Behavioral Activation mHealth Application for Smoking Cessation: A Randomized Controlled Pilot Trial.

BACKGROUND: Behavioral activation (BA) is an effective intervention for both depression and substance use disorders. Combining BA with a standard smoking cessation intervention may improve quit rates by addressing depressive symptoms, a key barrier to quitting. This study preliminarily evaluated the acceptability and efficacy of the BA-based Actify! mobile health application (mHealth app) for smoking cessation. METHODS: We conducted a pilot randomized controlled trial (n=242) comparing Actify! with the National Cancer Institute's (NCI) app for smoking cessation (QuitGuide) on acceptability (user satisfaction, app openings), smoking abstinence, and mechanisms of change (behavioral activation and depressive symptoms) at 8 weeks and 6 months post-randomization. Participants were US adults recruited online who smoked daily. RESULTS: Treatment satisfaction was uniformly higher in the Actify! arm. Number of app openings was similar across arms (M=34.3 openings over 8 weeks in both arms). Self-reported 30-day point prevalence abstinence (PPA) at 8 weeks was 12.6% for Actify! vs. 7.3% for QuitGuide. Differences in 30-day PPA continued through 6 months (18.5% for Actify! vs. 12.2% for QuitGuide). Changes between baseline and 8 weeks in depressive symptoms and behavioral activation favored Actify!. Planned subgroup analyses suggested greater benefit of Actify! among participants with pre-treatment mild to moderate depression symptom severity compared to those with no depression symptoms. CONCLUSIONS: Actify! showed considerable promise as a novel mHealth treatment, as evidenced by high usage and higher user satisfaction and quit rates than QuitGuide at both short- and long-term follow-up. The next step is to evaluate Actify! in a fully-powered efficacy trial. IMPLICATIONS: Study findings demonstrate the promise of a behavioral activation (BA)-based mobile health app (Actify!) for smoking cessation as a population-level intervention that can effectively address depressive symptoms as a risk factor for worse smoking treatment outcomes. The Actify! app is the first standalone BA-based app to demonstrate potential for improved acceptability and efficacy relative to a standard care comparison app, with user satisfaction and smoking quit rates descriptively exceeding those of the National Cancer Institute's QuitGuide app.

Dysanapsis Genetic Risk Predicts Lung Function Across the Lifespan.

Rationale Dysanapsis refers to a mismatch between airway tree caliber and lung size arising early in life. Dysanapsis assessed by computed tomography (CT) is evident by early adulthood and associated with chronic obstructive pulmonary disease (COPD) risk later in life. Objective By examining the genetic factors associated with CT-assessed dysanapsis, we aimed to elucidate its molecular underpinnings and physiological significance across the lifespan. Methods We performed a genome-wide association study (GWAS) of CT-assessed dysanapsis in 11,951 adults, including individuals from two population-based and two COPD-enriched studies. We applied colocalization analysis to integrate GWAS and gene expression data from whole blood and lung. Genetic variants associated with dysanapsis were combined into a genetic risk score that was applied to examine association with lung function in children from a population-based birth cohort (n=1,278) and adults from the UK Biobank (n=369,157). Measurements and Main Results CT-assessed dysanapsis was associated with genetic variants from 21 independent signals in 19 gene regions, implicating HHIP, DSP, and NPNT as potential molecular targets based on colocalization of their expression. Higher dysanapsis genetic risk score was associated with obstructive spirometry among 5 year old children and among adults in the 5th, 6th and 7th decades of life. Conclusions CT-assessed dysanapsis is associated with variation in genes previously implicated in lung development and dysanapsis genetic risk is associated with obstructive lung function from early life through older adulthood. Dysanapsis may represent an endo-phenotype link between the genetic variations associated with lung function and COPD.

Sexually Transmitted Infection Prevention Services for Women Experiencing Homelessness: A Safety-Net Health System Quality Improvement Initiative.

