OBJECTIVES/GOALS: Electronic cigarettes have become increasingly popular, with various combustion products generated in the process. Dihydroxyacetone (DHA), a carbohydrate made during the heating process. Exposures may reach high micromolar to low millimolar doses of DHA per day and no studies have been done to understand the effects of DHA in the heart. METHODS/STUDY POPULATION: Here, we examine if DHA contributes to these using rat cardiomyocytes, H9c2 cells, and rat cardiac tissues to DHA evaluating metabolic and mitochondrial effects. Using the cells, we will investigate metabolic and mitochondrial pathways using Seahorse, protein expression changes in nutrient sensing pathways, and understand dose-dependent effects of DHA in the heart. Metabolite pools will also be evaluated to understand the changes promoted by DHA. Oxidative stress as previously observed in other cell models will also be measured. Key findings in the cardiac cells will be investigated in the cardiac tissues exposed to DHA. RESULTS/ANTICIPATED RESULTS: We have previously shown DHA induces oxidative stress, metabolic changes, and mitochondrial dysfunction in various cell line models. Interestingly, these effects are highly cell-type dependent. E-cigarettes are known to have toxic cardiac effects, including arterial stiffness, endothelial dysfunction, vascular injury, and oxidative stress. Changes in glycolytic, fatty acid synthesis, and the citric acid cycle enzymes and metabolites were found in the H9c2 cells. We also observed increased mitochondrial ROS and fuel changes due to DHA exposure. In DHA exposed cardiac tissues, we observed oxidative stress and mitochondrial fission and fusion dynamics altered. DISCUSSION/SIGNIFICANCE: These data suggest further study at physiologically relevant doses is warranted to understand how DHA inhaled impacts the long-term health of vapers. As well as the regulation of DHA in e-cigarettes as it has been deemed as safe for topical applications and warned against inhalation.

OBJECTIVES/GOALS: To assess labels of drugs approved for Type 2 Diabetes (T2D) for the inclusion of geriatric sub-population data (ages 65-74, 75-84, ≥85) since January 1, 2013, in accordance with international guidance and US regulations in recognition of an aging populations and global demographics. METHODS/STUDY POPULATION: Utilizing FDA Guidance for Industry: Labeling for Human Prescription and Biological Products - Implementing the Physician’s Labeling Rule (PLR) Content and Format Requirements and the International Council for Harmonization of Technical Requirements (ICH) E7 guidance “Studies in Support of Special Populations: Geriatrics” as reference for assessing labels. The Center for Drug Evaluation and Research (CDER) new drugs/biologic approvals database was filtered for drugs approved between Jan. 1, 2013 and Dec. 31, 2022 with approved T2D indications. Examined original drug labels and supplements from Drugs@FDA for geriatric use efficacy and safety wording in Section 8.5 (Use in Specific Populations, Geriatric Use), for labels. Subpopulation data in labeling for ages 65-74, 75-84, and ≥85 was analyzed. RESULTS/ANTICIPATED RESULTS: Seven T2D drugs (Trulicity, Tresiba, Adlyxin, Ozempic, Steglatro, Kerendia, Mounjaro) approved within the specified time period were analyzed. In the current examination, all labels contain information regarding efficacy differences between ages 65+ and 75+, however, none contain information on efficacy for ≥85 populations. Four of the seven drugs have been updated with increased data from further efficacy trials for older adults conducted after initial approval. The remaining three drugs have only been reworded, or not changed at all, with no further efficacy trials conducted. DISCUSSION/SIGNIFICANCE: This research shows the gap in representation of older adults in clinical trial data and T2D drugs’ labeling. Despite having a higher usage of T2D drugs compared to the general population, older adults and especially the oldest-old (≥85) are underrepresented. Additional demographic requirements ensuring diversity in clinical trials is needed.

