Interaction of bacteroides fragilis with host proteins and effects of nitrogen limitation on the B. fragilis transcriptome.

Bacteroides fragilis is a member of the normal microbiota that resides in the human lower gastrointestinal tract. This bacterium is of clinical significance because it is the most frequently isolated Gram-negative obligate anaerobe from peritoneal abscesses and bloodstream infections. Human fibrinogen is a hexameric-glycoprotein that is important for fibrin-mediated abscess formation and limiting the spread of infection. B. fragilis can bind and degrade fibrinogen which may aid in its escape from abscesses into the bloodstream, thereby promoting bacteraemia. In addition to fibrinogen, binding of B. fragilis to fibronectin, a component of the extracellular matrix, found in association with fibrinogen at wound sites, has also been reported. An outer membrane protein, BF1705, expressed by B. fragilis was found to share homology with BspA from Tannerella forsythia which is known to bind fibrinogen. The gene encoding BF1705 was deleted from the B. fragilis NCTC 9343 genome in the present work using a markerless gene deletion technology. Proteins derived from the outer membranes of wild-type B. fragilis were able to bind fibronectin and fibrinogen in far-western blots. Similar protein extracts from the ΔBF1705 strain did not bind fibrinogen and fibronectin, which confirms the role of BF1705 in adhesive interactions with proteins of the host extracellular matrix. The possible involvement of BF1705 in fibrinogen degradation was ruled out because the ΔBF1705 strain still degraded fibrinogen. To identify the proteases involved in degradation of fibrinogen, four genes encoding putative extracellular metallo- and serine proteases in the size range 45-50 kDa were deleted from the NCTC 9343 genome. All of the single and multiple mutants defective in these selected proteases were still capable of degrading fibrinogen as determined by zymography. Expression of eight B. fragilis proteases in E. coli did not lead to detectable degradation of fibrinogen. These observations suggest that these proteases alone cannot degrade fibrinogen and either that an unidentified protease is responsible for degradation or that there is redundancy in the proteases involved. Under conditions of nitrogen limitation bacteria resort to scavenging nitrogen from the environment to replenish the depleting intracellular nitrogen content. By examining the differential regulation of the B. fragilis transcriptome under nitrogen replete and depleting conditions, a potential role for BF1705 and secreted proteases in nutrient binding and assimilation were studied. Growth on conventional glucose defined medium with ammonia as the nitrogen source was compared to growth in defined medium with glutamine as nitrogen source. A reduced doubling time and diauxic growth in the medium containing glutamine indicated nitrogen limitation. Comparison of the transcriptome derived from cultures of B. fragilis grown on either ammonia or glutamine by RNA-Seq did not reveal a significant upregulation of BF1705 in response to nitrogen limitation. This observation in conjunction with its inability to degrade fibrinogen suggests that the primary role of BF1705 might be as an adhesin and does not act directly in nutrient binding and degradation. Nevertheless, nitrogen limitation was found to induce the expression of four protease-encoding genes by over a 2-fold (adjusted p value < 0.05). The molecular weight of three of these proteases were identified to be within the size range of 45-55 kDa which corresponded to the lysis bands detected by fibrinogen zymography with wild-type B. fragilis protein extracts. Therefore the possible involvement of these three proteases in fibrinogen degradation could be assessed. A 155-fold upregulation (adjusted p value < 0.05) in asnB, encoding a homologue of asparagine synthetase B, under conditions of nitrogen limitation suggest a previously uncharacterised aspartate metabolism pathway for ammonia generation via arginine catabolism in B. fragilis. Ammonia thus formed might aid in sustaining B. fragilis growth under nitrogen deprived conditions. In addition to nitrogen assimilation, significant upregulation was observed in the expression of genes involved in regulation of oxidative stress and metronidazole resistance. The observed changes in the transcriptome will add to our understanding of the B. fragilis metabolism and potential assist with unravelling the mechanisms of infection mediated by this important opportunistic pathogen

Effect of the quality and outcomes framework on diabetes care in the United Kingdom: retrospective cohort study

Objectives To examine the management of diabetes between 2001 and 2007 in the United Kingdom and to assess whether changes in the quality of care reflect existing temporal trends or are a direct result of the implementation of the quality and outcomes framework

Predicting the Long-Term Effects of Cardiac Resynchronization Therapy on Mortality From Baseline Variables and the Early Response A Report From the CARE-HF (Cardiac Resynchronization in Heart Failure) Trial

