In underserved communities across New York City, uninsured adults encounter a greater risk of cardiovascular disease (CVD) and diabetes. The Heart-to-Heart Community Outreach Program (H2H) addresses these disparities by screening for CVD risk factors, identifying healthcare access barriers, and fostering community engagement in translational research at the Weill Cornell Medicine Clinical and Translational Science Award (CTSA) hub. Screening events are hosted in partnership with faith-based institutions. Participants provide a medical history, complete a survey, and receive counseling by clinicians with referrals for follow-up care. This study aims to quantify H2H screening participant health status; identify socioeconomic, health access, and health-related barriers disproportionately promoting the onset of CVD and diabetes; and develop long-term community partnerships to enable underserved communities to influence activities across the translational research spectrum at our CTSA hub. The population served is disproportionately non-white, and uninsured, with many low-income and underserved individuals. The program was developed in partnership with our Community Advisory Board to empower this cohort to make beneficial lifestyle changes. Leveraging partnerships with faith-based institutions and community centers in at-risk New York City neighborhoods, H2H addresses the increasing burden of diabetes and CVD risk factors in vulnerable individuals while promoting community involvement in CTSA activities, serving as a model for similar initiatives.

OBJECTIVES/SPECIFIC AIMS: To identify new ethical challenges in human subject research related to the use of cloud-based platforms for data collection. METHODS/STUDY POPULATION: Ethical analysis. RESULTS/ANTICIPATED RESULTS: The OHRP regulations protecting the data, privacy and confidentiality of human subjects and the Terms of Service regulations governing data use by cloud-based platforms are vastly different. The gap between these 2 sets of laws and regulations leaves human subjects vulnerable to harm during the data collection process via clod-based tools. DISCUSSION/SIGNIFICANCE OF IMPACT: Recognizing the risks related to data gathering via cloud-based platforms, and educating researchers and research subjects about these risks and how to minimize them will strengthen the protections of participants and will enhance the informed consent process resulting in increased trust and greater willingness to participate in human subject research.

ABSTRACT IMPACT: In alignment with principles of community engaged research, feedback from participants in this research study may influence infertility clinics to offer psychological support for individuals or couples experiencing high levels of psychosocial burden when pursuing fertility procedures, especially during periods of interrupted care or uncertainty. OBJECTIVES/GOALS: 1) To assess the psychosocial impact on patients whose fertility treatments were interrupted during the COVID-19 shutdown. 2) To assess the correlation of patient perceived risk at the time of treatment cessation compared to the resumption of treatment, both during an ongoing pandemic. METHODS/STUDY POPULATION: Female patients with scheduled fertility treatments at Mayo Clinic within 6 months of 3/15/2020, were contacted through the patient portal and invited to participate in this study. Interested patients were contacted by a study staff member to obtain their consent and HIPAA authorization and to schedule a phone or Zoom interview. Semi-structured interviews were conducted individually, or in partner dyads depending upon participant preference, and were recorded with their permission. Audio recordings were professionally transcribed and de-identified. Transcripts were qualitatively analyzed using NVivo 12 based on the principles of grounded theory. RESULTS/ANTICIPATED RESULTS: 26 participants were interviewed; 20 interviews were conducted individually and 3 were conducted in dyads with their partners. Initial themes from the interviews show that COVID-19 compounded existing psychosocial burden on individuals and couples undergoing fertility treatments. Women who were older in age, had prolonged history of infertility, or multiple unsuccessful treatment cycles reported feeling an increased urgency to proceed with fertility treatments due to the time sensitive care, which outweighed the perceived risks of COVID-19 to either themselves or the potential pregnancy. Patients also reported a desire for improved communication regarding their procedures and overall well-being, as well as options for counseling services for individuals or couples undergoing fertility treatments. DISCUSSION/SIGNIFICANCE OF FINDINGS: Participants indicated the need for increased psychological support for patients pursuing fertility treatments, especially during periods of interrupted care or uncertainty, as highlighted during the COVID 19 pandemic. Offering counseling as a routine part of the treatment process may mitigate this burden.

