OBJECTIVES/GOALS: Developing pharmacokinetic (PK) models to guide selective serotonin reuptake inhibitor (SSRI) dosing in youth is costly, time-intensive, and requires large numbers of participants. We evaluated the use of remnant blood samples from SSRI-treated youth and developed precision PK dosing strategies. METHODS/STUDY POPULATION: Following IRB approval, we used a clinical surveillance platform to identify patients with routine phlebotomy within 24 hours of escitalopram or sertraline dosing. Remnant blood samples were obtained from youth aged 5–18 years, escitalopram and sertraline concentrations were determined, and clinical characteristics (e.g., age, sex, weight, concomitant medications that inhibit sertraline or escitalopram metabolism) and phenotypes for CYP2C19, the predominant enzyme that metabolizes these SSRIs, were extracted from the electronic medical record (EMR). A population PK analysis of escitalopram and sertraline was performed using NONMEM. The influence of clinical variables, CYP2C19, and dosing was evaluated from simulated concentration-time curves. RESULTS/ANTICIPATED RESULTS: Over 21 months, we collected315 samples from escitalopram-treated patients (N=288) and 265 samples from sertraline-treated patients (N=255). In youth, escitalopram and sertraline exposure (concentrations over time) and specific pharmacokinetic parameters (e.g., clearance) were influenced by CYP2C19 phenotype, concomitant CYP2C19 inhibitors, and patient-specific characteristics. Escitalopram and sertraline concentrations from remnant blood samples were 3.98-fold higher and 3.23-fold higher, respectively, in poor metabolizers compared to normal metabolizers (escitalopram, p<0.001) and compared to normal, rapid, and ultrarapid metabolizers combined (sertraline, p<0.001). DISCUSSION/SIGNIFICANCE: Combining remnant blood sampling with pharmacogenetic-integrated EMR data can facilitate large-scale population PK analyses of escitalopram and sertraline in youth. This real-world approach can be used to rapidly develop precision SSRI dosing strategies, including slower titration and reduced target doses in CYP2C19 poor metabolizers.

Effectively addressing public health crises requires dynamic and nimble interdisciplinary collaborations across the translational spectrum, from bench to clinic to community. The Clinical and Translational Science Award (CTSA) Program hubs are uniquely suited to facilitate interdisciplinary collaborations across universities and academic medical centers. This paper describes the activities at the Columbia University CTSA Program hub to address a current public health crisis, the opioid epidemic. Columbia’s CTSA Program hub led a three-phase approach, based on the Conceptual Model of Transdisciplinary Scientific Collaboration as described by Stokols et al.: (1) a university-wide planning and brainstorming phase to identify key leaders across many domains who are influential in addressing the opioid epidemic, (2) a campus-wide and community outreach to identify all interested parties, and (3) ongoing targeted support for collaboration development. Preliminary metrics of success are interdisciplinary collaborations and grant funding. We describe recent examples of how interdisciplinary collaboration, academic-community partnership, and pilot funding contributed to the development and funding of innovative interdisciplinary research, including the New York site of the HEALing Communities initiative. The processes are now being used to support interdisciplinary approaches for other translational public health issues.

The critical processes driving successful research translation remain understudied. We describe a mixed-method case study protocol for analyzing translational research that has led to the successful development and implementation of innovative health interventions. An overarching goal of these case studies is to describe systematically the chain of events between basic, fundamental scientific discoveries and the adoption of evidence-based health applications, including description of varied, long-term impacts. The case study approach isolates many of the key factors that enable the successful translation of research into practice and provides compelling evidence connecting the intervention to measurable changes in health and medical practice, public health outcomes, and other broader societal impacts. The goal of disseminating this protocol is to systematize a rigorous approach, which can enhance reproducibility, promote the development of a large collection of comparable studies, and enable cross-case analyses. This approach, an application of the “science of translational science,” will lead to a better understanding of key research process markers, timelines, and potential points of leverage for intervention that may help facilitate decisions, processes, and policies to speed the sustainable translational process. Case studies are effective communication vehicles to demonstrate both accountability and the impacts of the public’s investment in research.

