OBJECTIVES/GOALS: Immunomodulatory drugs (IMiDs) are critical to multiple myeloma (MM) disease control. IMiDs act by inducing Cereblon-dependent degradation of IKZF1 and IKZF3, which leads to IRF4 and MYC downregulation (collectively termed the “Ikaros axis”). We therefore hypothesized that IMiD treatment fails to downregulate the Ikaros axis in IMiD resistant MM. METHODS/STUDY POPULATION: To measure IMiD-induced Ikaros axis downregulation, we designed an intracellular flow cytometry assay that measured relative protein levels of IKZF1, IKZF3, IRF4 and MYC in MM cells following ex vivo treatment with the IMiD Pomalidomide (Pom). We established this assay using Pom-sensitive parental and dose-escalated Pom-resistant MM cell lines before assessing Ikaros axis downregulation in CD38+CD138+ MM cells in patient samples (bone marrow aspirates). To assess the Ikaros axis in the context of MM intratumoral heterogeneity, we used a 35-marker mass cytometry panel to simultaneously characterize MM subpopulations in patient samples. Lastly, we determined ex vivo drug sensitivity in patient samples via flow cytometry. RESULTS/ANTICIPATED RESULTS: Our hypothesis was supported in MM cell lines, as resistant lines showed no IMiD-induced decrease in any Ikaros axis proteins. However, when assessed in patient samples, Pom treatment caused a significant decrease in IKZF1, IKZF3 and IRF4 regardless of IMiD sensitivity. Mass cytometry in patient samples revealed that individual Ikaros axis proteins were differentially expressed between subpopulations. When correlating this with ex vivo Pom sensitivity of MM subpopulations, we observed that low IKZF1 and IKZF3 corresponded to Pom resistance. Interestingly, most of these resistant populations still expressed MYC. We therefore assessed whether IMiD resistant MM was MYC dependent by treating with MYCi975. In 88% (7/8) of patient samples tested, IMiD resistant MM cells were sensitive to MYC inhibition. DISCUSSION/SIGNIFICANCE: While our findings did not support our initial hypothesis, our data suggest a mechanism where MYC expression becomes Ikaros axis independent to drive IMiD resistance, and resistant MM is still dependent on MYC. This suggests targeting MYC directly or indirectly via a mechanism to be determined may be an effective strategy to eradicate IMiD resistant MM.

OBJECTIVES/SPECIFIC AIMS: More men than women develop urinary stones and their prevalence alters in women with menopause suggesting a steroidal influence. In men the incidence of stones is highest during July and August suggesting that environmental factors such as Vitamin D (VitD), a steroid, may affect stone formation. Previous studies have found differences in the development of stones between men and women; however, the reasons for sex differences in stone formation and type remain unclear. METHODS/STUDY POPULATION: We examined VitD levels in men and women (n = 18,753) that had no diseases based on a lack of an ICD-9 or ICD-10 code in their electronic medical record. We found that normal, healthy women had significantly higher levels of sera VitD compared to men (p = 6x10-6). We then examined whether sex differences existed for key endpoints/data from the Mayo Clinic Urinary Stone Disease (USD) Registry, which has around 1,600 urinary stone patients that are well-phenotyped according to sex, age and stone type. RESULTS/ANTICIPATED RESULTS: Control women were found to have higher sera VitD levels than men, but the sex difference no longer exists in kidney stone disease patients. When we further separated by race, we found that differences in VitD levels reappeared; this suggests that race also plays a role in sera VitD variances. DISCUSSION/SIGNIFICANCE OF IMPACT: We are developing a disease severity score, which we will use to correlate to sera VitD levels in patients according to sex, age and race. Future analyses will take into account whether subjects had VitD and calcium supplementation. This project begins to explore the mechanism behind the sex differences known to exist in urinary stone disease, which is critically needed to provide improved diagnosis and therapy for this debilitating disease.

