No abstract

Emerging bacterial pathogens threaten global health and food security, and so it is important to ask whether these transitions to pathogenicity have any common features. We present a systematic study of the claim that pathogenicity is associated with genome reduction and gene loss. We compare broad-scale patterns across all bacteria, with detailed analyses of Streptococcus suis, an emerging zoonotic pathogen of pigs, which has undergone multiple transitions between disease and carriage forms. We find that pathogenicity is consistently associated with reduced genome size across three scales of divergence (between species within genera, and between and within genetic clusters of S. suis). Although genome reduction is also found in mutualist and commensal bacterial endosymbionts, genome reduction in pathogens cannot be solely attributed to the features of their ecology that they share with these species, that is, host restriction or intracellularity. Moreover, other typical correlates of genome reduction in endosymbionts (reduced metabolic capacity, reduced GC content, and the transient expansion of nonfunctional elements) are not consistently observed in pathogens. Together, our results indicate that genome reduction is a consistent correlate of pathogenicity in bacteria.

Glasgow Coma Scale scoring should not be considered accurate. A more simplified scoring system should be developed and validated.

Background When kidney transplants fail, transplant medications are discontinued to reduce immunosuppression-related risks. However, retransplant candidates are at risk for allosensitization which prolonging immunosuppression may minimize. We hypothesized that for these patients, a prolonged immunosuppression withdrawal after graft failure preserves nonsensitization status (PRA 0%) better than early immunosuppression withdrawal. Methods We retrospectively examined subjects transplanted at a single center between 7/1/1999-12/1/2009 with a non-death related graft loss. Subjects were stratified by timing of immunosuppression withdrawal after graft loss: early (≤3 months) or prolonged (>3 months). Retransplant candidates were eligible for the main study where the primary outcome was nonsensitization at retransplant evaluation. Non-retransplant candidates were included in the safety analysis only. Results We found 102 subjects with non-death related graft loss of which 49 were eligible for the main study. Nonsensitization rates at retransplant evaluation were 30% and 66% for the early and prolonged immunosuppression withdrawal groups respectively (p=0.01). After adjusting for cofactors such as blood transfusion and allograft nephrectomy, prolonged immunosuppression withdrawal remained significantly associated with nonsensitization (adjusted odds ratio=5.78, 95% C.I. [1.37-24.44]). No adverse safety signals were seen in the prolonged immunosuppression withdrawal group compared to the early immunosuppression withdrawal group. Conclusions These results suggest that prolonged immunosuppression may be a safe strategy to minimize sensitization in retransplant candidates and provide the basis for larger or prospective studies for further verification.