Lessons Learned: Large-Scale Perfused Cadaver Training in Three Different Curricular Environments.

BACKGROUND: Perfused cadavers are viable training models for operating room surgical skills, increasing fidelity of vascular anatomy, dissection, and tissue handling. In addition, perfused cadavers may have benefits in military medical training environments with a focus on hemorrhage control and vascular access. OBJECTIVES: We created a large-scale training exercise with perfused cadavers in three different environments and aim to share the curricular design and feedback from the exercise. METHODS: We conducted a 4-day simulation training exercise with 13 perfused cadavers in 3 different environments: hospital environment, the austere echelons of care environment, and a controlled-settings tent for hemorrhage control and needle decompression training. Through an anonymous online survey and an after-action review (AAR), we elicited feedback on advantages, disadvantages, costs, and comparison to models of porcine and fresh cadavers for procedures and existing courses. RESULTS: A total of 324 participants were trained with 13 perfused cadavers for over 4 days from a variety of specialties and on different procedures and surgical skills. Based on 130 respondents to the survey and the AAR, perfused cadavers were rated to have realistic arterial bleeding and bleeding control training. In addition, perfused cadavers provided increased realism and fidelity for surgical skills. There were disadvantages of logistical requirements, cleanup, costs, and mobility. CONCLUSION: Perfused cadavers can be implemented effectively for hemorrhage control training, surgical and procedure skills, and even exercises in austere environments, but require significant logistical and planning considerations. The training value is maximized with a progressive curriculum from hemorrhage control iterations to more invasive surgical procedures, such as thoracotomy and exploratory laparotomy.

Using Bibliometric Analysis to Map the Impact of a Simulation Program's Published Scholarly Works.

SUMMARY STATEMENT: Bibliometrics quantitatively evaluates the targeted literature sources and can help define research and scholarly publications' impact and demonstrate connections for authors, departments, or universities. This article presents a methodology for simulation programs to evaluate their influence in terms of both impact and scope of their published simulation-based healthcare scholarly output. Using the authors' home university and healthcare system as an example, the article outlines a methodology to map research and scholarly works networks within the systems, identify and map connections outside the system, and quantifiably score the overall impact of the simulation program's scholarly output using a common scoring metric, the h-index. This generates an objective measure of impact, rather than a subjective opinion of an organization's research and scholarly impact. The combination of an institutional h-index with mapping of simulation-based healthcare scholarly output provides a full, objective description of the institution's output and provides a benchmark for other simulation programs for comparison.

Mapping the Terrain of Faculty Development for Simulation: A Scoping Review.

ABSTRACT: Understanding what interventions and approaches are currently being used to improve the knowledge, skills, and effectiveness of instructors in simulation-based education is an integral step for carving out the future of simulation. The current study is a scoping review on the topic, to uncover what is known about faculty development for simulation-based education.We screened 3259 abstracts and included 35 studies in this scoping review. Our findings reveal a clear image that the landscape of faculty development in simulation is widely diverse, revealing an array of foundations, terrains, and peaks even within the same zone of focus. As the field of faculty development in simulation continues to mature, we would hope that greater continuity and cohesiveness across the literature would continue to grow as well. Recommendations provided here may help provide the pathway toward that aim.

More Than a Bruise: Two Cases of Morel-Lavallée Lesions in Active Duty Soldiers.

Soft tissue injuries are common in the military, generally producing simple hematomas without the need for intensive evaluation and management. In certain situations, a shearing effect between fascial planes whereby a disruption of the vasculature and lymphatic systems creates a "closed degloving injury" is more generally referred to as a Morel-Lavallée Lesion (MLL). With a consistent pool of blood, lymph, and pieces of soft tissue, an M7LL can cause significant poor cosmesis, chronic pain, and risk secondary infection if left undetected and untreated. Proper diagnosis can be made through the effective use of ultrasound and, if detected early enough, through conservative measures to include needle aspiration and compression sleeves. Prior cases describe chronic MLLs existing for extended periods of time, in some cases years, requiring operative intervention, and in some cases poor outcomes. We present two cases of active duty soldiers presenting with seemingly innocuous injuries found on closer evaluation to have MLL, treated in one case with needle aspiration and compression, in the other with operative management.

