Top emergency medicine faculty development papers since 2000: A Delphi study.

Objectives: Faculty development is essential for academic emergency physicians to maintain clinical skills and succeed in administrative and leadership roles and for career advancement and satisfaction. Faculty developers in emergency medicine (EM) may struggle to find shared resources to guide faculty development efforts in a way that builds on existing knowledge. We aimed to review the EM-specific faculty development literature since 2000 and come to a consensus about the most useful for EM faculty developers. Methods: A database search was conducted on the topic of faculty development in EM from 2000 to 2020. After identifying relevant articles, we performed a modified Delphi process in three rounds, using a team of educators with a range of experiences with faculty development and education research, to identify articles that would be most useful to a broad audience of faculty developers. Results: We identified 287 potentially relevant articles on the topic of EM faculty development, 244 from the initial literature search, 42 from manual review of the references of the papers meeting inclusion criteria, and one by our study group's recommendation. Thirty-six papers met final inclusion criteria and underwent full-text review by our team. The Delphi process yielded six articles that were deemed most highly relevant over the three rounds. Each of these articles is described here, along with summaries and implications for faculty developers. Conclusions: We present the most useful EM papers from the past two decades for faculty developers seeking to develop, implement, or revise faculty development interventions.

Consensus Finder web tool to predict stabilizing substitutions in proteins.

The consensus sequence approach to predicting stabilizing substitutions in proteins rests on the notion that conserved amino acids are more likely to contribute to the stability of a protein fold than non-conserved amino acids. To implement a prediction for a target protein sequence, one finds homologous sequences and aligns them in a multiple sequence alignment. The sequence of the most frequently occurring amino acid at each position is the consensus sequence. Replacement of a rarely occurring amino acid in the target with a frequently occurring amino acid from the consensus sequence is predicted to be stabilizing. Consensus Finder is an open-source web tool that automates this prediction. This chapter reviews the rationale for the consensus sequence approach and explains the options for fine-tuning this approach using Staphylococcus nuclease A as an example.

Larger active site in an ancestral hydroxynitrile lyase increases catalytically promiscuous esterase activity.

Hydroxynitrile lyases (HNL's) belonging to the α/ß-hydrolase-fold superfamily evolved from esterases approximately 100 million years ago. Reconstruction of an ancestral hydroxynitrile lyase in the α/ß-hydrolase fold superfamily yielded a catalytically active hydroxynitrile lyase, HNL1. Several properties of HNL1 differ from the modern HNL from rubber tree (HbHNL). HNL1 favors larger substrates as compared to HbHNL, is two-fold more catalytically promiscuous for ester hydrolysis (p-nitrophenyl acetate) as compared to mandelonitrile cleavage, and resists irreversible heat inactivation to 35 °C higher than for HbHNL. We hypothesized that the x-ray crystal structure of HNL1 may reveal the molecular basis for the differences in these properties. The x-ray crystal structure solved to 1.96-Å resolution shows the expected α/ß-hydrolase fold, but a 60% larger active site as compared to HbHNL. This larger active site echoes its evolution from esterases since related esterase SABP2 from tobacco also has a 38% larger active site than HbHNL. The larger active site in HNL1 likely accounts for its ability to accept larger hydroxynitrile substrates. Site-directed mutagenesis of HbHNL to expand the active site increased its promiscuous esterase activity 50-fold, consistent with the larger active site in HNL1 being the primary cause of its promiscuous esterase activity. Urea-induced unfolding of HNL1 indicates that it unfolds less completely than HbHNL (m-value = 0.63 for HNL1 vs 0.93 kcal/mol·M for HbHNL), which may account for the ability of HNL1 to better resist irreversible inactivation upon heating. The structure of HNL1 shows changes in hydrogen bond networks that may stabilize regions of the folded structure.

Spinal Epidural Abscess.

