CAF-1 and Rtt101p function within the replication-coupled chromatin assembly network to promote H4 K16ac, preventing ectopic silencing.

Replication-coupled chromatin assembly is achieved by a network of alternate pathways containing different chromatin assembly factors and histone-modifying enzymes that coordinate deposition of nucleosomes at the replication fork. Here we describe the organization of a CAF-1-dependent pathway in Saccharomyces cerevisiae that regulates acetylation of histone H4 K16. We demonstrate factors that function in this CAF-1-dependent pathway are important for preventing establishment of silenced states at inappropriate genomic sites using a crippled HMR locus as a model, while factors specific to other assembly pathways do not. This CAF-1-dependent pathway required the cullin Rtt101p, but was functionally distinct from an alternate pathway involving Rtt101p-dependent ubiquitination of histone H3 and the chromatin assembly factor Rtt106p. A major implication from this work is that cells have the inherent ability to create different chromatin modification patterns during DNA replication via differential processing and deposition of histones by distinct chromatin assembly pathways within the network.

Progranulin mutations result in impaired processing of prosaposin and reduced glucocerebrosidase activity.

Frontotemporal dementia (FTD) is a common neurogenerative disorder characterized by progressive degeneration in the frontal and temporal lobes. Heterozygous mutations in the gene encoding progranulin (PGRN) are a common genetic cause of FTD. Recently, PGRN has emerged as an important regulator of lysosomal function. Here, we examine the impact of PGRN mutations on the processing of full-length prosaposin to individual saposins, which are critical regulators of lysosomal sphingolipid metabolism. Using FTD-PGRN patient-derived cortical neurons differentiated from induced pluripotent stem cells, as well as post-mortem tissue from patients with FTLD-PGRN, we show that PGRN haploinsufficiency results in impaired processing of prosaposin to saposin C, a critical activator of the lysosomal enzyme glucocerebrosidase (GCase). Additionally, we found that PGRN mutant neurons had reduced lysosomal GCase activity, lipid accumulation and increased insoluble α-synuclein relative to isogenic controls. Importantly, reduced GCase activity in PGRN mutant neurons is rescued by treatment with saposin C. Together, these findings suggest that reduced GCase activity due to impaired processing of prosaposin may contribute to pathogenesis of FTD resulting from PGRN mutations.

Evaluation of Strategies for Measuring Lysosomal Glucocerebrosidase Activity.

Mutations in GBA1, which encode for the protein glucocerebrosidase (GCase), are the most common genetic risk factor for Parkinson's disease and dementia with Lewy bodies. In addition, growing evidence now suggests that the loss of GCase activity is also involved in onset of all forms of Parkinson's disease, dementia with Lewy bodies, and other dementias, such as progranulin-linked frontal temporal dementia. As a result, there is significant interest in developing GCase-targeted therapies that have the potential to stop or slow progression of these diseases. Despite this interest in GCase as a therapeutic target, there is significant inconsistency in the methodology for measuring GCase enzymatic activity in disease-modeling systems and patient populations, which could hinder progress in developing GCase therapies. In this review, we discuss the different strategies that have been developed to assess GCase activity and highlight the specific strengths and weaknesses of these approaches as well as the gaps that remain. We also discuss the current and potential role of these different methodologies in preclinical and clinical development of GCase-targeted therapies. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Action Learning Cohort Series: An Innovative Community-Engaged Approach for Translating Research Into Practice.

Cultivating strong partnerships among community and academic stakeholders expedites the translation of research findings into practice and communities by enhancing opportunities for research dissemination and implementation. However, the lack of systematic methods for community stakeholder engagement may decelerate the translational research process. The North Carolina Translational Research and Clinical Sciences Institute implemented an innovative approach to community engagement called the Action Learning Cohort (ALC) Series. The ALC Series, a workgroup extension of a professional conference, used action learning and systems thinking strategies to conceptualize and develop a product aimed at preventing, treating, and controlling hypertension in eastern North Carolina. We evaluated the acceptability and practicality of the ALC Series using survey, focus group, and interview pilot data. Action learning and systems thinking strategies led ALC stakeholders to develop and disseminate The Empathy Building Resource Guide: A Toolkit for Enhancing Patient-Provider Relationships in the Treatment, Management, and Prevention of Hypertension. Stakeholders rated the Series as satisfactory and acknowledged gains in knowledge and desire for engagement with fellow ALC stakeholders beyond the Series. The ALC Series approach is a potentially practical and acceptable model for systematically engaging community stakeholders in translating knowledge into a product that addresses health topics like hypertension.

