Structured processes to improve the quality and impact of clinical and translational research are a required element of the Clinical and Translational Sciences Awards (CTSA) program and are central to awardees’ strategic management efforts. Quality improvement is often assumed to be an ordinary consequence of evaluation programs, in which standardized metrics are tabulated and reported externally. Yet evaluation programs may not actually be very effective at driving quality improvement: required metrics may lack direct relevance; they lack incentive to improve on areas of relative strength; and the validity of inter-site comparability may be limited. In this article, we describe how we convened leaders at our CTSA hub in an iterative planning process to improve the quality of our CTSA program by intentionally focusing on how data collection activities can primarily advance continuous quality improvement (CQI) rather than strictly serve as evaluative tools. We describe our CQI process, which consists of three key components: (1) Logic models outlining goals and associated mechanisms; (2) relevant metrics to evaluate performance improvement opportunities; and (3) an interconnected and collaborative CQI framework that defines actions and timelines to enhance performance.

OBJECTIVES/SPECIFIC AIMS: Our primary objective is to determine whether the bacteria exerts its effect intra- or extra-cellularly. We have genomic and microscopy preliminary evidence indicating that the bacteria is capable of invading endometrial cells. Our secondary objective is to identify what type of impact the bacteria have on the host cells and whether they are capable of transforming the host cells from a benign into a malignant phenotype. We are currently testing a putative mechanism by which the bacteria may cause the overexpression of the hypoxia inducible factor (HIF), a hallmark of endometrial cancer. METHODS/STUDY POPULATION: We are utilizing our custom built optofluidics platform (microfluidics platform incorporated into an advanced microscope with optical laser tweezers) to isolate single cells from the endometrial tissues of 150 patients with and without endometrial cancer. We are utilizing single cell whole genome amplification followed by qPCR to identify if the bacteria is present intracellularly. We are coupling this procedure with standard microbiological invasion assays with endometrial cell line cultures and P.somerae. We are also utilizing our optofluidics platform to perform single cell transcriptomic amplification, followed by sequencing of cells invaded or in the presence of the bacteria to determine the impact in the transcriptome of the host cell. We are coupling this with western blots of factors hypothesized to be impacted by the bacteria in the overexpression of HIF. RESULTS/ANTICIPATED RESULTS: Based on our preliminary data we anticipate to find evidence that P.somerae is invading the host cells, in particular the cells in tumor tissues. We also expect to find that the intracellular presence of the bacteria is causing the overexpression of the HIF pathway, hence resulting in a cancerous phenotype. DISCUSSION/SIGNIFICANCE OF IMPACT: Our long-term goal is to develop primary prevention strategies that will reduce endometrial cancer incidence rates. A confirmation of our hypothesis could suggest that it is sufficient for endometrial cancer prevention efforts to eliminate P.somerae, in line with gastric and cervical cancer efforts. It could also mean that targeting P.somerae in cancer treatment is necessary to contain the disease and prevent recurrence.

OBJECTIVES/GOALS: Ebolavirus disease survivors report persistent, debilitating health concerns dubbed Post-Ebola Syndrome (PES). Attention to PES in young survivors is lacking, we describe PES in pediatric EVD survivors in Eastern Sierra Leone. Additionally, we introduce our proposal investigating differential presentations of PES in pediatric survivors. METHODS/STUDY POPULATION: EVD survivors were enrolled a median of 2.5 years after resolution of disease. Survivors were eligible if listed in a national register maintained by the Sierra Leone Association of Ebola Survivors. Household contacts (HCs) were identified by survivors. Participants were assigned into three comparison groups: pediatric (7-11), adolescent (12-17) and young adult (18-25). A self-reported symptom questionnaire, and a physical exam were conducted. Variables were clustered within organ system and compared across groups. RESULTS/ANTICIPATED RESULTS: Pediatric survivors had lower levels of long-term sequelae compared to adolescents and young adults. Symptoms and abnormal physical exam signs increase with age. Musculoskeletal, psychiatric, ophthalmologic, and GI signs and symptoms were significantly different between groups. Pediatric survivors had significantly more persistent sequelae than age-matched HCs with no history of EVD; particularly within the cardiac/GI (p=.006) and psychiatric/neurological (p=.025) clusters. PES is heterogeneous with respect to age, calling for a deeper understanding of age-based differences. Even the youngest group of survivors experienced significantly more sequelae than HCs, highlighting the elevated symptom burden in these children over their peers. DISCUSSION/SIGNIFICANCE: Understanding mechanistic drivers will ultimately improve targeted treatments for PES. We will characterize symptom groups defining PES in children, determine the relationship between accelerated aging and PES in this population, and test how immune profiles associated with accelerated aging relate to the development of PES in children.

