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Nature Jul 2023The function of a cell is defined by its intrinsic characteristics and its niche: the tissue microenvironment in which it dwells. Here we combine single-cell and spatial...
The function of a cell is defined by its intrinsic characteristics and its niche: the tissue microenvironment in which it dwells. Here we combine single-cell and spatial transcriptomics data to discover cellular niches within eight regions of the human heart. We map cells to microanatomical locations and integrate knowledge-based and unsupervised structural annotations. We also profile the cells of the human cardiac conduction system. The results revealed their distinctive repertoire of ion channels, G-protein-coupled receptors (GPCRs) and regulatory networks, and implicated FOXP2 in the pacemaker phenotype. We show that the sinoatrial node is compartmentalized, with a core of pacemaker cells, fibroblasts and glial cells supporting glutamatergic signalling. Using a custom CellPhoneDB.org module, we identify trans-synaptic pacemaker cell interactions with glia. We introduce a druggable target prediction tool, drug2cell, which leverages single-cell profiles and drug-target interactions to provide mechanistic insights into the chronotropic effects of drugs, including GLP-1 analogues. In the epicardium, we show enrichment of both IgG and IgA plasma cells forming immune niches that may contribute to infection defence. Overall, we provide new clarity to cardiac electro-anatomy and immunology, and our suite of computational approaches can be applied to other tissues and organs.
Topics: Humans; Cell Communication; Cellular Microenvironment; Fibroblasts; Glutamic Acid; Heart; Ion Channels; Multiomics; Myocardium; Myocytes, Cardiac; Neuroglia; Pericardium; Plasma Cells; Receptors, G-Protein-Coupled; Sinoatrial Node; Heart Conduction System
PubMed: 37438528
DOI: 10.1038/s41586-023-06311-1 -
Journal of Medical Ultrasound 2023The main cause of death in traumas is hypovolemic shock. Physical examination is limited to detect hemopericardium, hemoperitoneum, and hemopneumothorax. Computed... (Review)
Review
The main cause of death in traumas is hypovolemic shock. Physical examination is limited to detect hemopericardium, hemoperitoneum, and hemopneumothorax. Computed tomography (CT) is the gold standard for traumatic injury evaluation. However, CT is not always available, is more expensive, and there are transportation issues, especially in hemodynamically unstable patients. In this scenario, a rapid, reproducible, portable, and noninvasive method such as ultrasound emerged, directed for detecting hemopericardium, hemoperitoneum, and hemopneumothorax, in a "point of care" modality, known as the focused assessment with sonography for trauma (FAST) protocol. With decades of experience, spread worldwide, and recommended by the most prestigious trauma care guidelines, FAST is a bedside ultrasound to be performed when accessing circulation issues of trauma patients. It is indicated to hemodynamically unstable patients with blunt abdominal trauma, with penetrating trauma of the thoracoabdominal transition (where there is doubt of penetrating the abdominal cavity) and for any patient with the cause of the instability unknown. There are four regions to be examined in the traditional FAST protocol: pericardium (to detect cardiac tamponade), right upper abdominal quadrant, left upper abdominal quadrant, and pelvis (to detect hemoperitoneum). The called extended FAST (e-FAST) protocol also searches the pleural spaces for hemothorax and pneumothorax. It is important to know the false positives and false negatives of the protocol, as well as its limitations. FAST/e-FAST protocol is designed to provide a simple "yes or no" answer regarding the presence of bleeding. It is not intended to quantify the bleeding nor evaluate organ lesions due to its limited accuracy for these purposes. Moreover, the amount of bleeding and/or the identification of organ lesions will not change patient's management: Hemodynamically unstable patients with positive FAST must go to the operating room without delay. CT should be considered for hemodynamically stable patients.
PubMed: 37576415
DOI: 10.4103/jmu.jmu_12_23