Retrospective case studies of initiatives supported by the National Institutes of Health’s Clinical and Translational Science Award (CTSA) hubs can be used to identify facilitators and barriers of translational science. This case study investigates how a CTSA Expanded Access program adapted to changing FDA guidance issued in 2020 to support clinicians’ treatment of COVID-19 patients in Michigan. We studied how this program changed throughout the pandemic to support physicians’ requests for remdesivir, convalescent plasma, and other uses of unapproved drugs and novel medical devices. A protocol for retrospective translational science case studies of health interventions developed by CTSA evaluators was used for this case study. Data collection methods included seven interviews and a review of institutional data, peer-reviewed publications, news stories, and other public records. The barriers identified include evolving guidance, misalignment of organizational operations, and the complexity of the research infrastructure. The facilitators of translation include collaboration between research and care teams, increasing engagement with a broad network of supporters, and ongoing professional development for research staff. The findings of this case study can be used to inform future investigations of the principles underlying the translational process.

OBJECTIVES/GOALS: To identify the role of sialoglycans in the mechanisms underlying cancer-associated fibroblast-derived exosomes (CAFEX) immuno-regulatory properties. The central hypothesis is that CAFEX manipulates the immune response to allow immunoevasion and glycomic approaches can identify the signaling factors involved. METHODS/STUDY POPULATION: Cancer associated fibroblasts (CAFs) were isolated from primary head and neck tumors, expanded, characterized and cryopreserved prior to experimentation and isolation of CAFEX. Sialoglycan expression was determined using lectin-specific staining of cells and bead-captured CAFEX in combination with flow cytometry analysis. Siglec expression and expression of M2-macrophage markers were also determined by flow cytometry analysis and cytokine bead arrays. Inhibition studies involved either the enzymatic removal of cell-surface sialoglycans or alternatively, a specific small molecule analog inhibitor of sialoglycan transferases. RESULTS/ANTICIPATED RESULTS: Both CAFs and CAFEX expressed abundant levels of cell-surface sialoglycans. CAFEX induced an M2-macrophage phenotype in primary monocytes, based on surface marker expression and cytokine secretion profiles. The induction of the M2 phenotype in macrophages was attenuated upon the removal of sialoglycans from the surface of CAFEX either by enzymatic removal or via a small molecule inhibitor. CAFEX were also able to directly bind members of the Siglec family, which are sialoglycan specific lectin receptors expressed on immune cells, including macrophages. DISCUSSION/SIGNIFICANCE: Collectively, these studies suggest that surface presentation of sialoglycans by CAFEX may induce an immunosuppressive phenotype in monocytes/macrophages. Consequently, this may be a novel mechanism by which cells within the tumor bed facilitate immunoevasion during tumor progression.

OBJECTIVES/SPECIFIC AIMS: (1) Develop a concept map of ideas from diverse stakeholders on how to best improve training programs. (2) Assess the degree of consensus amongst stakeholders regarding importance and feasibility. (3) Identify which ideas are both important and feasible to inform policy and curricular interventions. METHODS/STUDY POPULATION: Concept mapping is a 4 step approach to data gathering and analysis. (1) Stakeholders [pediatricians (peds), MH professionals (MHPs), trainees, parents] were recruited to brainstorm ideas in response to this prompt: “To prepare future pediatricians for their role in caring for children and adolescents with mental and behavioral health conditions, residency training needs to...”. (2) Content analysis was used to edit and synthesize ideas. (3) A subgroup of stakeholders sorted ideas into groups and rated for importance and feasibility. (4) A large group of anonymous participants rated ideas for importance and feasibility. Multidimensional scaling and hierarchical cluster analysis grouped ideas into clusters. Average importance and feasibility were calculated for each cluster and were compared statistically in each cluster and between subgroups. Bivariate plots were created to show the relative importance and feasibility of each idea. The “Go-Zone” is where statements are feasible and important and can drive action planning. RESULTS/ANTICIPATED RESULTS: Content analysis was applied to 497 ideas resulting in 99 that were sorted by 40 stakeholders and resulted in 7 clusters: Modalities, Prioritization of MH, Systems-Based, Self-Awareness/Relationship Building, Clinical Assessment, Treatment, and Diagnosis Specific Skills. In total, 216 participants rated statements for importance, 209 for feasibility: 17% MHPs, 82% peds, 55% trainees. There was little correlation between importance and feasibility for each cluster. Compared with peds, MHPs rated Modalities, and Prioritization of MH higher in importance and Prioritization of MH as more feasible, but Treatment less feasible. Trainees rated 5 of 7 clusters higher in importance and all clusters more feasible than established practitioners. DISCUSSION/SIGNIFICANCE OF IMPACT: Statements deemed feasible and important should drive policy changes and curricular development. Innovation is needed to make important ideas more feasible. Differences between importance and feasibility in each cluster and between stakeholders need to be addressed to help training programs evolve.

