Acceleration of benzo(a)pyrene-induced colon carcinogenesis by Western diet in a rat model of colon cancer.

Colorectal cancer (CRC) is the third leading cause of cancer-related mortalities in the USA and around 52,550 people were expected to die from this disease by December 2023. The objective of this study was to investigate the effect of diet type on benzo(a)pyrene [B(a)P]-induced colon cancer in an adult male rat model, the Polyposis In the Rat Colon (PIRC) kindred type. Groups of PIRC rats (n = 10) were fed with AIN-76A regular diet (RD) or Western diet (WD) and received 25, 50 and 100 µg B(a)P/kg body wt. via oral gavage for 60 days. Rats fed diets alone, but no B(a)P, served as controls. After exposure, rats were euthanized; colon and liver samples were analyzed for activation of drug metabolizing enzymes (DMEs) CYP1A1, CYP1B1, SULT and GST. Plasma and tissue samples were analyzed by reverse phase-HPLC for B(a)P metabolites. In addition to these studies, DNA isolated from colon and liver tissues was analyzed for B(a)P-induced DNA adducts by the 32P-postlabeling method using a thin-layer chromatography system. Western diet consumption resulted in a marked increase in DME expression and B(a)P metabolite concentrations in rats that were administered 100 µg/kg B(a)P + WD (p < 0.05) compared to other treatment groups. Our findings demonstrate that WD accelerates the development of colon tumors induced by B(a)P through enhanced biotransformation, and the products of this process (metabolites) were found to bind with DNA and form B(a)P-DNA adducts, which may have given rise to colon polyps characterized by gain in tumor number, sizes, and dysplasia.

Imprinting and Reproductive Health: A Toxicological Perspective.

This overview discusses the role of imprinting in the development of an organism, and how exposure to environmental chemicals during fetal development leads to the physiological and biochemical changes that can have adverse lifelong effects on the health of the offspring. There has been a recent upsurge in the use of chemical products in everyday life. These chemicals include industrial byproducts, pesticides, dietary supplements, and pharmaceutical products. They mimic the natural estrogens and bind to estradiol receptors. Consequently, they reduce the number of receptors available for ligand binding. This leads to a faulty signaling in the neuroendocrine system during the critical developmental process of 'imprinting'. Imprinting causes structural and organizational differentiation in male and female reproductive organs, sexual behavior, bone mineral density, and the metabolism of exogenous and endogenous chemical substances. Several studies conducted on animal models and epidemiological studies provide profound evidence that altered imprinting causes various developmental and reproductive abnormalities and other diseases in humans. Altered metabolism can be measured by various endpoints such as the profile of cytochrome P-450 enzymes (CYP450's), xenobiotic metabolite levels, and DNA adducts. The importance of imprinting in the potentiation or attenuation of toxic chemicals is discussed.

Seminar: Scalable Preprocessing Tools for Exposomic Data Analysis.

BACKGROUND: The exposome serves as a popular framework in which to study exposures from chemical and nonchemical stressors across the life course and the differing roles that these exposures can play in human health. As a result, data relevant to the exposome have been used as a resource in the quest to untangle complicated health trajectories and help connect the dots from exposures to adverse outcome pathways. OBJECTIVES: The primary aim of this methods seminar is to clarify and review preprocessing techniques critical for accurate and effective external exposomic data analysis. Scalability is emphasized through an application of highly innovative combinatorial techniques coupled with more traditional statistical strategies. The Public Health Exposome is used as an archetypical model. The novelty and innovation of this seminar's focus stem from its methodical, comprehensive treatment of preprocessing and its demonstration of the positive effects preprocessing can have on downstream analytics. DISCUSSION: State-of-the-art technologies are described for data harmonization and to mitigate noise, which can stymie downstream interpretation, and to select key exposomic features, without which analytics may lose focus. A main task is the reduction of multicollinearity, a particularly formidable problem that frequently arises from repeated measurements of similar events taken at various times and from multiple sources. Empirical results highlight the effectiveness of a carefully planned preprocessing workflow as demonstrated in the context of more highly concentrated variable lists, improved correlational distributions, and enhanced downstream analytics for latent relationship discovery. The nascent field of exposome science can be characterized by the need to analyze and interpret a complex confluence of highly inhomogeneous spatial and temporal data, which may present formidable challenges to even the most powerful analytical tools. A systematic approach to preprocessing can therefore provide an essential first step in the application of modern computer and data science methods. https://doi.org/10.1289/EHP12901.