Chronic Disease Among African American Families: A Systematic Scoping Review.

INTRODUCTION: Chronic diseases are common among African Americans, but the extent to which research has focused on addressing chronic diseases across multiple members of African American families is unclear. This systematic scoping review summarizes the characteristics of research addressing coexisting chronic conditions among African American families, including guiding theories, conditions studied, types of relationships, study outcomes, and intervention research. METHODS: The literature search was conducted in PsycInfo, PubMed, Social Work Abstracts, Sociological Abstracts, CINAHL, and Family and Society Studies Worldwide to identify relevant articles published from January 2000 through September 2016. We screened the title and abstracts of 9,170 articles, followed by full-text screening of 530 articles, resulting in a final sample of 114 articles. Fifty-seven percent (n = 65) of the articles cited a guiding theory/framework, with psychological theories (eg, social cognitive theory, transtheoretical model) being most prominent. The most common conditions studied in families were depression (70.2%), anxiety (23.7%), and diabetes (22.8%), with most articles focusing on a combination of physical and mental health conditions (47.4%). RESULTS: In the 114 studies in this review, adult family members were primarily the index person (71.1%, n = 81). The index condition, when identified (79.8%, n = 91), was more likely to be a physical health condition (46.5%, n = 53) than a mental health condition (29.8%, n = 34). Among 343 family relationships examined, immediate family relationships were overwhelmingly represented (85.4%, n = 293); however, extended family (12.0%, n = 41) and fictive kin (0.6%, n = 2) were included. Most (57.0%, n = 65) studies focused on a single category of outcomes, such as physical health (eg, obesity, glycemic control), mental health (eg, depression, anxiety, distress), psychosocial outcomes (eg, social support, caregiver burden), or health behaviors (eg, medication adherence, disease management, health care utilization); however, 43.0% (n = 49) of studies focused on outcomes across multiple categories. Sixteen intervention articles (14.0%) were identified, with depression the most common condition of interest. CONCLUSION: Recognizing the multiple, simultaneous health issues facing families through a lens of family comorbidity and family multimorbidity may more accurately mirror the lived experiences of many African American families and better elucidate intervention opportunities than previous approaches.

A Cluster Randomized Trial of a Community-Based Intervention Among African-American Adults: Effects on Dietary and Physical Activity Outcomes.

Evidence of the effectiveness of community-based lifestyle behavior change interventions among African-American adults is mixed. We implemented a behavioral lifestyle change intervention, Heart Matters, in two rural counties in North Carolina with African-American adults. Our aim was to evaluate the effect of Heart Matters on dietary and physical activity behaviors, self-efficacy, and social support. We used a cluster randomized controlled trial to compare Heart Matters to a delayed intervention control group after 6 months. A total of 143 African-American participants were recruited and 108 completed 6-month follow-up assessments (75.5%). We used mixed regression models to evaluate changes in outcomes from baseline to 6-month follow-up. The intervention had a significant positive effect on self-reported scores of encouragement of healthy eating, resulting in an increase in social support from family of 6.11 units (95% CI [1.99, 10.22]) (p < .01). However, intervention participants also had an increase in discouragement of healthy eating compared to controls of 5.59 units (95% CI [1.46, 9.73]) among family (p < .01). There were no significant differences in changes in dietary behaviors. Intervention participants had increased odds (OR = 2.86, 95% CI [1.18, 6.93]) of increased frequency of vigorous activity for at least 20 min per week compared to control participants (p < .05). Individual and group lifestyle behavior counseling can have a role in promoting physical activity levels among rural African-American adults, but more research is needed to identify the best strategies to bolster effectiveness and influence dietary change. Trial Registration: Clinical Trials, NCT02707432. Registered 13 March 2016.

Proteasome inhibitor bortezomib is a novel therapeutic agent for focal radiation-induced osteoporosis.

