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.

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.

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.

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.

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.

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.

Alteration of benzo(a)pyrene biotransformation by resveratrol in ApcMin/+ mouse model of colon carcinogenesis.

Epidemiological surveys have revealed that environmental and dietary factors contribute to most of the human cancers. Our earlier studies have shown that resveratrol (RVT), a phytochemical reduced the tumor number, size and incidence of dysplasias induced by benzo(a)pyrene (BaP), an environmental toxicant in the ApcMin/+ mouse model of colon cancer. In this study we investigated to ascertain whether the preventive effects of RVT on BaP-induced colon carcinogenesis is a result of altered BaP biotransformation by RVT. For the first group of mice, 100 µg BaP/kg bw was administered in peanut oil via oral gavage over a 60 day period. For the second group, 45 µg RVT/kg bw was co-administered with BaP. For the third group, RVT was administered for 1 week prior to BaP exposure. Blood, colon and liver were collected from control and BaP/RVT-treated mice at 60 days post-BaP & RVT exposure. We have assayed activities and expression (protein & mRNA) of drug metabolizing enzymes such as cytochrome P4501A1 (CYP1A1), CYP1B1, and glutathione-S-transferase (GST) in colon and liver samples from the treatment groups mentioned above. An increased expression of CYP1A1 in liver and colon and of CYP1B1 in liver of BaP-treated mice was seen, while RVT inhibited the extent of biotransformation mediated by these enzymes in the respective tissue samples. In the case of GST, an increased expression in colon of BaP alone-treated mice was noted when RVT was administered prior to BaP or simultaneously with BaP. However, there is no change in liver GST expression between BaP and RVT treatment groups. The concentrations of BaP aqueous (phase II) metabolites were found to be greater than the organic (phase I) metabolites, suggesting that RVT slows down the phase I metabolism (metabolic activation) of BaP, while enhancing phase II metabolism (detoxification). Additionally, the BaP-DNA adduct concentrations measured in colon and liver of BaP + RVT-treated mice were low relative to their BaP counterparts. Taken together, our findings strongly suggest that RVT alleviates BaP-induced colon carcinogenesis by impairing biotransformation pathways and DNA adduct formation, and therefore holds promise as a chemopreventive agent.

Training to reduce LGBTQ-related bias among medical, nursing, and dental students and providers: a systematic review.

BACKGROUND: Lesbian, gay, bisexual, transgender and questioning (LGBTQ) individuals experience higher rates of health disparities. These disparities may be driven, in part, by biases of medical providers encountered in health care settings. Little is known about how medical, nursing, or dental students are trained to identify and reduce the effects of their own biases toward LGBTQ individuals. Therefore, a systematic review was conducted to determine the effectiveness of programs to reduce health care student or provider bias towards these LGBTQ patients. METHODS: The authors performed searches of online databases (MEDLINE/PubMed, PsycINFO, Web of Science, Scopus, Ingenta, Science Direct, and Google Scholar) for original articles, published in English, between March 2005 and February 2017, describing intervention studies focused on reducing health care student or provider bias towards LGBTQ individuals. Data extracted included sample characteristics (i.e., medical, nursing, or dental students or providers), study design (i.e., pre-post intervention tests, qualitative), program format, program target (i.e., knowledge, comfort level, attitudes, implicit bias), and relevant outcomes. Study quality was assessed using a five-point scale. RESULTS: The search identified 639 abstracts addressing bias among medical, nursing, and dental students or providers; from these abstracts, 60 articles were identified as medical education programs to reduce bias; of these articles, 13 described programs to reduce bias towards LGBTQ patients. Bias-focused educational interventions were effective at increasing knowledge of LGBTQ health care issues. Experiential learning interventions were effective at increasing comfort levels working with LGBTQ patients. Intergroup contact was effective at promoting more tolerant attitudes toward LGBTQ patients. Despite promising support for bias education in increasing knowledge and comfort levels among medical, nursing, and dental students or providers towards LGBTQ persons, this systematic review did not identify any interventions that assessed changes in implicit bias among students or providers. CONCLUSIONS: Strategies for assessing and mitigating implicit bias towards LGBTQ patients are discussed and recommendations for medical, nursing, and dental school curricula are presented.

Validation of research trajectory 1 of an Exposome framework: Exposure to benzo(a)pyrene confers enhanced susceptibility to bacterial infection.

The exposome provides a framework for understanding elucidation of an uncharacterized molecular mechanism conferring enhanced susceptibility of macrophage membranes to bacterial infection after exposure to the environmental contaminant benzo(a)pyrene, [B(a)P]. The fundamental requirement in activation of macrophage effector functions is the binding of immunoglobulins to Fc receptors. FcγRIIa (CD32a), a member of the Fc family of immunoreceptors with low affinity for immunoglobulin G, has been reported to bind preferentially to IgG within lipid rafts. Previous research suggested that exposure to B(a)P suppressed macrophage effector functions but the molecular mechanisms remain elusive. The goal of this study was to elucidate the mechanism(s) of B(a)P-exposure induced suppression of macrophage function by examining the resultant effects of exposure-induced insult on CD32-lipid raft interactions in the regulation of IgG binding to CD32. The results demonstrate that exposure of macrophages to B(a)P alters lipid raft integrity by decreasing membrane cholesterol 25% while increasing CD32 into non-lipid raft fractions. This robust diminution in membrane cholesterol and 30% exclusion of CD32 from lipid rafts causes a significant reduction in CD32-mediated IgG binding to suppress essential macrophage effector functions. Such exposures across the lifespan would have the potential to induce immunosuppressive endophenotypes in vulnerable populations.

Altered expression of histone deacetylases, inflammatory cytokines and contractile-associated factors in uterine myometrium of Long Evans rats gestationally exposed to benzo[a]pyrene.

