IDH3 mediates apoptosis of alveolar epithelial cells type 2 due to mitochondrial Ca2+ uptake during hypocapnia

In adult respiratory distress syndrome (ARDS) pulmonary perfusion failure increases physiologic dead-space (VD/VT) correlating with mortality. High VD/VT results in alveolar hypocapnia, which has been demonstrated to cause edema formation, atelectasis, and surfactant depletion, evoked, at least in part, by apoptosis of alveolar epithelial cells (AEC). However, the mechanism underlying the hypocapnia-induced AEC apoptosis is unknown. Here, using fluorescent live-cell imaging of cultured AEC type 2 we could show that in terms of CO2 sensing the tricarboxylic acid cycle enzyme isocitrate dehydrogenase (IDH) 3 seems to be an important player because hypocapnia resulted independently from pH in an elevation of IDH3 activity and subsequently in an increase of NADH, the substrate of the respiratory chain. As a consequence, the mitochondrial transmembrane potential (ΔΨ) rose causing a Ca2+ shift from cytosol into mitochondria, whereas the IDH3 knockdown inhibited these responses. Furthermore, the hypocapnia-induced mitochondrial Ca2+ uptake resulted in reactive oxygen species (ROS) production, and both the mitochondrial Ca2+ uptake and ROS production induced apoptosis. Accordingly, we provide evidence that in AEC type 2 hypocapnia induces elevation of IDH3 activity leading to apoptosis. This finding might give new insight into the pathogenesis of ARDS and may help to develop novel strategies to reduce tissue injury in ARDS

Distinct roles of XRCC4 and Ku80 in non-homologous end-joining of endonuclease- and ionizing radiation-induced DNA double-strand breaks

Non-homologous end-joining (NHEJ) of DNA double-strand breaks (DSBs) is mediated by two protein complexes comprising Ku80/Ku70/DNA-PKcs/Artemis and XRCC4/LigaseIV/XLF. Loss of Ku or XRCC4/LigaseIV function compromises the rejoining of radiation-induced DSBs and leads to defective V(D)J recombination. In this study, we sought to define how XRCC4 and Ku80 affect NHEJ of site-directed chromosomal DSBs in murine fibroblasts. We employed a recently developed reporter system based on the rejoining of I-SceI endonuclease-induced DSBs. We found that the frequency of NHEJ was reduced by more than 20-fold in XRCC4−/− compared to XRCC4+/+ cells, while a Ku80 knock-out reduced the rejoining efficiency by only 1.4-fold. In contrast, lack of either XRCC4 or Ku80 increased end degradation and shifted repair towards a mode that used longer terminal microhomologies for rejoining. However, both proteins proved to be essential for the repair of radiation-induced DSBs. The remarkably different phenotype of XRCC4- and Ku80-deficient cells with regard to the repair of enzyme-induced DSBs mirrors the embryonic lethality of XRCC4 knock-out mice as opposed to the viability of the Ku80 knock-out. Thus, I-SceI-induced breaks may resemble DSBs arising during normal DNA metabolism and mouse development. The removal of these breaks likely has different genetic requirements than the repair of radiation-induced DSBs

Understanding Why All Types of Motivation Are Necessary in Advanced Anaesthesiology Training Levels and How They Influence Job Satisfaction: Translation of the Self-Determination Theory to Healthcare