OBJECTIVES/GOALS: Our objective is to develop a Telenephrology dashboard for the 150,000 Veterans that obtain care through the Iowa City Veterans Affairs Health Care System. Our goal is to create a comprehensive and user-friendly tool for monitoring kidney health and facilitating remote nephrology consultations. METHODS/STUDY POPULATION: We structured our intervention according to the five stages of human-centered design: (1) Empathize, (2) Define, (3) Ideate, (4) Prototype and (5) Test. During the empathy stage, the principal investigator spent 10 hours immersed in the clinical setting observing how nephrologists approach a remote nephrology consultation. These observations were augmented by unstructured interviews with clinicians and patients to better understand the process and dynamics. Following this, a rapid ideation workshop was convened to generate creative solutions that balance technical requirements with the needs of clinicians and patients. These led to rapid prototyping and testing to identify what elements of the prototypes worked and which needed improvement. RESULTS/ANTICIPATED RESULTS: Through the empathy and define stages, three needs were identified: (1) clarity in visualizing data, (2) accuracy of information, and (3) balancing standardization with individualization. During the rapid ideation workshop, the concept of a four-frame dashboard was settled upon. This led to the creation of five prototypes, which were tested. These were reconciled and modified to make a final product. This final product, the Telenephrology Dashboard, contains 5 elements that support nephrologists and supporting staff: (1) a graph of kidney function over time, (2) tables synthesizing lab data, (3) options to drill down events to specific times, (4) customization of views, and (5) integration of kidney disease progression models. DISCUSSION/SIGNIFICANCE: A Telenephrology dashboard was created to facilitate remote nephrology consultations through a Human-Centered Design process. Our next steps include determining if this dashboard may improve end-user satisfaction, referring clinician satisfaction, access to specialist care, and patient outcomes.

OBJECTIVES/GOALS: To provide a translation of health sciences and research to a low-income population and elevate the role of science in personal health and career pathways through the implementation of a STEM-focused, researcher-led, school-community event. METHODS/STUDY POPULATION: Through a strong school district partnership, families from two urban, low-income, high-minority middle schools were invited to attend an academic-community event entitled, Full STEM Ahead in Lancaster, Pennsylvania. Thirty-five Penn State and community partners engaged participants in discovery-focused learning through activity stations. Topic areas included: 3D printing in medicine, herd immunity, HPV cancer prevention, lung health, and germ prevention. Evaluation data from participants and organizational partners was collected to assess process outcomes and qualitative feedback. This event was part of a randomized controlled trial to improve attitudes toward adolescent vaccination. RESULTS/ANTICIPATED RESULTS: Seventy-four parents and students participated in the two-hour event. Evaluation data indicated that 100% of participants who completed the evaluation rated the event as “good” or “excellent” and agreed that they “learned something new.” Specific qualitative feedback indicated that participants enjoyed the STEM information and various learning activities offered. School district leadership hopes to continue the partnership to host the event in future years and expand to other schools, offering an opportunity for academic-community collaboration. DISCUSSION/SIGNIFICANCE OF IMPACT: This event was an innovative approach to connect low-income communities with science and potentially effective in engaging participants in learning. Similar opportunities should be explored to bridge the gap between research and community engagement, especially to increase research awareness.

ABSTRACT IMPACT: This qualitative study describes health system barriers to high-quality care for Latino older adults with Alzheimer’s Disease and Related Dementias OBJECTIVES/GOALS: Compared to non-Latino Whites, Latino older adults are more likely to receive low-quality dementia care such as high-risk medications or services. Caregivers play a critical role in managing medical care for persons with dementia (PWD). Yet little is known about the perceptions and knowledge of dementia quality of care among Latino caregivers of PWD. METHODS/STUDY POPULATION: We used a qualitative research design and conducted interviews with Latino caregivers of PWD and caregiver advocates. We recruited both from community organizations, senior centers, and clinics. Our interview guide focused on experiences of caregiving, interactions with medical system, and knowledge and experiences managing behavioral and eating problems. We used Grounded Theory methodology for coding and analysis, focusing on contrasting and comparing experiences within and between caregivers and caregiver advocates. RESULTS/ANTICIPATED RESULTS: Preliminary results from interviews with two caregivers and two caregiver advocates illustrate that caregivers of persons with dementia have a difficult time receiving high quality care from primary care clinicians. All participants noted that many primary care doctors didn’t know how to diagnose ADRD and dismissed critical symptoms as part of old age. Caregivers also reported that they wished they had more information on what to expect with ADRD disease progression, noting they received little information from the formal medical care system. With respect to behavioral problems, caregiver advocates noted that primary care doctors often did not provide non-pharmacological alternatives to behavioral problems. DISCUSSION/SIGNIFICANCE OF FINDINGS: Findings from our pilot study demonstrate that there is a clear need to train primary care physicians who serve Latino older adults on ADRD care. Improved diagnosis and management could improve outcomes among Latino older adults with dementia.