Artificial Intelligence and the Simulationists.

SUMMARY STATEMENT: The recent introduction of ChatGPT, an advanced, easy-to-use, and freely available artificial intelligence (AI) program, created new possibilities across many industries and professions including healthcare simulation. ChatGPT has the potential to streamline healthcare simulation-based education while also providing insights for the scenario development process that conventional case development may miss. However, there are issues related to accuracy, relevance, and structure of the products produced by the ChatGPT AI program. This article examines 2 AI-generated simulation case examples highlighting strengths and weaknesses while providing guidance on the use of ChatGPT as a simulation resource.

Structure of puromycin-sensitive aminopeptidase and polyglutamine binding.

Puromycin-sensitive aminopeptidase (E.C. 3.4.11.14, UniProt P55786), a zinc metallopeptidase belonging to the M1 family, degrades a number of bioactive peptides as well as peptides released from the proteasome, including polyglutamine. We report the crystal structure of PSA at 2.3 Ǻ. Overall, the enzyme adopts a V-shaped architecture with four domains characteristic of the M1 family aminopeptidases, but it is in a less compact conformation compared to most M1 enzymes of known structure. A microtubule binding sequence is present in a C-terminal HEAT repeat domain of the enzyme in a position where it might serve to mediate interaction with tubulin. In the catalytic metallopeptidase domain, an elongated active site groove lined with aromatic and hydrophobic residues and a large S1 subsite may play a role in broad substrate recognition. The structure with bound polyglutamine shows a possible interacting mode of this peptide, which is supported by mutation.

Impaired activity and membrane association of most calpain-5 mutants causal for neovascular inflammatory vitreoretinopathy.

Neovascular inflammatory vitreoretinopathy (NIV) is a rare eye disease that ultimately leads to complete blindness and is caused by mutations in the gene encoding calpain-5 (CAPN5), with six pathogenic mutations identified. In transfected SH-SY5Y cells, five of the mutations resulted in decreased membrane association, diminished S-acylation, and reduced calcium-induced autoproteolysis of CAPN5. CAPN5 proteolysis of the autoimmune regulator AIRE was impacted by several NIV mutations. R243, L244, K250 and the adjacent V249 are on ß-strands in the protease core 2 domain. Conformational changes induced by Ca2+binding result in these ß-strands forming a ß-sheet and a hydrophobic pocket which docks W286 side chain away from the catalytic cleft, enabling calpain activation based on comparison with the Ca2+-bound CAPN1 protease core. The pathologic variants R243L, L244P, K250N, and R289W are predicted to disrupt the ß-strands, ß-sheet, and hydrophobic pocket, impairing calpain activation. The mechanism by which these variants impair membrane association is unclear. G376S impacts a conserved residue in the CBSW domain and is predicted to disrupt a loop containing acidic residues which may contribute to membrane binding. G267S did not impair membrane association and resulted in a slight but significant increase in autoproteolytic and proteolytic activity. However, G267S is also identified in individuals without NIV. Combined with the autosomal dominant pattern of NIV inheritance and evidence that CAPN5 may dimerize, the results are consistent with a dominant negative mechanism for the five pathogenic variants which resulted in impaired CAPN5 activity and membrane association and a gain-of-function for the G267S variant.

Interrater agreement between student and teacher assessments of endotracheal intubation skills in a self-directed simulation learning environment.

