To mediate the degradation of bio-macromolecules, lysosomes must traffic towards cargo-carrying vesicles for subsequent membrane fusion or fission. Mutations of the lysosomal Ca2+ channel TRPML1 cause lysosome storage disease (LSD) characterized by disordered lysosomal membrane trafficking in cells. Here we show that TRPML1 activity is required to promote Ca2+-dependent centripetal movement of lysosomes towards the perinuclear region, where autophagosomes accumulate, upon autophagy induction. ALG-2, an EF-hand-containing protein, serves as a lysosomal Ca2+ sensor that associates physically with the minus-end directed dynactin-dynein motor, while PI(3,5)P2, a lysosome-localized phosphoinositide, acts upstream of TRPML1. Furthermore, the PI(3,5)P2-TRPML1-ALG-2-dynein signaling is necessary for lysosome tubulation and reformation. In contrast, the TRPML1 pathway is not required for the perinuclear accumulation of lysosomes observed in many LSDs, which is instead likely caused by secondary cholesterol accumulation that constitutively activates Rab7-RILP-dependent retrograde transport. Collectively, Ca2+ release from lysosomes provides an on-demand mechanism regulating lysosome motility, positioning, and tubulation.

BackgroundCOVID-19 has fundamentally altered how education is delivered. Gordon et al. previously conducted a review of medical education developments in response to COVID-19, however, the field has rapidly evolved in the ensuing months. This scoping review aims to map the extent, range and nature of subsequent developments, summarizing the expanding evidence base and identifying areas for future research. MethodsThe authors followed the five stages of a scoping review outlined by Arskey and O'Malley. Four online databases and MedEdPublish were searched. Two authors independently screened titles, abstracts and full texts. Included articles described developments in medical education deployed in response to COVID-19 and reported outcomes. Data extraction was completed by two authors and synthesized into a variety of maps and charts. ResultsOne hundred twenty-seven articles were included: 104 were from North America, Asia and Europe; 51 were undergraduate, 41 graduate, 22 continuing medical education, and 13 mixed; 35 were implemented by universities, 75 by academic hospitals, and 17 by organizations or collaborations. The focus of developments included pivoting to online learning (n=58), simulation (n=24), assessment (n=11), well-being (n=8), telehealth (n=5), clinical service 2 reconfigurations (n=4), interviews (n=4), service provision (n=2), faculty development (n=2) and other (n=9). The most common Kirkpatrick outcome reported was Level 1, however, a number of studies reported 2a or 2b. A few described Levels 3, 4a, 4b or other outcomes (e.g. quality improvement). ConclusionsThis scoping review mapped the available literature on developments in medical education in response to COVID-19, summarizing developments and outcomes to serve as a guide for future work. The review highlighted areas of relative strength, as well as several gaps. Numerous articles have been written about remote learning and simulation and these areas are ripe for full systematic reviews. Telehealth, interviews and faculty development were lacking and need urgent attention. Practice Points• Most developments to date focused on pivoting to online learning and simulation, making these areas well poised for full systematic reviews.• Research on telehealth, interviews and faculty development to teach in remote environments was lacking and urgently needed.• Several exemplary articles demonstrated the power of collaboration, highlighting opportunities for enhanced cooperation in medical education in the future.

APPENDIX 1: Search StrategyPubMed (covid-19[tw] OR COVID19 [tw] OR OR OR OR severe acute respiratory syndrome coronavirus 2[nm] OR severe acute respiratory syndrome coronavirus 2[tw] OR 2019-nCoV[tw] OR 2019nCoV[tw] OR coronavirus[tw] OR coronavirus[mh] OR pandemic[tw]) AND ("Internship and Residency"[Mesh] OR "Students, Medical"[Mesh] OR "Education, Medical"[Mesh] OR "Schools, Medical"[Mesh] OR Intern[tiab] OR interns[tiab] OR "House officer"[tw] OR "house officers"[tw] OR Resident[ti] OR residents[ti] OR residency[ti] OR "medical education"[tw] OR fellow[tiab] OR fellows[tiab] OR "junior doctor"[tw] OR "junior doctors"[tw] OR "postgraduate"[tw] OR postgraduate[tw] OR "foundation year"[tw] OR "foundation program"[tw] OR "medical student"[tw] OR "medical students"[tw] OR "Curriculum"[mesh] OR curricul*[tiab] OR "medical school"[tw] OR "medical schools"[tw] OR "medical training"[tw] OR "undergraduate"[tw] OR "graduate"[tw] OR Learn*[tw] OR training[tw] OR trainer[tw] OR trainee*[tw] OR instructor*[tw] OR instructional[tw] OR educat*[tw] OR classroom*[tw] OR simulat*[tw] OR virtual[tw] OR ZOOM[tw]) AND ("2020/05/01"[Date -Publication] : "3000"[Date -Publication])

Background: The novel coronavirus disease was declared a pandemic in March 2020, which necessitated adaptations to medical education. This systematic review synthesises published reports of medical educational developments and innovations that pivot to online learning from workplacebased clinical learning in response to the pandemic. The objectives were to synthesise what adaptations/innovation were implemented (description), their impact (justification), and 'how' and 'why' these were selected (explanation and rationale). Methods: The authors systematically searched four online databases up to December 21, 2020. Two authors independently screened titles, abstracts and full-texts, performed data extraction, and assessed the risk of bias. Our findings are reported in alignment with the STORIES (STructured apprOach to the Reporting in healthcare education of Evidence Synthesis) statement and BEME guidance. Results: Fifty-five articles were included. Most were from North America (n ¼ 40), and nearly 70% focused on undergraduate medical education (UGME). Key developments were rapid shifts from workplace-based learning to virtual spaces, including online electives, telesimulation, telehealth, radiology, and pathology image repositories, live-streaming or pre-recorded videos of surgical procedures, stepping up of medical students to support clinical services, remote adaptations for clinical visits, multidisciplinary team meetings and ward rounds. Challenges included lack of personal interactions, lack of standardised telemedicine curricula and need for faculty time, technical resources, and devices. Assessment of risk of bias revealed poor reporting of underpinning theory, resources, setting, educational methods, and content. Conclusions: This review highlights the response of medical educators in deploying adaptations and innovations. Whilst few are new, the complexity, concomitant use of multiple methods and the specific pragmatic choices of educators offers useful insight to clinical teachers who wish to deploy such methods within their own practice. Future works that offer more specific details to allow replication and understanding of conceptual underpinnings are likely to justify an update to this review.

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