Parallel RNA and DNA analysis after deep sequencing (PRDD-seq) reveals cell type-specific lineage patterns in human brain.

Elucidating the lineage relationships among different cell types is key to understanding human brain development. Here we developed parallel RNA and DNA analysis after deep sequencing (PRDD-seq), which combines RNA analysis of neuronal cell types with analysis of nested spontaneous DNA somatic mutations as cell lineage markers, identified from joint analysis of single-cell and bulk DNA sequencing by single-cell MosaicHunter (scMH). PRDD-seq enables simultaneous reconstruction of neuronal cell type, cell lineage, and sequential neuronal formation ("birthdate") in postmortem human cerebral cortex. Analysis of two human brains showed remarkable quantitative details that relate mutation mosaic frequency to clonal patterns, confirming an early divergence of precursors for excitatory and inhibitory neurons, and an "inside-out" layer formation of excitatory neurons as seen in other species. In addition our analysis allows an estimate of excitatory neuron-restricted precursors (about 10) that generate the excitatory neurons within a cortical column. Inhibitory neurons showed complex, subtype-specific patterns of neurogenesis, including some patterns of development conserved relative to mouse, but also some aspects of primate cortical interneuron development not seen in mouse. PRDD-seq can be broadly applied to characterize cell identity and lineage from diverse archival samples with single-cell resolution and in potentially any developmental or disease condition.

Association between SARS-CoV-2 infection during pregnancy and postpartum depressive and anxiety symptoms: finding from the International Registry of Coronavirus Exposure in Pregnancy (IRCEP) study.

While there has been concern over the perinatal mental health implications of the COVID-19 outbreak, evidence on the risk of postpartum depression and anxiety following SARS-CoV-2 infection is limited. We studied this question using the International Registry of Coronavirus Exposure in Pregnancy, which included both a prospective and retrospective cohort. Study participants were required to have been tested for SARS-CoV-2 between the date of last menstrual period and delivery. The exposure of interest was SARS-CoV-2 infection during pregnancy, as well as COVID-19 severity (severe, moderate, mild, and asymptomatic). The outcome was postpartum depression and anxiety symptoms, assessed by the 4-item Patient Health Questionnaire. The final analytic cohort consisted of 3819 participants (COVID-19 positive: 771; COVID-19 negative: 3048). After adjusting for confounding by socio-demographics, prior obstetric and maternal health comorbidities, mothers with severe COVID-19 had an increased risk of depressive (aRR: 1.72; 95%CI: 1.18-2.52) and anxiety (aRR: 1.40; 0.98-2.00) symptoms. The strength of the association was attenuated for women with moderate COVID-19 (aRR = 1.12; 0.86-1.44 for depressive symptoms; aRR = 1.18; 0.96-1.44 for anxiety symptoms). No increased risk was observed for mild or asymptomatic illness. The findings can inform targeted interventions to minimize the risk of adverse COVID-19-related mental health outcomes for pregnant women.

The American Heart Association 2030 Impact Goal: A Presidential Advisory From the American Heart Association.

Each decade, the American Heart Association (AHA) develops an Impact Goal to guide its overall strategic direction and investments in its research, quality improvement, advocacy, and public health programs. Guided by the AHA's new Mission Statement, to be a relentless force for a world of longer, healthier lives, the 2030 Impact Goal is anchored in an understanding that to achieve cardiovascular health for all, the AHA must include a broader vision of health and well-being and emphasize health equity. In the next decade, by 2030, the AHA will strive to equitably increase healthy life expectancy beyond current projections, with global and local collaborators, from 66 years of age to at least 68 years of age across the United States and from 64 years of age to at least 67 years of age worldwide. The AHA commits to developing additional targets for equity and well-being to accompany this overarching Impact Goal. To attain the 2030 Impact Goal, we recommend a thoughtful evaluation of interventions available to the public, patients, providers, healthcare delivery systems, communities, policy makers, and legislators. This presidential advisory summarizes the task force's main considerations in determining the 2030 Impact Goal and the metrics to monitor progress. It describes the aspiration that these goals will be achieved by working with a diverse community of volunteers, patients, scientists, healthcare professionals, and partner organizations needed to ensure success.

Feelings of Culpability: Just Following Orders Versus Making the Decision Oneself.