OBJECTIVES/GOALS: AA are over-represented on the waitlist for kidney transplant and are often unaware of how waitlist acceptance practices differ across transplant programs and influence access to transplant. We will develop a culturally sensitive transplant program report card to communicate these variations. METHODS/STUDY POPULATION: Scientific Registry of Transplant Recipients (SRTR) data will be used to identity clinical factors strongly associated with AA access to transplant. Interviews and focus groups with AA kidney transplant candidates and their families will collect feedback on the SRTR report card and inform the development of the culturally sensitive report card. Additional focus groups will evaluate its effect on knowledge and medical decision making. We will collaborate with the stakeholders, including AA transplant candidates and their families, transplant programs, SRTR, and providers, to identify strategies to disseminate the report card in the AA community RESULTS/ANTICIPATED RESULTS: To date, no investigation has systematically collected feedback on the SRTR transplant program report card from AA candidates to ensure that the tool is accessible and effective in the AA community. We hypothesize that a culturally sensitive report card will improve AA candidates’ knowledge of program factors that impact access to transplant and enable informed decisions about where they pursue a transplant evaluation. The results of this study have the potential to change how AA patients are counselled while seeking transplantation. DISCUSSION/SIGNIFICANCE OF IMPACT: A culturally sensitive report card can reach more AA patients and enable more informed decision making by providing education about differences in transplant programs that may impact their access to transplant. In the future, we will design a trial to evaluate the prototype.

OBJECTIVES/GOALS: Recent research has attempted to identify diagnostic, prognostic, and predictive biomarkers, however, currently, no biomarkers can accurately diagnose GBC and predict patients prognosis. Using machine learning, we can utilize high-throughput RNA sequencing with clinicopathologic data to develop a predictive tool for GBC prognosis. METHODS/STUDY POPULATION: Current predictive models for GBC outcomes often utilize clinical data only. We aim to build a superior algorithm to predict overall survival in GBC patients with advanced disease, using machine learning approaches to prioritize biomarkers for GBC prognosis. We have identified over 80 fresh frozen GBC tissue samples from Rochester, Minnesota, Daegu, Korea, Vilnius, Lithuania, and Calgary, Canada. We will perform next-generation RNA sequencing on these tissue samples. The patients clinical, pathologic and survival data will be abstracted from the medical record. Random forests, support vector machines, and gradient boosting machines will be applied to train the data. Standard 5-fold cross validation will be used to assess performance of each ML algorithm. RESULTS/ANTICIPATED RESULTS: Our preliminary analysis of next generation RNA sequencing from 18 GBC tissue samples identified recurrent mutations in genes enriched in pathways in cytoskeletal signaling, cell organization, cell movement, extracellular matrix interaction, growth, and proliferation. The top three most significantly altered pathways, actin cytoskeleton signaling, hepatic fibrosis/hepatic stellate cell activation, and epithelial adherens junction signaling, emphasized a molecular metastatic and invasive fingerprint in our patient cohort. This molecular fingerprint is consistent with the previous knowledge of the highly metastatic nature of gallbladder tumors and is also manifested physiologically in the patient cohort. DISCUSSION/SIGNIFICANCE: Integrative analysis of molecular and clinical characterization of GBC has not been fully established, and minimal improvement has been made to the survival of these patients. If overall survival can be better predicted, we can gain a greater understanding of key biomarkers driving the tumor phenotype.

OBJECTIVES/GOALS: Rib fractures are common traumatic thoracic injuries and are associated with high rates of morbidity and mortality. In those age ≥ 65, the rate of these complications double. This study sought to identify the extent to which injury-related predictors influence clinical outcomes in geriatric patients with rib fractures. METHODS/STUDY POPULATION: A retrospective 5-year review was performed of a single Level 1 Trauma center registry. Geriatric patients (≥65 years of age) diagnosed with rib fractures from January 1, 2014 to December 31, 2019 were included. The primary outcome of interest was in-hospital mortality. Secondary outcomes included hospital and intensive care unit length of stay (HLOS and ICU LOS, respectively) and discharge disposition, as a surrogate for loss of independence. Further, subgroup analysis based on number of rib fractures (i.e. <4 and ≥4 rib fractures) was performed. RESULTS/ANTICIPATED RESULTS: 2,134 adult trauma patients were admitted with at least one rib fracture. Of these, 1,037 (49%) were ≥ 65 years old. This cohort had a mean age of 78.6 years old, injury severity score (ISS) of 11.4, HLOS of 7.4 days and 29% required ICU care with mean ICU LOS of 1.9 days. Only 36% were discharged home compared to 64% who were discharged to a care facility and thus had a loss of independence. Overall mortality was 6.3%. Compared to survivors, non-survivors had a higher ISS (19.3 vs. 10.8, p = < 0.0001) and longer ICU LOS (7.1 vs. 6.5 days, p = 0.04). Analysis based on number of rib fractures showed that those with ≥4 rib fractures had significantly higher mortality (8% vs. 4%, p = 0.008), longer HLOS (8.7 vs. 6.1 days, p < 0.0001), longer ICU LOS (2.6 vs. 1.3 days, p < 0.0001), and significantly lower discharge to home (32% vs. 39%, p = 0.02). DISCUSSION/SIGNIFICANCE: To our knowledge, this is the largest single-center study of geriatric patients with rib fractures. In this study, the observed mortality in patients ≥65 years of age was 6.3% which represents a lower mortality rate than historically reported. Despite this, only 36% were able to be discharged directly to home.

