Practical Applications of ChatGPT in Undergraduate Medical Education.

ChatGPT is a chatbot developed by OpenAI that has garnered significant attention for achieving at or near a passing standard on the United States Medical Licensing Exam (USMLE). Currently, researchers and users are exploring ChatGPT's broad range of potential applications in academia, business, programming, and beyond. We attempt outline how ChatGPT may be applied to support undergraduate medical education during the preclinical and clinical years, and highlight possible concerns regarding its use which necessitates the creation of formal policies and training by medical schools.

The #Tweetorial: an Underutilized Teaching Tool in Undergraduate Medical Education?

Tweetorials are short, self-contained Twitter threads that provide a concise overview of a topic. Recently, they have gained prominence in the Twitter medical community (#MedTwitter) as a medium for teaching and reviewing topics from foundational medical physiological concepts through to complex clinical case presentations. With medical schools increasingly utilizing case-based learning in their curricula, the Tweetorial may have a role in bridging the foundational and clinical sciences while challenging the clinical decision-making acumen of learners. We outline how Tweetorials may be utilized to support self-directed, asynchronous learning amidst increasingly brimming medical curricula and provide undergraduate medical students real-time access to educators, and discuss limitations that may hamper their implementation.

And Still She Rises: Policies for Improving Women's Health for a More Equitable Post-Pandemic World.

The COVID-19 pandemic has spawned crises of violence, hunger and impoverishment. Maternal and Infant Health Canada (MIHCan) conducted this policy action study to explore how changes that have arisen during the COVID-19 pandemic may catalyze potential improvements in global women's health toward the creation of a more equitable post-pandemic world. In this mixed methods study, 280 experts in women's health responded to our survey and 65 subsequently participated in focus groups, including professionals from India, Egypt/Sudan, Canada and the United States/Mexico. From the results of this study, our recommendations include augmenting mental health through more open dialogue, valuing and compensating those working on the frontlines through living wages, paid sick leave and enhanced benefits and expanding digital technology that facilitates flexible work locations, thereby freeing time for improving the wellbeing of caregivers and families and offering telemedicine and telecounseling, which delivers greater access to care. We also recommend bridging the digital divide through the widespread provision of reliable and affordable internet services and digital literacy training. These policy recommendations for employers, governments and health authorities aim to improve mental and physical wellbeing and working conditions, while leveraging the potential of digital technology for healthcare provision for those who identify as women, knowing that others will benefit. MIHCan took action on the recommendation to improve mental health through open conversation by facilitating campaigns in all study regions. Despite the devastation of the pandemic on global women's health, implementing these changes could yield improvements for years to come.

Patient Perspectives on the Digitization of Personal Health Information in the Emergency Department: Mixed Methods Study During the COVID-19 Pandemic.

BACKGROUND: Although the digitization of personal health information (PHI) has been shown to improve patient engagement in the primary care setting, patient perspectives on its impact in the emergency department (ED) are unknown. OBJECTIVE: The primary objective was to characterize the views of ED users in British Columbia, Canada, on the impacts of PHI digitization on ED care. METHODS: This was a mixed methods study consisting of an online survey followed by key informant interviews with a subset of survey respondents. ED users in British Columbia were asked about their ED experiences and attitudes toward PHI digitization in the ED. RESULTS: A total of 108 participants submitted survey responses between January and April 2020. Most survey respondents were interested in the use of electronic health records (79/105, 75%) and patient portals (91/107, 85%) in the ED and were amenable to sharing their ED PHI with ED staff (up to 90% in emergencies), family physicians (up to 91%), and family caregivers (up to 75%). In addition, 16 survey respondents provided key informant interviews in August 2020. Interviewees expected PHI digitization in the ED to enhance PHI access by health providers, patient-provider relationships, patient self-advocacy, and postdischarge care management, although some voiced concerns about patient privacy risk and limited access to digital technologies (eg, smart devices, internet connection). Many participants thought the COVID-19 pandemic could provide momentum for the digitization of health care. CONCLUSIONS: Patients overwhelmingly support PHI digitization in the form of electronic health records and patient portals in the ED. The COVID-19 pandemic may represent a critical moment for the development and implementation of these tools.

Distinct focal adhesion protein modules control different aspects of mechanotransduction.

Focal adhesions (FAs) are macromolecular complexes that regulate cell adhesion and mechanotransduction. By performing fluorescence recovery after photobleaching (FRAP) and fluorescence loss after photoactivation (FLAP) experiments, we found that the mobility of core FA proteins correlates with their function. Structural proteins such as tensin, talin and vinculin are significantly less mobile in FAs than signaling proteins such as FAK (also known as PTK2) and paxillin. The mobilities of the structural proteins are directly influenced by substrate stiffness, suggesting that they are involved in sensing the rigidity of the extracellular environment. The turnover rates of FAK and paxillin, as well as kindlin2 (also known as FERMT2), are not influenced by substrate stiffness. By using specific Src and FAK inhibitors, we reveal that force-sensing by vinculin occurs independently of FAK and paxillin phosphorylation. However, their phosphorylation is required for downstream Rac1-driven cellular processes, such as protrusion and cell migration. Overall, we show that the FA is composed of different functional modules that separately control mechanosensing and the cellular mechano-response.

Vinculin controls talin engagement with the actomyosin machinery.

