Over the past two decades, there has been an exponential and enthusiastic adoption of simulation in healthcare education internationally. Medicine has learned much from professions that have established programs in simulation for training, such as aviation, the military and space exploration. Increased demands on training hours, limited patient encounters, and a focus on patient safety have led to a new paradigm of education in healthcare that increasingly involves technology and innovative ways to provide a standardized curriculum. A robust body of literature is growing, seeking to answer the question of how best to use simulation in healthcare education. Building on the groundwork of the Best Evidence in Medical Education (BEME) Guide on the features of simulators that lead to effective learning, this current Guide provides practical guidance to aid educators in effectively using simulation for training. It is a selective review to describe best practices and illustrative case studies. This Guide is the second part of a two-part AMEE Guide on simulation in healthcare education. The first Guide focuses on building a simulation program, and discusses more operational topics such as types of simulators, simulation center structure and set-up, fidelity management, and scenario engineering, as well as faculty preparation. This Guide will focus on the educational principles that lead to effective learning, and include topics such as feedback and debriefing, deliberate practice, and curriculum integration - all central to simulation efficacy. The important subjects of mastery learning, range of difficulty, capturing clinical variation, and individualized learning are also examined. Finally, we discuss approaches to team training and suggest future directions. Each section follows a framework of background and definition, its importance to effective use of simulation, practical points with examples, and challenges generally encountered. Simulation-based healthcare education has great potential for use throughout the healthcare education continuum, from undergraduate to continuing education. It can also be used to train a variety of healthcare providers in different disciplines from novices to experts. This Guide aims to equip healthcare educators with the tools to use this learning modality to its full capability.

Acute exposure to ionizing radiation can cause lethal damage to the gastrointestinal (GI) tract, a condition called the GI syndrome. Whether the target cells mediating the GI syndrome are derived from the epithelium or endothelium, and whether the target cells die by apoptosis or other mechanisms, are controversial issues. Studying mouse models, we found that selective deletion of the pro-apoptotic genes Bak1 and Bax from the GI epithelium or from endothelial cells did not protect mice from developing the GI syndrome after subtotal body gamma irradiation. In contrast, selective deletion of p53 from the GI epithelium, but not endothelial cells, sensitized irradiated mice to the GI syndrome. Transgenic mice overexpressing p53 in all tissues were protected from the GI syndrome after irradiation. These results suggest that the GI syndrome is caused by death of GI epithelial cells by a mechanism that is regulated by p53 but independent of apoptosis.

Following a mass-casualty nuclear disaster, effective medical triage has the potential to save tens of thousands of lives. In order to best use the available scarce resources, there is an urgent need for biodosimetry tools to determine an individual’s radiation dose. Initial triage for radiation exposure will include location during the incident, symptoms, and physical examination. Stepwise triage will include point of care assessment of less than or greater than 2 Gy, followed by secondary assessment, possibly with high throughput screening, to further define an individual’s dose. Given the multisystem nature of radiation injury, it is unlikely that any single biodosimetry assay can be used as a stand-alone tool to meet the surge in capacity with the timeliness and accuracy needed. As part of the national preparedness and planning for a nuclear or radiological incident, we reviewed the primary literature to determine the capabilities and limitations of a number of biodosimetry assays currently available or under development for use in the initial and secondary triage of patients. Understanding the requirements from a response standpoint and the capability and logistics for the various assays will help inform future biodosimetry technology development and acquisition. Factors considered include: type of sample required, dose detection limit, time interval when the assay is feasible biologically, time for sample preparation and analysis, ease of use, logistical requirements, potential throughput, point-of-care capability, and the ability to support patient diagnosis and treatment within a therapeutically relevant time point.

