Articles: human.
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There is growing evidence suggesting that the dysregulation of circular RNAs (circRNAs) plays a significant role in various myocardial disorders, including myocardial ischemia (MI). This study aimed to explore the function of hsa_circ_0068655 (circ_0068655) in hypoxia-induced cardiomyocyte injury. ⋯ Circ_0068655 silencing ameliorated hypoxia-induced human cardiomyocyte injury through the miR-370-3p/BCL2L11 axis.
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Anesthesia and analgesia · Nov 2024
Cannabinoids and General Anesthetics: Revisiting Molecular Mechanisms of Their Pharmacological Interactions.
Cannabis has been used for recreation and medical purposes for more than a millennium across the world; however, its use's consequences remain poorly understood. Although a growing number of surgical patients are regular cannabis consumers, little is known regarding the pharmacological interactions between cannabis and general anesthetics; consequently, there is not a solid consensus among anesthesiologists on the perioperative management of these patients. The existing evidence about the molecular mechanisms underlying pharmacological interactions between cannabinoids and anesthetic agents, both in animal models and in humans, shows divergent results. ⋯ Animal studies have reported that cannabinoids enhance the analgesic effect of opioids due to a synergistic interaction of the endogenous cannabinoid system (ECS) with the endogenous opioid system (EOS) at the spinal cord level and in the central nervous system. However, human data reveals that cannabis users show higher scores of postoperative pain intensity as well as increased requirements of opioid medication for analgesia. This review aims to improve understanding of the molecular mechanisms and pharmacological interactions between cannabis and anesthetic drugs and the clinical outcomes that occur when these substances are used together.
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Warfighters are exposed to life-threatening injuries daily and according to the Joint Trauma System Military Clinical Practice Guideline-Global Snake Envenomation Management snakebites are a concerning threat in all theaters of operation. Snake venom is a complex mixture of toxins including phospholipases A2 (PLA2) and snake venom metalloproteinases (SVMP) that produce myotoxic, hemotoxic, and cytotoxic injuries. Antibody-based antivenom is the standard of care but new approaches including small-molecule inhibitors have gained attention in recent years. Doxycycline is an effective inhibitor of human metalloproteinases and PLA2. The enzymatic activities of 3 phylogenetically distinct snakes: Agkistrodon piscivorus, Naja kaouthia, and Daboia russelii were tested under inhibitory conditions using doxycycline. ⋯ Doxycycline reduced PLA2- and SVMP-related lethality, particularly in A. piscivorus envenomings and in a limited capacity with D. russelii revealing its promise as a treatment for snakebites. In addition, CK activity, a common indicator of muscle damage was inhibited in mice that received doxycycline-treated venom. The doxycycline concentrations identified in the ED50 studies correspond to 1,456 to 5,061 mg dosages for a 70 kg human. Factors including venom yield and snake species would affect the actual dosage needed. Studies into high-dose doxycycline safety and its effectiveness against several snake species is needed to fully translate its use into humans. Based on this work, doxycycline could be used as a treatment en route to higher echelons of care, providing protection from muscle damage and reducing lethality in different snake species.
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Mayo Clinic proceedings · Nov 2024
Mayo Clinic Tapestry Study: A Large-Scale Decentralized Whole Exome Sequencing Study for Clinical Practice, Research Discovery, and Genomic Education.
To execute a large-scale, decentralized, clinical-grade whole exome sequencing study, coined Tapestry, for clinical practice, research discovery, and genomic education. ⋯ A large, decentralized, clinical Exome+ assay study in a tertiary medical center detects actionable germline variants, educates patients as well as providers, and offers access to big data for discovery that advances human health.
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In prolonged care scenarios, where medical evacuations are significantly delayed, the treatment and transport of casualties with extremity musculoskeletal injuries will drain combat units' human resources. Developing enhanced splinting techniques to restore casualty mobility and function can alleviate this drain. To guide this development, a panel of tactical combat and wilderness medicine experts was assembled to determine which extremity musculoskeletal injuries had the greatest impact on unit capabilities, and the materials available for splinting these injuries. ⋯ Although the combined impact of knee and ankle ligamentous injuries were ranked the highest, limitations in relative rankings and the existence of effective low-cost treatments for these injuries suggest that greater gains in unit effectiveness would come from focusing on developing solutions for fractures with higher human resource cost, such as leg and arm fractures. This information can be used to develop enhanced splints that can preserve unit readiness in the field.