The identification of Staphylococcus aureus factors required for pathogenicity and growth in human blood

Staphylococcus aureus is a human commensal but also has devastating potential as an opportunist pathogen. S. aureus bacteraemia is often associated with an adverse outcome. To identify potential targets for novel control approaches we have identified S. aureus components that are required for growth on human blood. An ordered transposon mutant library was screened, identifying 9 genes involved specifically in haemolysis or growth on human blood agar compared to the parental strain. Three genes (purA, purB and pabA) were subsequently found to be required for pathogenesis in the zebrafish embryo infection model. The pabA growth defect was specific to the red blood cell component of human blood, showing no growth difference compared to the parental strain on human serum, human plasma, sheep or horse blood. PabA is required in the tetrahydrofolate (THF) biosynthesis pathway. The pabA growth defect was found to be due to a combination of loss of THF-dependent dTMP production by the enzyme ThyA and an increased demand for pyrimidines in human blood. Our work highlights pabA and the pyrimidine salvage pathway as potential targets for novel therapeutics and suggests a previously undefined role for a human blood factor in the activity of sulphonamide antibiotics

Health screening, cardiometabolic disease and adverse health outcomes in individuals with severe mental illness

Background: Poor physical health in severe mental illness (SMI) remains a major issue for clinical practice. Aims: To use electronic health records of routinely collected clinical data to determine levels of screening for cardiometabolic disease and adverse health outcomes in a large sample (n = 7718) of patients with SMI, predominantly schizophrenia and bipolar disorder. Method: We linked data from the Glasgow Psychosis Clinical Information System (PsyCIS) to morbidity records, routine blood results and prescribing data. Results: There was no record of routine blood monitoring during the preceding 2 years for 16.9% of the cohort. However, monitoring was poorer for male patients, younger patients aged 16–44, those with schizophrenia, and for tests of cholesterol, triglyceride and glycosylated haemoglobin. We estimated that 8.0% of participants had diabetes and that lipids levels, and use of lipid-lowering medication, was generally high. Conclusions: Electronic record linkage identified poor health screening and adverse health outcomes in this vulnerable patient group. This approach can inform the design of future interventions and health policy

Impact of socioeconomic deprivation on rate and cause of death in severe mental illness

Background: Socioeconomic status has important associations with disease-specific mortality in the general population. Although individuals with Severe Mental Illnesses (SMI) experience significant premature mortality, the relationship between socioeconomic status and mortality in this group remains under investigated.<p></p> Aims: To assess the impact of socioeconomic status on rate and cause of death in individuals with SMI (schizophrenia and bipolar disorder) relative to the local (Glasgow) and wider (Scottish) populations.<p></p> Methods: Cause and age of death during 2006-2010 inclusive for individuals with schizophrenia or bipolar disorder registered on the Glasgow Psychosis Clinical Information System (PsyCIS) were obtained by linkage to the Scottish General Register Office (GRO). Rate and cause of death by socioeconomic status, measured by Scottish Index of Multiple Deprivation (SIMD), were compared to the Glasgow and Scottish populations.<p></p> Results: Death rates were higher in people with SMI across all socioeconomic quintiles compared to the Glasgow and Scottish populations, and persisted when suicide was excluded. Differences were largest in the most deprived quintile (794.6 per 10,000 population vs. 274.7 and 252.4 for Glasgow and Scotland respectively). Cause of death varied by socioeconomic status. For those living in the most deprived quintile, higher drug-related deaths occurred in those with SMI compared to local Glasgow and wider Scottish population rates (12.3% vs. 5.9%, p = <0.001 and 5.1% p = 0.002 respectively). A lower proportion of deaths due to cancer in those with SMI living in the most deprived quintile were also observed, relative to the local Glasgow and wider Scottish populations (12.3% vs. 25.1% p = 0.013 and 26.3% p = <0.001). The proportion of suicides was significantly higher in those with SMI living in the more affluent quintiles relative to Glasgow and Scotland (54.6% vs. 5.8%, p = <0.001 and 5.5%, p = <0.001). Discussion and conclusions: Excess mortality in those with SMI occurred across all socioeconomic quintiles compared to the Glasgow and Scottish populations but was most marked in the most deprived quintiles when suicide was excluded as a cause of death. Further work assessing the impact of socioeconomic status on specific causes of premature mortality in SMI is needed

Staphylococcus aureus Induces Eosinophil Cell Death Mediated by α-hemolysin

Staphylococcus aureus, a major human pathogen, exacerbates allergic disorders, including atopic dermatitis, nasal polyps and asthma, which are characterized by tissue eosinophilia. Eosinophils, via their destructive granule contents, can cause significant tissue damage, resulting in inflammation and further recruitment of inflammatory cells. We hypothesised that the relationship between S. aureus and eosinophils may contribute to disease pathology. We found that supernatants from S. aureus (SH1000 strain) cultures cause rapid and profound eosinophil necrosis, resulting in dramatic cell loss within 2 hours. This is in marked contrast to neutrophil granulocytes where no significant cell death was observed (at equivalent dilutions). Supernatants prepared from a strain deficient in the accessory gene regulator (agr) that produces reduced levels of many important virulence factors, including the abundantly produced α-hemolysin (Hla), failed to induce eosinophil death. The role of Hla in mediating eosinophil death was investigated using both an Hla deficient SH1000-modified strain, which did not induce eosinophil death, and purified Hla, which induced concentration-dependent eosinophil death via both apoptosis and necrosis. We conclude that S. aureus Hla induces aberrant eosinophil cell death in vitro and that this may increase tissue injury in allergic disease

‘Letting the right one in’: Provider contexts for recruitment to initial teacher education in the United Kingdom

We exploit policy differences within the UK to investigate provider context and recruitment to initial teacher education (ITE). We identify three dimensions of variation: conceptions of professionalism, universal or context specific preparation and costs and benefits to providers. University-led ITE programmes used similar criteria and processes in each jurisdiction, but there were differences between university-led and school-led recruitment. Our study suggests that the current shortfall in recruitment to ITE in England may be a product of the contextual constraints which schools experience. It also suggests that school-led recruitment may tend to emphasise short-term and school-specific needs

Public Awareness and Risk Perceptions of Endocrine Disrupting Chemicals: A Qualitative Study

Endocrine disrupting chemicals (EDCs) are exogenous chemicals found in food, consumer products, and the environment. EDCs are ubiquitous in modern life and exposure is associated with many negative health effects, such as reproductive disorders, metabolic disorders, and cancer. Scientists have deemed EDCs as a serious public health risk, yet the public’s perceptions of these chemicals is poorly understood. This study aimed to qualitatively explore how aware the public is of EDCs and their attitudes, beliefs, and perceptions of EDC risk. Thirty-four participants (aged 19–65 years) took part in the six focus groups. Discussions were transcribed verbatim and Nvivo 11 was used for thematic analysis. Our results indicated that awareness of EDCs was low. Themes of EDC risk perception included perceived control, perceived severity, and similarity heuristics. Risk alleviation strategies were also discussed. Future research should use quantitative methodology and a larger sample size to validate the findings from this study. Findings from this study may aid the development of effective risk communication strategies and public health interventions

Learning disability, autism and the Criminal Procedure (Scotland) Act

This paper aims to investigate the use of Part VI of the Criminal Procedure (Scotland) Act 1995 (CPSA) for people with Learning Disability (LD) and/or Autism. This is in the context of a recent review commissioned by the Scottish Government into whether the provisions in the Mental Health (Care and Treatment) (Scotland) Act 2003 (MHA) meet the needs of these groups which would also affect associated legislation such as CPSA