ABSTRACT IMPACT: The implementation of nasal nitric oxide (nNO) as a diagnostic tool to understand the phenotypic/genotypic profiles of Primary Ciliary Dyskinesia (PCD) in Puerto Rico (PR) will be translated in early disease diagnosis, avoidance of comorbidities, and increase survival in our population. OBJECTIVES/GOALS: This study aims to evaluate the role of nNO levels in PCD diagnosis in the Puerto Rican population. Also, we aim to describe the clinical, genetic, and physiological characteristics of PCD in Puerto Ricans to develop a better understanding of the disease. METHODS/STUDY POPULATION: We plan to conduct a cross-sectional study on participants recruited from patients of the Pediatric Rare Lung and Asthma Institute in PR. We will compare nNO levels among genetically confirmed PCD patients, suspected PCD patients with variant of unknown significance (VUS) mutations, suspected PCD patients without genetic mutations, and age-matched healthy subjects. We plan to analyze clinical data and genetic variants to understand the natural history of the disease. The nNO measurements will be completed following previous published protocols. We will also assess the accuracy of the nNO measurements by repeating the measurements two weeks after the initial measurement. RESULTS/ANTICIPATED RESULTS: We hypothesize that many of the VUS present in our population may represent potential new founder mutations not previously reported in the literature. Our expectation is to identify new atypical PCD phenotypes contemplating the heterogenous genetic Puerto Rican pool. We anticipate that nNO levels will help to screen, identify, and confirm diagnosis of patients with clinical PCD in PR. Our findings will be translated in avoidance of further comorbidities and mortality due to earlier disease PCD diagnosis and will expand our genetic understanding about PCD in PR and other diverse populations with heterogenous genetic admixture. DISCUSSION/SIGNIFICANCE OF FINDINGS: We present a significant and novel research proposal that plan to impact the quality of life of patients living with PCD in PR. The implementation of state-of-the-art diagnostic tools like nNO measurement will positively impact and expand our current capabilities to diagnose rare lung diseases like PCD on the island.

OBJECTIVES/SPECIFIC AIMS: (1) Assess if the total duration of EEG suppression during a protocolized exposure to general anesthesia predicts cognitive performance in multiple cognitive domains immediately following emergence from anesthesia. (2) Assess if the total duration of EEG suppression in the same individuals predicts the rate of cognitive recovery in a three-hour period following emergence from anesthesia. METHODS/STUDY POPULATION: This was a non-specified substudy of NCT01911195, a multicenter investigation taking place at the University of Michigan, University of Pennsylvania, and Washington University in St. Louis. 30 healthy volunteers aged 20-40 years were recruited to receive general anesthesia. Participants in the anesthesia arm were anesthetized for three hours at isoflurane levels compatible with surgery (1.3 MAC). Multichannel sensor nets were used for EEG acquisition during the anesthetic exposure. EEG suppression was detected through automated voltage-thresholded classification of 2-second signal epochs, with concordance assessed across sensors. Following return of responsiveness to verbal commands, participants completed up to three hours of serial cognitive tests assessing executive function, reaction time, cognitive throughput, and working memory. Non-linear mixed effects models will be used to estimate the initial cognitive deficit and the rate of cognitive recovery following anesthetic exposure; these measures of cognitive function will be assessed in relation to total duration of suppression during anesthesia. RESULTS/ANTICIPATED RESULTS: Participants displayed wide variability in the total amount of suppression during anesthesia, with a median of 31.2 minutes and range from 0 minutes to 115.2 minutes. Initial analyses suggest that greater duration of burst suppression had a weak relationship with participants’ initial cognitive deficits upon return of responsiveness from anesthesia. Model generation of rate of recovery following anesthetic exposure is pending, but we anticipate this will also have a weak relationship with burst suppression. DISCUSSION/SIGNIFICANCE OF IMPACT: In healthy adults receiving a standardized exposure to anesthesia without surgery, burst suppression appears to be a poor predictor of post-anesthesia cognitive task performance. This suggests that burst suppression may have limited utility as a predictive marker of post-operative cognitive functioning, particularly in young adults without significant illness.

