ABSTRACT IMPACT: The impact of this study is to encourage health professionals to screen for violent experiences as potential risk factors for CVD and adapt interventions from the non-abused in children as in adults. OBJECTIVES/GOALS: This study aims to assess the relationship between child sexual abuse and cardiovascular risk factors (CVDRF) that present in children. The objectives will provide the prevalence of CVDRF, their association with types of sexual victimization, and a score to assess the impact. METHODS/STUDY POPULATION: This study is a chart review, cross-sectional study. The Puerto Rico Health Justice Center (PRHJC) is a forensic, transdisciplinary, victim-centered, trauma-informed, and evidence-based service. The demographic variables collected are age, sex; the cardiovascular risk factors variables include a level of physical activity, tobacco exposure/alcohol, vital signs (blood pressure, BMI), lipid profile, and C-reactive protein. Sexual violence variables are the type of victimization (sexual assault, sexual molestation), the number of victimizations, and the relationship with the offender. RESULTS/ANTICIPATED RESULTS: A previous study, which examined types of evidence related to the prosecution of sexual violence cases, found that among female victims, 54% was a victim of sexual assault, and 59% had at least one health concern. The study’s hypothesis includes that older and female victims have a higher prevalence of cardiovascular disease risk factors. Also, children victims of sexual assault will have more cardiovascular risk factors than victims of sexual molestation. The age group, sex, number of victimizations, and relationship with the offender will also impact the relationship between the type of victimization and cardiovascular risk factors. DISCUSSION/SIGNIFICANCE OF FINDINGS: Early identification of child sexual abuse is needed to prevent long-term health impacts. The study’s results will be significant in developing clinical guidelines for health care providers to identify child sexual abuse as a predictor of cardiovascular risk factors and encourage victim advocates to identify cardiovascular risk factors.

ABSTRACT IMPACT: Specific recommendations will be suggested in this presentation as to how a health equity lens can be applied to implementation science frameworks. OBJECTIVES/GOALS: This systematic review consolidated literature on how implementation science (IS) frameworks (e.g., RE-AIM) have been used in cancer prevention services (e.g., screening, tobacco cessation programs) to reduce health disparities. METHODS/STUDY POPULATION: The systematic review was conducted in accordance with PRISMA and registered with PROSPERO. Searches were conducted in Ovid MEDLINE, PubMed, PsycINFO, CINAHL, and EMBASE between January-May 2020. Search strategies used the combinations of terms related to implementation science frameworks, cancer prevention and/or intervention, and all search algorithms were validated by a public health librarian. RESULTS/ANTICIPATED RESULTS: A total of 1,025 articles were screened and 84 were deemed eligible for full-text screening. After full-text screening, n=27 articles were included for data abstraction and synthesis. Of the 27 studies that used an implementation science framework, only one-third of studies (N=9, 33.3%) used an IS framework to address cancer-related health disparities. Of those nine studies, six of them used the Consolidated Framework for Implementation Research (CFIR) to guide, inform, and/or adapt the implementation of a cancer prevention intervention to target health disparities. However, the variability in how this framework was applied remains a challenge. DISCUSSION/SIGNIFICANCE OF FINDINGS: Recommendations for how various IS frameworks can be used to address cancer prevention disparities will be presented, such as, guiding principles on how to intentionally select domains within the CFIR that will capture input from key stakeholders in health disparities populations.

ABSTRACT IMPACT: Leveraging partnerships with faith-based institutions and community centers in at-risk NYC neighborhoods, the H2H Program breaks down barriers to engaging with the medical establishment and addresses the increasing burden of diabetes and CVD risk factors in the most vulnerable individuals. OBJECTIVES/GOALS: Screening for modifiable risk factors is critical for cardiovascular disease (CVD) risk reduction. Low-income, urban communities often encounter barriers to care. Community-academic outreach partnerships are vital in addressing such disparities and promoting health equity and culturally targeted interventions among high-risk populations. METHODS/STUDY POPULATION: In 2010, the Weill Cornell Clinical and Translational Science Center along with Weill Cornell Medicine (WCM) and Hunter-Bellevue School of Nursing (HBSON) launched Heart to Heart (H2H), a community outreach program partnering with faith-based centers to offer free health screenings and education to some of New York City’s (NYC) most vulnerable communities. Participants work with undergraduate, nursing, medical and dietician students to complete a demographics and health questionnaire followed by vital signs and point-of-care blood testing. Participants then receive personalized health education, nutrition and lifestyle counseling by student volunteers, precepted by WCM Primary Care and HBSON faculty. Participants are provided information on local free or low-cost clinics as necessary for follow-up. RESULTS/ANTICIPATED RESULTS: To date H2H held 125 events and 5,952 screenings. Mean age of the participants was 54.3 (SD 39.6) and 3,682 (63.1%) were female. 74.2% identified as non-white. 42.1% were uninsured. 32.3% reported annual income of less than $20k. 18.3% of participants reported not having seen a doctor in the past year. 40.7% reported preexisting hypertension, of which 74.5% were on medication and 78% with sub-optimal control. 15.7% had been previously diagnosed with diabetes, of which 75.8% were on medication and 41.4% with sub-optimal control (HbA1c <7). 37.7% had been diagnosed with dyslipidemia previously, of which 47.4% were on medication and 62.1% with sub-optimal control. Screenings revealed, 56.9% had undiagnosed hypertensive blood pressures, 4.7% had an elevated HbA1c >6.5, and 49.2% had dyslipidemia. DISCUSSION/SIGNIFICANCE OF FINDINGS: H2H screening revealed significant cardiovascular health disparities, many of which were poorly controlled or newly discovered. Cross-institutional academic partnerships can empower communities with knowledge of their health status and help facilitate access to medical care to further address health risk factors.