BACKGROUND: Practical skill assessment is an important part of the learning process to confirm competencies in acquired medical knowledge. OBJECTIVE: This study aimed to compare the assessments of endotracheal intubation skills using the HybridLab® methodology between students and teacher in terms of interobserver reliability. METHODS: Reliability analysis was performed with observational data (data are reported according to STROBE guidelines). The study was conducted in two countries, the Lithuanian University of Health Science (LUHS) and Pennsylvania State University (PSU) in the US, between 1 January and 30 June 2020. A total of 92 students (60 from LUHS and 32 from PSU) were trained in endotracheal intubation using an algorithm-driven hybrid learning method. At the end of the training session, the participants had to complete the evaluation scenario, which was assessed by one of the students and evaluated remotely by a single teacher. The student assessment of the endotracheal intubation procedure was compared with the teacher's assessment using correlation and estimation of the intraclass correlation coefficient. RESULTS: Overall, the medians of the student and teacher assessments were both 100% (0%). Spearman's correlation coefficient between the student and teacher assessments was 0.879 (p = 0.001). The intraclass correlation coefficient used for interobserver variations between the students and teacher was 0.883 (95% confidence interval from 0.824 to 0.923). CONCLUSIONS: The algorithm-driven hybrid learning method allows students to reliably assess endotracheal intubation skills to a level comparable with that of the teacher's evaluation. This learning method has the potential to be a cost-effective and efficient way to provide high-quality education while also saving human resources.

S-acylation regulates the membrane association and activity of Calpain-5.

Calpain-5 (CAPN5) is a member of the calpain family of calcium-activated neutral thiol proteases. CAPN5 is partly membrane associated, despite its lack of a transmembrane domain. Unlike classical calpains, CAPN5 contains a C-terminal C2 domain. C2 domains often have affinity to lipids, mediating membrane association. We recently reported that the C2 domain of CAPN5 was essential for its membrane association and the activation of its autolytic activity. However, despite the removal of the C2 domain by autolysis, the N-terminal fragment of CAPN5 remained membrane associated. S-acylation, also referred to as S-palmitoylation, is a reversible post-translational lipid modification of cysteine residues that promotes membrane association of soluble proteins. In the present study several S-acylated cysteine residues were identified in CAPN5 with the acyl-PEG exchange method. Data reported here demonstrate that CAPN5 is S-acylated on up to three cysteine residues including Cys-4 and Cys-512, and likely Cys-507. The D589N mutation in a potential calcium binding loop within the C2 domain interfered with the S-acylation of CAPN5, likely preventing initial membrane association. Mutating specific cysteine residues of CAPN5 interfered with both its membrane association and the activation of CAPN5 autolysis. Taken together, our results suggest that the S-acylation of CAPN5 is critical for its membrane localization which appears to favor its enzymatic activity.

Phylogenetic and genetic characterization of influenza A H9N2 viruses isolated from backyard poultry in selected farms in Ghana.

INTRODUCTION: Avian influenza viruses (AIV) cause significant economic losses to poultry farmers worldwide. These viruses have the ability to spread rapidly, infect entire poultry flocks, and can pose a threat to human health. The National Influenza Centre (NIC) at the Noguchi Memorial Institute for Medical Research in collaboration with the Ghana Armed forces (GAF) and the U.S. Naval Medical Research Unit No. 3, Ghana Detachment (NAMRU-3) performs biannual surveillance for influenza viruses among poultry at military barracks throughout Ghana. This study presents poultry surveillance data from the years 2017 to 2019. METHODOLOGY: Tracheal and cloacal swabs from sick and healthy poultry were collected from the backyards of GAF personnel living quarters and transported at 4°C to the NIC. Viral ribonucleic acid (RNA) was isolated and analyzed for the presence of influenza viruses using real-time polymerase chain reaction (PCR) assays. Viral nucleic acids extracted from influenza A-positive specimens were sequenced using universal influenza A-specific primers. RESULTS: Influenza A H9N2 virus was detected in 11 avian species out of 2000 samples tested. Phylogenetic analysis of viral haemagglutinin (HA) protein confirms the possibility of importation of viruses from North Africa and Burkina Faso. Although the detected viruses possess molecular markers of virulence and mammalian host adaptation, the HA cleavage site anlaysis confirmed low pathogenicity of the viruses. CONCLUSIONS: These findings confirm the ongoing spread of H9 viruses among poultry in Ghana. Poultry farmers need to be vigilant for sick birds and take the appropriate public health steps to limit the spread to other animals and spillover to humans.

