OBJECTIVES/GOALS: To adapt and evaluate motivational interviewing (MI) as a tool for better understanding the beliefs that underlie vaccine hesitancy and effectively respond to these beliefs with emphasis on reaching underserved communities disproportionately impacted by COVID-19. METHODS/STUDY POPULATION: Our group reviewed the principals for motivational interviewing, rationale for vaccination, and likely beliefs underlying hesitancy and developed a guide for MI to address vaccine hesitancy. We recruited lay members of Black and Hispanic communities in Washington, DC and Baltimore, MD. 90-minute zoom facilitator training sessions included didactic material, questions and discussion, and role playing. We were not successful recruiting unvaccinated individuals to provide written consent to be followed re vaccination status. Facilitators indicated incorporating MI in their job-related and informal interactions. Surveys were developed to obtain feedback regarding beliefs underlying hesitancy, perceptions of MI effectiveness, and more recently (Oct 2022), evolving concerns regarding the pandemic. RESULTS/ANTICIPATED RESULTS: 67% of facilitators were Black, their average age was 39 years, and 67% had at least a high school education. All had received a COVID-19 vaccination. 82% endorsed utilizing MI in discussions receiving the COVID-19 vaccine. 46% of the facilitators endorsed that MI was moderately effective (46%) in clarifying objections and very effective (50%) in persuading friends, family, and co-workers to consider getting vaccinated. The most common elicited objections to the vaccine were side-effects (21%) and beliefs in government conspiracies (21%). In the second survey respondents indicated receiving another booster followed by getting their children vaccinated as the most common identified concerns. DISCUSSION/SIGNIFICANCE: MI can be adapted to address vaccine hesitancy in underserved minority groups and appears promising for identifying beliefs underlying hesitancy and possibly for increasing vaccination rates among these communities.

OBJECTIVES/GOALS: Histopathological descriptions of kidney tissue provide more information about kidney disease severity and prognosis than serum measures, yet most patients with chronic kidney disease do not undergo kidney biopsy. We aim to develop a method to determine the degree of renal injury in patients with diabetes and hypertension without the need for biopsy. METHODS/STUDY POPULATION: Clinical data and renal tissue samples were collected from 864 patients undergoing tumor-associated nephrectomy in seven medical centers in the United States. Exclusion criteria included age < 18, presence of pyelonephritis or non-diabetic or hypertensive renal disease or incomplete clinical or histopathologic data. 19 histologic parameters were scored in a blinded manner by one renal pathologist. We examined the relationship between and functional variables (such as estimated glomerular filtration rate (eGFR)). Polynomial regression analysis was performed to model histopathologic variables and important clinical parameters such as eGFR RESULTS/ANTICIPATED RESULTS: 607 samples met inclusion criteria and were stratified as: control (no history of diabetes or hypertension, n = 160), hypertension alone (n = 224) and both diabetes and hypertension (n = 223). Interstitial fibrosis (IF) and glomerulosclerosis (GS) had the strongest correlations with eGFR. Regression analysis was used to model histopathologic score for a given eGFR. We found that diabetes and hypertension modified the relationship between tubulointerstitial fibrosis and eGFR. For example, while hypertensive patients without diabetes had 33% IF at an eGFR of 30 ml/min/1.73m2 (r2 = 0.64, p<0.01), hypertensive patients with diabetes had 32% IF at an eGFR of 30 ml/min/1.73m2 (r2 = .43, p<0.01) and control patients had approximately 23% IF at an eGFR of 30 ml/min/1.73m2 (r2 = 0.22, p<0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: Here, we describe the relationship between renal structural changes and renal function and show that hypertension significantly modifies the relationship at a given eGFR. These data can be used to reasonably predict renal structural changes given clinical information without the need for renal biopsy and may provide prognostic value.

OBJECTIVES/GOALS: This project aims to improve the design of medical technology for global health by addressing gaps in engineering education. Our primary goal is to develop open educational resource’curriculum boosters’ that can be added to existing BME curricula to build skills in transdisciplinary collaboration, practical ethics, and failure resilience. METHODS/STUDY POPULATION: A phasic mixed-method research strategy has been employed. The Needs Analysis includes a systematic review and meta-analysis of existing knowledge regarding the three conceptual pillars of Transdisciplinary Collaboration, Practical Ethics, and Integrated Resilience. The Behavioral Study includes surveys, interviews, observations, and biometric data collection from working engineers, engineering students, global health stakeholders, and clinicians. The Validation Study will be conducted via small group workshops, a semester-long engineering design course, and a summer study-abroad course. Data collected will be analyzed and used to refine the proposed educational strategies. RESULTS/ANTICIPATED RESULTS: The final educational strategies will be structured into 'curriculum boosters' and published as open educational resource materials. The boosters and their supporting data will be made available to other engineering education programs with the goal of promoting widespread adoption and integration of these methods. DISCUSSION/SIGNIFICANCE: The long-term outcome of this ongoing work is to train a new generation of engineers prepared to participate adeptly in the co-design of technological solutions for complex global healthcare challenges by working ‘with, not for,’ clinicians, communities, and other stakeholders in peripheral healthcare settings.

