OBJECTIVES/GOALS: Research on mild cognitive impairment (MCI) risk factors in type 2 diabetes mellitus (T2DM) is scarce; however, MCI is a concern in T2DM as it can adversely impact self-care behaviors. This study aims to estimate the proportion of MCI and describe its sociodemographic, clinical, psychosocial, and lifestyle characteristics in older adults with T2DM. METHODS/STUDY POPULATION: Cross-sectional pilot study of 60 adults (aged ≥50yrs) with a diagnosis of T2DM will be recruited at a diabetes center located in San Juan, Puerto Rico. Data on sociodemographic, clinical, psychosocial (depressive symptoms and social support), and lifestyle characteristics related to diabetes self-management (diabetes self-care activities and activities of daily living) will be collected through face-to-face interviews using validated questionnaires. Our primary outcome will be MCI assessed via the Spanish-language version of the Montreal Cognitive Assessment (MoCA-S). The proportion of adults with MCI (MoCA-S score<26) will be estimated, and the sociodemographic, lifestyle, psychosocial, and clinical characteristics of older adults will be compared across MCI status using bivariate analysis. RESULTS/ANTICIPATED RESULTS: Expected results include an estimate of the proportion of MCI among older adults with T2DM, which we hypothesize will be higher in our study than in Puerto Rico’s older adult population (previously reported as 17%). Additionally, we will describe the sociodemographic, clinical, psychosocial, and lifestyle characteristics that significantly differ by MCI status in older adults with T2DM. We expect that those with MCI will be more likely to be females, have lower education and annual income, longer time with a diabetes diagnosis, worse psychosocial profiles (higher levels of depressive symptoms and lower levels of social support), and worse lifestyle profiles (poorer glycemic control and lower activities of daily living score) than those without MCI. DISCUSSION/SIGNIFICANCE: This pilot study is a first step to understanding MCI among older adults with T2DM in Puerto Rico, a Hispanic population with a higher prevalence of T2DM than their US non-Hispanic White counterparts. Its findings can guide the design and implementation of a larger epidemiological study aimed at understanding MCI risk factors among adults with T2DM.

Access to local, population specific, and timely data is vital in understanding factors that impact population health. The impact of place (neighborhood, census tract, and city) is particularly important in understanding the Social Determinants of Health. The University of Rochester Medical Center’s Clinical and Translational Science Institute created the web-based tool RocHealthData.org to provide access to thousands of geographically displayed publicly available health-related datasets. The site has also hosted a variety of locally curated datasets (eg., COVID-19 vaccination rates and community-derived health indicators), helping set community priorities and impacting outcomes. Usage statistics (available through Google Analytics) show returning visitors with a lower bounce rate (leaving a site after a single page access) and spent longer at the site than new visitors. Of the currently registered 1033 users, 51.7% were from within our host university, 20.1% were from another educational institution, and 28.2% identified as community members. Our assessments indicate that these data are useful and valued across a variety of domains. Continuing site improvement depends on new sources of locally relevant data, as well as increased usage of data beyond our local region.