OBJECTIVES/SPECIFIC AIMS: To translate a behavioral theory–informed, evidence-based, face-to-face health education program into an mHealth lifestyle intervention for African-Americans (AAs). METHODS/STUDY POPULATION: This mixed methods study consisted of 4 phases, using an iterative development process to intervention design with the AA community. In Phase 1, we held focus groups with AA community members and church partners (n=23) to gain insight regarding the needs and preferences of potential app end users. In Phase 2, the interdisciplinary research team synthesized input from Phase 1 for preliminary app design and content development. Phase 3 consisted of a sequential 3-meeting series with the church partners (n=13) for iterative app prototyping (assessment, cultural tailoring, final review). Phase 4 was a single group pilot study among AA church congregants (n=50) to assess app acceptability, usability, and satisfaction. RESULTS/ANTICIPATED RESULTS: Phase 1 focus groups indicated preferences for general and health related apps: multifunctional; high-quality graphics/visuals; evidence-based, yet simple health information; and social networking capability. Phase 2 integrated these preferences into the preliminary app prototype. Feedback from Phase 3 was used to refine the FAITH! App prototype for pilot testing. Phase 4 pilot testing indicated high acceptability, usability, and satisfaction of the FAITH! App. DISCUSSION/SIGNIFICANCE OF IMPACT: This study illustrates the process of using formative and CBPR approaches to design a culturally relevant, mHealth lifestyle intervention to address CV health disparities within the AA community. Given the positive perceptions of the app, our study supports the use of an iterative development process by others interested in implementing an mHealth lifestyle intervention for racial/ethnic minority communities.

OBJECTIVES/GOALS: The goal of this project was to conduct a preliminary assessment of in vivo feasibility early on in the drug-discovery process in an effort to expedite the translation of novel drug scaffolds to potential clinical candidates. The data gathered in this study will be used to direct analog synthesis of our current lead compounds through rational drug design. METHODS/STUDY POPULATION: Based on virtual and physical high-throughput screening efforts and subsequent similarity searching, we identified a set of potent and selective spermine oxidase (SMOX) inhibitors adhering to a common structural scaffold. In order to address potential barriers to in vivo use, we then conducted a robust optimization analysis in an effort to identify analogs with improved drug-like characteristics. Docking simulations to predict binding were performed and visualized using molecular modeling software (MOE and PyMol). ADMET properties were calculated using a variety of software resources including SwissADME and CDD Vault. RESULTS/ANTICIPATED RESULTS: Through these optimization efforts, we were able to successfully identify analogs with improved drug-like characteristics, including increases in predicted CNS penetration, isosteric replacement of metabolically labile functional groups, increased lipophilicity, and elimination of structural attributes suggestive of off-target activity. Analogs were ranked according to predicted binding and properties of in vivo feasibility. Compounds achieving the highest scores were then selected as scaffolds to guide analog synthesis. DISCUSSION/SIGNIFICANCE: Despite evidence implicating induction of SMOX as a mechanism contributing to neuronal pathology, the lack of potent and selective inhibitors with profiles conducive for in vivo use has significantly impeded clinical investigation of this target. In this presentation, rational drug design focusing on translational optimization will be discussed.

OBJECTIVES/GOALS: While disease subtypes are critical for precision medicine, most projects use unipartite clustering methods such as k-means which are not fully automated, do not provide statistical significance, and are difficult to interpret. These gaps were addressed through bipartite networks and tested for generalizability on three national databases. METHODS/STUDY POPULATION: Data. All participants with self-reported stroke from the 2010 Health and Retirement Study (HRS), with cases (n=798) having one or more 8 depressive symptoms measured by the Centers for the Epidemiological Study–Depression 8 scale, and controls (n=389) with none of those symptoms. The replication data set consisted of independent identically-defined participants (cases=725, controls=190) from 1998 HRS. Method. (1) Bipartite network analysis and modularity maximization to automatically identify patient-symptom biclusters with significance. (2) Rand Index to measure the replicability of symptom co-occurrences in the replication data. (3) ExplodeLayout to visualize and interpret the subtypes. (4) R libraries to generalize the methods, upload them to CRAN, and then tested on the N3C and All of Us platforms. RESULTS/ANTICIPATED RESULTS: The analysis identified 4 depressive symptom subtypes (https://postimg.cc/Ny8YwXJW) which had significant modularity (Q=0.26, z=3.03, P DISCUSSION/SIGNIFICANCE: We developed generalizable methods to automatically identify biclusters, measure the clustering significance, and visualize the results for interpretation. These methods were successfully tested on three national level data bases. Such generalizable methods should accelerate the analysis of subtypes, and the design of targeted interventions.