OBJECTIVES/GOALS: The extent that Clinical and Translational Science Award (CTSA) programs offer resources accessible online for training in community-engaged research (CEnR) core competencies is unknown. This study cataloged CEnR resources accessible online from CTSAs and mapped resources to CEnR core competencies. METHODS/STUDY POPULATION: Eight domains of CEnR core competencies were identified: knowledge/perceptions of CEnR; personal traits necessary for CEnR; knowledge of/relationships with communities; training for performing CEnR; CEnR methods; program evaluation; resource sharing and communication; and dissemination and advocacy. A systematic review of CEnR resources accessible online from CTSAs was conducted between July 2018 and May 2019. Resource content was independently reviewed by two reviewers and scored for inclusion of each domain of CEnR core competencies. Domain scores across all resources and inter-rater reliability in scoring domains were assessed using descriptive statistics and Cohen’s kappa coefficients. RESULTS/ANTICIPATED RESULTS: Overall, 214 resources available from 24 CTSAs were eligible for full review. Scoring discrepancies for at least one domain within a resource initially occurred in 51% of resources. “CEnR methods” (50.5%; 108 of 214) and “Knowledge of/relationships with the community” (40.2%; 86 of 214) were most frequently addressed and “Program evaluation” (12.1%; 26 of 214) and “Dissemination and advocacy” (11.2%; 24 of 214) were least frequently addressed domains. Additionally, challenges were noted in navigating CTSA websites to access CEnR resources, and CEnR competency nomenclature was not standardized. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings guide CEnR stakeholders to identify CEnR resources accessible online and gaps to address in CEnR resource development. Standardized nomenclature for CEnR competencies is needed for effective CEnR resource classification. Uniform organization of CTSA websites may maximize navigability. CONFLICT OF INTEREST DESCRIPTION: In addition to the funding information listed previously (see above), within the last three years, R.J. Piasecki has been employed as: Project Coordinator, CEnR Online Learning Project, Johns Hopkins University School of Nursing (Current) Temporary Employee (Doctoral Student Intern), Michigan State University Institute for Health Policy (Current) Clinical RN, Intrastaff at the Johns Hopkins Health System (Past) Research Data Analysis Assistant, Maryland Institute for Emergency Medical Services (Past - contracted)

Objectives/Goals: This study aimed to explore Puerto Rican adolescents’ mental health experiences, focusing on risk and protective factors, and cultural perspectives on mental health. Methods/Study Population: Three focus groups were conducted: two with 20 adolescents aged 12 to 18 years of both genders and one with five adults who work with adolescents. Data were analyzed using interpretative phenomenological analysis. Results/Anticipated Results: The majority of participants in both groups of adolescents identified five key themes: social pressures, barriers to discussing mental health, the impact of social media, coping strategies, and institutional interventions. The adult focus group highlighted adolescent mental health problems, support systems, family and social factors, the church’s role, and recommended interventions. Discussion/Significance of Impact: The findings emphasize that social and familial pressures, mental health stigma, and social media significantly impact adolescent mental health. Coping strategies, such as sports, art, and nature, were also identified. These themes underscore the need for safe, supportive spaces, and targeted approaches to address youth mental health.

OBJECTIVES/GOALS: Inflammation-promoting exposures, including hyperglycemia and inflammatory cytokines, are common in the development and progression of multiple cancers. Here, we determine if high glucose drives the dysregulation of XRCC1, changing BER/SSBR capacity, and increasing resistance to DNA damaging agents. METHODS/STUDY POPULATION: Here, we acutely exposed cell lines models with 30 mM glucose to mimic hyperglycemic changes and monitored the gene and protein expression of STAT3 and XRCC1. We selected the osteosarcoma cell line U2OS, with high STAT3 activation before glucose challenge, and the non-tumorigenic human embryonic kidney cell line HEK293T, with low STAT3 activation before glucose challenge, to dissect the role STAT3 plays in dysregulating DNA repair. We also examined changes in STAT3 occupancy at the XRCC1 promoter following glucose challenge using chromatin immunoprecipitation (ChIP). Finally, we measured changes in the sensitivity to the alkylating agent methyl methanesulfonate (MMS) induced by the glucose challenge using cell survival and DNA strand break analysis. RESULTS/ANTICIPATED RESULTS: High glucose challenge increases the phosphorylation and activation of STAT3 and subsequently increases XRCC1 gene and protein content in the cell. Acute high glucose activated STAT3, driving the subsequent expression of XRCC1 in U2OS and HEK293T cells through increased STAT3 occupancy at the XRCC1 promoter. High glucose also reduced sensitivity to MMS, increasing cell survival. The most significant increase in resistance to MMS occurred in the HEK293T, which also showed the largest increase in XRCC1 protein expression following the glucose challenge. Increased survival correlated with the faster resolution of DNA strand breaks in glucose-challenged cell lines. DISCUSSION/SIGNIFICANCE: This work has identified a novel regulatory mechanism by which high glucose drives the expression of XRCC1 through STAT3 activation, increasing DNA repair and resistance to the DNA damaging agent MMS. These data suggest dietary choices induce sustained XRCC1 expression and may contribute to chemoresistance and poor survival outcomes in cancers.