OBJECTIVES/GOALS: This project adopts a multifaceted approach to improving aquaculture management practices in Kenya’s Lake Victoria region by identifying fish pathogens, measuring algal toxin levels in commonly consumed fish, surveying fish farming practices, and educating the public. METHODS/STUDY POPULATION: Limited existing data on the state of floating cage culture in Kenya influenced our decision to begin this portion of the project with a brief literature review of potential Nile tilapia pathogens. Databases were screened for mention of disease in either wild or caged Nile tilapia, with emphasis given to those in Lake Victoria. Results were compiled into a spreadsheet and analyzed for frequently occurring pathogens. The next portion involved creating an interview style survey to assess current cage culture management practices in the region. Editing was done to ensure questions remained unbiased, non-leading, culturally sensitive, multilingual and relevant to the situation. Data went through a quality control screening and analysis was conducted through the R programming language. RESULTS/ANTICIPATED RESULTS: Beginning with mortality, of the 93 farms surveyed, data analysis revealed that there is a higher probability that farms will have a mortality of approximately 20%, over the course of a production cycle. For biosecurity and fish health practices, data shows that 97% of farms do not disinfect scooping nets or other fish handling materials when moving from one cage to another. During the 2022-2023 production cycle, 44% of farms experienced fish kills of over 50 fish. 73% of the 93 farms do not contact any organization when a fish kill occurs. In a qualitative answer, it also appears that many farm workers dispose of their dead fish within the lake, feed it to livestock or dogs, or eat it. Algae blooms have been experienced at 80% of the farms surveyed and 43% of farms say they have seen fish gasping at the surface for air. DISCUSSION/SIGNIFICANCE: While farms are implementing good management practices in the areas of cage design, stocking, and feeding practices, there is room for improvement in fish health, biosecurity, and managing algal blooms. The findings provide insight into the areas that should be considered when taking action to improve the welfare of the region.

Institutional Development Awards for Clinical and Translational Research (IDeA-CTR) networks, funded by NIH/NIGMS, aim to advance CTR infrastructure to address historically unmet state and regional health needs. Success depends on the response to actionable feedback to IDeA-CTR leadership from network partners and governance groups through annual surveys, interviews, and governance body recommendations. The Great Plains IDeA-CTR applied internal formative meta-evaluation to evaluate dispositions of 172 governance recommendations from 2017 to 2021. Results provided insights to improve the classification and quality of recommendations, credibility of evaluation processes, responsiveness to recommendations, and communications and governance in a complex CTR network comprising multiple coalitions.

OBJECTIVES/GOALS: Changes associated with placental vasculature contribute to the progression of gestational hypertensive disease preeclampsia. Caudal-type homeobox-2 (CDX2) regulates trophoblast stem cell differentiation. In this study, we investigate the role of placental CDX2 cells in healthy pregnancy and in conditions of preeclampsia. METHODS/STUDY POPULATION: To understand the role of CDX2 cells, here we collected human placenta samples from the prospectively enrolled cohort and also the de-identified cohort (n=84). We studied CDX2 distribution, and function using a lentivirus-based approach. We studied the CDX2 expression and functional differences using transcriptomics and examined the function in invasion and vasculogenesis in the presence and absence of the new target genes we have discovered in our study. RESULTS/ANTICIPATED RESULTS: Analysis of healthy human placenta samples showed that CDX2-expressing cells were present in fetal chorionic regions and are associated with HLA-G and cytokeratin-7 confirming their trophoblast identity. CDX2 cells demonstrated the potential to form a capillary network akin to endothelial cells. Placental samples from healthy (n=6) and preeclampsia (n=8) patients revealed higher levels of CDX2 expression in preeclampsia. Within preeclampsia CDX2 cells, Natriuretic peptide receptor 1 (NPR1), RET oncogene, and Homeobox D10 (HOXD10) were significantly differentially regulated, including a unique long-non-coding anti-sense RNA (KANSL1-AS1) that affected the function of CDX2 and trophoblast cells in invasion and normal vasculogenesis. DISCUSSION/SIGNIFICANCE: In sum, based on these observations, the present study postulates that CDX2 cells present in a healthy human placenta may serve as a prospective cellular reservoir for angiogenesis. Conversely, altered gene programs within CDX2 cells cause aberrant vascular function that could contribute to the progression of preeclampsia.

