A DNA vaccine for West Nile virus (WNV) was evaluated to determine whether its use could protect fish crows (Corvus ossifragus) from fatal WNV infection. Captured adult crows were given 0.5 mg of the DNA vaccine either orally or by intramuscular (IM) inoculation; control crows were inoculated or orally exposed to a placebo. After 6 weeks, crows were challenged subcutaneously with 105 plaque-forming units of WNV (New York 1999 strain). None of the placebo inoculated–placebo challenged birds died. While none of the 9 IM vaccine–inoculated birds died, 5 of 10 placebo-inoculated and 4 of 8 orally vaccinated birds died within 15 days after challenge. Peak viremia titers in birds with fatal WNV infection were substantially higher than those in birds that survived infection. Although oral administration of a single DNA vaccine dose failed to elicit an immune response or protect crows from WNV infection, IM administration of a single dose prevented death and was associated with reduced viremia.

The relationship between neighborhood/individual characteristics and pediatric intensive care unit (PICU) outcomes is largely unexplored. We hypothesized that individual- level racial/ethnic minority status and neighborhood-level low socioeconomic status and minority concentration would adversely affect children’s severity of illness on admission to the PICU. Retrospective analyses (1/1/2007–5/ 23/2011) of clinical, geographic, and demographic data were conducted at an academic, tertiary children’s hospital PICU. Clinical data included age, diagnosis, insurance, race/ethnicity, Pediatric Index of Mortality 2 score on presentation to the PICU (PIM2), and mortality. Residential addresses were geocoded and linked with 2010 US Census tract data using geographic information systems geocoding techniques. Repeated measures models to predict PIM2 and mortality were constructed using three successive models with theorized covariates including the patient’s race/ethnicity, the predominant neighborhood racial/ethnic group, interactions between patient race/ethnicity and neighborhood race/ethnicity, neighborhood socioeconomic status, and insurance type. Of the 5,390 children, 57.8 %were Latino and 70.1 %possessed government insurance. Latino children (β = 0.31; p < 0.01), especially Latino children living in a Latino ethnic enclave (β = 1.13; p < 0.05), had higher PIM2 scores compared with non-Latinos. Children with government insurance (β = 0.29; p < 0.01) had higher PIM2 scores compared to children with other payment types and median neighborhood income was inversely associated with PIM2 scores (β = −0.04 per $10,000/year of income; p < 0.05). Lower median neighborhood income, Latino ethnicity, Latino children living in a predominantly Latino neighborhood, and children possessing government insurance were associated with a higher severity of illness on PICU admission. The reasons why these factors affect critical illness severity require further exploration.

Background Mixed donor-host chimerism, established through hematopoietic cell transplantation (HCT), is a highly reproducible strategy for the induction of tolerance towards solid organs. Here, we ask whether a nonmyeloablative conditioning regimen establishing mixed donor-host chimerism leads to tolerance of highly antigenic vascularized composite allografts. Methods Stable mixed chimerism was established in dogs given a sublethal dose (1–2 Gy) total body irradiation before and a short course of immunosuppression after dog leukocyte antigen-identical marrow transplantation. Vascularized composite allografts from marrow donors were performed after a median of 36 (range 4-54) months after HCT. Results All marrow recipients maintained mixed donor-host hematopoietic chimerism and accepted composite tissue grafts for periods ranging between 52 and 90 weeks; in turn, marrow donors rejected vascularized composite allografts from their respective marrow recipients within 18–29 days. Biopsies of muscle and skin of vascularized composite allografts from mixed chimeras showed few infiltrating cells compared to extensive infiltrates in biopsies of vascularized composite allografts from marrow donors. Elevated levels of CD3+ FoxP3+ T-regulatory cells were found in skin and muscle of vascularized composite allografts of mixed chimeras compared to normal tissues. In mixed chimeras, increased numbers of T-regulatory cells were found in draining compared to non-draining lymph nodes of vascularized composite allografts. Conclusion These data suggest that nonmyeloablative HCT may form the basis for future clinical applications of solid organ transplantation and that T-regulatory cells may function towards maintenance of the vascularized composite allograft.