A novel algorithm-driven hybrid simulation learning method to improve acquisition of endotracheal intubation skills: a randomized controlled study.

BACKGROUND: Simulation-based training is a clinical skill learning method that can replicate real-life situations in an interactive manner. In our study, we compared a novel hybrid learning method with conventional simulation learning in the teaching of endotracheal intubation. METHODS: One hundred medical students and residents were randomly divided into two groups and were taught endotracheal intubation. The first group of subjects (control group) studied in the conventional way via lectures and classic simulation-based training sessions. The second group (experimental group) used the hybrid learning method where the teaching process consisted of distance learning and small group peer-to-peer simulation training sessions with remote supervision by the instructors. After the teaching process, endotracheal intubation (ETI) procedures were performed on real patients under the supervision of an anesthesiologist in an operating theater. Each step of the procedure was evaluated by a standardized assessment form (checklist) for both groups. RESULTS: Thirty-four subjects constituted the control group and 43 were in the experimental group. The hybrid group (88%) showed significantly better ETI performance in the operating theater compared with the control group (52%). Further, all hybrid group subjects (100%) followed the correct sequence of actions, while in the control group only 32% followed proper sequencing. CONCLUSIONS: We conclude that our novel algorithm-driven hybrid simulation learning method improves acquisition of endotracheal intubation with a high degree of acceptability and satisfaction by the learners' as compared with classic simulation-based training.

COVID-19 Antibody Prevalence From July to September 2020: One Army Infantry Brigade's Experience.

OBJECTIVES: Lab companies developed serology tests for antibody detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with United States Food and Drug Administration (FDA) emergency use authorization. Antibody detection uses purified proteins of SARS-CoV-2 to determine antibody binding via enzyme-linked immunosorbent assay, chemiluminescent immunoassay (CLIA), or colloidal gold-based immunochromatographic assay. With the advent of coronavirus disease 2019 (COVID-19), nucleic acid amplification technology (NAAT) SARS-CoV-2 testing for active infection was not widely available to healthy, active-duty Soldiers. The purpose of this surveillance survey was to determine the prevalence of prior SARS-CoV-2 infection and symptoms of COVID-19 within a mechanized infantry brigade. MATERIALS AND METHODS: Active-duty military Servicemembers (= 18 years) from a mechanized infantry brigade provided serum samples for testing for the Elecsys® Anti-SARS-CoV-2 qualitative antibody test from June to September 2020 at Joint Base Lewis McChord (JBLM). In addition, participants filled out a questionnaire for symptoms and exposure to COVID-19 from January to September 2020. The surveillance team collected and analyzed antibody testing results and questionnaires from participants for antibody positivity rates and symptom prevalence. RESULTS: A total of 264 participants were tested, with one (0.4%) participant testing positive for the SARS-CoV-2 antibody. On the questionnaire, 144 of 264 (54.5%) endorsed symptoms of COVID-19 from January to September 2020. The most common symptoms were headache (35%), rhinorrhea (34%), cough (35%), and sore throat (31%). A total of 31 respondents (12%) had been quarantined as a trace contact to a COVID-19 positive patient. CONCLUSIONS: While there are limitations inherent to SARS-CoV-2 antibody testing and the survey, prevalence of prior SARS-CoV-2 infection is low. In this sample, symptoms for COVID-19 were prevalent with significant days of duty lost. Prevalence of prior SARS-CoV-2 infection in this sample may be generalizable to the larger brigade. Prevalence of symptoms of possible COVID-19 are not generalizable to the larger brigade. There is utility to further studies of SARS-CoV-2 antibody prevalence in military populations for purposes of vaccination triaging and deployment readiness.