OBJECTIVES/GOALS: The purpose of this study was to investigate how suggestibility and social susceptibility relate to alcohol use in young adult non-dependent alcohol users, and the role of trait anxiety in this relationship. We hypothesized that greater trait anxiety would be associated with higher levels of alcohol misuse, and this would be mediated by suggestibility. METHODS/STUDY POPULATION: Study participants enrolled in the NIAAA screening and assessment protocol completed questionnaires on suggestibility, anxiety, and alcohol use. The Multidimensional Iowa Suggestibility Scale (MISS) is a 95-question self-report assessment of suggestibility. Trait anxiety is assessed with the State Trait Anxiety Inventory-Trait (STAI-T). Alcohol measures included the Alcohol Use Disorder Identification Test (AUDIT). Structured Clinical Interviews for DSM-IV or DSM-5 disorders were conducted, and non-dependent participants (N = 113) were considered. A median split was conducted (median age = 35.1 years), with the focus of this study on the younger individuals (N = 55). RESULTS/ANTICIPATED RESULTS: Initial analyses showed that suggestibility, alcohol misuse, and trait anxiety all had significant positive correlations with one another. To better understand the relationship of peer influence, specifically, with drinking and anxiety, MISS subscale of Peer Conformity was analyzed. MISS total score and Peer Conformity were positively correlated with AUDIT Total as well as STAI-T Score. STAI-T Score was additionally positively correlated with AUDIT Total (all p2 = 0.222). We also looked at Peer Conformity in place of MISS Total (R2 = 0.213). In both models, only suggestibility measures were significant predictors of harmful alcohol use (p<0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: In young social drinkers, there were significant positive associations between suggestibility, risky alcohol use, and trait anxiety. These results suggest that suggestibility may be a modifiable risk factor for risky alcohol consumption. Future directions include using mediation models to explore the associations between suggestibility, anxiety, and alcohol misuse.

Objectives/Goals: The goal of this project was to engineer 3D lung models by embedding human epithelial cells and fibroblasts within hybrid-hydrogels containing human decellularized extracellular matrix (dECM) from healthy and fibrotic lungs. This platform will enable us to study cell–matrix interactions involved lung fibrosis pathogenesis. Methods/Study Population: To incorporate dECM into hybrid-hydrogels it must be digested and functionalized. We determined the best conditions for pepsin digesting dECM from healthy and fibrotic human lung by collecting samples every 12 hours up to 96 hours and measuring total protein (BCA assay), total amine concentration (ninhydrin assay), and protein fragment size (SDS PAGE). Next, several molar excesses of Traut’s reagent were tested and functionalization was verified by comparing amine content (ninhydrin assay) to thiol content (Ellman’s assay). Hydrogel stiffness was measured initially and after stiffening using parallel-plate rheology. Results/Anticipated Results: The dECM was successfully pepsin-digested, with the 48-hour time point yielding the highest free amine levels. A 75-molar excess of Traut’s reagent was best for converting free amines to thiols. Dynamic stiffening allowed the creation of hybrid-hydrogels mimicking both healthy (1–5 kPa) and fibrotic (>10 kPa) lung microenvironments. We anticipate that this model will demonstrate differential fibroblast activation based on hybrid-hydrogel dECM source (healthy or fibrotic), microenvironmental stiffness, and cell source (healthy or fibrotic). Validation of this 3D co-culture system could accelerate drug discovery by providing a more accurate in vitro platform for high-throughput screening. Discussion/Significance of Impact: This work advances pulmonary fibrosis modeling by creating human dECM-based hydrogels that recapitulate the cellular and mechanical microenvironment of healthy and diseased lung, potentially enabling us to uncover novel therapeutic targets and improving drug efficacy testing in vitro.