The link between extracellular-matrix-bound integrins and intracellular F-actin is essential for cell spreading and migration. Here, we demonstrate how the actin-binding proteins talin and vinculin cooperate to provide this link. By expressing structure-based talin mutants in talin null cells, we show that while the C-terminal actin-binding site (ABS3) in talin is required for adhesion complex assembly, the central ABS2 is essential for focal adhesion (FA) maturation. Thus, although ABS2 mutants support cell spreading, the cells lack FAs, fail to polarize and exert reduced force on the surrounding matrix. ABS2 is inhibited by the preceding mechanosensitive vinculin-binding R3 domain, and deletion of R2R3 or expression of constitutively active vinculin generates stable force-independent FAs, although cell polarity is compromised. Our data suggest a model whereby force acting on integrin-talin complexes via ABS3 promotes R3 unfolding and vinculin binding, activating ABS2 and locking talin into an actin-binding configuration that stabilizes FAs.

RIAM and vinculin binding to talin are mutually exclusive and regulate adhesion assembly and turnover.

Talin activates integrins, couples them to F-actin, and recruits vinculin to focal adhesions (FAs). Here, we report the structural characterization of the talin rod: 13 helical bundles (R1-R13) organized into a compact cluster of four-helix bundles (R2-R4) within a linear chain of five-helix bundles. Nine of the bundles contain vinculin-binding sites (VBS); R2R3 are atypical, with each containing two VBS. Talin R2R3 also binds synergistically to RIAM, a Rap1 effector involved in integrin activation. Biochemical and structural data show that vinculin and RIAM binding to R2R3 is mutually exclusive. Moreover, vinculin binding requires domain unfolding, whereas RIAM binds the folded R2R3 double domain. In cells, RIAM is enriched in nascent adhesions at the leading edge whereas vinculin is enriched in FAs. We propose a model in which RIAM binding to R2R3 initially recruits talin to membranes where it activates integrins. As talin engages F-actin, force exerted on R2R3 disrupts RIAM binding and exposes the VBS, which recruit vinculin to stabilize the complex.

Vinculin regulates the recruitment and release of core focal adhesion proteins in a force-dependent manner.

BACKGROUND: Cells sense the extracellular environment using adhesion receptors (integrins) linked to the intracellular actin cytoskeleton through a complex network of regulatory proteins that, all together, form focal adhesions (FAs). The molecular basis of how these sensing units are regulated, how they are implicated in transducing mechanical stimuli, and how this leads to a spatiotemporal coordination of FAs is unclear. RESULTS: Here we show that vinculin, through its links to the talin-integrin complex and F-actin, regulates the transmission of mechanical signals from the extracellular matrix to the actomyosin machinery. We demonstrate that the vinculin interaction with the talin-integrin complex drives the recruitment and release of core FA components. The activation state of vinculin is itself regulated by force, as underscored by our observation that vinculin localization to FAs is dependent on actomyosin contraction. Using a variety of vinculin mutants, we establish which components of the cell-matrix adhesion network are coordinated through direct and indirect associations with vinculin. Moreover, using cyclic stretching, we demonstrate that vinculin plays a key role in the transmission of extracellular mechanical stimuli leading to the reorganization of cell polarity. Of particular importance is the actin-binding tail region of vinculin, without which the cell's ability to repolarize in response to cyclic stretching is perturbed. CONCLUSIONS: Overall our data promote a model whereby vinculin controls the transmission of intracellular and extracellular mechanical cues that are important for the spatiotemporal assembly, disassembly, and reorganization of FAs to coordinate polarized cell motility.

Specific ß-containing integrins exert differential control on proliferation and two-dimensional collective cell migration in mammary epithelial cells.

Understanding how cell cycle is regulated in normal mammary epithelia is essential for deciphering defects of breast cancer and therefore for developing new therapies. Signals provided by both the extracellular matrix and growth factors are essential for epithelial cell proliferation. However, the mechanisms by which adhesion controls cell cycle in normal epithelia are poorly established. In this study, we describe the consequences of removing the ß1-integrin gene from primary cultures of mammary epithelial cells in situ, using CreER. Upon ß1-integrin gene deletion, the cells were unable to progress efficiently through S-phase, but were still able to undergo collective two-dimensional migration. These responses are explained by the presence of ß3-integrin in ß1-integrin-null cells, indicating that integrins containing different ß-subunits exert differential control on mammary epithelial proliferation and migration. ß1-Integrin deletion did not inhibit growth factor signaling to Erk or prevent the recruitment of core adhesome components to focal adhesions. Instead the S-phase arrest resulted from defective Rac activation and Erk translocation to the nucleus. Rac inhibition prevented Erk translocation and blocked proliferation. Activated Rac1 rescued the proliferation defect in ß1-integrin-depleted cells, indicating that this GTPase is essential in propagating proliferative ß1-integrin signals. These results show that ß1-integrins promote cell cycle in mammary epithelial cells, whereas ß3-integrins are involved in migration.

Fluorescence recovery after photobleaching.

This chapter describes the use of microscope-based fluorescence recovery after photobleaching (FRAP). To quantify the dynamics of proteins within a subcellular compartment, we first outline the general aspects of FRAP experiments and then provide a detailed protocol of how to measure and analyse the most important parameters of FRAP experiments such as mobile fraction and half-time of recovery.