OBJECTIVES/GOALS: Chronic low back pain (cLBP) is associated with gait impairments. Gait may serve as an important biomarker for improvement following therapy interventions; however, gait has not been sufficiently studied in relationship to pain and function in cLBP. METHODS/STUDY POPULATION: Adults with cLBP completed a two-minute-walk-test around a 37.5 m oval track while wearing an inertial measurement unit (IMU—Lifeware LLC, Pittsburgh, PA) over the L5 spinous process. Step time average, step time variability, step length, and symmetry (harmonic ratio) were calculated based on linear trunk accelerations, and gait speed was calculated based on distance walked. Participants completed the PEG tool (Pain, Enjoyment, General activity; scores closer to 10 indicate worse pain) to quantify pain intensity/interference and the PROMIS Physical Function SF-6b tool (mean t-scores=50 +/- 10; higher scores indicate better function) to quantify physical function. Pearson correlation coefficient (r) was used to determine strength of associations between gait and pain/physical function. RESULTS/ANTICIPATED RESULTS: Eleven adults (8 female, age 40 +/- 17, pain duration≥3 months) with cLPB participated in this study after completing an informed consent process approved by the University of Pittsburgh Institutional Review Board. Participants with a history of cancer, spinal cord compression, discitis, or activity restrictions prohibiting them from protocol completion were excluded. The mean PEG scores and PROMIS Physical Function t-scores were 2.8 +/- 1.8 and 47.8 +/- 8.2 respectively. There was a moderate-strong correlation between step time average and PEG (r=0.67, p=0.02), and a moderate-strong correlation between gait speed and PROMIS Physical Function (r=0.62, p=0.04). There were no other significant associations. DISCUSSION/SIGNIFICANCE: Gait speed and step time may be important movement biomarkers to consider when evaluating patients with cLBP. Generalizability of results are limited by the small study cohort and this cohort's relatively low pain burden and high level of physical function.

OBJECTIVES/GOALS: Access to pediatric subspecialty care varies by sociodemographic factors. Providers for gender diverse youth (GDY) are rare, and GDY face health disparities, stigma, and discrimination. We examined the association between GDY access to medical and mental health care and rurality, race, parental education, and other GDY-specific factors. METHODS/STUDY POPULATION: We surveyed parents of GDY (<18 years old) across the United States. Participants were recruited through online communities and listserves specific to parents of GDY. We determined associations between access to gender-specific medical or mental health providers and rurality, race, parental education, as well as other GDY-specific factors including age, time since telling their parent their gender identity, parent-adolescent communication, parent stress, and gender identity using chi-square or Fisher’s exact tests. We calculated adjusted odds ratios using logistic regression models. RESULTS/ANTICIPATED RESULTS: We surveyed 166 parents and caregivers from 31 states. The majority (73.2%) identified as white, 66.5% had earned a bachelor’s degree or higher, and 7.6% lived in a zip code designated rural by the Federal Office of Rural Health Policy. We found no evidence of association between reported GDY access to medical or mental health care and race, parental education, or rurality. We did find a significant univariate association between access to mental health care and feminine (either female or transfeminine/transfemale) gender identity (p = 0.033, OR 2.60, 95% CI 1.06 – 6.36). After controlling for parent-adolescent communication in a backwards elimination logistic regression model, it was no longer significant (p = 0.137, OR 2.05, 95% CI 0.80 – 5.25). DISCUSSION/SIGNIFICANCE OF IMPACT: Despite rurality, race, and parental education impacting access to pediatric subspecialty care, we failed to find these associations among GDY accessing gender care. There is a need to better understand structural and societal barriers to care for this population including the impact of stigma and discrimination.