OBJECTIVES/SPECIFIC AIMS: This study aims to understand the potential immunomudualtory effect of APOL1 variants in auto-antigen activated myeloid cells by assessing lysosomal integrity in activated cells expressing APOL1. The primary stimuli were: 1. ssRNA hY3 as a proxy for the Ro immune complex; 2. in an bulk RNA seq model, interferon-response gene, Siglec 1, as a read out of interferon activity. The primary outcomes were: 1. Myeloid cell APOL1 expression both in primary macrophage cultures and ex-vivo patient derived macrophages; 2. Lysosome integrity as measured by fluorescence intensity of lysotracker dye on light microscopy. METHODS/STUDY POPULATION: All recruited subjects provided written informed consent as per the NEW YORK UNIVERSITY Division of Rheumatology-wide Specimen and Matched Phenotype Linked Examination (SAMPLE) protocol. Subjects were African American; SLE subjects met 4 American College of Rheumatology criteria for SLE. Healthy donor monocytes representing each genotype in duplicate (reference allele: G0/G0; heterozygote variant: RV/G0; and homozygote variant RV/RV) were cultured with GM-CSF to yield macrophages which were incubated in serum free media or with hY3 ssRNA (TLR 7/8 agonist) to yield inflammatory M1 macrophages. Fold increase of APOL1 in untreated vs hY3 treated macrophages was measured using qPCR. Live cells were then cultured on glass chamber slides with DNA dye, DAPI, and Lysotracker red, a fluorescent dye that stains acidic lysosomes. As a proof of concept, interferon response gene, Signlec1, and APOL1 transcriptional activity in peripheral blood monocytes (PBMCs) were measured and correlated in 17 SLE patients by RNA seq. RESULTS/ANTICIPATED RESULTS: Regardless of genotype, hY3 increased APOL1 expression by 29 (+/−18.4) fold (P = 0.007 vs no treatment). Genotyping of the qPCR product showed concordance with the chromosomal DNA with the RV heterozygotes expressing both alleles. To examine lysosomal membrane integrity, live hY3-treated macrophages were stained with lysosotracker dye and fluorescence intensity was measured. Compared to reference allele carrying macrophages, each additional variant allele corresponded with a lesser degree of lysosome compartment staining. In SLE PBMCs, we found that APOL1 was highly expressed, and significantly correlated with Siglec1 (F=10.5; P = 0.005) supporting an association between circulating interferons and APOL1 accumulation in monocytes. DISCUSSION/SIGNIFICANCE OF IMPACT: Given that the “cytokine milieu” in SLE elicits APOL1 expression, induces inflammatory cell metabolic rewiring, and stimulates autophagy thereby exposing defects in autophagic flux, this gene-environment interaction may underpin the relationship between chronic inflammation and heightened APOL1 polymorphism-attributed cardiovascular risk. These data support further inquiry into the intersection between chronic autoimmunity and APOL1’s functional role in the vascular microenvironment. The in vitro studies herein extend our prior work by demonstrating a mechanistic link between SLE-associated inflammation, APOL1 risk variant status and CVD via a lysosomal defect which converges on common autophagic and metabolic pathways in mononuclear cells.

Objectives/Goals: This study tests how fiber microstructural integrity and myelination levels within the cingulum connectome are associated with information processing speed (IPS) in relapsing-remitting multiple sclerosis (RRMS). We investigate the functional impact of structural coherence, myelin content, and white matter hyperintensities (WMH) load on IPS. Methods/Study Population: Data from 63 RRMS and 25 healthy controls (HC) were used. We hypothesize that the structural integrity of the cingulum bundle and its structural network – or connectome – is distinctly associated with IPS function in people with RRMS (vs. HC) due to myelin-related plasticity across the wiring. Using diffusion spectrum imaging and high-resolution tract segmentation, we constructed individualized white matter connectomes. Diffusion quantitative anisotropy (QA) and myelin fractions (MWF) were used to quantify structural coherence and myelination. WMH load was measured with T2-FLAIR imaging. Bayesian–Pearson correlations, mixed-linear, and moderation models explored how fiber-specific QA, MWF, and WMH load relate to IPS function in RRMS, as measured by Symbol Digit Modalities Test (SDMT). Results/Anticipated Results: We theorize that (1) QA in the cingulum connectome correlates with SDMT performance dimensionally, indicating that structural coherence in the white matter supports IPS function among both groups; (2) increased myelination will strengthen the positive association between QA and SDMT scores, suggesting that connectome-specific myelin content facilitates IPS; (3) conversely, WMH load within the cingulum connectome is expected to inversely correlate with SDMT scores, reflecting the detrimental impact of lesion burden on IPS function; (4) myelination in specialized tracts within the cingulum connectome play a compensatory role to support IPS function in the RRMS group. These investigations can offer a mechanistic clue to potential neuroplastic targets for cognitive interventions in MS. Discussion/Significance of Impact: By linking white matter integrity to cognitive function at the connectome level, this study can support neuroregenerative strategies to mitigate cognitive burden in RRMS. Our findings may advance understanding of how structural coherence, tract myelination, and WMH affect IPS, shaping personalized prognostic and therapeutic interventions.