Studies applying the self-determination theory have shown that intrinsic motivation and autonomous regulation lead to job satisfaction and to better job performance. What has not been worked out clearly yet are the effects of extrinsic motivation and controlled regulation on affect, job performance and job satisfaction. However, it has been described that controlled regulation is often necessary for mundane tasks. In anaesthesiology, routine daily tasks can be perceived as mundane by those who have achieved a certain level of training (e.g., consultants). Therefore, it was hypothesised that consultants have high expressions of all motivational qualities. Furthermore, it was hypothesised that job satisfaction of anaesthesiologists is correlated with autonomous motivation. The hypotheses were tested in a cross-sectional study design within a group of anaesthesiologists. The study participants reported the same pattern throughout the motivational continuum. Consultants reported the highest levels of all motivational qualities, including controlled regulation, as well as the highest levels of job satisfaction. Junior residents reported high levels of amotivation and extrinsic regulation. The lowest levels of identified regulation and job satisfaction were reported by the group of attendings. Job satisfaction was positively correlated with intrinsic motivation and negatively correlated with amotivation. Therefore, our findings from the field of anaesthesiology show that the expressions of high levels of controlled regulation might be necessary for specialists to engage in mundane daily tasks. Intrinsic motivation and autonomous regulation are necessary for job satisfaction and the presence of controlled regulation and extrinsic behavioural regulation have no declining effects. Furthermore, the decrease of amotivation will lead to enhanced job satisfaction and the resulting consequences will be extensive. Junior residents need to be supported with the aim to enhance their feeling of autonomy and competence in order to decrease amotivation and to foster autonomous regulation and hence to increase job satisfaction and well-being. Further special focus should be on attendings to counteract their lacking identification with the job. Hereby, the provision of feedback and professional perspectives might foster the process of re-identification

Efficacy of an Integrated Simulation-Based Education Approach to Train Non-Technical Skills in Medical Undergraduate Students

Introduction: Non-technical skills (NTS) are essential to maintain best patient care and to enhance patient safety. Therefore, the early integration and implementation of non-technical skills (NTS) training during undergraduate medical education has not only been repeatedly emphasized but is crucial to ensure patient safety. However, there is a gap in knowledge on how to effectively convey and thereby enhance NTS in under- or postgraduate medical training. Although medical educators are eager to convey NTS, the best approach to do so is yet to be found. Next to didactic and teaching approaches, the design of the curriculum, in the sense of an integrated curricula, might have an influence in conveying NTS effectively. Therefore, we investigated if repetitive simulation-based training enhanced the NTS of medical undergraduates. Methods: 945 undergraduate students in their 1st, 2nd, 3rd and 4th year of medical studies who attended mandatory emergency simulation trainings at the medical faculty in Hamburg participated in this prospective observational study. The trainings are designed to align to a learning spiral (vertically integrated curriculum) and build upon each other, resulting in repetitive and advanced training. Each training has a preset training-specific standardized simulation scenarios. To determine progress in NTS performance, the NTS of the students were assessed during each training with the Anaesthesiology Students’ NTS (AS-NTS) taxonomy, which is composed of three dimensions. Differences in performance between the investigated cohorts of students were calculated with an analysis of variance (Welch’s ANOVA) and with a follow-up post hoc test (Games-Howell), and the significant differences were analysed. Results: The NTS of the undergraduate students improved with every ascending training and, hence, year of medical school. The overall NTS performance of the 4thyear undergraduate students differed significantly compared to the 1st, 2nd and 3rd year undergraduate students performances, F = 6.72 (4, 439.6), p ≤ 0.001. The greatest improvement was detected on dimension one of the AS-NTS (“Planning tasks, prioritising and problem-solving”) (F = 6.75 (4, 434.5), p ≤ 0.001), where 4th year undergraduates performed at a significantly higher skill level than the 1st, 2nd and 3rd year undergraduate students. On dimension two (“Teamwork and Leadership”) and three (“Team orientation”), significant differences were pronounced between the 4th year and 1st year undergraduate students (F = 3.56 (4, 442.9), p = 0.010; F = 4.50 (4, 441.0), p = 0.001). The lowest skill improvement was observed on dimension two. Conclusions: NTS are essential skills to complement technical skills and hereby ensure patient safety. The early longitudinal and vertical integration of NTS training in undergraduate medical curricula (learning spiral) is an effective approach to enhance and foster the NTS of future doctors

National consensus on entrustable professional activities for competency-based training in anaesthesiology.