The mechanisms which regulate HSC regeneration following myelosuppressive injury are not well understood. We identified epidermal growth factor (EGF) to be highly enriched in the bone marrow (BM) serum of mice bearing deletion of Bak and Bax in Tie2+ cells (Tie2Cre;Bak1−/−;Baxfl/− mice), which displayed radioprotection of the HSC pool and 100% survival following lethal dose total body irradiation (TBI). BM HSCs from wild type mice expressed functional EGFR and systemic administration of EGF promoted the recovery of the HSC pool in vivo and the improved survival of mice following TBI. Conversely, administration of erlotinib, an EGFR antagonist, significantly decreased both HSC regeneration and mice survival following TBI. VavCre;EGFRfl/+ mice also demonstrated delayed recovery of BM stem/progenitor cells following TBI compared to VavCre;EGFR+/+ mice. Mechanistically, EGF reduced radiation-induced apoptosis of HSCs and mediated this effect via repression of the proapoptotic protein, PUMA. EGFR signaling regulates HSC regeneration following myelosuppressive injury.

p53 functions in the heart to promote myocardial injury after multiple types of stress. However, how p53 regulates radiation-induced myocardial injury, which develops after radiation therapy, is not well understood. Here, we utilize the Cre-loxP system to demonstrate that p53 functioned in endothelial cells to protect mice from myocardial injury after whole-heart irradiation. Mice with an endothelial cell-specific deletion of p53 succumbed to heart failure after whole-heart irradiation due to myocardial necrosis, systolic dysfunction and cardiac hypertrophy. Moreover, the onset of cardiac dysfunction was preceded by alterations in myocardial vascular permeability and density, which resulted in cardiac ischemia and myocardial hypoxia. Mechanistic studies using primary cardiac endothelial cells irradiated in vitro indicated that p53 signaling caused mitotic arrest and protected cardiac endothelial cells against radiation-induced mitotic catastrophe. Furthermore, mice lacking the cyclin-dependent kinase inhibitor p21, which is a transcriptional target of p53, were also sensitized to myocardial injury after wholeheart irradiation. Together, our results demonstrate that the p53/p21 axis functions to prevent radiation-induced myocardial injury in mice.

Background: There is increasing demand for managing depressive and/or anxiety disorders among primary care patients. Problem-solving therapy (PST) is a brief evidence-and strength-based psychotherapy that has received increasing support for its effectiveness in managing depression and anxiety among primary care patients.Methods: We conducted a systematic review and meta-analysis of clinical trials examining PST for patients with depression and/or anxiety in primary care as identified by searches for published literature across 6 databases and manual searching. A weighted average of treatment effect size estimates per study was used for meta-analysis and moderator analysis.

BackgroundOleate-enriched triacylglycerides are well-suited for lubricant applications that require high oxidative stability. Fatty acid carbon chain length and degree of desaturation are key determinants of triacylglyceride properties and the ability to manipulate fatty acid composition in living organisms is critical to developing a source of bio-based oil tailored to meet specific application requirements.ResultsWe sought to engineer the oleaginous yeast Yarrowia lipolytica for production of high-oleate triacylglyceride oil. We studied the effect of deletions and overexpressions in the fatty acid and triacylglyceride synthesis pathways to identify modifications that increase oleate levels. Oleic acid accumulation in triacylglycerides was promoted by exchanging the native ∆9 fatty acid desaturase and glycerol-3-phosphate acyltransferase with heterologous enzymes, as well as deletion of the Δ12 fatty acid desaturase and expression of a fatty acid elongase. By combining these engineering steps, we eliminated polyunsaturated fatty acids and created a Y. lipolytica strain that accumulates triglycerides with > 90% oleate content.ConclusionsHigh-oleate content and lack of polyunsaturates distinguish this triacylglyceride oil from plant and algal derived oils. Its composition renders the oil suitable for applications that require high oxidative stability and further demonstrates the potential of Y. lipolytica as a producer of tailored lipid profiles.Electronic supplementary materialThe online version of this article (10.1186/s13068-018-1131-y) contains supplementary material, which is available to authorized users.

Crew resource management (CRM) has the potential to improve safety culture and reduce patient safety errors across different hospitals and inherent cultures, but hospital-wide implementations have not been studied. The authors examined the impact of a systematic CRM implementation across 8 departments spanning 3 hospitals and 2 campuses. The Hospital Survey on Patient Safety Culture (HSOPS) was administered electronically to all employees before CRM implementation and about 2 years after; changes in percent positive composite scores were compared in pre-post analyses. Across all respondents, there was a statistically significant increase in composite score for 10 of the 12 HSOPS dimensions ( P < .05). These significant results persisted across the 8 departments studied and among both practitioners and staff. Consideration of score changes across dimensions reveals that the teamwork and communication dimensions of patient safety culture may be more highly influenced by CRM training than supervisor and management dimensions.