OBJECTIVES/GOALS: Specific aims are to: (Qualitative aim) Develop a new measure of cancer-related self-efficacy in partners (BCSES-P) and obtain feedback on the items (Quantitative) Evaluate the psychometric properties of the BCSES-P including: dimensionality, factor analysis, and construct validity assessing the relationships posited METHODS/STUDY POPULATION: 2-Phase Approach: 1) Item development and 1) Item testing Phase 1 Stage 1: Literature review to identify additional covariates Stage 2: Focus groups and individual interviews to determine partners’ needs Sample size: 20 partners (18 years of age or older, identifying as being in a committed relationship with a BCS) Design: cross-sectional, qualitative interviews Stage 3: Develop candidate items Stage 4: Cognitive interviews Stage 5: Finalize items with research team Phase 2 Preliminary psychometric testing Dimensionality Internal consistency reliability Construct validity Sample size: 150 partners Design: cross-sectional, online survey RESULTS/ANTICIPATED RESULTS: The BCSES-P will be unidimensional as assessed by exploratory factor analysis. The BCSES-P will demonstrate an internal consistency coefficient of 0.70 or above. Construct validity of the BCSES-P will be demonstrated by support of the following theoretical relationships: Cancer-related self-efficacy will be positively related to marital satisfaction and sexual functioning (social well-being) and the distal outcome, overall QoL. Cancer-related self-efficacy will be negatively related to fatigue (physical well-being), fear of recurrence, depression, and anxiety (psychological well-being). DISCUSSION/SIGNIFICANCE OF IMPACT: Findings will guide intervention development to improve partners’ quality of life The BCSES-P will be the first scale to measure partners’ cancer-related self-efficacy. This study will highlight a holistic approach to studying the long-term effects of breast cancer on partners.

OBJECTIVES/GOALS: Socioeconomic status (SES) affects risk of disease and access to therapies. The expanded access (EA) pathway allows for the clinical use of investigational products for patients who have serious illness but no Food and Drug Administration (FDA)-approved therapeutic options. The SES of patients who receive EA is unknown. METHODS/STUDY POPULATION: We reviewed the patients who were approved for treatment through a single-patient EA pathway between 2018 and 2023. Using Michigan Medicine (MM) DataDirect software linked to the MM electronic medical record system, we linked the EA pathway patients to neighborhood data from the National Neighborhood Data Archive (NaNDA) to compare neighborhood related markers of affluence among EA patients and others treated at MM. We used descriptive statistics to compare variables between EA pathway patients and residents of the state of Michigan or the local county surrounding MM (Washtenaw County), using US Census tract data to provide context for these findings. RESULTS/ANTICIPATED RESULTS: MM patients who received EA treatments were more likely to come from neighborhoods that showed markers of high SES compared to residents of the state of Michigan but not Washtenaw County. This includes the proportion of persons living in poverty (12.5% EA / 13.4% Michigan / 12.4% Washtenaw) and education in the form of a bachelor’s degree or higher (32.2% / 30.6% / 57.2%). This varied by the disease being treated. Oncology patients were more likely to be from areas with less poverty and more education (12.4% / 76.8%) than the EA average. EA patients being treated for infectious diseases were from areas with more poverty and less education (13.5% / 26.7%). DISCUSSION/SIGNIFICANCE: Patients treated at Michigan Medicine using treatments obtained through the EA pathway came from areas that were, on average, more affluent than residents of the state of Michigan as a whole. This finding warrants more research to ensure equitable access to these therapies for patients in disadvantaged neighborhoods.