OBJECTIVES/GOALS: The purpose of this study is to understand how hemodynamics during dialysis in End-Stage Renal Disease (ESRD) patients on hemodialysis (HD) affect white matter health and how those effects cause cognitive impairments. METHODS/STUDY POPULATION: We collected demographic data, comorbidities, intradialytic measurements of blood pressure and cerebral oximetry, cognitive measures in several domains using NIH Toolbox Cognition Battery, diffusion-weighted and anatomical MRIs for 20 participants on HD. Specific tracts were identified using tractography and were used to calculate the average DTI measurements in each tract. Regression analysis was used to examine the relationship between mean DTI measurements of white matter integrity and cognitive performance scores. In addition, we compared diffusion MRI and T1 anatomical images of 16 healthy age-matched controls from a previous study. RESULTS/ANTICIPATED RESULTS: In our cohort 18 participants had imaging data that could be used in the analysis. We found widespread decreases in DTI white matter integrity compared to healthy age-matched controls, mean whole-brain fractional anisotropy was .3218 in the HD cohort and .3472 in controls p = .0018. Decreased integrity was found in most of the tracts identified but more decreased in tracts implicated in cognition. Partial regression analysis identified significant relationships between the white matter integrity of the left superior longitudinal fasciculus and overall fluid cognitive performance, R = .5525, p = .0174 before multiple comparisons correction when controlling for differences due to age. DISCUSSION/SIGNIFICANCE OF IMPACT: We found a widespread decrease in white matter integrity and significant correlations between cognitive performance and specific tract integrity in our HD cohort using regions identified by tractography imaging analysis. This analysis shows that HD patients have decreased white matter health and identifies several tracts that are important for cognitive performance in HD patients.

OBJECTIVES/GOALS: The objective of this study is to examine the independent and combined effectiveness of a multiple micronutrient supplementation and responsive caregiving intervention on early child development in southwestern Guatemala. METHODS/STUDY POPULATION: We conducted a double blind, 2 x 2, cluster randomized controlled trial combining micronutrient supplementation and responsive caregiving treatments. We enrolled 309 infants (6-18 months) and 387 preschoolers (36-52 months) at nutritional risk (height-for-age z-score < -1) (51% male; 17% indigenous ethnicity; 76% of caregivers completed ≤ primary school). The supplementation arm received a maize-soy product fortified with 21 micronutrients for 6 months; the control was fortified with B2. The responsive caregiving intervention was adapted from the UNICEF Care for Child Development program and delivered over 6 home visits. We examined changes in early child development from baseline (2015) to endline (2017) using the Bayley Scales of Infant and Toddler Development III and Bracken Scales of School Readiness. RESULTS/ANTICIPATED RESULTS: Among infants, age standardized Bayley cognitive development scores declined over time in each treatment arm. Infant Bayley motor development scores significantly increased in the combined multiple micronutrient supplementation + responsive caregiving arm (â^† = 3.67 [95% CI: 0.17, 7.17], p = 0.04). Among preschoolers, school readiness decreased over time in each treatment arm. The rates of change in infant development and preschooler school readiness did not differ between treatment arms. Further analysis will explore effect modification of the intervention by pre-specified child and household factors. DISCUSSION/SIGNIFICANCE: Combined multiple micronutrient supplementation and responsive caregiving supported motor development while cognitive and school readiness were not impacted by the intervention. These findings will inform the effectiveness and beneficiaries of multisectoral interventions to promote early child development in adverse environments.