In five experiments (N = 1,490), participants were asked to imagine themselves as programmers of self-driving cars who had to decide how to program the car to respond in a potential accident: spare the driver or spare pedestrians. Alternatively, participants imagined that they were a mayor grappling with difficult moral dilemmas concerning COVID-19. Either they, themselves, had to decide how to program the car or which COVID-19 policy to implement (high-agency condition) or they were told by their superior how to act (low-agency condition). After learning that a tragic outcome occurred because of their action, participants reported their felt culpability. Although we expected people to feel less culpable about the outcome if they acted in accordance with their superior's injunction than if they made the decision themselves, participants actually felt more culpable when they followed their superior's order. Some possible reasons for this counterintuitive finding are discussed.

Clinical-Community Partnerships to Identify Patients With Food Insecurity and Address Food Needs.

INTRODUCTION: More than 42 million people in the United States are food insecure. Although some health care entities are addressing food insecurity among patients because of associations with disease risk and management, little is known about the components of these initiatives. METHODS: The Systematic Screening and Assessment Method was used to conduct a landscape assessment of US health care entity-based programs that screen patients for food insecurity and connect them with food resources. A network of food insecurity researchers, experts, and practitioners identified 57 programs, 22 of which met the inclusion criteria of being health care entities that 1) screen patients for food insecurity, 2) link patients to food resources, and 3) target patients including adults aged 50 years or older (a focus of this assessment). Data on key features of each program were abstracted from documentation and telephone interviews. RESULTS: Most programs (n = 13) focus on patients with chronic disease, and most (n = 12) partner with food banks. Common interventions include referrals to or a list of food resources (n = 19), case managers who navigate patients to resources (n = 15), assistance with federal benefit applications (n = 14), patient education and skill building (n = 13), and distribution of fruit and vegetable vouchers redeemable at farmers markets (n = 8). Most programs (n = 14) routinely screen all patients. CONCLUSION: The programs reviewed use various strategies to screen patients, including older adults, for food insecurity and to connect them to food resources. Research is needed on program effectiveness in improving patient outcomes. Such evidence can be used to inform the investments of potential stakeholders, including health care entities, community organizations, and insurers.

State-Level Farmers Market Activities: A Review of CDC-Funded State Public Health Actions That Support Farmers Markets.

CONTEXT: Introducing farmers markets to underserved areas, or supporting existing farmers markets, can increase access and availability of fruits and vegetables and encourage healthy eating. Since 2003, the Centers for Disease Control and Prevention (CDC)'s Division of Nutrition, Physical Activity, and Obesity (DNPAO) has provided guidance and funding to state health departments (SHDs) to support the implementation of interventions, including activities around farmers markets, to address healthy eating, and improve the access to and availability of fruits and vegetables at state and community levels. OBJECTIVE: For this project, we identified state-level farmers market activities completed with CDC's DNPAO funding from 2003 to 2013. State-level was defined as actions taken by the state health department that influence or support farmers market work across the state. DESIGN AND PARTICIPANTS: We completed an analysis of SHD farmers market activities of 3 DNPAO cooperative agreements from 2003 to 2013: State Nutrition and Physical Activity Programs to Prevent Obesity and Other Chronic Diseases; Nutrition, Physical Activity and Obesity Program; and Communities Putting Prevention to Work. To identify state farmers market activities, data sources for each cooperative agreement were searched using the key words "farm," "market," "produce market," and "produce stand." State data with at least one state-level farmers market action present were then coded for the presence of itemized activities. RESULTS: Across all cooperative agreements, the most common activities identified through analysis included the following: working on existing markets and nutrition assistance benefit programs, supporting community action, and providing training and technical assistance. Common partners were nutrition assistance benefit program offices and state or regional Department of Agriculture or agricultural extension offices. IMPLICATIONS FOR POLICY & PRACTICE: Common farmers market practices and evidence-based activities, such as nutrition assistance benefits programs and land-use policies, can be adopted as methods for farmers market policy and practice work. CONCLUSION: The activities identified in this study can inform future planning at the state and federal levels on environment, policy, and systems approaches that improve the food environment through farmers markets.

Common ways Americans are incorporating fruits and vegetables into their diet: intake patterns by meal, source and form, National Health and Nutrition Examination Survey 2007-2010.

