An International Virtual COVID-19 Critical Care Training Forum for Healthcare Workers.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic resulted in redeployment of non-critical care-trained providers to intensive care units across the world. Concurrently, traditional venues for delivery of medical education faced major disruptions. The need for a virtual forum to fill knowledge gaps for healthcare workers caring for patients with coronavirus disease (COVID-19) was apparent in the early stages of the pandemic. Objective: The weekly, open-access COVID-19 Critical Care Training Forum (CCCTF) organized by the American Thoracic Society (ATS) provided a global audience access to timely content relevant to their learning needs. The goals of the forum were threefold: to aid healthcare providers in assessment and treatment of patients with COVID-19, to reduce provider anxiety, and to disseminate best practices. Methods: The first 13 ATS CCCTF sessions streamed live from April to July 2020. Structured debriefs followed each session and participant feedback was evaluated in planning of subsequent sessions. A second set of 14 sessions streamed from August to November 2020. Content experts were recruited from academic institutions across the United States. Results: As of July 2020, the ATS CCCTF had 2,494 live participants and 7,687 downloads for a total of 10,181 views. The majority of participants had both completed training (58.6%) and trained in critical care (53.8%). Physicians made up a majority (82.2%) of the audience that spanned the globe (61% were international attendees). Conclusion: We describe the rapid and successful implementation of an open-access medical education forum to address training and knowledge gaps among healthcare personnel caring for patients with COVID-19.

Mst1/2 kinases restrain transformation in a novel transgenic model of Ras driven non-small cell lung cancer.

Non-small cell lung cancer remains a highly lethal malignancy. Using the tamoxifen inducible Hnf1b:CreERT2 (H) transgenic mouse crossed to the LsL-KrasG12D (K) transgenic mouse, we recently discovered that an Hnf1b positive cell type in the lung is sensitive to adenoma formation when expressing a mutant KrasG12D allele. In these mice, we observe adenoma formation over a time frame of three to six months. To study specificity of the inducible Hnf1b:CreERT2 in the lung, we employed lineage tracing using an mTmG (G) reporter allele. This technique revealed recombined, GFP+ cells were predominantly SPC+. We further employed this technique in HKG mice to determine Hnf1b+ cells give rise to adenomas that express SPC and TTF1. Review of murine lung tissue confirmed a diagnosis of adenoma and early adenocarcinoma, a pathologic subtype of non-small cell lung cancer. Our expanded mouse model revealed loss of Mst1/2 promotes aggressive lung adenocarcinoma and large-scale proteomic analysis revealed upregulation of PKM2 in the lungs of mice with genetic deletion of Mst1/2. PKM2 is a known metabolic regulator in proliferating cells and cancer. Using a human lung adenocarcinoma cell line, we show pharmacologic inhibition of Mst1/2 increases the abundance of PKM2, indicating genetic loss or pharmacologic inhibition of Mst1/2 directly modulates the abundance of PKM2. In conclusion, here we report a novel model of non-small cell lung cancer driven by a mutation in Kras and deletion of Mst1/2 kinases. Tumor development is restricted to a subset of alveolar type II cells expressing Hnf1b. Our data show loss of Mst1/2 regulates levels of a potent metabolic regulator, PKM2.

Mutant p53R175H promotes cancer initiation in the pancreas by stabilizing HSP70.

Pancreatic cancer remains a highly lethal malignancy. We have recently shown that simultaneous expression of Kras and mutant Tp53R175H promotes invasive ductal adenocarcinoma from pancreatic ductal cells. We hypothesized specific mutations in TP53 have divergent mechanisms of transforming ductal cells. In order to understand the role of mutant TP53 in transforming pancreatic ductal cells, we used a lentiviral system to express mutant TP53R175H and TP53R273H, two of the most frequently mutated TP53 alleles in pancreatic cancer patients, in immortalized, but not transformed, pancreatic ductal epithelial cells carrying a KRAS mutation (HPNE:KRASG12D). Mutant TP53 expression enhanced colony formation and an RPPA assay results revealed TP53R175H uniquely induced HSP70 expression in HPNE:KRASG12D cells. In the context of TP53R175H expression; we observed nuclear localization of HSP70. We performed immunoprecipitation experiments to show mutant p53R175H binds to HSP70. We also provide evidence mutant p53R175H is important for HSP70 stability and, more importantly, HSP70 is required for mutant p53 stability. These data are critical in the context of events leading to cellular transformation in the pancreas.

A review of undergraduate interprofessional simulation-based education (IPSE).

Interprofessional simulation-based education (IPSE) is becoming an increasingly popular educational strategy worldwide within undergraduate healthcare curricular. The purpose of the literature review was to examine qualitative, quantitative and mixed/multi-method research studies featuring undergraduate IPSE. A literature review was conducted using CINAHL, MEDLINE, and PsycINFO databases from January 1999 to September 2011 and pre-set criteria. The criteria used to screen all 120 abstracts included: (a) the article pertained to both simulation and undergraduate IPE and (b) the article reported a research study. Eighteen articles which met the pre-set criteria were included in the literature review. All studies featured outcome measures; many were purposely designed and lacked psychometric development and evaluation. Key IPSE drivers included capacity planning, preparedness for disaster management and improving patient care through the evaluation of teambuilding, teamwork skills or communicating within inter-disciplinary teams. Studies evaluated/explored either student or teacher perspectives of learning within the context of IPSE or both. The IPSE learning processes varied considerably in relation to duration, fidelity and professions involved. The scenarios ranged from managing adults admitted to hospital settings, mass casualty/mock disaster patient management to the use of training wards. The majority of the articles identified common IPSE outcomes relating to increased confidence, knowledge, leadership, teamwork, and communication skills. Based on the findings of this review, the authors suggest that further multi-site, longitudinal research studies are required to provide evidence of the transferability of skills developed during IPSE and their overall impact on both undergraduate education and healthcare.