OBJECTIVES/GOALS: The overall objective of this study is to determine if medial arterial calcification (MAC) is an independent predictor of diabetes and to evaluate the relationship between MAC, periodontitis and Type II diabetes mellitus. METHODS/STUDY POPULATION: A retrospective case-control model analyzing radiographs for periodontitis and MAC to identify potential biomarkers for underlying systemic conditions, such as diabetes. Charts of patients attending UPENN School of Dental Medicine clinics between 2015 and 2022 were reviewed. Demographics, medical and dental history, diabetic status (identified by POC blood glucose level, fasting blood glucose and/or A1C), and medication history were documented amongst other variables. Patients aged 18 years or older with diabetes and having full mouth intraoral radiographs (FMX), panoramic radiographs and CBCTs were included. Patients with radiographs of poor quality were excluded. Multivariate analysis was used to determine possible associations between diabetes and periodontitis among persons with or without MAC. RESULTS/ANTICIPATED RESULTS: In our pilot study involving 28 participants, 53% of the population with moderate or severe periodontitis had MAC. By the Fisher’s Exact Test, there was an association, meaning those with more periodontal disease are more likely to have MAC (p=0.014). Sixty-three percent of patients with diabetes had MAC, while 19% of patients without evidence of diabetes also had MAC, (p=0.067). There was not enough evidence of association between diabetes and presence of MAC at this time, due to a small sample size, however there was a high prevalence of MAC among the diabetics. We hypothesized that periodontitis, a condition that shares many risk factors with diabetes would also be associated with incident MAC. Findings from this study will be key for the implementation of preventive screening protocols and referral systems. DISCUSSION/SIGNIFICANCE: Diabetes is on the rise and about half of diabetics are undiagnosed. CBCT imaging frequently used in dentistry can detect incidental findings such as MAC. This study has the potential of detecting statistically significant links between MAC, periodontitis and diabetes, hence serving as a sensitive radiographic biomarker for diabetes.

OBJECTIVES/GOALS: There is a need for high-quality and efficient translation of health technologies in the Ontario healthcare system. The goal of this project is to understand the decision-making processes of government expert groups developing recommendations for the system-level implementation of pharmacogenomic testing. METHODS/STUDY POPULATION: This prospective observational case study includes the Ontario Health Pharmacogenomics (PGx) Working Group focused on developing recommendations for a PGx testing implementation strategy in the province. Ontario Health is the government agency that oversees provincial healthcare planning and service delivery. Using qualitative ethnographic methods, we will observe and document the working group’s activities over a 10-month period. Data collection involves meeting recordings, correspondences, researcher field notes, decision-making processes, and group characteristics. Using descriptive statistics and inductive qualitative analyses, the data will be examined to build theory and frameworks for knowledge translation. RESULTS/ANTICIPATED RESULTS: The results will be presented through a case report, process maps, decision milestones, visualizations, and procedural recommendations for future expert groups. This study will contribute to the body of foundational knowledge about translational sciences and support the National Center for Advancing Translational Sciences’guiding principles. To enhance translational processes and train the future translational workforce, this research can be used for educational initiatives. In addition, the observed processes will inform a theory about how expert recommendations are developed in public healthcare systems. DISCUSSION/SIGNIFICANCE: This research addresses a current gap in understanding around translational processes, government decision-making, and the development of recommendations for the adoption, implementation, and dissemination of the novel health technologies transforming public healthcare in Canada.

OBJECTIVES/GOALS: The Fulkerson Home Food Inventory (HFI) is widely used to assess the home food environment, a key target of behavioral weight loss trials. However, no standardized report is available. We created publicly available procedures to automate and standardize HFI reporting, yielding a personalized report to enhance this measures clinical utility. METHODS/STUDY POPULATION: Parents in the TEENS adolescent behavioral weight loss trial complete the HFI at 0-, 2-, 4-, 8-, and 12m and receive personalized reports at each timepoint. In REDCap, participants identify foods available in their home. HFI syntax is applied to calculate the obesogenic home food availability score. Categories of foods found are identified, with specific guidance provided to enhance their home food environment. Prior to automation, procedures were time intensive and error prone. To address this, HFI data are exported into Excel by a PowerShell (v7.2) command-line script using Python (v3.10) with the REDCap API. Results are calculated with F# (v6.0) using Microsoft Excel Interop API and inserted into a report template with F# using the Microsoft Publisher Interop API. This process is repeated at each timepoint. RESULTS/ANTICIPATED RESULTS: The new automated procedures significantly reduce time to generate reports and enhance accuracy. Procedures yield a 2-page individualized report that includes the obesogenic home food environment score and identifies categories of healthy items found (e.g., fruits, vegetables, whole grains) as well as areas of improvement (e.g., high-fat dairy products, processed meats). Specific items found in each category are identified. The report identifies food found in the home (e.g., chicken nuggets) with suggested healthier substitutions (e.g., lean chicken breast). This syntax and commands will be made publicly available for use in the scientific and clinical community. DISCUSSION/SIGNIFICANCE: These publicly available procedures optimize, automate, and standardize reporting for the HFI. Procedures improve efficiency within large-scale clinical trials and yield a personalized report to enhance the clinical utility of this measure and empower participants to make informed decisions about their health behaviors.

