Cellular glutathione content in the organ of Corti and its role during ototoxicity.

Glutathione (GSH) is the major scavenger of reactive oxygen species (ROS) inside cells. We used live confocal imaging in order to clarify the role of GSH in the biology of the organ of Corti, the sensory epithelium of the cochlea, before, during and after the onset of hearing and in ~1 year old mice. GSH content was measured using monochlorobimane (MCB), a non-fluorescent cell permeant bimane that reacts with GSH, forming a fluorescent adduct through a reaction catalyzed by glutathione-S-transferase. GSH content increased significantly in inner hair cells during maturation in young adult animals, whereas there was no significant change in the outer hair cells. However, the GSH content in inner hair cells was significantly reduced in ~1 year old mice. The GSH content of supporting cells was comparatively stable over these ages. To test whether the GSH content played a significant protective role during ototoxicity, GSH synthesis was inhibited by buthionine sulfoximine (BSO) in organotypic cochlear explant cultures from immature mice. BSO treatment alone, which reduced GSH by 65 and 85% in inner hair cells and outer hair cells respectively, did not cause any significant cell death. Surprisingly, GSH depletion had no significant effect on hair cell survival even during exposure to the ototoxic aminoglycoside neomycin. These data suggest that the involvement of ROS during aminoglycoside-induced hair cell death is less clear than previously thought and requires further investigation

Rising to the challenge: acute stress appraisals and selection centre performance in applicants to postgraduate specialty training in anaesthesia

AcceptedArticle in Press© 2015 Springer Science+Business Media Dordrecht The ability to work under pressure is a vital non-technical skill for doctors working in acute medical specialties. Individuals who evaluate potentially stressful situations as challenging rather than threatening may perform better under pressure and be more resilient to stress and burnout. Training programme recruitment processes provide an important opportunity to examine applicants’ reactions to acute stress. In the context of multi-station selection centres for recruitment to anaesthesia training programmes, we investigated the factors influencing candidates’ pre-station challenge/threat evaluations and the extent to which their evaluations predicted subsequent station performance. Candidates evaluated the perceived stress of upcoming stations using a measure of challenge/threat evaluation—the cognitive appraisal ratio (CAR)—and consented to release their demographic details and station scores. Using regression analyses we determined which candidate and station factors predicted variation in the CAR and whether, after accounting for these factors, the CAR predicted candidate performance in the station. The CAR was affected by the nature of the station and candidate gender, but not age, ethnicity, country of training or clinical experience. Candidates perceived stations involving work related tasks as more threatening. After controlling for candidates’ demographic and professional profiles, the CAR significantly predicted station performance: ‘challenge’ evaluations were associated with better performance, though the effect was weak. Our selection centre model can help recruit prospective anaesthetists who are able to rise to the challenge of performing in stressful situations but results do not support the direct use of challenge/threat data for recruitment decisions.Funding was granted as a pilot for selection to acute specialities from the Department of Health (England). M.J.R.’s research post was funded through this grant, as were sessional time allocations for T.C.E.G. All opinions in the manuscript are those of the authors only and recommendations or policy from the DH should not be inferred from this work

Safety culture and the 5 steps to safer surgery: an intervention study.

BACKGROUND: Improvements in safety culture have been postulated as one of the mechanisms underlying the association between the introduction of the World Health Organisation (WHO) Surgical Safety Checklist with perioperative briefings and debriefings, and enhanced patient outcomes. The 5 Steps to Safer Surgery (5SSS) incorporates pre-list briefings, the three steps of the WHO Surgical Safety Checklist (SSC) and post-list debriefings in one framework. We aimed to identify any changes in safety culture associated with the introduction of the 5SSS in orthopaedic operating theatres. METHODS: We assessed the safety culture in the elective orthopaedic theatres of a large UK teaching hospital before and after introduction of the 5SSS using a modified version of the Safety Attitude Questionnaire - Operating Room (SAQ-OR). Primary outcome measures were pre-post intervention changes in the six safety culture domains of the SAQ-OR. We also analysed changes in responses to two items regarding perioperative briefings. RESULTS: The SAQ-OR survey response rate was 80% (60/75) at baseline and 74% (53/72) one yr later. There were significant improvements in both the reported frequency (P<0.001) and perceived importance (P=0.018) of briefings, and in five of the six safety culture domain scores (Working Conditions, Perceptions of Management, Job Satisfaction, Safety Climate and Teamwork Climate) of the SAQ-OR (P<0.001 in all cases). Scores in the sixth domain (Stress Recognition) decreased significantly (P=0.028). CONCLUSIONS: Implementation of the 5SSS was associated with a significant improvement in the safety culture of elective orthopaedic operating theatres

The Global Boundary Stratotype Section and Point (GSSP) for the base of the Albian Stage, of the Cretaceous, the Col de Pré-Guittard section, Arnayon, Drôme, France

