Nitrogen in Diamond.

Nitrogen is ubiquitous in both natural and laboratory-grown diamond, but the number and nature of the nitrogen-containing defects can have a profound effect on the diamond material and its properties. An ever-growing fraction of the supply of diamond appearing on the world market is now lab-grown. Here, we survey recent progress in two complementary diamond synthesis methods-high pressure high temperature (HPHT) growth and chemical vapor deposition (CVD), how each is allowing ever more precise control of nitrogen incorporation in the resulting diamond, and how the diamond produced by either method can be further processed (e.g., by implantation or annealing) to achieve a particular outcome or property. The burgeoning availability of diamond samples grown under well-defined conditions has also enabled huge advances in the characterization and understanding of nitrogen-containing defects in diamond-alone and in association with vacancies, hydrogen, and transition metal atoms. Among these, the negatively charged nitrogen-vacancy (NV-) defect in diamond is attracting particular current interest in account of the many new and exciting opportunities it offers for, for example, quantum technologies, nanoscale magnetometry, and biosensing.

Implementation of a teaching programme to improve doctors' awareness of DVLA guidelines: a multicentre study.

INTRODUCTION: Over half of the UK population holds a driver's licence. Driver and Vehicle Licensing Authority (DVLA) guidelines are available for conditions from most specialties. Despite this, no focused training occurs in the undergraduate or postgraduate setting. We evaluate the impact of a teaching programme to improve guideline awareness. METHODS: A 25-point questionnaire was designed using the current DVLA guidelines. Five questions were included for the following fields: neurology, cardiology, drug and alcohol abuse, visual disorders and respiratory. This was distributed to doctors in training at five hospitals. Four weeks later, a single-session teaching programme was implemented. The questionnaire was redistributed. Preintervention and postintervention scores were compared using the Wilcoxon rank sum test. RESULTS: 139 preteaching and 144 post-teaching questionnaires were completed. Implementation of a single-session teaching programme significantly improved the knowledge of DVLA guidelines in all five areas explored. Median scores: neurology, preteaching 40%, post-teaching 100%, p<0.001; cardiology, 0%, 100%, p<0.001; drug and alcohol misuse, 0%, 100%, p<0.001; visual disorders, 40%, 100%, p<0.001; respiratory disorders, 20%, 100%, p<0.001; and overall, 28%, 92%, p<0.001. CONCLUSIONS: Knowledge of DVLA guidelines among our cohort was poor. Implementation of a single-session teaching programme can significantly improve guideline knowledge and awareness, serving as a cost-effective intervention.

Natural and synthetic flavonoid modulation of TRPC5 channels.

BACKGROUND AND PURPOSE: The TRPC5 proteins assemble to create calcium-permeable, non-selective, cationic channels. We sought novel modulators of these channels through studies of natural products. EXPERIMENTAL APPROACH: Intracellular calcium measurements and patch clamp recordings were made from cell lines. Compounds were generated by synthetic chemistry. KEY RESULTS: Through a screen of natural products used in traditional Chinese medicines, the flavonol galangin was identified as an inhibitor of lanthanide-evoked calcium entry in TRPC5 overexpressing HEK 293 cells (IC50 0.45 µM). Galangin also inhibited lanthanide-evoked TRPC5-mediated current in whole-cell and outside-out patch recordings. In differentiated 3T3-L1 cells, it inhibited constitutive and lanthanide-evoked calcium entry through endogenous TRPC5-containing channels. The related natural flavonols, kaempferol and quercetin were less potent inhibitors of TRPC5. Myricetin and luteolin lacked effect, and apigenin was a stimulator. Based on structure-activity relationship studies with natural and synthetic flavonols, we designed 3,5,7-trihydroxy-2-(2-bromophenyl)-4H-chromen-4-one (AM12), which inhibited lanthanide-evoked TRPC5 activity with an IC50 of 0.28 µM. AM12 also inhibited TRPC5 activity evoked by the agonist (-)-Englerin A and was effective in excised outside-out membrane patches, suggesting a relatively direct effect. It inhibited TRPC4 channels similarly, but its inhibitory effect on TRPC1-TRPC5 heteromeric channels was weaker. CONCLUSIONS AND IMPLICATIONS: The data suggest that galangin (a natural product from the ginger family) is a TRPC5 inhibitor and that other natural and synthetic flavonoids contain antagonist or agonist capabilities at TRPC5 and closely related channels depending on the substitution patterns of both the chromone core and the phenyl ring.

Knowledge of Driving Vehicle Licensing Agency guidelines among NHS doctors: a multicentre observational study.