OBJECTIVES/GOALS: The objective of this study is to assess the feasibility and preliminary impact of a physiotherapy protocol for developing an individualized home-based physical activity program to increase physical activity (PA) levels in sedentary older adults with Type II Diabetes Mellitus (T2DM) living in Puerto Rico (PR). METHODS/STUDY POPULATION: This will be a pilot study with two phases. In phase 1, we will design a novel patient-centered home-based PA program protocol for adults ≥65 years with T2DM based on the Information-Motivation-Behavioral Skills model. Its content validity will be assessed through focus groups with 10 experts and 10 older adults and analyzed using a directed content analysis. Phase 2 we will be program implementation using a one-group, repeated measures design with 12 adults ≥65 years with T2DM. PA levels will be assessed by recording active minutes with a Fitbit. Risk of falls, balance, strength, and physical function will be assessed through standardized tests validated for this population. Statistical analysis will include descriptive statistics, comparisons via chi-square/Fisher’s exact test, and non-parametric tests. RESULTS/ANTICIPATED RESULTS: We expect to recruit a minimum of 12 participants and to administer the program for 12 weeks at a frequency of two visits per week. We anticipate that implementing and supervising the home-based PA protocol will be feasible as determined by recruitment and retention rates, patients’ satisfaction, and compliance with the program. We also expect that this protocol will increase physical activity levels, improve general strength, balance, physical function, and reduce the risk of falls in sedentary older adults with T2DM. DISCUSSION/SIGNIFICANCE: As the third cause of death in PR, T2DM represents a public health challenge. An effective home-based PA program may decrease morbidity and mortality rates in older adults by increasing PA and functional health. This study will provide data for planning a randomized controlled trial to assess its effectiveness in the outcomes of interest.

ABSTRACT IMPACT: This research takes a transcriptomic approach to parse genes and molecular pathways that underlie the fear memory circuitry and, in doing so, identifies therapeutic targets that can further be developed into treatments for fear disorders, such as post-traumatic stress disorder. OBJECTIVES/GOALS: Normal fear learning produces avoidance behavior that promotes survival, but excessive and persistent fear after trauma can lead to development of phobias and post-traumatic stress disorder (PTSD). Our goal is to understand the mechanism and identify novel genetic targets underlying fear responses. METHODS/STUDY POPULATION: Involvement of the basolateral amygdala (BLA) in fear acquisition is well established and requires activation of N-methyl-D-aspartic acid receptors (NMDARs). At a cellular level, NMDAR activation leads to production of nitric oxide (NO) by a process mediated by interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS). To elucidate mechanisms underlying the role of the PSD95-nNOS-NO pathway in conditioned fear, here we use rodent behavioral paradigms, pharmacological treatment with a small molecule PSD95-nNOS inhibitor, RNA-sequencing, and an AAV-mediated knockdown of the nNOS gene in the BLA. RESULTS/ANTICIPATED RESULTS: We show that treatment with ZL006 attenuates rodent cued-fear consolidation. Additionally, with RNA-sequencing, expression of 516 genes was altered in the BLA following fear expression; of these genes, 83 were restored with systemic ZL006 treatment. Network data and gene ontology enrichment analyses further revealed that cGMP effects, insulin-like growth factor binding, and cognition-related pathways were significantly altered. Finally, we show that a BLA-specific knockdown of nNOS attenuates cued fear consolidation, without adverse effects on other memory and motor behaviors. DISCUSSION/SIGNIFICANCE OF FINDINGS: Via a model of NMDAR-mediated fear consolidation, our results reveal novel pathways and genetic targets that underlie plasticity of fear memory circuitry. Importantly, these results will inform future therapeutic strategies for targeting fear related disorders like PTSD.