OBJECTIVES/GOALS: The global incidence of calcific aortic valve disease (CAVD) increased 3.5-fold since 1990. No preventative or therapeutic pharmaceutical therapies exist for CAVD. We will establish the therapeutic potential of osteoclast-derived exosomes though characterization of contents and mechanisms of action to protect against mineralization. METHODS/STUDY POPULATION: Exosomes were purified from conditioned media collected from murine myeloid precursor cells, RAW264.7 (control), and osteoclasts induced to differentiate from RAW264.7 cells (OD). Protein content of exosomes was determined using proteomic analyses. Nucleic acid contents will be identified by sequencing mRNA, miRNA, and DNA. The calcification prevention and reabsorption abilities of control and OD exosomes will be tested using human valvular interstitial cells (VIC) and smooth muscle cell calcification assays and acellular osteologic disc assays, respectively. Comparison between cellular and acellular systems will help identify mechanisms of action, and demonstrate potential therapeutic viability of OD exosomes in preventative vs resorptive treatments. RESULTS/ANTICIPATED RESULTS: OD exosomes, but not control exosomes, prevented calcification in VIC in vitro. OD exosomes contained osteoclast-specific proteins including TRAP, MMP6, cathepsin K, and bone reabsorption factors including V type proton pumps, ATPases, and integrins. These genes are also involved in resorptive activities, and were highly upregulated in OD compared to control exosomes. We anticipate miRNA signatures associated with mineral resorption will also be present. Increased knowledge of exosome cargo will illuminate their mechanism of action and allow future work to engineer increased efficacy. We also anticipate a therapeutic response when OD exosomes are applied after calcification has begun, showing exosomes promote calcium reabsorption. DISCUSSION/SIGNIFICANCE: Establishing therapeutic potential and examining mechanisms of action will pave the way for OD exosomes as a CAVD treatment. Analysis of exosome contents will determine active molecules to be enhanced in future studies. This work will lay a foundation for moving into aortic valve organoid models, which are accepted by the FDA for preclinical trials.

OBJECTIVES/GOALS: The purpose of this secondary data analysis was to identify latent subgroups of seriously ill adults based on multiple chronic conditions and mortality risk using the CCI. This study was conducted by performing a secondary analysis of data from a randomized controlled trial of seriously ill patients receiving palliative care. METHODS/STUDY POPULATION: A cross-sectional analysis of baseline CCI data was conducted. 381 seriously ill adults receiving palliative care were in the original study. Latent subgroups were identified based on the CCI by conducting a latent class analysis in MPlus. The LCA was modeled on each of the 19 disease items as binary latent predictor variables, an additional binary variable representing presence of any disease not accounted for by the CCI, and a final categorical variable representing the total CCI score divided based on clinically significant cutoffs including zero, low (> = 1-<2), moderate (> = 2-<5), and high CCI (> = 5). RESULTS/ANTICIPATED RESULTS: Three distinct latent subgroups were identified based on the CCI. Latent subgroup 1 included those with a low-moderate CCI consisting of MCC and non-Metastatic Cancers (n = 178), with 45% of this group having chronic obstructive pulmonary disease. The second two subgroups included individuals with a high CCI or a score greater than or equal to 5. Latent subgroup 2 (n = 64) was comprised of individuals with MCC and non-metastatic cancer. Latent subgroup 3 (n = 139) included individuals with metastatic cancer. DISCUSSION/SIGNIFICANCE OF IMPACT: In a sample of seriously ill adults with MCC, latent subgroups were identified consisting of individuals with low, moderate, or high CCI. The low to moderate CCI group consists of individuals with chronic conditions including COPD, congestive heart failure, myocardial infarction, cardiovascular disease. There were two subgroups with high CCI scores and the differentiating factor between the two subgroups was the presence of metastatic cancer in latent subgroup 3. The identification of latent subgroups sets the groundwork for further analyses to compare differences in symptom burden, quality of life, and functional status between groups. The findings have the potential to inform future studies seeking to better characterize seriously adults with MCC based on their disease burden and mortality risk.

