Faculty Bibliography

Exposure to arsenic affects millions of people globally. Changes in the epigenome may be involved in pathways linking arsenic to health or serve as biomarkers of exposure. This study investigated associations between prenatal and early-life arsenic exposure and epigenetic age acceleration (EAA) in adults, a biomarker of morbidity and mortality. DNA methylation was measured in peripheral blood mononuclear cells (PBMCs) and buccal cells from 40 adults (median age = 49 years) in Chile with and without high prenatal and early-life arsenic exposure. EAA was calculated using the Horvath, Hannum, PhenoAge, skin and blood, GrimAge, and DNA methylation telomere length clocks. We evaluated associations between arsenic exposure and EAA using robust linear models. Participants classified as with and without arsenic exposure had a median drinking water arsenic concentration at birth of 555 and 2 μg/l, respectively. In PBMCs, adjusting for sex and smoking, exposure was associated with a 6-year PhenoAge acceleration [B (95% CI) = 6.01 (2.60, 9.42)]. After adjusting for cell-type composition, we found positive associations with Hannum EAA [B (95% CI) = 3.11 (0.13, 6.10)], skin and blood EAA [B (95% CI) = 1.77 (0.51, 3.03)], and extrinsic EAA [B (95% CI) = 4.90 (1.22, 8.57)]. The association with PhenoAge acceleration in buccal cells was positive but not statistically significant [B (95% CI) = 4.88 (-1.60, 11.36)]. Arsenic exposure limited to early-life stages may be associated with biological aging in adulthood. Future research may provide information on how EAA programmed in early life is related to health.

Background/UNASSIGNED:Research on the efficacy of ketamine in treating depression and 3,4-methylenedioxymethamphetamine (MDMA) in treating post-traumatic stress disorder have been widely covered by the media. Given recent widespread coverage of the efficacy of these drugs, it is important to determine whether such coverage influences prevalence of recreational use. While longitudinal studies would be most ideal for assessing this, to acquire preliminary data, we tested survey items assessing this potential phenomenon in a population known for high prevalence of use of these drugs. Method/UNASSIGNED:= 209) were surveyed about drug use. Questions were included to assess their perceived likelihood of recent media coverage about medical benefits associated with use of ketamine and MDMA affecting their own use. Results/UNASSIGNED:Two-thirds (66.8%) of participants had ever used ecstasy/MDMA and 22.6% had ever used ketamine. The plurality of participants reported that media coverage about ketamine (46.1%) and MDMA (39.9%) did not affect their likelihood of using. 10.1% and 21.0% of participants reported increased likelihood of using ketamine and MDMA, respectively. 52.3% of those reporting past-month ketamine use and 6.1% of those reporting no lifetime use reported being more likely to use in response to media coverage about ketamine. 28.6% of those reporting past-month ecstasy use and 5.5% of those reporting no lifetime use reported being more likely to use in response to media coverage about MDMA. Discussion/UNASSIGNED:Media coverage about the medical benefits of ketamine and MDMA might influence specific subsets of people to use.

Non-adherence to antihypertensive medications is a major cause of uncontrolled hypertension, leading to cardiovascular morbidity and mortality. Ensuring consistent medication possession is crucial in addressing non-adherence. Community-based medication delivery is a strategy that may improve medication possession, adherence, and blood pressure (BP) reduction. Our program in Kenya piloted a community medication delivery program, coupled with blood pressure monitoring and adherence evaluation. Between September 2019 and March 2020, patients who received hypertension care from our chronic disease management program also received community-based delivery of antihypertensive medications. We calculated number of days during which each patient had possession of medications and analyzed the relationship between successful medication delivery and self-reported medication adherence and BP. A total of 128 patient records (80.5% female) were reviewed. At baseline, mean systolic blood pressure (SBP) was 155.7 mmHg and mean self-reported adherence score was 2.7. Sixty-eight (53.1%) patients received at least 1 successful medication delivery. Our pharmacy dispensing records demonstrated that medication possession was greater among patients receiving medication deliveries. Change in self-reported medication adherence from baseline worsened in patients who did not receive any medication delivery (+0.5), but improved in patients receiving 1 delivery (-0.3) and 2 or more deliveries (-0.8). There was an SBP reduction of 1.9, 6.1, and 15.5 mmHg among patients who did not receive any deliveries, those who received 1 delivery, and those who received 2 or more medication deliveries, respectively. Adjusted mixed-effect model estimates revealed that mean SBP reduction and self-reported medication adherence were improved among individuals who successfully received medication deliveries, compared to those who did not. A community medication delivery program in western Kenya was shown to be implementable and enhanced medication possession, reduced SBP, and significantly improved self-reported adherence. This is a promising strategy to improve health outcomes for patients with uncontrolled hypertension that warrants further investigation.

We present a hierarchical integrated model of self-regulation in which executive function is the cognitive component of the model, together with emotional, behavioral, physiological, and genetic components. These five components in the model are reciprocally and recursively related. The model is supported by empirical evidence, primarily from a single longitudinal study with good measurement at each level of the model. We also find that the model is consistent with current thinking on related topics such as cybernetic theory, the theory of allostasis and allostatic load, and the theory of skill development in harsh and unpredictable environments, referred to as "hidden talents." Next, we present literature that the integrative processes are susceptible to environmental adversity, poverty-related risk in particular, while positive social interactions with caregivers (e.g., maternal sensitivity) would promote self-regulatory processes or mitigate the adverse effect of early risk on the processes. A hierarchical integrative model of self-regulation advances our understanding of self-regulatory processes. Future research may consider broader social contexts of the integrative self-regulation system, such as neighborhood/community contexts and structural racism. This can be an integral step to provide children with equitable opportunities to thrive, even among children living in socioeconomically and psychosocially disadvantaged environments.

INTRODUCTION:The aim of this study was to assess the association of peripheral neuropathy (PN) as defined by monofilament insensitivity with mild cognitive impairment (MCI) and dementia in older adults with and without diabetes. METHODS:We conducted a cross-sectional analysis of 3,362 Black and White participants in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) who underwent monofilament testing at visit 6 (2016-2017, age 71-94 years). Participants' cognitive status was classified by an adjudication committee as cognitively normal, MCI, or dementia after completing a comprehensive battery of neurocognitive assessments. We used logistic regression to evaluate the association of PN with MCI or dementia overall and stratified by diabetes status after adjusting for traditional dementia risk factors. We also compared age-adjusted brain MRI measures among a subset (N = 1,095) of participants with versus without PN. RESULTS:Overall, the prevalence of MCI (21.9% vs. 16.7%) and dementia (7.8% vs. 3.9%) were higher among participants with versus without PN (both p < 0.05). After adjustment, PN was positively associated with MCI or dementia in the overall study population (OR 1.45, 95% CI 1.23, 1.73). Results were similar by diabetes status (diabetes: OR 1.38, 95% CI 1.03-1.87; no diabetes: OR 1.48, 95% CI 1.20-1.83; p-for-interaction = 0.46). Age-adjusted total and lobar brain volumes were significantly lower in participants with versus without PN (both, p < 0.05). DISCUSSION/CONCLUSIONS:PN as defined by monofilament insensitivity was associated with cognitive status independent of vascular risk factors and regardless of diabetes status. Our findings support a connection between PN and cognitive impairment, even in the absence of diabetes.