BACKGROUND: Consistent use of sexually transmitted infection (STI) prevention methods is proven to decrease transmission of STIs. Yet, rates continue to rise within the US, particularly among high-risk populations. Women experiencing homelessness may face barriers to access reproductive healthcare. This quality improvement (QI) initiative sought to examine perceived barriers to STI prevention and opportunities for expanding STI prevention services and education for women experiencing homelessness. METHODS: Surveys were administered during a one-day health event in August 2023 at a clinic that predominately serves persons experiencing homelessness in North Texas. Respondents included adult, non-pregnant, English-speaking, individuals assigned female at birth with a history of homelessness. Demographic characteristics, sexual history, participants' knowledge of STIs, and perceived barriers to obtaining sexual health care were gathered. Participants had the opportunity to suggest methods for improving access to STI care. RESULTS: Among participants (n = 36), over half (59%) were tested for STIs within the past year. Most preferred condoms for STI prevention. The average knowledge score among questions about STI transmission and methods of prevention was 65%, with the lowest scores observed among trichomoniasis (39% correct), pre-exposure prophylaxis (PrEP; 31%), and dental dams (25%). Common barriers included cost (33%) and side effects (33%). One-third (36%) of participants reported no barriers to the use of prevention products. CONCLUSIONS: Findings highlight the need for educational opportunities among this population to increase knowledge of STI transmission and prevention. Patients may benefit from clinicians emphasizing education and increasing the visibility of services.

Design and Pilot Results from Million Veteran Program Return Of Actionable Genetic Results (MVP-ROAR) Study.

BACKGROUND: As a mega-biobank linked to a national healthcare system, the Million Veteran Program (MVP) can directly improve the health care of participants. To determine the feasibility and outcomes of returning medically actionable genetic results to MVP participants, the program launched the MVP Return Of Actionable Results (MVP-ROAR) Study, with familial hypercholesterolemia (FH) as an exemplar actionable condition. METHODS: The MVP-ROAR Study consists of a completed single-arm pilot phase and an ongoing randomized clinical trial (RCT), in which MVP participants are recontacted and invited to receive clinical confirmatory gene sequencing testing and a telegenetic counseling intervention. The primary outcome of the RCT is 6-month change in low-density lipoprotein cholesterol (LDL-C) between participants receiving results at baseline and those receiving results after 6 months. RESULTS: The pilot developed processes to identify and recontact participants nationally with probable pathogenic variants in low-density lipoprotein receptor (LDLR) on the MVP genotype array, invite them to clinical confirmatory gene sequencing, and deliver a telegenetic counseling intervention. Among participants in the pilot phase, 8 (100%) had active statin prescriptions after 6 months. Results were shared with 16 first-degree family members. Six-month ΔLDL-C (low-density lipoprotein cholesterol) after the genetic counseling intervention was -37 mg/dL (95% CI: -12 to -61; p=0.03). The ongoing RCT will determine between-arm differences in this primary outcome. CONCLUSION: While underscoring the importance of clinical confirmation of research results, the pilot phase of the MVP-ROAR Study marks a turning point in MVP and demonstrates the feasibility of returning genetic results to participants and their providers. The ongoing RCT will contribute to understanding how such a program might improve patient health care and outcomes.

Assessing a Continuing Education Course for Dental Hygienists to Improve HPV and HPV Vaccine Knowledge and Self-efficacy.

Human papillomavirus is the most common sexually transmitted infection and causes anogenital and oropharyngeal cancers. Although HPV-related cancers can be prevented through vaccination, HPV vaccination rates are low compared to other vaccines. One of the strongest indicators for vaccination is provider recommendation, and dental health providers are well positioned to promote HPV vaccination among their patients. The purpose of this study was to determine if a continuing education (CE) course could improve dental hygienists' HPV-related knowledge and self-efficacy related to HPV vaccination recommendations. Data were collected from a sample of participants (n = 202) at a large dental hygiene conference in the southern US. A pre- and post-tests were administered with the CE course and differences in HPV vaccine knowledge and self-efficacy in counseling, recommending, and referring for the HPV vaccine were analyzed using SAS. HPV vaccine knowledge overall significantly increased post-CE (p < .001) and improvement was seen among several specific knowledge areas. However, knowledge regarding the common sites of HPV-related oral and oropharyngeal cancers remained moderate (82% correct) even after the CE intervention. There was no significant change from pre-test to post-test in participants' self-efficacy related to counseling patients about the HPV vaccine, recommending the HPV vaccine to patients, or referring patients for the vaccine. This study demonstrates that continuing education can improve dental hygienists' HPV-related knowledge. Since dental providers may play an important role in HPV-related cancer prevention, future work should develop continuing education tools that can motivate changes in self-efficacy and ultimately improve practice behaviors.

