ABSTRACT IMPACT: Through this research, I will transform the standard of care for infants with single ventricle physiology by incorporating the Capute Scales and General Movement Assessment into day-to-day clinical care for these infants, leading to early detection of neurodevelopmental disabilities and access to proven therapies. OBJECTIVES/GOALS: Our objective was to establish a new protocol to detect and quantify developmental delays in multiple domains in infants with single ventricle physiology, a type of congenital heart disease. This population is at high risk for neurodevelopmental disabilities. METHODS/STUDY POPULATION: We implemented a novel protocol using the Capute Scales and General Movement Assessment to evaluate early language, cognitive, and motor development in infants with single ventricle physiology. The infants were evaluated between 1-5 months of age in the cardiac neurodevelopmental program. We defined our primary outcomes as (1) language and (2) cognitive developmental quotients as per the Capute Scales and (3) results of the General Movement Assessment. We hypothesized that infants with single ventricle physiology would have typical language and cognitive development and normal General Movement Assessment results at their initial evaluation. RESULTS/ANTICIPATED RESULTS: We recruited ten infants with single ventricle physiology. All ten infants had typical language development, and nine of the ten had typical cognitive development, as measured by the Capute Scales. All of the infants had gross motor delay. Due to medical instability, we only evaluated four infants with the General Movement Assessment. All four of the infants had a normal result, suggesting that their central nervous system motor pathways were maturing appropriately. In future studies, we will track the neurodevelopmental outcomes of each participant as they mature. We expect to see a decrease in expressive language development and preserved receptive language and cognitive development. DISCUSSION/SIGNIFICANCE OF FINDINGS: The combination of General Movement Assessment and Capute Scales in the evaluation of infants with single ventricle physiology will provide early identification and intervention for these high-risk children, allowing access to proven treatments and therapies.

ABSTRACT IMPACT: This study evaluates the long term effects of pharmacologic weaning therapy for opiate exposed infants. OBJECTIVES/GOALS: Infants born to chronic opioid users often suffer from neonatal abstinence syndrome (NAS), a condition characterized by tremors, diarrhea, hyperirritability and an inconsolable high-pitched cry. Symptoms are treated with pharmacologic weaning therapy, but long-term effects of this treatment have not been established. METHODS/STUDY POPULATION: A sample of infants born between 2011-2017 was obtained from a large metropolitan hospital system. All infants who were exposed to opioids and received a Finnegan score were included in the sample (N=1,807). The analysis utilizes three dependent variables to measure developmental delay: motor delay, language delay or any delay, which includes general/non-specific delay in addition to motor and language delay. The treatment is defined as receipt of pharmacologic therapy with methadone or morphine. Maximum Finnegan score was also included as a continuous measure of the extent of the infant’s withdrawal symptoms. Linear models were utilized to determine a relationship between pharmacologic therapy and developmental delay with Maximum Finnegan score as an interaction term. RESULTS/ANTICIPATED RESULTS: In the linear models examining the main effects of weaning therapy on developmental delay, there was no relationship between pharmacologic therapy and motor delay (p=.260), language delay (p=.542) or any developmental delay (p=.176). When maximum Finnegan score was entered into the model as an interaction term the relationships were not significant. DISCUSSION/SIGNIFICANCE OF FINDINGS: These results suggest that while pharmacologic weaning is an appropriate treatment for withdrawal symptoms in infants, it is not a deterrent against developmental delays associated with NAS. This provides support suggest an increased focus on non-pharmacologic interventions such as breastfeeding as the first line of treatment for NAS infants.

ABSTRACT IMPACT: Learning Health System (LHS) Science that trains postdoctoral scholars from diverse professional backgrounds in methodological and professional skills to implement rigorous research in health care systems and populations, and to disseminate the findings of such research to improve healthcare delivery OBJECTIVES/GOALS: The WFUHS CTSA developed an innovative TL1 in Learning Health System (LHS) Science that trains postdoctoral scholars from diverse professional backgrounds in methodological and professional skills to implement rigorous research in health care systems and populations, and to disseminate the findings of such research to improve healthcare delivery METHODS/STUDY POPULATION: Training is centered around formal LHS science coursework and mentored research projects that address a pressing health system issue. Projects are closely guided by a primary mentor and a multidisciplinary mentoring team. Program mission and competencies were carefully evaluated in a competency-course matrix to design new courses for the LHS Certificate and MS program in Translational and Health System Science (THSS). Course domains include biomedical informatics; improvement and implementation science; system science and organizational change management; stakeholder engagement, leadership, and research management; ethics of health systems research; and health systems research methods. Scholars set up Individual Development Plans (IDP) and self-assess 7 domains of LHS core competencies. RESULTS/ANTICIPATED RESULTS: The first professionally diverse group of scholars (MD, PhD, DrPH, PharmD) began the program in Summer 2020; onboarding was conducted virtually. Scholars currently conduct most of their research and training in a virtual, synchronous format. Each developed a detailed IDP and LHS research project, which was reviewed by their LHS mentoring teams (includes a primary mentor, co-mentor, TL1 core faculty mentor, peer mentor, and health system mentor). Coursework, leading to a 1-year certificate or 2-year MS degree, was selected based on individual background and career goals and was begun in August 2020. In addition to the courses noted above, Scholars are embedded in a healthcare improvement team. We use the process of a LHS and hold weekly TL1 leadership meetings to swiftly address challenges and implement improvements DISCUSSION/SIGNIFICANCE OF FINDINGS: We envision that TL1 Scholars will build independent LHS research programs or lead health system innovation. Program evaluation includes assessments of Scholar fluency in LHS competencies and attainment of key milestones during and after training. Annual TL1 faculty retreats will address program fidelity and implementation of program refinements

