Global Health Education Revamped: Implementation of a Cross-Cultural Virtual Elective Through Continuous Improvement Methods.

Introduction: Virtual platforms can increase access to global health (GH) education and cross-cultural communication. The Cleveland-Cusco Connection (CCC) is a virtual GH elective between medical schools in the USA and Peru. This elective was held annually from 2020 to 2023, with monthly virtual sessions held in English and Spanish to facilitate bidirectional learning about healthcare systems, culture, and barriers to care in both nations. Using student surveys throughout the electives, we report the outcomes, barriers, and changes of the CCC over 3 years. Methods: We administered pre- and post-elective surveys to students in the elective in their native languages. We evaluated self-reported non-native language skills, health systems, GH knowledge, and cultural sensitivity. We also surveyed students about course efficacy in achieving learning objectives and areas for improvement. We performed non-parametric statistical analyses to evaluate trends in survey responses. Results: Over three academic years, 92 students participated in CCC. Students from the US had statistically significant increases in their self-reported understanding of the Peruvian healthcare and medical education systems (p = 0.013). US students also saw an increase in cultural sensitivity scores, with statistically significant increases in the knowledge (p = 0.035) and motivation components (p = 0.031). The most frequently reported challenges encountered throughout the course included: competing coursework assignments, scheduling conflicts, and language barriers. Discussion: Cross-cultural virtual electives demonstrate effectiveness in teaching trainees about international healthcare systems and can improve cultural sensitivity. Strategies to improve the elective include reducing workload, improving engagement for partner countries, and teaching bilingually. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01941-6.

14-3-3 signal adaptor and scaffold proteins mediate GPCR trafficking.

Receptor trafficking is pivotal for the temporal and spatial control of GPCR signaling and is regulated by multiple cellular proteins. We provide evidence that GPCRs interact with 14-3-3 signal adaptor/scaffold proteins and that this interaction regulates receptor trafficking in two ways. We found GPCR/14-3-3 interaction signals can be agonist-induced or agonist-inhibited. Some GPCRs associate with 14-3-3 proteins at the cell membrane and agonist treatments result in disrupted GPCR/14-3-3 interaction signals. The diminished GPCR/14-3-3 interaction signals are temporally correlated with increased GPCR/ß-arrestin interaction signals in response to agonist treatment. Other GPCRs showed agonist-induced GPCR/14-3-3 interaction signal increases that occur later than agonist-induced GPCR/ß-arrestin interaction signals, indicating that GPCR/14-3-3 interaction occurred after receptor endocytosis. These two types of GPCR/14-3-3 interaction patterns correlate with different receptor trafficking patterns. In addition, the bioinformatic analysis predicts that approximately 90% of GPCRs contain at least one putative 14-3-3 binding motif, suggesting GPCR/14-3-3 association could be a general phenomenon. Based on these results and collective evidence, we propose a working model whereby 14-3-3 serves as a sorting factor to regulate receptor trafficking.

G-protein-coupled receptors mediate 14-3-3 signal transduction.

G-protein-coupled receptor (GPCR)-interacting proteins likely participate in regulating GPCR signaling by eliciting specific signal transduction cascades, inducing cross-talk with other pathways, and fine tuning the signal. However, except for G-proteins and ß-arrestins, other GPCR-interacting proteins are poorly characterized. 14-3-3 proteins are signal adaptors, and their participation in GPCR signaling is not well understood or recognized. Here we demonstrate that GPCR-mediated 14-3-3 signaling is ligand-regulated and is likely to be a more general phenomenon than suggested by the previous reports of 14-3-3 involvement with a few GPCRs. For the first time, we can pharmacologically characterize GPCR/14-3-3 signaling. We have shown that GPCR-mediated 14-3-3 signaling is phosphorylation-dependent, and that the GPCR/14-3-3 interaction likely occurs later than receptor desensitization and internalization. GPCR-mediated 14-3-3 signaling can be ß-arrestin-independent, and individual agonists can have different potencies on 14-3-3 and ß-arrestin signaling. GPCRs can also mediate the interaction between 14-3-3 and Raf-1. Our work opens up a new broad realm of previously unappreciated GPCR signal transduction. Linking GPCRs to 14-3-3 signal transduction creates the potential for the development of new research directions and provides a new signaling pathway for drug discovery.

ERK and ß-arrestin interaction: a converging point of signaling pathways for multiple types of cell surface receptors.

ß-Arrestin, a signal adaptor protein, mediates intracellular signal transductions through protein-protein interactions by bringing two or more proteins in proximity. Extracellular signal-regulated kinase (ERK), a protein kinase in the family of mitogen-activated protein kinases (MAPKs), is involved in various receptor signal pathways. Interaction of ERK with ß-arrestin or formation of ERK/ß-arrestin signal complex occurs in response to activation of a variety of cell surface receptors. The ERK/ß-arrestin signal complex may be a common transducer to converge a variety of extracellular stimuli to similar downstream intracellular signaling pathways. By using a cell-based protein-protein interaction LinkLight assay technology, we demonstrate a direct interaction between ERK and ß-arrestin in response to extracellular stimuli, which can be sensitively and quantitatively monitored. Activations of G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), and cytokine receptors promote formation of the ERK/ß-arrestin signal complex. Our data indicate that the ERK/ß-arrestin signal complex is a common transducer that participates in a variety of receptor signaling pathways. Furthermore, we demonstrate that receptor antagonists or kinase inhibitors can block the agonist-induced ERK and ß-arrestin interaction. Thus, the ERK/ß-arrestin interaction assay is useful for screening of new receptor modulators.