OBJECTIVES/GOALS: To develop the Adherence to Medications In Latinx adults with Depression and Anxiety (AMILDA) intervention using community engaged research principles, AMILDA will integrate culturally tailored messaging to improve depression and anxiety symptoms and adherence to antidepressant medications. METHODS/STUDY POPULATION: Bilingual steering committee members representing primary care and behavioral health professionals from 2 primary care clinics, and 1 lay community member met monthly for 1 year to develop the intervention. One clinic is an academic health center and the other is a federally qualified health center. Members identified, developed, and voted on the interventions components, therapeutic goals, and the mechanisms underlying its effectiveness that needed to be studied. To evaluate AMILDAs components, we conducted an observational study of health care providers (N=13) and Latinx adults with depression and/or anxiety (patients; N=26) from both clinics, and community pharmacists (N=9) from surrounding pharmacies to gather feedback. Based on their input, we revised the intervention. RESULTS/ANTICIPATED RESULTS: AMILDA consists of culturally tailored collaborative drug therapy management with a collaborative practice agreement between the physician and pharmacist. Patients recently started on an antidepressant receive language and culturally concordant motivational interviewing, teach back, and infographics; AMILDA is designed to improve symptoms, adherence, and health determinants. Most provider, pharmacist, and patient participants reported that AMILDA could be beneficial. Several participants indicated a lack of understanding about a US pharmacists scope of practice. Recommendations included ensuing language concordance, incorporating more statistics and scientific data, using images that are relatable, avoiding idioms and stereotypes, taking the time to build rapport, and being friendly. DISCUSSION/SIGNIFICANCE: AMILDA will be tested in a pilot effectiveness randomized controlled study to determine if it improves depression and anxiety symptoms and adherence to antidepressants among Latinx adults compared with enhanced usual care. The mechanisms to be assessed include self-efficacy, antidepressant knowledge, and personal health literacy.

OBJECTIVES/SPECIFIC AIMS: To improve translational research, we have developed a program called Duke Multidisciplinary Education and Research in Translational Sciences (Duke MERITS). Duke MERITS will facilitate cross-disciplinary collaboration among faculty involved in foundational, clinical and/or health care research and in turn also prepare them to train the next generation of translational researchers. METHODS/STUDY POPULATION: The program aims are (1) to define metrics and outcomes measures so faculty can track their progress and identify impact of their collaborative research in translational sciences; (2) to offer a multi-modal faculty development series to promote team science, improve didactic teaching, and incorporate innovative resources to promote interdisciplinary approach to translational research; (3) to provide module-based hands-on-training sessions in bench to bedside research and training in translational grant writing to facilitate the development of multidisciplinary research collaborations. The present study describes results from Aim 1 and includes (a) development of baseline outcome assessment tools necessary to gauge the impact of our programs on both the participating faculty and the research culture within Duke University, (b) impact of a specific course offering in Translational Medicine. In order to achieve this, we conducted multiple focus group sessions with faculty self-identified as junior-, mid-, or advanced-career, a mixed group at any career level and included a group of graduate students and postdoctoral trainees to study the impact of a graduate level course in Translational Aspects of Pathobiology. The activities during these translational science focus groups were designed to define what successful translational science is, to determine what resources support translational Science at Duke, and to decide what resources we need in order to enhance Duke’s position as a leader in research and scientific education. RESULTS/ANTICIPATED RESULTS: We identified that translational science is changing standards while incorporating leadership, teamwork, collaborations, and movement primarily focusing on the overall goal of improving all aspects of health. Participants categorized their field of study and the fields of their coparticipants most frequently as basic discovery and a combination of intervention and health services. The most frequently identified pros/benefits of performing translational science at Duke include industry connections, collaborations with other departments resulting in disciplines being bridged, improving patient care, and access to resources as well as money. The most frequently identified cons/barriers of performing translational science includes the expensiveness, silos, and lack of resources willing to absorb risks. DISCUSSION/SIGNIFICANCE OF IMPACT: The identification of these defined factors from the focus groups has allowed us to issue a comprehensive, sliding Likert scale-based anonymous survey from the secure RedCap system and is being rolled out throughout Duke University, including schools of medicine, nursing, Trinity, biomedical engineering. We envision that Duke MERITS education program will facilitate interprofessional efforts, which we define as a team science approach to identify the clinical “roadblock” and then seek an innovative approach or technology to help overcome this “roadblock”? It can facilitate institutional and departmental recognition in faculty career development. The common goal is to gain fundamental new insights that will result in significant improvement of the existing “standard of care” and meet the challenges of dwindling extramural support.