OBJECTIVES/SPECIFIC AIMS: The objective of this study is to develop patient-derived “personalized” organotypic models of human distal airways, in which basal stem cells (BCs) isolated from the pre-/terminal conducting airway region are co-cultured with autologous stromal cells from the same region to reproduce patient-specific distal airway epithelial-stromal units and their remodeling in COPD. METHODS/STUDY POPULATION: We established a protocol to isolate and propagate epithelial BCs, fibroblasts, and endothelial cells from the distal airways of normal and COPD lung donors. Heterogeneous cellular and molecular phenotypes in the human distal airways were characterized using immunofluorescence and single-cell RNA sequencing. Patient-specific distal airway epithelial-stromal units were reconstructed by co-culturing BCs and autologous stromal cells using an air-liquid interface-based airway wall model and a bronchosphere-based 3D distal airway organoid assay. RESULTS/ANTICIPATED RESULTS: Histologic analysis of derived epithelial-stromal units revealed heterogeneous patient-specific phenotypes characterized by hypo-/hyper-/metaplastic lesions (hypo-regenerative phenotype, mucous cell hyperplasia, squamous metaplasia, distal-to-proximal repatterning) in the epithelial compartment, accompanied, in some samples, by stromal remodeling. Candidate epithelial-stromal cross-talk mechanisms were identified using quantitative real-time RT-PCR analysis of autologous epithelial and stromal compartments of established patient-specific distal airway unit models. DISCUSSION/SIGNIFICANCE OF IMPACT: Epithelial and stromal cells isolated from distal airways of subjects with and without COPD can be assembled into functional, organ-level tissue which mimics the architecture of human distal airways and, in patients with COPD, reproduces several distal airway remodeling phenotypes. Patient-specific models of distal airway epithelial-stromal cross-talk established in this study can be used to identify candidate pathways that mediate disease-relevant airway remodeling and potentially utilized as pre-clinical platforms for developing personalized therapeutic approaches to suppress the progression of distal airway remodeling in chronic lung diseases, including COPD.

Objectives/Goals: (1) Conduct a pilot study documenting prevalence of tinnitus in a sample of Puerto Rican adults at the Audiology Clinic of the Medical Sciences Campus-University of Puerto Rico, (2) categorize patterns of tinnitus, (3) document intervention received for tinnitus, and (4) study sociodemographic characteristics of Puerto Rican adult participants with tinnitus. Methods/Study Population: A descriptive retrospective study was performed reviewing 121 clinical records of patients seen at the Audiology Intramural Clinic of the Medical Sciences Campus of the Universidad de Puerto Rico between 2022 and 2023. They were analyzed to determine the prevalence of tinnitus among this cohort. The study was submitted to the Office of Human Participants for revision and approval under the exempt category. The data were used to categorize the type of tinnitus, episodic versus constant, tonal versus non-tonal and the sociodemographic description of the sample. Results/Anticipated Results: From these 121 records, 70.2% (n = 85) were females and 29% (n = 29.8) were males. Subject ages ranged between 21 and 65 years. About 30% reported being single 30.6% (n = 37), followed by 21.5% (n = 26) reporting being married. From the 62 revised clinical records of subjects that reported tinnitus, 24% (n = 29) classified their tinnitus, in terms of how long they experience its presence, as constant, while 14% (n = 17) classified their tinnitus as intermittent. From the 62 revised clinical records, 44 participants (36.4%) described their tinnitus as tonal and 64.6 % as a complex sound of those patients 38 (31.4%) reported the tinnitus as a high-frequency pitch sound. Of the 62 patient records, the majority (98.4%) informed that they never received the treatment for tinnitus. Discussion/Significance of Impact: The results indicate that more than half of adults evaluated in the UPR Audiology Intramural Clinic (51%) had tinnitus. Age range was broad developing at any age but most prevalent in middle-aged females. Manifested permanent as a tonal or a complex sound. About 98.4% informed that they never received treatment, therefore, there is a need to ensure intervention.

