DEB-FAPy-dG Adducts of 1,3-Butadiene: Synthesis, Structural Characterization, and Formation in 1,2,3,4-Diepoxybutane Treated DNA.

Metabolic activation of the human carcinogen 1,3-butadiene (BD) by cytochrome 450 monooxygenases gives rise to a genotoxic diepoxide, 1,2,3,4-diepoxybutane (DEB). This reactive electrophile alkylates guanine bases in DNA to produce N7-(2-hydroxy-3,4-epoxy-1-yl)-dG (N7-DE-dG) adducts. Because of the positive charge at the N7 position of the purine heterocycle, N7-DEB-dG adducts are inherently unstable and can undergo spontaneous depurination or base-catalyzed imidazole ring opening to give N6 -[2-deoxy-D-erythro-pentofuranosyl]-2,6-diamino-3,4-dihydro-4-oxo-5-N-1-(oxiran-2-yl)propan-1-ol-formamidopyrimidine (DEB-FAPy-dG) adducts. Here we report the first synthesis and structural characterization of DEB-FAPy-dG adducts. Authentic standards of DEB-FAPy-dG and its 15 N3 -labeled analogue were used for the development of a quantitative nanoLC-ESI+ -HRMS/MS method, allowing for adduct detection in DEB-treated calf thymus DNA. DEB-FAPy-dG formation in DNA was dependent on DEB concentration and pH, with higher numbers observed under alkaline conditions.

Prevalence of suicide risk among a national sample of individuals referred from a primary care subpopulation, 2017-2020.

Over the past decade, the age-adjusted suicide rate has increased by 35.2% in the United States. In primary care, practitioners often interact with patients at risk of dying by suicide, yet little is known about the prevalence of suicide risk in primary care populations. Patient data from 2017-2020, consisting of a national sample of patients referred from primary care and enrolled in collaborative care behavioral health services (n = 37 666), were analyzed. Controlling for demographic characteristics, logistic models were used to compare suicide risk prevalence by behavioral health diagnosis. An estimated 9.96% (95% confidence interval [CI]: 9.65-10.27)-or approximately 3751 individuals-of the total sample screened positively for suicide risk. Compared with individuals diagnosed with generalized anxiety disorder, individuals diagnosed with bipolar disorder had 8.21 times the odds (95% CI: 6.66-10.10) of screening for suicide risk. Practitioners and health care systems may benefit from adding suicide risk screeners as a standard practice for referred patients, which may lead to further development of clinical pathways and provider training. The high rate of suicide risk across the sample suggests that more research is needed to understand suicide risk prevalence across primary care and collaborative care populations.