OBJECTIVES/GOALS: Scientists are increasingly confronted with 'science critical' #_msocom_1 belief systems. The politicization of science fuels hesitancy towards evidence-based therapies. To overcome these barriers, we aim to devise strategies to communicate clinical translational science (CTS) through art. METHODS/STUDY POPULATION: A two-year pilot artist-in-residency (AIR) program embedded in the Translational Research Immersion Program (TRIP). Since 2009, TRIP contributes to CTS Workforce Development (WD) through a 10-week mentored, curriculum-rich summer undergraduate research experience. Students are recruited from 5 regional institutions, 6 HBCUs, and the University of Puerto Rico. AIR is composed of 3 phases: the “Immersive Phase” where the artist gains intensive exposure to the scientific process through the lived experience of TRIP students, the “Productive Phase” where the artist conceptualizes the process of CTS into works of art, and the “Engagement Phase” where the CTS workforce, artists, and community members coalesce around science-to-art materializations. RESULTS/ANTICIPATED RESULTS: In 2022 & 2023 the AIR participated in ~35hrs of CTS research seminars, panel discussions, and professional skills workshops. Additional TRIP student-AIR interaction occurred in focus groups including visits to mentor’s labs. An AIR-led workshop culminated in an Empowering CTS Communication event where TRIP students engaged with community members through elevator pitches of their CTS summer project on a speed-rotating basis. A month-long art-CTS exhibition planned for 3/2024 will feature contributions from AIR, TRIP students, and ITMAT community members. Qualitative insights were that TRIP is an effective art-science incubator, students strengthened their CTS communication skills, art functions as an icebreaker between science and communities with an ocean of opportunities for science education. DISCUSSION/SIGNIFICANCE: AIR embedded into existing CTS WD programs is proposed as creative approach to strengthen the reputation of science in the public. CTS-informed art functions as connective tissue between public and CTS workforce. The hands-on experience to adopt art as a science communication tool is a powerful soft skill for the next generation of CTS investigators.

OBJECTIVES/GOALS: Heart failure (HF) is a clinical condition that notably affects the lives of patients in rural areas. The partnering of a rural satellite hospital with an urban academic medical center may provide geographically underrepresented populations with HF an opportunity to access controlled clinical trials (CCTs). METHODS/STUDY POPULATION: We report our experience in screening, consenting and enrolling subjects at the VCU Health Community Memorial Hospital (VCU-CMH) in rural South Hill, Virginia, that is part of the larger VCU Health network, with the lead institution being VCU Health Medical College of Virginia Hospitals (VCU-MCV), Richmond, VA. Subjects were enrolled in a clinical trial sponsored by the National Institutes of Health (ClinicalTrials.gov: NCT03797001) and assigned to treatment with an anti-inflammatory drug for HF or placebo. We used the electronic health record and remote guidance and oversight from the VCU-MCV resources using a closed-loop communication network to work with local resources at the facility to perform screening, consenting and enrollment. RESULTS/ANTICIPATED RESULTS: One hundred subjects with recently decompensated HF were screened between January 2019 and August 2021, of these 61 are enrolled to date: 52 (85 %) at VCU-MCV and 9 (15%) at VCU-CMH. Of the subjects enrolled at VCU-CMH, 33% were female, 77% Black, with a mean age of 5210 years. DISCUSSION/SIGNIFICANCE: The use of a combination of virtual/remote monitoring and guidance of local resources in this trial provides an opportunity for decentralization and access of CCTs for potential novel treatment of HF to underrepresented individuals from rural areas.

OBJECTIVES/GOALS: Currently physicians are able to order CT Chest/Abd/Pelvis images as STAT or Routine. STAT images denote an emergency and are done immediately. We aim to determine the percentage of CT images that are inappropriately ordered as STAT, determine physician image ordering habits, and develop targeted interventions to encourage appropriate STAT image ordering. METHODS/STUDY POPULATION: A fishbone diagram helped reveal possible causes of inappropriate STAT image ordering. Based on the fishbone diagram, a survey was created to assess CT image ordering habits amongst radiology and internal medicine residents and attending physicians. All CT Chest/Abd/Pelvis images ordered over a 3 month period of time (July-Oct 2017) was obtained. The dataset included whether the image was ordered Stat vs Routine, time of image order, physician name and location, and reason for the imaging study.The STAT images were evaluated based on the explanation provided in the CT image order. Currently 2 radiology residents, 2 internal medicine residents, and 2 internal medicine hospitalists are evaluating all STAT CT images to determine appropriateness and how long they are willing to wait for the image to result in a read. RESULTS/ANTICIPATED RESULTS: Analysis of all CT Chest/Abd/Pelvis imaging orders revealed that 51% (1710/3345) of them were ordered as STAT. The preliminary analysis of 227 STAT images showed that 6% were inappropriate. We anticipate results of our survey to show differences in how long a STAT vs Routine image orders should take amongst Radiology and Internal Medicine clinicians. We also anticipate our survey to show differences in factors that warrant STAT imaging amongst the different medical fields. We anticipate that the clinician manual evaluation of all STAT CT image will reveal a large percentage of imaging orders to be inappropriate. All STAT imaging that were flagged as inappropriate will be characterized by the department who ordered the image and the reason provided for the imaging to assess for common themes. DISCUSSION/SIGNIFICANCE OF IMPACT: STAT images are the new routine with more images ordered STAT than Routine. Inappropriate STAT imaging results in truly urgent patients not getting the medical care they need. Many images ordered stat could potentially be switched to routine. By evaluating why clinicians are ordering STAT CT image inappropriately, we will be able to develop targeted interventions to decrease inappropriate STAT CT imaging.