OBJECTIVE: We explored how Americans aged ≥2 years who consumed the recommended amount of fruits and vegetables on a given day incorporated fruits and vegetables into their diet compared with those who did not consume recommended amounts. DESIGN: We used 1 d of dietary recall data from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 to examine cross-sectional differences in mean intakes of fruits and vegetables in cup-equivalents by meal, source and form between the two groups. SETTING: USA. SUBJECTS: NHANES 2007-2010 participants aged ≥2 years (n 17 571) with 1 d of reliable 24 h recall data. RESULTS: On a given day, the proportions of fruits and vegetables consumed at different meals were similar between those who consumed recommended amounts and those who did not. Among adults, 59-64 % of their intake of fruits was consumed at breakfast or as a snack and almost 90 % came from retail outlets regardless of whether they consumed the recommended amount or not. Adults who consumed the recommended amount of fruits ate more fruits in raw form and with no additions than those who did not. Among children and adults, 52-57 % of vegetables were consumed at dinner by both groups. Retail outlets were the main source of vegetables consumed (60-68 %). CONCLUSIONS: Our findings indicate that habits of when, where and how consumers eat fruits and vegetables might not need to change but increasing the amount consumed would help those not currently meeting the recommendation.

UV irradiation accelerates amyloid precursor protein (APP) processing and disrupts APP axonal transport.

Overexpression and/or abnormal cleavage of amyloid precursor protein (APP) are linked to Alzheimer's disease (AD) development and progression. However, the molecular mechanisms regulating cellular levels of APP or its processing, and the physiological and pathological consequences of altered processing are not well understood. Here, using mouse and human cells, we found that neuronal damage induced by UV irradiation leads to specific APP, APLP1, and APLP2 decline by accelerating their secretase-dependent processing. Pharmacological inhibition of endosomal/lysosomal activity partially protects UV-induced APP processing implying contribution of the endosomal and/or lysosomal compartments in this process. We found that a biological consequence of UV-induced γ-secretase processing of APP is impairment of APP axonal transport. To probe the functional consequences of impaired APP axonal transport, we isolated and analyzed presumptive APP-containing axonal transport vesicles from mouse cortical synaptosomes using electron microscopy, biochemical, and mass spectrometry analyses. We identified a population of morphologically heterogeneous organelles that contains APP, the secretase machinery, molecular motors, and previously proposed and new residents of APP vesicles. These possible cargoes are enriched in proteins whose dysfunction could contribute to neuronal malfunction and diseases of the nervous system including AD. Together, these results suggest that damage-induced APP processing might impair APP axonal transport, which could result in failure of synaptic maintenance and neuronal dysfunction.

Using Behavioral Risk Factor Surveillance System Data to Estimate the Percentage of the Population Meeting US Department of Agriculture Food Patterns Fruit and Vegetable Intake Recommendations.

Most Americans do not eat enough fruits and vegetables with significant variation by state. State-level self-reported frequency of fruit and vegetable consumption is available from the Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System (BRFSS). However, BRFSS cannot be used to directly compare states' progress toward national goals because of incongruence in units used to measure intake and because distributions from frequency data are not reflective of usual intake. To help states track progress, we developed scoring algorithms from external data and applied them to BRFSS 2011 data to estimate the percentage of each state's adult population meeting US Department of Agriculture Food Patterns fruit and vegetable intake recommendations. We used 24-hour dietary recall data from the National Health and Nutrition Examination Survey, 2007-2010, to fit sex- and age-specific models that estimate probabilities of meeting recommendations as functions of reported consumption frequency, race/ethnicity, and poverty-income ratio adjusting for intraindividual variation. Regression parameters derived from these models were applied to BRFSS to estimate the percentage meeting recommendations. We estimate that 7%-18% of state populations met fruit recommendations and 5%-12% met vegetable recommendations. Our method provides a new tool for states to track progress toward meeting dietary recommendations.

Networking to Improve Nutrition Policy Research.

Effective nutrition and obesity policies that improve the food environments in which Americans live, work, and play can have positive effects on the quality of human diets. The Centers for Disease Control and Prevention's (CDC's) Nutrition and Obesity Policy Research and Evaluation Network (NOPREN) conducts transdisciplinary practice-based policy research and evaluation to foster understanding of the effectiveness of nutrition policies. The articles in this special collection bring to light a set of policies that are being used across the United States. They add to the larger picture of policies that can work together over time to improve diet and health.

Presenilins regulate neurotrypsin gene expression and neurotrypsin-dependent agrin cleavage via cyclic AMP response element-binding protein (CREB) modulation.