Meta-analysis of primary care delivered buprenorphine treatment retention outcomes.

Background: Currently, the capacity to provide buprenorphine treatment (BT) is not sufficient to treat the growing number of people in the United States with opioid use disorder (OUD). We sought to examine participant retention in care rates of primary care delivered BT programs and to describe factors associated with retention/attrition for participants receiving BT in this setting.Objectives: A PRISMA-guided search of various databases was performed to identify the articles focusing on efficacy of BT treatment and OUD.Method: A systematic literature search identified 15 studies examining retention in care in the primary care setting between 2002 and 2020. Random effects meta-regression were used to identify retention rates across studies.Results: Retention rates decreased across time with a mean 0.52 rate at one year. Several factors were found to be related to retention, including: race, use of other drugs, receipt of counseling, and previous treatment with buprenorphine.Conclusions: While we only investigate BT through primary care, our findings indicate retention rates are equivalent to the rates reported in the specialty care literature. More work is needed to examine factors that may impact primary care delivered BT specifically and differentiate participants that may benefit from care delivered in specialty over primary care as well as the converse.

Affirming and Inclusive Care Training for Medical Students and Residents to Reduce Health Disparities Experienced by Sexual and Gender Minorities: A Systematic Review.

Purpose: Providing inclusive and comprehensive gender-affirming care is critical to reducing health disparities (gaps in care) experienced by sexual and gender minorities (SGM). Currently, little is known about how medical students and residents are being trained to address the health needs of SGM persons or of the most effective methods. Methods: We conducted a systematic review of the research literature from 2000 to 2020 on the effectiveness of teaching medical students and residents on knowledge, attitudes, and skills in addressing the health of SGM persons and the strength of the research sample, design, and methods used. Results: We identified a total of 36 articles that assessed the impact of medical student and resident education on knowledge, comfort, attitudes, confidence, and skills in working with SGM patients. All studies utilized quasi-experimental designs, and found efficacious results. No study examined the impact of training on patient outcomes. Conclusion: Future studies will need to be powered and designed to assess the impact of training on patient outcomes.

How to be a GREAT mentor.

Formal training in how to mentor is not generally available to students, postdoctoral fellows, or junior faculty. We provide here a framework to develop as a mentor, using the GREAT model. This includes giving opportunities and opening doors; reaching out to help students identify their strengths and reach their goals; encouraging them by serving as a positive example; advising each mentee as an individual; and training them for independent thinking. In this personal view, we expand on each of these steps to illustrate how to develop a personalized mentoring style of your own. By combining these approaches, you as a mentor can work with your mentees to develop an effective and productive mentoring relationship.NEW & NOTEWORTHY We provide here a framework to develop as a mentor, using the GREAT model. This includes giving opportunities and opening doors; reaching out to help students identify their strengths and reach their goals; encouraging them by serving as a positive example; advising each mentee as an individual; and training them for independent thinking.

The role of histological subtypes in the survival of patients diagnosed with cutaneous or mucosal melanoma in the United States of America.

BACKGROUND: Literature presents limited information on histological subtypes and their association with other factors influencing the survival of melanoma patients. To explore the risk of death due to melanoma associated with histological subtypes, this retrospective study used the Surveillance, Epidemiology, and End Results program (SEER) data from 1998 to 2019. METHODS: A total of 27,532 patients consisting of 15,527 males and 12,005 females. The Hypertabastic Accelerated Failure Time model was used to analyze the impact of histology on the survival of patients with cutaneous or mucosal melanoma. RESULTS: The median survival time (MST) for cutaneous patients was 149 months, whereas those diagnosed with mucosal melanoma was 34 months. Nodular melanoma had a hazard ratio of 3.40 [95% CI: (2.94, 3.94)] compared to lentigo maligna melanoma. Across all histological subtypes, females had a longer MST, when compared to males. The hazard ratio (HR) of distant to localized melanoma was 9.56 [95% CI: (7.58, 12.07)]. CONCLUSIONS: Knowledge of patients' histological subtypes and their hazard assessment would enable clinicians and healthcare providers to perform personalized treatment, resulting in a lower risk of complication and higher survivability of melanoma patients. Significant factors were stage of the disease, age, histology, sex, and income. Focus should be placed on high-risk populations with severe and aggressive histological subtypes. Programs that emphasize preventive measures such as awareness, education, and early screening could reduce risk.

