Mediation Analysis of High Blood Pressure Targets, Arrhythmias, and Shock Mortality

International audienc

Promoting the achievement in schools of children and young people in care

As of March 2017, there were 72,670 children and young people in care in England. The number of looked after children has continued to increase steadily over the last eight years. Sixty per cent of these children are in care because of abuse or neglect and three-quarters are placed in foster care arrangements. Children and young people who are in or have experienced care remain one of the lowest performing groups in terms of educational outcomes. The average Attainment 8 score for children in care is 19.3 compared to 44.5 for non-looked after children and 19.3 for children in need. In 2017 there was an increase in the percentage of children in care achieving a pass in English and Mathematics from 17.4% to 17.5% and also in entering EBacc. Care leavers can experience poorer employment and health outcomes after leaving school compared to their peers. They are over-represented amongst the offender population and those who experience homelessness. However, research is emerging to show that children and young people in care can have very positive experiences of school if they are supported effectively to reach their full potential academically and socially. The purpose of this report is to share practice in local authorities (LA) from across England and Wales that is contributing to improved outcomes and school experiences for children and young people in care. The case studies were all undertaken as part of the Promoting the Achievement of Looked after Children (PALAC) programme between 2014 and 2017. This report presents an account of the programme, including the activities undertaken by the participants and the outcomes of the programme to date for pupils in care and staff in the participating virtual schools (VS) and local authorities

Adsorption at cell surface and cellular uptake of silica nanoparticles with different surface chemical functionalizations: impact on cytotoxicity

International audienceSilica nanoparticles are particularly interesting for medical applications because of the high inertness and chemical stability of silica material. However, at the nanoscale their innocuousness must be carefully verified before clinical use. The aim of this study was to investigate the in vitro biological toxicity of silica nanoparticles depending on their surface chemical functionalization. To that purpose, three kinds of 50 nm fluorescent silica-based nanoparticles were synthesized: 1) sterically stabilized silica nanoparticles coated with neutral polyethylene glycol (PEG) molecules, 2) positively charged silica nanoparticles coated with amine groups and 3) negatively charged silica nanoparticles coated with carboxylic acid groups. RAW 264.7 murine macrophages were incubated for 20 hours with each kind of nanoparticles. Their cellular uptake and adsorption at the cell membrane were assessed by a fluorimetric assay and cellular responses were evaluated in terms of cytotoxicity, pro-inflammatory factor production and oxidative stress. Results showed that the highly positive charged nanoparticle, were the most adsorbed at cell surface and triggered more cytotoxicity than other nanoparticles types. To conclude, this study clearly demonstrated that silica nanoparticles surface functionalization represents a key parameter in their cellular uptake and biological toxicity

In situ measurement of bovine serum albumin interaction with gold nanospheres

Here we present in situ observations of adsorption of bovine serum albumin (BSA) on citratestabilized gold nanospheres. We implemented scattering correlation spectroscopy as a tool to quantify changes in the nanoparticle Brownian motion resulting from BSA adsorption onto the nanoparticle surface. Protein binding was observed as an increase in the nanoparticle hydrodynamic radius. Our results indicate the formation of a protein monolayer at similar albumin concentrations as those found in human blood. Additionally, by monitoring the frequency and intensity of individual scattering events caused by single gold nanoparticles passing the observation volume, we found that BSA did not induce colloidal aggregation, a relevant result from the toxicological viewpoint. Moreover, to elucidate the thermodynamics of the gold nanoparticle-BSA association, we measured an adsorption isotherm which was best described by an anti-cooperative binding model. The number of binding sites based on this model was consistent with a BSA monolayer in its native state. In contrast, experiments using poly-ethylene glycol capped gold nanoparticles revealed no evidence for adsorption of BSA

Circulating Levels of Adiponectin, Leptin, Fetuin-A and Retinol-Binding Protein in Patients with Tuberculosis: Markers of Metabolism and Inflammation