ABSTRACT IMPACT: Study findings can guide improvements of the Summer Food Service Program to maximize the program’s desired effects on child summer nutrition and related health outcomes. OBJECTIVES/GOALS: The Summer Food Service Program (SFSP) addresses food insecurity during summer months. Project specific aims are to: 1. Describe characteristics of children participating in the SFSP. 2. Determine the nutritional quality of the SFSP foods. 3. Evaluate changes in children’s food insecurity, diet quality, and body mass index by SFSP participation. METHODS/STUDY POPULATION: A single group, prospective, staggered cohort design will be used for the proposed study. Two cohorts of 30 (N=60) elementary students and their parents will be recruited during the 2021-22 and 2022-23 school year. Each participant will complete a measurement session at three time-points: Baseline (spring), Post-Program (program end), and Follow-Up (following spring). Parents will complete an online survey about household food insecurity and family socio-demographic characteristics. Children will complete three 24-hour dietary recall interviews, and their heights, weight and percent body fat will be measured. The menus of at least ten SFSP sites will be analyzed to determine the nutritional adequacy of the site menus by using the Healthy Eating Index-2015. RESULTS/ANTICIPATED RESULTS: Study hypotheses are as followed: Aim 1. Not all of the children participating in the SFSP are from food-insecure or low-income households. Aim 2. Meals served at the SFSP will be higher in sugar and fat and lower in fruits and vegetables compared to recommendations in the 2015-2020 Dietary Guidelines for Americans. Additionally, the Healthy Eating Index-2015 score of the SFSP menus will be lower than that of the National School Lunch Program menus. Aim 3. Consistent SFSP participation will have a positive effect on reducing food insecurity, but not on increasing diet quality and reducing body mass index and percent body fat in children. DISCUSSION/SIGNIFICANCE OF FINDINGS: Program user information will determine if the program is reaching the target audience. Program managers will utilize menu analysis results to improve their menu nutritional quality. Changes in food insecurity, diet quality and anthropometric measures will inform whether the program needs to be improved to prevent any untoward excess weight gain.

ABSTRACT IMPACT: Our research focuses on determining rural-urban disparities in chronic obstructive pulmonary disease (COPD) management to improve COPD health outcomes in rural areas. OBJECTIVES/GOALS: Several methods exist to distinguish rural from urban areas, but it is not clear which method relates most directly to rural-urban health care disparities. To address this, we compared different measures of rurality to measures of chronic obstructive pulmonary disease (COPD) processes of care among a national sample of veterans. METHODS/STUDY POPULATION: Retrospective analysis of patients with COPD (2016-2019 by ICD-10 codes) using national Veterans Affairs (VA) data. We assessed rurality by: 1) patient’s residential address, 2) assigned primary care clinic address, and 3) drive time from the patient’s residence to closest primary care clinic. Rurality designations of the residential address and primary care clinic address into urban, rural, and highly rural areas are based on the Rural Urban Commuting Area (RUCA) codes. The dependent variables were binary outcomes of: 1) documentation of a pulmonary clinic encounter and 2) evidence of spirometry to confirm the diagnosis of COPD. RESULTS/ANTICIPATED RESULTS: Of 6,765,951 veterans, 1,157,002 (17%) had COPD (Table 1). Although approximately 40% of patients with COPD reside in addresses that are rural and highly rural, a large majority are assigned to primary care clinics in urban areas (82.8%) and reside within 30 minutes to the closest primary care clinic (76.7%) (Table 2). Compared to defining rurality based on patient’s residential address or drive time to closest primary care, defining rurality based on the assigned primary care clinic address was associated with a larger disparity in rates of pulmonary encounter. In contrast, the drive time from the patient’s residence to the closest primary care was the strongest predictor of receipt of spirometry (Figure 1 and Table 3). DISCUSSION/SIGNIFICANCE OF FINDINGS: Estimates of the severity of rural-urban disparities varied based on the definition of rurality used. For two process measures, definitions of rurality based on where the patient received primary care generated more evidence of disparities than definitions based solely on the patient’s residential address.