An Analysis of COVID-19 Mortality During the Dominancy of Alpha, Delta, and Omicron in the USA.

BACKGROUND: The objective of the study was to measure the risk of death due to COVID-19 in relation to individuals' characteristics, and severity of their disease during the dominant periods of Alpha, Delta, and Omicron variants have influenced mortality rates. METHODS: This study was conducted using COVID-19 Centers for Disease Control and Prevention (CDC) Case Surveillance Public Data Taskforce for 57 states, and United States territories between January 1, 2020 and March 20, 2022. Multivariable binary Hyperbolastic regression of type I was used to analyzes the data. RESULTS: Seniors and ICU-admitted patients had the highest risk of death. For each additional percent increase in fully vaccinated individuals, the odds of death deceased by 1%. The odds of death prior to vaccine availability, compared to post vaccine availability, was 1.27. When comparing the time periods each variant was dominant, the odds of death was 3.45-fold higher during Delta compared to Alpha. All predictor variables had P-values ≤.001. CONCLUSION: There was a noticeable difference in the odds of death among subcategories of age, race/ethnicity, sex, PMCs, hospitalization, ICU, vaccine availability, variant, and percent of fully vaccinated individuals.

Transforming Medical Education to Provide Gender-Affirming Care for Transgender and Gender-Diverse Patients: A Policy Brief.

Transgender and gender-diverse (TGD) patients experience a greater burden of health disparities compared with their heterosexual/cisgender counterparts. Some of the poorer health outcomes observed in these populations are known to be associated with the prevalence of implicit bias, bullying, emotional distress, alcoholism, drug abuse, intimate partner violence, sexually transmitted infections (eg, human immunodeficiency virus and human papilloma virus), and cancer. The TGD populations face unique barriers to receiving both routine and gender-affirming health care (acquiring hormones and gender-affirming surgeries). Additional barriers to implementing affirming care training for TGD patients are lack of expertise among medical education faculty and preceptors both in undergraduate and in graduate medical education programs. Drawing on a systematic review of the literature, we propose a policy brief aimed at raising awareness about gender-affirming care among education planners and policy makers in government and advisory bodies.

Curricular Interventions in Medical Schools: Maximizing Community Engagement Through Communities of Practice.

This article explains the importance of a communities of practice (CoP) model for continually aligning medical education and clinical transformation with contemporary health issues. It describes the evolution and advantages of using CoP as a model for transforming medical education and clinical practice and applies the CoP methodology to addressing the changing needs of socially vulnerable populations (LGBTQ [lesbian, gay, bisexual, transgender, and queer/questioning], persons experiencing homelessness, and migrant farm workers). In conclusion, this article describes CoP-led activities, achievements, and value creation in medical education by the National Center for Medical Education Development and Research established at the Meharry Medical College.

Saliva as a diagnostic tool to measure polycyclic aromatic hydrocarbon exposure in dental patients exposed to intimate partner violence (IPV).

BACKGROUND: Social habits such as tobacco use, alcohol consumption, and chemically contaminated diet contribute to poor oral health. Intimate Partner Violence (IPV) is a global public health epidemic which can exacerbate the prevalence of health conditions affecting a victim's lifespan. This study investigates using saliva as a biomarker for detecting levels of benzo(a)pyrene [B(a)P]; a toxicant present in cigarette smoke and barbecued meat in a population of IPV + female patients. METHODS: A cross-sectional IRB-approved study utilized 63 female participants (37 African Americans [AA], and 26 non-African Americans [NAA]), who provided consent for the study. Participants submitted samples of saliva, as well as questionnaires about demographics, health history, and a well-validated (IPV) screen. RESULTS: The prevalence of IPV was greater in AA compared to NAA. While the concentrations of PAHs/B(a)P detected in saliva of IPV samples in NAA were generally within the range of B(a)P reported for saliva from elsewhere, the concentrations were high in some IPV positive samples. Among the B(a)P metabolites, the concentrations of B(a)P 7,8-diol, B(a)P 3,6- and 6,12-dione metabolites were greater than the other metabolite in both AA and non-AA groups who were positive. CONCLUSION: Our study supports the use of saliva as a potential "diagnostic rheostat" to identify toxicants that may exacerbate/precipitate systemic disease in female victims of IPV. In addition, our study is the first to report that IPV may precipitate the accumulation of B(a)P in oral cavity that can alter inflammatory cascades and increase risk of poor health outcomes in this population of patients.