OBJECTIVES/GOALS: As of 2021, the lung transplantation waiting list has a mortality rate of 7.6 deaths per 100 patient-years. Bioengineered human organs is an emerging field of tissue engineering with a goal of developing suitable organs for transplantation. The focus of the project is to evaluate the efficacy of bioengineered lungs using a human-to-swine model. METHODS/STUDY POPULATION: This project will involve designing and assessing the bioengineered lung by establishing a human-to-pig xenotransplantation survival model. The project aims to evaluate how well the bioengineered lung functions within a living model. The bioengineered lung is constructed using swine connective tissue scaffolding, which has been recellularized with human cells. Anatomically, the lung will resemble a swine lung but will possess the immunological and cellular markers of human tissue. The proposed model will initially assess the immunological response of swine to human lung tissue. Lung function will be assessed during surgery using pulmonary vein gas samples and tissue sampling. Following the end of the study, additional tissues samples will be taken to evaluate the immunological response to the tissue. RESULTS/ANTICIPATED RESULTS: Xenotransplantation and bioengineered organs are two new emerging fields of research that have just begun to enter the large animal testing phase. This model will provide a novel human-to-pig xenotransplant survival model that will be used to test the efficacy of bioengineered lungs function in a dynamic living organism. The design has taken the principles of immunology learned from the current clinical and xenotransplant research and has incorporated this knowledge into the known pig-to-pig transplant models. We anticipate that this model design will be easily reproducible and can be expanded to other bioengineered organs as an effective means to test functionality. DISCUSSION/SIGNIFICANCE: The COVID-19 pandemic’s aftermath may lead to an increased demand for lung transplants. Bioengineered lungs could provide an additional source of organs to supplement current availability. This novel approach has the potential to offer a means to test several different types of bioengineered organs in the future.

While mentors can learn general strategies for effective mentoring, existing mentorship curricula do not comprehensively address how to support marginalized mentees, including LGBTQIA+ mentees. After identifying best mentoring practices and existing evidence-based curricula, we adapted these to create the Harvard Sexual and Gender Minority Health Mentoring Program. The primary goal was to address the needs of underrepresented health professionals in two overlapping groups: (1) LGBTQIA+ mentees and (2) any mentees focused on LGBTQIA+ health. An inaugural cohort (N = 12) of early-, mid-, and late-career faculty piloted this curriculum in spring 2022 during six 90-minute sessions. We evaluated the program using confidential surveys after each session and at the program’s conclusion as well as with focus groups. Faculty were highly satisfied with the program and reported skill gains and behavioral changes. Our findings suggest this novel curriculum can effectively prepare mentors to support mentees with identities different from their own; the whole curriculum, or parts, could be integrated into other trainings to enhance inclusive mentoring. Our adaptations are also a model for how mentorship curricula can be tailored to a particular focus (i.e., LGBTQIA+ health). Ideally, such mentor trainings can help create more inclusive environments throughout academic medicine.

We assessed the rigor and reproducibility (R&R) activities of institutions funded by the National Center for Advancing Translational Sciences (NCTSA) through a survey and website search (N = 61). Of 50 institutional responses, 84% reported incorporating some form of R&R training, 68% reported devoted R&R training, 30% monitored R&R practices, and 10% incentivized them. Website searches revealed 9 (15%) freely available training curricula, and 7 (11%) institutional programs specifically created to enhance R&R. NCATS should formally integrate R&R principles into its translational science models and institutional requirements.

OBJECTIVES/GOALS: SalmonellaTyphi primarily persists in human chronic carriers by forming biofilms on gallstones in the gallbladder (GB). We developed a mouse model of GB chronic carriage, and using this model, aim to detect Salmonella in living mice and track the progression of GB carriage with bioluminescent S.Typhimurium and in vivoimaging. METHODS/STUDY POPULATION: S.Typhimurium 14028 (WT) was transduced with the lux operon from the S. Typhimurium Xen33 strain from Perkin Elmer©, creating 14028lux. 129X1/SvJ mice were fed a lithogenic diet for 6 weeks to induce gallstone formation. After cessation of diet, these mice were infected with 5x103-1x104 colony forming units (CFU) of either the 14028lux isolate, WT (non-luminescent) isolate, or an equal volume of sterile saline. Mice were serially imaged (IVIS SpectrumCT) every 2-3 days for up to 63 days. Images were quantified by measuring average radiance over selected regions of interest. The presence of bioluminescent bacteria in specific organs was confirmed by imaging the abdominal cavity post-mortem. Organs were homogenized and CFUs per mg of tissue were quantified and compared between each group. RESULTS/ANTICIPATED RESULTS: Compared to the controls, mice infected with 14028lux showed luminescence in the abdomen as early as three days post-infection. Within 15 days, the resolution was sufficient to discriminate signal in specific organs, notably the gallbladder, liver, spleen, and cecum. The presence of bacteria was confirmed in these organs via direct imaging and by quantifying CFUs in the tissues. At 63 days post-infection, we identified >103 CFUs and significant luminescence in the GB of a portion of 14028lux-infected mice. For all days post-infection, 14028lux-infected mice that lacked observable luminescence had <100 CFUs/mg tissue. DISCUSSION/SIGNIFICANCE: We have developed a technique using bioluminescent S.Typhimurium and in vivo imaging that, without sacrificing infected mice, enables us to reliably distinguish between mice that have maintained gallbladder chronic carriage >60 days and those that have cleared infection.