OBJECTIVES/SPECIFIC AIMS: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections (SSTIs) recurrence ranges from 16% to 43% and presents significant challenges to clinicians, patients, and families. The number of emergency department visits for SSTIs increased from 1993 to 2005 from 0.48 to 1.16 ED visits per 100 US residents (95% CI 0.94 to 1.39; p<0.001); high safety-net status EDs saw a 4-fold increase in visits. The CA-MRSA Project (CAMP2) comparative effectiveness research (CER) study aims to evaluate a home-based intervention implemented by Community Health Workers (CHWs) or “promotoras” to prevent recurrence and transmission of CA-MRSA in primarily low-income, minority patients presenting to primary care with SSTIs. The intervention disseminates and implements methods found effective in the REDUCE MRSA trial. The present analysis was conducted using publically available data set to characterize the national patterns of healthcare utilization for treatment of SSTIs. METHODS/STUDY POPULATION: An analysis was conducted using data downloaded from the CDC National Ambulatory Medical Care Survey (NAMCS) and the CDC National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2012 (most recent data available) to evaluate the addition of Emergency Departments (EDs) as compared to Ambulatory Care as recruitment sources for a clinical trial to reduce CA-MRSA SSTI recurrence and household transmission. “Low-income” population was defined using “Expected Source of Payment” categories “Medicaid” and “Uninsured,” and ICD-9-CM dermatologic diagnosis codes for SSTIs and ICD-9-CM Procedure Codes for Incision and Drainage (I&D) were used to define a visit for SSTI treatment. RESULTS/ANTICIPATED RESULTS: In all patients, I&D was performed at a higher rate in EDs as compared with the ambulatory care setting (49.57 vs. 1.44 per 10,000 US residents in Medicaid and Uninsured; 44.48 vs. 5.24 per 10,000 US residents in all other insurance types). Nationally, low-income patients are 4 times more likely to have I&D procedure performed (OR 4.05, 95% CI 0.614–26.759, p<0.0001) and 5 times more likely to be diagnosed with an SSTI (OR 5.10, 95% CI 2.987–8.707, p<0.001) in the ED setting. DISCUSSION/SIGNIFICANCE OF IMPACT: These results confirm that low income patients seek primary care for SSTIs in both EDs and ambulatory care, such as Federally Qualified Health Centers (FQHCs). This also confirms the trend we have experienced in FQHCs in NYC, many of whom refer patients to the ED for the I&D procedure, and those patients return to the FQHC for follow-up. Thus, the most comprehensive test of using CHWs to disseminate and implement the findings from the REDUCE MRSA trial would engage both EDs and Ambulatory Care/FQHCs for patient identification and recruitment.

Objectives/Goals: • Investigate culturally-specific beliefs, caregiving approaches, care preferences, and unmet needs among Asian American, Native Hawaiian, and Pacific Islander (AANHPI) care partners supporting persons living with dementia • Apply identified findings toward culturally-adapting caregiving resources for AANHPI dementia care partners Methods/Study Population: Qualitative data from the Better Together Dementia Care Study and Asian American, Native Hawaiian, and Pacific Islander (AANHPI) Dementia Caregiving Study were analyzed to investigate culturally-specific beliefs, caregiving approaches, preferences, and unmet needs of AANHPI dementia care partners. Both studies remotely conducted and recorded semi-structured interviews (1.5–2.5 hours), with care partners and providers though interview protocols were distinct. Transcripts were AI-generated, through Zoom or Trint, and analyzed using thematic content analysis by two coders. Apriori codes drawn from literature and inductively-identified codes were identified and coded. Preliminary findings informed sociocultural strategies used to adapt existing care partner resources for use in these groups. Results/Anticipated Results: Preliminary analysis of care partner (CP) interviews (N = 8; 4 romantic partners, 4 adult children), revealed differences in caregiving experiences and networks. CPs supporting care receivers (CR) who had emigrated away from extended family networks reported a lack of instrumental support. Most CR (7/8) had adult children, many of whom (6/8) provided some care, though half of CR-child relationships were distant or had past difficulties. Romantic partners were primary CPs while co-caregiving with children; Adult children served as primary CPs for unpartnered CRs (n = 4). Adapted CP resources integrated these findings, acknowledging the complexities of fulfilling traditional filial expectations in light of difficult past relationships. Formal services were framed as an extension of family-coordinated care. Discussion/Significance of Impact: Care partners of immigrants may have limited local family support and may benefit from formal services. Adult children may provide care, though this may be complicated by poor past relationship quality. AANHPI care partners may benefit from culturally-adapted resources which address these issues, though resource acceptability-testing is needed.

