RESUMO
Cell death can be executed by regulated apoptotic and nonapoptotic pathways, including the iron-dependent process of ferroptosis. Small molecules are essential tools for studying the regulation of cell death. Using time-lapse imaging and a library of 1,833 bioactive compounds, we assembled a large compendium of kinetic cell death modulatory profiles for inducers of apoptosis and ferroptosis. From this dataset we identify dozens of ferroptosis suppressors, including numerous compounds that appear to act via cryptic off-target antioxidant or iron chelating activities. We show that the FDA-approved drug bazedoxifene acts as a potent radical trapping antioxidant inhibitor of ferroptosis both in vitro and in vivo. ATP-competitive mechanistic target of rapamycin (mTOR) inhibitors, by contrast, are on-target ferroptosis inhibitors. Further investigation revealed both mTOR-dependent and mTOR-independent mechanisms that link amino acid metabolism to ferroptosis sensitivity. These results highlight kinetic modulatory profiling as a useful tool to investigate cell death regulation.
Assuntos
Ferroptose/fisiologia , Aminoácidos/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Sistema Livre de Células , Humanos , Indóis/farmacologia , Quelantes de Ferro/farmacologia , Cinética , Bibliotecas de Moléculas Pequenas , Serina-Treonina Quinases TOR/antagonistas & inibidoresRESUMO
INTRODUCTION: We aimed to search the literature for global surgical curricula, assess if published resources align with existing competency frameworks in global health and surgical education, and determine if there is consensus around a fundamental set of competencies for the developing field of academic global surgery. METHODS: We reviewed SciVerse SCOPUS, PubMed, African Medicus Index, African Journals Online (AJOL), SciELO, Latin American and Caribbean Health Sciences Literature (LILACS) and Bioline for manuscripts on global surgery curricula and evaluated the results using existing competency frameworks in global health and surgical education from Consortium of the Universities for Global Health (CUGH) and Accreditation Council for Graduate Medical Education (ACGME) professional competencies. RESULTS: Our search generated 250 publications, of which 18 were eligible: (1) a total of 10 reported existing competency-based curricula that were concurrent with international experiences, (2) two reported existing pre-departure competency-based curricula, (3) six proposed theoretical competency-based curricula for future global surgery education. All, but one, were based in high-income countries (HICs) and focused on the needs of HIC trainees. None met all 17 competencies, none cited the CUGH competency on "Health Equity and Social Justice" and only one mentioned "Social and Environmental Determinants of Health." Only 22% (n = 4) were available as open-access. CONCLUSION: Currently, there is no universally accepted set of competencies on the fundamentals of academic global surgery. Existing literature are predominantly by and for HIC institutions and trainees. Current frameworks are inadequate for this emerging academic field. The field needs competencies with explicit input from LMIC experts to ensure creation of educational resources that are accessible and relevant to trainees from around the world.
Assuntos
Currículo , Educação de Pós-Graduação em Medicina , Acreditação , Competência Clínica , Saúde GlobalRESUMO
Healthcare is expensive and often inaccessible to many. As a result, surgeons must consider simple, less expensive interventions when possible. For wound care, an older but quite effective cleaning agent is Dakin's solution (0.5% sodium hypochlorite), an easily made mixture of 100 milliliters (ml) bleach with 8 teaspoons (tsp) baking soda into a gallon of clean water or 25 ml bleach and 2 tsp baking soda into a liter of water. Gauze is then wet with this solution, placed on the wound, and replaced every 24 hours as needed. Our team of surgeons in Haiti and the United States is currently using Dakin's solution for wound care following orthopedic surgery and finds it to be a low-cost, safe, and effective treatment for post-surgical wound care for both resource-limited and non-resource strained environments. This report aims to update the current literature and encourage the consideration of Dakin's solution for modern wound care.