OBJECTIVES/GOALS: There is an interest in developing a bioprosthetic ovary for ovarian tissue transplantation. The properties of the ovarian extracellular matrix need to be better understood in order to replicate the human ovary. We tested the effects of an encapsulating hydrogel at different rigidities on bovine primordial follicle activation, growth, and survival. METHODS/STUDY POPULATION: Bovine primordial follicles were isolated from ovarian cortex. A mean of 9.9 follicles (range 3-24) were encapsulated per bead in either 1% or 5 % alginate across 4 experiments. The encapsulated follicles were subsequently crosslinked in a calcium sulfate solution. Follicles were then cultured for 8 days with light microscopy imaging taken every other day along with media exchanges. Follicles were then examined using immunofluorescence. Growth and survival curves were constructed and all statistical analyses were performed using Graph Pad Prism 9. RESULTS/ANTICIPATED RESULTS: A total of 372 follicles were encapsulated across 32 beads (16 in 1% alginate and 16 in 5% alginate). There were no differences in initial follicle size between the two conditions (33.53 µm vs. 32.45 µm, p=0.47). At the end of 8 days, there was no difference between follicle size (59.55 vs. 56.06, p=0.48). Additionally, there was no difference in survival between 1% and 5% alginate encapsulation (57.75% vs. 52.43%. p=0.40). Immunofluorescence is being performed on encapsulated follicles to confirm the presence of DDX4, a molecular marker of oocytes, after 8 days in culture. Additional encapsulated follicles have also been submitted for histologic sectioning and hematoxylin and eosin staining to better characterize the viability and health of these follicles after 8 days in culture. DISCUSSION/SIGNIFICANCE: There was no significant difference in growth or survival between primordial follicles cultured in 1% or 5% alginate gels. Immunofluorescent analysis confirmed the presence of viable follicles at the end of 8 days of culture. Future work needs to further explore how factors in the ovarian extracellular matrix impact follicle maintenance and growth.

OBJECTIVES/GOALS: Patients frequently need or desire fat grafting to improve common issues such as implant visibility and contour deformity, often done as a second, staged procedure following immediate reconstruction. This study aimed to identify which patient factors and reconstructive techniques predict the need for revision with AFG after IBBR METHODS/STUDY POPULATION: Patients who underwent IBBR with either tissue expanders or implants following mastectomy from 2017 to 2021 were identified. Demographics, comorbidities, and the postoperative course were reviewed. The primary outcome variable was AFG after the initial reconstruction. Univariate and regression analyses were performed to identify factors predictive of AFG. RESULTS/ANTICIPATED RESULTS: Five-hundred twenty-nine patients were included in our analysis, with 43% having AFG. Univariate regression displayed single-stage reconstruction (OR=0.53, 95% 0.37-0.75) and previous radiation (OR 0.59, 95% 0.35-0.99) negatively predicted the need for AFG, while bilateral breast reconstruction (BBR) was a predictor (OR 2.32, 95% 1.58-3.4). On multivariate analysis, decreasing age and BBR remained predictive of AFG. The odds of AFG decreased by 3% for every one-unit increase in age (95% CI [0.96, 0.99]). Interestingly, neither pre-pectoral breast reconstruction nor specimen weight:implant ratio was associated with increased need for AFG on univariate/multivariate analysis. DISCUSSION/SIGNIFICANCE: Patients requiring AFG were likely younger and had undergone BBR with tissue expanders. Plane of implant did not appear to affect need for AFG. Knowledge of these predictive factors may help plastic surgeons in preoperative counseling before implant-based breast reconstruction.