ABSTRACT IMPACT: This is the first study to use QUINT analyses to examine heterogeneity of treatment effect for group medical visits among individuals with type 2 diabetes. QUINT is a data driven method that assumes no a priori assumptions regarding effect moderators - an important step in the path towards personalized medicine. OBJECTIVES/GOALS: To examine heterogeneity of treatment effect (HTE) in Jump Start, a trial that compared the effectiveness of group medical visits (GMVs) focused on medication management only versus the addition of intensive weight management (WM) on glycemic control for patients with type 2 diabetes and body mass index >=27kg/m^2. METHODS/STUDY POPULATION: Jump Start patients (n=263) were randomized to a GMV-based medication management plus low carbohydrate diet-focused WM program (WM/GMV; n = 127) or GMV-based medication management only (GMV; n = 136) for diabetes control. We used QUalitative INteraction Trees (QUINT), a tree-based clustering method, to determine if there were subgroups of patients who derived greater benefit from either WM/GMV or GMV. Subgroup predictors included 32 baseline demographic, clinical, and psychosocial factors. Outcome was hemoglobin A1c (HbA1c). We conducted internal validation via bootstrap resampling to estimate bias in the range of mean outcome differences among arms. RESULTS/ANTICIPATED RESULTS: QUINT analyses indicated that for patients who had not previously attempted weight loss, WM/GMV resulted in better glycemic control than GMV alone (mean difference in HbA1c improvement = 1.48%). For patients who had previously attempted weight loss and had lower cholesterol and blood urea nitrogen levels, GMV alone was better than WM/GMV (mean difference in HbA1c improvement = 1.51%). Internal validation resulted in moderate corrections in the mean HbA1c differences between arms; however, differences remained in the clinically significant range. DISCUSSION/SIGNIFICANCE OF FINDINGS: Among patients with diabetes and BMI>=27kg/m^2, a low-carbohydrate, weight loss focus may better improve HbA1c in those who have never attempted weight loss. A medication management focus may be better in those who have attempted weight loss and have lower cholesterol and blood urea nitrogen.

OBJECTIVES/GOALS: CEnR plays a crucial role in rapidly translating science to improve health by bridging gaps between research and practice although skills development is critical to enable successful community/academic partnerships. We have developed a curriculum mapped to CEnR domains and competencies that meets the needs of community partners and investigators. METHODS/STUDY POPULATION: We located three comprehensive efforts to identify CEnR domains and competencies that we aligned to develop our curriculum, which we then mapped to these competencies. The first was undertaken by a NCATS Joint Workgroup which identified curricula, resources, tools, strategies, and models for innovative training programs. Using Competency Mapping, they developed a framework for curriculum mapping that included eight domains, each with two to five competencies of knowledge, attitudes, and skills. The second aligned CEnR competencies with online training resources across the CTSA consortium, while the third focused on Dissemination and Implementation training. Informed by a conceptual model to advance health equity, we adapted and integrated these frameworks into a set of six educational modules. RESULTS/ANTICIPATED RESULTS: Although many CEnR training programs have been developed, few curricula are mapped to identified domains and competencies, and fewer still address institutional and community barriers to effective CEnR training. However, many outstanding curricula effectively address these competencies, and our curriculum draws from and builds upon these programs of excellence, including those from our sister CTSA hubs. Our modules serve our local community by educating and empowering faculty, students, and community partners. To date, no CEnR curriculum has been implemented at our institution that meets the needs of all parties who play a significant role in community-engaged research (e.g., IRB members, investigators, and community-based partners). This curriculum thus fills an important gap in our workforce training. DISCUSSION/SIGNIFICANCE: This educational program is designed to educate and empower investigators, trainees, students, and community partners to engage in effective CEnR that promotes community projects and fosters relationships and trust. Following evaluation, we will offer the curriculum for use by others interested in using or adapting it for their own programming.

OBJECTIVES/SPECIFIC AIMS: Central neuropathic pain is a severely disabling consequence of conditions that cause tissue damage in the central nervous system (CNS) such as multiple sclerosis (MS) and neuromyelitis optica (NMO). It impacts mood, mobility and quality of life, but is often refractory to common treatments. Scrambler Therapy is an emerging non-invasive pain modifying technique that utilizes transcutaneous electrical stimulation of nociceptive fibers with the intent of re-organizing maladaptive signaling pathways. It has been examined for treatment of peripheral neuropathy with favorable safety and efficacy outcomes, but its use in central neuropathic pain has not been reported. We aim to explore acceptability and safety of Scrambler Therapy through a Phase II sham-controlled trial in NMO, and describe its use to date in central neuropathic pain. METHODS/STUDY POPULATION: Two patients with longstanding central neuropathic pain who failed multiple drug trials were treated as proof-of-concept, supporting the recent launch of a Phase II randomized controlled trial in NMO where patients receive 10 daily Scrambler treatments versus sham. Safety and acceptability from those recruited to date will be reported. Acceptability is measured by adherence and responses to patient surveys. RESULTS/ANTICIPATED RESULTS: We plan to recruit 22 patients, randomized 1:1 into experimental and sham arms. We will present acceptability and safety data for Scrambler use in patients with NMO who have been recruited by the time of this conference, as well as effectiveness data from two cases that have been completed outside of the trial. One case involved a 65-year-old woman with a 4-year history of central neuropathic pain following a C3-C5 TM. Her numerical rating scale (NRS) pain score was reduced to 0/10 from a baseline score of 5/10. The second case involved a 52-year-old woman with a 13-year history of pain following a medullary cavernoma bleed. Her baseline NRS pain score was 9/10, which was reduced to 0.5/10 post-treatment. No adverse events were reported. Pain relief was sustained at 30 days’ post-treatment. DISCUSSION/SIGNIFICANCE OF IMPACT: We are investigating the acceptability and efficacy of Scrambler Therapy for central neuropathic pain treatment in NMO. Proof-of-concept was supported by two patients whose pain scores improved considerably more in response to this treatment than with previous pharmacologic and non-pharmacologic interventions. Results from this trial may support future investigation in other disorders that cause damage in the CNS, including MS and TM.