OBJECTIVES/SPECIFIC AIMS: The off-target and organ-specific toxicities observed in cancer immunotherapy present an obstacle to T-cell-based therapeutics. A recent clinical trial underscored the need for improved methods to define TCR specificity after melanoma patients treated with TCR engineered T-cells suffered from fatal cardiovascular toxicity arising from the unpredicted recognition of a muscle-specific peptide. METHODS/STUDY POPULATION: To address this drawback to T-cell-based immunotherapies, we developed a novel protein engineering approach to define the peptide specificity of a given TCR. Here, directed evolution in a yeast display system produced a large scale peptide library, where recognition by the melanoma reactive DMF5 TCR acted as the guiding selective pressure. After this technique identified a panel of putative cross reactive peptides, sequence analysis and computational modeling followed by kinetic binding experiments and structural analysis determined the DMF5 TCR recognizes 2 distinct classes of peptides through chemically distinct mechanisms. RESULTS/ANTICIPATED RESULTS: This information led to the rational, structure-based design of additional cross reactive peptides and introduced a unique approach to screen the human proteome and identify the TCR targets which triggered undesired autoimmunity when this molecule was used in clinical trials. DISCUSSION/SIGNIFICANCE OF IMPACT: The distinct chemical nature of the 2 peptide classes suggest TCRs are more cross reactive than previously thought, presenting an obstacle to cell-based immunotherapy. Defining the peptide specificity of TCRs is of high interest to the immunology community, and will lead to improved approaches to designing engineered TCRs for cell therapy.

OBJECTIVES/SPECIFIC AIMS: In this study, we aim to describe temporal trends in opioid abuse among adolescents and 11-21years and young adults 22-35years with Sickle cell disease hospitalized for sickle cell crisis. We also aim to evaluate clinical and healthcare utilization outcomes of opioid abuse in the same population. In addition, we hope to assess for difference in effect by age category. METHODS/STUDY POPULATION: Our study is a cross-sectional study of data secondarily sourced from the 2007-2014 National Inpatient Sample(NIS), a component of the Healthcare Utilization Project (HCUP). Variables were identified using ICD-9-CM codes. We selected inpatient stays for patients aged 11-35 years admitted for sickle cell crisis. Opioid abuse was the primary outcome of interest. Secondary outcomes were inpatient mortality, total charge, length of stay and select clinical outcomes. We analyzed our data for trends and outcomes. We performed trend analysis of prevalence rates between 2007-2014 by age categories. Propensity-Matched Score regression models were deployed to assess for associations between opioid abuse and outcomes while adjusting for relevant covariates. Sub-group analysis of opioid abuse by age was assessed for outcomes of interest. Trend analysis was performed on Joinpoint Software v4.6.0, (National Cancer Institute, NIH, Bethesda, MD). Outcome analysis was performed on SAS v9.4 (SAS Institute, Cary, NC). Statistical significance was set at 95% and p-value of 0.05, two-tailed. RESULTS/ANTICIPATED RESULTS: Of 86,827 inpatients admitted for sickle cell crisis, 2,363 (2.73%) had a diagnosis of opioid abuse while 84,464 (97.27%)did not abuse opioids. 27,004 (31.01%) of admitted patients were 11-21 years while 59,823 (68.99%) were 21-35 years. We found statistically significant APCs (Annual Percentage Change) showing increasing trends in both age categories for years under review, (18.47% [95% CI 15.39-21.63]; p-value <0.001 in young adults vs. 10.31% [95% CI 3.58-17.49]; p-value 0.009 in adolescents). The difference in APCs between both age categories were also significant (−8.16% [95% CI [−14.26-2.05]; p-value 0.009). There were no parallelism or coincidence in the trend lines. Opioid abuse was found to be associated with significantly longer length of stay (7.74 vs 6.05 days), higher total charge ($40,797 vs $32,164), (aOR 1.44; 95% CI [1.19-1.75]) seizures, sepsis (aOR 1.62; 95% CI [1.35-1.94]) and pulmonary hypertension (aOR 1.36; 95% CI [1.12-1.66]). No significant association was found for inpatient mortality, transfusion, cardiac dysrhythmias, pulmonary embolism and acute kidney injury. Significant interaction existed between opioid abuse and age for total charge (for $41,869 vs $29,371 among adolescents & $40,632 vs $32,550 among young adults; interaction p-value 0.03). DISCUSSION/SIGNIFICANCE OF IMPACT: Trends show a significant increase in the prevalence of opioid abuse among adolescents and an increasingly higher prevalence when adolescents transition to young adults. Opioid abuse among sickle cell patients is associated with significant poor healthcare resource utilization and clinical outcomes. Public health interventions to prevent worsening opioid abuse prevalence are expected to improve patient outcomes.