OBJECTIVES/GOALS: The objective of this presentation is to describe different recruitment tools implemented by the Miami Clinical and Translational Science Institute (CTSI) to facilitate participant recruitment into research studies. METHODS/STUDY POPULATION: Participant recruitment is critical to the success of all research studies. In the effort of advancing clinical and translational science and to help investigators recruit volunteers for research studies, the University of Miami has two recruitment tools: 1) Consent to Contact (CTC), an opt-in research registry where University of Miami Health System patients are asked for permission to be contacted about studies matching their demographic and/or health profiles; and 2) UMiamiHealthResearch.org (UMHR), implemented with the Michigan CTSA, a community-based registry for volunteers to sign up and be contacted about studies. Study investigators can use these tools once they have obtained IRB approval for their research. RESULTS/ANTICIPATED RESULTS: The CTC was launched in 2016; to date, over 130,000 patients have enrolled in CTC; 69 studies have been approved with over 75,000 patients’contact information released to study teams. UMHR was launched in 2020. To date, the site lists 237 studies. A total of 2,727 portal visitors have expressed interest in participating in specific studies. Study team members were successful in engaging interested participants, and enrolling participants into studies. Overall, teams reported a positive impact on recruitment. Data collection on utilization and satisfaction of these recruitments tools is ongoing. In addition, focus groups of study team members are being conducted to identify best practices for using these tools, and findings will be presented. DISCUSSION/SIGNIFICANCE: The CTC and UMHR recruitment tools have demonstrated positive impact in helping study teams identify potentially eligible research volunteers. The continued promotion of these tools at the University of Miami Health System and in the community will be crucial to the recruitment process and execution of research studies.

OBJECTIVES/GOALS: Early age at menopause has been linked to increased risk of cardiovascular disease; however, there is limited evidence for a relationship between early menopause and heart failure (HF). We examined whether early menopause is associated with incident HF among women in the southeastern United States. METHODS/STUDY POPULATION: The Southern Community Cohort Study enrolled ~86,000 low-income black and white adults from 2002 to 2009. Participants for this analysis were 11,948 women who were postmenopausal at enrollment, had no history of HF, and were on Medicaid or Medicare. HF events were ascertained using ICD-9 codes 428.x via linkage of the cohort with CMS Research Identifiable Files through December 31, 2010. Early menopause was defined as self-reported age at menopause less than 45 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed from multivariable Cox regression models, overall and by race, adjusting for demographic, lifestyle, and reproductive factors, including reason for menopause. RESULTS/ANTICIPATED RESULTS: At baseline, mean age was 58±9 years, and 65% of participants were black. Among women with early menopause, 76% (n = 4,836) had menopause due to hysterectomy or oophorectomy. In women with later menopause, 74% (n = 4,102) reported natural menopause. During a median follow-up of 5.0 years (range 3.1-6.7), 2,157 incident HF events occurred. Compared with women with later onset of menopause, those with early menopause had increased HF risk (HR: 1.27, 95% CI: 1.10–1.47). Risk of HF associated with early menopause was similar in white and black women (p-value for interaction: 0.13). DISCUSSION/SIGNIFICANCE OF IMPACT: In this largely low-income population, early menopause was associated with an increased risk of developing HF. Women with early menopause represent a potential target population for future interventions to decrease risk of HF and cardiovascular risk factors.