OBJECTIVES/GOALS: Insertable devices (IDs) for obstetric fistula (OF) management are feasible, acceptable, but not accessible; implementation determinants in low and middle-income countries (LMICs) are unknown. Thus, the purpose of this study was to understand pre-adoption facilitators and barriers among global stakeholders for a therapeutic ID for OF in LMICs. METHODS/STUDY POPULATION: Stakeholders, including researchers (n = 11), clinicians (n = 4), government officials (n = 2), and administrators (n = 4), were purposefully identified from various sectors involved in understanding and addressing the needs of women with OF: clinical care, academia, international health, civil society, and government. Twenty-one individuals were interviewed about their perceptions of IDs for OF self-management and their implementation. Interviews were audio-recorded and transcribed. The Consolidated Framework for Implementation Research (CFIR) guided data collection and analysis. Thematic analyses were carried out within Nvivo v.12. RESULTS/ANTICIPATED RESULTS: Determinants of implementation of an ID for OF self-management (by CFIR domain) include: (1) intervention characteristics—relative advantage and cost; (2) individual characteristics—knowledge and beliefs about the innovation; (3) inner setting-- organizational culture, implementation climate, tension for change, and compatibility; (4) outer setting-- patient needs and resources and external policy and incentives; (5) process—opinion leaders and collaboration. Facilitators include: tension for change for low-cost, accessible IDs; relative advantage over existing tools; development of partnerships; and identification of implementation champions. Barriers include: need for educational strategies to encourage clinical provider acceptability; lack of evidence of the optimal beneficiary. DISCUSSION/SIGNIFICANCE OF IMPACT: Tools for therapeutic OF self-management could be integrated into comprehensive OF programming. Employing the CFIR as an overarching typology allows for comparison across contexts and settings where OF care occurs and may be useful for clinicians, researchers, and policy-makers interested in implementing IDs for OF self-management in LMICs. CONFLICT OF INTEREST DESCRIPTION: I am working with colleagues at the non-profit Restore Health on developing an insertable cup for therapeutic self-management of obstetric fistula in LMICs

OBJECTIVES/SPECIFIC AIMS: Anxiety is prevalent in early childhood and, when left untreated, increases children’s risk for chronic anxiety and depression later in life. Maternal risk factors (e.g. income and marital status) have also been shown to heighten their children’s risk for the development of the aforementioned psychopathology. Sleep plays a critical role in behavior regulation, is affected in depression, and is influenced by a wide range of demographic and psychological variables. The purpose of this study was to examine the relationship between maternal sleep and the presence in their children of reported symptoms relating to anxiety, depression, and behavior regulation. METHODS/STUDY POPULATION: Children (n=59, aged: 4-9 years (M = 6.069, SD = 1.006, 59.3% female) and their mothers were sampled from clinic and community settings and were administered questionnaires. Maternal sleep quality was assessed by the Pittsburgh Sleep Quality Index, which captures both numeric and self-reported categories relating to an individual’s perception of their sleep. Child anxiety and depression were assessed via parent-reported Child Behavioral Checklist (CBCL). Maternal depression symptoms were assessed with the Beck Depression Inventory (BDI). Associations between these measures were analyzed by ANOVA with post-hoc analysis and linear regression as appropriate. RESULTS/ANTICIPATED RESULTS: A statistically significant difference was observed in the mean child CBCL scores when children were sub-set into maternal categories of self-reported days of dysfunction due to sleepiness over the past month. Mean child CBCL T-score domains with statistically significant differences were: attention problems (F = 4.935, p = 0.004), depression problems (F = 3.073, p = 0.035), ADHD (F = 4.422, p = 0.007), oppositional defiant (F = 2.865, p = 0.045), and total t-score (F = 3.073, p = 0.035). Maternal mean DBI scores were also statistically significantly different when grouped by days of maternal dysfunction due to sleepiness (F = 9.791, p < 0.001). There was no relation between these CBCL categories and maternal DBI scores. DISCUSSION/SIGNIFICANCE OF IMPACT: Maternal self-reported days of dysfunction due to sleepiness may potentially increase risk for their children to develop further psychopathology independent of mothers’ depression symptomatology. These findings highlight the need for broader assessment clinically of children’s environments with additional focus on maternal function given the potential impact on their children’s functional outcomes.