OBJECTIVES/GOALS: To describe preliminary results of Alzheimer’s and dementia caregivers’ (CGs) mobile app use and intention to adopt mHealth apps for their own chronic condition self-management. To discuss implications for designing and implementing mHealth interventions for CGs. METHODS/STUDY POPULATION: This study aims to recruit 110 racially and ethnically diverse family caregivers (CGs) who have a chronic condition, provide care for persons with Alzheimer’s disease or related dementias, and have access to a mobile device. This is a cross-sectional correlational study collecting data with computer-assisted telephone interviews stored through REDCap. The study survey was created using existing surveys about mobile app use; relevant, well-validated research instruments; and questions from the U.S. Census and other national surveys. CGs are being actively recruited from the Baltimore-Washington metropolitan area using various recruitment strategies that have been effective in prior studies. RESULTS/ANTICIPATED RESULTS: The majority of CGs used websites (86%), mobile devices (68%) or apps (53%) to manage their own health. CGs using health-related apps were tracking their exercise (60%), diet (60%), medical records (50%), and physical health measures (50%). More than 4 out of 5 (82%) predicted they would use mobile apps to self-manage their chronic condition, though only 68% actually planned to use them. 86% of CGs were using mobile apps for non-health related purposes, with the most popular app being weather (90%), followed by social media (74%), music/entertainment (68%), and banking/business apps (63%). CGs used weather and social media apps most often (2 or more times/day) and spent 9 hours/week on apps. DISCUSSION/SIGNIFICANCE OF IMPACT: Websites and mobile apps appear to be feasible modes to deliver health interventions to CGs. Researchers should consider including features of apps most frequently used by CGs, such as the weather, ways to connect with others, and music/entertainment, when delivering mHealth interventions to CGs.

