The JAK-STAT pathway is critical in ventilator-induced diaphragm dysfunction.

Mechanical ventilation (MV) is one of the lynchpins of modern intensive-care medicine and is life saving in many critically ill patients. Continuous ventilator support, however, results in ventilation-induced diaphragm dysfunction (VIDD) that likely prolongs patients' need for MV and thereby leads to major associated complications and avoidable intensive care unit (ICU) deaths. Oxidative stress is a key pathogenic event in the development of VIDD, but its regulation remains largely undefined.

Inhibition of Janus kinase signaling during controlled mechanical ventilation prevents ventilation-induced diaphragm dysfunction.

Controlled mechanical ventilation (CMV) is associated with the development of diaphragm atrophy and contractile dysfunction, and respiratory muscle weakness is thought to contribute significantly to delayed weaning of patients. Therefore, therapeutic strategies for preventing these processes may have clinical benefit. The aim of the current study was to investigate the role of the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in CMV-mediated diaphragm wasting and weakness in rats.

Exercise performance and peripheral vascular insufficiency improve with AMPK activation in high-fat diet-fed mice.

Intermittent claudication is a form of exercise intolerance characterized by muscle pain during walking in patients with peripheral artery disease (PAD). Endothelial cell and muscle dysfunction are thought to be important contributors to the etiology of this disease, but a lack of preclinical models that incorporate these elements and measure exercise performance as a primary end point has slowed progress in finding new treatment options for these patients. We sought to develop an animal model of peripheral vascular insufficiency in which microvascular dysfunction and exercise intolerance were defining features.

Nephrilin peptide modulates a neuroimmune stress response in rodent models of burn trauma and sepsis.

Sepsis occurs three times more often in burns than in other types of trauma, suggesting an overlap or synergy between underlying immune mechanisms in burn trauma and sepsis. Nephrilin peptide, a designed inhibitor of mTORC2, has previously been shown to modulate a neuroimmune stress response in rodent models of xenobiotic and metabolic stress. Here we investigate the effect of nephrilin peptide administration in different rodent models of burn trauma and sepsis.

Mammalian target of rapamycin complex 2 regulates inflammatory response to stress.

Objective And Design: To explore the role of mammalian target of rapamycin 2 (mTORC2) in the activation of inflammatory and oxidative responses in rodent models of acute injury and metabolic stress.

Material: The impact of nephrilin, an inhibitor of mTORC2 complex, was assessed in three CD-1 mouse models of acute xenobiotic stress and in a hypertensive Dahl rat model of metabolic stress.

Methods: Animals received daily subcutaneous bolus injections of saline or 4 mg/kg nephrilin.

A nuclear complex of rictor and insulin receptor substrate-2 is associated with albuminuria in diabetic mice.

Background: Signaling events associated with diabetic nephropathy are not well understood. Triangulation of events triggered by unrelated bioactive peptides nephrilin and anephril, both of which inhibit albuminuria in diabetic mice, could reveal a common subset of events associated with albuminuria.

Methods: db/db mice received 20 microg/day anephril or nephrilin for 7 weeks.

Bioactive peptides control receptor for advanced glycated end product-induced elevation of kidney insulin receptor substrate 2 and reduce albuminuria in diabetic mice.

Background/aims: Sixteen-week-old db/db mice exhibit significantly elevated blood glucose and albuminuria. Kidney mesangial cell matrix expansion and collagen IV synthesis correlate with disease progression, but the underlying mechanism is unclear.

Methods: Adaptive biochemical datasets were generated in cultured 293 kidney cells and in db/db mice.

Early adoption of new drug treatments: the role of continuing medical education and physician adaptivity.

The influence of continuing medical education (CME) on the adoption of new treatments is widely regarded as self-evident. Less well understood is how the dynamics of dissemination of new healthcare practices are influenced by the intersection of education with the adaptive characteristics of providers. We developed and validated a 43-item online instrument (eSAIL) for measuring adaptive style and used it to investigate the interplay of physician adaptivity with key components of effective medical education.