The shift in learning environments due to the COVID-19 pandemic necessitates a closer look at course design, faculty approaches to teaching, and student interaction, all of which may predict learner achievement and satisfaction. Transitioning to an online environment requires the reinvention, reimagining, and applying of “e-flavors” of general learning theory. With this shift to online learning comes the opportunity for misunderstandings and “myths” to occur, which may stand in the way of faculty embracing online learning and fully realizing its potential. This article seeks to address several myths and misconceptions that have arisen in higher education during the rapid shift to online teaching and learning. While not comprehensive, these myths represent a snapshot of common challenges. These are we can transfer our in-person course design to online; adult learners do not need an empathetic approach; and online teaching and learning is socially isolating. Through an appreciative inquiry framework, we present each myth in the context of relevant literature and invite faculty with varied online teaching experience to share their own case studies that illustrate how they have “busted” these myths with the goal to identify existing examples of locally effective practices for the express purpose of replication that leads to positive change.

Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.

Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) was an extraordinary example of a public-private partnership (PPP) that brought together over thirty organizations and hundreds of individuals to address one of the most pressing global health needs in recent decades. In particular, ACTIV provided a key avenue for testing numerous therapeutics for their potential benefit in treating the SARS-CoV-2 virus or the resulting symptoms of acute COVID-19 infection. Given the speed and scale at which ACTIV designed and implemented master protocols across global networks that it was simultaneously working to create, the PPP can provide valuable lessons for best practices and avoiding pitfalls the next time the world is faced with a global pandemic of a novel pathogen. This report provides a general overview of the ACTIV partnership to set the stage and context for the subsequent articles in this issue that will relay these lessons learned.

Objectives/Goals: Our team has developed a 24-well donor-derived skeletal muscle microphysiological system (MPS) to study signaling pathways associated with a variety of muscle diseases. 3D muscle will be utilized to evaluate pharmacologic interventions for these muscle conditions to improve both muscle mass and function. Methods/Study Population: In this study, muscle MPS were formed from healthy young female and male subjects. 3D muscle underwent a 21-day differentiation with an electrical stimulation (e-stim) regimen twice daily beginning on Day 14. Functional assessments in permeabilized fibers of both sexes included isometric and isotonic calcium-induced contractions, allowing for the characterization of force-pCa (-log[Ca2+]), force-velocity and force-power relationships. Samples from Day 17 and Day 21 will be assessed for pro-growth protein signaling via western blotting and a subset of samples will be analyzed by histology and microscopy for fiber type and size. Finally, culture media pre- and post-terminal e-stim on Day 21 will be collected for extracellular vesicle (EV) isolation and EVs will be assessed by standard proteomics analysis. Results/Anticipated Results: Permeabilized fibers from both sexes reproduced the well-established sigmoidal force-pCa and the curvilinear force-velocity and force-power relationships reported in native striated muscle. Maximum specific force and force-pCa relationship were not different between sexes. Isotonic contractile measurements revealed that these male and female fibers also exhibit similar force-velocity and force-power relationships. We anticipate that 3D muscles from day 17 compared to day 21 will exhibit higher levels of pro-growth protein signaling due to e-stim application and no differences in fiber type or size between sexes. Additionally, we expect that EV quantity will depend upon 3D muscle maturity and presence of e-stim. Discussion/Significance of Impact: This study demonstrates the similarities of functional characteristics and exercise (or e-stim) adaptation between native human skeletal muscle and 3D bioengineered skeletal muscle. Ultimately, this data further validates the muscle MPS system to study muscle diseases and to enhance the translation of therapeutics to clinical settings.

