Summary GCN2 is one of four ‘stress kinases’ that block translation by phosphorylating eIF2α. GCN2 is thought to bind uncharged tRNAs to ‘sense’amino acids availability. In mammals, myeloid cells expressing indoleamine dioxygenases locally deplete tryptophan, which is detected by GCN2 in T cells to cause proliferative arrest. GCN2-deficient T cells were reported to ectopically enter the cell cycle when tryptophan was limiting. Using GCN2-deficient strains crossed to TCR transgenic backgrounds, we found GCN2 is essential for induction of stress target genes such as CHOP. However, GCN2-deficient CD8+ T cells fail to proliferate in limiting tryptophan, arginine, leucine, lysine or asparagine, the opposite of what previous studies concluded. In vitro and in vivo proliferation experiments show that GCN2-deficient CD8+ T cells have T cell-intrinsic proliferative and trafficking defects not observed in CD4+ T cells. Thus GCN2 is required for normal cytotoxic T cell function.
The COVID-19 pandemic has impacted the whole world and raised concerns about its effects on different human organ systems. Early detection of COVID-19 may significantly increase the rate of survival; thus, it is critical that the disease is detected early. Emerging technologies have been used to prevent, diagnose, and manage COVID-19 among the populace in the USA and globally. Numerous studies have revealed the growing implementation of novel engineered systems during the intervention at various points of the disease’s pathogenesis, especially as it relates to comorbidities and complications related to cardiovascular and respiratory organ systems. In this review, we provide a succinct, but extensive, review of the pathogenesis of COVID-19, particularly as it relates to angiotensin-converting enzyme 2 (ACE2) as a viral entry point. This is followed by a comprehensive analysis of cardiovascular and respiratory comorbidities of COVID-19 and novel technologies that are used to diagnose and manage hospitalized patients. Continuous cardiorespiratory monitoring systems, novel machine learning algorithms for rapidly triaging patients, various imaging modalities, wearable immunosensors, hotspot tracking systems, and other emerging technologies are reviewed. COVID-19 effects on the immune system, associated inflammatory biomarkers, and innovative therapies are also assessed. Finally, with emphasis on the impact of wearable and non-wearable systems, this review highlights future technologies that could help diagnose, monitor, and mitigate disease progression. Technologies that account for an individual’s health conditions, comorbidities, and even socioeconomic factors can drastically reduce the high mortality seen among many COVID-19 patients, primarily via disease prevention, early detection, and pertinent management.
Carle Illinois College of Medicine (CIMED) opened its doors in 2018 as an allopathic medical school under provisional accreditation by the Liaison Committee of Medical Education (LCME) and in 2014, the LCME mandated that all U.S. medical schools implement the process of internal continuous quality improvement (CQI). Here, the authors take a retrospective look at how CIMED utilized frequent and granular student feedback to contribute to continuous quality improvement (CQI) during the school’s Respiratory course, by citing specific examples of changes and student satisfaction outcomes from the inaugural class (2018) to the second class (2019). The authors outline how this cycle of evaluation and action can effectively incorporate students into the CQI process to enhance student success via faculty-student partnership. Furthermore, the authors discuss the nuance of feedback interpretation by the involved faculty and advocate for CQI based on a deeper understanding of the student experience such that change initiated by CQI may extend beyond benchmark data collection. The authors discuss how dynamic feedback may be helpful in achieving equipoise between long-standing principles of medical pedagogy and newer trends in medical education, while still maintaining student satisfaction and continuing to develop a culture of quality improvement.
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