The Effect of Naloxone Access Laws on Fatal Synthetic Opioid Overdose Fatality Rates.

BACKGROUND: Increases in fatal synthetic opioid overdoses over the past 8 years have left states scrambling for effective means to curtail these deaths. Many states have implemented policies and increased service capacity to address this rise. To better understand the effectiveness of policy level interventions we estimated the impact of the presence of naloxone access laws (NALs) on synthetic opioid fatalities at the state level. METHODS: A multivariable longitudinal linear mixed model with a random intercept was used to determine the relationship between the presence of NALs and synthetic opioid overdose death rates, while controlling for, Good Samaritan laws, opioid prescription rate, and capacity for medication for opioid use disorder (MOUD), utilizing a quadratic time trajectory. Data for the study was collected from the National Vital Statistics System using multiple cause-of-death mortality files linked to drug overdose deaths. RESULTS: The presence of an NAL had a significant (univariate P-value = .013; multivariable p-value = .010) negative relationship to fentanyl overdose death rates. Other significant controlling variables were quadratic time (univariate and multivariable P-value < .001), MOUD (univariate P-value < .001; multivariable P-value = .009), and Good Samaritan Law (univariate P-value = .033; multivariable P-value = .018). CONCLUSION: Naloxone standing orders are strongly related to fatal synthetic opioid overdose reduction. The effect of NALs, MOUD treatment capacity, and Good Samaritan laws all significantly influenced the synthetic opioid overdose death rate. The use of naloxone should be a central part of any state strategy to reduce overdose death rate.

The Exposome and Nutritional Pharmacology and Toxicology: A New Application for Metabolomics.

The exposome refers to all of the internal and external life-long exposures that an individual experiences. These exposures, either acute or chronic, are associated with changes in metabolism that will positively or negatively influence the health and well-being of individuals. Nutrients and other dietary compounds modulate similar biochemical processes and have the potential in some cases to counteract the negative effects of exposures or enhance their beneficial effects. We present herein the concept of Nutritional Pharmacology/Toxicology which uses high-information metabolomics workflows to identify metabolic targets associated with exposures. Using this information, nutritional interventions can be designed toward those targets to mitigate adverse effects or enhance positive effects. We also discuss the potential for this approach in precision nutrition where nutrients/diet can be used to target gene-environment interactions and other subpopulation characteristics. Deriving these "nutrient cocktails" presents an opportunity to modify the effects of exposures for more beneficial outcomes in public health.

Big Data to Knowledge Analytics Reveals the Zika Virus Epidemic as Only One of Multiple Factors Contributing to a Year-Over-Year 28-Fold Increase in Microcephaly Incidence.

During the 2015-2016 Zika Virus (ZIKV) epidemic in Brazil, the geographical distributions of ZIKV infection and microcephaly outbreaks did not align. This raised doubts about the virus as the single cause of the microcephaly outbreak and led to research hypotheses of alternative explanatory factors, such as environmental variables and factors, agrochemical use, or immunizations. We investigated context and the intermediate and structural determinants of health inequalities, as well as social environment factors, to determine their interaction with ZIKV-positive- and ZIKV-negative-related microcephaly. The results revealed the identification of 382 associations among 382 nonredundant variables of Zika surveillance, including multiple determinants of environmental public health factors and variables obtained from 5565 municipalities in Brazil. This study compared those factors and variables directly associated with microcephaly incidence positive to ZIKV and those associated with microcephaly incidence negative to ZIKV, respectively, and mapped them in case and control subnetworks. The subnetworks of factors and variables associated with low birth weight and birthweight where birth incidence served as an additional control were also mapped. Non-significant differences in factors and variables were observed, as were weights of associations between microcephaly incidence, both positive and negative to ZIKV, which revealed diagnostic inaccuracies that translated to the underestimation of the scope of the ZIKV outbreak. A detailed analysis of the patterns of association does not support a finding that vaccinations contributed to microcephaly, but it does raise concerns about the use of agrochemicals as a potential factor in the observed neurotoxicity arising from the presence of heavy metals in the environment and microcephaly not associated with ZIKV. Summary: A comparative network inferential analysis of the patterns of variables and factors associated with Zika virus infections in Brazil during 2015-2016 coinciding with a microcephaly epidemic identified multiple contributing determinants. This study advances our understanding of the cumulative interactive effects of exposures to chemical and non-chemical stressors in the built, natural, physical, and social environments on adverse pregnancy and health outcomes in vulnerable populations.