Bone atrophy and its related fragility fractures are frequent, late side effects of radiotherapy in cancer survivors and have a detrimental impact on their quality of life. In another study, we showed that parathyroid hormone 1-34 and anti-sclerostin antibody attenuates radiation-induced bone damage by accelerating DNA repair in osteoblasts. DNA damage responses are partially regulated by the ubiquitin proteasome pathway. In the current study, we examined whether proteasome inhibitors have similar bone-protective effects against radiation damage. MG132 treatment greatly reduced radiation-induced apoptosis in cultured osteoblastic cells. This survival effect was owing to accelerated DNA repair as revealed by γH2AX foci and comet assays and to the up-regulation of Ku70 and DNA-dependent protein kinase, catalytic subunit, essential DNA repair proteins in the nonhomologous end-joining pathway. Administration of bortezomib (Bzb) reversed the loss of trabecular bone structure and strength in mice at 4 wk after focal radiation. Histomorphometry revealed that Bzb significantly increased the number of osteoblasts and activity in the irradiated area and suppressed the number and activity of osteoclasts, regardless of irradiation. Two weeks of Bzb treatment accelerated DNA repair in bone-lining osteoblasts and thus promoted their survival. Meanwhile, it also inhibited bone marrow adiposity. Taken together, we demonstrate a novel role of proteasome inhibitors in treating radiation-induced osteoporosis.-Chandra, A., Wang, L., Young, T., Zhong, L., Tseng, W.-J., Levine, M. A., Cengel, K., Liu, X. S., Zhang, Y., Pignolo, R. J., Qin, L. Proteasome inhibitor bortezomib is a novel therapeutic agent for focal radiation-induced osteoporosis.

Heart Matters: a study protocol for a community based randomized trial aimed at reducing cardiovascular risk in a rural, African American community.

BACKGROUND: African Americans living in the rural south have the highest prevalence of cardiovascular disease (CVD) risk in the United States. Given this geographic and racial disparity, intervention implementation needs to be evaluated for effectiveness and feasibility with African Americans in the rural south. METHODS: The trial developed out of a community-based participatory research partnership, Project GRACE, and community partners who are collaborators throughout the study. Heart Matters is a randomized stepped wedge trial that will assess the effectiveness of a 12-month behavioral change intervention adapted from PREMIER, an evidence-based treatment targeting multiple CVD risk factors. 140 participants will be recruited through 8 community- or faith-based organizations to participate in the intervention. Through matched pair randomization, organizations will be randomized to begin immediately after baseline data collection (Arm 1) or delayed 6 months (Arm 2). Data collection will occur at baseline, 6, 12, and 18 months. The primary outcome is change in body weight. In addition to assessing effectiveness, the study will also evaluate process and feasibility outcomes through quantitative and qualitative data collection. DISCUSSION: This study will contribute to CVD prevention research and likely have a positive impact on the rural, African American community where the trial occurs. Our study is unique in its use of community partnerships to develop, implement, and evaluate the intervention. We expect that this approach will enhance the feasibility of the trial, as well as future dissemination and sustainability of the intervention. TRIAL REGISTRATION: Clinical Trials, NCT02707432 . Registered 13 March 2016.

Cell cycle regulation of silent chromatin formation.

Identical genes in two different cells can stably exist in alternate transcriptional states despite the dynamic changes that will occur to chromatin at that locus throughout the cell cycle. In mammals, this is achieved through epigenetic processes that regulate key developmental transitions and ensure stable patterns of gene expression during growth and differentiation. The budding yeast Saccharomyces cerevisiae utilizes silencing to control the expression state of genes encoding key regulatory factors for determining cell-type, ribosomal RNA levels and proper telomere function. Here, we review the composition of silent chromatin in S. cerevisiae, how silent chromatin is influenced by chromatin assembly and histone modifications and highlight several observations that have contributed to our understanding of the interplay between silent chromatin formation and stability and the cell cycle. This article is part of a Special Issue entitled: Histone chaperones and Chromatin assembly.

Family Health Equity in Chronic Disease Prevention and Management.