OBJECTIVES/GOALS: The Michigan Institute for Clinical & Health Research Community Engagement (MICHR CE) has collaborated for 15+ years with underserved communities on public health issues. As Michigan’s sole CTSA institution, we aim to advance the science of community engagement in translational science statewide. METHODS/STUDY POPULATION: MICHR CE PACE (Promoting Academic-Community Engagement) will advance clinical and translational science. Key steps include: 1) form a PACE Steering Committee; 2) PACE Trainings with community-academic partner Detroit Urban Research Center; 3) PACE Training Manual; 4) community Grand Rounds to bridge academic-community insights; and 5) community resources (e.g., toolkits). PACE projects will spotlight community-engaged research (CEnR) via diverse media including social media and community-level communications. The PACE ScienCE initiative will embody cultural humility by addressing power imbalances, emphasizing trust. We will utilize assessments and root cause analyses to navigate CEnR barriers. RESULTS/ANTICIPATED RESULTS: Anticipated results from MICHR CE’s planned approach with PACE include strengthened academic-community relationships. Formation of the PACE Steering Committee and collaborations are expected to foster more structured and impactful CEnR trainings. The PACE Training Manual will become a foundational resource for CEnR best practices. Community Grand Rounds will reveal increased interdisciplinary insights and community trust. All PACE projects will utilize diverse media to enhance CEnR visibility and community-level access. Lastly, by addressing power disparities via PACE ScienCE, we foresee enhanced trust, reduced barriers, and more transparent community-academic collaborations. DISCUSSION/SIGNIFICANCE: This strategy, based on co-planned efforts and community consultations, aims to reshape Michigan’s CEnR landscape and offers a replicable model for other regions. The insights gained will guide community-academic collaborations promoting translational, inclusive, and efficient community engagement.

OBJECTIVES/SPECIFIC AIMS: Analyze data from the first 30 children enrolled in a prospective cohort study evaluating the ability of specific serum biomarkers to distinguish children with traumatic brain injuries (TBI) from children with orthopedic injuries (OI). METHODS/STUDY POPULATION: Children ages 0<5 years were eligible if they presented to the emergency department within 6 hours of injury. Children were identified as having a TBI if they sustained a head injury and were found to have an acute injury on head CT. Children were identified as having an OI if they sustained a musculoskeletal injury significant enough to necessitate radiography per clinical care. Individual (eg, age) and clinical (eg, radiography findings) factors, as well as serum biomarkers [eg, ubiquitin C-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP)] were collected at time of enrollment. TBI and OI groups were compared using Wilcoxon rank-sum and Kruskal-Wallis tests. RESULTS/ANTICIPATED RESULTS: This cohort consisted of 13 children with TBI (7 with isolated skull fractures, 1 with intracranial injury, and 5 with both a skull fracture and an intracranial injury) and 17 with OI (12 with fractures). Most patients were male (67%) and White (67%), and this did not differ between groups (p>0.1). Children with TBI were significantly younger than children with OI, with an average (±standard deviation) age of 15±13 and 39±13 months, respectively (p<0.01). There was not a significant difference in time from injury to biomarker collection between TBI and OI patients at 4.1±1.8 and 5.8±2.6 hours, respectively (p=0.07). Median (IQR) levels of GFAP were significantly higher (p<0.01) in children with TBI, relative to children with OI: 220 (67–421) pg/mL Versus 37 (25–74) pg/mL, respectively. Median (IQR) levels of UCH-L1 were also significantly higher (p<0.01) in the TBI group, relative to children with OI: 444 (377–449) pg/mL Versus 248 (140–417) pg/mL, respectively. In a subanalysis comparing median biomarker levels across three study groups (ie, TBI with an isolated skull fracture, TBI with an intracranial injury, and OI), group differences remained significant for both biomarkers with TBI patients having higher levels, relative to OI patients, of both GFAP (p<0.01) and UCH-L1 (p=0.02). DISCUSSION/SIGNIFICANCE OF IMPACT: GFAP and UCH-L1 hold promise to improve the diagnosis of TBI in very young children. Identification of a marker of TBI that can be done in the acute care setting would advance the diagnosis of TBI in very young children, a vulnerable population for whom identification of neurological symptoms can be challenging.

OBJECTIVES/GOALS: Familial Hypercholesterolemia (FH) is a common disorder that is vastly underdiagnosed and causes an increased risk for sudden cardiac death. Cardiology providers (CHCPs) are in an ideal position to care for patients with FH. This research aimed to understand the practice behaviors of CHCPs in the screening, diagnosis, and management of FH. METHODS/STUDY POPULATION: An explanatory mixed methods design was utilized for this study. Adaptation of an existing FH knowledge tool guided survey development. The results of the quantitative survey, along with the Knowledge to Action framework and Theory of Planned Behavior, guided development of the interview protocol. Convenience and snowball sampling recruited CHCPs in the Division of Cardiology at Columbia University Irving Medical Center (CUIMC). Descriptive statistical analysis was performed on survey data. Qualitative interviews were conducted with survey respondents who volunteered to participate. Interviews were audio recorded, transcribed, and analyzed thematically. A descriptive review of the educational materials offered by the Division of Cardiology was conducted to identify FH knowledge domains presented. RESULTS/ANTICIPATED RESULTS: CHCPs with MDs, at CUIMC for 6-10 years, in clinical practice for 1-5 years, and in Inpatient Services had the highest average total FH knowledge scores. CHCPs with RNs, at CUIMC for less than 1 year, in clinical practice for 6-10 years, and in Cath Lab had the lowest average FH knowledge scores. Twenty interviews were completed, and four themes emerged- variability in FH care; issues related to addressing FH at institutional, practice setting and individual levels; importance of identifying FH early; and intervention approaches to overcome barriers to caring for FH patients in cardiology. CHCPs with MDs or with experiential FH knowledge were the only CHCPs to describe FH care beyond the point of screening. The document review revealed that only MDs were provided four lectures over the course of 4 years pertaining to FH. DISCUSSION/SIGNIFICANCE: CHCPs with didactic or experiential FH knowledge provided care beyond screening. Future interventions should increase didactic and experiential FH knowledge by incorporating institutional, local, and national FH resources. Improving the FH care CHCPs provide, can reduce FH-related morbidity and mortality as well as improve FH health outcomes.

