfs the PIP3 headgroup with minimal bilayer penetration, yielding the shallowest membrane position yet described for a lipid binding domain. This binding interaction displaces the PIP3 headgroup from its lowest energy position and orientation in the bilayer, but the headgroup remains within its energetically accessible depth and angular ranges. Finally, the optimized docking geometry explains previous biophysical findings including mutations observed to disrupt membrane binding, and the rapid lateral diffusion observed for PIP3-bound GRP1 PH domain on supported lipid bilayers

Predictors of nurses’ and midwives’ intentions to provide maternal and child healthcare services to adolescents in South Africa

BACKGROUND: Adolescent mothers are at a much higher risk for maternal mortality compared to mothers aged 20 years and above. Newborns born to adolescent mothers are also more likely to have low birth weight, with the risk of long-term effects such as early onset of adult diabetes than newborns of older mothers. Few studies have investigated the determinants of adequate quality maternal and child healthcare services to pregnant adolescents. This study was conducted to gain an understanding of nurses’ and midwives’ intentions to provide maternal and child healthcare and family planning services to adolescents in South Africa. METHODS: A total of 190 nurses and midwives completed a cross-sectional survey. The survey included components on demographics, knowledge of maternal and child healthcare (MCH) and family planning (FP) services, attitude towards family planning services, subjective norms regarding maternal and child healthcare and family planning services, self-efficacy with maternal and child healthcare and family planning services, and intentions to provide maternal and child healthcare and family planning services to adolescents. Pearson’s correlation analysis was conducted to determine the association between knowledge, attitude, subjective norms, self-efficacy, and intention variables for FP and MCH services. A 2-step linear regression analysis was then conducted for both FP and MCH services to predict the intentions to provide FP and MCH services to adolescents. RESULTS: Self-efficacy to conduct MCH services (β = 0.55, p < 0.01) and years of experience as a nurse- midwife (β = 0.14, p < 0.05) were associated with stronger intentions to provide the services. Self-efficacy to provide FP services (β = 0.30, p < 0.01) was associated with stronger intentions to provide FP services. CONCLUSIONS: Self-efficacy has a strong and positive association with the intentions to provide both MCH and FP services, while there is a moderate association with attitude and norms. There is a need to improve and strengthen nurses’ and midwives’ self-efficacy in conducting both MCH and FP services in order to improve the quality and utilization of the services by adolescents in South Africa.IS

Experiences of mental illness stigma, prejudice and discrimination: A review of measures

Background: There has been a substantial increase in research on mental illness related stigma over the past 10 years, with many measures in use. This study aims to review current practice in the survey measurement of mental illness stigma, prejudice and discrimination experienced by people who have personal experience of mental illness. We will identify measures used, their characteristics and psychometric properties. Method. A narrative literature review of survey measures of mental illness stigma was conducted. The databases Medline, PsychInfo and the British Nursing Index were searched for the period 1990-2009. Results: 57 studies were included in the review. 14 survey measures of mental illness stigma were identified. Seven of the located measures addressed aspects of perceived stigma, 10 aspects of experienced stigma and 5 aspects of self-stigma. Of the identified studies, 79% used one of the measures of perceived stigma, 46% one of the measures of experienced stigma and 33% one of the measures of self-stigma. All measures presented some information on psychometric properties. Conclusions: The review was structured by considering perceived, experienced and self stigma as separate but related constructs. It provides a resource to aid researchers in selecting the measure of mental illness stigma which is most appropriate to their purpose. © 2010 Brohan et al; licensee BioMed Central Ltd

Role of the Endogenous Antioxidant System in the Protection of Schistosoma mansoni Primary Sporocysts against Exogenous Oxidative Stress

Antioxidants produced by the parasite Schistosoma mansoni are believed to be involved in the maintenance of cellular redox balance, thus contributing to larval survival in their intermediate snail host, Biomphalaria glabrata. Here, we focused on specific antioxidant enzymes, including glutathione-S-transferases 26 and 28 (GST26 and 28), glutathione peroxidase (GPx), peroxiredoxin 1 and 2 (Prx1 and 2) and Cu/Zn superoxide dismutase (SOD), known to be involved in cellular redox reactions, in an attempt to evaluate their endogenous antioxidant function in the early-developing primary sporocyst stage of S. mansoni. Previously we demonstrated a specific and consistent RNA interference (RNAi)-mediated knockdown of GST26 and 28, Prx1 and 2, and GPx transcripts, and an unexpected elevation of SOD transcripts in sporocysts treated with gene-specific double-stranded (ds)RNA. In the present followup study, in vitro transforming sporocysts were exposed to dsRNAs for GST26 and 28, combined Prx1/2, GPx, SOD or green-fluorescent protein (GFP, control) for 7 days in culture, followed by assessment of the effects of specific dsRNA treatments on protein levels using semi-quantitative Western blot analysis (GST26, Prx1/2 only), and larval susceptibility to exogenous oxidative stress in in vitro killing assays. Significant decreases (80% and 50%) in immunoreactive GST26 and Prx1/2, respectively, were observed in sporocysts treated with specific dsRNA, compared to control larvae treated with GFP dsRNA. Sporocysts cultured with dsRNAs for GST26, GST28, Prx1/2 and GPx, but not SOD dsRNA, were significantly increased in their susceptibility to H2O2 oxidative stress (60–80% mortalities at 48 hr) compared to GFP dsRNA controls (∼18% mortality). H2O2-mediated killing was abrogated by bovine catalase, further supporting a protective role for endogenous sporocyst antioxidants. Finally, in vitro killing of S. mansoni sporocysts by hemocytes of susceptible NMRI B. glabrata snails was increased in larvae treated with Prx1/2, GST26 and GST28 dsRNA, compared to those treated with GFP or SOD dsRNAs. Results of these experiments strongly support the hypothesis that endogenous expression and regulation of larval antioxidant enzymes serve a direct role in protection against external oxidative stress, including immune-mediated cytotoxic reactions. Moreover, these findings illustrate the efficacy of a RNAi-type approach in investigating gene function in larval schistosomes