ObjectivesThis study was designed to investigate whether selected baseline variables and early response markers predict the effects of cardiac resynchronization therapy (CRT) on long-term mortality.BackgroundCardiac resynchronization therapy reduces long-term morbidity and mortality in patients with moderate or severe heart failure and markers of cardiac dyssynchrony, but not all patients respond to a similar extent.MethodsIn the CARE-HF (Cardiac Resynchronization in Heart Failure) study, 813 patients with heart failure and markers of cardiac dyssynchrony were randomly assigned to receive or not receive CRT in addition to pharmacological treatment and were followed for a median of 37.6 months. A model including assigned treatment, 15 pre-specified baseline variables, and 8 markers of response at 3 months was constructed to predict all-cause mortality.ResultsOn multivariable analysis, plasma concentration of amino terminal pro–brain natriuretic peptide (univariate and multivariable model chi-square test: 105.0 and 48.4; both p < 0.0001) and severity of mitral regurgitation (chi-square test: 44.0 and 17.9; both p < 0.0001) at 3 months, regardless of assigned treatment, were the strongest predictors of mortality. Ischemic heart disease as the cause of ventricular dysfunction (chi-square test: 34.9 and 7.4; p < 0.0001 and p = 0.0066), being in New York Heart Association functional class IV (chi-square test: 18.8 and 9.6; p < 0.0001 and p = 0.0020), or having less interventricular mechanical delay (chi-square test: 29.8 and 8.8; p < 0.0001 and p = 0.0029) at baseline all predicted a worse outcome. However, the reduction in mortality in patients assigned to CRT was similar before (hazard ratio: 0.602; 95% confidence interval: 0.468 to 0.774) and after (hazard ratio: 0.679; 95% confidence interval: 0.494 to 0.914) adjustment for variables measured at baseline and at 3 months.ConclusionsPatients who have more severe mitral regurgitation or persistently elevated amino terminal pro–brain natriuretic peptide despite treatment for heart failure, including CRT, have a higher mortality. However, patients assigned to CRT had a lower mortality even after adjusting for variables measured before and 3 months after intervention. The effect of CRT on mortality cannot be usefully predicted using such information. (CARE-HF CArdiac Resynchronization in Heart Failure; NCT00170300

Association of after school sedentary behaviour in adolescence with mental wellbeing in adulthood

Sedentary behaviour is associated with poorer mental health in adolescence but no studies have followed participants into mid-life. We investigated the association between after-school sedentary behaviours (screen time and homework) in adolescence with mental wellbeing in adulthood when participants were aged 42.Participants (n=2038, 59.2% female) were drawn from The 1970 British Cohort Study (BCS70). At age 16 respondents were asked separate questions about how long they spent in three types of screen based activities (TV, video films, computer games) and homework 'after school yesterday'. Mental well-being and psychological distress were assessed at the age 42 sweep in 2012 using the Warwick-Edinburgh Mental Well-being Scale (WEMWBS) and Malaise Inventory, respectively.After adjustment for all covariates, participants reporting more than 3hrs of after school screen time as an adolescent had -1.74 (95% CI, -2.65, -0.83) points on the WEMWBS compared with adults reporting less than 1 hr screen time as an adolescent. Participants that reported high screen time both at age 16 (≥3hrs/d) and age 42 (≥3hrs/d TV viewing) demonstrated even lower scores (-2.91; -4.12, -1.69). Homework was unrelated to wellbeing after adjustment for covariates. The longitudinal association between adolescent screen time and adult psychological distress was attenuated to the null after adjustment for covariates.Screen time in adolescence was inversely associated with mental wellbeing in adulthood

Anti-Diabetic Study of Flower Extract of Eugenia Jambolona In Rats

We are learning more about the role that integrated medicine plays in treating metabolic illnesses. This is partially based on an abundance of scientific data regarding therapeutic herbs, including those with promise to treat diabetes, and in part on the WHO's and other governmental organizations’ support for the practise. The anti-diabetic effect of number of flowers of Eugenia jambolana (EJA) was evaluated in the current study on streptozotocin-induced diabetic rats. The The study's primary goal was to look into the potential antidiabetic effects of sub-chronic oral administration of E. jambolana flowers infusion in rats with STZ-induced diabetes. In diabetic experimental rats, the floral extract considerably reduced blood sugar and cholesterol levels when given 400 mg/kg of body weight are the dosage. It also increased liver glycogen and total protein levels, enhanced reduced Hb1AC, serum level, and antioxidant levels, as well as impaired glucose tolerance. Additionally, it raised liver glycogen and total protein levels as well as glucose tolerance. A common hypoglycemic medication called Glibenclamide was used to compare the hypoglycemic efficacy.The preclinical investigation's results could be useful for phase 2 clinical studies that aim to reduce the morbidity and mortality of diabetes mellitus exacerbated by drug-induced hypoglycemia by implementing integrated medicine

Access to interpreting services in England: secondary analysis of national data

Background: Overcoming language barriers to health care is a global challenge. There is great linguistic diversity in the major cities in the UK with more than 300 languages, excluding dialects, spoken by children in London alone. However, there is dearth of data on the number of non-English speakers for planning effective interpreting services. The aim was to estimate the number of people requiring language support amongst the minority ethnic communities in England. Methods: Secondary analysis of national representative sample of subjects recruited to the Health Surveys for England 1999 and 2004. Results: 298,432 individuals from the four main minority ethnic communities (Indian, Pakistani, Bangladeshi and Chinese) who may be unable to communicate effectively with a health professional. This represents 2,520,885 general practice consultations per year where interpreting services might be required. Conclusion: Effective interpreting services are required to improve access and health outcomes of non-English speakers and thereby facilitate a reduction in health inequalities

