ZIKV Inhibitors Based on Pyrazolo[3,4-d]pyridazine-7-one Core: Rational Design, In Vitro Evaluation, and Theoretical Studies.

The Zika virus (ZIKV) is believed to cause birth defects, and no anti-ZIKV drugs have been approved by medical organizations to date. Starting from antimicrobial lead compounds with a pyrazolo[3,4-d]pyridazine-7-one scaffold, we synthesized 16 derivatives and screened their ability to interfere with ZIKV infection utilizing a cell-based phenotypic assay. Of these, five compounds showed significant inhibition of ZIKV with a selective index value greater than 4.6. In particular, compound 9b showed the best anti-ZIKV activity with a selectivity index of 22.4 (half-maximal effective concentration = 25.6 µM and 50% cytotoxic concentration = 572.4 µM). Through the brine shrimp lethality bioassay, 9b, 10b, 12, 17a, and 19a showed median lethal dose values in a range of 87.2-100.3 µg/mL. Compound 9b was also targeted to the NS2B-NS3 protease of ZIKV using molecular docking protocols, in which it acted as a noncompetitive inhibitor and strongly bound to five key amino acids (His51, Asp75, Ser135, Ala132, Tyr161). Utilizing the pharmacophore model of 9b, the top 20 hits were identified as prospective inhibitors of NS2B-NS3 protease, and six of them were confirmed for their stability with the protease via redocking and molecular dynamics simulations.

Analysis of Periodontal Conditions in the Provinces of Vietnam: Results From the National Dental Survey.

Nationwide dental health surveys are crucial for providing essential information on dental health and dental condition-related problems in the community. However, the relationship between periodontal conditions and sociodemographic data has not been well investigated in Vietnam. With data from the National Oral Health Survey in 2019, we performed several machine learning methods on this dataset to investigate the impacts of sociodemographic features on gingival bleeding, periodontal pockets, and Community Periodontal Index. From the experiments, LightGBM produced a maximum AUC (area under the curve) value of 0.744. The other models in descending order were logistic regression (0.705), logiboost (0.704), and random forest (0.684). All methods resulted in significantly high overall accuracies, all exceeding 90%. The results show that the gradient boosting model can predict well the relationship between periodontal conditions and sociodemographic data. The investigated model also reveals that the geographic region has the most significant influence on dental health, while the consumption of sweet foods/drinks is the second most crucial. These findings advocate for a region-specific approach for the dental care program and the implementation of a sugar-risk food reduction program.

Mifepristone and misoprostol compared with misoprostol alone for second-trimester abortion: a randomized controlled trial.

OBJECTIVE: To estimate the clinical benefit of pretreatment with mifepristone followed by misoprostol compared with misoprostol alone for second-trimester abortion. METHODS: Two hundred sixty women with live fetuses of gestational ages 14-21 weeks were enrolled in a randomized, placebo-controlled, double-blind trial in Vietnam. Eligible consenting women received either mifepristone or placebo to take on their own at home and were scheduled to return to the hospital the next day. At the hospital, women were given 400 micrograms buccal misoprostol every 3 hours, up to five doses, until both the fetus and placenta were expelled. Efficacy was evaluated 15 hours after misoprostol dosing began and the procedure was considered complete if uterine evacuation was achieved without recourse to surgical evacuation. RESULTS: Pretreatment with mifepristone resulted in more than twice the chance of complete uterine evacuation in 15 hours (79.8% compared with 36.9%, relative risk 2.16, 95% confidence interval 1.70-2.75). The mean induction-to-abortion interval for complete uterine evacuations was statistically significantly shorter among participants pretreated with mifepristone compared with those given misoprostol alone (8.1, standard deviation 2.8, range 2.5-14.8; and 10.6, standard deviation 2.5, range 6.5-15.5 hours, respectively; P<.001). The side-effect profiles for the two regimens did not differ significantly and acceptability of the treatments was high. CONCLUSION: Mifepristone-misoprostol is more efficacious and faster than misoprostol alone. Services offering home administration of mifepristone as pretreatment could optimize efficacy and acceptability of medical abortions for women with gestations 14-21 weeks since the last menstrual period. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00784186. LEVEL OF EVIDENCE: I.