Context: In the early months of the response to the coronavirus disease 2019 (COVID-19) pandemic, the Johns Hopkins University School of Medicine (JHUSOM) (Baltimore, Maryland) leadership reached out to faculty to develop and implement virtual clinical clerkships after all in-person medical student clinical experiences were suspended. Objective: To develop and implement a digital slide-based virtual surgical pathology clinical elective to meet the demand for meaningful and robust virtual clinical electives in response to the temporary suspension of in-person clinical rotations at JHUSOM. Design: The Virtual Surgical Pathology (VSP) elective was modeled after the in-person surgical pathology elective, to include virtual previewing and sign-out with standardized cases supplemented by synchronous and asynchronous pathology educational content. Results: Validation of existing web communications technology and slide scanning systems was performed by feasibility testing. Curriculum development included drafting of course objectives and syllabus, Blackboard course site design, electronic-lecture creation, communications with JHUSOM leadership, scheduling, and slide curation. Subjectively, the weekly schedule averaged 35–40 hours to asynchronous, synchronous, and independent content, approximately 10–11 hours of which were synchronous. As of February 2021, VSP has hosted 35 JHUSOM and eight non-JHUSOM students, who have provided positive subjective and objective course feedback. Conclusions: The Johns Hopkins VSP elective provided meaningful clinical experience to 43 students in a time of immense online education need. Added benefits of implementing VSP included increased medical student exposure to pathology as a medical specialty and demonstration of how digital slides have the potential to improve standardization of the pathology clerkship curriculum.
Directed transport delivers proteins to specific cellular locations and is one mechanism by which cells establish and maintain polarized cellular architectures. The atypical cadherin Fat3 directs the polarized extension of dendrites in retinal amacrine cells by influencing the distribution of cytoskeletal regulators during retinal development, however the mechanisms regulating the distribution of Fat3 remain unclear. We report a novel Kinesin/Kif5 Interaction domain (Kif5-ID) in Fat3 that facilitates Kif5B binding, and determines the distribution of Fat3 cytosolic domain constructs in neurons and MDCK cells. The Kif5-ID sequence is conserved in the neurotrophin receptor P75NTR, which also binds Kif5B, and Kif5-ID mutations similarly result in P75NTR mislocalization. Despite these similarities, Kif5B-mediated protein transport is differentially regulated by these two cargos. For Fat3, the Kif5-ID is regulated by alternative splicing, and the timecourse of splicing suggests that the distribution of Fat3 may switch between early and later stages of retinal development. In contrast, P75NTR binding to Kif5B is enhanced by tyrosine phosphorylation and thus has the potential to be dynamically regulated on a more rapid time scale.
Aims: Inverted appendices are rare, but have the potential to cause diagnostic confusion among endoscopists and pathologists. The aim of this study was to describe the clinicopathological features of inverted appendices seen at our institution over the last 30 years. Methods and results: Twenty-one inverted appendices were identified and the clinical and pathological features reviewed. Patients were predominantly middleaged women. Most cases were detected incidentally on colonoscopy. Endoscopically, inverted appendices appeared polypoid in the proximal caecum. All resections featured associated pathological processes, including endometriosis (n = 3), inflammatory mucocoele (n = 1), low-grade appendiceal mucinous neoplasm (n = 2), traditional serrated adenoma (n = 1) and inflammatory fibroid polyp (n = 1). Five cases were endoscopically mischaracterised as caecal polyps and removed via polypectomy; initial pathological impressions were erroneous in most cases. All polypectomies featured a dome-like configuration covered by mucosa on the convex surface; the majority had aggregates of ganglion cells and neural plexi embedded in muscularis propria. The vast majority of cases, regardless of the procedure, showed lymphoid aggregates. Among post-polypectomy patients with follow-up, none experienced perforation-associated morbidity despite the histological presence of muscularis propria. Conclusions: The diagnosis of an inverted appendix should be considered in polypectomy specimens from the caecum or appendiceal orifice with (i) dome-like tissue configuration covered by mucosa on the convex surface, (ii) a deep, robust smooth muscle component with ganglion cells (muscularis propria) and (iii) associated lymphoid aggregates. Prompt recognition on H&E will avoid unnecessary time and resource investment.
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