OBJECTIVES/SPECIFIC AIMS: We hypothesized that increasing percent calories from MUFA (%MUFA) would be associated an increased FFM/FM index. METHODS/STUDY POPULATION: Nine consecutive HFpEF patients with obesity participated in a 12-week pilot feasibility trial of UFA supplementation (NCT03310099). Subjects were educated at baseline by a dietitian on UFA rich foods including high MUFA choices such as extra-virgin olive oil, canola oil and avocados. Participants were given a list of items, corresponding serving sizes and asked to eat at least one serving of these UFA rich foods per day for 12 weeks. Adherence was encouraged through weekly phone calls by the dietitian. Standardized 5-pass 24-hour dietary recall was performed by a dietitian at baseline and 12 weeks. The recalls were analyzed to establish intake of MUFA in percent calories (%kcals) with Nutrition Data Systems for Research software (NDSR). Body composition including FM%, fat free mass percent of body weight (FFM%) and ratio of FFM to FM (FFM/FM Index) was measured with bioelectrical impedance analysis (RJL systems) at baseline and 12 weeks. Statistical analysis was performed with SPSS (24.0). Spearman rank test was used for correlations. Values are expressed as numbers and percentages or as median and interquartile range (IQR). RESULTS/ANTICIPATED RESULTS: Subjects were mostly female (56%) with a median age 56 (IQR 50-59). Baseline median body mass index (kg/m2) was 36.7 (36.2-48.0), median FM% was 44.5 (IQR 32.5-53.4), median FFM% was 55.5 (IQR 46.7-67.5) and median FFM/FM Index was 1.25 (IQR 0.88-2.1).The only significant change was an increase in %MUFA from baseline 12.4% (IQR 6.9-14.3) to 12 weeks 21.8% (17.6-36.9) (p = 0.008). Increased %MUFA was highly associated with increased FFM% (r = 0.783, p = 0.013) (Figure 1A), decreased FM%(r = −0.783, p = 0.013)(Figure 1B) and increased FFM/FM index (r = 0.800, p = 0.010) (Figure 1C). All correlations remained statistically significant after adjustment for changes in energy intake. DISCUSSION/SIGNIFICANCE OF IMPACT: Increasing dietary %MUFA is protective against negative changes in body composition in patients with obesity and HFpEF, independent of changes in caloric intake. Future work should focus on whether the correlation found in this pilot study translate in improved body composition and finally, exercise tolerance and clinical outcomes.

OBJECTIVES/SPECIFIC AIMS: Provide an innovative, integrative, and interdisciplinary training program which will leverage a unique and internationally recognized strength of BU and establish an environment that facilitates translational team science interactions with MD scientists and clinicians, thereby synergistically bridging research strengths with interdisciplinary approaches. METHODS/STUDY POPULATION: This overall mission of the RMTP is pursued through 2 independent aims. Aim 1: Provide an innovative, integrative, and interdisciplinary training program which will leverage a unique and internationally recognized strength of BU. Aim 2: Establish an environment that facilitates translational team science interactions with MD scientists and clinicians, thereby synergistically bridging research strengths with interdisciplinary approaches. To achieve these aims, we have developed a specialized didactic curriculum that is fully integrated in graduate school training and can be shared for the benefit of others outside of the BU community. We are also developing online iPSC practicum workshops for more efficient distribution of didactic content. Interdisciplinary team science approaches to stem cell research related to cures for human diseases are fostered across investigators across diverse hubs at BU, BU Medical Center, the Charles River Campus and the Framingham Heart Study. All methodology, data and materials are provided in a transparent and open-source manner to benefit the greater scientific community and ensure rigorous reproducibility. RESULTS/ANTICIPATED RESULTS: As a nascent TL1 training program, we are just arriving at the end of our second year. At this point, 5 out of a total of 11 appointed trainees have concluded RMTP support, all of whom have transitioned into biomedical science-related pursuits; 2 predoctoral trainees were awarded F31 fellowships, 2 postdoctoral trainees were awarded career transition grants (K99/R00 and LERN fellowship), and 1 postdoctoral trainee became a Senior Scientist at a Biopharmaceutical company. Given the quality of our trainees and their RMTP mentors, we anticipate that close to 100% of those supported by this mechanism will continue their career development in the biomedical sciences. DISCUSSION/SIGNIFICANCE OF IMPACT: Implementation of the RMTP TL1 would not only serve to increase the capacity of trainees within the CReM, but would also extend the scope of regenerative medicine research to other CTSI-participating hubs and more broadly to other scientific disciplines.