ABSTRACT IMPACT: This study will generate preliminary data to address a critical, care transition-related patient safety gap involving medication use among children with medical complexity. OBJECTIVES/GOALS: The objectives of this study are: (1) to understand care transition-related medication safety risks for children with medical complexity (CMC), and (2) through a participatory, human centered design (PD) approach, to develop an early prototype intervention to address identified safety risks. METHODS/STUDY POPULATION: The study population includes children with medical complexity (CMC), a medically fragile pediatric population with intensive healthcare needs. CMC rely on multiple and complex medication regimens and/or medical devices for optimal functioning. Parents of CMC report multiple unmet healthcare needs. For Aim 1, we will conduct observations and interviews with ˜15 clinicians as well as semi-structured interviews with ˜30 family caregivers during three care transition experiences: from Cardiac ICU to home, Neonatal ICU to home, and those between primary care/specialty clinic to home. For Aim 2, we will conduct participatory design sessions with up to 5 participants (separately for clinicians and family caregivers) from each of the three care transition settings to co-design a prototype intervention. RESULTS/ANTICIPATED RESULTS: The study is currently recruiting family caregivers of CMC for aim 1 research activities, with interviews planned to be completed in February/March 2021. Transcribed interviews will be used to inform development of patient journey maps. A patient journey map helps to visually depict healthcare services through the patient and family lens, and highlights important ‘touch points’ along the patient journey (e.g., decisions, encounters, constraints, emotional states, etc.) that shape the patient and family experience. The journey map will distill findings from qualitative data and generate a concise visual story focused on the medication use experience of CMC as they transition between the hospital and their home. Individual journey maps will also be combined to generate a consolidated journey map. DISCUSSION/SIGNIFICANCE OF FINDINGS: An-in-depth understanding of medication safety risks unique to the context of CMC care would be essential to develop interventions that are useful, scalable, and sustainable. This is even more important because current interventions are primarily adopted from adult care settings with mixed outcomes.

ABSTRACT IMPACT: The UTMB Institute for Translational Sciences (ITS) seeks to advance the field of community engagement and facilitate competency in community-engaged and community-based participatory research as a means of expanding team science to integrate community involvement and to assist investigators in building relationships that enable them to contribute to community initiatives. OBJECTIVES/GOALS: The UTMB ITS recently implemented a new Community Health Small Grants program to promote and enhance community-campus partnerships. Our goal is to better translate science from discovery to clinical practice and public health through community-engaged research, education, and dissemination. METHODS/STUDY POPULATION: Applications were solicited from community and academic research partners. Community partners may include existing collaborative groups, community health centers, health departments, nonprofits, schools, social services agencies, practice-based research networks, or Community Advisory Boards. Academic partners may include faculty and/or students. The PI may be a community or academic partner. While this Grants Program will transition to the ITS Pilot Project Program, it will utilize a separate review process and scoring rubric focused on immediate and future community benefit, project feasibility, organizational fit, and other factors unique to community-based partnership projects. RESULTS/ANTICIPATED RESULTS: We received an enthusiastic response to our RFA, based upon a long-standing program of a sister CTSA hub. Proposals received include target populations representative of our most vulnerable’‘ children, the elderly, those lacking access to health care, and those for whom language is a barrier. One addresses the Institution’s and the CEC’s need to conduct community needs assessments to enable the implementation of evidence-based programs driven by data and metrics identified and developed by our communities. Each awarded proposal demonstrates a significant and sometimes critical need for the project. Partnerships are anticipated to have significant impacts on the community and its population. DISCUSSION/SIGNIFICANCE OF FINDINGS: We generate, test, and disseminate team science, education and best practices through stakeholder involvement. Our Community Health Small Grants program aims to involve community in our scientific teams and to involve academics in community-derived projects as well as foster relationships and trust.

ABSTRACT IMPACT: This work will inform the need for more trauma-informed approaches to violence screenings among marginalized populations by health care providers. OBJECTIVES/GOALS: Female sex workers (FSW) experience high rates of intimate partner violence (IPV) which may have negative reproductive health consequences. Routine IPV screening by healthcare providers (HCP) is recommended. This study examines how FSW experience IPV assessments by HCP. METHODS/STUDY POPULATION: This qualitative descriptive study is nested within EMERALD, a longitudinal cohort study of street-based FSW. EMERALD assesses a structural community-level intervention on HIV and STI risks among FSW. Participants were recruited for EMERALD using time-location sampling to identify a sampling frame of venues and times where sex work is likely to occur. Inclusion criteria for this qualitative study include: participating in EMERALD, age 18-49, and willingness to participate in one phone interview. Twenty-two semi-structured individual qualitative interviews were conducted. Two coders, using thematic analysis, applied deductive codes and inductive coding to identify themes. RESULTS/ANTICIPATED RESULTS: Three themes emerged from participant interviews regarding IPV screening. Inconsistent screening practices: Despite frequent reproductive health visits among participants, many women did not recall IPV screening by a HCP. Stigma as a barrier to disclosure: Women described feeling judged by HCP regarding their frequency of visits for reproductive concerns, sex work, and substance use and did not trust disclosing violence to HCP. Transactional health encounters: During visits, HCP were focused on addressing women’s immediate concerns; if the HCP did ask about IPV women felt the questions were asked part of a required protocol and not driven by a concern to deeply understand their lives. DISCUSSION/SIGNIFICANCE OF FINDINGS: FSW described inconsistent IPV screening practices by HPC. Participants expressed feeling stigmatized by HCP and that encounters with HCP did not foster trust for women to disclose IPV experiences. There is a need for HPC training in universal IPV screening focused on relationship and trust building to facilitate disclosure.

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.