Blue Light Enhances Bacterial Clearance and Reduces Organ Injury During Sepsis.

Objectives: The physiology of nearly all mammalian organisms are entrained by light and exhibit circadian rhythm. The data derived from animal studies show that light influences immunity, and these neurophysiologic pathways are maximally entrained by the blue spectrum. Here, we hypothesize that bright blue light reduces acute kidney injury by comparison with either bright red or standard, white fluorescent light in mice subjected to sepsis.

Blue light reduces organ injury from ischemia and reperfusion.

Evidence suggests that light and circadian rhythms profoundly influence the physiologic capacity with which an organism responds to stress. However, the ramifications of light spectrum on the course of critical illness remain to be determined. Here, we show that acute exposure to bright blue spectrum light reduces organ injury by comparison with bright red spectrum or ambient white fluorescent light in two murine models of sterile insult: warm liver ischemia/reperfusion (I/R) and unilateral renal I/R.

CaMKIV-dependent preservation of mTOR expression is required for autophagy during lipopolysaccharide-induced inflammation and acute kidney injury.

Autophagy, an evolutionarily conserved homeostasis process regulating biomass quantity and quality, plays a critical role in the host response to sepsis. Recent studies show its calcium dependence, but the calcium-sensitive regulatory cascades have not been defined. In this study, we describe a novel mechanism in which calcium/calmodulin-dependent protein kinase IV (CaMKIV), through inhibitory serine phosphorylation of GSK-3β and inhibition of FBXW7 recruitment, prevents ubiquitin proteosomal degradation of mammalian target of rapamycin (mTOR) and thereby augments autophagy in both the macrophage and the kidney.

Augmenting autophagy to treat acute kidney injury during endotoxemia in mice.

Objective: To determine that 1) an age-dependent loss of inducible autophagy underlies the failure to recover from AKI in older, adult animals during endotoxemia, and 2) pharmacologic induction of autophagy, even after established endotoxemia, is of therapeutic utility in facilitating renal recovery in aged mice.

Design: Murine model of endotoxemia and cecal ligation and puncture (CLP) induced acute kidney injury (AKI).

Setting: Academic research laboratory.

Calcium supplementation during sepsis exacerbates organ failure and mortality via calcium/calmodulin-dependent protein kinase kinase signaling.

Background: Calcium plays an essential role in nearly all cellular processes. As such, cellular and systemic calcium concentrations are tightly regulated. During sepsis, derangements in such tight regulation frequently occur, and treating hypocalcemia with parenteral calcium administration remains the current practice guideline.

CaMKIα regulates AMP kinase-dependent, TORC-1-independent autophagy during lipopolysaccharide-induced acute lung neutrophilic inflammation.

Autophagy is an evolutionarily conserved cytoplasmic process regulated by the energy rheostats mammalian target of rapamycin and AMP kinase (AMPK) that recycles damaged or unused proteins and organelles. It has been described as an important effector arm of immune cells. We have shown that the cytoplasmically oriented calcium/calmodulin-dependent protein kinase (CaMK)Iα regulates the inflammatory phenotype of the macrophage (M).

Calcium/calmodulin-dependent protein kinase (CaMK) Ialpha mediates the macrophage inflammatory response to sepsis.

Dysregulated Ca(2+) handling is prevalent during sepsis and postulated to perpetuate the aberrant inflammation underlying subsequent organ dysfunction and death. The signal transduction cascades mediating these processes are unknown. Here, we identify that CaMKIα mediates the Mϕ response to LPS in vitro and the inflammation and organ dysfunction of sepsis in vivo.

Incidental radiographic findings after injury: dedicated attention results in improved capture, documentation, and management.

Background: With liberal use of computed tomography in the diagnostic management of trauma patients, incidental findings are common and represent a major patient-care and medical-legal concern. Consequently, we began an initiative to capture, notify, and documentadequately incidental finding events with a dedicated incidental finding coordinator. We hypothesized a dedicated incidental finding coordinator would increase incidental finding capture and promote notification, follow-up, and documentation of incidental finding events.

Abdominal wall infections with in situ mesh.

Background: Synthetic mesh is used commonly in the repair of abdominal wall hernias. Infection at the surgical site where mesh is present poses a formidable clinical problem.

Methods: The current surgical literature was reviewed to formulate accepted approaches to the management of hernia repairs with infected mesh.