Entrustable Professional Activities (EPA) are specialty specific tasks or responsibilities, combining the clinical workplace and the long-demanded competency-based medical education. The first step to transform time-based into EPA-based training is to reach consensus on core EPAs that describe sufficiently the workplace. We aimed to present a nationally validated EPA-based curriculum for postgraduate training in anaesthesiology. Using a predefined and validated list of EPAs, we applied a Delphi consensus approach, involving all German chair directors of anaesthesiology. We then conducted a subsequent qualitative analysis. Thirty-four chair directors participated in the Delphi survey (77% response) and twenty-five completed all the questions (56% overall response). Reflected by the intra-class-correlation, the consensus on the importance (ICC: 0.781, 95% CI [0.671, 0.868]) and the year of entrustment (ICC: 0.973, 95% CI [0.959, 0.984]) of each EPA reached high levels of agreement among the chair directors. The comparison of data assessed in the preceding validation and present study showed excellent and good levels of agreement (ICC entrustment: 0.955, 95% CI [0.902, 0.978]; ICC importance: 0.671, 95% CI [-0.204, 0.888]). The adaptation process, based on the qualitative analysis, resulted in a final set of 34 EPAs. We present an elaborate, fully described and nationally validated EPA-based curriculum, reflecting a broad consensus among different stakeholders of anaesthesiology. We hereby provide a further step towards competency-based postgraduate anaesthesiology training

Can Different Admissions to Medical School Predict Performance of Non-Technical Skill Performance in Simulated Clinical Settings?

Non-technical skills (NTS) in medical care are essential to ensure patient safety. Focussing on applicants’ NTS during medical school admission could be a promising approach to ensure that future physicians master NTS at a high level. Next to pre-university educational attainment, many selection tests have been developed worldwide to facilitate and standardise the selection process of medical students. The predictive validity of these tests regarding NTS performance in clinical settings has not been investigated (yet). Therefore, we explored the predictive validities and prognosis of the Hamburg MMI (HAM-Int), HAM-Nat, PEA, and waiting as well as other quota (as example) designated by the Federal Armed Forces) for NTS performance in clinical emergency medicine training of medical students. During 2017 and 2020, N = 729 second, third, and fourth year students were enrolled within the study. The mean age of participants was 26.68 years (SD 3.96) and 49% were female students. NTS of these students were assessed during simulation scenarios of emergency training with a validated rating tool. Students admitted via waiting quota and designated by the Armed Forces performed significantly better than students admitted by excellent PEA (p = 0.026). Non-EU students performed significantly inferior (p = 0.003). Our findings provide further insight to explain how and if admission to medical school could predict NTS performance of further physicians

Enhanced Recovery After Cardiac Surgery: Where Do We Stand?

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Purpose of Review</jats:title> <jats:p>Enhanced recovery after surgery (ERAS) protocols are multimodal and multi-professional strategies to enhance postoperative convalescence and thereby reduce the length of hospital stay and hospital-associated complications. This review provides an up-to-date overview about basic principles of enhanced recovery after surgery protocols, their transfer into cardiac surgery, and their current state of evidence. It is supposed to offer clinical implications for further adaptations and implementations of such protocols in cardiac surgery.</jats:p> </jats:sec><jats:sec> <jats:title>Recent Findings</jats:title> <jats:p>ERAS protocols are a story of success in numerous surgical disciplines and led to a paradigm shift in perioperative care and the establishment of ERAS Cardiac Society, a non-profit organization that provides evidence-based guidelines and recommendations for further development of enhanced recovery protocols, trying to harmonize the many existing efforts of individual approaches for cardiac surgery.</jats:p> </jats:sec><jats:sec> <jats:title>Summary</jats:title> <jats:p>Promising results from comprehensive ERAS protocols in cardiac surgery emerged. Nevertheless, there is a paucity of high-quality data about holistic approaches in cardiac surgery and further efforts need to be promoted.</jats:p> </jats:sec&gt

Distinct roles of XRCC4 and Ku80 in

non-homologous end-joining of endonucleaseand ionizing radiation-induced DNA double-strand break