Dual-substance use disorder couples: An integrative review and proposed theoretical model.

Committed romantic relationships between two individuals with Substance Use Disorder (or dual-SUD couples) are prevalent. Dual-SUD couples have poor treatment engagement and outcomes. Research has established a reciprocal link between relationship dynamics (e.g., conflict, intimacy) and substance use. Thus, the couple's relationship presents a distinct social context for both partner's substance use. Dual-SUD couples face unique challenges due to substance use being a shared behavior that may serve as a rewarding source of compatibility, closeness, and short-term relationship satisfaction despite it being at the cost of other alternative sources of substance-free reinforcement. Yet, treatment options for these couples are scarce. Dual-maladaptive health behaviors (e.g., dual-substance use) are challenging to treat; however, theory and preliminary research suggests that transformation of couple's joint motivation toward adaptive health behavior change may result in a more satisfying relationship and improved treatment outcomes for both individuals. The current paper reviews the extant literature on dual-SUD couples from theoretical, empirical, and treatment research and proposes an expanded paradigm regarding how we understand dual-SUD couples with the aim of informing basic research and treatment development.

A Coordinated Data Analysis of Four Studies Exploring Age Differences in Social Interactions and Loneliness During a Global Pandemic.

OBJECTIVES: Examining loneliness and social isolation during population-wide historical events may shed light on important theoretical questions about age differences, including whether these differences hold across different regions and the time course of the unfolding event. We used a systematic, preregistered approach of coordinated data analysis (CDA) of 4 studies (total N = 1,307; total observations = 18,492) that varied in design (intensive repeated-measures and cross-sectional), region, timing, and timescale during the first year of the coronavirus disease 2019 pandemic. METHODS: We harmonized our data sets to a common period within 2020-2021 and created a common set of variables. We used a combination of ordinary least squares regression and multilevel modeling to address the extent to which there was within- and between-person variation in the associations between social isolation and loneliness, and whether these associations varied as a function of age. RESULTS: Within- and between-person effects of social interactions were negatively associated with loneliness in 1 study; in follow-up sensitivity analyses, these patterns held across early and later pandemic periods. Across all data sets, there was no evidence of age differences in the within-person or between-person associations of social interactions and loneliness. DISCUSSION: Applying the CDA methodological framework allowed us to detect common and divergent patterns of social interactions and loneliness across samples, ages, regions, periods, and study designs.

Exposure to neighborhood violence, and laboratory-based and ambulatory cognitive task performance in adulthood.

OBJECTIVE: Exposure to neighborhood violence may have negative implications for adults' cognitive functioning, but the ecological sensitivity of these effects has yet to be determined. We first evaluated the link between exposure to neighborhood violence and two latent constructs of cognitive function that incorporated laboratory-based and ambulatory, smartphone-based, cognitive assessments. Second, we examined whether the effect of exposure to violence was stronger for ambulatory assessments compared to in-lab assessments. METHODS: We used data from 256 urban-dwelling adults between 25 and 65 years old (M = 46.26, SD = 11.07); 63.18% non-Hispanic Black, 9.21% non-Hispanic White, 18.41% Hispanic White, 5.02% Hispanic Black, and 4.18% other. Participants completed baseline surveys on neighborhood exposures, cognitive assessments in a laboratory/research office, and ambulatory smartphone-based cognitive assessments five-times a day for 14 days. RESULTS: Exposure to neighborhood violence was associated with poorer performance in a latent working memory construct that incorporated in-lab and ambulatory assessments, but was not associated with the perceptual speed construct. The effect of exposure to neighborhood violence on the working memory construct was explained by its effect on the ambulatory working memory task and not by the in-lab cognitive assessments. CONCLUSION: This study shows the negative effect that exposure to neighborhood violence may have on everyday working memory performance in urban-dwelling adults in midlife. Results highlight the need for more research to determine the sensitivity of ambulatory assessments to quantify the effects of neighborhood violence on cognitive function.

