Geospatial Assessment to Improve Time to Treatment (GAITT).

INTRODUCTION: Geographic information systems (GIS) can optimize trauma systems by identifying ways to reduce time to treatment. Using GIS, this study analyzed a system in Maryland served by Johns Hopkins Suburban Hospital and the University of Maryland Capital Region Medical Center. It was hypothesized that including Walter Reed National Military Medical Center (WRNMMC) in the Maryland trauma system in an access simulation would provide increased timely access for a portion of the local population. MATERIALS AND METHODS: Using ArcGIS Online, catchment areas with and without WRNMMC were built. Catchment areas captured Johns Hopkins Suburban Hospital, University of Maryland Capital Region Medical Center, and WRNMMC at 5-, 10-, 15-, 20-, 25-, 30-, 45-, and 60-min. Various time conditions were simulated (12 am, 8 am, 12 pm, and 5 pm) on a weekday and weekend day. Data was enriched with 19 variables addressing population size, socioeconomic status, and diversity. RESULTS: All catchment areas benefited on at least one time-day simulation, but the largest increases in mean population coverage were in the 0-5 (10.5%), 5-10 (12.3%), and 10-15 min (5.7%) catchment areas. These areas benefited regardless of time-day simulation. The lowest increase in mean population coverage was seen in the 20-25-min catchment area (0.1%). Subgroup analysis revealed that all socioeconomic status and diversity groups gained coverage. CONCLUSIONS: This study suggests that incorporating WRNMMC into the Maryland trauma system might yield increased population coverage for timely trauma access. If incorporated, WRNMMC may provide nonstop or flexible coverage, possibly in different traffic scenarios or while civilian centers are on diversion status.

Polymorphisms in the CD1d promoter that regulate CD1d gene expression are associated with impaired NKT cell development.

CD1d-restricted NKT cells comprise an innate-like T cell population that exerts significant influence over early events in the developing immune response. The frequency of NKT cells is highly variable in humans and in mice, but the basis for this variability remains unclear. In this study, we report a striking deficiency of type I NKT cells in the wild-derived inbred strains PWD/PhJ, SPRET/EiJ, and CAST/EiJ. Investigation of the underlying basis for the lack of type I NKT cells revealed that one strain, PWD/PhJ, exhibited a significant impairment in thymocyte and splenocyte CD1d gene and protein expression. Accordingly, both thymocytes and bone marrow-derived dendritic cells from PWD mice exhibited a significant impairment in the ability to present α-galactosylceramide to NKT cells. The impaired PWD CD1d gene expression was due to impaired CD1d promoter activity. Fine-mapping of the promoter activity revealed that two single nucleotide substitutions at positions -331 and -164 in the proximal promoter were each sufficient to account for the diminished PWD CD1d promoter activity. Examination of the strain distribution pattern of these polymorphisms revealed that, of 19 strains analyzed, only PWD and PWK mice possessed both CD1d promoter polymorphisms. A subsequent examination of the PWK strain revealed that it also exhibited impaired thymocyte CD1d expression and very low numbers of NKT cells. Taken together, these results provide new insight into the control of CD1d gene expression, and they have implications for the evolution of CD1d and type I NKT cells.

Translational control of NKT cell cytokine production by p38 MAPK.

NKT cells are known to rapidly produce a large amount of cytokines upon activation. Although a number of signaling pathways that regulate the development of NKT cells have been identified, the signaling pathways involved in the regulation of NKT cell cytokine production remain unclear. In this study, we show that the p38 MAPK pathway is dispensable for the development of NKT cells. However, NKT cell cytokine production and NKT-mediated liver damage are highly dependent on activation of this pathway. p38 MAPK does not substantially affect cytokine gene expression in NKT cells, but it regulates the synthesis of cytokines through the Mnk-eIF4E pathway. Thus, in addition to gene expression, translational regulation by p38 MAPK could be a novel mechanism that contributes to the overall production of cytokine by NKT cells.