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Sepsis is associated with increased expression of TNF-α with subsequent activation of nuclear factorkappa B (NF-κB). The glucocorticoid receptor (GR) and NF-κB function as mutual antagonists and induction of the latter is believed to play a major role in the acquired glucocorticoid resistance that occurs in some septic patients. GR expression and function has been reported to be elevated in septic muscle suggesting a limited effect of the activated NF-κB on GR function in this context. In this study, the L6 myocyte cell line was used as an in vitro model for a sepsis-like condition in skeletal muscle. While short or long term treatment with TNF-α had no effect on GR expression, glucocorticoid-dependent downregulation of GR occurred with a kinetic profile that is accelerated relative to that observed in most cells. This downregulation was not affected by co-treatment or prior priming of L6 cells with TNF-α. The synthetic glucocorticoid, dexamethasone (DEX) blunted TNF-α-stimulated NF-κB activation in L6 cells. However, although effective at activating an NF-κB transcriptional response, TNF-α treatment exerted a minimal effect in myoblasts and no effect in myotubes on GR transcriptional activity. This limited impact of TNF-α on GR activity was not universal as TNF-α and DEX exerted an additive effect on the reduction in myosin heavy chain (MHC) protein expression caused by either agent alone. Thus, the selective perseverance of GR function in the presence of increased levels of glucocorticoids and TNF-α during sepsis or other inflammatory states may exacerbate muscle protein breakdown.

Purpose We evaluated the psychometric properties of a revised version of the Parental Monitoring of Diabetes Care (PMDC) questionnaire designed to evaluate parental supervision and monitoring of adolescent diabetes care behaviors. The revised measure was intended to capture a broad range of ways used by parents to gather information about youth adherence to diabetes care. Methods 267 caregivers of 12–18 year old adolescents with type 1 diabetes completed the PMDC-R. Measures of parental knowledge of youth illness management, illness management behavior and metabolic control were also obtained. Results The PMDC-R demonstrated good internal consistency (alpha coefficient =.91) and test-rest reliability (r=.79, p <.001). Supporting the instrument’s construct validity, a bifactor model with one primary factor and three secondary factors had an acceptable fit to the data [comparative fit index (CFI) = .92, and root mean square error of approximation (RMSEA) = .06]. Concurrent validity was also supported. In structural equation models, parental monitoring as assessed by the PMDC-R had a significant direct effect on parental knowledge of adolescent diabetes management and through knowledge, an indirect effect on adolescent diabetes management and metabolic control. Conclusions The PMDC-R displayed strong psychometric properties and represents an important next step in refining the measurement of parental monitoring for youth with chronic illnesses.