ABSTRACT IMPACT: Disparities are multifactorial in etiology we seek to elucidate the effects of social determinants of health such as race on the outcomes of autologous flap reconstruction. OBJECTIVES/GOALS: Immediate breast reconstruction has increased in recent years yet, racial and socioeconomic disparities in the receipt of postmastectomy breast reconstruction persist. We review the usage of autologous flaps for immediate breast reconstruction in a single institution with a diverse population to determine the effect of radiation on flap survival. METHODS/STUDY POPULATION: The database of a Southeastern tertiary referral center was queried for patients who received autologus flaps for immediate reconstruction following mastectomy. Patients were stratified based on whether they received no radiation (TRAM), neoadjuvant radiation (TRAM + Pre-XRT), or post-reconstruction radiation (TRAM + PMRT). So far, we have identified 91 patients (157 breasts) meeting inclusion criteria from 2006 to 2017. Patient demographics and outcomes were compared based on radiation status. The primary outcome (reconstructive success) was defined as breast reconstruction without flap loss. Comorbidities, socioeconomic status, and method of reconstruction were collected. Statistical analysis included t-tests, chi-square tests and logistic regression were appropriate using R. RESULTS/ANTICIPATED RESULTS: At the moment, we focus on outcomes of transverse rectus abdominus flaps and are adding information on 4 other flap-based methods. There were 68 in the solely TRAM group, 33 in TRAM+Pre-XRT and 56 in TRAM+PMRT with equivalent demographics between all groups for Age, Race and BMI (Table 1). In terms of race most patients self-identified as White (68%), followed by Black (24%) and Other (8%), p=0.172. There was a statistically significant difference in the incidence of tobacco use with the type of radiation used (p=0.007) with the PTRAM+ PMRT group having the highest percentage. When analyzing major and minor complications based on radiation received or reconstructive success there was no significant difference regardless of radiation treatment with the group overall achieving a 97.4% success rate (p=0.229). DISCUSSION/SIGNIFICANCE OF FINDINGS: Despite the known racial disparities in healthcare and the deleterious effects of radiation therapy on wound healing, there was no significant difference found in the incidence of major or minor complications in patients receiving neoadjuvant or post-reconstruction radiation therapy regardless of patient demographics.

ABSTRACT IMPACT: Regional health issues can be best addressed at the population-level and input from the communities is vital for prioritization of health issues. OBJECTIVES/GOALS: The Great Plains IDeA-CTR (GP IDeA-CTR) was developed to increase clinical and translational research (CTR) that can address regional health priorities. Here we describe a collaborative process used to identify regional health priorities using existing surveillance data and community input. METHODS/STUDY POPULATION: We used a participatory approach that included a partnership between the GP IDeA CTR Community-Engagement and Biostatistics, Epidemiology, and Research Design Cores to ensure priorities were data driven and also aligned with community-based perceptions of need. First, aggregated surveillance data across Nebraska, North Dakota, and South Dakota was presented to the GP IDeA CTR Community Advisory Board (CAB). Second, CAB members formed small groups and considered the information and generated priority health area lists. Third, small group lists were considered and discussed by the full CAB to finalize priority areas. Finally, the CAB reviewed the priorities annually thereafter. RESULTS/ANTICIPATED RESULTS: We identified priority areas for CTR that included (1) behavioral health, (2) injury prevention, (3) obesity, (4) technology to improve health care access, (5) connecting clinical/community services, and (5) addressing health disparities. These priorities align with population-based surveillance data that show lack of mental health care access, high prevalence of obesity, higher incidence of accidents, and existing racial, ethnic, and geographic health disparities. The CAB highlighted that research was also needed to improve how people can access the health innovations developed through CTR to address the other priority health issues with a goal to have an impact on population health. DISCUSSION/SIGNIFICANCE OF FINDINGS: By integrating data- and community-driven approaches we identified regional health priority areas that if addressed, can have significant impact in the GP IDeA CTR region. The priorities are listed on all GP IDeA-CTR funding announcements to encourage CTR in these areas.

ABSTRACT IMPACT: Improved understanding of the relationship between level of response to alcohol and body weight in the context of other contributing factors will help inform prevention and intervention efforts regarding obesity. OBJECTIVES/GOALS: We evaluated the association between level of response to alcohol and weight status across the spectrum of alcohol misuse. We hypothesized that lower level of response to alcohol would be associated with heavier weight, after controlling for obesity risk factors like food addiction, impulsivity, and low socioeconomic status. METHODS/STUDY POPULATION: Adult participants (N=587) enrolled in NIAAA’s natural history study completed Self-Rating of the Effects of Alcohol (SRE), a retrospective measure of level of response to alcohol, along with Lifetime Drinking History (LDH); Yale Food Addiction (FA) Scale; Barratt Impulsiveness Scale (BIS); Delayed Discounting Task (DDT). Structured Clinical Interviews for DSM disorders were conducted to identify individuals with current alcohol use disorder (AUD). Body mass index (BMI), computed from height and weight measured during the study, and used to stratify participants into 3 groups: normal weight (N=222), overweight (N=219), or obese (N=146). RESULTS/ANTICIPATED RESULTS: SRE scores during heaviest drinking period were lowest in the heavier weight group, after accounting for FA, impulsivity, alcohol-related, and demographic variables (ê•2=238.5, p=0.002, Cox and Snell Pseudo R2=0.43). Compared to the obese group, normal weight and overweight groups had fewer FA symptoms and higher BIS cognitive complexity (p values<0.01) but similar rates of current AUD. Relative to the obese group, the normal weight group was more likely to be White, and to have lower household incomes but more education, more years of heavy drinking (LDH), and steeper delayed discounting, p values ≤0.03. The overweight group had a higher proportion of males than did the obese group, p<0.001. DISCUSSION/SIGNIFICANCE OF FINDINGS: Lower level of response during heaviest drinking period was significantly associated with current weight status, suggesting a relationship between alcohol sensitivity and BMI. Future work will explore pharmacokinetic-pharmacodynamic and additional risk factors underlying this relationship.