OBJECTIVES/GOALS: Minoritized populations experience a large burden of Alzheimer’s Disease; interventions are often delayed and underrepresented communities’ participation in clinical trial research is low. Lack of information has been proposed as a barrier to clinical research enrollment of minoritized populations. METHODS/STUDY POPULATION: Brain Train, a cluster randomization trial, evaluated the role of education in increasing willingness to participate in research. A 3 segment program was developed whereas segment 3 had two versions: clinical trial education or healthy brain aging video. Brain Train was presented to multicultural communities with participants of at least 50 y/o throughout WNY. The primary outcome measure is evaluating the percent change in responding yes to would you be interested in participating in a clinical trial? before and after segment 3. The secondary outcome measure and exploration of barriers are measured by a Research Attitude Questionnaire. Demographic information such as age, race, gender, socioeconomic status, and educational attainment is collected. The statistical model is a generalized linear mixed model. RESULTS/ANTICIPATED RESULTS: Sixteen sessions with 281 participants were completed to generate the pilot dataset. We see 59.29 % of individuals answered yes before segment 3 and 46.02% answered yes after the educational intervention. Our data shows there is a 13.3% decrease in clinical trial participation interest after the educational intervention. Through our RAQ responses, our data shows significance when it comes to our participants’answers to questions regarding society needing to devote more resources to medical research (p=0.04). Trust emerged as the most significant barrier when it comes to one’s willingness to participate in medical research and clinical trials (p=0.03). DISCUSSION/SIGNIFICANCE: Our preliminary results from the first sixteen events suggest that the power of education is not sufficient to overcome barriers to clinical trial participation for underrepresented communities. Instead, trust appears to be the most significant barrier. Trust building strategies should be explored to answer this research question.

OBJECTIVES/GOALS: Policy makers are interested in understanding scientific collaborations that translate knowledge into population health. The objective of this study is to compare the translational research collaboration of the Hispanic Alliance of Clinical and Translational Research in 2020 and 2023 by using Social Network Analysis (SNA). METHODS/STUDY POPULATION: We conducted a systematic document review of all the Hispanic Alliance Calls for Pilot Projects from 2020 to 2023 including key attributes of the investigators and collaborators such as academic institution, highest degree, and collaborator type. Scientific collaboration was defined as two or more researchers working together in grant proposal for a pilot project application. Study data was recorded and tracked using an Excel spreadsheet. R Statistical software was used to analyze and map the networks resulting from collaboration interactions comparing the 2020 Call and 2023 Call. Network statistics were performed including nodes, isolates, edges, components, density, diameter, average degree, and the size of the main component. RESULTS/ANTICIPATED RESULTS: A total of 134 investigators comprised the overall network. The network are predominantly clinician (49.3%) and basic researchers (25.4%). Preliminary results shows that diversity of disciplines and affiliations in the collaborative relationships increased across time. Findings demonstrated that the number of nodes/actors increased from 16 to 65 comparing 2020 to 2023 and the edges/relationships from 12 to 53. The number of translational research cluster increased from 4 to 13 comparing 2020 to 2023. More extensive collaborative cluster occurred across time with over 15 researchers collaborating. A mentor was the key player connecting these research clusters. DISCUSSION/SIGNIFICANCE: This study provides critical data to mapping the IDeA CTR translational research collaboration patterns. Research collaboration increased across time. This innovative approach serves to foster data-driven decision-making to enhance collaboration, diversity, and program outcomes. It offers valuable insights for policy and practice.

Within Wisconsin, our residents experience some of the worst health disparities in the nation. Public reporting on disparities in the quality of care is important to achieving accountability for reducing disparities over time and has been associated with improvements in care. Disparities reporting using statewide electronic health records (EHR) data would allow efficient and regular reporting, but there are significant challenges with missing data and data harmonization. We report our experience in creating a statewide, centralized EHR data repository to support health systems in reducing health disparities through public reporting. We partnered with the Wisconsin Collaborative for Healthcare Quality (the “Collaborative”), which houses patient-level EHR data from 25 health systems including validated metrics of healthcare quality. We undertook a detailed assessment of potential disparity indicators (race and ethnicity, insurance status and type, and geographic disparity). Challenges for each indicator are described, with solutions encompassing internal (health system) harmonization, central (Collaborative) harmonization, and centralized data processing. Key lessons include engaging health systems in identifying disparity indicators, aligning with system priorities, measuring indicators already collected in the EHR to minimize burden, and facilitating workgroups with health systems to build relationships, improve data collection, and develop initiatives to address disparities in healthcare.

The Advancing the Science of Mentorship: Future Directions for Sustainable Implementation and Evaluation of Mentorship Education for the Clinical and Translational Science Workforce conference was held in Madison, Wisconsin, in April 2023. The conference provided an engaging and scholarly forum for clinical and translational researchers from diverse backgrounds and career stages (including leaders at Clinical and Translational Science Award (CTSA) hubs and affiliated institutions) with a professional interest and commitment to improving and diversifying workforce development and fostering a climate of inclusive excellence through best practices in mentorship. Outcomes from the conference include an online resource and a new Community of Practice.

