Articles: function.
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Axial spondyloarthritis is an immune-mediated inflammatory condition involving the sacroiliac joints, spine, and peripheral joints. It affects approximately 1% of adults in the US and is associated with impaired physical function and reduced quality of life. ⋯ Axial spondyloarthritis predominantly affects the sacroiliac joints and spine but is also associated with extraskeletal manifestations such as uveitis, psoriasis, and inflammatory bowel disease. Physical therapy and NSAIDs are first-line treatments, but most patients require therapy with biologics (anti-TNF or anti-IL-17 agents) or JAK inhibitors to achieve improvement in signs and symptoms, inflammation control, and reduced progression of structural damage.
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A well-recognized molecular entity involved in pain-related neuroplasticity is the N-methyl-D-aspartate receptor (NMDAR), which is crucial for developing chronic pain. Likewise, the pannexin 1 (Panx1) channel has been described as necessary for initiating and maintaining neuropathic pain, driving nociceptive signals dependent on spinal NMDAR through several possible mechanisms. Through behavioral, pharmacological, and molecular approaches, our study in male rats has revealed several key findings: (1) neurons located in spinal cord laminae I and II express functional Panx1 channels in both neuropathic and sham rats. ⋯ Notably, while 10Panx successfully alleviates hyperalgesia, it does not alter pSrc expression; and (4) NMDA-stimulated YOPRO-1 uptake in neurons of laminae I-II of spinal cord slices were prevented by the NMDAR antagonist D-AP5, the Src inhibitor PP2 (but not PP3), as well as with the 10Panx and carbenoxolone. Therefore, NMDAR activation in dorsal horn neurons triggers an NMDAR-Src-Panx1 signaling pathway, where Panx1 acts as an enhancing effector in neuropathic pain. This implies that disrupting the NMDAR-Panx1 communication (eg, through Src inhibitors and/or Panx1 blockers) may offer a valuable strategy for managing some forms of chronic pain.
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Critical care medicine · Dec 2024
Evaluation of a Physiologic-Driven Closed-Loop Resuscitation Algorithm in an Animal Model of Hemorrhagic Shock.
Appropriate resuscitation from hemorrhagic shock is critical to restore tissue perfusion and to avoid over-resuscitation. The objective of this study was to test the ability of a closed-loop diagnosis and resuscitation algorithm called resuscitation from shock using functional hemodynamic monitoring using invasive monitoring (ReFit1) and minimally invasive monitoring (ReFit2) to identify, treat, and stabilize a porcine model of severe hemorrhagic shock. ⋯ Our physiologically based functional hemodynamic monitoring-centered closed-loop resuscitation system can effectively diagnose and treat cardiovascular shock due to hemorrhage and air embolism.
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Critical care medicine · Dec 2024
Inability to Sit-to-Stand in Medical ICUs Survivors: When and Why We Should Care.
To investigate the prevalence and association with mortality of inability to perform sit-to-stand independently in critically ill survivors 3 months following medical ICU (MICU) discharge. ⋯ Inability to sit-to-stand affects about 36% of MICU survivors even at 3 months post-ICU discharge, highlighting rehabilitation challenges. Revisiting sit-to-stand ability post-ICU discharge is warranted. Additionally, using sit-to-stand as a screening tool for interventions to improve return of its function and mortality is suggested.