Sex Differences in Embryonic Gonad Transcriptomes and Benzo[a]pyrene Metabolite Levels After Transplacental Exposure.

Polycyclic aromatic hydrocarbons like benzo[a]pyrene (BaP) are generated during incomplete combustion of organic materials. Prior research has demonstrated that BaP is a prenatal ovarian toxicant and carcinogen. However, the metabolic pathways active in the embryo and its developing gonads and the mechanisms by which prenatal exposure to BaP predisposes to ovarian tumors later in life remain to be fully elucidated. To address these data gaps, we orally dosed pregnant female mice with BaP from embryonic day (E) 6.5 to E11.5 (0, 0.2, or 2 mg/kg/day) for metabolite measurement or E9.5 to E11.5 (0 or 3.33 mg/kg/day) for embryonic gonad RNA sequencing. Embryos were harvested at E13.5 for both experiments. The sum of BaP metabolite concentrations increased significantly with dose in the embryos and placentas, and concentrations were significantly higher in female than male embryos and in embryos than placentas. RNA sequencing revealed that enzymes involved in metabolic activation of BaP are expressed at moderate to high levels in embryonic gonads and that greater transcriptomic changes occurred in the ovaries in response to BaP than in the testes. We identified 490 differentially expressed genes (DEGs) with false discovery rate P-values < 0.05 when comparing BaP-exposed to control ovaries but no statistically significant DEGs between BaP-exposed and control testes. Genes related to monocyte/macrophage recruitment and activity, prolactin family genes, and several keratin genes were among the most upregulated genes in the BaP-exposed ovaries. Results show that developing ovaries are more sensitive than testes to prenatal BaP exposure, which may be related to higher concentrations of BaP metabolites in female embryos.

Pre-Exposure Prophylaxis Training among Medical Schools in the United States.

Pre-Exposure Prophylaxis (PrEP) has been shown to be an effective method of HIV prevention for men who have sex with-men (MSM) and -transgender women (MSTGWs), serodiscordant couples, and injection drug users; however fewer than 50 000 individuals currently take this regimen. Knowledge of PrEP is low among healthcare providers and much of this lack of knowledge stems from the lack or exposure to PrEP in medical school. We conducted a cross sectional survey of medical schools in the United States to assess the degree to which PrEP for HIV prevention is taught. The survey consisted Likert scale questions assessing how well the students were prepared to perform each skill associated with PrEP delivery, as well as how PrEP education was delivered to students. We contacted 141 medical schools and 71 responded to the survey (50.4%). PrEP education was only reported to be offered at 38% of schools, and only 15.4% reported specific training for Lesbian, Gay, Bisexual, and Transgender (LGBT) patients. The most common delivery methods of PrEP content were didactic sessions with 11 schools reporting this method followed by problem-based learning, direct patient contact, workshops, and small group discussions. Students were more prepared to provide PrEP to MSM compared to other high-risk patients. Few medical schools are preparing their students to prescribe PrEP upon graduation. Further, there is a need to increase the number of direct patient contacts or simulations for students to be better prepared.

Recommendations for Increasing Physician Provision of Pre-Exposure Prophylaxis: Implications for Medical Student Training.

There is growing evidence that pre-exposure prophylaxis (PrEP) prevents HIV acquisition. However, in the United States, approximately only 4% of people who could benefit from PrEP are currently receiving it, and it is estimated only 1 in 5 physicians has ever prescribed PrEP. We conducted a scoping review to gain an understanding of physician-identified barriers to PrEP provision. Four overarching barriers presented in the literature: Purview Paradox, Patient Financial Constraints, Risk Compensation, and Concern for ART Resistance. Considering the physician-identified barriers, we make recommendations for how physicians and students may work to increase PrEP knowledge and competence along each stage of the PrEP cascade. We recommend adopting HIV risk assessment as a standard of care, improving physician ability to identify PrEP candidates, improving physician interest and ability in encouraging PrEP uptake, and increasing utilization of continuous care management to ensure retention and adherence to PrEP.

