Levels and confounders of morning cortisol collected from adolescents in a naturalistic (school) setting

Salivary cortisol is widely used in research but little is known about the typical, or expected, functioning of the HPA-axis in adolescents in naturalistic settings, nor whether the extensive array of confounders documented in the literature is applicable in this situation. In a school-based study, 2995 15-year-old pupils provided two saliva samples, 30min apart, in morning sessions timed to capture peak cortisol decline. The collection protocol was a balance between the large sample size obtainable in a school situation and a limited number of samples, constrained by the school timetable. In addition, pupils completed a questionnaire containing items previously shown to be associated with cortisol levels (e.g. time since awakening and life events), and their height and weight were measured. Outcome measures were cortisol levels at Times 1 and 2, and change (per minute) in cortisol between the two time points. Median (IQR) cortisol levels for males and females were 10.5 (8.1) and 11.6 (9.3)nmol/L at Time 1, and 8.2 (6.0) and 8.1 (6.5)nmol/L at Time 2. 73% had a decline in cortisol level of more than 10% across the two time points, compatible with the expected diurnal pattern. In bivariate analyses, cortisol sampled on Monday, times of measurement and since awakening, prior smoking and several life events were associated with cortisol levels at Times 1 and 2 in both sexes. However, in multivariate analysis, few of these variables remained after controlling for times of measurement and since awakening and, in addition, the final models differed between the sexes. Two events (friend dying and splitting with a boy/girlfriend) predicted cortisol levels in both sexes while age, maturity, recent eating and smoking were predictors only in males. Several factors associated with cortisol change differed from those observed for absolute levels. Further adjustment for school clustering affected some associations, particularly time of measurement. This study managed many of the problems found in naturalistic research on cortisol and provides norms for morning cortisol levels in 15-year-old adolescents.     

Primary prostatic epithelial cell binding to human bone marrow stroma and the role of a2b1 integrin

Prostate cancer selectively metastasises to the bone. To investigate the importance of prostate epithelial cell adhesion to bone marrow cells in this process we examined the binding of human primary prostatic epithelial cells (PEC) to human bone marrow stromal cultures (BMS). We found that PEC derived from both malignant and benign tissue showed greater adhesion to BMS than to benign prostatic fibroblasts (median difference was 340% and 200% respectively), skin fibroblasts or plastic tissue culture plates. Adhesion to BMS grown from the bone marrow of patients with prostatic skeletal metastases was no different from those grown from normal bone marrow. The role of integrin molecules in these cell interactions was determined. Collagen type I and fibronectin were found to increase PEC adhesion whereas vitronectin and laminin did not. Inhibition studies demonstrated that although there was heterogeneity between samples, antibodies against the integrins a2 and b1 consistently inhibited PEC binding to BMS. This result was more marked for PEC derived from malignant tissue. However studies investigating the effects of disintegrins and anti-a3 and anti-a5 integrins indicated that for a percentage of patients these integrins and RGD (arginine, glycine, aspartamine)-dependent binding pathways were also involved. In summary, the results indicate that BMS are adherent to primary PEC derived from both malignant and benign tissue. The integrin a2b1 is a major contributor to this interaction.     

A quality improvement study for medical devices usage in an acute healthcare setting

Abstract

The objectives of this study were, for a large NHS Trust, to (1) Implement a medical devices training information system which connects the medical equipment inventory to the electronic staff record. (2) Monitor the changes in safety-related practice in the Trust after implementation (3) Examine the association between training compliance and Trust-wide adverse incident data for high risk medical devices. (4) Identify possible gaps in training course content from adverse incident data. A new system was made available, showing medical devices training records for staff in each location. Relevant staff members were trained on how to set up courses, record training, adjust training requirements and view reports. Training practice, compliance and adverse incidents for high-risk equipment were monitored over 30?months after implementation. Trends and changes in training practice were analysed. The Trust now has monitoring information on medical devices training available that had previously been absent. Training compliance increased from 23% to 59%. The frequency and severity of adverse incidents remained relatively constant throughout and was not associated with the increased uptake of training Trust-wide. Training gaps were identified. A Trust-wide system for recording medical devices training has provided training assurance. After implementation changes in practice with training have been identified. It was not possible to show a direct association between increased training compliance and reduced medical device-related incidents Trust-wide. There were specific training courses where changes in content could increase the safe use of medical devices.     

The role of isocitrate lyase and the glyoxylate cycle in Escherichia coli growing under glucose limitation

Escherichia coli changes its metabolism in response to environmental circumstances, and metabolic adaptations are evident in hungry bacteria growing slowly in glucose-limited chemostats. The role of isocitrate lyase (AceA) was examined in E. coli growing under glucose limitation. AceA activity was elevated in a strain-dependent manner in the commonly used E. coli K-12 laboratory strains MG1655 and MC4100, but an aceA disruption surprisingly increased fitness under glucose limitation in both strains. However, in bacteria adapted to limiting glucose in long-term chemostats, mutations outside aceA changed its role from a negative to a positive influence. These results suggest that a recently proposed pathway of central metabolism involving the glyoxylate cycle enzymes is redundant in wild-type bacteria, but may take on a beneficial role after context adaptation. Interestingly, the aceA gene sequence did not alter during prolonged selection, so mutations in unidentified genes changed the metabolic context of unaltered AceA from a negative to a positive influence in bacteria highly adapted to limiting glucose.