Racially and ethnically minoritized individuals, first-generation college students, and women are significantly underrepresented in science, technology, engineering, and mathematics (STEM) careers. This lack of equal representation limits creativity and progress in these fields and perpetuates systemic barriers that discourage students from pursuing STEM pathways. This special communication introduces the three-tiered mentorship model employed in the Teen Science Ambassador Program (TSAP), which incorporates senior mentors, near-peer mentors, and high school ambassadors (i.e., mentees) to promote education, hands-on research, and career development in STEM for underrepresented students. We discuss the benefits and challenges of the three-tiered model and offer recommendations for optimizing its effectiveness to enhance mentorship experiences for all participants. Findings from the TSAP program suggest that the three-tiered approach benefited all participants: high school ambassadors gained STEM skills and confidence, near-peer mentors developed leadership and communication abilities, and senior mentors improved mentorship skills. However, the effectiveness of near-peer mentorship is highly dependent on clearly defined roles and structured involvement. Thus, feedback collected from each mentorship tier was used to inform subsequent iterations of the program. The layered mentorship structure fostered a sense of community and belonging, which is crucial for retaining individuals from underrepresented groups in STEM.

OBJECTIVES/SPECIFIC AIMS: We hypothesize that both NGF and TNF-α contribute to oral cancer pain by upregulating pro-nociceptive inflammatory cytokines. METHODS/STUDY POPULATION: In total, 48 oral cancer patients were evaluated and their pain scores were measured using a validated oral cancer pain questionnaire. Presence of perineural invasion (PNI) was identified from patients’ pathology reports. We utilized The NIH Cancer Genome Atlas (TCGA) Head and Neck Cancer cohort to investigate the association between pain and genes related to NGF, TNF-α, and their receptors (TRKA, P75, TNF-α receptor 1, and TNF-α receptor 2) in oral cancer samples by employing PNI as a surrogate for pain. Demographic characteristics, clinical characteristics, and genes were analyzed using logistic regression models. A xenograft cancer pain model was created by inoculating human oral cancer cells (HSC-3) into the mouse hind paw. Mice (n=6 per group) were treated with anti-NGF alone, anti-TNF-α alone, a combination of anti-NGF and anti-TNF-α, or PBS (vehicle control). Nociceptive behaviors were measured using an electronic paw withdrawal assay. Paw volume was measured using a plethysmometer. Cytokines in the paw tissues were measured using a multiplex assay kit with 28 cytokines. RESULTS/ANTICIPATED RESULTS: Oral cancer patients with PNI report significantly more pain compared with patients without PNI in our patient cohort (p<0.05). From analysis of TCGA data, we found that PNI is significantly associated with lymphovascular invasion, pathological nodal invasion, and pathological tumor staging (all p<0.05). In adjusted models, we observed that the NGF receptor p75NTR (NGFR) and the TNF-α receptor 1 (TNFRSF1A) were associated with PNI (both p<0.05) and significantly correlated to each other (r=0.25, p<0.001). High levels of TNF-α were present in HSC-3 cell lines and the mouse xenograft cancers. In mice with cancer pain, combined treatment with anti-NGF and anti-TNF-α together provided more effective pain control compared with either anti-NGF or anti-TNF-α treatment alone (p<0.05). We found significantly increased levels of MIP3a, IL-1b, IL-2, IL-4, IL-28b, IL-23, IL17a, IL-31, and IL-33 in cancer mice compared with normal mice (all p<0.05). The combination therapy significantly reduced cytokines MIP3a, IL-1b, IL-4, IL-28b, IL-31, and IL-33 (all p<0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: We show that targeting both NGF and TNF-α provides more effective pain relief in an oral cancer model. These results suggest that therapeutic strategies aimed at both pathways could yield improved pain management for oral cancer patients.