OBJECTIVES/GOALS: Uterine fibroids (UF), non-cancerous myometrial neoplasms, affect 11 million women in the US. In qualitative research, experiences of Black women (BW) and Latinas (HL) with UF are understudied. UF etiology is poorly understood, and most symptoms are focused on decreasing UF symptoms. This study will showcase a translational approach in studying UF. METHODS/STUDY POPULATION: A community-engaged research process will be used throughout the study. We have a partnership with the Fibroid Foundation (FF), a UF advocacy organization. For our first aim, we have held community-engagement (CE) studios to provide insight for best practices in creating and implementing culturally appropriate studies with ethnoracially diverse women regarding topics of UF. Our CE studios set the foundation for the second aim, which will be in-depth interviews assessing the sociocultural impacts among pre-menopausal BW and HL with UF. The women will be recruited through the FFs social media platform. To address lack of treatment options in UF, we will be focusing on JAK 2/3 pathway. We will be performing immunofluorescence on tissue microarrays on over 100 patient samples with extensive clinical and survey data. RESULTS/ANTICIPATED RESULTS: We held two CE studios, one with BW with UF and another with HL without UF. These participants were chosen as patient stakeholders. One theme from the CE studio was that both groups mentioned a cultural impact around menstrual health and UF discussions. The participant stakeholders provided insight to other influences in their journey that will be used to develop the interview guide questions for Aim 2. We expect the individual interviews to show similar experiences as our CE studio experiences. We anticipate more in-depth conversations about the sociocultural and ethnoracial factors impacting UF treatment. For Aim 3, we hypothesize that there will be increased JAK 2/3 expression in UF of patients with higher sympton burden and larger fibroid volume. DISCUSSION/SIGNIFICANCE: Implementing a community-engaged research framework provides a foundation for qualitative and translational gynecologic research in BW and HL. This project will contribute insight to their UF experience. There is a lack of innovative treatments, and we have access to valuable patient tissue and data that can be used for potential molecular targets.

OBJECTIVES/GOALS: Current clinical practice recommends occlusive dressings (e.g., film and hydrocolloid) for wounds with variable regenerative capacities. However, clinical evidence suggests that occlusion may hinder regeneration. Our objective was to test the impact of occlusion on regeneration using animal models. METHODS/STUDY POPULATION: The murine wound-induced hair neogenesis (WIHN) is a well-established model of regeneration characterized by de novo hair follicle (HF) formation in the center of large full-thickness wounds. The quantity of neogenic HFs depends on the robustness of Wnt signaling. Optimal tissue mechanics is also required for WIHN. Utilizing the murine WIHN model, we tested the hypothesis that wound occlusion impedes regeneration. We determined how (i) the timing and duration of wound occlusion impacts WIHN, (ii) Wnt signaling influences the occlusion-induced effects on regeneration and (iii) occlusion alters the tissue mechanics of the wound, which establishes the morphogenetic field needed for WIHN. RESULTS/ANTICIPATED RESULTS: Occlusion completely eliminated WIHN. Only a brief period of occlusion between post-wound days 0-3 or 4-7 was sufficient to abrogate WIHN. Microarray and qPCR of open and occluded wounds demonstrated that occlusion promotes fibrosis by upregulating TGF-β2 and mechanotransduction, a mechanosensitive profibrotic pathway. Recruitment of these potent profibrotic pathways generated a symmetrically rigid wound incapable of de novo HF regeneration. Using transgenic animal models with enhanced Wnt signaling, we determined that the ligand-dependent Wnt signaling protected against the occlusion-induced inhibition of WIHN, as well as the occlusion-induced upregulation of both profibrotic pathways. DISCUSSION/SIGNIFICANCE: In animal models, occlusion promoted fibrosis at the expense of regeneration during acute wound healing. Augmented Wnt signaling protected against this effect. Occluding wounds may reduce regeneration. Further studies are warranted to validate these findings.