ABSTRACT IMPACT: This poster will demonstrate how input from a CTSI Community Advisory Board was used to develop a large, annual dissemination event focused on health disparities, health equity, and community engagement. OBJECTIVES/GOALS: The NYU Langone Annual Health Disparities Symposium began in response to the NYU-H+H CTSI’s Community Advisory Board, which expressed a desire to 1) learn about health disparities research at NYU, H+H, and beyond; 2) build connections and interdisciplinary collaborations; 3) support bidirectional dissemination between community and researchers. METHODS/STUDY POPULATION: The annual symposium, a collaboration between NYU Langone’s CTSI, Department of Population Health, Office of Diversity Affairs, and the NYU-CUNY Prevention Research Center, features a keynote, a series of rapid-fire talks, panels on current controversies in population health and the work of the Community Engagement Cores of NYC-based CTSAs, and poster sessions. Each year the event is focused around a specific theme, with the 2020 theme being ‘Research Into Action’. Audience members include faculty, staff, students, health care providers, community health workers, and representatives from community-based organizations, health care facilities, and the NYC Department of Health and Mental Hygiene. For the very first time, the event was held virtually days and CME/CNE credits were provided free of cost. RESULTS/ANTICIPATED RESULTS: The conference explored how institutions have turned research into action, and speakers addressed the ways in which COVID-19 has highlighted structural inequities that have existed across time. 585 attendees participated in the event, with 63 claiming an average of 7.8 hours of continuing education credits. 46 individuals completed the post-event evaluation, with 95% agreeing/strongly agreeing that the symposium increased their awareness of health disparities research taking place at NYU, H+H, and beyond, 91% agreeing/strongly agreeing that they are likely to apply the information learned to their own work, and 91% agreeing/strongly agreeing that the symposium increased their interest in health disparities research. 86% were very/extremely satisfied with the quality of the meeting overall. DISCUSSION/SIGNIFICANCE OF FINDINGS: The 2020 event had the greatest proportion of health care provider attendees (24%), likely due to the opportunity to earn CME/CNE credits. Attendance also grew over the years, from 150 in 2015 to 585 in 2020. This increase is likely due to increased awareness of the event, as well as well as virtual the format, which made it more convenient for attendees.

OBJECTIVES/SPECIFIC AIMS: Community health coalitions (CHC) aim to improve local cultures of health, health behaviors, and health outcomes. However, challenges sustaining partnerships and activities limit CHC impact. Traditional CHC evaluations survey members about perceived effectiveness, failing to capture underlying network structures and community health outcomes. Thus, we applied a mixed-methods evaluation in eight rural Indiana CHC, triangulating social network analysis [(SNA), conducted in 2017], functioning effectiveness [Coalition Self-Assessment Survey (CSAS), also 2017], and latest county health statistics (2015–2016) to assess existing CHC building efforts, inform best practices, and facilitate the adoption of evidence-based programming. METHODS/STUDY POPULATION: Across the eight rural Indiana CHC, relationships between the three evaluation components were analyzed using Pearson’s correlations. We are now collaborating with Purdue’s Nutrition Education Program Community Wellness Coordinators to scale up evaluation efforts throughout Indiana. RESULTS/ANTICIPATED RESULTS: CHC effectiveness was positively correlated with the average number of connections CHC members held in the network (mean indegree) and negatively correlated with the presence of a network broker (eigenvector centrality). However, effective leadership was positively correlated with opioid deaths and treatment, food insecurity, smoking during pregnancy, lack of healthcare coverage, and fair/ poor health status, and negatively correlated with prenatal care. Effective operating norms was positively correlated with smoking during pregnancy and preterm births, and negatively correlated with prenatal care. Effective action outcomes was positively correlated with opioid deaths and treatments, smoking during pregnancy, preterm births, and fair/ poor health status, and negatively correlated with respondents reporting they had no personal doctor. DISCUSSION/SIGNIFICANCE OF IMPACT: Interestingly, CHC effectiveness was positively correlated with poor county health outcomes related to infant well-being. Thus, CHC may develop in counties with a high unmet need for effective pregnancy and infant services. Alternatively, the prevalent CHC focus on obesity prevention may eclipse programmatic efforts to improve infant well-being. Longitudinal evaluations and scaling up evaluation efforts across Indiana are being pursued to clarify trajectories and inform best practices, which in turn should provide recommendations for network structures to improve CHC effectiveness and county health.