Presenilins, the catalytic components of the γ-secretase complex, are upstream regulators of multiple cellular pathways via regulation of gene transcription. However, the underlying mechanisms and the genes regulated by these pathways are poorly characterized. In this study, we identify Tequila and its mammalian ortholog Prss12 as genes negatively regulated by presenilins in Drosophila larval brains and mouse embryonic fibroblasts, respectively. Prss12 encodes the serine protease neurotrypsin, which cleaves the heparan sulfate proteoglycan agrin. Altered neurotrypsin activity causes serious synaptic and cognitive defects; despite this, the molecular processes regulating neurotrypsin expression and activity are poorly understood. Using γ-secretase drug inhibitors and presenilin mutants in mouse embryonic fibroblasts, we found that a mature γ-secretase complex was required to repress neurotrypsin expression and agrin cleavage. We also determined that PSEN1 endoproteolysis or processing of well known γ-secretase substrates was not essential for this process. At the transcriptional level, PSEN1/2 removal induced cyclic AMP response element-binding protein (CREB)/CREB-binding protein binding, accumulation of activating histone marks at the neurotrypsin promoter, and neurotrypsin transcriptional and functional up-regulation that was dependent on GSK3 activity. Upon PSEN1/2 reintroduction, this active epigenetic state was replaced by a methyl CpG-binding protein 2 (MeCP2)-containing repressive state and reduced neurotrypsin expression. Genome-wide analysis revealed hundreds of other mouse promoters in which CREB binding is similarly modulated by the presence/absence of presenilins. Our study thus identifies Tequila and neurotrypsin as new genes repressed by presenilins and reveals a novel mechanism used by presenilins to modulate CREB signaling based on controlling CREB recruitment.

Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure.

Exposure to cyanide causes a spectrum of cardiac, neurological, and metabolic dysfunctions that can be fatal. Improved cyanide antidotes are needed, but the ideal biological pathways to target are not known. To understand better the metabolic effects of cyanide and to discover novel cyanide antidotes, we developed a zebrafish model of cyanide exposure and scaled it for high-throughput chemical screening. In a screen of 3120 small molecules, we discovered 4 novel antidotes that block cyanide toxicity. The most potent antidote was riboflavin. Metabolomic profiling of cyanide-treated zebrafish revealed changes in bile acid and purine metabolism, most notably by an increase in inosine levels. Riboflavin normalizes many of the cyanide-induced neurological and metabolic perturbations in zebrafish. The metabolic effects of cyanide observed in zebrafish were conserved in a rabbit model of cyanide toxicity. Further, humans treated with nitroprusside, a drug that releases nitric oxide and cyanide ions, display increased circulating bile acids and inosine. In summary, riboflavin may be a novel treatment for cyanide toxicity and prophylactic measure during nitroprusside treatment, inosine may serve as a biomarker of cyanide exposure, and metabolites in the bile acid and purine metabolism pathways may shed light on the pathways critical to reversing cyanide toxicity.

Regulation of calcium phosphate formation by native amelogenins in vitro.

Our previous in vitro studies have shown that recombinant full-length porcine amelogenin rP172 can transiently stabilize amorphous calcium phosphate (ACP) and uniquely guide the formation of well-aligned bundles of hydroxyapatite (HA) crystals, as seen in the secretory stage of amelogenesis. This functional capacity is dependent on the hydrophilic C-terminal domain of full-length amelogenin. However, we have also found that native phosphorylated (single S-16 site) forms of full-length (P173) and C-terminal cleaved (P148) amelogenins can stabilize ACP for > 2 d and prevent HA formation. The present study was carried out to test the hypothesis that, at reduced concentrations, native full-length P173 also has the capacity to guide ordered HA formation. The effect of P148 and P173 concentrations (0.2-2.0 mg/ml) on the rate of spontaneous calcium phosphate precipitation was monitored via changes in solution pH, while mineral phases formed were assessed using TEM. At higher P173 concentrations (1.0-2.0 mg/ml), limited mineral formation occurred and only ACP nanoparticles were observed during a 48 h period. However, at 0.4 mg/ml P173, a predominance of organized bundles of linear, needle-like HA crystals were observed. At 0.2 mg/ml of P173, limited quantities of less organized HA crystals were found. Although P148 similarly stabilized ACP, it did not guide ordered HA formation, like P173. Hence, the establishment of the hierarchical enamel structure during secretory stage amelogenesis may be regulated by the partial removal of full-length amelogenin via MMP20 proteolysis, while predominant amelogenin degradation products, like P148, serve to prevent uncontrolled mineral formation.

Vital signs: fruit and vegetable intake among children - United States, 2003-2010.

