Isomer-nonspecific action of dichlorodiphenyltrichloroethane on aryl hydrocarbon receptor and G-protein-coupled receptor 30 intracellular signaling in apoptotic neuronal cells.

Extended residual persistence of the pesticide dichlorodiphenyltrichloroethane (DDT) raises concerns about its long-term neurotoxic effects. Little is known, however, about DDT toxicity during the early stages of neural development. This study demonstrated that DDT-induced apoptosis of mouse embryonic neuronal cells is a caspase-9-, caspase-3-, and GSK-3ß-dependent process, which involves p,p'-DDT-specific impairment of classical ERs. It also provided evidence for DDT-isomer-nonspecific alterations of AhR- and GPR30-mediated intracellular signaling, including changes in the levels of the receptor and receptor-regulated mRNAs, and also changes in the protein levels of the receptors. DDT-induced stimulation of AhR-signaling and reduction of GPR30-signaling were verified using selective ligands and specific siRNAs. Co-localization of the receptors was demonstrated with confocal microscopy, and the presence of functional GPR30 was detected by electrophysiology. This study demonstrates that stimulation of AhR-signaling and impairment of GPR30-signaling play important roles in the propagation of DDT-induced apoptosis during the early stages of neural development.

Quality assessment in the pediatric trauma care system.

The goal of the pediatric trauma care system is to prevent death, disability, and suffering of injured children. Quality assessment (QA), the evaluation of clinical performance and quality, is essential not only for formal accreditation processes, but also for day-to-day trauma center operation. QA involves three basic types of performance measures: input, process, and outcome. Input measures are inventories of the resources of a given institution, such as the availability of a surgeon on a 24-hour-a-day in-house basis. They give baseline descriptions of facilities and do not monitor performance directly. Process measures attempt to verify that the system is using its resources appropriately in response to demands, which at Children's Hospital of Pittsburgh (CHP), involves tracking all admitted patients from injury to discharge with the assistance of a system of audit screens to help identify problem cases. The methodology of the Major Trauma Outcome Study (MTOS) provides basic outcome data by identifying unexpected survivors and deaths. However, the few cases identified (four of 316 patients submitted to MTOS; 1.3%) limit conclusions regarding trauma center performance. Performance measures, when applied to admitted trauma patients, allow timely recognition of individual complications and problem trends. QA provides necessary data for important clinical decisions and resource allocations that affect trauma center operation.