OBJECTIVES/GOALS: The primary goals of this study are 1) expand our understanding of the neural circuitry influenced by the neuropeptide Neuromedin U (NMU) via its receptor Neuromedin U Receptor 2 (NMUR2), and 2) provide alternative top-down mechanisms for how NMU regulates high fat food intake and cocaine taking. METHODS/STUDY POPULATION: Immunohistochemistry (IHC) for NMUR2 and cell markers was performed on rat brain tissue containing the medial prefrontal cortex (mPFC). To identify the source of the presynaptic NMUR2, anterograde tracing from the paraventricular nucleus or dorsal raphe nucleus to the mPFC utilizing an AAV2- dsRed-synaptobrevin fusion protein were performed (n=3) and will be followed by IHC. Using in vivo calcium imaging technology (InScopix nVista), neuronal activity (calcium transients) was recorded from the mPFC of two awake, freely behaving rats. Each animal underwent a single session of 30 minutes baseline activity, intraperitoneal NMU administration, and 30 minutes of post-treatment activity. Activity was then processed and recorded as distinct events using the InScopix data acquisition software. RESULTS/ANTICIPATED RESULTS: Medial prefrontal cortex staining for NMUR2 revealed a characteristic “beads on a string” motif, consistent with presynaptic receptor expression. Furthermore, we expect the anterograde tracing experiment will show colocalization of the dsRed-synaptobrevin fusion protein with NMUR2 on synaptic inputs into the medial prefrontal cortex. Following quantification of pre- and post- treatment events using the InScopix data acquisition software, total events during the pre- and post-treatment time periods were calculated. In these studies, both animals demonstrated a clear increase in calcium transient activity between pre- and post- treatment evaluations, suggesting that NMU administration increases the neuronal activity of neurons in the prefrontal cortex. DISCUSSION/SIGNIFICANCE: This research provides a new site of action for the known therapeutic effects of NMU. We demonstrate the presence of presynaptic NMUR2 in the mPFC and show that systemic administration of NMU increases mPFC neuronal activity. This illustrates NMU may act as a top-down mediator for substance use disorders and binge eating behaviors.

OBJECTIVES/SPECIFIC AIMS: Cervical fusion is commonly performed for the management of degenerative disc disease, which can cause spinal stenosis and radiculopathy. Adjacent segment disease (ASD) is an adverse postsurgical outcome experienced by some patients as new radiculopathy, stenosis, or other symptomatic sequelae. We sought to assess whether fusion extension past the cervicothoracic junction reduces the risk of distal ASD after multilevel fusions ending at C7-T3. METHODS/STUDY POPULATION: We retrospectively reviewed all first-time patients undergoing instrumented cervical fusion of at least 2 spinal levels and whose distal level of fusion ranged from C7-T3, at the Johns Hopkins Medical Institutions, from 1999 to 2013. The primary outcome was reoperation for distal ASD. Using multiple logistic regression, ANOVA, and χ2 analysis, we determined the odds of ASD due to age, gender, distal level of fusion, surgical approach (anterior, posterior, or combined), smoking status, and race. RESULTS/ANTICIPATED RESULTS: Of the 158 patients who met the selection criteria, the mean age was 58.7±13.8 years, and 95 (60.1%) were female. Ten patients (6.3%) underwent reoperation for ASD. Patients whose fusions ended at C7 were significantly more likely to develop ASD and undergo reoperation (70%, p=0.007) than those whose fusions ended at T1. There were no differences in age, proximal fusion level, smoking status, BMI, gender, and patient-reported race between the reoperation and non-reoperation groups. Following a multivariable analysis, extending the distal fusion to T1 was again found to be protective against reoperation (OR=0.07, p=0.020). DISCUSSION/SIGNIFICANCE OF IMPACT: Our study shows that for multilevel instrumented cervical fusions that terminate within the cervicothoracic junction, fusion distal to the C7 vertebra is associated with decreased odds of reoperation for symptomatic ASD. Therefore, this study provides clinical evidence that may help surgeons determine the optimal distal fusion segment for multilevel fusions ending at C7-T3.