BACKGROUND: Eating more fruits and vegetables adds underconsumed nutrients to diets, reduces the risks for leading causes of illness and death, and helps manage body weight. This report describes trends in the contributions of fruits and vegetables to the diets of children aged 2-18 years. METHODS: CDC analyzed 1 day of 24-hour dietary recalls from the National Health and Nutrition Examination Surveys from 2003 to 2010 to estimate trends in children's fruit and vegetable intake in cup-equivalents per 1,000 calories (CEPC) and trends by sex, age, race/ethnicity, family income to poverty ratio, and obesity status. Total fruit includes whole fruit (all fruit excluding juice) and fruit juice (from 100% juice, foods, and other beverages). Total vegetables include those encouraged in the Dietary Guidelines for Americans, 2010 (i.e., dark green, orange, and red vegetables and legumes), white potatoes, and all other vegetables. RESULTS: Total fruit intake among children increased from 0.55 CEPC in 2003-2004 to 0.62 in 2009-2010 because of significant increases in whole fruit intake (0.24 to 0.40 CEPC). Over this period, fruit juice intake significantly decreased (0.31 to 0.22 CEPC). Total vegetable intake did not change (0.54 to 0.53 CEPC). No socio-demographic group met the Healthy People 2020 target of 1.1 CEPC vegetables, and only children aged 2-5 years met the target of 0.9 CEPC fruits. CONCLUSIONS: Children's total fruit intake increased because of increases in whole fruit consumption, but total vegetable intake remained unchanged. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Increased attention to the policies and food environments in multiple settings, including schools, early care and education, and homes might help continue the progress in fruit intake and improve vegetable intake.

Childhood obesity task forces established by state legislatures, 2001-2010.

INTRODUCTION: States and communities are considering policy and environmental strategies, including enacting legislation, to reduce and prevent childhood obesity. One legislative approach has been to create task forces to understand key issues and develop a course of action. The goal of this study was to describe state-level, childhood obesity task forces in the United States created by legislation from 2001 through 2010. METHODS: We used the Center for Disease Control and Prevention's Division of Nutrition, Physical Activity, and Obesity database to identify state-level childhood obesity task forces created through legislation from 2001 through 2010. RESULTS: We identified 21 states that had enacted legislation creating childhood obesity task forces of which 6 had created more than one task force. Most task forces were charged with both gathering and reviewing information and making recommendations for obesity-prevention actions in the state. Most legislation required that task forces include representation from the state legislature, state agencies, community organizations, and community members. CONCLUSION: Evaluation of the effectiveness of obesity-prevention task forces and the primary components that contribute to their success may help to determine the advantages of the use of such strategies in obesity prevention.

An Adaptive, Algorithm-based Text Message Intervention to Promote Health Behavior Adherence in Type 2 Diabetes: Treatment Development and Proof-of-Concept Trial.

BACKGROUND: Most individuals with type 2 diabetes (T2D) struggle to adhere to one or more health behaviors. Text message interventions (TMIs) have the potential to improve adherence but have had mixed effects on diet and activity in T2D. We developed an eight-week, adaptive, algorithm-driven TMI to promote physical activity, diet, self-care, and well-being. Then, in a single-arm trial, we assessed its feasibility, acceptability, and preliminary efficacy in 15 individuals with T2D and suboptimal adherence. METHODS: Participants received daily text messages and were asked to rate the utility of each message (0=not helpful, 10=very helpful). These ratings were used by an algorithm to select subsequent messages based on each participant's prior ratings. We assessed intervention feasibility by rates of message transmission/response and acceptability through ratings of message utility and burden. Finally, we examined pre-post changes in diabetes self-care, diet, physical activity, and psychological outcomes and calculated effect sizes (Cohen's d). RESULTS: All text messages were delivered, and participants provided ratings for 79% of messages, above our a priori thresholds for feasibility. Participants rated the individual messages and overall TMI as subjectively useful (utility: 8.1 [SD=2.1] and 7.8 [SD=2.0], respectively) and not burdensome (burden: 0.8 [SD=1.8]). The intervention led to significant, medium- to large-sized improvements in self-care (d=0.77), diet (d=0.99), and activity (d=0.61) but minimal change in psychological outcomes. CONCLUSIONS: The TMI was feasible and well-accepted, and it led to promising improvements in adherence-related outcomes. These findings should be confirmed in a larger randomized controlled trial.

Cell lineage analysis with somatic mutations reveals late divergence of neuronal cell types and cortical areas in human cerebral cortex.