Etiology of preterm birth (PTB) is multifactorial; therefore, decreasing the incidence of PTB is a major challenge in the field of obstetrics. Epidemiological studies have reported an association between toxicants and PTB. However, there are no studies on the role of benzo[a]pyrene (BaP), an environmental toxicant, in the incidence of PTB. We first assessed the effects of BaP (150 and 300 µg kg(-1) body weight) dosed via gavage from day 14 to 17 of pregnancy on gestation length in Long Evans rats. We further assessed the histopathology of the uterus, expression of inflammatory cytokines, contractile-associated factors, histone deacetylases (HDACs) and NFқB-p65 in myometrium collected on day 22 postpartum versus vehicle-treated controls. In our study, rats exposed to BaP delivered prematurely (P < 0.05) compared to control. Hematoxylin and eosin staining of uterus showed squamous metaplasia, glandular and stromal hyperplasia in BaP-exposed rats versus control. The concentrations of BaP metabolites measured by high-pressure liquid chromatography were higher in uterine myometrium of BaP-exposed rats while they were undetectable in controls. Quantitative real-time polymerase chain reaction showed significant increases in mRNA expression of interleukin-1ß and -8, tumor necrosis factor-α, connexin 43, cyclo-oxygenase-2 and prostaglandin F2α receptor as compared to controls (P < 0.05). Western blot analysis revealed that BaP exposure caused decreases in class I HDACs 1 and 3 and increases in class II HDAC 5, cyclo-oxygenase-2 and nuclear translocation of NFκB-p65 relative to controls. Our results suggest that gestational exposure to BaP increases incidence of PTB through epigenetic changes that causes increases in the expression of contractile-associated factors through the NFκB pathway. Copyright © 2015 John Wiley & Sons, Ltd.

Metabolism of benzo(a)pyrene by subcellular fractions of gastrointestinal (GI) tract and liver in Apc(Min) mouse model of colon cancer.

Given the fact that increased dietary intake of polycyclic aromatic hydrocarbons (PAHs; a family of environmental toxicants) leads to the formation and development of colon tumors, the ability of the gastrointestinal tract to process these compounds is important from the viewpoint of toxicity/carcinogenesis. Benzo(a)pyrene (BaP), a prototypical PAH compound is released into the environment from automobile exhausts, cigarette smoke, and industrial emissions. Additionally, considerable intake of BaP is expected in people who consume barbecued foods and a diet rich in saturated fat. In exposed animals, BaP becomes activated to potent metabolites that interfere with target organ function and as a consequence cause toxicity and cancer. Therefore, knowledge of BaP metabolism in the digestive system will be of importance in the management of cancers of the digestive tract. The objective of our study was to study the metabolism of BaP by subcellular fractions (nuclear, cytosolic, mitochondrial, and microsomal) of the gastrointestinal tract and liver. Subcellular fractions were isolated by differential centrifugation from the stomach, jejunum, colon, and liver tissues of Apc(Min) mice that received a subchronic dose of 25 µg/kg BaP. The fractions were incubated with 1 and 3 µM BaP. Subsequent to incubation, samples were extracted with ethyl acetate and analyzed for BaP metabolites by reverse-phase HPLC equipped with fluorescence detection. Among the different fractions tested, microsomal BaP metabolism was higher than the rest of the fractions in all the samples analyzed. Additionally, a BaP exposure concentration-dependent effect on metabolite levels generated by the subcellular fractions was recorded. The BaP metabolites identified were the following: BaP-9,10-diol; BaP-4,5-diol; BaP-7,8-diol; 9(OH) BaP; 3(OH) BaP; BaP-3,6-dione; and BaP-6,12-dione. While the diol group of metabolites was frequently detected, among diones, the 3,6 and 6,12-dione metabolites were infrequently detected. Among the diol metabolites, the preponderance of BaP-7,8-dihydrodiol is interesting, since this metabolite is a precursor to the DNA-reactive BaP-7,8-dihydrodiol epoxide (BPDE) that has been linked to BaP-induced cancer.

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.

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 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.

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 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.

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.

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.

Benzo[a]pyrene potentiates the pathogenesis of abdominal aortic aneurysms in apolipoprotein E knockout mice.

The objective of this study was to determine the effect of benzo[a]pyrene (BaP), an abundant environmental polycyclic aromatic hydrocarbon compound, on the pathogenesis of abdominal aortic aneurysms (AAA). Earlier studies have shown that BaP promotes vasculopathy, including atherosclerosis, a predisposing factor for AAA development. In two experimental arms, 203 apolipoprotein E knockout (ApoE-/-) mice were evaluated in 4 groups: BaP, angiotensin II (AngII), BaP+AngII and control. Mice in the first arm were exposed to 5mg/kg/week of BaP for 42 days, and in the second arm to 0.71mg/kg daily for 60 days. In arm one, AAA incidence was higher in the BaP+AngII (14/28) versus AngII (8/27) group (p < 0.05), rupture (n=3) was observed only in BaP+AngII treated mice (p < 0.05). In the second arm, AAA incidence did not differ between AngII (17/30) and BaP+AngII (16/29) groups. However, intact AAA diameter was larger in the BaP+AngII (2.3 ± 0.1mm) versus AngII (1.9 ± 0.1mm) group (p < 0.05), but AAA rupture did not differ (p=NS). In both experimental arms, BaP+AngII mice showed increased expression of tumor necrosis factor alpha (TNF-α), cyclophilin A (Cyp A), and matrix metalloproteinase-9 (MMP9) (p < 0.05). No AAA occurred in control or BaP groups. These findings suggest the role of BaP exposure in potentiating AAA pathogenesis, which may have potential public health significance.