Articles: human
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Pegbelfermin (BMS-986036), a PEGylated human fibroblast growth factor 21 (FGF21) analogue, has previously been shown to improve markers of metabolism and liver fibrosis in obese patients with type 2 diabetes. In this phase 2a study, we aimed to evaluate the safety and efficacy of pegbelfermin in patients with non-alcoholic steatohepatitis. ⋯ Bristol-Myers Squibb.
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Painful and disabling musculoskeletal disorders remain prevalent. In rats trained to perform repetitive tasks leading to signs and dysfunction similar to those in humans, we tested whether manual therapy would prevent the development of the pathologies and symptoms. We collected behavioral, electrophysiological, and histological data from control rats, rats that trained for 5 weeks before performing a high-repetition high-force (HRHF) task for 3 weeks untreated, and trained rats that performed the task for 3 weeks while being treated 3x/week using modeled manual therapy (MMT) to the forearm (HRHF + MMT). ⋯ Neurons from HRHF rats had a heightened proportion of ongoing activity and altered conduction velocities compared with control and MMT-treated rats. Median nerve branches in HRHF rats contained increased numbers of CD68 macrophages and degraded myelin basic protein, and showed increased extraneural collagen deposition, compared with the other groups. We conclude that the performance of the task for 3 weeks leads to increased ongoing activity in nociceptors, in parallel with behavioral and histological signs of neuritis and nerve injury, and that these pathophysiologies are largely prevented by MMT.
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Angiopoietins are postulated diagnostic biomarkers in children and adults with severe sepsis and septic shock. The diagnostic value of angiopoietins in children less than 5 years old has not been established, nor has their effect on permeability in the capillary microvasculature. We aim to determine if levels of angiopoietin-1 or -2 (angpt-1, -2) are diagnostic for severe sepsis/shock in young children and whether they affect the permeability of cultured human dermal microvascular endothelial cells (HDMEC). ⋯ Angpt-2 levels and the angpt-2/1 ratio are appropriate diagnostic biomarkers of severe sepsis/septic shock in children less than 5 years old. Neither angpt-1 nor -2 affects basal HDMEC permeability alone or modulates TNF induced capillary leak.
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Infant cardiopulmonary bypass (CPB) increases intestinal permeability leading to endotoxemia. Alkaline phosphatase (AP) reduces endotoxin toxicity in vitro but its effects on endotoxemia in human disease are poorly understood. We assessed the association between serum AP activity and endotoxemia in infants undergoing CPB and determined the effect of ex vivo addition of AP on endotoxemia. ⋯ Endotoxemia is common in infants undergoing CPB. Native AP activity and endotoxemia are inversely related and ex vivo addition of exogenous AP reduces whole blood EAA. Future research should evaluate AP as a therapy to reduce the harmful effects of endotoxemia following infant CPB.