BACKGROUND: Wasting is known as a prominent feature of tuberculosis (TB). To monitor the disease state, markers of metabolism and inflammation are potentially useful. We thus analyzed two major adipokines, adiponectin and leptin, and two other metabolic markers, fetuin-A and retinol-binding protein 4 (RBP4). METHODS: The plasma levels of these markers were measured using enzyme-linked immunosorbent assays in 84 apparently healthy individuals (=no-symptom group) and 46 patients with active pulmonary TB around the time of treatment, including at the midpoint evaluation (=active-disease group) and compared them with body mass index (BMI), C-reactive protein (CRP), chest radiographs and TB-antigen specific response by interferon-γ release assay (IGRA). RESULTS: In the no-symptom group, adiponectin and leptin showed negative and positive correlation with BMI respectively. In the active-disease group, at the time of diagnosis, leptin, fetuin-A and RBP4 levels were lower than in the no-symptom group [adjusted means 2.01 versus 4.50 ng/ml, P<0.0001; 185.58 versus 252.27 µg/ml, P<0.0001; 23.88 versus 43.79 µg/ml, P<0.0001, respectively]. High adiponectin and low leptin levels were associated with large infiltrates on chest radiographs even after adjustment for BMI and other covariates (P=0.0033 and P=0.0020). During treatment, adiponectin levels increased further and then decreased. Leptin levels remained low. Initial low levels of fetuin-A and RBP4 almost returned to the normal reference range in concert with reduced CRP. CONCLUSIONS: Our data and recent literature suggest that low fat store and underlying inflammation may regulate these metabolic markers in TB in a different way. Decreased leptin, increased adiponectin, or this ratio may be a promising marker for severity of the disease independent of BMI. We should further investigate pathological roles of the balance between these adipokines

Modular assembly of proteins on nanoparticles

Generally, the high diversity of protein properties necessitates the development of unique nanoparticle bio-conjugation methods, optimized for each different protein. Here we describe a universal bio-conjugation approach which makes use of a new recombinant fusion protein combining two distinct domains. The N-terminal part is Glutathione S-Transferase (GST) from Schistosoma japonicum, for which we identify and characterize the remarkable ability to bind gold nanoparticles (GNPs) by forming gold–sulfur bonds (Au–S). The C-terminal part of this multi-domain construct is the SpyCatcher from Streptococcus pyogenes, which provides the ability to capture recombinant proteins encoding a SpyTag. Here we show that SpyCatcher can be immobilized covalently on GNPs through GST without the loss of its full functionality. We then show that GST-SpyCatcher activated particles are able to covalently bind a SpyTag modified protein by simple mixing, through the spontaneous formation of an unusual isopeptide bond

Reproductive health and access to healthcare facilities: risk factors for depression and anxiety in women with an earthquake experience

<p>Abstract</p> <p>Background</p> <p>The reproductive and mental health of women contributes significantly to their overall well-being. Three of the eight Millennium Development Goals are directly related to reproductive and sexual health while mental disorders make up three of the ten leading causes of disease burden in low and middle-income countries. Among mental disorders, depression and anxiety are two of the most prevalent. In the context of slower progress in achieving Millennium Development Goals in developing countries and the ever-increasing man-made and natural disasters in these areas, it is important to understand the association between reproductive health and mental health among women with post-disaster experiences.</p> <p>Methods</p> <p>This was a cross-sectional study with a sample of 387 women of reproductive age (15-49 years) randomly selected from the October 2005 earthquake affected areas of Pakistan. Data on reproductive health was collected using the Centers for Disease Control reproductive health assessment toolkit. Depression and anxiety were measured using the Hopkins Symptom Checklist-25, while earthquake experiences were captured using the Harvard Trauma Questionnaire. The association of either depression or anxiety with socio-demographic variables, earthquake experiences, reproductive health and access to health facilities was estimated using multivariate logistic regression.</p> <p>Results</p> <p>Post-earthquake reproductive health events together with economic deprivation, lower family support and poorer access to health care facilities explained a significant proportion of differences in the experiencing of clinical levels of depression and anxiety. For instance, women losing resources for subsistence, separation from family and experiencing reproductive health events such as having a stillbirth, having had an abortion, having had abnormal vaginal discharge or having had genital ulcers, were at significant risk of depression and anxiety.</p> <p>Conclusion</p> <p>The relationship between women's post-earthquake mental health and reproductive health, socio-economic status, and health care access is complex and explained largely by the socio-cultural role of women. It is suggested that interventions that consider gender differences and that are culturally appropriate are likely to reduce the incidence.</p