OBJECTIVES/GOALS: This study seeks to comprehensively evaluate the extent to which participants in clinical trials (CT) for Atopic Dermatitis (AD) accurately mirror the demographics and characteristics of the broader AD-affected populations. We will achieve this objective by analyzing data from AD CTs spanning the years 2011 to 2022. METHODS/STUDY POPULATION: We examined completed trials for 10 FDA approved treatments for AD, utilizing data sourced fromclinicaltrials.gov [http://clinicaltrials.gov]. In light of the increased number of AD clinical trials over the past decade, we tailored our search parameters to encampass all trials related to approved treatments from 2011-2022. To assess the characteristics of the participant population in these trials, information including inclusion and exclusion criteria, age, location, sex, and disease severity were collected for each trial. Furthermore, race and ethnicity data were also extracted and analyzed. Additionally, comparisons were drawn between trials completed before and after April 2017, when the FDA began requiring that researchers publish race and ethnicity data toclinicaltrials.gov [http://clinicaltrials.gov]. RESULTS/ANTICIPATED RESULTS: Across 67 CTs examined, 45% of trials were restricted to adult patients, 28% were restricted to pediatric patients, and 27% included both. 77% of CTs occurred in urban settings and 23% occurred in rural settings according to the The Economic Research Service definition. 36% of CTs included mild-to-moderate AD patients, and 64% of CTs included moderate-to-severe AD patients. Race distribution of CTs revealed 67% White, 14% Black/African American, 16% Asian, and 3% others. 13% of participants identified as Hispanic or Latino. With further analysis, we will determine whether there is a difference in ethnic distribution between trials completed before and after April 2017, when the FDA started requiring race/ethnicity data to be submitted. DISCUSSION/SIGNIFICANCE: The findings highlight a significant concern in AD CTs: the insufficient representation of Black and Asian populations. The findings emphasize the need for a more inclusive selection process that accurately reflects the diversity of patients. Failing to do so could undermine the assessment of treatment effectiveness in such populations.

OBJECTIVES/GOALS: To compare the herbal medicine (HM) programs of the U.S. to those of different countries–including the European Union, South Korea, China, and India–and to examine each regulatory body’s process for obtaining market approval for HM drugs. METHODS/STUDY POPULATION: The European Union, South Korea, China, and India’s respective HM regulatory programs were examined and compared to the U.S. FDA’s HM process. These specific regulatory bodies were chosen based on the country’s long history with HM and/or the robustness of their existing HM review processes. International HM programs were researched using official government websites and journals published by independent, external research institutions that were accessed via USC’s library services. Data regarding the efficacy of HM policies such as HM IND approval rates, number of marketed HM drugs, and establishment of unique HM sectors will be collected. RESULTS/ANTICIPATED RESULTS: Investigational New Drug (INDs) applications regarding HM from each country will be categorized and displayed according to their approval status in order to provide insight on a HM program’s efficiency. Results also included a table displaying common challenges for approval for HM drugs across federal regulatory bodies. If applicable, effective solutions implemented to address some of these obstacles that proved to be effective will also be displayed in the form of a table. DISCUSSION/SIGNIFICANCE: Tables displaying the collective flaws of international HM programs and the resulting regulatory solutions can provide clearer guidance for companies seeking to submit HM INDs and for the U.S. FDA seeking to develop improved HM regulations.

Objectives/Goals: Obesity has been classified as a global epidemic and origin of numerous health issues. The central hypothesis of this study is that psychological measures, DNA methylation, and gene transcription will predict obesity-related outcomes after lifestyle interventions, and such interventions may alter DNA methylation profiles. Methods/Study Population: This study consisted of a randomized-controlled trial examining the effects of lifestyle +/- stress reduction interventions in 285 highly stressed parents with obesity, followed for 2 years. Full participants received nutrition and activity counseling, and were randomized to either a stress reduction intervention or a contact control. Those who otherwise qualified for the study but unable to fully participate were included in a no intervention control group. The intervention consisted of 12 weeks of nutrition and activity counseling +/- 2-hour weekly stress reduction interventions using MBSR and CBT-based strategies. DNA methylation was assessed using Illumina EPIC arrays. Results/Anticipated Results: Using linear mixed models (LMMs), this study will first examine the hypothesis that baseline psychological measures and pre-existing methylation sites associated with obesity and glycemic control (e.g., ABCG1, ATP10A, TXNIP, SREBF1, RNF39, and SOCS3) predict changes in BMI, HOMA-IR, and HgbA1C post-intervention and at 1 and 2 year follow-ups. Using sites that demonstrate statistical significance, we will develop a polymethylation risk score predictor of change in BMI. Next, we will examine the hypothesis that interventions which reduce obesity may also lead to improvements in epigenetic aging using LMMs to determine if changes in BMI or HOMA-IR predict changes in epigenetic age acceleration over the course of the study. Discussion/Significance of Impact: This work examines whether psychological factors and/or epigenetic markers may be used in patient stratification at initiation of treatment, enabling improved treatment selection, fewer years of obesity and decreased risk of comorbidities. This proposal also asks whether lifestyle interventions impact the aging process itself.