Vaccination of dogs in an African city interrupts rabies transmission and reduces human exposure.

Despite the existence of effective rabies vaccines for dogs, dog-transmitted human rabies persists and has reemerged in Africa. Two consecutive dog vaccination campaigns took place in Chad in 2012 and 2013 (coverage of 71% in both years) in the capital city of N'Djaména, as previously published. We developed a deterministic model of dog-human rabies transmission fitted to weekly incidence data of rabid dogs and exposed human cases in N'Djaména. Our analysis showed that the effective reproductive number, that is, the number of new dogs infected by a rabid dog, fell to below one through November 2014. The modeled incidence of human rabies exposure fell to less than one person per million people per year. A phylodynamic estimation of the effective reproductive number from 29 canine rabies virus genetic sequences of the viral N-protein confirmed the results of the deterministic transmission model, implying that rabies transmission between dogs was interrupted for 9 months. However, new dog rabies cases appeared earlier than the transmission and phylodynamic models predicted. This may have been due to the continuous movement of rabies-exposed dogs into N'Djaména from outside the city. Our results show that canine rabies transmission to humans can be interrupted in an African city with currently available dog rabies vaccines, provided that the vaccination area includes larger adjacent regions, and local communities are informed and engaged.

RBM10 Modulates Apoptosis and Influences TNF-α Gene Expression.

Recent evidence suggests that protein encoded by the RNA Binding Motif 10 (RBM10) gene has the ability to modulate apoptosis. The objective of this study was to test this hypothesis by manipulating RBM10 expression levels and examining the downstream consequences. The results showed that transient overexpression of RBM10 correlated with significantly elevated levels of tumour necrosis factor alpha (TNF-α) mRNA and soluble TNF-α (sTNF-α) protein, and increased apoptosis (phosphatidyl serine exposure on the outer cell membrane and nuclear condensation). Stable RNA interference-mediated RBM10 knockdown clones were less susceptible to TNF-α-mediated apoptosis, and had decreased sTNF-α protein levels. Elevated levels of TNF-α associated with RBM10 overexpression resulted from increased TNF-α transcription, not TNF-α mRNA stabilization. These results suggest that RBM10 has the ability to modulate apoptosis, and that it does so via a mechanism involving alterations to TNFR super family-mediated signaling. These data provide the first direct evidence that human RBM10 can function as an apoptosis modulator and cytokine expression regulator.

Maternal hemodynamics after oxytocin bolus compared with infusion in the third stage of labor: a randomized controlled trial.

OBJECTIVE: To assess the effects of oxytocin bolus or infusion on maternal hemodynamics in the third stage of labor. METHODS: In a randomized, double-blind, double-dummy fashion, 99 women received an intravenous oxytocin bolus (10 IU push) and 102 women received an infusion (10 IU in 500 mL saline at 125 mL/h) at delivery of the anterior shoulder. Mean arterial pressure and heart rate were measured every minute for 10 minutes, then every 5 minutes for the next 20 minutes. These serial measurements were analyzed using a 2-factor analysis of variance for repeated measures. RESULTS: Serial mean arterial pressure measures varied significantly between groups (interaction effect, P = .002). Mean arterial pressure (+/- standard deviation) nadirs were reached after 10 minutes, 80.9 (+/- 11.0) mm Hg in the bolus group compared with 77.0 (+/- 12.1) mm Hg in the dilute infusion group. The mean difference (95% confidence interval) between groups was 4.0 (0.7-7.2) mm Hg. Serial heart rate measures also varied between groups (interaction effect, P < .001). Mean heart rate (+/- standard deviation) peaked 1 minute after the oxytocin infusion, 115 (+/- 27) beats per minute (bpm) in the bolus group compared with 109 (+/- 21) bpm in the dilute infusion group. The mean difference (95% confidence interval) between groups was 6.6 bpm (-0.1 to 13.3). The dilute oxytocin infusion group experienced a greater mean estimated blood loss (423.7 mL compared with 358.1 mL, P = .029, t test), increased use of additional oxytocics (35.3% compared with 22.2%, P = .044, Fisher exact test) and a greater drop in hemoglobin (admission minus postpartum) (17.4g/L compared with 11.4g/L, P = .002, t test) compared with the oxytocin bolus group. CONCLUSION: Bolus oxytocin of 10 IU is not associated with adverse hemodynamic responses and can safely be administered to women with intravenous access in the third stage of labor for postpartum hemorrhage prophylaxis. LEVEL OF EVIDENCE: I.