ABSTRACT IMPACT: Understanding the mechanism underlying the DASH diet may shed light on the physiologic process by which nutrition influences blood pressure and potentially lead the way to new therapeutics that target ion channels. OBJECTIVES/GOALS: Hypertension is a disease of the westernized world, as it stems from lifestyle habits. Lower salt consumption reduces blood pressure, yet DASH diet is much more effective, lowering blood pressure as efficiently as one anti-hypertensive drug. The precise mechanism through which DASH achieves its effect is not understood, and this is the project goal. METHODS/STUDY POPULATION: We hypothesize that exposing hypertensive volunteers to a high potassium and low sodium DASH diet will change the composition of renal ion channel in an aldosterone-dependent manner, leading to excretion of both sodium and potassium and a reduction in blood pressure. To assess how the nutritional change changes ion channel composition in the kidneys’ epithelium in aldosterone-induced manner, we will monitor urine exosomes, which contain epithelial cell membranes. We designed an in-hospital nutritional studies recruiting 20 volunteers. Patients will consume carefully designed menu, and measurements will be collected daily: blood pressure, biologic samples including blood and urine electrolytes, aldosterone, and urine for exosomes. RESULTS/ANTICIPATED RESULTS: We have collected data from 5 research volunteers so far.following exposure to the high potassium diet, Aldosterone blood levels increased while blood level of both potassium and sodium was maintained within normal limits. Urinary ratio of electrolytes, sodium:potassium was reversed 5-7 days following nutritional change from 6 to 1. Both manual and automated 24-hour blood pressure measurements confirmed blood pressure reduction following nutritional change. The following illustrates the impact the diet had on a participant’s 24-hour ambulatory blood pressure. Daily mean blood pressure was reduced from 120/76 mmHG to 112/68, mean awake blood pressure was reduced from 125/80 mmHG to 117/72 mmHG, and mean sleep blood pressure was reduced from 112/69 to 103/60 mmHG DISCUSSION/SIGNIFICANCE OF FINDINGS: Understanding the mechanism underlying the DASH diet may shed light on the physiologic process by which nutrition influences blood pressure and potentially lead the way to new therapeutics that target ion channels. By introducing our participants to a healthier lifestyle, they could maintain lower blood pressure without requiring medication.

ABSTRACT IMPACT: Currently, there are no medications to treat metabolic syndrome and our research sheds light on a potential therapeutic that could prove beneficial for this disease that affects one-third of the US population. OBJECTIVES/GOALS: Our goal was to determine the role of the GI tract in MetS, specifically how approved GI-directed medications affect metabolic parameters. Thus, we assessed the effects of mesalamine, a common therapeutic utilized to treat mild to moderate UC, on metabolic parameters in comorbid UC and MetS patients METHODS/STUDY POPULATION: This was a retrospective study with data extracted from Cerner’s HealthFacts database across the United States (US). Inclusion criteria included adult patients (≥18 years old) with a diagnosis of UC and at least 3 of the 5 metabolic risk factors which included i) dyslipidemia, ii) low HDL, iii) hyperglycemia, iv) hypertension, and v) increased abdominal obesity as determined by elevated BMI. A total of 6197 patients across the US between the years of 2007 and 2017 were included. We pulled patients who had a mesalamine prescription within +/- 7 days of an encounter in which they were diagnosed with UC (index date) and the closest values to 3 and 12 months after the index date. Mean age for patients was 53.8 ±19.9, with predominance of female sex (52.9%) and white race (78.0%). RESULTS/ANTICIPATED RESULTS: There was an observed reduction in BMI, fasting glucose, and increase in HDL levels post start of mesalamine treatment along with a decrease in inflammatory markers (ESR and CRP) (p<0.001). DISCUSSION/SIGNIFICANCE OF FINDINGS: The GI tract contributes to numerous disorders associated with metabolic dysfunction. Our retrospective analysis revealed mesalamine treatment in comorbid UC and MetS patients improved metabolic parameters, providing evidence that targeting the GI tract in these individuals potentially improves dysregulated metabolic processes.

ABSTRACT IMPACT: A better understanding of the spectrum of problematic opioid use will lead to more targeted treatments. OBJECTIVES/GOALS: It is unclear how to approach treatment of individuals with problematic opioid use who do not clearly meet criteria for opioid use disorder (OUD). We aim to characterize clinical, demographic, and medication use at time of identification of problematic opioid use across the spectrum as well as identify predictors of poor outcomes. METHODS/STUDY POPULATION: A national sample of Veterans coded as having opioid abuse or dependence were previously categorized as (1) high likelihood of OUD, (2) limited aberrant opioid use, and (3) prescribed opioid use with no evidence of aberrant use based on chart review. We will describe how individuals in these three categories differ demographically and clinically. We will then use a trained binary logistic regression model to predict whether individuals with limited aberrant opioid use more closely resemble category (1) or (3). Cox proportional hazards models will be used to predict all-cause mortality, suicide-related mortality, opioid-overdose related mortality, and hospitalization over a three-year period using the three categories as predictors and adjusting for relevant covariates. RESULTS/ANTICIPATED RESULTS: We anticipate that Veterans with a high likelihood of OUD will be more likely to experience homelessness and have more psychiatric comorbidities (especially PTSD). We hypothesize that Veterans with prescribed opioid use and no evidence of misuse will be significantly older, more likely to have disability, medical comorbidities (ie., chronic pain, cancer), more prescriptions for non-opioid analgesics, and be prescribed higher doses of opioids. Using a trained binary logistic regression model, we predict that Veterans with limited aberrant opioid use will more closely resemble Veterans with a high likelihood of OUD. We expect that all categories of problematic opioid use will have a high risk of mortality, with a high likelihood of OUD associated with the greatest risk of premature death. DISCUSSION/SIGNIFICANCE OF FINDINGS: Identifying and better characterizing individuals with limited aberrant opioid use may be an important opportunity to intervene prior to development of severe OUD. Future research will focus on targeting interventions to this population, which may have specific needs that are separate from classic OUD or simple pain-related opioid dependence.

