Residing in a Food Desert and Adverse Cardiovascular Events in US Veterans With Established Cardiovascular Disease.

Residents living in a "food desert" are known to be at a higher risk for developing cardiovascular disease (CVD). However, national-level data regarding the influence of residing in a food desert in patients with established CVD is lacking. Data from veterans with established atherosclerotic CVD who received outpatient care in the Veterans Health Administration system between January 2016 and December 2021 were obtained, with follow-up information collected until May 2022 (median follow-up: 4.3 years). A food desert was defined using the United States Department of Agriculture criteria, and census tract data were used to identify Veterans in these areas. All-cause mortality and the occurrence of major adverse cardiovascular events (MACEs; a composite of myocardial infarction/stroke/heart failure/all-cause mortality) were evaluated as the co-primary end points. The relative risk for MACE in food desert areas was evaluated by fitting multivariable Cox models adjusted for age, gender, race, ethnicity, and median household income, with food desert status as the primary exposure. Of the 1,640,346 patients (mean age 72 years, women 2.7%, White 77.7%, Hispanic 3.4%), 25,7814 (15.7%) belonged to the food desert group. Patients residing in food deserts were younger; more likely to be Black (22% vs 13%)or Hispanic (4% vs 3.5%); and had a higher prevalence of diabetes mellitus (52.7% vs 49.8%), chronic kidney disease (31.8% vs 30.4%,) and heart failure (25.6% vs 23.8%). Adjusted for covariates, food desert patients had a higher risk of MACE (hazard ratio 1.040 [1.033 to 1.047]; p <0.001) and all-cause mortality (hazard ratio 1.032 [1.024 to 1.039]; p <0.001). In conclusion, we observed that a large proportion of US veterans with established atherosclerotic CVD reside in food desert census tracts. Adjusting for age, gender, race, and ethnicity, residing in food deserts was associated with a higher risk of adverse cardiac events and all-cause mortality.

Exercising empathy: Pharmacists possess skills to increase coronavirus vaccine confidence.

The coronavirus disease 2019 (COVID-19) vaccines are the essential public health intervention to confer immunity against severe acute respiratory syndrome coronavirus 2, while decreasing the risks of severe COVID-19 disease, hospitalizations, and death associated with natural infection. Public health experts agree that the public health interventions of social distancing and face coverings will only be able to successfully curtail the COVID-19 pandemic in the United States when combined with the highly effective COVID-19 vaccines. The risk for severe COVID-19 is higher in Americans with highly prevalent metabolic and cardiovascular chronic conditions as well as vulnerable demographics, such as minorities and pregnant women. Unfortunately, experience with past unethical health practices can influence current vaccine confidence in people of color and women of childbearing age. Pharmacists are well-positioned in myriad health care settings across the nation to listen to these concerns and have the conversations necessary to increase vaccine confidence. Similar to effective roles that pharmacists have had in other health prevention efforts such as smoking cessation, pharmacists possess the motivational interviewing skills to guide patients from the "precontemplation" to the "action" stages of health behavior change. This nonjudgmental, mutual understanding will help identify the individual factors influencing vaccine decision-making and bring us closer to achieving "community immunity."

Rapid and sustained antidepressant properties of an NMDA antagonist/monoamine reuptake inhibitor identified via transporter-based virtual screening.

Rational design of lead compounds targeting monoamine transporters (MATs) is critical to developing novel therapeutics to treat psychiatric disorders including depression and substance abuse. A 3-D dopamine transporter (DAT) computer model was used to virtually screen a commercially available small molecule library for high DAT affinity drug-like compounds. One hit, coded "MI-4", inhibited human dopamine, norepinephrine, and serotonin transporters in vitro. In vivo administration in mice induced robust, dose-dependent antidepressant-like behaviors in learned helplessness models (tail suspension and forced swim tests). Moreover, chronic administration (21day, 10mg/kg, bid) reduced drinking latencies comparable to fluoxetine (10mg/kg, bid) in the novelty-induced hypophagia test, which requires chronic treatment to produce antidepressant-like effects. MI-4 (10mg/kg, bid) produced rapid (three-day) antidepressant-like effects in the social avoidance test following 10days of social defeat stress. Unlike ketamine, chronic administration of MI-4 increased social interaction scores while improving resiliency to the mood-altering effects of stress to over 70%. Importantly, MI-4 exhibited minimal abuse liability in behavioral and neurological models (conditioned place preference and dopamine in vivo microdialysis). MI-4 was found to be Ro-25-6981, an ifenprodil analog and reputed NMDA antagonist. The data suggest that Ro-25-6981, previously known for rapid-acting glutamatergic antidepressant actions, may also functionally inhibit monoamine reuptake and produces sustained antidepressant effects in vivo. This demonstrates, as proof of principle, the viability of combining these mechanisms to produce rapid and sustained antidepressant-like effects. Overall, these findings suggest MAT computational model-based virtual screening is a viable method for identifying antidepressant lead compounds of unique scaffold.

Identification of a novel selective serotonin reuptake inhibitor by coupling monoamine transporter-based virtual screening and rational molecular hybridization.

Ligand virtual screening (VS) using the vestibular binding pocket of a 3-D monoamine transporter (MAT) computational model followed by in vitro pharmacology led to the identification of a human serotonin transporter (hSERT) inhibitor with modest affinity (hSERT K(i) = 284 nM). Structural comparison of this VS-elucidated compound, denoted MI-17, to known SERT ligands led to the rational design and synthesis of DJLDU-3-79, a molecular hybrid of MI-17 and dual SERT/5-HT(1A) receptor antagonist SSA-426. Relative to MI-17, DJLDU-3-79 displayed 7-fold improvement in hSERT binding affinity and a 3-fold increase in [(3)H]-serotonin uptake inhibition potency at hSERT/HEK cells. This hybrid compound displayed a hSERT:hDAT selectivity ratio of 50:1, and a hSERT:hNET (human norepinephrine transporter) ratio of >200:1. In mice, DJLDU-3-79 decreased immobility in the tail suspension test comparable to the SSRI fluvoxamine, suggesting that DJLDU-3-79 may possess antidepressant properties. This proof of concept study highlights MAT virtual screening as a powerful tool for identifying novel inhibitor chemotypes and chemical fragments for rational inhibitor design.