High-risk Escherichia coli clones that cause neonatal meningitis and association with recrudescent infection.

Neonatal meningitis is a devastating disease associated with high mortality and neurological sequelae. Escherichia coli is the second most common cause of neonatal meningitis in full-term infants (herein NMEC) and the most common cause of meningitis in preterm neonates. Here, we investigated the genomic relatedness of a collection of 58 NMEC isolates spanning 1974-2020 and isolated from seven different geographic regions. We show NMEC are comprised of diverse sequence types (STs), with ST95 (34.5%) and ST1193 (15.5%) the most common. No single virulence gene profile was conserved in all isolates; however, genes encoding fimbrial adhesins, iron acquisition systems, the K1 capsule, and O antigen types O18, O75, and O2 were most prevalent. Antibiotic resistance genes occurred infrequently in our collection. We also monitored the infection dynamics in three patients that suffered recrudescent invasive infection caused by the original infecting isolate despite appropriate antibiotic treatment based on antibiogram profile and resistance genotype. These patients exhibited severe gut dysbiosis. In one patient, the causative NMEC isolate was also detected in the fecal flora at the time of the second infection episode and after treatment. Thus, although antibiotics are the standard of care for NMEC treatment, our data suggest that failure to eliminate the causative NMEC that resides intestinally can lead to the existence of a refractory reservoir that may seed recrudescent infection.

Development and utility of a clinical research informatics application for participant recruitment and workflow management for a return of results pilot trial in familial hypercholesterolemia in the Million Veteran Program.

Objective: The development of clinical research informatics tools and workflow processes associated with re-engaging biobank participants has become necessary as genomic repositories increasingly consider the return of actionable research results. Materials and Methods: Here we describe the development and utility of an informatics application for participant recruitment and enrollment management for the Veterans Affairs Million Veteran Program Return Of Actionable Results Study, a randomized controlled pilot trial returning individual genetic results associated with familial hypercholesterolemia. Results: The application is developed in Python-Flask and was placed into production in November 2021. The application includes modules for chart review, medication reconciliation, participant contact and biospecimen logging, survey recording, randomization, and documentation of genetic counseling and result disclosure. Three primary users, a genetic counselor and two research coordinators, and 326 Veteran participants have been integrated into the system as of February 23, 2023. The application has successfully handled 3367 task requests involving greater than 95 000 structured data points. Specifically, application users have recorded 326 chart reviews, 867 recruitment telephone calls, 158 telephone-based surveys, and 61 return of results genetic counseling sessions, among other available study tasks. Conclusion: The development of usable, customizable, and secure informatics tools will become increasingly important as large genomic repositories begin to return research results at scale. Our work provides a proof-of-concept for developing and using such tools to aid in managing the return of results process within a national biobank.

Centralized Interactive Phenomics Resource: an integrated online phenomics knowledgebase for health data users.

