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Background: The impact of marital status on cardiovascular disease (CVD) remains controversial in the general population. Aim: The present investigation sought to delineate the association between marital status and long-term major non-fatal and fatal CVD, along with all-cause mortality within the scope of the RIFLE project (Risk Factors and Life Expectancy). Methods: We examined the incidences of CVD, including cerebrovascular accidents and coronary heart disease (CHD), as well as all-cause mortality. In total, 47,167 individuals (46% female, average age 50 ± 9 years) were included in the analysis. Marital status at inception was categorized into married (inclusive of married or cohabitating) versus unmarried cohorts (including widowed, separated, divorced, or single individuals). Results: Compared to their married counterparts, unmarried subjects demonstrated a heightened risk for CVD in both females and males. Throughout a median follow-up span of 7.4 years (interquartile range from 6 to 9 years), married participants, adjusting for standard risk factors, exhibited reduced mortality rates attributed to CHD [hazard ratio (HR) 0.54 (95% confidence interval (CI) 0.33–0.86)) and all causes (HR 0.75 (95% CI 0.62–0.91)] within the aggregate population; this reduction persisted for both CHD-specific [HR 0.39 (95% CI 0.51–0.90)]and all-cause mortality [HR 0.68 (95% CI 0.51–0.90)], independent of traditional risk factors in women. No associations were evident between matrimonial status and any measured outcomes in males. Conclusions: Within primary care settings, marital status should be considered a potential correlate of long-term CHD and overall mortality risks, especially among women. [ABSTRACT FROM AUTHOR]

Introduction: Intraamniotic microparticle injection is a novel technique for the treatment of myelomeningocele (MMC) in which microparticles are delivered in-utero in a minimally invasive fashion to bind to and protect the exposed spinal cord. This technique could offer earlier intervention and greater access to prenatal treatment of MMC. Here we demonstrate progress on the engineering of the microparticles to promote binding to the MMC defect. We hypothesized that when the particle's surface charge was decreased and delivery concentration increased, particles would bind to the MMC defect more frequently and more specifically., Methods: Alginate microparticles underwent surface modification to alter the particle charge. Dye-loaded alginate, alginate- dextran sulfate, and alginate- chitosan were injected on e17 into the amnion of a rat model of MMC and the incidence of successful binding and specificity of particle binding to the MMC defect were calculated. Specificity of binding was described using a defect-to-skin brightness ratio based on specimen imaging. Comparisons were made with chi-square, p< 0.05 marked significance., Results: There was no difference in the incidence of successful binding at e17 with 0.6 mg/fetal kg between the three tested alginate particles. However, alginate- dextran sulfate bound most specifically to the defect (p< 0.05). Alginate-dextran sulfate also demonstrated more frequent binding at higher doses than lower doses (79% at 1.2 mg/kg vs 38% at 0.6 mg/kg and 24% at 0.8 mg/kg, p< 0.01 for both). Specificity was not sacrificed at higher dose injections: defect-to-skin brightness ratio of 5.4 at 1.2 mg/kg vs 1.8 at 0.6 mg/kg (p< 0.05) CONCLUSION: We demonstrate that the intraamniotic injection of alginate-dextran sulfate microparticles at high concentration bind more frequently and more specifically to MMC defects than the previously tested unmodified alginate microparticles., (Copyright © 2021. Published by Elsevier Inc.)

The HIV pandemic has affected over 38 million people worldwide with close to 26 million currently accessing antiretroviral therapy (ART). A major challenge in the long-term treatment of HIV-1 infection is nonadherence to ART. Long-acting antiretroviral (LA-ARV) formulations, that reduce dosing frequency to less than once a day, are an urgent need that could tackle the adherence issue. Here, we have developed two LA-ART interventions, one an injectable nanoformulation, and the other, a removable implant, for the delivery of a synergistic two-drug ARV combination comprising a pre-clinical nonnucleoside reverse transcriptase inhibitor (NNRTI), Compound I, and the nucleoside reverse transcriptase inhibitor (NRTI), 4'-ethynyl-2-fluoro-2'-deoxyadenosine. The nanoformulation is poly(lactide- co -glycolide)-based and the implant is a copolymer of ω-pentadecalactone and p- dioxanone, poly(PDL- co -DO), a novel class of biocompatible, biodegradable materials. Both the interventions, packaged independently with each ARV, released sustained levels of the drugs, maintaining plasma therapeutic indices for over a month, and suppressed viremia in HIV-1-infected humanized mice for up to 42 days with maintenance of CD4 + T cells. These data suggest promise in the use of these new drugs as LA-ART formulations in subdermal implant and injectable mode., (© 2021 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)