OBJECTIVES: Over half of the UK population holds a driver's licence. The DVLA have produced guidelines to ensure drivers with medical conditions drive safely. Doctors should ensure that patients are given appropriate information and advice if they have a medical condition affecting their driving. We sought to evaluate doctors' knowledge of DVLA guidelines. DESIGN: A 25-point questionnaire was designed from DVLA guidelines ('The DVLA Questionnaire'). Five questions were included for each of neurology, cardiology, drug and alcohol abuse, visual, and respiratory disorders. SETTING: Ealing Hospital, Northwick Park Hospital, Watford General Hospital, Norfolk and Norwich University Hospital and Leeds Teaching Hospitals Trust. PARTICIPANTS: 140 UK doctors. MAIN OUTCOME MEASURES: Questionnaire scores assessing knowledge of DVLA guidelines in five specialty areas. RESULTS: The median overall questionnaire score was 28%, interquartile range 20-36% and range 0-100% [Watford 28%, Leeds 30%, Norfolk and Norwich 36%, Ealing 30%, Northwick Park 28%]. There were no significant differences between the scores for each centre (p = 0.1332), Mean scores for specialty areas were: neurology 33.1%, standard deviation 22.1; cardiology 35.6%, standard deviation 26.9; drug and alcohol abuse 30.6%, standard deviation 23.8; visual disorders 33.9%, standard deviation 23.5 and respiratory disorders 20.3%, standard deviation 24.8; overall score 30.7%. There was no significant difference between the scores of the specialty areas (p = 0.4060). CONCLUSIONS: Knowledge of DVLA guidelines in our cohort was low. There is a need for increased awareness among hospital doctors through focused education on driving restrictions for common medical conditions. Improving physician knowledge in this area may help optimise patient safety.

A semi-quantitative and thematic analysis of medical student attitudes towards M-Learning.

RATIONALE, AIMS AND OBJECTIVES: Smartphone and mobile application technology have in recent years furthered the development of novel learning and assessment resources. 'MBChB Mobile' is a pioneering mobile learning (M-Learning) programme at University of Leeds, United Kingdom and provides all senior medical students with iPhone handsets complete with academic applications, assessment software and a virtual reflective environment. This study aimed to evaluate the impact of MBChB Mobile on student learning. METHODS: Ethical approval was granted to invite fourth and fifth year medical students to participate in a semi-quantitative questionnaire: data were collected anonymously with informed consent and analysed where appropriate using chi-squared test of association. Qualitative data generated through focus group participation were subjected to both content and thematic analysis. RESULTS: A total of 278 of 519 (53.6%) invited participants responded. Overall, 72.6% of students agreed that MBChB Mobile enhanced their learning experience; however, this was significantly related to overall usage (P < 0.001) and self-reported mobile technology proficiency (P < 0.001). Qualitative data revealed barriers to efficacy including technical software issues, non-transferability to different mobile devices, and perceived patient acceptability. CONCLUSIONS: As one of the largest evaluative and only quantitative study of smartphone-assisted M-Learning in undergraduate medical education, MBChB Mobile suggests that smartphone and application technology enhances students' learning experience. Barriers to implementation may be addressed through the provision of tailored learning resources, along with user-defined support systems, and appropriate means of ensuring acceptability to patients.

Pregnenolone sulphate-independent inhibition of TRPM3 channels by progesterone.

Transient Receptor Potential Melastatin 3 (TRPM3) is a widely expressed calcium-permeable non-selective cation channel that is stimulated by high concentrations of nifedipine or by physiological steroids that include pregnenolone sulphate. Here we sought to identify steroids that inhibit TRPM3. Channel activity was studied using calcium-measurement and patch-clamp techniques. Progesterone (0.01-10µM) suppressed TRPM3 activity evoked by pregnenolone sulphate. Progesterone metabolites and 17ß-oestradiol were also inhibitory but the effects were relatively small. Dihydrotestosterone was an inhibitor at concentrations higher than 1µM. Corticosteroids lacked effect. Overlay assays indicated that pregnenolone sulphate, progesterone and dihydrotestosterone bound to TRPM3. In contrast to dihydrotestosterone, progesterone inhibited nifedipine-evoked TRPM3 activity or activity in the absence of an exogenous activator, suggesting a pregnenolone sulphate-independent mechanism of action. Dihydrotestosterone, like a non-steroid look-alike compound, acted as a competitive antagonist at the pregnenolone sulphate binding site. Progesterone inhibited endogenous TRPM3 in vascular smooth muscle cells. Relevance of TRPM3 or the progesterone effect to ovarian cells, which have been suggested to express TRPM3, was not identified. The data further define a chemical framework for competition with pregnenolone sulphate at TRPM3 and expand knowledge of steroid interactions with TRPM3, suggesting direct steroid binding and pregnenolone sulphate-independent inhibition by progesterone.