OBJECTIVES/SPECIFIC AIMS: The goal of this initiative was to address this cancer health disparity in the Appalachian counties and help participants develop, implement and evaluate evidence-based “PN” that effectively and positively impacts patient and outcomes of the HealthyWomen Program. Following were the objectives of this training program: (1) To understand the broad range of roles and responsibilities associated with “PN”, including care coordination and case management, in the Pennsylvania HealthyWoman Program in Pennsylvania and the National Breast and Cervical Cancer Early Detection Program. (2) To identify and assess local resources and expertise for evidence-based “PN” in the HealthyWoman Program. (3) To utilize “PN” in association with public education and targeted outreach initiatives in the HealthyWoman Program. (4) To implement strategies to manage and evaluate “PN” for the HealthyWoman Program. METHODS/STUDY POPULATION: The series of PN training was held at Pittsburgh, Camp-Hill, Wilkes-Barre and Philadelphia during June 2017. In total, 86 participants attended the training program at one of these 4 locations. Attendees represented organizations that provided breast, cervical and colorectal cancer outreach, screening and treatment. The participants of the training were solicited by regional program managers of the HealthyWoman Program of the PA Department of Health. The Harold Freeman model for patient navigation model was used to train the participants on the concepts of patient navigation. The training was built upon the Health Belief Model and Chronic Care Model, which defined the specific program constructs. The curriculum covered 2 important aspects, that is, clinical knowledge related to breast and cervical cancer along with aspects of patient navigation. Participants represented small, and large academic institutions/health care systems, cancer centers, federally qualified health centers, health departments as well as community-based screening programs and organizations. RESULTS/ANTICIPATED RESULTS: A total of 86 participants were trained; 78% had formal education and training in health-related field. In total, 62% of the participants had previous experience of patient navigation; 42% had training in social service related field and 50% had prior experience as community health worker. The demographic details reflected that majority of the participants (94%) were female. Most of the participants (30%) belonged to 50–64 years of age group followed by 30–39 years (23%) and 40–49 years (22%) of age group, respectively. As part of ethnic distribution, 70% of the participants were White Americans followed by Black/African Americans (17%). Furthermore, association of previous training in health and social service field with and without experience as a community health worker (n=84) and Navigator (n=86) was also analyzed. Among the participants, 44% had both community health worker experiences along with a prior training in social service related field whereas 42% of the respondents only had prior social service related training. This association of previous training in social service related field and prior community health worker experience was statistically significant with a p value of <0.05. Additionally, 81% of the participants who had previous experience in health-related training also possessed the prior experience as community health worker. Also, 81% of the participants who had previous training in health-related field also had a prior experience of patient navigation. In all, 38% of the participants who had a previous experience in social service field also had a prior experience of patient navigation. DISCUSSION/SIGNIFICANCE OF IMPACT: The training program established a pool of patient navigators which will contribute towards reducing the cancer health disparity in the Appalachian region of Pennsylvania. The participants reflected a wide diversity in the navigators’ backgrounds and differences across programs in their choices of patient navigators. It is important to consider this diversity when designing curricula materials and the methods of delivery in a patient navigation training program. As PN training programs are developed and implemented, further data is needed to guide practitioners and administrators in their efforts to include separate curriculum and materials for experienced and lay navigators. In addition, it is also important to assess the role and involvement of patient navigators in research and clinical trials. In total, 82% of the participants when asked agreed to be contacted for participation in research studies. Specific curriculum which includes research could be designed for further development of patient navigators. PN training and implementation knowledge is critical to the development of standards and best practices in this emergent area of cancer care.

OBJECTIVES/SPECIFIC AIMS: There is no consensus on what constitutes translational research. To effectively support translation of research into practical settings, universities must determine who is involved, in which disciplines, and what results. In addition, it is unclear whether these researchers would see “translational research” as describing their work. METHODS/STUDY POPULATION: A survey assessing perceptions, successes, and barriers to the application of research was distributed to faculty, fellows, and graduate students within the University of Michigan. This survey included a question on the definition of translational research. RESULTS/ANTICIPATED RESULTS: Investigators of every rank and school participated (n=865), and all schools reported forms of applied research. Over 70% of participants said it was important to use research results beyond academia, and those responses represented diverse successes ranging from product development to artistic endeavors. Common barriers to such as lack of time and funding were also widely experienced. The definitions of translational research were divided between strictly health-oriented or broadly focused application. However, both definitions and familiarity with the term differed by field. DISCUSSION/SIGNIFICANCE OF IMPACT: Translation of research is widespread throughout the university, and many would define translational research to include their research discipline. Strategic university policies could benefit society by enhancing translation and application across many disciplines.

OBJECTIVES/GOALS: Congenital anomalies (CA) are common, but the cause is often unknown. The interplay between known environmental teratogens, such as medication use in pregnancy, and genetic predisposition impacts CA risk, but such interactions are poorly understood. We test the hypothesis that pharmacogenomic (PGx) variation impacts CA risk. METHODS/STUDY POPULATION: We performed a drug absorption, distribution, metabolism, and excretion (ADME) gene-wide association study (GWAS), which tests for a possible association between ADME gene single nucleotide polymorphisms and individuals with CAs. This analysis was performed in BioVU and utilized billing codes to identify 5,845 cases, individuals with at least one CA, and 50,059 controls of genetically European ancestry. Using Plink software we analyzed 5,398 SNPs in 292 ADME genes across cases and controls. Results from this analysis drove us to further investigate the association between CA risk and SLC22A1-3. Next, we performed PrediXcan analyses to estimate the association between genetically predicted gene expression (GPGE) of SLC22A1-3 genes across all available tissues in the GTEx resource and CA risk. RESULTS/ANTICIPATED RESULTS: The ADME GWAS identified multiple variants on chromosome 6 in the region of SCL22A1-3 that were associated with the risk for CAs. The most significant variants were rs2048327, rs2292334, rs3088442, rs1810126, rs376563, and rs7758229, p DISCUSSION/SIGNIFICANCE: The combination of the known crucial pharmacological roles of OCT1-3 and the results of our ADME GWAS / PrediXcan analyses demonstrates that PGx burden, specifically variation in the SLC22A1-3 genes, influences the risk of developing CAs. This new understanding has the potential to personalize care for pregnant individuals to reduce the risk of CAs.

