Ambient PM2.5 Temporal Variation and Source Apportionment in Mbarara, Uganda

Air pollution is the leading environmental cause of death globally, and most mortality occurs in resource-limited settings such as sub-Saharan Africa. The African continent experiences some of the worst ambient air pollution in the world, yet there are relatively little African data characterizing ambient pollutant levels and source admixtures. In Uganda, ambient PM2.5 levels exceed international health standards. However, most studies focus only on urban environments and do not characterize pollutant sources. We measured daily ambient PM2.5 concentrations and sources in Mbarara, Uganda from May 2018 through February 2019 using Harvard impactors fitted with size-selective inlets. We compared our estimates to publicly available levels in Kampala, and to World Health Organization (WHO) air quality guidelines. We characterized the leading PM2.5 sources in Mbarara using x-ray fluorescence and positive matrix factorization. Daily PM2.5 concentrations were 26.7 µg m–3 and 59.4 µg m–3 in Mbarara and Kampala, respectively (p < 0.001). PM2.5 concentrations exceeded WHO guidelines on 58% of days in Mbarara and 99% of days in Kampala. In Mbarara, PM2.5 was higher in the dry as compared to the rainy season (30.8 vs. 21.3, p < 0.001), while seasonal variation was not observed in Kampala. PM2.5 concentrations did not vary on weekdays versus weekends in either city. In Mbarara, the six main ambient PM2.5 sources identified included (in order of abundance): traffic-related, biomass and secondary aerosols, industry and metallurgy, heavy oil and fuel combustion, fine soil, and salt aerosol. Our findings confirm that air quality in southwestern Uganda is unsafe and that mitigation efforts are urgently needed. Ongoing work focused on improving air quality in the region may have the greatest impact if focused on traffic and biomass-related sources

Pre-induction cervical ripening using two different dinoprostone vaginal preparations: A randomized clinical trial of tablets and slow release retrievable insert

Objective: The current study compared the safety and efficacy of two different dinoprostone preparations (dinoprostone vaginal tablets & dinoprostone slow release retrievable vaginal insert) to ripen the cervix at term. Materials and methods: Women admitted for pre-induction cervical ripening were included in a randomized controlled trial. Eligible women were randomly assigned to receive Dinoprostone either in the form of vaginal tablets or slow release retrievable vaginal insert. Study outcomes included time to vaginal delivery and time to onset of labor intervals and vaginal delivery rate. Results: No statistically significant difference was found between the two groups regarding the main outcome measures, however, the probability of successful vaginal delivery was independently related to the type of dinoprostone preparation used to ripen the cervix (proportional hazard, 1.366; 95% CI, 1.010–1.847; P, 0.043) and the parity (proportional hazard, 1.412; 95% CI, 1.041–1.915; P, 0.026). Conclusion: Both dinoprostone preparations were effective and potentially safe. The probability of successful vaginal delivery was higher with dinoprostone vaginal tablets while use of dinoprostone vaginal insert was associated with better patients’ acceptability. clinicaltrials.gov: NCT01635439. Keywords: Dinoprostone, Dinoprostone slow release retrievable vaginal insert, Dinoprostone vaginal tablets, Pre-induction cervical ripenin

Reformulating a Pharmacophore for 5‑HT_2A Serotonin Receptor Antagonists

Several pharmacophore models have been proposed for 5-HT_2A serotonin receptor antagonists. These typically consist of two aromatic/hydrophobic moieties separated by a given distance from each other, and from a basic amine. Although specified distances might vary, the models are relatively similar in their general construction. Because our preliminary data indicated that two aromatic (hydrophobic) moieties might not be required for such action, we deconstructed the serotonin-dopamine antipsychotic agent risperidone (<b>1</b>) into four smaller structural fragments that were thoroughly examined in 5-HT_2A receptor binding and functional (i.e., two-electrode voltage clamp (TEVC) and intracellular calcium release) assays. It was apparent that truncated risperidone analogues behaved as antagonists. In particular, 6-fluoro-3-(1-methylpiperidin-4-yl)­benzisoxazole (<b>4</b>) displayed high affinity for 5-HT_2A receptors (<i>K</i>_i of ca. 12 nM) relative to risperidone (<i>K</i>_i of ca. 5 nM) and behaved as a potent 5-HT_2A serotonin receptor antagonist. These results suggest that multiple aromatic (hydrophobic) moieties are <i>not</i> essential for high-affinity 5-HT_2A receptor binding and antagonist activity and that current pharmacophore models for such agents are very much in need of revision