OBJECTIVES/SPECIFIC AIMS: Emotional processing theory and some observations suggest that activation of subjective and physiological distress during therapeutic exposure and habituation across exposure sessions are key to improvement. This study sought to determine whether initial subjective and physiological activation and between-session habituation would predict PTSD symptom reduction after a series of written trauma narrative exposure sessions. METHODS/STUDY POPULATION: In total, 29 urban-residing African-American participants with PTSD participated in four 30-minute writing sessions. Writing sessions 1 and 2 were 12 hours apart and session 3 and 4 were performed 1 week later, also 12 hours apart. PTSD symptoms were measured at baseline, after session 2, and 1 week after all 4 writing sessions with the Clinician Administered PTSD Scale. During each session, Subjective Units of Distress Scores (SUDS) were assessed 4 times and heart rate was measured continuously. RESULTS/ANTICIPATED RESULTS: Participants exhibited PTSD symptom improvement and habituation of subjective distress, but not physiological arousal, across writing sessions. First session baseline-corrected SUDS maximum and SUDS decrease from the initial to the final writing session were both positively associated with symptom improvement. DISCUSSION/SIGNIFICANCE OF IMPACT: Increased subjective, but not physiological, distress in the first exposure session and diminished subjective distress across sessions may be a helpful marker of emotional processing for clinicians and predictor of symptom improvement after written trauma narrative exposure.

ABSTRACT IMPACT: Our findings could potentially identify CVD at-risk persons living with HIV who might benefit from aggressive risk-reduction. OBJECTIVES/GOALS: PWH have higher rates of CVD than the general population yet CVD risk prediction models rely on traditional risk factors and fail to capture the heterogeneity of CVD risk in PWH. Here we identify protein biomarkers that are able to discriminate between CVD cases and controls in PWH, and we assess their added benefit beyond traditional risk factors. METHODS/STUDY POPULATION: We analyzed 459 baseline protein expression levels from five OLINK panels in a matched CVD (MI, coronary revascularization, stroke, CVD death) case-control study with 390 PWH from INSIGHT trials (131 cases, 259 controls). We formed 200 datasets via bootstrap. For each bootstrap set, a two-component partial least squares discriminant model (PLSDA) was fit. The importance of each variable in the discrimination of cases and controls in the PLSDA projection was assessed by the variable importance in projection (VIP) score. Proteins with average VIP scores > 1 were used in penalized logistic regression models with elastic net penalty, and proteins were ranked based on the number of times the protein had a nonzero coefficient. Proteins in the top 25th percentile were considered to have high discrimination. RESULTS/ANTICIPATED RESULTS: Participants had mean age 47 years, 13% were females, 4.9% had CVD at baseline and 69% were on ART at baseline. Eight proteins including the hepatocyte growth factor and interleukin-6 were identified as able to distinguish between CVD cases and controls within PWH. A protein score (PS) of the top-ranked proteins was developed using the bootstrap (for weights) and the entire data. The PS was found to be predictive of CVD independent of established CVD and HIV factors (Odds ratio: 2.17 CI: 1.58-2.99). A model with the PS and traditional risk factors had a 5.9% improvement in AUC over the baseline model (AUC=0.731 vs 0.69), which is an increase in model predictive power of 18%. Individuals with a PS above the median score were 3.1 (CI: 1.83- 5.41) times more likely to develop CVD than those with a protein score below the median score. DISCUSSION/SIGNIFICANCE OF FINDINGS: A protein score developed improved discrimination of PWH with CVD and those without, and helped identify PWH with high risk for developing CVD. If validated, this score and/or the individual proteins could be used in addition with established factors to identify CVD at-risk individuals who might benefit from aggressive risk-reduction.

OBJECTIVES/GOALS: Flavorings differ between brands and tobacco products, potentially altering the sensory perceptions. This study aimed to examine discrepancies in flavor preference across various non-cigarette tobacco products among a national representative sample of US adult regular tobacco users. METHODS/STUDY POPULATION: Data from the Population Assessment of Tobacco and Health (PATH) Study Wave 3 (W3) were used. Weighted prevalence of flavor preference for various tobacco products, including electronic nicotine delivery systems (ENDS), traditional cigars, cigarillos/filtered cigars, hookah and snus/smokeless, was presented for 9,037 adult current and new former users of multiple flavored tobacco products. Within-subject flavor discrepancies were assessed using generalized estimating equations (GEE) models considering the complex sampling design of the PATH study. RESULTS/ANTICIPATED RESULTS: Most regular users of a flavored tobacco products reported using one flavor category per product. Fruit flavors, followed by tobacco, were the most common flavor categories among ENDS (32% and 25%, respectively) and hookah users (44% and 36%, respectively). Tobacco flavor was the most common among regular users of traditional cigars (80%), cigarillos/filtered cigars (55%), and smokeless tobacco (79%). Polytobacco users of ENDS and traditional cigars had the largest discrepancy, where about 68-76%% used different flavor categories when switching products. Conversely, polytobacco users of traditional cigars and cigarillos/filtered cigars had the lowest discrepancy (23-25%). DISCUSSION/SIGNIFICANCE OF IMPACT: Many consumers of multiple tobacco products had different flavor preferences when switching between products. In the event of a partial or full flavor ban for ENDS, these findings raise questions about consumer loyalty to a particular tobacco product or a particular flavor category. Conflict of Interest Description: MLG serves as a paid consultant for Johnson & Johnson and has received research grant from Pfizer, manufacturers of smoking cessation medications. The other authors have no conflicts to declare. CONFLICT OF INTEREST DESCRIPTION: MLG serves as a paid consultant for Johnson & Johnson and has received research grant from Pfizer, manufacturers of smoking cessation medications. The other authors have no conflicts to declare.