Following the unanimous approval of the Executive Committee on the International Union of Geological Sciences as notified on April 8, 2016, the Global boundary Stratotype Section and Point for the base of the Albian Stage of the Cretaceous is defined at the first occurrence datum of the planktonic foraminiferan Microhedbergella renilaevis Huber and Leckie, 2011 at a level 37.4 meters above the base of the Marnes Bleues Formation and 40 cm above the base of the Niveau Kilian marker bed in the section SSE of the Col de Pré-Guittard, Arnayon, Drôme, France. The first occurrence of Microhedbergella renilaevis is placed within a 100-m section of argillaceous sediments with 28 secondary markers including calcareous nannofossils, planktonic foraminifera, an inoceramid bivalve, ammonites, stable carbon isotopes, and local marker beds

New and simple algorithms for stable flow problems

Stable flows generalize the well-known concept of stable matchings to markets in which transactions may involve several agents, forwarding flow from one to another. An instance of the problem consists of a capacitated directed network, in which vertices express their preferences over their incident edges. A network flow is stable if there is no group of vertices that all could benefit from rerouting the flow along a walk. Fleiner established that a stable flow always exists by reducing it to the stable allocation problem. We present an augmenting-path algorithm for computing a stable flow, the first algorithm that achieves polynomial running time for this problem without using stable allocation as a black-box subroutine. We further consider the problem of finding a stable flow such that the flow value on every edge is within a given interval. For this problem, we present an elegant graph transformation and based on this, we devise a simple and fast algorithm, which also can be used to find a solution to the stable marriage problem with forced and forbidden edges. Finally, we study the stable multicommodity flow model introduced by Kir\'{a}ly and Pap. The original model is highly involved and allows for commodity-dependent preference lists at the vertices and commodity-specific edge capacities. We present several graph-based reductions that show equivalence to a significantly simpler model. We further show that it is NP-complete to decide whether an integral solution exists

Longitudinal impact of process-oriented guided inquiry learning on the attitudes, self-efficacy and experiences of pre-medical chemistry students

A follow-up study was conducted with foundation-year chemistry students who were taught in an inquiry- and role-based, small-group active learning environment in order to evaluate their attitudes, experiences and self-efficacy during pre-medical chemistry courses. The study adopted a mixedmethods research design that involved both experimental and comparison groups. Using the CAEQ (Chemistry Attitudes and Experiences Questionnaire) and the ASCI v2 (Attitude toward the Study of Chemistry Inventory), the findings of this study indicated that inquiry-based chemistry learning experience improves the students’ intellectual accessibility and emotional satisfaction as well as develops their self-efficacy levels while pursuing intensive pre-medical courses in chemistry. The results of the qualitative data analyses using a course experience questionnaire indicated that the process-oriented guided inquiry learning (POGIL) experience helped the students succeed in rigorous pre-medical chemistry courses and gained some process skills required in the medical programme as listed by the AAMC (American Association of Medical Colleges)

The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

Background: The main source of 5-HT in body is in enterchromafin cells of intestine, different studies mentioned different roles for endogenous 5-HT and receptors involved and it is not clearified the mechanism of action of endogenous 5-HT. Objectives: To study the role of endogenous 5-HT on modulation of contraction and relaxation responses induced by electrical field stimulation (EFS) in different regions of the rat intestine. Materials and Methods: Segments taken from the rat duodenum, jejunum, mid and terminal ileum were vertically mounted, connected to a transducer and exposed to EFS with different frequencies in the absence and presence of various inhibitors of enteric mediators i. e. specific 5-HT receptor antagonists. Results: EFS-induced responses were sensitive to TTX and partly to atropine, indicating a major neuronal involvement and a cholinergic system. Pre-treatment with WAY100635 (a 5-HT1A receptor antagonist) and granisetron up to 10.0 µM, GR113808 (a 5-HT4 receptor antagonist), methysergide and ritanserin up to 1.0 µM, failed to modify responses to EFS inall examined tissues. In the presence of SB258585 1.0 µM (a 5-HT6 receptor antagonist) there was a trend to enhance contraction in the proximal part of the intestine and reduce contraction in the distal part. Pre-treatment with SB269970A 1.0 µM (5-HT7 receptor antagonist) induced a greater contractile response to EFS at 0.4 Hz only in the duodenum. Conclusions: The application of 5-HT1A, 5-HT2, 5-HT3, 5-HT4, 5-HT6 and 5-HT7 receptor antagonists, applied at concentrations lower than 1.0 µM did not modify the EFS-induced contraction and relaxation responses, whichsuggests the unlikely involvement of endogenous 5-HT in mediating responses to EFS in the described test conditions. Keywords: Electric Stimulation Therapy; Serotonin 5-HT1 Receptor Antagonists; Intestine, Smal