Introduction/Purpose: Efforts to improve chronic disease outcomes among US adults highlight families, particularly support from families, as a key aspect of disease prevention and management. To date, however, an overwhelming focus on individual-level outcomes and unidirectional support (eg, from a family caregiver to an identified care recipient) belies the existence of co-occurring health concerns and interdependent care. There are increasing calls for more sophisticated and intensive family health interventions that better integrate family-level factors, processes, and outcomes to provide comprehensive family support services in health care and community-based settings. Methods: This commentary provides key considerations for advancing this work while centering family health equity and families themselves in health initiatives. Results: Several critical barriers are identified and discussed. For example, a narrow focus on family and inadequate measures of family-level disease burden make it challenging to understand how the disproportionate burden of chronic disease observed among individuals of lower socioeconomic status and certain racial and ethnic groups compounds and complicates family health experiences. In addition, limited attention to the interaction between individuals, families, and broader sociocultural factors that influence family resources and constraints, such as racism, hamper program design, implementation, and evaluation. Conclusion: To center families in efforts to reduce chronic disease disparities, it is necessary to move beyond superficial attention to the complexity of disease prevention and management within the family context. This commentary serves to enhance understanding of important drivers of family-level chronic disease outcomes, while providing important considerations for advancing research and practice.

Assessing the pre-implementation context for financial navigation in rural and non-rural oncology clinics.

Background: Financial navigation (FN) is an evidence-based intervention designed to address financial toxicity for cancer patients. FN's success depends on organizations' readiness to implement and other factors that may hinder or support implementation. Tailored implementation strategies can support practice change but must be matched to the implementation context. We assessed perceptions of readiness and perceived barriers and facilitators to successful implementation among staff at nine cancer care organizations (5 rural, 4 non-rural) recruited to participate in the scale-up of a FN intervention. To understand differences in the pre-implementation context and inform modifications to implementation strategies, we compared findings between rural and non-rural organizations. Methods: We conducted surveys (n = 78) and in-depth interviews (n = 73) with staff at each organization. We assessed perceptions of readiness using the Organizational Readiness for Implementing Change (ORIC) scale. In-depth interviews elicited perceived barriers and facilitators to implementing FN in each context. We used descriptive statistics to analyze ORIC results and deductive thematic analysis, employing a codebook guided by the Consolidated Framework for Implementation Research (CFIR), to synthesize themes in barriers and facilitators across sites, and by rurality. Results: Results from the ORIC scale indicated strong perceptions of organizational readiness across all sites. Staff from rural areas reported greater confidence in their ability to manage the politics of change (87% rural, 76% non-rural) and in their organization's ability to support staff adjusting to the change (96% rural, 75% non-rural). Staff at both rural and non-rural sites highlighted factors reflective of the Intervention Characteristics (relative advantage) and Implementation Climate (compatibility and tension for change) domains as facilitators. Although few barriers to implementation were reported, differences arose between rural and non-rural sites in these perceived barriers, with non-rural staff more often raising concerns about resistance to change and compatibility with existing work processes and rural staff more often raising concerns about competing time demands and limited resources. Conclusions: Staff across both rural and non-rural settings identified few, but different, barriers to implementing a novel FN intervention that they perceived as important and responsive to patients' needs. These findings can inform how strategies are tailored to support FN in diverse oncology practices.

Investigating Health Context Using a Spatial Data Analytical Tool: Development of a Geospatial Big Data Ecosystem.

BACKGROUND: Enabling the use of spatial context is vital to understanding today's digital health problems. Any given location is associated with many different contexts. The strategic transformation of population health, epidemiology, and eHealth studies requires vast amounts of integrated digital data. Needed is a novel analytical framework designed to leverage location to create new contextual knowledge. The Geospatial Analytical Research Knowledgebase (GeoARK), a web-based research resource has robust, locationally integrated, social, environmental, and infrastructural information to address today's complex questions, investigate context, and spatially enable health investigations. GeoARK is different from other Geographic Information System (GIS) resources in that it has taken the layered world of the GIS and flattened it into a big data table that ties all the data and information together using location and developing its context. OBJECTIVE: It is paramount to build a robust spatial data analytics framework that integrates social, environmental, and infrastructural knowledge to empower health researchers' use of geospatial context to timely answer population health issues. The goal is twofold in that it embodies an innovative technological approach and serves to ease the educational burden for health researchers to think spatially about their problems. METHODS: A unique analytical tool using location as the key was developed. It allows integration across source, geography, and time to create a geospatial big table with over 162 million individual locations (X-Y points that serve as rows) and 5549 attributes (represented as columns). The concept of context (adjacency, proximity, distance, etc) is quantified through geoanalytics and captured as new distance, density, or neighbor attributes within the system. Development of geospatial analytics permits contextual extraction and investigator-initiated eHealth and mobile health (mHealth) analysis across multiple attributes. RESULTS: We built a unique geospatial big data ecosystem called GeoARK. Analytics on this big table occur across resolution groups, sources, and geographies for extraction and analysis of information to gain new insights. Case studies, including telehealth assessment in North Carolina, national income inequality and health outcome disparity, and a Missouri COVID-19 risk assessment, demonstrate the capability to support robust and efficient geospatial understanding of a wide spectrum of population health questions. CONCLUSIONS: This research identified, compiled, transformed, standardized, and integrated multifaceted data required to better understand the context of health events within a large location-enabled database. The GeoARK system empowers health professionals to engage more complex research where the synergisms of health and geospatial information will be robustly studied beyond what could be accomplished today. No longer is the need to know how to perform geospatial processing an impediment to the health researcher, but rather the development of how to think spatially becomes the greater challenge.