OBJECTIVES/GOALS: * Describe the Community Engaged Research Core (CERC) Researcher Training Program modules and objectives. * Examine the expansion and reach of the CERC Researcher Training Program across various institutions/organizations. METHODS/STUDY POPULATION: Through joint efforts from Meharry Medical College and Vanderbilt University Medical Center, the Community Engaged Research Core (CERC) Researcher Training Program began as a resource to provide CERC post-docs with knowledge of the basic principles of community engaged research (CEnR). It has since expanded to reach researchers at different institutions/organizations. This series examines topics from ethics to dissemination of research findings. The purpose of this project is to describe the CERC Researcher Training Program modules and present the expansion and reach of the training series. We examined both online training requests and series evaluations to determine: (1) participant reach, (2) number of module requests, and (3) purpose for using training modules. RESULTS/ANTICIPATED RESULTS: Since its inception in 2018, the program has expanded to reach 16 institutions/organizations across the United States. On average, 45 researchers register for the training series and approximately 16 researchers participate each year. As time progresses, the number of registrants and attendees continues to increase. To date, there have been 110 online training module requests. The majority (~75%) of participants are requesting content for self-training purposes, while others are using the information to train others in their home institutions/organizations (~25%). Researchers are using modules for a range of reasons including recruitment, career development, and developing their own CEnR training. DISCUSSION/SIGNIFICANCE: CEnR has the ability to make research better in how it is planned, executed and disseminated. Implementing the CERC researcher training series and expanding its reach demonstrates the desire and need to alleviate health disparities through researcher and community partnerships.

OBJECTIVES/GOALS: Age-specific N-glycosylation occurs on follicle- stimulating hormone (FSH) in pituitaries of post-menopausal women and results in a higher ratio of fully glycosylated to hypoglycosylated FSH. Our goal is to identify in vivo the N-glycosylation pathway enzymes and the regulatory mechanisms in gonadotropes of young and old female mice. METHODS/STUDY POPULATION: Pituitaries were isolated from female mice (at 4m and 8m; n=5 per group) carrying an Fshb-Cre transgene on a Rosa mT/mG genetic background and the GFP-tagged gonadotropes were purified by FACS. RNA-Seq analysis, and subsequent qPCR assays were performed on GFP+ cells from pituitaries of female mice at 4m (reproductively young), 8m (reproductively mid age) and ≥ 12m (reproductively old) of age. To identify the role of progesterone signaling in age-dependent N-glycosylation in gonadotropes, a gonadotrope-specific knockout of Pgr was achieved. Gonadotropes from these mutant mice at 4-, 8-, and ≥12 months of age (n=5 per group) were isolated for qPCR analysis of N-glycosylation enzyme gene expression. Predicted progesterone receptor (PR) promoter binding sequences was performed using JASPAR. RESULTS/ANTICIPATED RESULTS: RNA-seq identified 28 differentially expressed N-glycosylation enzyme-encoding mRNAs in gonadotropes of female mice at 4- and 8-months. Three genes showed significant differences between ages (Man2a1, Man1c1, and B4galt5.), and further qPCR analyses revealed six out of eight genes analyzed showed age-dependent expression, including Man2a1, Man1c1, and B4galt5. The promoters of all N-glycosylation enzyme genes showed strong predicted binding sequences for PR. Further qPCR analysis showed age-and genotype-dependent differences in N-glycosylation enzyme expression in Pgr cKO females, with the most striking differences observed at 13 months, where B4galt5, Man1a2, Mgat5, and Man2a1 were downregulated in Pgr cKO gonadotropes compared to controls. DISCUSSION/SIGNIFICANCE: We identified changes in the N-glycosylation machinery in female mouse gonadotropes and confirmed the age- and Pr-dependent regulation of the corresponding mRNAs. Our results provide insights into the mechanisms at the level of the pituitary by which old age-specific FSH glycoform regulates osteoporosis and weight gain in post-menopausal women.