OBJECTIVES/GOALS: Analyze how the Endowment HIREC ‘s Mentoring and Career Coach Model A productive mentoring relationship is essential to advance researchers into being independent and bring extramural funds. METHODS/STUDY POPULATION: Provide Hispanic researchers mentoring and career coaching to strengthen their pathway as researcher. The HiREC’s Career Coach and Mentoring Component (CCMC) is an innovated approach to support long-lasting research mentoring relationships in our institution. This approach was developed to advance research to eliminate health disparities, promote multidisciplinary translational research in a Minority Institution and sustain research infrastructure and services, career, and workforce development initiatives. Promising Faculty are target and early and mid-career investigators interested in pursuing a research career. To implement the CCMC with the Visiting Endowed Chair a HiREC Advisory Leadership Group in Mentoring will be established, with researchers from Puerto Rico, and US mainland. RESULTS/ANTICIPATED RESULTS: Three Hispanic mid-career women from the School of Medicine and one from the School of Health Professions from the University of Puerto Rico received a HiREC Advanced Research Award of $50,000. The awardees achieved their goals; completed their research plan, research infrastructure needs, peer-reviewed publications, and submission of a competitive grant. They also provided successful perspectives on mentoring relationships in a Minority institution. Each one showed the mentor’s and mentee’s experiences as fundamental for their research advancements, productivity, leadership, and successful results. HiIREC’s mentoring component with the Visiting Endowed Chairs improves a healthy work environment and expands the research agenda for each awardee sustaining the institutional research culture. DISCUSSION/SIGNIFICANCE: A productive mentoring relationship is essential to advance researchers into being independent and bring extramural funds. Four mentees received formal, long-term guidance and endowment funds for their research infrastructure requirements with successful outcomes. HiREC contributes to building up an institutional mentoring program.

Translation of critical and broadly impactful health advancements is stymied by insufficient scientific scrutiny of barriers and roadblocks in the process. The Clinical & Translational Science Award (CTSA) funding opportunity announcement released in July 2021 makes clear the distinction between translational research and translational science (TS) and urges a shift from the former to the latter. This represents a significant shift in the overall scientific direction of the CTSA program and necessitates corresponding shifts in CTSA hub operations. To better support TS, the Team Science Core of the Duke CTSA hub designed and facilitated a virtual retreat for hub personnel that (1) enabled organizational learning about TS and (2) identified anticipated challenges and opportunities. A post-retreat survey was utilized to assess the degree to which the retreat met its stated goals. Our survey received a 62% response rate; 100% of respondents would recommend the session to others. Respondents also reported gains in all areas assessed, with evidence for greater understanding of TS and increased perspective of the value and relevance of TS. In this paper, we provide a roadmap for designing and implementing facilitated TS retreats, which we argue is a key step in TS capacity building through workforce development.

