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014) and GFR on admission (
= 0.004) were independently associated with development of AKI. The number of days of hypertonic saline infusion (
= 0.79) without the persistence of hyperchloremia and highest serum chloride levels (
= 0.23) were not predictive of AKI development.
In patients with traumatic brain injury, admission GFR and prolonged hyperchloremia rather than the highest chloride level or the duration of hypertonic saline infusion were associated with the development of AKI.
In patients with traumatic brain injury, admission GFR and prolonged hyperchloremia rather than the highest chloride level or the duration of hypertonic saline infusion were associated with the development of AKI.Cardiomyocytes (CMs) derived from induced pluripotent stem cells (iPSCs) provide an in vitro model of the human myocardium. Complex 3D scaffolded culture methods improve the phenotypical maturity of iPSC-CMs, although typically at the expense of throughput. We have developed a novel, scalable approach that enables the use of iPSC-CM 3D spheroid models in a label-free readout system in a standard 96-well plate-based format. Spheroids were accurately positioned onto recording electrodes using a magnetic gold-iron oxide nanoparticle approach. Remarkably, both contractility (impedance) and extracellular field potentials (EFPs) could be detected from the actively beating spheroids over long durations and after automated dosing with pharmacological agents. The effects on these parameters of factors, such as co-culture (including human primary cardiac fibroblasts), extracellular buffer composition, and electrical pacing, were investigated. Beat amplitudes were increased greater than 15-fold by co-culture with fibroblasts. Optimization of extracellular Ca2+ fluxes and electrical pacing promoted the proper physiological response to positive inotropic agonists of increased beat amplitude (force) rather than the increased beat rate often observed in iPSC-CM studies. Mechanistically divergent repolarizations in different spheroid models were indicated by their responses to BaCl2 compared with E-4031. These studies demonstrate a new method that enables the pharmacological responses of 3D iPSC-CM spheroids to be determined in a label-free, standardized, 96-well plate-based system. This approach could have discovery applications across cardiovascular efficacy and safety, where parameters typically sought as readouts of iPSC-CM maturity or physiological relevance have the potential to improve assay predictivity.
Carotid artery stenting (CAS) has increasingly emerged as an alternative strategy to carotid endarterectomy in the treatment of patients with symptomatic carotid stenosis. Optimal timing for CAS after symptoms onset remains unclear. We aimed to evaluate the safety and efficacy of CAS when performed in an emergency setting.
We performed a retrospective analysis of CAS patients admitted to our CSC with symptomatic extracranial carotid occlusion or significant stenosis from January 2014-September 2019. Emergency CAS was defined as CAS performed during the same hospitalization from TIA/stroke onset, whereas elective CAS as CAS performed on a subsequent admission. The primary outcome was defined as the occurrence of any stroke, myocardial infarction, or death related to the procedure at 3 months of follow-up. Secondary outcomes included periprocedural complications and the rate of restenosis/occlusion at follow-up. Logistic regression and survival analyses were used to compare outcomes and restenosis at follow-up.
We identified 75 emergency and 104 elective CAS patients. Emergency CAS patients had significantly higher rates of ipsilateral carotid occlusion (17% vs. 2%, p < 0.001) and use of general anesthesia (19% vs. 4%, p = 0.001) than elective CAS. There were no significant differences between emergency and elective CAS in the primary (5.7% vs. 1%, p = 0.161) and secondary (9% vs. 4.8%, p = 0.232) outcomes. We did not find differences in the rate of restenosis/occlusion (7% vs. 11.6%; log-rank test p = 0.3) at a median of 13 months follow-up.
In our study, emergency CAS in symptomatic patients might have a similar safety and efficacy profile to elective CAS at 3 months and long-term follow-up.
In our study, emergency CAS in symptomatic patients might have a similar safety and efficacy profile to elective CAS at 3 months and long-term follow-up.Background Venous neointimal hyperplasia and venous stenosis (VS) formation can result in a decrease in arteriovenous fistula (AVF) patency in patients with end-stage renal disease. There are limited therapies that prevent VNH/VS. Systemic delivery of simvastatin has been shown to reduce VNH/VS but local delivery may help decrease the side effects associated with statin use. We determined if microparticles (MP) composed of cyclodextrins loaded with simvastatin (MP-SV) could reduce VS/VNH using a murine arteriovenous fistula model with chronic kidney disease. Methods and Results Male C57BL/6J mice underwent nephrectomy to induce chronic kidney disease. Four weeks later, an arteriovenous fistula was placed and animals were randomized to 3 groups 20 μL of PBS or 20 μL of PBS with 16.6 mg/mL of either MP or MP-SV. Animals were euthanized 3 days later and the outflow veins were harvested for quantitative reverse transcriptase-polymerase chain reaction analysis and 28 days later for immunohistochemistical staining with morphometric analysis. Doppler ultrasound was performed weekly. Gene expression of vascular endothelial growth factor-A (Vegf-A), matrix metalloproteinase-9 (Mmp-9), transforming growth factor beta 1 (Tgf-β1), and monocyte chemoattractant protein-1 (Mcp-1) were significantly decreased in MP-SV treated vessels compared with controls. find more There was a significant decrease in the neointimal area, cell proliferation, inflammation, and fibrosis, with an increase in apoptosis and peak velocity in MP-SV treated outflow veins. MP-SV treated fibroblasts when exposed to hypoxic injury had decreased gene expression of Vegf-A and Mmp-9. Conclusions In experimental arteriovenous fistulas, periadventitial delivery of MP-SV decreased gene expression of Vegf-A, Mmp-9, Tgf-β1 and Mcp-1, VNH/VS, inflammation, and fibrosis.
Read More: https://www.selleckchem.com/products/i-bet-762.html
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