Yale Journal of Biology and Medicine最新文献

Healthcare systems intend to address health needs of a community, but unfortunately may also inadvertently exacerbate the climate crisis through increased greenhouse gas (GHG) emissions. Clinical medicine has not evolved to promote sustainability practices. New attention to the enormous impact of healthcare systems on GHG emissions and an escalating climate crisis has resulted in some institutions taking proactive measures to mitigate these negative effects. Some healthcare systems have made large-scale changes to conserve energy and materials, resulting in significant monetary savings. In this paper, we share our experience with developing an interdisciplinary work "green" team within our outpatient general pediatrics practice to implement changes, albeit small, to reduce our workplace carbon footprint. We share our experience with reducing paper usage by consolidating vaccine information sheets into a single use information sheet with quick response (QR) codes. We also share ideas for all workplaces to raise awareness of sustainability practices and to foster new ideas to address the climate crisis in both our professional and personal realms. These can help promote hope for the future and shift the collective mindset about climate action.

Background: The discontinuation of the Step 2 Clinical Skills Exam (CS) by the United States Medical Licensing Examination (USMLE) eliminated the need for personal travel to testing centers. The carbon emissions associated with CS have not been previously quantified. Objective: To estimate the annual carbon emissions generated by travel to CS Testing Centers (CSTCs) and to explore differences across geographic regions. Methods: We conducted a cross-sectional, observational study by geocoding medical schools and CSTCs to calculate the distance between them. We obtained data from the 2017 matriculant databases of the Association of American Medical Colleges (AAMC) and the American Association of Colleges of Osteopathic Medicine (AACOM). The independent variable was the location as defined by USMLE geographic regions. The dependent variables were distance traveled to CSTCs and estimated carbon emissions in metric tons CO₂ (mtCO2) calculated using three models. In model 1 all students used single occupancy vehicles; in model 2, all carpooled; and in model 3, half traveled by train and half by single occupancy vehicle. Results: Our analysis included 197 medical schools. The mean out-of-town travel distance was 280.67 miles (IQR: 97.49-383.42). The mtCO2 associated with travel was 2,807.46 for model 1; 3,135.55 for model 2; and 635.34 for model 3. The Western region traveled the farthest, while the Northeast traveled significantly less than other regions. Conclusion: The annual estimated carbon emissions from travel to CSTCs was approximately 3,000 mtCO2. Northeastern students traveled the shortest distances; the average US medical student expended 0.13 mtCO2. Medical leaders must consider the environmental impact of medical curricula and pursue accordant reforms.

Globally, more people die from cardiovascular disease than any other cause. Extreme heat can have serious implications for heart health, especially in people with pre-existing cardiovascular conditions. In this review, we examined the relationship between heat and the leading causes of cardiovascular diseases as well as the proposed physiological mechanisms for the deleterious effect of heat on the heart. The body's response to high temperatures, including dehydration, increased metabolic demand, hypercoagulability, electrolyte imbalances, and systemic inflammatory response, can place a significant strain on the heart. Epidemiological studies showed that heat can result in ischemic heart disease, stroke, heart failure, and arrhythmia. However, targeted research is needed to understand the underlying mechanisms of hot temperatures on these main causes of cardiovascular disease. Meanwhile, the absence of clinical guidance on how to manage heart diseases during heat events highlights the need for cardiologists and other health professionals to lead the charge in addressing the critical relationship between a warming climate and health.

Many chemicals and toxicants are released into our ecosystem and environment every day, which can cause harmful effects on human populations. Agricultural compounds are used in most crop production and have been shown to cause negative health impacts, including effects on reproduction and other pathologies. Although these chemicals can be helpful for pest and weed control, the compounds indirectly impact humans. Several compounds have been banned in the European Union but continue to be used in the United States. Recent work has shown most toxicants affect transgenerational generations more than the directly exposed generations through epigenetic inheritance. While some toxicants do not impact the directly exposed generation, the later generations that are transgenerational or ancestrally exposed suffer health impacts. Due to impacts to future generations, exposure becomes an environmental justice concern. The term "environmental justice" denotes the application of fair strategies when resolving unjust environmental contamination. Fair treatment means that no group should bear a disproportionate share of negative environmental consequences resulting from industrial, municipal, and commercial operations. This article illustrates how research on directly exposed generations is often prioritized over studies on transgenerational generations. However, research on the latter generations suggests the need to take environmental justice concerns seriously moving forward, as future generations could be unduly shouldering harms, while not enjoying benefits of production.