OBJECTIVES/GOALS: The effect of the Direct-Acting Antiviral (DAA) on hepatic histopathological features from patients treated for HCV has not been thoroughly evaluated. The goals of this retrospective study were to determines differences between the liver biopsies collected before and after DAA treatment and correlated the histopathology with clinical outcome. METHODS/STUDY POPULATION: Spectral imaging was used to evaluate differences in intrahepatic macrophage (CD68, CD14, CD16, MAC 387, and CD163) and T cell (CD3, CD4, CD8, CD45, and FoxP3) phenotypes in paired liver biopsies collected from the same patient before (n=10) and after (n=10) achieving SVR (Figure 1). Imaging analysis and machine learning algorithms were used to evaluate changes in these key immune cells. We also compared differential gene expression of over 700 genes using RNA isolated from liver biopsies with NanoString. RESULTS/ANTICIPATED RESULTS: Multispectral imaging analysis showed a significant increase of proinflammatory/M1-like (e.g., CD14+) and anti-inflammatory/M2-like macrophage (e.g., CD163+) phenotypes in pre-treatment versus post-treatment biopsies, respectively. Gene expression analysis revealed enrichment of inflammatory (HLA-B, STAT1, CXCL10) and interferon induced-antiviral (ISG15, OAS3, MX1 and IFIT1) genes in the pre-treatment vs the post-treatment group. Cell deconvolution analysis also showed a significant increase of M1-like macrophages in the pre-treatment group when compared to the post-treatment group or controls. Upregulation of genes associated with cell proliferation and differentiation (c-KIT and Fos) was observed in the post-treatment biopsies of patients with persistent inflammatory infiltrates. DISCUSSION/SIGNIFICANCE: Protein and gene expression profiles observed in patients before DAA therapy showed a strong macrophage-mediated inflammatory response against HCV infection in the liver that shifted significantly to a tissue remodeling microenvironment after treatment.

OBJECTIVES/SPECIFIC AIMS: Our overall goals are: 1. To engage, inform and educate children and families on clinical research and increase their understanding of the goals and process of participation in research studies/clinical trials; 2. To Increase participation of children, especially those who are disproportionately underrepresented, in clinical research in the Western New York region and beyond. METHODS/STUDY POPULATION: The University at Buffalo Clinical Translational Science Institute conducted meetings in schools, community coalitions while holding focus groups with children with chronic conditions and their families and community health workers to identify the general perceptions of research. These conversations then informed the development of a children’s activity book about research. Completed in 2017, our “Sofia Learns about Research” activity book presents research in a non-threatening way by presenting a child with asthma who walks through the process of learning about research, being recruited and participating in research. The book explains basic concepts about research coupled with fun games and the possibility to color. Over 1,000 copies of the activity book have been disseminated to second to fourth graders via afterschool programs, community events, and medical practice waiting rooms. Recipients of the book are directed to short surveys to provide feedback on the book and their perception of research. The parents are also given the option to sign-up for the Buffalo Research Registry in order to be contacted about research opportunities. RESULTS/ANTICIPATED RESULTS: Response has been very positive, with parents and community participants saying “It’s not just a storybook. The activities keep kids entertained while learning new concepts.” In children informally polled via a brief questionnaire pre and post story reading at an afterschool program, there was an increase in those interested in participating in a research study. In a recent event sponsored by the CTSI Community Engagement Core and other UB organizations, a group of fifty children from diverse background colored with enthusiasm several activity pages and obtained stickers for their “Research Passport”. In a recent teacher focus group we learned that the book content may fit the Science Curriculum and plan on reading sessions in inner-city schools after approval from the district. A pilot reading activity in a Montessori program revealed that second grade children were able to understand and complete the activities in the book. We are obtaining further feedback form teachers and parents in order to design simple protocol to be submitted for IRB approval to obtain more formal feed-back and outcomes in future readings. In parents and focus groups several respondents have indicated its relevance to older populations and English-language learners as well. The book has recently been translated into Spanish and Arabic through a partnership with the International Institute of Buffalo, which “welcomes, connects and empowers the foreign born”. Some of the book’s images have been modified in order to be sensitive to the readers’ culture and we are in the process of collaborating with the International Institute to disseminate it to their clients. We are in the initial phase of planning a mobile application which we anticipate will significantly enhance dissemination. DISCUSSION/SIGNIFICANCE OF IMPACT: This presentation will describe the development process, the underpinning concepts and our plans and current progress towards a more formal community and school dissemination and evaluation. This project was made possible by Team Science in that the expertise of a millennial pre-medical student and an anthropologist with high community involvement was coupled with that of a senior clinical translational researcher. Moreover, much research and attention was devoted to the creation of images that are culturally inclusive. To this end, with the exception of the cover page, we have intentionally created the book in black and white so that the child may use his/her imagination and color the way he/she sees the protagonists and the environment. Great attention was devoted to names of the protagonists with the names of the two main characters being among the most common in the world in numerous countries. Also, the book lends itself to a mobile application which will allow the reader to change colors and shapes of the protagonists to fit his/her cultural background. We are in the early planning stages and will share our progress as part of this presentation. We have strived to disseminate the book with a broad approach in our community. This phase is being followed by a more formal dissemination phase via libraries, schools and community events. This part of the project exemplifies the challenge between wanting to disseminate the book broadly while obtaining formal feedback and outcomes in compliance with regulations protecting the anonymity and/or confidentiality of children and families. Therefore for this second phase of dissemination IRB approval is being sought in order to collect more quantitative and qualitative data on the impact of the book. We have already conducted a focus group with teachers to overcome the challenges around informed consent, especially in the public school system. Our initial findings suggest this resource will improve knowledge and perception of research among children and their families. To our knowledge most of the materials explaining research to children are geared to older children and are often sponsored by pharmaceutical companies for a specific trial. If successful, this book can have a profound impact in reaching out to children outside of the research and medical environments, with the ultimate goal of increasing the child’s and family’s willingness to participate in clinical research and clinical trials.

