Bioluminescent Imaging of Trypanosoma brucei Shows Preferential Testis Dissemination Which May Hamper Drug Efficacy in Sleeping Sickness

Monitoring Trypanosoma spread using real-time imaging in vivo provides a fast method to evaluate parasite distribution especially in immunoprivileged locations. Here, we generated monomorphic and pleomorphic recombinant Trypanosoma brucei expressing the Renilla luciferase. In vitro luciferase activity measurements confirmed the uptake of the coelenterazine substrate by live parasites and light emission. We further validated the use of Renilla luciferase-tagged trypanosomes for real-time bioluminescent in vivo analysis. Interestingly, a preferential testis tropism was observed with both the monomorphic and pleomorphic recombinants. This is of importance when considering trypanocidal drug development, since parasites might be protected from many drugs by the blood-testis barrier. This hypothesis was supported by our final study of the efficacy of treatment with trypanocidal drugs in T. brucei-infected mice. We showed that parasites located in the testis, as compared to those located in the abdominal cavity, were not readily cleared by the drugs

Prevalence of hypertensive disorders of pregnancy at or beyond 39 weeks gestational age and associated maternal complications

Objective Estimate the prevalence of hypertensive disorder of pregnancy (HDP) at term, define population characteristics, and calculate adverse maternal outcomes. Methods Retrospective study. Results We included 4,702,468 pregnancies. HDP increased linearly from 4.5% (2014) to 6.0% (2018). HDP was more frequent among black (PR 1.19), obese (PR 2.31 to 3.70), with gestational (PR 1.87) or pregestational diabetes (PR 2.16). Increased transfusion (PR 2.52), intensive care unit admission (PR 3.38), and unplanned hysterectomy (PR 1.78) with HDP.  Conclusion Our study quantifies the increased risks for maternal and neonatal complications related to the development of HDP at or beyond 39 weeks among nulliparous women

Use of the Renal Artery Doppler to Identify Small for Gestational Age Fetuses at Risk for Adverse Neonatal Outcomes

Objective: To measure the sensitivity and positive predictive value (PPV) for an adverse neonatal outcome among growth-restricted fetuses (FGR) comparing the cerebral–placental ratio (CPR) with the cerebral–renal ratio (CRR). Methods: Retrospective analysis of 92 women who underwent prenatal ultrasound at the University of Maryland and the University of Padua. Renal, middle cerebral and umbilical artery Doppler waveforms were recorded for all scans during the third trimester. The last scan prior to delivery was included for analysis. We calculated the test characteristics of the pulsatility indices (PI) of the umbilical and renal arteries in addition to the derived CPR and CRR to detect a composite adverse neonatal outcome. Results: The test characteristics of the four Doppler ratios to detect increased risk for the composite neonatal outcome demonstrated that the umbilical artery pulsatility index had the best test performance (sensitivity 64% (95% CI: 47–82%), PPV 24% (95% CI: 21–27), and positive likelihood ratio 2.7 (95% CI: 1.4–5.2)). There was no benefit to using the CRR compared with the CPR. The agreement between tests was moderate to poor (Kappa value CPR compared with CRR: 0.5 (95%CI 0.4–0.70), renal artery PI:−0.1 (95% CI −0.2–0.0), umbilical artery PI: 0.5 (95% CI 0.4–0.7)). Only the umbilical artery had an area under the receiver operating curve that was significantly better compared with the CPR as a reference (p-value < 0.01). Conclusions: The data that we present do not support the use of renal artery Doppler as a useful clinical test to identify a fetus at risk for an adverse neonatal outcome. Within the various indices applied to this population, umbilical artery Doppler performed the best in identifying the fetuses at risk for an adverse perinatal outcome

Impact of labor induction at 39 weeks gestation compared with expectant management on maternal and perinatal morbidity among a cohort of low-risk women

OBJECTIVE: To determine maternal and perinatal outcomes after induction of labor (IOL) at 39 weeks compared with expectant management. METHODS: This is a retrospective national cohort study from the National Center for Health Statistics birth database. The study included singleton, low-risk pregnancies with a non-anomalous fetus delivered at 39-42 weeks gestation between 2015 and 2018. Maternal outcomes available included chorioamnionitis (Triple I), blood transfusion, intensive care unit (ICU) admission, uterine rupture, cesarean delivery (CD), and cesarean hysterectomy. Fetal and infant outcomes included stillbirth, 5-min Apgar ≤3, prolonged ventilation, seizures, ICU admission, and death within 28 days. We compared women undergoing IOL at 39 weeks to those managed expectantly. Non-adjusted and adjusted relative risks (aRRs) were estimated using multivariate log-binomial regression analysis. RESULTS: There were 15,900,956 births available for review of which 5,017,524 met inclusion and exclusion criteria. For the maternal outcomes, the IOL group was less likely to require a CD (aRR 0.880; 95% CI [0.874-0.886]; value \u3c .01) or develop Triple I (aRR 0.714; 95% CI [0.698-0.730]; value \u3c .01) but demonstrated a small increase in the cesarean hysterectomy rate (aRR 1.231; 95% CI [1.029-1.472]; value \u3c .01). Among perinatal outcomes, the stillbirth rate (aRR 0.195; 95% CI [0.153-0.249]; value \u3c .01), 5-min Apgar ≤3 (aRR 0.684; 95% CI [0.647-0.723]; value \u3c .01), prolonged ventilation (aRR 0.840; 95% CI [0.800-0.883]; value \u3c .01), neonatal intensive care (NICU) admission (aRR 0.862; 95% CI [0.849-0.875]; value \u3c .01) were lower after 39 week IOL compared with expectant management. There were no differences in risk for neonatal seizures (aRR 0.848; 95% CI [0.718-1.003]; value 0.011) or death (aRR 1.070; 95% CI [0.722-1.586]; value 0.660). CONCLUSIONS: IOL at 39 weeks of gestation in a low-risk cohort is associated with a lower risk of CD and maternal infection, stillbirth, and lower neonatal morbidity. There was no effect on the risk for neonatal seizures or death