Benzo(a)pyrene-induced cytotoxicity, cell proliferation, DNA damage, and altered gene expression profiles in HT-29 human colon cancer cells.

In the US alone, around 60,000 lives/year are lost to colon cancer. In order to study the mechanisms of colon carcinogenesis, in vitro model systems are required in addition to in vivo models. Towards this end, we have used the HT-29 colon cancer cells, cultured in Dulbecco's Modified Eagle Medium (DMEM), which were exposed to benzo(a)pyrene (BaP), a ubiquitous and prototypical environmental and dietary toxicant at 1, 10, 100 nM and 1, 5, 10, and 25 µM concentrations for 96 h. Post-BaP exposure, growth, cytotoxicity, apoptosis, and cell cycle changes were determined. The BaP metabolite concentrations in colon cells were identified and measured. Furthermore, the BaP biotransformation enzymes were studied at the protein and mRNA levels. The BaP exposure-induced damage to DNA was assessed by measuring the oxidative damage to DNA and the concentrations of BaP-DNA adducts. To determine the whole repertoire of genes that are up- or downregulated by BaP exposure, mRNA transcriptome analysis was conducted. There was a BaP exposure concentration (dose)-dependent decrease in cell growth, cytotoxicity, and modulation of the cell cycle in the treatment groups compared to untreated or dimethylsulfoxide (DMSO: vehicle for BaP)-treated categories. The phase I biotransformation enzymes, CYP1A1 and 1B1, showed BaP concentration-dependent expression. On the other hand, phase II enzymes did not exhibit any marked variation. Consistent with the expression of phase I enzymes, elevated concentrations of BaP metabolites were generated, contributing to the formation of DNA lesions and stable DNA adducts, which were also BaP concentration-dependent. In summary, our studies established that biotransformation of BaP contributes to cytotoxicity, proliferation of tumor cells, and alteration of gene expression by BaP. • Benzo(a)pyrene (BaP) is an environmental and dietary toxicant. • BaP causes cytotoxicity in cultured HT-29 colon cancer cells. • mRNA transcriptome analyses revealed that BaP impacts cell growth, cell cycle, biotransformation, and DNA damage.

Use of an Exposome Approach to Understand the Effects of Exposures From the Natural, Built, and Social Environments on Cardio-Vascular Disease Onset, Progression, and Outcomes.

Obesity, diabetes, and hypertension have increased by epidemic proportions in recent years among African Americans in comparison to Whites resulting in significant adverse cardiovascular disease (CVD) disparities. Today, African Americans are 30% more likely to die of heart disease than Whites and twice as likely to have a stroke. The causes of these disparities are not yet well-understood. Improved methods for identifying underlying risk factors is a critical first step toward reducing Black:White CVD disparities. This article will focus on environmental exposures in the external environment and how they can lead to changes at the cellular, molecular, and organ level to increase the personal risk for CVD and lead to population level CVD racial disparities. The external environment is defined in three broad domains: natural (air, water, land), built (places you live, work, and play) and social (social, demographic, economic, and political). We will describe how environmental exposures in the natural, built, and social environments "get under the skin" to affect gene expression though epigenetic, pan-omics, and related mechanisms that lead to increased risk for adverse CVD health outcomes and population level disparities. We also will examine the important role of metabolomics, proteomics, transcriptomics, genomics, and epigenomics in understanding how exposures in the natural, built, and social environments lead to CVD disparities with implications for clinical, public health, and policy interventions. In this review, we apply an exposome approach to Black:White CVD racial disparities. The exposome is a measure of all the exposures of an individual across the life course and the relationship of those exposures to health effects. The exposome represents the totality of exogenous (external) and endogenous (internal) exposures from conception onwards, simultaneously distinguishing, characterizing, and quantifying etiologic, mediating, moderating, and co-occurring risk and protective factors and their relationship to disease. Specifically, it assesses the biological mechanisms and underlying pathways through which chemical and non-chemical environmental exposures are associated with CVD onset, progression and outcomes. The exposome is a promising approach for understanding the complex relationships among environment, behavior, biology, genetics, and disease phenotypes that underlie population level, Black: White CVD disparities.