ABSTRACT IMPACT: Our data identify a novel candidate for combination strategy in melanoma treatment, and can inform clinicians in their decision-making process regarding therapeutic intervention for melanoma patients. OBJECTIVES/GOALS: Soluble adenylyl cyclase (sAC) is a novel source of cyclic AMP (cAMP). In melanoma, nuclear sAC localization has an established diagnostic utility and we newly found that nuclear sAC functions as a tumor suppressor by inhibiting Hippo pathway, which affects treatment response. Here, we examine the effect of nuclear sAC on melanoma treatment response. METHODS/STUDY POPULATION: We developed a doxycycline inducible system for increasing sAC activity only in the nucleus. We assessed whether nuclear sAC activity affects treatment response, using BRAFV600 human melanoma cell lines. Using a clonogenic assay, we examined how nuclear sAC activity affects growth inhibition in the presence of a BRAF inhibitor, vemurafenib. Our findings will be confirmed in vivo using tumor xenografts. After tumor formation in NSG mice, mice will be randomized to be fed normal or doxycycline chow for nuclear sAC induction, then subdivided to receive vehicle or vemurafenib to examine the effect of nuclear sAC activity on treatment response in vivo. We will also compare melanoma biopsies collected before and after treatment with BRAF inhibitors to assess how nuclear sAC staining affects tumor morphology in vivo. RESULTS/ANTICIPATED RESULTS: So far, nuclear sAC activity has rendered SkMel178 and M263 cell lines more susceptible to vemurafenib. Cell viability was inversely correlated both with vemurafenib and with doxycycline concentration. Cell viability after vemurafenib treatment was dramatically reduced when nuclear sAC was activated. It appears that nuclear sAC enhances the sensitivity of BRAF mutant melanomas to vemurafenib in vitro. We anticipate that xenografts of these cells in mice will be more susceptible to vemurafenib when nuclear sAC is activated. We also anticipate that positive nuclear sAC staining will correlate with a favorable response to therapy. DISCUSSION/SIGNIFICANCE OF FINDINGS: Targeted therapy with BRAF inhibitors is used in late-stage melanomas, but its use is limited as patients invariably acquire resistance. Here, we identified nuclear sAC activation as a novel candidate for combination strategy. Our data will also inform clinicians how best to integrate this biomarker into their decision-making regarding therapy.

ABSTRACT IMPACT: Findings from this study will better characterize the role of hearing loss in falls risk among patients with vestibulopathy and identify groups that are most at risk for falls. OBJECTIVES/GOALS: Vestibular dysfunction and hearing loss are independent risk factors for experiencing falls. The purpose of this study is to determine the extent, if any, to which hearing loss contributes to falls in patients with concomitant vestibular dysfunction presenting to a specialty vestibular clinic. METHODS/STUDY POPULATION: A retrospective chart review of patients ≥18 years who underwent vestibular evaluation at our institution from June 1, 2015 to October 7, 2020 will be conducted. Patients who underwent vestibular evaluation also received audiologic evaluation and degree of hearing loss will be characterized by the 4-frequency pure-tone average (0.5, 1, 2, and 4 kHz) of the better hearing ear. Falls status will be determined by the response to the following question administered at clinic-check in, ‘Have you fallen in the last 90 days?’ Demographics, comorbidities, and falls-associated medications will also be collected. RESULTS/ANTICIPATED RESULTS: A total of 3,265 unique patients who underwent vestibular evaluation in the study time period were identified. Patients will be categorized into discrete groups (benign paroxysmal positional vertigo, unilateral hypofunction, bilateral hypofunction, central dysfunction, and normal) based on laboratory results. Regression models will be developed to evaluate the potential association between degree of hearing loss and falls in patients with different types of vestibular dysfunction, while adjusting for demographics, comorbidities, and falls-associated medications. DISCUSSION/SIGNIFICANCE OF FINDINGS: Findings from this study will better characterize the role of hearing loss in falls risk among patients with vestibulopathy and identify groups that are most at risk for falls. This study may potentially indicate the importance of hearing evaluation in the work-up of patients with vestibulopathy.