The mammalian cerebral cortex shows functional specialization into regions with distinct neuronal compositions, most strikingly in the human brain, but little is known in about how cellular lineages shape cortical regional variation and neuronal cell types during development. Here, we use somatic single nucleotide variants (sSNVs) to map lineages of neuronal sub-types and cortical regions. Early-occurring sSNVs rarely respect Brodmann area (BA) borders, while late-occurring sSNVs mark neuron-generating clones with modest regional restriction, though descendants often dispersed into neighboring BAs. Nevertheless, in visual cortex, BA17 contains 30-70% more sSNVs compared to the neighboring BA18, with clones across the BA17/18 border distributed asymmetrically and thus displaying different cortex-wide dispersion patterns. Moreover, we find that excitatory neuron-generating clones with modest regional restriction consistently share low-mosaic sSNVs with some inhibitory neurons, suggesting significant co-generation of excitatory and some inhibitory neurons in the dorsal cortex. Our analysis reveals human-specific cortical cell lineage patterns, with both regional inhomogeneities in progenitor proliferation and late divergence of excitatory/inhibitory lineages.

Rapid behavior-based identification of neuroactive small molecules in the zebrafish.

Neuroactive small molecules are indispensable tools for treating mental illnesses and dissecting nervous system function. However, it has been difficult to discover novel neuroactive drugs. Here, we describe a high-throughput, behavior-based approach to neuroactive small molecule discovery in the zebrafish. We used automated screening assays to evaluate thousands of chemical compounds and found that diverse classes of neuroactive molecules caused distinct patterns of behavior. These 'behavioral barcodes' can be used to rapidly identify new psychotropic chemicals and to predict their molecular targets. For example, we identified new acetylcholinesterase and monoamine oxidase inhibitors using phenotypic comparisons and computational techniques. By combining high-throughput screening technologies with behavioral phenotyping in vivo, behavior-based chemical screens can accelerate the pace of neuroactive drug discovery and provide small-molecule tools for understanding vertebrate behavior.

The role of positive psychological constructs in diet and eating behavior among people with metabolic syndrome: A qualitative study.

Positive Psychological (PP) constructs (e.g., optimism and gratitude) may impact the adherence to healthy behaviors, including diet, though prior studies have shown mixed findings. This qualitative study explored the relationships between PP constructs and dietary behaviors among 21 adults with metabolic syndrome through semi-structured interviews. Directed content analysis led to five themes: eating healthfully leads to PP constructs, PP constructs lead to eating healthfully, eating healthfully prevents negative emotions, healthy behaviors associated with diet, and an upward healthy spiral. Given the close relationship between PP constructs and diet, these may be targeted to improve diet in risk populations through interventions that promote well-being.

A Care Management Intervention for Noncardiac Chest Pain: Treatment Development and Feasibility Assessment.

ABSTRACT.Objective: Noncardiac chest pain is common and can cause distress, impair quality of life, and lead to recurrent evaluation. It is often multifactorial in etiology and influenced by psychological factors. The objective of this study was to describe the development, implementation, and preliminary feasibility of an 8-week multicomponent care management intervention.Methods: Participants with noncardiac chest pain were recruited from primary care clinics, ambulatory cardiac stress testing, and the emergency department (ED) at an urban academic hospital from March 2019 to November 2019. The care management team consisted of a nurse, cardiologist, and psychiatrist. Following a 1-time consultation visit with the cardiologist and nurse, evaluation and treatment recommendations were conveyed to the participant's primary care physician. The nurse completed 8 weekly phone calls with the participant to provide support, introduce therapeutic principles, and assist with care coordination under the supervision of a psychiatrist. Intervention feasibility was assessed on 7 domains. To examine preliminary efficacy, the number of ED visits was recorded, and participants completed pre-post measures of psychological health and health-related quality of life and Likert scales of chest pain symptom severity, frequency, and impact.Results: The intervention was developed and implemented in 3 patients who completed 100% of the consultation visits and a mean of 95.8% of study phone calls. There were no adverse events or ED visits. Mean scores for chest pain severity, chest pain frequency, chest pain impact, depression, anxiety, and somatization all improved. No other trends were observed.Conclusions: The findings suggest that a care management intervention may be feasible with potential to improve chest pain symptoms and psychological outcomes. A larger, randomized trial is needed to explore the efficacy of this intervention.Trial Registration: ClinicalTrials.gov identifier: NCT04904198.