Alcohol consumption and cognitive performance: a <scp>M</scp> endelian randomization study

Aims: To use Mendelian randomization to assess whether alcohol intake was causally associated with cognitive function. Design: Mendelian randomization using a genetic variant related to alcohol intake (ADH1B rs1229984) was used to obtain unbiased estimates of the association between alcohol intake and cognitive performance. Setting: Europe. Participants: More than 34000 adults. Measurements: Any versus no alcohol intake and units of intake in the previous week was measured by questionnaire. Cognitive function was assessed in terms of immediate and delayed word recall, verbal fluency and processing speed. Findings: Having consumed any versus no alcohol was associated with higher scores by 0.17 standard deviations (SD) [95% confidence interval (CI)=0.15, 0.20] for immediate recall, 0.17 SD (95% CI=0.14, 0.19) for delayed recall, 0.17 SD (95% CI=0.14, 0.19) for verbal fluency and 0.12 SD (95% CI=0.09, 0.15) for processing speed. The minor allele of rs1229984 was associated with reduced odds of consuming any alcohol (odds ratio=0.87; 95% CI=0.80, 0.95; P=0.001; R2=0.1%; F-statistic=47). In Mendelian randomization analysis, the minor allele was not associated with any cognitive test score, and instrumental variable analysis suggested no causal association between alcohol consumption and cognition: -0.74 SD (95% CI=-1.88, 0.41) for immediate recall, -1.09 SD (95% CI=-2.38, 0.21) for delayed recall, -0.63 SD (95% CI=-1.78, 0.53) for verbal fluency and -0.16 SD (95% CI=-1.29, 0.97) for processing speed. Conclusions: The Mendelian randomization analysis did not provide strong evidence of a causal association between alcohol consumption and cognitive ability

The First Global Integrated Marine Assessment: World Ocean Assessment I

We used satellite-derived sea-surface-temperature (SST) data along with in-situ data collected along a meridional transect between 18.85 and 20.25°N along 69.2°E to describe the evolution of an SST filament and front during 25 November to 1 December in the northeastern Arabian Sea (NEAS). Both features were &#8764; 100 km long, lasted about a week and were associated with weak temperature gradients (&#8764; 0.07°C km⁻¹). The in-situ data were collected first using a suite of surface sensors during a north–south mapping of this transect and showed the existence of a chlorophyll maximum within the filament. This surface data acquisition was followed by a high-resolution south–north CTD (conductivity–temperature–depth) sampling along the transect. In the two days that elapsed between the two in-situ measurements, the filament had shrunk in size and moved northward. In general, the current direction was northwestward and advected these mesoscale features. The CTD data also showed an SST front towards the northern end of the transect. In both these features, the chlorophyll concentration was higher than in the surrounding waters. The temperature and salinity data from the CTD suggest upward mixing or pumping of water from the base of the mixed layer, where a chlorophyll maximum was present, into the mixed layer that was about 60 m thick. A striking diurnal cycle was evident in the chlorophyll concentration, with higher values tending to occur closer to the surface during the night. The in-situ data from both surface sensors and CTD, and so also satellite-derived chlorophyll data, showed higher chlorophyll concentration, particularly at sub-surface levels, between the filament and the front, but there was no corresponding signature in the temperature and salinity data. Analysis of the SST fronts in the satellite data shows that fronts weaker than those associated with the filament and the front had crossed the transect in this region a day or two preceding the sampling of the front

Comparisons of depression, anxiety, well-being, and perceptions of the built environment amongst adults seeking social, intermediate and market-rent accommodation in the former London Olympic Athletes' Village.

The Examining Neighbourhood Activities in Built Living Environments in London (ENABLE London) study provides a unique opportunity to examine differences in mental health and well-being amongst adults seeking social, intermediate (affordable rent), and market-rent housing in a purpose built neighbourhood (East Village, the former London 2012 Olympic Athletes' Village), specifically designed to encourage positive health behaviours. Multi-level logistic regression models examined baseline differences in levels of depression, anxiety and well-being across the housing groups. Compared with the intermediate group, those seeking social housing were more likely to be depressed, anxious and had poorer well-being after adjustment for demographic and health status variables. Further adjustments for neighbourhood perceptions suggest that compared with the intermediate group, perceived neighbourhood characteristics may be an important determinant of depression amongst those seeking social housing, and lower levels of happiness the previous day amongst those seeking market-rent housing. These findings add to the extensive literature on inequalities in health, and provide a strong basis for future longitudinal work that will examine change in depression, anxiety and well-being after moving into East Village, where those seeking social housing potentially have the most to gain