OBJECTIVES/GOALS: Under enrollment of trials is a continued challenge in clinical research. In response, the Oregon Clinical and Translational Research Institute (OCTRI), the CTSA at Oregon Health & Science University (OHSU), launched a central resource, OCTRI Recruitment, to equip researchers with the knowledge and tools needed for recruitment success. METHODS/STUDY POPULATION: OCTRI Recruitment focused programmatic development in response to the voice of OHSU researchers. In 2018, a qualitative assessment project, “Clinical Research Recruitment Methods at OHSU”, was launched, which included a survey (N=100) and optional interview (N=24), to determine recruitment method utilization and experience, along with opinions on the needs and culture of recruitment at OHSU. In 2022, as part of the same protocol project, a second survey was deployed (N=31), to determine changes in recruitment method use and to identify further recruitment challenges. OCTRI Recruitment also obtains continual informal input on perceived recruitment challenges and opportunities through engagement within the OHSU research team community. RESULTS/ANTICIPATED RESULTS: 2018 survey and interviews showed: many researchers relied on their clinic’s patient population for recruitment (74%); were unaware of available tools to recruit OHSU patients, especially informatics tools (5-22%); and were not aware of and minimally use methods to recruit outside OHSU (<40%). In response, OCTRI Recruitment developed and began recruitment consultations, guidance materials, and educational seminars. In 2022, survey results showed an increase in the use of informatics-based recruitment tools (2-14%+) and increased use of methods focused on individuals outside of OHSU (1-7%+). Additionally, a review of studies post OCTRI Recruitment consultation over three years (N=51) showed that of those studies, 40% increased enrollment numbers and 61% increased team’s confidence level post consult. DISCUSSION/SIGNIFICANCE: This approach to program creation allowed for a uniquely targeted development of services in response to the voice of OHSU researchers and recruitment challenges. Based on additional data, efforts have begun to address the recruitment challenges of a study opportunity website, participant compensation methods, and community-based recruitment.

OBJECTIVES/GOALS: Bronchiolitis is a major cause of PICU admission, yet identifying best practices is limited by the lack of existing databases containing the needed demographic and clinical variables. We used probabilistic linkage to join the Virtual Pediatric System (VPS) and Pediatric Health Information Systems (PHIS) databases to overcome this data barrier. METHODS/STUDY POPULATION: We performed a single site study joining VPS and PHIS data. These national databases contain clinical (VPS) and billing and resource use (PHIS) data. Limits on the use of patient identifiers (PI) for multi-center research, makes direct linkage techniques impossible. To demonstrate that probabilistic linkage can accurately link VPS and PHIS records, we obtained our single site VPS and PHIS records and linked them using probabilistic linkage without PI and compared this to a gold standard linkage created with PI. We also compared demographic features of linked and unlinked records to assess the ability of probabilistic linkage to create a representative sample. RESULTS/ANTICIPATED RESULTS: We obtained 920 VPS records of patients with bronchiolitis and linked 91% (839/920) to a PHIS record with 4 (0.5%) false-positive matches. Characteristics of linked and unlinked records are compared in Table 1. Comparison of probabilistically linked and unlinked records showed no difference in median age in years (0.7 [Interquartile range (IQR) 0.3-1.5] v 0.7 [IQR 0.2-1.5], p = 0.76), median number of complex chronic conditions (0 [IQR 0-1] v 0 [IQR 0-1], p = 0.16), median Pediatric Index of Mortality 3 severity of illness scores (-4.6 [IQR -4.7 – 4.4] v -4.6 [IQR -4.7 – 4.4], p = 0.44), median days of PICU stay (4 [IQR 3-6] v 4 [IQR 2-6], p = 0.36), proportion female ( 44% v 46%, p = 0.82), or proportion of patients intubated (28% v 24%, p = 0.41). DISCUSSION/SIGNIFICANCE: Probabilistic linkage creates an accurate combined VPS-PHIS database. Extending our methodology to join data from all 38 hospitals contributing to VPS and PHIS will allow creation of a large database containing the demographic, treatment, and outcome data needed to enable Comparative Effectiveness Research of bronchiolitis care.

Research experience is often important for academic and career development. This paper describes the implementation and impact of a training program for temporary research assistants (RAs) at an academic medical center. The program includes a 9-month didactic lecture series covering research and professional development skills, a Quality Improvement project focused on improving research processes, and manuscript writing. Overall, the program goals of increasing confidence, self-efficacy, job satisfaction, and well-being, as well as providing an opportunity for career exploration, were met. Thus, this program has the potential to support temporary RAs and enhance their early research experiences.