Neuromuscular complications of critical illness.

Neuromuscular sequelae are common in the critically ill. Critical illness polyneuropathy and critical illness myopathy are neuromuscular complications of sepsis or iatrogenic complications of treatments required in intensive care. This article discusses the diagnosis, treatment, and prognosis of these disorders based on a literature review. This review found that glycemic control, early mobilization, and judicious use of steroids and neuromuscular blocking agents are the primary approaches to reduce the incidence and severity of neuromuscular complications in affected patients.

The microphthalmia-associated transcription factor requires SWI/SNF enzymes to activate melanocyte-specific genes.

The microphthalmia transcription factor (Mitf) activates melanocyte-specific gene expression, is critical for survival and proliferation of melanocytes during development, and has been described as an oncogene in malignant melanoma. SWI/SNF complexes are ATP-dependent chromatin-remodeling enzymes that play a role in many developmental processes. To determine the requirement for SWI/SNF enzymes in melanocyte differentiation, we introduced Mitf into fibroblasts that inducibly express dominant negative versions of the SWI/SNF ATPases, Brahma or Brahma-related gene 1 (BRG1). These dominant negative SWI/SNF components have been shown to inhibit gene activation events that normally require SWI/SNF enzymes. We found that Mitf-mediated activation of a subset of endogenous melanocyte-specific genes required SWI/SNF enzymes but that cell-cycle regulation occurred independently of SWI/SNF function. Activation of tyrosinase-related protein 1, a melanocyte-specific gene, correlated with SWI/SNF-dependent changes in chromatin accessibility at the endogenous locus. Both BRG1 and Mitf could be localized to the tyrosinase-related protein 1 and tyrosinase promoters by chromatin immunoprecipitation, whereas immunofluorescence and immunoprecipitation experiments indicate that Mitf and BRG1 co-localized in the nucleus and physically interacted. Together these results suggest that Mitf can recruit SWI/SNF enzymes to melanocyte-specific promoters for the activation of gene expression via induced changes in chromatin structure at endogenous loci.