Financial Assistance Processes and Mechanisms in Rural and Nonrural Oncology Care Settings.

PURPOSE: Patients with cancer are at heightened risk of experiencing financial hardship. Financial navigation (FN) is an evidence-based approach for identifying and addressing patient and caregiver financial needs. In preparation for the implementation of a multisite FN intervention, we describe existing processes (ie, events and actions) and mechanisms (ie, how events work together) connecting patients to financial assistance, comparing rural and nonrural practices. METHODS: We conducted in-depth, semistructured interviews with stakeholders (ie, administrators, providers, and staff) at each of the 10 oncology care sites across a single state (five rural and five nonrural practices). We developed process maps for each site and analyzed stakeholder perspectives using thematic analysis. After reporting findings back to stakeholders, we synthesized themes and process maps across rural and nonrural sites separately. RESULTS: Eighty-three stakeholders were interviewed. We identified six core elements of existing financial assistance processes across all sites: distress screening (including financial concerns), referrals, resource connection points, and pharmaceutical, insurance, and community/foundation resources. Processes differed by rurality; however, facilitators and barriers to identifying and addressing patient financial needs were consistent. Open communication between staff, providers, patients, and caregivers was a primary facilitator. Barriers included insufficient staff resources, challenges in routinely identifying needs, inadequate preparation of patients for anticipated medical costs, and limited tracking of resource availability and eligibility. CONCLUSION: This study identified a clear need for systematic implementation of oncology FN to equitably address patient and caregiver financial hardship. Results have informed our current efforts to implement a multisite FN intervention, which involves comprehensive financial toxicity screening and systematization of intake and referrals.

Everyday reasoning abilities in persons with Parkinson's disease.

Parkinson's disease (PD) patients develop progressive cognitive decline. The degree to which such decline impacts instrumental activities of daily living (IADL) among individuals in the early stages of PD without dementia is not well documented. The Everyday Cognitive Battery Reasoning subtest (ECB) was used to assess ability to solve everyday reasoning tasks for IADL among 19 non-demented older adults with PD in comparison to 20 older adults without PD. The two groups were similar in age, education, race and gender. Individuals with PD had significantly lower scores (M = 61.98, SD = 12.03) than the comparison group (M = 69.80, SD = 9.48). Individuals with PD, who do not have dementia, may be more likely to experience difficulties in IADL requiring reasoning including medication use, finances, and nutrition. Even more serious implications lie in the capacity to make treatment choices.

Trust in Community-Engaged Research Partnerships: A Methodological Overview of Designing a Multisite Clinical and Translational Science Awards (CTSA) Initiative.

Community-engaged research (CEnR) builds on the strengths of the Clinical and Translational Science Awards (CTSA) framework to address health in underserved and minority communities. There is a paucity of studies that identify the process from which trust develops in CEnR partnerships. This study responds to the need for empirical investigation of building and maintaining trust from a multistakeholder perspective. We conducted a multi-institutional pilot study using concept mapping with to better understand how trust, a critical outcome of CEnR partnerships, can act as "social capital." Concept mapping was used to collect data from the three stakeholder groups: community, health-care, and academic research partners across three CTSAs. Concept mapping is a mixed-methods approach that allows participants to brainstorm and identify factors that contribute to a concept and describe ways in which those factors relate to each other. This study offers important insights on developing an initial set of trust measures that can be used across CTSAs to understand differences and similarities in conceptualization of trust among key stakeholder groups, track changes in public trust in research, identify both positive and negative aspects of trust, identify characteristics that maintain trust, and inform the direction for future research.

