Epigenome-wide mediation analysis of the relationship between psychosocial stress and cardiometabolic risk factors in the Health and Retirement Study (HRS).

Background: Exposure to psychosocial stress is linked to a variety of negative health outcomes, including cardiovascular disease and its cardiometabolic risk factors. DNA methylation has been associated with both psychosocial stress and cardiometabolic disease; however, little is known about the mediating role of DNA methylation on the association between stress and cardiometabolic risk. Thus, using the high-dimensional mediation testing method, we conducted an epigenome-wide mediation analysis of the relationship between psychosocial stress and ten cardiometabolic risk factors in a multi-racial/ethnic population of older adults (n = 2668) from the Health and Retirement Study (mean age = 70.

Epigenome-wide association study of long-term psychosocial stress in older adults.

Long-term psychosocial stress is strongly associated with negative physical and mental health outcomes, as well as adverse health behaviours; however, little is known about the role that stress plays on the epigenome. One proposed mechanism by which stress affects DNA methylation is through health behaviours. We conducted an epigenome-wide association study (EWAS) of cumulative psychosocial stress ( = 2,689) from the Health and Retirement Study (mean age = 70.

Associations Between Cognitive Impairment Severity and Barriers to Healthcare Engagement Among Older Adults.

To assess whether older adults with a cognitive impairment were more likely to report challenges interacting with medical providers, or to avoid needed medical care. Data for this exploratory, cross-sectional analysis were from older adults ( = 493) ages 60-82 participating in the "LitCog" cohort study. Multivariable generalized linear models compared cognitive impairment (none, mild, moderate, severe) with validated measures of healthcare engagement.

Trajectories of perceived susceptibility to COVID-19 over a year: The COVID-19 & chronic conditions (C3) cohort study.

The U.S. public health response to coronavirus disease 2019 (COVID-19) has been widely criticized as having downplayed the potential implications COVID-19 could have on one's personal health.

Perceptions of Signs of Addiction Among Opioid Naive Patients Prescribed Opioids in the Emergency Department.

Objectives: Patient knowledge deficits related to opioid risks, including lack of knowledge regarding addiction, are well documented. Our objective was to characterize patients' perceptions of signs of addiction.

Methods: This study utilized data obtained as part of a larger interventional trial.

Patient-Reported Opioid Pill Consumption After an ED Visit: How Many Pills Are People Using?

Objectives: Recent guidelines advise limiting opioid prescriptions for acute pain to a three-day supply; however, scant literature quantifies opioid use patterns after an emergency department (ED) visit. We sought to describe opioid consumption patterns after an ED visit for acute pain.

Design: Descriptive study with data derived from a larger interventional study promoting safe opioid use after ED discharge.

Longitudinal Investigation of Older Adults' Ability to Self-Manage Complex Drug Regimens.

Objectives: We sought to investigate older patients' ability to correctly and efficiently dose multidrug regimens over nearly a decade and to explore factors predicting declines in medication self-management.

Design: Longitudinal cohort study funded by the National Institute on Aging.

Setting: One academic internal medicine clinic and six community health centers.

A Multifaceted Intervention to Improve Patient Knowledge and Safe Use of Opioids: Results of the ED EMC Randomized Controlled Trial.

Objectives: Despite increased focus on opioid prescribing, little is known about the influence of prescription opioid medication information given to patients in the emergency department (ED). The study objective was to evaluate the effect of an Electronic Medication Complete Communication (EMC ) Opioid Strategy on patients' safe use of opioids and knowledge about opioids.

Methods: This was a three-arm prospective, randomized controlled pragmatic trial with randomization occurring at the physician level.

Implementation fidelity of patient-centered prescription label to promote opioid safe use.

Purpose: Patient-centered labels may improve safe medication use, but implementation challenges limit use. We assessed implementation of a patient-centered "PRN" (as needed) label entitled "Take-Wait-Stop" (TWS) with three deconstructed steps replacing traditional wording.

Methods: As part of a larger investigation, patients received TWS prescriptions (eg, Take: 1 pill if you have pain; Wait: at least 4 h before taking again; Stop: do not take more than 6 pills in 24 h).

Who Is Keeping Their Unused Opioids and Why?

Objective: To better understand patients' reasoning for keeping unused opioid pills.

Methods: As part of a larger study, patients were asked their plans for their unused opioids. Responses were categorized as "dispose," "keep," and "don't know.

Adaptive increases in expression and vasodilator activity of estrogen receptor subtypes in a blood vessel-specific pattern during pregnancy.

Normal pregnancy is associated with adaptive hemodynamic, hormonal, and vascular changes, and estrogen (E2) may promote vasodilation during pregnancy; however, the specific E2 receptor (ER) subtype, post-ER signaling mechanism, and vascular bed involved are unclear. We tested whether pregnancy-associated vascular adaptations involve changes in the expression/distribution/activity of distinct ER subtypes in a blood vessel-specific manner. Blood pressure (BP) and plasma E2 were measured in virgin and pregnant (day 19) rats, and the thoracic aorta, carotid artery, mesenteric artery, and renal artery were isolated for measurements of ERα, ERβ, and G protein-coupled receptor 30 [G protein-coupled ER (GPER)] expression and tissue distribution in parallel with relaxation responses to E2 (all ERs) and the specific ER agonist 4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)-tris-phenol (PPT; ERα), diarylpropionitrile (DPN; ERβ), and G1 (GPER).

Cooperative Role of Mineralocorticoid Receptor and Caveolin-1 in Regulating the Vascular Response to Low Nitric Oxide-High Angiotensin II-Induced Cardiovascular Injury.

Aldosterone interacts with mineralocorticoid receptor (MR) to stimulate sodium reabsorption in renal tubules and may also affect the vasculature. Caveolin-1 (cav-1), an anchoring protein in plasmalemmal caveolae, binds steroid receptors and also endothelial nitric oxide synthase, thus limiting its translocation and activation. To test for potential MR/cav-1 interaction in the vasculature, we investigated if MR blockade in cav-1-replete or -deficient states would alter vascular function in a mouse model of low nitric oxide (NO)-high angiotensin II (AngII)-induced cardiovascular injury.

Critical Role of Striatin in Blood Pressure and Vascular Responses to Dietary Sodium Intake.

Striatin is a protein regulator of vesicular trafficking in neurons that also binds caveolin-1 and Ca(2+)-calmodulin and could activate endothelial nitric oxide synthase. We have shown that striatin colocalizes with the mineralocorticoid receptor and that mineralocorticoid receptor activation increases striatin levels in vascular cells. To test whether striatin is a regulator of vascular function, wild-type and heterozygous striatin-deficient mice (Strn(+/-)) were randomized in crossover intervention to restricted (0.

Dissociation of hyperglycemia from altered vascular contraction and relaxation mechanisms in caveolin-1 null mice.

Hyperglycemia and endothelial dysfunction are associated with hypertension, but the specific causality and genetic underpinning are unclear. Caveolin-1 (cav-1) is a plasmalemmal anchoring protein and modulator of vascular function and glucose homeostasis. Cav-1 gene variants are associated with reduced insulin sensitivity in hypertensive individuals, and cav-1(-/-) mice show endothelial dysfunction, hyperglycemia, and increased blood pressure (BP).