ABSTRACT IMPACT: This study will provide the essential characterization of intrinsic neural activity in human brain organoids, both at the single cell and network levels, to harness for translational purposes. OBJECTIVES/GOALS: Brain organoids are 3D, stem cell-derived neural tissues that recapitulate neurodevelopment. However, to levy their full translational potential, a deeper understanding of their intrinsic neural activity is essential. Here, we present our preliminary analysis of maturing neural activity in human forebrain organoids. METHODS/STUDY POPULATION: Forebrain organoids were generated from human iPSC lines derived from healthy volunteers. Linear microelectrode probes were employed to record spontaneous electrical activity from day 77, 100, and 130 organoids. Single unit recordings were collected during hour-long recordings, involving baseline recordings followed by glutamatergic blockade. Subsequently, tetrodotoxin, was used to abolish action potential firing. Single units were identified via spike sorting, and the spatiotemporal evolution of baseline neural properties and network dynamics was characterized. RESULTS/ANTICIPATED RESULTS: Nine organoids were recorded successfully (n=3 per timepoint). A significant difference in number of units was seen across age groups (F (2,6) = 6.4178, p = 0.0323). Post hoc comparisons by the Tukey HSD test showed significantly more units in day 130 (51.67 ±14.15) than day 77 (16.33 ±14.98) organoids. Mean firing rates were significantly different in organoids based on age, with drug condition also trending toward significance (F (6,12) = 9.97; p = 0.0028 and p = 0.08 respectively). Post hoc comparisons showed a higher baseline firing rate in day 130 (0.99Hz ±0.30) organoids than their day 77 counterparts at baseline (0.31Hz ±0.066) and glutamate blockade (0.31Hz ±0.045). Preliminary network analysis showed no modularity or small-world features; however, these features are expected to emerge as organoids mature. DISCUSSION/SIGNIFICANCE OF FINDINGS: Initial analysis of brain organoid activity demonstrates changes in single unit properties as they mature. Additional work in this area, as well as further network analyses, will confer better sense of how to rationally utilize brain organoids for translational purposes.

OBJECTIVES/GOALS: In spite of significant growth in undergraduate research, there is little accessible RCR training material targeting this group. The goal of this project was to develop level appropriate RCR materials and test them for effectiveness of teaching basic knowledge of RCR. It was developed cognizant of the type of learning preferred by this group. METHODS/STUDY POPULATION: Todays undergraduate students are digital natives accustomed to using on-line resources for learning and value the ability to work independently. An asynchronous, online series of eight RCR modules were developed using PowerPoint. Audio instruction was overlaid over the presentations and uploaded to YouTube. Each module includes quiz at the end that must be completed with a 90% score in order to continue and students can retake each quiz until correct. Case studies, a plagiarism game, and additional resources such as infographics created by the Office of Research Integrity were included. 275 first year undergraduates completed the pilot and the on-line retrospective pre-post assessment that included 28 Likert scale items and two open-ended questions that were analyzed with RapidMiner. RESULTS/ANTICIPATED RESULTS: Participants rated their ability prior to and after the course to recognize the roles/responsibilities of a mentor, maintain and organize data records, recognize what constitutes research misconduct and multiple types of plagiarism, define ethics of authorship and the types of peer review, recognize responsible handling of human and animal subjects and to define collaborative research. Responses were analyzed using t-Tests and all items showed a significant increase. Students reported between a 28% and 50% increase in knowledge in each topic and gains in understanding where to report RCR violations. Text analysis using RapidMiner provided developers with suggestions on how to enhance the project. Students reported finding the course concise and easy to understand and valued the included case studies. DISCUSSION/SIGNIFICANCE: This study demonstrated that RCR materials developed specifically for todays undergraduate students, presented an easily accessible format, effectively conveys the basics of RCR. The on-line, asynchronous format made it accessible to those for whom in person course is not possible. This model fills the gap in RCR training for early researchers.