Objectives/Goals: This study’s objective was to explore how a personal cancer diagnosis impacts the social connectedness (i.e., quality, structure, and functions of social relationships) of adolescent/young adult cancer survivors (AYACS, patients diagnosed with cancer between 15 and 39 years old), to inform intervention development fostering social health. Methods/Study Population: In this qualitative study (part of larger study assessing AYACS’ psychosocial challenges), participants were 15–25 years old at the time of cancer diagnosis and within 6 years of cancer diagnosis. Participants (and consenting parents of participants 18 years old and older) had to have fluency in written and spoken English and access to a computer or smartphone. Qualitative interviewers utilized an interview guide to conduct individual participant interviews. Interviews were audio-recorded and transcribed verbatim. Thematic analysis was used to analyze data using a phenomenological approach to explore how a personal cancer diagnosis impacted social connectedness. Qualitative data related to social connectedness (corresponding to code “Relationships and Support”) are presented. Results/Anticipated Results: Three themes emerged through thematic analysis: (1) AYACS experience substantial heterogeneity related to social support needs; (2) AYACS leverage multiple relationships and resources when seeking support after a personal cancer diagnosis; (3) AYACS’ individual experiences were unique in that some noted positive changes, whereas others noted negative changes in relationships within social networks, specifically with peers. Discussion/Significance of Impact: AYACS experience various social support needs, and leverage multiple relationships when seeking social support. These translational findings create a foundation to develop AYACS social programming, foster peer relationships, and incorporate social science methods to aid intervention development to strengthen AYACS’ social connectedness.

ABSTRACT IMPACT: This work provides context from the patient perspective on the impact of hospital policies on their birthing experiencing during the first peak of the pandemic. OBJECTIVES/GOALS: The goal of this study was to report the intrapartum care experiences from people giving birth during the COVID-19 pandemic in the United States. Place of birth included hospital, birth center and home births. METHODS/STUDY POPULATION: Studies that involved patient-related data collection are hindered by pandemic-related changes in clinical practices and research policies. Our aim was to assess patient experience during a pandemic, we explored data collection via a large online community of pregnant women. We asked if women who birthed during COVID-19 changed their birth setting and if they experienced less respectful care, more pressure to undergo induction and/or cesarean birth and newborn separation. We also wanted to explore whether there were differences in the care experience depending on the race of the woman. Open ended questions on care experiences were included and content analysis conducted. Bivariate analysis was conducted comparing those from high versus less COVID-19 impacted areas and by race (White/Black self-identifying). RESULTS/ANTICIPATED RESULTS: The mean age was 31.5 years (SD = 5.0), 80.7% identified as White, 85.0% married, and 85.3% privately insured (N=388). Bivariate unadjusted analyses comparing high vs. low impact COVID-19 states, 22.3% considered changing their place of birth versus 12.7% in less impacted areas (p<.05): no difference pressure for induction/cesarean based on region. In bivariate unadjusted analysis comparing White and Black people, Black people had higher odds of pressure for cesarean or induction compared to White (OR 10.3, 95% CI 2.2 to 48.6, p=.0003). Black people had lower respect scores vs. White (68.7 vs. 72.3 p<.01) and higher odds of preterm birth 3.7 (1.1 to 12.4, p=0.04). Content analysis themes were institutional policies, changes in care, hospital staff interactions, sub-par care, support during birth and mental health. DISCUSSION/SIGNIFICANCE OF FINDINGS: The analysis demonstrated differences among participants from highly versus less impacted COVID-19 states. Disparities persisted with Black women reporting lower respect, pressure for interventions and more preterm birth when compared to White participants. Limitations include use of a convenience sample and self-reported data.

OBJECTIVES/SPECIFIC AIMS: We will use a structured evaluation framework, the payback framework, to document the outcomes of 15 case studies of pilot projects supported by Georgia CTSA from 2007 to 2014. METHODS/STUDY POPULATION: We will use a case study approach including bibliometric analyses of publications associated with the selected projects, document review (e.g., investigator curriculum vitae, biannual project reports) and investigator interviews. RESULTS/ANTICIPATED RESULTS: We will document outcomes in 5 “payback categories”: (1) knowledge, (2) research targeting, capacity building, and absorption, (3) policy and product development, (4) health benefits, and (5) broader economic benefits. DISCUSSION/SIGNIFICANCE OF IMPACT: This study will aid in characterizing the returns resulting from this research funding and identify its strengths and weaknesses. This study will inform our understanding of the diversity and breadth of outcomes resulting from Georgia CTSA-supported research, and the value pilot projects provide to clinical and translational science and the broader community.