OBJECTIVES/GOALS: eHealth programs centered on cognitive behavior therapy (CBT) can be supported by physical therapists to feasibly deliver psychologically-informed physical therapy (PIPT). This study assessed patient and physical therapist (PT) perspectives of adding a CBT-based eHealth program to physical therapy. METHODS/STUDY POPULATION: In our uncontrolled pilot study, PTs were trained in motivational interviewing (MI) to support patient engagement with a 7-module eHealth CBT-based pain self-management program that accompanied a course of PT. Interviews were conducted with a convenience sample of 13 patients with chronic back and/or neck pain and 9 PTs to evaluate experiences with the eHealth program, perceived benefits, barriers and facilitators to integration, and future recommendations for implementation from both perspectives. Interview data were recorded, transcribed, and analyzed using qualitative content analysis for core themes. RESULTS/ANTICIPATED RESULTS: Patients benefited from the eHealth program, especially relaxation (69% of respondents) and meditation/mindfulness (62%). Time and technology were barriers for eHealth engagement (23% and 15%). Most (92%) patients reported their therapist reviewed eHealth progress, although one-third of patients wanted more discussion and feedback on eHealth content. PTs felt the eHealth program was valuable (67%), user-friendly (56%), and took minimal effort to support (78%). Some (44%) therapists felt more confident after MI training to support patient engagement. PTs recommended offering patients tablets (i.e., iPads) for clinic or home use and additional therapist training in MI. DISCUSSION/SIGNIFICANCE: PTs and patients valued a clinician-supported eHealth program, suggesting an acceptable option for PIPT. Future implementation work aims to identify optimal therapist training in MI and additional strategies to overcome time or technology barriers.

OBJECTIVES/GOALS: Residents of environmental justice (EJ) communities experience significantly higher rates of negative health outcomes associated with poor air quality. Low-cost air sensors may supplement regulatory monitoring to better measure air pollution at local scales, but widespread application of this technology remains limited due to many challenges. METHODS/STUDY POPULATION: To address these obstacles, we designed a training program to equip community and academic research partners with the skills and knowledge to successfully apply low-cost sensors in community-engaged environmental health research. The R esearch Innovations using Sensor Technology in Environmental Justice Communities (RISE Communities) program was established through an NIEHS R25 award in 2022 and has three specific aims: 1) Foster community-academic partnerships through research education, training, and team development activities, 2) Provide technical training in the application of low-cost sensors for indoor, outdoor, and personal air monitoring in EJ communities, and 3) Establish a community of practice to address air quality in communities nationwide. RESULTS/ANTICIPATED RESULTS: We hosted our first cohort in August 2023, training five community-academic research teams in team collaboration, community-engaged research, and technical skills for collecting and analyzing data from PurpleAir sensors. Each team received 12 sensors to take to their home EJ communities to begin their projects. Community of practice development continues through interactive webinars and development of a web-based repository of training videos and discussion board posts. Evaluation data show high participant learning and satisfaction, with mean confidence scores improving on 6/8 metrics. Evaluation data also suggest several areas for improvement such as more time spent in teams for planning and additional opportunities for interaction within the cohort and with program instructors for problem-solving. DISCUSSION/SIGNIFICANCE: Effective training for team-based community-engaged research requires careful planning for team development and study implementation. Longitudinal training and support for the technical aspects of utilizing air sensors is also critical to team success. The RISE Communities program is actively recruiting for future training cohorts.