OBJECTIVES/SPECIFIC AIMS: The National HIV/AIDS strategy aims to increase retention in care (RIC) to reduce HIV transmission and mortality. Previous studies have evaluated clinic-level interventions such as appointment reminders and peer navigation. However, few studies have investigated the association between multiple clinic-level factors and RIC among PLWH across the United States. We conducted a multi-site cohort study to identify clinic-level factors associated with RIC in the United States from 2010-2016. METHODS/STUDY POPULATION: We included PLWH with at least one HIV primary care visit from 2010-2016 at seven sites of the Center for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS). Individual-level data collected as part of routine clinical care were abstracted from the electronic health record. Clinic-level data were gathered through a survey and included questions on site characteristics (i.e. clinic volume) as well as services available at the site during each year of the study: peer navigation, RIC posters/brochures, laboratory test timing, flexible scheduling, appointment reminder types, and stigma support services defined as intensive HIV education and advocacy regarding support to address stigma at outreach visits. RIC was defined as ≥2 encounters per year, ≥90 days apart, observed until death, administrative censoring (December 31, 2016), or loss to follow-up (no visit for >12 months with no future visits). Poisson panel regression with robust error variance, clustering by site and adjusting for calendar year, age (modeled with a cubic spline), sex, race/ethnicity, and HIV transmission risk factor, was used to estimate incident rate ratios (IRR) with 95% confidence intervals (CI) for RIC. Clustering by site has been shown to absorb for clustering that could occur at the individual level as well. RESULTS/ANTICIPATED RESULTS: Among 21,046 patients contributing 103,348 person-years, 67% of person-years were RIC. Text appointment reminders (IRR = 1.13; 95% CI: 1.03-1.24) and stigma support services (IRR=1.11; 95% CI:1.04-1.19) were significantly associated with RIC. RIC disparities in individual-level patient characteristics were observed even after accounting for clinic-level characteristics. Older patients were more likely to be RIC demonstrated through year comparisons due to the use of a spline; for age 50 years (IRR = 1.07, 95% CI: 1.06-1.08) and 60 years (IRR = 1.15, 95% CI: 1.13-1.17) compared to 45 years. Female PLWH were more likely to be RIC compared to males (IRR = 1.03, 95% CI: 1.02-1.05) and Hispanic PLWH were more likely to be RIC compared to white, non-Hispanic PLWH (IRR = 1.09, 95% CI: 1.05-1.13). Although commonly found to be associated with worse RIC, Black race and injection drug use were not associated with RIC in this population. DISCUSSION/SIGNIFICANCE OF IMPACT: In this multi-site US cohort study from 2010-2016, availability of text appointment reminders and stigma support services at a clinic were associated with approximately 10% higher probability of RIC than at clinics without those services. RIC disparities persisted with respect to individual-level characteristics of age, sex, and race/ethnicity even after accounting for these clinic-level factors. Prospective studies examining the impact of these clinic-level factors and individual-level uptake of these services on RIC are needed.

OBJECTIVES/SPECIFIC AIMS: The population of cancer survivors is rapidly growing in the United States. Long term and late effects of cancer, combined with ongoing management of other chronic conditions, make cancer survivors particularly vulnerable to polypharmacy and its adverse effects. We examined patterns of prescription medication use and polypharmacy in a population-based sample of cancer survivors. METHODS/STUDY POPULATION: Using data from the Medical Expenditure Panel Survey (MEPS), we matched cancer survivors (n=5216) to noncancer controls (n=19,588) by age, sex, and survey year. We defined polypharmacy as using 5 or more unique medications. We also estimated proportion of respondents prescribed specific medications within therapeutic classes and total prescription expenditures. RESULTS/ANTICIPATED RESULTS: A higher proportion of cancer survivors were prescribed 5 or more unique medications (64.0%, 95% CI 62.3%–65.8%) compared with noncancer controls (51.5%, 95% CI 50.4%–52.6%), including drugs with abuse potential. Across all therapeutic classes, a higher proportion of newly (≤1 year since diagnosis) and previously (>1 years since diagnosis) diagnosed survivors were prescribed medications compared to controls, with large differences in central nervous system agents (65.8% vs. 57.4% vs. 46.2%), psychotherapeutic agents (25.4% vs. 26.8% vs. 18.3%), and gastrointestinal agents (31.9% vs. 29.6% vs. 22.0%). Specifically, nearly 10% of cancer survivors were prescribed benzodiazepines and/or opioids compared to about 5% of controls. Survivors had more than double prescription expenditures (median $1633 vs. $784 among noncancer controls). Findings persisted similarly across categories of age and comorbidity. DISCUSSION/SIGNIFICANCE OF IMPACT: Cancer survivors were frequently prescribed a higher number of unique medications and inappropriate medications or drugs with abuse potential, increasing risk of adverse drug events, financial toxicity, poor adherence, and drug-drug interactions. Adolescent and young adult survivors appear at increased risk of polypharmacy.