Modulation of Gene Silencing by Cdc7p via H4 K16 Acetylation and Phosphorylation of Chromatin Assembly Factor CAF-1 in Saccharomyces cerevisiae.

CAF-1 is an evolutionarily conserved H3/H4 histone chaperone that plays a key role in replication-coupled chromatin assembly and is targeted to the replication fork via interactions with PCNA, which, if disrupted, leads to epigenetic defects. In Saccharomyces cerevisiae, when the silent mating-type locus HMR contains point mutations within the E silencer, Sir protein association and silencing is lost. However, mutation of CDC7, encoding an S-phase-specific kinase, or subunits of the H4 K16-specific acetyltransferase complex SAS-I, restore silencing to this crippled HMR, HMRae** Here, we observed that loss of Cac1p, the largest subunit of CAF-1, also restores silencing at HMRae**, and silencing in both cac1Δ and cdc7 mutants is suppressed by overexpression of SAS2 We demonstrate Cdc7p and Cac1p interact in vivo in S phase, but not in G1, consistent with observed cell cycle-dependent phosphorylation of Cac1p, and hypoacetylation of chromatin at H4 K16 in both cdc7 and cac1Δ mutants. Moreover, silencing at HMRae** is restored in cells expressing cac1p mutants lacking Cdc7p phosphorylation sites. We also discovered that cac1Δ and cdc7-90 synthetically interact negatively in the presence of DNA damage, but that Cdc7p phosphorylation sites on Cac1p are not required for responses to DNA damage. Combined, our results support a model in which Cdc7p regulates replication-coupled histone modification via a CAC1-dependent mechanism involving H4 K16ac deposition, and thereby silencing, while CAF-1-dependent replication- and repair-coupled chromatin assembly per se are functional in the absence of phosphorylation of Cdc7p consensus sites on CAF-1.

LRRK2 kinase activity regulates lysosomal glucocerebrosidase in neurons derived from Parkinson's disease patients.

Mutations in LRRK2 and GBA1 are common genetic risk factors for Parkinson's disease (PD) and major efforts are underway to develop new therapeutics that target LRRK2 or glucocerebrosidase (GCase). Here we describe a mechanistic and therapeutic convergence of LRRK2 and GCase in neurons derived from patients with PD. We find that GCase activity was reduced in dopaminergic (DA) neurons derived from PD patients with LRRK2 mutations. Inhibition of LRRK2 kinase activity results in increased GCase activity in DA neurons with either LRRK2 or GBA1 mutations. This increase is sufficient to partially rescue accumulation of oxidized dopamine and alpha-synuclein in PD patient neurons. We have identified the LRRK2 substrate Rab10 as a key mediator of LRRK2 regulation of GCase activity. Together, these results suggest an important role of mutant LRRK2 as a negative regulator of lysosomal GCase activity.

Perceptions of Rural African American Adults About the Role of Family in Understanding and Addressing Risk Factors for Cardiovascular Disease.

PURPOSE: African Americans (AAs) in rural south and southeast regions of the United States have among the highest prevalence of cardiovascular disease (CVD) in the country. The purpose of this qualitative, exploratory study is to understand family influences on CVD-related knowledge and health-related behaviors among rural AA adults. DESIGN: Qualitative descriptive study design using a community-based participatory research approach. SETTING: Two rural North Carolina counties. PARTICIPANTS: Eligible participants were AA adults (at least 21 years of age), who self-reported either CVD diagnosis or selected CVD risk factor(s) for themselves or for an adult family member (N = 37). METHOD: Directed content analysis of semistructured interviews by community and academic partners. RESULTS: Family health history and familial norms and preferences influenced participants' CVD-related knowledge, beliefs, and health-related behaviors. Participants reported their families were helpful for increasing motivation for and overcoming barriers to healthy behaviors, including hard-to-access community resources and physical challenges. Conversely, and to a lesser extent, participants also reported that family members hindered or had little influence (positive or negative) on their engagement in healthy behaviors. CONCLUSION: Family played an important role in helping individuals overcome personal and community-related challenges. Efforts to reduce CVD burden among rural AAs should seek to understand the family-related facilitators, barriers, and processes associated with CVD knowledge and risk-reduction behaviors.