OBJECTIVE: Development of clinical phenotypes from electronic health records (EHRs) can be resource intensive. Several phenotype libraries have been created to facilitate reuse of definitions. However, these platforms vary in target audience and utility. We describe the development of the Centralized Interactive Phenomics Resource (CIPHER) knowledgebase, a comprehensive public-facing phenotype library, which aims to facilitate clinical and health services research. MATERIALS AND METHODS: The platform was designed to collect and catalog EHR-based computable phenotype algorithms from any healthcare system, scale metadata management, facilitate phenotype discovery, and allow for integration of tools and user workflows. Phenomics experts were engaged in the development and testing of the site. RESULTS: The knowledgebase stores phenotype metadata using the CIPHER standard, and definitions are accessible through complex searching. Phenotypes are contributed to the knowledgebase via webform, allowing metadata validation. Data visualization tools linking to the knowledgebase enhance user interaction with content and accelerate phenotype development. DISCUSSION: The CIPHER knowledgebase was developed in the largest healthcare system in the United States and piloted with external partners. The design of the CIPHER website supports a variety of front-end tools and features to facilitate phenotype development and reuse. Health data users are encouraged to contribute their algorithms to the knowledgebase for wider dissemination to the research community, and to use the platform as a springboard for phenotyping. CONCLUSION: CIPHER is a public resource for all health data users available at https://phenomics.va.ornl.gov/ which facilitates phenotype reuse, development, and dissemination of phenotyping knowledge.

Evaluation of taurine and carnitine concentrations in whole blood, plasma, skeletal muscle and cardiac muscle in dogs.

Little is known about how plasma and whole blood taurine and plasma carnitine correlate to concentrations in skeletal and cardiac muscle and the effects of diet in dogs. The purpose of this study was to evaluate the correlation among plasma, skeletal and cardiac muscle carnitine and taurine and whole blood taurine and determine the effect of diet. The study protocol was approved by the Pet Food Solutions Institutional Animal Care and Use Committee. Thirty-three mixed-breed hounds and 32 beagles were evaluated at Day 0 then removed from their baseline diet and randomized to a test diet: high animal protein, grain-inclusive (HA-GI), low animal protein, grain-free (LA-GF), low animal protein, grain-inclusive (LA-GI), or high animal protein, grain-free (HA-GF). Blood was drawn every 30 days and endomyocardial (mixed breeds only) and skeletal muscle biopsies were collected at Days 0 and 180. The correlations between plasma and whole blood taurine, or plasma carnitine and skeletal and cardiac muscle concentrations were weak (p < 0.01-0.05). Mixed-breed hounds had increased (p = 0.029) whole blood taurine compared to beagles. Plasma taurine was lower with diet HA-GF, (p = 0.009) however, all diets had increased taurine from Day 0 and were, on average within the laboratory reference range. Dogs fed the HA-GI diet had increased cardiac muscle carnitine esters (p = 0.014). Increased carnitine esters were also appreciated in cardiac muscle in all diets from Day 0 to 180 (p = 0.0001). On Day 180 mixed-breed hounds had increased skeletal total carnitine (p < 0.001) compared to all time points and breeds. This study observed no correlation between plasma, whole blood, skeletal and cardiac muscle taurine concentrations but noted some effects between time, breed and diet.

Prospective associations of psychedelic treatment for co-occurring alcohol misuse and posttraumatic stress symptoms among United States Special Operations Forces Veterans.

This study evaluated prospective associations of ibogaine and 5-MeO-DMT treatment for risky alcohol use and post-traumatic stress disorder (PTSD) symptoms among United States (US) Special Operations Forces Veterans (SOFV). Data were collected during standard clinical operations at pre-treatment and 1-month (1 m), 3-months (3 m), and 6-months (6 m) post-treatment in an ibogaine and 5-MeO-DMT treatment program in Mexico. Of the 86 SOFV that completed treatment, 45 met criteria for risky alcohol use at pre-treatment (mean age = 44; male = 100%; White = 91%). There was a significant reduction in alcohol use from pre-treatment (M = 7.2, SD = 2.3) to 1 m (M = 3.6; SD = 3.5) post-treatment, which remained reduced through 6 m (M = 4.0; SD = 2.9; p < .001, partial eta squared = .617). At 1 m, 24% were abstinent, 33% were non-risky drinking, and 42% were risky drinkers. At 6 m, 16% were abstinent, 31% were non-risky drinking, and 53% were risky drinkers. There were no differences between responders (abstinent/non-risky drinkers) and non-responders (risky drinkers) in demographics/clinical characteristics. However, there were significant and very large differences between responders and non-responders in PTSD symptom (p < .01, d = -3.26) and cognitive functioning change (p < .01, d = -0.99). Given these findings, future clinical trials should determine whether psychedelic-assisted therapy holds promise for individuals with complex trauma and alcohol misuse who have not been successfully treated with traditional interventions.