ABSTRACT IMPACT: This research suggests that African American and Latinx smokers who bear a disproportionate burden of tobacco-related harms are able to switch to e-cigarettes that present reduced harm to the user due to their similar reinforcement profile to cigarettes. OBJECTIVES/GOALS: Complete switching from combustible to electronic cigarettes (ECs) reduces harm to the user. For ECs to be a viable substitute, they need to be rewarding enough for regular use, indicated by factors such as craving and dependence (reinforcement value). Little is known about short-term changes in reinforcement value across trajectories of EC use. METHODS/STUDY POPULATION: Participants were randomized 2:1 to switch to a nicotine salt pod system EC or continue smoking (assessment-only control) in a 6-week trial. 114 African American (n=60) and Latinx (n=54) smokers were randomized to receive ECs and are included in the current investigation. At week 6, participants were classified by use trajectory: exclusive smokers (n=16), exclusive EC users (n=32), or dual users (n=66). Participants reported on their EC, cigarette, and total nicotine dependence (cigarette + EC dependence), cigarette and EC use, and nicotine craving and withdrawal at baseline and week 6. Cotinine and exhaled carbon monoxide were assessed at baseline and week 6. RESULTS/ANTICIPATED RESULTS: Participants who completely switched from smoking to ECs (exclusive EC users) and those that partially switched (dual users), maintained cotinine levels (ps>.05) and showed reductions in cigarette dependence and withdrawal (ps<.01). However, exclusive EC users showed no significant changes in total nicotine dependence from baseline to week 6 (p=.123), while dual users showed increased total nicotine dependence (p<.001). Dual users displayed similar levels of EC dependence as exclusive EC users but a lesser reduction in cigarette dependence. Exclusive EC users and dual users showed reductions in craving and withdrawal from baseline to week 6. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study is among the first to prospectively examine changes in dependence, craving, and withdrawal among an understudied sample of smokers making a switch attempt. Smokers who completely switch to ECs maintain nicotine levels and dependence, suggesting that they have a similar reinforcement profile to cigarettes and facilitate switching.

OBJECTIVES/GOALS: Women within the ages of 65-75 have a lower incidence of heart failure than men.However,after the age of 75, the incidence of HF in womentriples,matchingthat of men.(Lloyd-Jones etal., 2002)Overall, women with heart failure live longer at the expense of presenting moresevere symptoms and poorer perceived quality of life.Generally, women with heart failurereceive suboptimal treatment throughout their lifetime. In fact, women are more likely todevelop heart failure after myocardial infarction. This trend is, in part, because physicians areless strict when treating them.(Chou et al., 2007)Studies in heart failure by ethnicity have shown that, despite equal access to healthcare, Hispanic women have higher rates of readmission than Non-Hispanic-white (NHW) women. (Durstenfeld, Ogedegbe, Katz, Park, &Blecker, 2016)One study in Boston demonstrated that Puerto Rican Women have higher rates of diabetes, obesity, and chronic kidney disease compared to blacks and NHW women.(Todorova, Tejada, & Castaneda-Sceppa, 2014)These are cardiovascular risk factors that warrant further study in Puerto Rican women living on the island, but data are lacking. Objective: The purpose of this study is to evaluate the gender disparities in presentation, management, and outcomes in Puerto Rican Hispanic hospitalized for heart failure METHODS/STUDY POPULATION: To this end, we will perform a secondary analysis of data from the PR CardiovascularSurveillance Study (PRCSS). We will extract personal data from 4,461 medical records of patients admitted with heart failure (ICD-9 Codes 428) at 21 hospitals in Puerto Rico, during theyears2007, 2009 and 2011. For statistical methods, we will implement chi-square and t-tests at a significance level of 0.05. RESULTS/ANTICIPATED RESULTS: We expect to find that women will have: fewer interventions, less optimized heart failure medication, higher BNP, older age of diagnosis, but paradoxically better outcome than male counterparts of the same age. DISCUSSION/SIGNIFICANCE OF IMPACT: With this study, we would like to raise awareness about gender-specific health disparities Puerto Rican Hispanic women with heart failure experience while hospitalized.