Articles: function.
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Induced pluripotent stem cells (iPSCs) have enabled the generation of various difficult-to-access cell types such as human nociceptors. A key challenge associated with human iPSC-derived nociceptors (hiPSCdNs) is their prolonged functional maturation. While numerous studies have addressed the expression of classic neuronal markers and ion channels in hiPSCdNs, the temporal development of key signaling cascades regulating nociceptor activity has remained largely unexplored. ⋯ However, effective inhibition of forskolin-induced PKA-II activation by opioid receptor agonists required 70 days of in vitro differentiation. Our results identify a pronounced time difference between early expression of functionally important ion channels and emergence of regulatory metabotropic sensitizing and desensitizing signaling only at advanced stages of in vitro cultivation, suggesting an independent regulation of ionotropic and metabotropic signaling. These data are relevant for devising future studies into the development and regulation of human nociceptor function and for defining time windows suitable for hiPSCdN-based drug discovery.
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Pulmonary artery catheters provide important information about cardiac function, mixed venous oxygenation, and right-sided pressures and potentially provide temporary pacing ability. ⋯ The overall risk of serious complications with right heart catheter placement and manipulation is low and often outweighed by its benefits, specifically pressure monitoring and pacing.
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Breathlessness is the most common symptom in individuals with pleural effusion and is often disabling. The pathophysiology of breathlessness associated with pleural effusion is complex. ⋯ Impaired hemidiaphragm function and a compensatory increase in respiratory drive to maintain ventilation appear to be an important mechanism of breathlessness associated with pleural effusion. Thoracocentesis reduces diaphragm distortion and improves its movement; these changes appear to reduce respiratory drive and associated breathlessness by improving the neuromechanical efficiency of the diaphragm.
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Diabetes mellitus is the most common metabolic disease with >500 million people affected worldwide and currently 8,7 million in Germany. About 90% of diabetes cases are due to type 2 diabetes mellitus (T2D). This form of diabetes is characterized by an increased release of proinflammatory adipokines, endothelial dysfunction and hyperglycemia, among others. ⋯ People with diabetes are therefore generally considered a high-risk cardiovascular group and require special attention in the diagnosis and treatment of cardiovascular disease. Contributing factors to reduce high cardiovascular risk include a healthy lifestyle, normalization of blood pressure, optimization of blood lipid levels, and specific diabetes therapy tailored to cardiovascular risk. This review addresses the specific treatment options for reducing cardiovascular risk in patients with diabetes mellitus.
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The administration of epinephrine after severe refractory hypotension, shock, or cardiac arrest restores systemic blood flow and major vessel perfusion but may worsen cerebral microvascular perfusion and oxygen delivery through vasoconstriction. The authors hypothesized that epinephrine induces significant microvascular constriction in the brain, with increased severity after repetitive dosing and in the aged brain, eventually leading to tissue hypoxia. ⋯ Intravenous application of epinephrine induced marked cerebral microvascular constriction, intravascular hemoglobin desaturation, and paradoxically, an increase in brain tissue oxygen levels, likely due to reduced transit time heterogeneity.