ABSTRACT IMPACT: This study aims to advance the understanding of the biological mechanisms associated with feeding disturbances in infants born to diabetic mothers through non-invasive salivary gene expression analyses and body composition measurements at birth. OBJECTIVES/GOALS: To determine if non-invasive salivary gene expression analyses and body composition measurements at birth could elucidate biological mechanisms associated with aberrant feeding behaviors and disrupted metabolic profiles commonly seen in infants born to diabetic mothers. METHODS/STUDY POPULATION: This prospective cohort study enrolls subjects born at ≥35 weeks’ gestation without a history of intrauterine growth restriction or major congenital anomalies. The diabetic cohort is defined as infants born to mothers with gestational diabetes or type 2 diabetes. The primary outcome is salivary expression of the hunger signaling genes, AMPK and NPY2R. Secondary outcomes include infant body composition measurements, obtained by skinfold measurement and/or air displacement plethysmography, and salivary expression of the adipokines, leptin, ghrelin, and adiponectin. Multiple logistic regression will be used to determine which factors are associated with AMPK and NPY2R expression. RESULTS/ANTICIPATED RESULTS: We propose that poor oral intake seen in infants of diabetic mothers may be due to alterations in the expression of hunger signaling genes (decreased expression of AMPK; increased expression of NPY2R) resulting in a diminished feeding drive in these large for gestational age infants. In addition, infant adiposity and the expression of genes involved in the adipoinsular axis will be inversely proportional to feeding volume intake. Namely, increased neonatal fat mass will be associated with increased expression of leptin and decreased expression of ghrelin and adiponectin. DISCUSSION/SIGNIFICANCE OF FINDINGS: Infants of diabetic mothers are at higher risk of poor oral feeding in the newborn period. This study aims to elucidate the link between neonatal body composition, adipoinsular axis, and hunger signaling to explain this unique feeding phenotype.

ABSTRACT IMPACT: This study will help determine whether ecological momentary assessment is feasible in assessing changes in negative affect and the occurrence of non-suicidal self-injury (NSSI) in military Veterans with post-traumatic stress disorder; if so it will allow for further examination of correlates of NSSI which will inform treatment efforts. OBJECTIVES/GOALS: Given the advantages of ecological momentary assessment (EMA), and the lack of research on non-suicidal self-injury (NSSI) in military populations, the goal of the current pilot study is to determine the feasibility of using EMA to assess daily changes in post-traumatic stress disorder (PTSD) symptoms, negative affect and NSSI in veterans with PTSD. METHODS/STUDY POPULATION: Twenty military veterans with post-traumatic stress disorder (PTSD) who have engaged in non-suicidal self-injury (NSSI) in the previous 12 months will be recruited. Participants will complete assessments 4 times per day for 28 days at randomly scheduled times. Assessments will measure PTSD symptoms, negative emotions, and NSSI urges and behaviors. At the conclusion of the 28-day study period, participants will complete measures that ask about their experiences in the study, (e.g., the acceptability of the daily surveys and the accessibility of the web-based surveys). Feasibility will be determined with regard to the success of recruiting eligible participants and compliance with daily survey completion. Variability in PTSD symptoms, negative affect, and NSSI urges and behaviors also will be determined. RESULTS/ANTICIPATED RESULTS: It is anticipated that this study will successfully recruit 20 veterans with PTSD with a history of engaging in NSSI within the previous 12 months. It is also anticipated that daily survey completion rates will be approximately 90% based on previous research using EMA with veterans with PTSD and that participants will indicate satisfaction with the procedures of the study. It is anticipated that participants will demonstrate variability in PTSD symptoms, indicated by changes in the number of symptoms endorsed and the intensity of those symptoms experienced. Finally, it is anticipated that participants will demonstrate variability in negative emotions (fear, hostility, guilt, and sadness).

DISCUSSION/SIGNIFICANCE OF FINDINGS: Findings from this study will support the use of EMA in a subsequent large-scale investigation examining time-varying symptoms of PTSD and negative affect as antecedents to NSSI. Information from this large-scale study will in turn be used to inform treatments that may to decrease NSSI in veterans by targeting specific symptoms and negative emotions.

ABSTRACT IMPACT: We present a minimally-invasive approach to monitoring heavy metal exposures in geographically disperse populations; this framework may encourage and facilitate greater participation in a broad range of related clinical studies that require biosampling. OBJECTIVES/GOALS: We hypothesize that microneedle array (MA) extraction of interstitial fluid (ISF) will enable minimally-invasive quantitation of heavy metal (HM) exposure. We establish analytical parameters for ICP-MS analysis of HMs in ISF, quantify baseline HM content in ISF vs other fluids, and characterize a mixed HM exposure model. METHODS/STUDY POPULATION: Recent advances in ISF extraction and analysis suggest a minimally-invasive to monitor HM exposure longitudinally in both urban and dispersed communities. ISF can be collected with MAs and is a rich source of disease and exposure biomarkers. To refine analytical methods, Human subjects with no underlying skin disease were recruited into the IRB-approved study. Each subject had blood and urine collected. ISF was also collected using 3D-printed MA-holders. The fluids were analyzed, using ICP-MS, to quantify the levels of uranium (U), cadmium (Cd), vanadium (V), and arsenic (As). Additionally, we analyzed 2,770 subjects from the public NHANES dataset from 2018-2019. Python and Scikit-learn were used to analyze the demographics, survey responses, and metal concentrations for these individuals. RESULTS/ANTICIPATED RESULTS: While several studies have described the surface water and sediment content of toxic metals, determining biological loads remains challenging due to the need to collect blood or urine from a dispersed rural population over time. Our preliminary results suggest similar HM concentrations in ISF, compared with blood in a small unexposed population. Analysis of subjects from the NHANES public datasets suggest similar baseline blood HM concentrations in diverse subject populations with some differences in Cd depending on smoking and e-cigarette usage. Correlation maps also suggest possible synergy between different metals with cobalt and chromium showing the highest correlation. The initial results from this study have been applied to develop a mixed HM exposure model in rats for further translational testing. DISCUSSION/SIGNIFICANCE OF FINDINGS: We present a minimally-invasive HM monitoring approach. Exposure to multiple HMs is suspected to have additive or synergistic harmful health effects. We ultimately envision a wearable microneedle patch that could be mailed to individuals or distributed through community centers, worn for a few hours, and returned to a central laboratory.