The Million Veteran Program 1990-1991 Gulf War Era Survey: An Evaluation of Veteran Response, Characteristics, and Representativeness of the Gulf War Era Veteran Population.

To address gaps in understanding the pathophysiology of Gulf War Illness (GWI), the VA Million Veteran Program (MVP) developed and implemented a survey to MVP enrollees who served in the U.S. military during the 1990-1991 Persian Gulf War (GW). Eligible Veterans were invited via mail to complete a survey assessing health conditions as well as GW-specific deployment characteristics and exposures. We evaluated the representativeness of this GW-era cohort relative to the broader population by comparing demographic, military, and health characteristics between respondents and non-respondents, as well as with all GW-era Veterans who have used Veterans Health Administration (VHA) services and the full population of U.S. GW-deployed Veterans. A total of 109,976 MVP GW-era Veterans were invited to participate and 45,270 (41%) returned a completed survey. Respondents were 84% male, 72% White, 8% Hispanic, with a mean age of 61.6 years (SD = 8.5). Respondents were more likely to be older, White, married, better educated, slightly healthier, and have higher socioeconomic status than non-respondents, but reported similar medical conditions and comparable health status. Although generally similar to all GW-era Veterans using VHA services and the full population of U.S. GW Veterans, respondents included higher proportions of women and military officers, and were slightly older. In conclusion, sample characteristics of the MVP GW-era cohort can be considered generally representative of the broader GW-era Veteran population. The sample represents the largest research cohort of GW-era Veterans established to date and provides a uniquely valuable resource for conducting in-depth studies to evaluate health conditions affecting 1990-1991 GW-era Veterans.

HPV self-sampling among women in the United States: preferences for implementation.

PURPOSE: With the inclusion of primary HPV testing in 2018 U.S. Preventive Services Taskforce guidelines, at-home HPV self-sampling may provide a future option for cervical cancer screening, especially among hard-to-reach populations in the U.S. This study evaluated the association of implementation preferences with the willingness of at-home HPV self-sampling. METHODS: We conducted a cross-sectional study in 2018 among U.S. women ages 30-65 years, without a hysterectomy (n = 812). The outcome was willingness to have at-home HPV self-sampling (yes/no). Primary predictor variables (i.e., information source, methods of payment, methods of sending or receiving self-sampling kits) measured self-sampling implementation preferences. Adjusted logistic regression identified associations with willingness to have at-home HPV self-sampling. RESULTS: Participants who preferred receiving information from healthcare providers (OR = 2.64; 95% CI 1.54,4.52) or from media or other sources (OR = 2.30; 95% CI 1.51,3.48) had higher HPV self-sampling willingness than participants who did not prefer those sources. Participants who did not want to pay for self-sampling (OR = 0.21; 95% CI 0.14,0.32) or did not know if they would pay for self-sampling (OR = 0.35; 95% CI 0.22,0.54) had lower odds of HPV self-sampling willingness compared to participants willing to pay. Participants who did not know which method they preferred for receiving a self-sampling kit (OR = 0.15, 95% CI 0.07,0.31) or preferred delivering the sample to the lab themselves (OR = 0.59; 95% CI 0.36,0.96) had lower odds for self-sampling willingness compared to participants who preferred the mail. CONCLUSION: Understanding the preferences of women regarding the implementation of HPV self-sampling can improve uptake in cervical cancer screening, especially among hard-to-reach populations.

Supervised exercise training improves cardiorespiratory fitness and reduces perioperative risk in peripheral artery disease patients with intermittent claudication.

