Transactions of the American Clinical and Climatological Association

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While advances in our understanding of mechanical ventilation have improved mortality from acute respiratory distress syndrome, recent studies indicate a rising incidence of post-ventilation mental health sequelae, including post-traumatic stress disorder (PTSD). Concurrent research on the physiology of dyspnea provides insights about the role of multiple sources of sensory information underlying respiratory discomfort along with the contribution of efferent-afferent dissociation to dyspnea, and the subsequent relationship of dyspnea to a range of affective responses, including fear and anxiety...

Voltage gated Na channels (NaV ) are essential for excitation of tissues. Mutations in NaV s cause a spectrum of human disease from autism and epilepsy to cardiac arrhythmias to skeletal myotonias. The carboxyl termini (CT) of NaV channels are hotspots for disease-causing mutations and are richly invested with protein interaction sites. We have focused on the regulation of NaV by two proteins that bind in this region: calmodulin (CaM) and non-secreted fibroblast growth factors (iFGF or FHF). CaM regulates NaV gating, mediating Ca2+ -dependent inactivation (CDI) in a channel isoform-specific manner, while Ca2+ -free CaM (apo-CaM) binding broadly regulates NaV opening and suppresses the arrhythmogenic late Na current ( I Na-L )...

Microvascular endothelial activation/dysfunction has emerged as an important mechanistic pathophysiological process in the development of morbidity and mortality in life-threatening infections. The angiopoietin-Tie2 system plays an integral role in the regulation of microvascular endothelial integrity. Angiopoietin-1 (Ang-1), produced by platelets and pericytes, is the cognate agonistic ligand for Tie2, promoting endothelial quiescence and inhibiting microvascular leak. Angiopoietin-2 (Ang-2), released from activated endothelial cells in Weibel-Palade bodies, competes with Ang-1 for binding to Tie-2, thereby promoting endothelial activation/dysfunction and microvascular leak...

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Despite the advent of more targeted therapies, glucocorticoids (steroids) remain in chronic use (defined as > 3 months or more) by an estimated 0.5% of the population. Steroids yield symptomatic benefits for systemic and local inflammation as well as disease-modifying properties in rheumatoid arthritis, the most common disorder for their chronic use. Despite their many benefits, steroids have been associated with a myriad of common side effects. Observational studies of steroid safety are limited by confounding by indication, and randomized controlled trials have been too short and too small to understand their true safety profile...

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