The C2 domain of calpain 5 contributes to enzyme activation and membrane localization.

The enzymatic characteristics of the ubiquitous calpain 5 (CAPN5) remain undescribed despite its high expression in the central nervous system and links to eye development and disease. CAPN5 contains the typical protease core domains but lacks the C terminal penta-EF hand domain of classical calpains, and instead contains a putative C2 domain. This study used the SH-SY5Y neuroblastoma cell line stably transfected with CAPN5-3xFLAG variants to assess the potential roles of the CAPN5 C2 domain in Ca2+ regulated enzyme activity and intracellular localization. Calcium dependent autoproteolysis of CAPN5 was documented and characterized. Mutation of the catalytic Cys81 to Ala or addition of EGTA prevented autolysis. Eighty µM Ca2+ was sufficient to stimulate half-maximal CAPN5 autolysis in cellular lysates. CAPN5 autolysis was inhibited by tri-leucine peptidyl aldehydes, but less effectively by di-Leu aldehydes, consistent with a more open conformation of the protease core relative to classical calpains. In silico modeling revealed a type II topology C2 domain including loops with the potential to bind calcium. Mutation of the acidic amino acid residues predicted to participate in Ca2+ binding, particularly Asp531 and Asp589, resulted in a decrease of CAPN5 membrane association. These residues were also found to be invariant in several genomes. The autolytic fragment of CAPN5 was prevalent in membrane-enriched fractions, but not in cytosolic fractions, suggesting that membrane association facilitates the autoproteolytic activity of CAPN5. Together, these results demonstrate that CAPN5 undergoes Ca2+-activated autoproteolytic processing and suggest that CAPN5 association with membranes enhances CAPN5 autolysis.

Single-domain antibodies for functional targeting of the signaling scaffold Shoc2.

The accurate transmission of signals by the canonical ERK1/2 kinase pathway critically relies on the proper assembly of an intricate multiprotein complex by the scaffold protein Shoc2. However, the details of the mechanism by which Shoc2 guides ERK1/2 signals are not clear, in part, due to the lack of research tools targeting specific protein binding moieties of Shoc2. We report generation and characterization of single domain antibodies against human Shoc2 using a universal synthetic library of humanized nanobodies. Our results identify eight synthetic single-domain antibodies and show that two evaluated antibodies have binding affinities to Shoc2 in the nanomolar range. High affinity antibodies were uniquely suited for the analysis of the Shoc2 complex assembly. Selected single-domain antibodies were also functional in intracellular assays. This study illustrates that Shoc2 single-domain antibodies can be used to understand functional mechanisms governing complex multiprotein signaling modules and have promise in application for therapies that require modulation of the ERK1/2-associated diseases.

Development of an Innovative Nonanimal Training Model for Infant Pleural Effusion Drainage via Pigtail Catheter Placement.

BACKGROUND: Chest tube placement is an important skill for providers and bedside nurses caring for critically ill infants, allowing for the evacuation of pleural fluid and pneumothoraces. No realistic simulation models are commercially available for trainees to practice and learn this skill on infants. PURPOSE: Our objective was to develop an inexpensive and reproducible model for percutaneous pleural pigtail placement for pleural fluid removal via the Seldinger technique. METHODS: The model was developed using hardware material and a discarded infant resuscitation manikin. The rib cage was constructed using electrical cable wires. Discarded and expired 250-mL bags of intravenous fluids were placed inside the chest cavity to simulate pleural fluid. Shelf liner was wrapped around the chest and abdomen of the infant model to simulate the skin layer. Pediatric critical care faculty performed the procedure on the final model and scored it for realism and utility for teaching. Without including the discarded manikin and fluid bags, the cost of the materials for the model was less than $20. RESULTS: Eight pediatric critical care faculty tested the pleural pigtail placement model. All faculty agreed the model provides a realistic simulated reproduction of placing a pleural pigtail, felt the model was simple to use, and indicated they would use it as a teaching tool in the future. IMPLICATIONS FOR PRACTICE: An effective model for pleural pigtail placement can be inexpensively constructed using discarded bags of intravenous fluid and easy-to-find hardware materials. IMPLICATIONS FOR RESEARCH: Future studies are needed to assess whether this model helps providers and nurses develop and maintain the clinical skills for successful percutaneous pleural pigtail catheter placement.Video Abstract available at https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx?videoId=35&autoPlay=true.