OBJECTIVES/SPECIFIC AIMS: Addressing Disparities in Asian Populations through Translation research (ADAPT) is a community-research partnership funded by the Tufts Clinical Translational Sciences Institute (CTSI). Founded in 2011, this collaborative brings together 7 Chinatown-serving community-based organizations and academic researchers with the goal of improving health for the local Chinatown community and beyond. The goal of this research project was to document the best practices, lessons learned, and process through which ADAPT has developed and grown. The aim of this project is to disseminate the model to other CTSAs who are currently engaged in METHODS/STUDY POPULATION: We used a combination of qualitative interviews and content analysis to gather data on the evolution of ADAPT over the last 5 years. Current members from both community organizations and the university/medical center were interviewed about their experiences participating in ADAPT. When possible, interviews were recorded and transcribed verbatim. Deidentified transcripts and administrative documents including meeting minutes, conference summaries, bylaws, and mission statements were coded using Dedoose analytic software. RESULTS/ANTICIPATED RESULTS: Established community-based participatory research (CBPR) principles, including mutual respect, transparency, and commitment, are viewed as necessary, but not sufficient. Patience—both with other members and with the group as a work in progress—is highlighted as being a necessary characteristic of participants. Time and funding are 2 of the most important resources, and the majority of members agree that there is no substitute for “skin in the game.” Attempts at last minute, opportunistic engagement were provided as examples of what had not worked. One ongoing tension is the balance between process and product. Individual members are beholden to organizations to different degrees, and the need to produce something in the form of publications or grant money can limit the amount of time members can commit to the collaborative. At the same time, these products are unlikely to materialize if members are not invested in the process of growing and sustaining the collective. DISCUSSION/SIGNIFICANCE OF IMPACT: Out of the 7 community organizations who currently participate in ADAPT, only 1 is explicitly focused on health in the traditional sense. The others are primary service organizations, but because they understand the impact of the social determinants of health on the local community—including housing, employment, education, nutrition, among other factors—the research collaborative is able to leverage the knowledge and expertise of the academic researchers and the community partners to focus on health topics most salient to the local Chinatown community.

OBJECTIVES/GOALS: Transgender, non-binary, and gender expansive (TGE) patients experience significant barriers to high-quality care including limited provider expertise and pathologization within health documentation. This study aimed to evaluate the use of gender-affirming language within free text medical notes of TGE patients. METHODS/STUDY POPULATION: We conducted a qualitative analysis of free text medical notes in adult (> age 18 years) TGE patients seen in inpatient and outpatient medicine and general surgery clinics between January 2019 and January 2022 at three independent health systems in San Francisco. TGE patients were identified based on self-identified gender identity, sex assignment at birth, and legal sex. We conducted a thematic analysis to assess use of gender-affirming language, including self-identified pronouns, chosen names, gendered and gender-neutral descriptors, sex-related traits, and pathologizing language. RESULTS/ANTICIPATED RESULTS: Within pilot data, we found inconsistent use of gender-affirming language within notes, with pronounced variability within the history of present illness, the clinical one liner, and the problem list. Within one liners, many did not include patient-identified pronouns (81%), omitted chosen names (53%), and utilized gendered language that was misaligned with patient self-identified gender identity (27%) - frequently including the use of outdated terms i.e. female-to-male and transsexual. Many problem lists included gender-related care, with some describing hormonal and surgical interventions and others utilizing language to pathologize trangender status. DISCUSSION/SIGNIFICANCE: Our study identifies gaps in the use of gender-affirming language in medical notes. Of particular significance in the era of open notes wherein patients can view their medical records, our study offers a framework for assessing and increasing gender-affirming language use within free text medical notes that can be applied across health systems.