Audience: The aim of this simulation case is to educate senior medical students, resident physicians, and advanced practice providers on the recognition, diagnosis, and management of spinal epidural abscesses. This scenario is most applicable to the emergency medicine setting but can be applied to the outpatient office or urgent care settings. Introduction: Spinal epidural abscess is an infection leading to an epidural collection of purulent material. This uncommon condition is estimated to occur less than 12 times per 100,000 hospital admissions.1,2 However, this infection can lead to devastating neurological sequelae via cord compression, spinal vascular interruption, and inflammatory etiologies;3,4 thus, prompt diagnosis is essential. Unfortunately, spinal epidural abscesses may be difficult to identify clinically due to variable clinical presentations. The goal of this scenario is to increase awareness of this critical diagnosis.Detailed history-taking to identify risk factors will aid in the recognition of spinal epidural abscesses. Many of the risk factors are related to increased infectious risk from hematogenous spread, iatrogenic inoculation, or direct extension.1 Individuals with conditions including intravenous (IV) drug use, alcohol abuse, diabetes, human immunodeficiency virus (HIV), cancer, hepatic disease, renal disease, and other immunocompromising conditions are at increased risk of developing epidural abscesses.1 Primary infectious sources include dental abscesses, endocarditis, vertebral osteomyelitis, and soft tissue infections. Spinal procedures including spinal surgeries, paraspinal injections, and placement of epidural catheters or stimulators can also predispose to infection.2,4Classic symptoms for spinal epidural abscesses include fever, back pain and neurological changes.1,5 Back pain is the most frequent presenting symptom, occurring about 70%-90% of the time.1 However, fever is the least frequent presenting symptom4 and neurological findings only occur in about one-third of cases.2 Neurological symptoms include motor weakness, sensory changes, urinary retention, overflow urinary incontinence, bowel dysfunction, hyperreflexia, radicular pain, spinal shock or cauda equina syndrome.1,4Laboratory findings may include systemic leukocytosis and elevated inflammatory markers. Whereas leukocytosis is estimated to be present in two-thirds of cases,2 Davis, et al. showed that with the concurrent presence of a risk factor, an elevated erythrocyte sedimentation rate (ESR) had 100% sensitivity and 67% specificity for spinal epidural abscesses.5Magnetic resonance imaging (MRI) with gadolinium contrast is the preferred imaging modality for diagnosing spinal epidural abscesses. Computed tomography (CT) with myelography can be considered if MRI is contraindicated.1 Given that abscesses may be multifocal, further spinal imaging beyond a single spinal segment should be considered during evaluation. Lumbar puncture is not recommended due to risk of iatrogenic infectious spread.Treatment of epidural abscesses includes obtaining blood cultures and prompt antibiotic administration with early surgical evaluation to determine if operative intervention is warranted. Staphylococcus aureus is the most common microbial cause, contributing to about two-thirds of cases.3,4 Other microbial causes include coagulase-negative Staphylococcus (ie, Staphylococcus epidermidis), Streptococcus, gram-negative bacilli (ie, Pseudomonas aeruginosa and E. coli), and less commonly, anaerobic bacteria, fungi, mycobacteria and parasites.1,2 Empiric antibiotic treatments generally include vancomycin and a third- or fourth- generation cephalosporin.2,4This simulation session will highlight the importance of recognizing and aggressively treating this uncommon but potentially devastating condition. Educational Objectives: After this simulation case, learners will be able to diagnose and manage patients with spinal epidural abscesses. Specifically, learners will be able to:Obtain a detailed history, including past infectious, surgical, procedural and social history to evaluate for epidural abscess risk factors. Describe clinical signs and symptoms of spinal epidural abscesses and understand that initial clinical presentations can be variable.Perform a focused neurological exam including evaluation of motor, sensory, reflexes, and rectal tone.Order appropriate laboratory testing and imaging modalities for spinal epidural abscess diagnosis, including a post-void bladder residual volume.Select appropriate antibiotics for empiric treatment of spinal epidural abscess depending on patient presentation.Disposition the patient to appropriate inpatient care. Educational Methods: The authors conducted this simulation case with a standardized patient. We encourage inclusion of a standardized patient versus a mannequin to provide appropriate motor and sensory exams. For those without a standardized patient program, the authors suggest utilizing a faculty member as the patient. Regardless of individual used, it is strongly recommended that facilitators rehearse the case with the individual in the patient role ahead of time in order to ensure that their performance reflects an accurate neurologic exam. A debriefing session and small-group discussion followed the simulation to review the clinical presentation, diagnosis, management, and treatment of spinal epidural abscesses. This case can also be adapted as an oral boards case. Research Methods: Residents were provided a survey at the completion of the debriefing session to rate different aspects of the simulation, as well as to provide qualitative feedback on the scenario. This survey is specific to our institution's simulation center. Results: While qualitative feedback from the residents was positive, it was viewed as a straightforward case. Our initial presenting symptom was difficulty ambulating with a fever at home, if asked. The residents appreciated performing a neurologic exam on a standardized patient versus attempting this on a mannequin.Our simulation center's feedback form is based on the Center of Medical Simulation's Debriefing Assessment for Simulation in Healthcare (DASH) Student Version Short Form with the inclusion of required qualitative feedback if an element was scored less than a 6 or 7. This session received all 7 scores (extremely effective/outstanding) other than one 5 score for the element assessing if the instructor set the stage for an engaging learning experience. The learner's feedback for this 5 score was "kinda went right into the case which was ok." Our form also includes an area for general feedback about the case at the end. Comments included "Great sim. Expert case writing," "Fun case and learned a lot," and "Great case! Appreciated feedback on consulting and the difficult consultant situation." Discussion: This is a cost-effective method for reviewing epidural abscess. We chose a chief complaint and history that was slightly atypical from "classic" presentations, but not so esoteric that the residents felt cheated at the end of the scenario. When using a standardized patient in a scenario that may involve a sensitive physical exam, we review with learners and the standardized patient what expectations are during the pre-brief session. For example, residents may say, "we would like to check to see if rectal tone is intact," and then the standardized patient would verbalize back the expected physical exam findings. Topics: Medical simulation, spinal epidural abscess, spinal cord compression, infectious disease.

Wnt5a potentiates TGF-ß signaling to promote colonic crypt regeneration after tissue injury.

Reestablishing homeostasis after tissue damage depends on the proper organization of stem cells and their progeny, though the repair mechanisms are unclear. The mammalian intestinal epithelium is well suited to approach this problem, as it is composed of well-delineated units called crypts of Lieberkühn. We found that Wnt5a, a noncanonical Wnt ligand, was required for crypt regeneration after injury in mice. Unlike controls, Wnt5a-deficient mice maintained an expanded population of proliferative epithelial cells in the wound. We used an in vitro system to enrich for intestinal epithelial stem cells to discover that Wnt5a inhibited proliferation of these cells. Surprisingly, the effects of Wnt5a were mediated by activation of transforming growth factor-ß (TGF-ß) signaling. These findings suggest a Wnt5a-dependent mechanism for forming new crypt units to reestablish homeostasis.