The impact of simulation-based medical education on resident management of emergencies in pediatric anesthesiology.

BACKGROUND: Resident education in pediatric anesthesiology is challenging. Traditional curricula for anesthesiology residency programs have included a combination of didactic lectures and mentored clinical service, which can be variable. Limited pediatric medical knowledge, technical inexperience, and heightened resident anxiety further challenge patient care. We developed a pediatric anesthesia simulation-based curriculum to address crises related to hypoxemia and dysrhythmia management in the operating room as an adjunct to traditional didactic and clinical experiences. AIMS: The primary objective of this trial was to evaluate the impact of a simulation curriculum designed for anesthesiology residents on their performance during the management of crises in the pediatric operating room. A secondary objective was to compare the retention of learned knowledge by assessment at the eight-week time point during the rotation. METHODS: In this prospective, observational trial 30 residents were randomized to receive simulation-based education on four perioperative crises (Laryngospasm, Bronchospasm, Supraventricular Tachycardia (SVT), and Bradycardia) during the first week (Group A) or fifth week (Group B) of an eight-week rotation. Assessment sessions that included two scenarios (Laryngospasm, SVT) were performed in the first week, fifth week, and the eighth week of their rotation for all residents. The residents were assessed in real time and by video review using a 7-point checklist generated by a modified Delphi technique of senior pediatric anesthesiology faculty. RESULTS: Residents in Group A showed improvement between the first week and fifth week assessment as well as between first week and eighth week assessments without decrement between the fifth week and eighth week assessments for both the laryngospasm and SVT scenarios. Residents in Group B showed improvement between the first week and eighth week assessments for both scenarios and between the fifth week and eighth week assessment for the SVT scenario. CONCLUSION: This adjunctive simulation-based curriculum enhanced the learner's management of laryngospasm and SVT management and is a reasonable addition to didactic and clinical curricula for anesthesiology residents.

Switchable CAR-T cells mediate remission in metastatic pancreatic ductal adenocarcinoma.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a disease of unmet medical need. While immunotherapy with chimeric antigen receptor T (CAR-T) cells has shown much promise in haematological malignancies, their efficacy for solid tumours is challenged by the lack of tumour-specific antigens required to avoid on-target, off-tumour effects. Switchable CAR-T cells whereby activity of the CAR-T cell is controlled by dosage of a tumour antigen-specific recombinant Fab-based 'switch' to afford a fully tunable response may overcome this translational barrier. DESIGN: In this present study, we have used conventional and switchable CAR-T cells to target the antigen HER2, which is upregulated on tumour cells, but also present at low levels on normal human tissue. We used patient-derived xenograft models derived from patients with stage IV PDAC that mimic the most aggressive features of PDAC, including severe liver and lung metastases. RESULTS: Switchable CAR-T cells followed by administration of the switch directed against human epidermal growth factor receptor 2 (HER2)-induced complete remission in difficult-to-treat, patient-derived advanced pancreatic tumour models. Switchable HER2 CAR-T cells were as effective as conventional HER2 CAR-T cells in vivo testing a range of different CAR-T cell doses. CONCLUSION: These results suggest that a switchable CAR-T system is efficacious against aggressive and disseminated tumours derived from patients with advanced PDAC while affording the potential safety of a control switch.