Nucleophilic Additions and Substitutions of 2,3-Epoxy-2,3-dihydro-1,4-naphthoquinone Derivatives

Derivatives of 1,4-napthoquinone are known to possess numerous biological activities, including potential anti-cancer properties, which is made possible by their propensity for reacting with nucleophiles. Here, we study the reactions of 2,3-epoxy-2-methyl-2,3-dihydro-1,4-nathoquinone with alkylthiols, alkylamines, and arylamines. Two different classes of products were identified, a single addition product, 2-alkylthio-3-methyl-1,4-naphthoquinone, and a double addition product, 2-alkylthio-3-alkylthioalkyl-1,4-naphthoquinone. When 2,3-epoxy-2-methyl-2,3-dihydro-1,4-nathoquinone reacted with alkylthiols in the presence of a base, the strength of the base determined which class of product was formed as the major product. With a weak base, like N-methylimidazole, only a single addition product was identified, while with a strong base, like triethylamine, the major product was the double addition product. In the formation of the double addition product a slightly acidic alpha-methyl proton from a single addition product is further replaced by the alkylthiol via Michael addition process. Currently, we are able to identify one major product in the reaction of 2,3-epoxy-2-methyl-2,3-dihydro-1,4-naphthoquinone with alkylamines, that is, a single addition product

Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid- 19

The Supplementary Index contains information including the demographics of the clinical trial. The only races/ ethnicities identified are Non- Hispanic Whites, Non- Hispanic Blacks, and Hispanics.Hydroxychloroquine has been widely administered to patients with Covid-19 without robust evidence supporting its use. In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed.Funded by the National Institutes of HealthDOI: 10.1056/NEJMoa2012410, https://www.nejm.org/doi/full/10.1056/NEJMoa2012410

Gender Differences in In-Hospital Outcomes After Coronary Artery Bypass Grafting

Women historically have a greater risk of operative mortality than men after coronary artery bypass grafting (CABG). There is paucity of contemporary data in gender outcomes of surgical revascularization and understanding modifiable factors that contribute to gender differences are critical for quality improvement and practice change. We, therefore, sought to examine whether the gender gap in CABG outcomes is closing in the contemporary era by conducting a retrospective analysis from the Nationwide Inpatient Sample database from 2003 to 2012. We included all patients who underwent isolated CABG surgery (n = 2,272,998; female n = 623,423 [27.4%]; male n = 1,649,575 [72.6%]). The annual rate of CABG surgeries decreased by 53.7% in men and 57.8% in women over the 10-year study period. Although internal mammary artery use in women was less frequent than in men in 2003 (77.4% vs 81.9%, p <0.001), a significant uptrend closed this gap by 2012 (86.2% vs 87.0%, ptrend 0.003). Overall, unadjusted in-hospital mortality was greater in women (3.2% vs 1.8%, p <0.001). Female gender remained an independent predictor of mortality after multivariate adjustment (odds ratio 1.40, 95% CI 1.36 to 1.43, p <0.001) across all age groups. However, in-hospital mortality decreased at a faster rate in women (3.8% to 2.7%, RR 1229.1%, ptrend 0.002) than in men (2.2% to 1.6%, RR 1225.7%, ptrend <0.001) from 2003 to 2012. In conclusion, CABG rates in the United States are decreasing over time, yet in-hospital mortality continues to improve. Women have worse in-hospital outcomes than men; however, the gender gap is slowly closing