OBJECTIVES/SPECIFIC AIMS: The objective of the study is to examine the ability of iTBS to improve depression and executive impairment in depressed older adults. If effective, this treatment will have the potential to improve the quality of life in LLD. METHODS/STUDY POPULATION: From 12- 2016 to date older adults (60 – 85 y/o) in a major depressive episode, with evidence of executive dysfunction (on the NIH Tool Box battery) were enrolled. iTBS protocol: This brief paradigm (3 min 9 seconds duration) was administered on weekdays for four weeks (20 sessions total). Stimulation intensity was set up to 120% of the observed motor threshold. Depression primary outcome: Change in the Montgomery Asberg Depression Rating Scale (MADRS) from baseline to the end of iTBS course. Executive function primary outcome: Change in executive measures from the electronic NIH Tool Box cognitive domain battery8. Executive secondary outcome: Change in scores from baseline to the end of iTBS on the Frontal Systems Behavior Scale (FrSBe), this self reported instrument measures dys-executive behavior. Statistical Analysis: paired t-test examined changes in depression and executive variables from baseline to post iTBS. Pearson correlation examined the association between degree of mood improvement and degree of improvement in executive function. SPSS v 24 was used for all analyses. RESULTS/ANTICIPATED RESULTS: We examined 11 subjects. Primary outcomes: Patients showed a significant decrease in scores on the Montgomery Asberg Depression Rating Scale (MADRS) from baseline Mean (M) = 27.73, Standard Deviation (SD) 8.2 to the end of 4 weeks of iTBS: M = 15.91, SD = 10.05, t = 7.4, p < .001. The Flanker Inhibitory Control and attention test significantly improved from baseline M = 91.0, SD = 7 to the end of iTBS M = 98.7, SD = 12.8, t = −2.9, p = .014 (higher scores at week 4 denote improvement). The List Sorting Working Memory test and the Dimensional Change Card sort a measure of cognitive flexibility improved but did not reach statistical significance. The self reported executive measure improved from baseline M = 48.6, SD = 9.4 to post iTBS M = 39.4, SD = 8.5, t = 3.8, p = .003 (lower scores at week 4 denote improvement). We also examined whether the degree of improvement in depression related to the degree of improvement in executive function. We found positive correlations between change in mood scores with iTBS with change in executive scores with iTBS, with a strong relationship with working memory r = 0.34. Tolerability and Side effects: Common side effects were twitching in facial muscles during the stimulation (n =11), headaches (n =10) and pain or discomfort at the stimulation site and face (n =4). One participant withdrew due to intolerance to the stimulation. DISCUSSION/SIGNIFICANCE OF IMPACT: The iTBS paradigm was effective in improving mood and executive function in older adults. Both the psychometric measure and the self reported executive function measure (indicative of dysexecutive behavior) reflected improvements post iTBS. Improvement in executive function was correlated with depression improvement. We targeted the Dorso Lateral Prefrontal cortex, which exhibits decreased connectivity with the dorsal anterior cingulate in depressed elderly and is a key in orchestration of executive function. Our findings are consistent with the conceptualization of depression as a circuit level disorder affecting interconnected networks involving mood and cognition. Although we demonstrated potential therapeutic effects, the mechanism of action of iTBS remains unknown. We are presently conducting a randomized controlled trial to examine the effects of iTBS on brain connectivity using functional MRI. Results of this study underway will hopefully demonstrate engagement of the TMS target and contribute to a neurocircuitry based approach treatment of geriatric depression.

OBJECTIVES/SPECIFIC AIMS: Peer groups are one of the strongest determinants of alcohol use and misuse. Furthermore, social influence plays a significant role in alcohol use across the lifespan. One of the factors that most consistently predicts successful treatment outcomes for alcohol use disorders is one’s ability to change their social network. However, the concept of social influence as defined by suggestibility or susceptibility to social influence has not yet been studied as it relates to drinking behavior and acute subjective response to alcohol. Our objective was to examine the relationship between suggestibility and alcohol consumption and responses, using an intravenous alcohol self-administration (IV-ASA) paradigm in social drinkers. METHODS/STUDY POPULATION: Healthy, social drinkers (n=20) completed a human laboratory session in which they underwent the IV-ASA paradigm. This consisted of an initial 25-minute priming phase, where participants were prompted to push a button to receive individually standardized IV alcohol infusions, followed by a 125-minute phase during which they could push the button for additional infusions. IV-ASA measures included the peak and average breath alcohol concentration (BrAC) and number of button presses. Subjective responses were assessed using the Drug Effects Questionnaire (DEQ) and Alcohol Urge Questionnaire (AUQ) collected serially during the session. Participants completed the Multidimensional Iowa Suggestibility Scale (MISS) to assess suggestibility. The Alcohol Effects Questionnaire (AEFQ) was used to assess alcohol expectancies and the Timeline Followback questionnaire measured recent drinking history. RESULTS/ANTICIPATED RESULTS: After controlling for drinking history, greater suggestibility significantly predicted greater average BrAC, greater peak BrAC, and a greater number of button presses (p=0.03, p=0.02, p=0.04, respectively) during the early open bar phase. Suggestibility significantly predicted subjective alcohol effects following the priming phase which included “Feel,” “Want,” “High,” and “Intoxicated” and was trending for “Like” (p=0.02, p=0.03, p=0.01, p=0.03, p=0.054, respectively) as well as AUQ (p=0.03). After controlling for drinking history, suggestibility significantly predicted “Feel,” “Like,” “High,” and “Intoxicated” peak scores during the open bar phase (p=0.03, p=0.009, p=0.03, p=0.03, respectively). There was no association between suggestibility and “Want More” alcohol. Suggestibility was positively associated with three positive expectancies (global positive; p=0.04, social expressiveness; p=0.005, relaxation; p=0.03), and one negative expectancy (cognitive and physical impairment; p=0.02). DISCUSSION/SIGNIFICANCE OF IMPACT: These results indicate that social drinkers that were more suggestible had higher alcohol consumption, greater acute subjective response to alcohol, and more positive alcohol expectancies. As such, susceptibility to social influence may be an important determinant of alcohol consumption, and may provide insight into harmful drinking behavior such as binge drinking. Future analyses should examine the impact of suggestibility on alcohol-related phenotypes across the spectrum of drinking from social to binge and heavy drinking patterns.