INTRODUCTION: This study examined to what extent supervised aerobic and resistance exercise combined with continued unsupervised exercise training improves cardiorespiratory fitness and corresponding perioperative risk in peripheral artery disease (PAD) patients with intermittent claudication. METHODS: A total of 106 patients (77% male) were enrolled into the study, alongside 155 healthy non-PAD control participants. Patients completed supervised exercise therapy (aerobic and resistance exercises of the upper and lower limbs) twice a week for 10 weeks. Thereafter, 52 patients completed 12 weeks of an unsupervised tailored home-based exercise. Pain-free walking distance (PWD), maximum walking distance (MWD), peak oxygen uptake ([Formula: see text]) and perioperative risk were assessed before and after both exercise interventions. RESULTS: Patients were highly unconditioned relative to healthy controls ([Formula: see text]=11.9 vs 24.2ml/kg/min, p=<0.001) with 91% classified as high perioperative risk (peak oxygen uptake <15ml/kg/min). Supervised exercise increased PWD (+44±81m, p=<0.001), MWD (+44±71m, p=<0.001) and [Formula: see text] (+1.01±1.63ml/kg/min, p=<0.001) and lowered perioperative risk (91% to 85%, p=<0.001). When compared with supervised exercise, the improvements in PWD were maintained following unsupervised exercise (+11±91m vs supervised exercise, p=0.572); however, MWD and [Formula: see text] decreased (-15±48m, p=0.030 and -0.34±1.11ml/kg/min, p=0.030, respectively) and perioperative risk increased (+3%, p=<0.001) although still below baseline (p=<0.001). CONCLUSIONS: Supervised aerobic and resistance exercise training and, to a lesser extent, unsupervised tailored exercise improves walking capacity and cardiorespiratory fitness and reduces perioperative risk in PAD patients with intermittent claudication.

HOPX-associated molecular programs control cardiomyocyte cell states underpinning cardiac structure and function.

Genomic regulation of cardiomyocyte differentiation is central to heart development and function. This study uses genetic loss-of-function human-induced pluripotent stem cell-derived cardiomyocytes to evaluate the genomic regulatory basis of the non-DNA-binding homeodomain protein HOPX. We show that HOPX interacts with and controls cardiac genes and enhancer networks associated with diverse aspects of heart development. Using perturbation studies in vitro, we define how upstream cell growth and proliferation control HOPX transcription to regulate cardiac gene programs. We then use cell, organoid, and zebrafish regeneration models to demonstrate that HOPX-regulated gene programs control cardiomyocyte function in development and disease. Collectively, this study mechanistically links cell signaling pathways as upstream regulators of HOPX transcription to control gene programs underpinning cardiomyocyte identity and function.

The impact of spiritual well-being and social support on substance use treatment outcomes within a sample of predominantly Black/African American adults.

INTRO: Substance use and associated problems often return following treatment for substance use disorder (SUD), which disproportionally impact Black/African American (AA) individuals. Social support and spiritual well-being are sources of recovery capital identified as particularly important among Black/AA adults. Social support and spiritual well-being are also posited mechanisms in 12-step; thus, this study tested the effects of social support and spiritual well-being on substance use outcomes over time, distinct from 12-step involvement, among Black/AA adults post-SUD treatment. The study hypothesized that social support and spiritual well-being would demonstrate significant interactions with time, respectively, on substance use frequency and substance use consequences, above the effect of 12-step involvement. METHOD: The study drew data from a study of 262 adults (95.4 % Black/AA) entering residential SUD treatment (NCT#01189552). Assessments were completed at pretreatment and at 3-, 6-, and 12-months posttreatment. Two generalized linear mixed models (GLMM) tested the effects of social support and spiritual well-being, above the effect of 12-step involvement, on substance use frequency and substance use consequences over the course of 12-months posttreatment. RESULTS: Higher spiritual well-being predicted significantly less frequent substance use during recovery (ß = 0.00, p = .03). Greater 12-step involvement predicted significantly fewer substance use consequences during recovery (ß = 0.00, p = .02). In post hoc analyses the effect of spiritual well-being and 12-step involvement dissipated by 3.5- and 6.6-months posttreatment, respectively. The study found no significant effects of social support over time. DISCUSSION: Spiritual well-being and 12-step involvement are associated with lower substance use and substance use consequences, respectively, in the early months of posttreatment recovery among Black/AA adults. These findings contribute to the growing recovery capital literature informing paths to recovery and sources of support outside of 12-step affiliation. However, these effects diminish over time.