OBJECTIVES/SPECIFIC AIMS: To compare functional differences in WJ-MSCs-derived from term Versus preterm infants. METHODS/STUDY POPULATION: WJ-MSCs were enzymatically digested from umbilical cord tissue from Term (gestational age ≥37 wk, n=4) and Preterm (gestational age ≤32 wk, n=5) neonates. Cells were characterized by (1) surface antigen markers using flow cytometry, (2) ability to differentiate into adipogenic, chondrogenic, and osteogenic lineages following in vitro stimulation, (3) colony forming unit efficiency, (4) proliferation rates, and (5) cell motility assay. RESULTS/ANTICIPATED RESULTS: WJ-MSCs were successfully isolated from both Preterm and Term groups. Cells adhered to plastic and displayed characteristic spindle-shaped morphology when cultured under standard conditions. WJ-MSCs from both groups expressed surface antigen markers CD73, CD90, and CD146 (≥90%) and did not express hematopoietic markers HLA-DR, CD79, or CD117 (<5%). Preterm and Term cells were capable of differentiating into osteogenic, chondrogenic, and adipogenic lineages. There were no significant differences between the groups when evaluated by colony forming efficiency, proliferation rates, or cell motility. DISCUSSION/SIGNIFICANCE OF IMPACT: These preliminary findings suggest that WJ-MSCs derived from full-term or preterm neonates have similar functional characteristics. Future studies will focus on the regenerative potential of WJ-MSCs from preterm and term infants following changes in the microenvironment (eg, oxygen tension, inflammatory stimulation).

OBJECTIVES/SPECIFIC AIMS: The Life’s Simple 7 (LS7) metric was created by the American Heart Association with the goal of educating the public on seven modifiable factors that contribute to heart health. While it is well documented that these ideal health behaviors lower risk of cardiovascular disease (CVD) in the general population, the association between the LS7 ideal health metrics and end stage renal disease (ESRD) risk has not been examined in a lower socioeconomic population at high risk for both ESRD and CVD. Our objective is to examine the association between the LS7 score and incident ESRD in a cohort of white and black men and women in the southeastern US, where rates of CVD and ESRD are high. METHODS/STUDY POPULATION: The Southern Community Cohort Study recruited ~86,000 low-income blacks and whites in the southeastern US (2002-2009). Utilizing a nested case-control design, our analysis included 1628 incident cases of ESRD identified via linkage of the cohort with the United States Renal Data System (USRDS) from January 1, 2002 to March 31, 2015. Controls (n = 4884) were individually matched 3:1 with ESRD cases based on age, sex, and race. Demographic, medical, and lifestyle information were obtained via baseline questionnaire. The AHA definitions for ideal health were used for non-smoking (never or quit >12 months), body mass index (BMI<25kg/m2) and physical activity (>75 min/week of vigorous physical activity or >150min/week of moderate/vigorous activity). Modified definitions were used for consuming a healthy diet [Healthy Eating Index (HEI10) score>70] and for blood pressure, fasting plasma glucose, and total cholesterol, based on self-reported no history of diagnosis of hypertension, diabetes, and hypercholesterolemia, respectively. The number of ideal health parameters were summed to generate the LS7 score, which ranged from 0-7 with higher scores indicating more ideal health. Adjusted odds ratios (95% confidence intervals) for incident ESRD associated with LS7 score were calculated using conditional logistic regression models, adjusting for income and education. The SCCS ESRD case-cohort dataset will be available by TS 2019 and analyses will be completed to adjust for baseline estimated glomerular filtration rate (eGFR) as a marker of kidney function and to examine whether eGFR modifies the relationship between LS7 and incident ESRD. RESULTS/ANTICIPATED RESULTS: At baseline, mean age was 54 years, 55% (3600) of participants were women, and 87% (5656) were black. A total of 58% (943) of ESRD cases were non-smokers compared to 54% (2633) of controls. ESRD cases had higher prevalence of BMI>25 kg/m2 (81% vs. 74%), hypertension (84% vs. 59%), hypercholesterolemia (48% vs. 34%), and diabetes (66% vs. 22%) compared to controls. A total of 18% (839) of controls and 12% (194) of ESRD cases met ideal exercise recommendations, and 20% of either cases (302) or controls (916) had a HEI10 score above 70. The median LS7 score for controls and ESRD cases was 3 and 2, respectively, and 17% (983) of participants had a low score (0-1) while 2% (105) met 6 or 7 ideal health metrics. Higher LS7 score was associated with lower odds of ESRD (P-trend<0.001). Participants with LS7 score >3 (above median) had 75% reduced odds of ESRD (OR 0.25; 95% CI 0.22, 0.29) compared to those with a score of 2 or less. DISCUSSION/SIGNIFICANCE OF IMPACT: In the SCCS population, the presence of any 3 or more ideal health behaviors is associated with reduced odds of developing ESRD. The components of the LS7 represent important modifiable risk factors that may be targets for future interventions driven by the patient. The attributable risk due to each factor is needed to dissect which ideal behaviors are the most beneficial.