ABSTRACT IMPACT: Implementation of proteomics as a diagnostic tool for Nontuberculous mycobacteria (NTM) infection can provide a more accurate, efficient and cost-effective means for effectively diagnosing disease and enacting timely management decisions which can revolutionize patient care. OBJECTIVES/GOALS: Proteomic analysis is a proven diagnostic modality enabling rapid identification of microorganisms. We sought to apply proteomics to detect proteins unique to the most clinically relevant NTM. We then determined whether these unique proteomes could be used to successfully identify NTM species from in vitro cocktail preparations. METHODS/STUDY POPULATION: NTM reference strains for M. avium, m. intracellulare, m.chimaera, m. abscessus abscessus, m. abscessus massiliense and m. abscessus boletti were cultured in vitro and subjected to proteomic analysis using Liquid Chromatography tandem-Mass Spectrometry (LCMS). Tandem Mass Tag (TMT) data acquisition utilized an MS3 approach for data collection using Proteome Discoverer 2.4.

A comparative analysis of the proteome of each of these six species was performed quantitatively using LCMS. The process was repeated for three technical replicates and analyzed using the SEQUEST algorithm. Only high scoring peptides were considered utilizing a false discovery rate (FDR) of 1%. Once species-specific proteins were identified, we validated detection in individual and mixed samples of the six reference strains. RESULTS/ANTICIPATED RESULTS: The proteomic profiling of the six NTM reference strains successfully demonstrated proteins unique to each of the MAC species and MABC subspecies. Proteomic MAC species analysis produced between 327 to 2,540 unique peptides for each of the 3 species. MABC proteomic analysis identified between 17-74 unique peptides for each of the 3 subspecies. Fifteen different mixed preparations of MAC and MABC were then subjected to LCMS analysis and compared against the proteome profiles already curated for the six strains. We accurately identified at least one NTM in the majority of the samples (10/15). In three samples (3/15), the NTM was not correctly identified; in two of the samples (2/15) we were unable to determine the identity of NTM within the preparation. Further database curation will be performed to hone these results. DISCUSSION/SIGNIFICANCE OF FINDINGS: Proteomic analysis of in vitro reference strains successfully demonstrated protein fingerprints specific to six common disease-causing strains of NTM. Such findings can be used to evaluate clinical samples enabling more efficient diagnostic specificity. Further research will focus on identification of NTM in sputum samples of infected patients.

ABSTRACT IMPACT: Glucocorticoid steroids are commonly used despite known dose-dependent cardiovascular toxicity, yet little is known about a) how patients with other cardiovascular risk factors use glucocorticoids, and b) how risks of glucocorticoid treatment might vary depending on a patient’s baseline cardiovascular risk. OBJECTIVES/GOALS: Up to one-third of RA patients use long-term glucocorticoids (GCs) despite a known, dose-dependent association with increased risk of major adverse cardiovascular events (MACE). We aim to evaluate patterns of GC use among RA patients with other MACE risk factors (i.e. diabetes, smoking), and examine how GC use may potentiate these risk factors. METHODS/STUDY POPULATION: We used claims data from Veterans Health Administration to identify 6,090 RA patients with ≥1 rheumatology clinic visit during 2013-2017. We used logistic regression to evaluate associations between incident MACE between 2013-2018, recent long-term GC use, and 5 MACE risk factors: hypertension, diabetes, hyperlipidemia, smoking, and prior MACE. We included two-way interaction terms between GC use and each risk factor. We used a claims-based algorithm to define MACE as any of acute MI, ischemic stroke, TIA, sudden death, or coronary revascularization, between index date and 12/31/2018. We defined index date as first rheumatology visit after meeting RA diagnostic criteria, and recent long-term GC use as ≥90 days’ supply dispensed over 2 years prior to index date. RESULTS/ANTICIPATED RESULTS: Among 2,884 eligible patients,1,553 (54%) had MACE risk factors, and 97 (3%) had prior MACE (Table 1). Overall, 16% of patients recently used long-term GC, compared to 17% of patients with MACE risk factors, and 22% of patients with prior MACE. Incident MACE occurred in 308 (11%) patients, 24% of whom had recent long-term GC use. Recent long-term GC use was independently associated with increased incident MACE (Table 2). While no interaction term was statistically significant overall, differences in odds of incident MACE were seen across levels of recent GC use for several risk factors, particularly diabetes (OR 2.10, 95% CI [0.93-4.77]), tobacco use (OR 2.88, 95% CI [1.16-7.14]) and prior MACE (OR 2.41, 95% CI [0.73-7.95]). DISCUSSION/SIGNIFICANCE OF FINDINGS: Long-term GC use is common among RA patients with MACE risk factors. In this cohort, 25% of patients with incident MACE had recently used long-term GC. Long-term GC use may potentiate effects of comorbidities like diabetes and smoking, disproportionately increasing MACE risk in certain patients.