Impact of 8 lifestyle factors on mortality and life expectancy among United States veterans: The Million Veteran Program.

BACKGROUND: Lifestyle medicine has been proposed as a way to address the root causes of chronic disease and their associated health care costs. OBJECTIVE: This study aimed to estimate mortality risk and longevity associated with individual lifestyle factors and comprehensive lifestyle therapy. METHODS: Age- and sex-specific mortality rates were calculated on the basis of 719,147 veterans aged 40-99 y enrolled in the Veteran Affairs Million Veteran Program (2011-2019). Hazard ratios and estimated increase in life expectancy were examined among a subgroup of 276,132 veterans with complete data on 8 lifestyle factors at baseline. The 8 lifestyle factors included never smoking, physical activity, no excessive alcohol consumption, restorative sleep, nutrition, stress management, social connections, and no opioid use disorder. RESULTS: On the basis of 1.12 million person-years of follow-up, 34,247 deaths were recorded. Among veterans who adopted 1, 2, 3, 4, 5, 6, 7, and 8 lifestyle factors, the adjusted hazard ratios for mortality were 0.74 (0.60-0.90), 0.60 (95% CI: 0.49, 0.73), 0.50 (95% CI: 0.41, 0.61), 0.43 (95% CI: 0.35, 0.52), 0.35 (95% CI: 0.29, 0.43), 0.27 (95% CI: 0.22, 0.33), 0.21 (95% CI: 0.17, 0.26), and 0.13 (95% CI: 0.10, 0.16), respectively, as compared with veterans with no adopted lifestyle factors. The estimated life expectancy at age 40 y was 23.0, 26.5, 28.8, 30.8, 32.7, 35.1, 38.3, 41.3, and 47.0 y among males and 27.0, 28.8, 33.1, 38.0, 39.2, 41.4, 43.8, 46.3, and 47.5 y for females who adopted 0, 1, 2, 3, 4, 5, 6, 7, and 8 lifestyle factors, respectively. The difference in life expectancy at age 40 y was 24.0 y for male veterans and 20.5 y for female veterans when comparing adoption of 8-9 lifestyle factors. CONCLUSIONS: A combination of 8 lifestyle factors is associated with a significantly lower risk of premature mortality and an estimated prolonged life expectancy.

Epigenetic Age Acceleration and Chronological Age: Associations With Cognitive Performance in Daily Life.

DNA methylation-derived epigenetic clocks offer the opportunity to examine aspects of age acceleration (ie, the difference between an individual's biological age and chronological age), which vary among individuals and may better account for age-related changes in cognitive function than chronological age. Leveraging existing ambulatory cognitive assessments in daily life from a genetically diverse sample of 142 adults in midlife, we examined associations between 5 measures of epigenetic age acceleration and performance on tasks of processing speed and working memory. Covarying for chronological age, we used multilevel models to examine associations of epigenetic age acceleration (Horvath 1, Horvath 2, Hannum, PhenoAge, and GrimAge clocks) with both average level and variability of cognitive performance. Positive age acceleration (ie, epigenetic age greater than chronological age) was associated with poorer mean processing speed (Horvath 1 and 2) and working memory (GrimAge). Higher chronological age was also associated with poorer mean processing speed and working memory performance. Further, positive age acceleration was generally associated with greater intraindividual variability in working memory and processing speed tasks, whereas being chronologically older was associated with less intraindividual variability. Although further work is needed, our results indicate age acceleration effects have comparable or greater size as those for chronological age differences, suggesting that epigenetic age acceleration may account for additional risk and interindividual variation in cognitive performance above chronological age.