ABSTRACT IMPACT: The development of marketing materials such as flyers and brochures will ultimately be used to promote integration of special populations who are traditionally underrepresented into research by informing and attracting scholars and investigators of available consultative and analytic services that are provided by the ISP Core staff. OBJECTIVES/GOALS: The development of informative and memorable marketing materials is to increase awareness of the ISP Core and its service functions to help with the integration of special populations, as well as promoting scholar and investigator use of these services. METHODS/STUDY POPULATION: After assessing how many CTSA hubs market their ISP services, a flyer and brochure were developed using Adobe InDesign to include information commonly found on CTSA hubs. Flyers and brochures were chosen because they make information physically available outside of a website and be sent to email listservs, making it possible to reach more scholars and investigators. The marketing materials will contain sections to explain the purpose of NJACTS and the ISP Core, list related special populations and available service functions, introduce the ISP Core leadership team, provide examples of past consulting work and contact information for investigators to request service consultations. Flyers will be emailed digitally to listservs and distributed physically along with printed tri-fold brochures to investigators. RESULTS/ANTICIPATED RESULTS: The primary anticipated result from the development of marketing materials include an increased awareness and utilization of ISP Core services and an increased inclusion of special populations in research with NJACTS. The impact of these marketing materials maybe assessed by providing investigators with a short survey when ISP services are requested, which will ask how investigators learned about ISP and its services. DISCUSSION/SIGNIFICANCE OF FINDINGS: Through the work of creating physical marketing materials, the ISP Core will have a method to effectively distribute information about its services, ultimately promoting investigators at all stages to integrate special populations into their research.

OBJECTIVES/SPECIFIC AIMS: To assess the efficacy of exogenous administration of MSCs in animal models of HIE. METHODS/STUDY POPULATION: Adhering to the Systematic Review Protocol for Animal Intervention Studies, a systematic search of English articles was performed using MEDLINE, Web of Science, CINAHL, and Google Scholar. Search term items included mesenchymal stem/stromal cell, hypoxic ischemic encephalopathy, asphyxia, cerebral ischemia, and neonatology. We selected randomized and nonrandomized studies that examined in vivo neonatal models of induced HIE. We excluded studies that combined MSCs with an adjunct therapy. Data were collected on study specifics, MSC characteristics, and outcome measurements. The primary outcome was efficacy of MSC treatment, assessed by functional neurologic measures (cognitive, motor, sensory). Risk of bias was assessed using the SYRCLE’s risk of bias tool and we used the ARRIVE guidelines to describe the quality of study reporting. RESULTS/ANTICIPATED RESULTS: A total of 17 preclinical publications focusing on MSC therapy for HIE met our inclusion criteria. Fifteen of the studies (88%) induced HIE in rodents by ligating the common carotid artery followed by a period of hypoxic exposure. Nine (53%) studies derived their MSCs from rodent bone marrow, whereas the other investigators provided xenografts from human bone marrow or umbilical cord-derived MSCs. Range of MSC dose was between 0.25 and 3.5× 106 cells with 71% of the experiments transplanting the MSCs intranasally or intracerebral. Three studies (18%) administered multiple doses. The cylinder rearing test was the most common (73%) sensorimotor functional outcome performed in the first month following the establishment of HIE. All studies demonstrated a reduction in asymmetrical paw preference after receiving MSC therapy. Lesional size was assessed, using neuroimaging or histologic evaluations, and the majority of studies showed a decreased insult following MSC therapy. DISCUSSION/SIGNIFICANCE OF IMPACT: MSC treatment demonstrates improved functional and structural outcomes that are encouraging for future translational studies.