ABSTRACT IMPACT: Advanced cardiac magnetic resonance imaging techniques can help to protect cancer patients from cardiotoxicity from immunotherapy with a more sensitive assessment of cardiac function with strain imaging for detection of abnormal cardiac function in the setting of normal left ventricular ejection fraction. OBJECTIVES/GOALS: Immune checkpoint inhibitors (ICI) are associated with fatal cardiotoxicity. Cardiac magnetic resonance (CMR) imaging can assess ICI-associated cardiotoxicity, but the utility of CMR strain imaging is unknown. We present a study of patients with ICI-associated cardiotoxicity evaluated with fast strain-encoded (fast-SENC) CMR. METHODS/STUDY POPULATION: This prospective study was approved by the institutional IRB and informed consent was obtained from 15 patients (5 patients with ICI-associated cardiotoxicity, 10 controls patients) between August 2018 and January 2020. All patients with ICI-associated cardiotoxicity had abnormal troponin values and evidence of cardiotoxicity on T2-weighted and/or delayed enhancement CMR images. All patients underwent standard CMR assessment with steady state free precession cine images, T2-weighted imaging, and delayed gadolinium enhancement imaging. Additionally, free-breathing SENC images were obtained and then processed by a team of blinded cardiovascular imaging specialists using Myostrain software (Morrisville, USA). RESULTS/ANTICIPATED RESULTS: Left ventricular ejection fraction (LVEF) was normal in both groups (ï,³53%). Global longitudinal LV strain was significantly depressed in the ICI cardiotoxicity group versus controls (-12.8 ±3.2% vs. -16.6 ±1.9%, p=0.028). The average global circumferential LV strain was mildly abnormal (defined as strain > -17) in the ICI cardiotoxicity group and trended towards a higher value compared with controls (-16.0 ±2.6% vs -17.8 ±1.7%, p=0.103). The average number of dysfunctional segments (defined as strain > -10) was significantly higher in the ICI cardiotoxicity group (6.8 ±4.2 vs. 1.0 ±1.7, p=0.017). The proportion of abnormal myocardium was higher in the ICI cardiotoxicity group (66 ±21% vs. 45 ±18%, p=0.050), as well as the proportion of myocardium found to be dysfunctional (26 ±22% vs. 3.0 ±6.0%, p=0.041). DISCUSSION/SIGNIFICANCE OF FINDINGS: Despite having preserved LVEF, patients who met criteria for ICI-associated cardiotoxicity had both global and regional abnormal LV strain. Fast-SENC imaging may provide a sensitive tool for detection of early cardiotoxicity in this population. This study is limited by its small cohort and a larger prospective study would be of value.

ABSTRACT IMPACT: Our research would be the first therapeutic to both prevent and treat osteoarthritis - helping 27 millions U.S. citizens alone immediately. OBJECTIVES/GOALS: Our objective is to conjugate hyaluronic acid binding peptides (HABP) to anionic hollow nanoparticle (hNP), and allowing the HABP-hNP complex to penetrate into osteoarthritic cartilage, bind to exposed HA, prevent further degradation, and restore the compressive strength of articular cartilage. METHODS/STUDY POPULATION: N-isopropyl acrylamide, 2-acrylamindo-2-methyl-1-propanesulfonic acid, N,N’-bis(acryoyl)cystamine, and Acrylic Acid, in fluorescent batches rhodamine b isothiocyanate (RBITC), were polymerized via precipitation reaction. HA binding peptide, GAHWQFNALTVRGSG-Hydrazide (GAH-Hyd), was covalently bonded to the hNP using DMTMM chemistry. The reaction was halted by diluting the solution 10:1 with milliQ water and purified using tangential flow filtration. The dynamic viscosity of the six treatments were analyzed in a 70 kDa HA. Using a rheometer (Discovery HR-3) with a 20 mm parallel plate geometry, TA Instruments, New Castle, DE), a frequency sweep (0.01 -1000 Hz, 2.512 Pa) was conducted to measure the storage modulus of each solution. RESULTS/ANTICIPATED RESULTS: GAH-Hyd was successfully conjugated to the surface of the hNP and zeta-potential shows a significant increase in surface charge from -21.41 mV for unconjugated hNP to -8.94 mV for 65 GAH conjugated hNP, confirming conjugation. The hNPs need 65 ±10 GAH per nanoparticle to significantly bind to HA, shown by increasing the dynamic viscosity of the solution. The minimum concentration of 65 GAH-hNP required to significantly bind to HA is 313 µM. These data from our study display the ability to functionalized the surface of polymeric hNPs with site specific peptides and their ability to bind to diseased tissue. We expect the GAH-hNP system will restore the compressive strength of OA cartilage and prevent further HA degradation in ex vivo aggrecan depleted cartilage plugs. DISCUSSION/SIGNIFICANCE OF FINDINGS: Binding to exposed HA within the ECM of cartilage protects the HA from further degradation, halting the progression of OA. 65 GAH-hNP binds to HA at a 313 µM. Our system can be translated and used to treat a multitude of conditions by conjugating tissue specific peptides to the surface of our hNPs and delivery site specific therapeutics to diseases tissue.