ABSTRACT IMPACT: This study deepens knowledge with respect to the associations between depression, cardiometabolic conditions, and accelerated aging with a clinically accessible marker in a population with disproportionate risk for comorbidity. OBJECTIVES/GOALS: The aim of this secondary analysis is to examine associations between DNA methylation age acceleration (DNAm AA) and depressive symptoms in African American women (AAW) considering the presence of cardiometabolic conditions (CMCs) including hypertension, diabetes, obesity. METHODS/STUDY POPULATION: Genomic and longitudinal clinical data (collected 2015-2020) from the Intergenerational Impact of Genetic and Psychosocial Factors on Blood Pressure Study (InterGEN) cohort (n=227) were utilized for this analysis. DNA methylation age (estimated by the Horvath method) incorporates DNA methylation status at 353 CpG sites. DNAm AA is the residual of DNA methylation age regressed on chronological age in a linear model. Spearman’s correlations and linear regression examine the relationship between DNAm AA and depressive symptoms (Beck Depression Inventory) and cardiometabolic status. The potential association and impact of SES, trauma, substance use, and stress were also considered. RESULTS/ANTICIPATED RESULTS: Contrary to our hypothesis, DNAm AA did not associate with the severity of depressive symptoms. Correlation between DNAm AA and affective symptom subscore (BDI) approached significance (p = 0.06). We observed significant correlations between DNAm AA and specific depressive symptoms including participants’ reported disappointment, disgust, or hatred toward themselves (p < 0.05), difficulty with making decisions (p < 0.05), and worry about their physical health (p < 0.05). DNAm AA was also significantly correlated with BMI (p > 0.001). Significant relationships were not evident in the subsequent regression analysis examining potential relationships between DNAm AA and depression. To our knowledge, this is the first study to examine associations between DNAm AA and depressive symptoms in AAW. DISCUSSION/SIGNIFICANCE OF FINDINGS: Depression limits life quality and quantity and is highly comorbid in CMCs. AAW have a high risk of comorbidity. This study deepens knowledge with respect to the associations between depression, CMCs, and aging with a clinically accessible marker in a population with disproportionate risk.

OBJECTIVES/SPECIFIC AIMS: Our objective was to examine serum E2 levels in dcSSc males in relation to disease characteristics (i.e autoanitbody profile and internal organ involvement) and its impact on survival. METHODS/STUDY POPULATION: We measured serum E2 levels in 83 dcSSc men >50 years old from the University of Pittsburgh Scleroderma Center and healthy controls of similar age. Using statistical modeling, we examined the associations between circulating E2 levels, internal organ involvement, autoantibody profiles, and survival. RESULTS/ANTICIPATED RESULTS: Male dcSSc patients had significantly higher serum E2 levels compared to healthy male controls and compared to dcSSc post-menopausal women of similar age. Male dcSSc patients with high serum E2 levels had significantly more heart involvement and worse survival. Using Cox regression modeling for risk of death, increasing serum E2 levels in anti-Scl-70 antibody positive dcSSc males were associated an increased risk of death. DISCUSSION/SIGNIFICANCE OF IMPACT: DcSSc male patients have higher levels of E2 compared to healthy controls and dcSSc postmenopausal women. Elevated serum E2 levels in dcSSc males >50 are associated with heart involvement and, if anti-Scl-70 antibody positive, worse survival. Our current study expands on our previous work, not only that that E2 exerts pro-fibrotic effects on skin, but also internal organ involvement, overall survival. These data suggest an important role of estrogen imbalance in SSc.

OBJECTIVES/GOALS: Childhood psychiatric symptoms are highly comorbid. Their co-occurrence and association with negative life outcomes is partially explained by deficits in executive control, or processes enabling self-regulation. Here, we test a novel executive neural target in three fMRI tasks and its relevance to shared psychopathology. METHODS/STUDY POPULATION: We studied 60 children [15 F/45 M; mean age (SD)=11.6 years (1.62)] with diverse diagnoses including attention deficit disorder (n=26) and autism spectrum disorder (n=22). We extracted a latent general factor of psychopathology using principal component analyses applied to parent-report Child Behavior Checklist syndrome scores. Subjects completed 3 executive control fMRI probes, tapping adaptive control, working memory, and inhibition. Correlational psychophysiological interaction (cPPI) analysis measured correlations between executive control-related modulations of activity in 414 network-affiliated parcels. We selected parcels exhibiting control-related cross-network correlations as well as control-related activity across all tasks and tested them for association with psychopathology. RESULTS/ANTICIPATED RESULTS: cPPI connectivity matrices were thresholded and graphs were identified using the Network-Based Statistic toolbox (p90th percentile PC) as well as control-related activation (>10% activated voxels; p DISCUSSION/SIGNIFICANCE: Our results examine cross-network interactions between brain regions during 3 fMRI tasks and their role in explaining individual variation in psychopathology. As executive control links to both comorbidity and life outcomes, identifying the clinically-relevant neural correlates of controlled behavior may lead to transdiagnostic treatments.