Objective: We aim to comprehensively describe the transcriptional activity and signaling of pulmonary parenchymal and immune cells before and after cardiopulmonary bypass (CPB) by using a multi-omic approach coupled with functional cellular assays. We hypothesize that key signaling pathways from specific cells within the lung alter pulmonary endothelial cell function resulting in worsening or improving disease. Methods: We collected serial tracheobronchial lavage samples from intubated patients less than 2-years-old undergoing surgery with CPB. Samples were immediately processed for single cell RNA sequencing (10x Genomics). Cell clustering, cell-type annotation, and visualization were performed, and differentially expressed genes (DEG) between serial samples were identified. Metabolomic and proteomic analyses were performed on the supernatant using mass spectrometry and a multiplex assay (SomaScan) respectively. Functional assays were done using electric cell-substrate impedance sensing to measure resistance across human pulmonary microvascular endothelial cells (HPMECs). Results: Analysis of eight patients showed a heterogeneous mixture of pulmonary parenchymal and immune cells. Cell clustering demonstrated time-dependent changes in the transcriptomic signature indicating altered cellular phenotypes after CPB. DEG analysis was represented by genes involved in host defense, innate immunity, and the mitochondrial respiratory transport chain. Ingenuity pathway analysis showed upregulation of the integrated stress response across all cell types after CPB. Metabolomic analysis demonstrated upregulation of ascorbate and aldarate metabolism. Unbiased proteomic analysis revealed upregulation of proteins involved in cytokine and chemokine pathways. Post-CPB patient supernatant improved HMPEC barrier function, suggesting a protective cellular response to CPB. Conclusion: Children who undergo CPB for cardiac surgery have distinct cell populations, transcriptional activity, and metabolism that change over time. The response to ischemia-reperfusion injury in the lower airway of children appears to be protective, with the need to identify potential targets through future investigations.

Essential hypertension is caused by the interaction of genetic, behavioral, and environmental factors. Abnormalities in the regulation of renal ion transport cause essential hypertension. The renal dopaminergic system, which inhibits sodium transport in all the nephron segments, is responsible for at least 50% of renal sodium excretion under conditions of moderate sodium excess. Dopaminergic signals are transduced by two families of receptors that belong to the G protein-coupled receptor (GPCR) superfamily. D₁-like receptors (D₁R and D₅R) stimulate, while D2-like receptors (D₂R, D₃R, and D₄R) inhibit adenylyl cyclases. The dopamine receptor subtypes, themselves, or by their interactions, regulate renal sodium transport and blood pressure. We review the role of the D₁R and D₃R and their interaction in the natriuresis associated with volume expansion. The D₁R- and D₃R-mediated inhibition of renal sodium transport involves PKA and PKC-dependent and -independent mechanisms. The D₃R also increases the degradation of NHE3 via USP-mediated ubiquitinylation. Although deletion of Drd1 and Drd3 in mice causes hypertension, DRD1 polymorphisms are not always associated with human essential hypertension and polymorphisms in DRD3 are not associated with human essential hypertension. The impaired D₁R and D₃R function in hypertension is related to their hyper-phosphorylation; GRK4γ isoforms, R65L, A142V, and A486V, hyper-phosphorylate and desensitize D₁R and D₃R. The GRK4 locus is linked to and GRK4 variants are associated with high blood pressure in humans. Thus, GRK4, by itself, and by regulating genes related to the control of blood pressure may explain the "apparent" polygenic nature of essential hypertension.