OBJECTIVES/SPECIFIC AIMS: We aim to examine the epidemiological characteristics of prosopagnosia by querying and analyzing a large deidentified clinical data set from 12 New York City-based hospitals and Federally Qualified Health Centers (FQHCs). The PCORI-funded New York City Clinical Data Research Network (NYC-CDRN) contains ~4.5 million deidentified ICD-coded electronic health records (EHRs) with comprehensive longitudinal information on demographics, patient visits, clinical conditions/diagnoses, laboratory and radiology results, medications, and clinical procedures. The NYC-CDRN will be expanded to include other data sources, including insurance claims, social determinant of health, patient reported outcomes, and patient generated data. The central hypothesis was that systematic mining of this database would reveal new epidemiological information about prosopagnosia. We developed a computable phenotype for prosopagnosia, using the International Classification of Diseases version 9 (ICD-9). The computable phenotype consisted of the diagnostic code for the condition under study, prosopagnosia (ICD-9 code 368.16), as well as the codes for known surrogate diagnoses. We expected to identify cases of acquired prosopagnosia, where the condition occurs only after brain damage, due to stroke, trauma, or meningitis for example, and cases of developmental prosopagnosia, where the condition is present from an early age, with no history of brain damage. The goals of this project were to provide new information about the condition’s prevalence rate in the New York City area, which could be furthermore translated into wider geographical areas and to yield novel details about its antecedents and comorbid conditions. METHODS/STUDY POPULATION: To determine the presence of the diagnosis of interest, prosopagnosia, and common co-occurring conditions among a New York City-based study population, we investigated a large database in collaboration with the NYC-CDRN. At the time the large database was mined it contained ~4 million ICD-9 coded EHRs. We first created a search paradigm; applicable for screening the database that consists of ICD-9 coded EHRs. We generated a list of ICD-9 codes indicative for the patients’ difficulties with the perception of faces (368.16), which indicates the presence of the condition as part of the psychophysical visual disturbances complex, and this code identified 871 patients. Furthermore, we collected codes that indicate the presence of conditions that are known to be surrogate diagnoses of prosopagnosia. ICD-9 codes for surrogate diagnoses included for example, 854.* (coding for personal history of traumatic brain injury, n=1,409), 434.01, 434.11, and 434.91 (coding for cerebral thrombosis, embolus and artery occlusion unspecified with cerebral infarction, n=19,409), and 191.2 (coding for malignant neoplasm of the temporal lobe, n=566). In October 2015, coding was changed to the new ICD-10 coding system. No additional patients were revealed from the data set when the cohort was searched for the presence of corresponding ICD-10 codes, as institutions are currently in transition from ICD-9 to ICD-10. Using this search query with the large database, we extracted novel information about the epidemiological and demographical distribution of prosopagnosia and furthermore, gained new knowledge about commonly associated diseases. The fact that it must be presumed that the majority of diagnoses of prosopagnosia have been made on the basis of patients’ self-reports and clinicians’ judgments represents a limiting factor in this study. We are currently exploring machine-learning strategies to identify potential false-negative cases among the patients with surrogate diagnoses. RESULTS/ANTICIPATED RESULTS: Investigations and application of our search query revealed a total number of n=129,549 patients carrying either the diagnosis code for prosopagnosia or the codes for the known surrogate diagnoses. There were 871 patients who carried the ICD-9 code 368.16, indicating the potential presence of prosopagnosia among other visual disturbances. Remaining patients (n=128,678) carried codes for known surrogate diagnoses, contained in the search query. Statistical analyses revealed elevated odds ratios for men (OR=1.55, 95% CI: 1.36, 1.77, p<0.0001), and for Black/African Americans Versus White individuals (OR=2.09, 95% CI: 1.74, 2.51, p<0.0001). DISCUSSION/SIGNIFICANCE OF IMPACT: Currently, the prevalence of prosopagnosia remains unknown. Face blind individuals are struggling to recognize their social contacts by their face only in every day life and are therefore prone to experience reduced quality of life. We searched the large NYC-based clinical database, containing more than 4.5 million deidentified ICD-coded health records, for cases of prosopagnosia to shed light into its prevalence and epidemiological characteristics. We furthermore, mined the database for cases carrying known surrogate diagnoses to explore the magnitude and characteristics of individuals potentially under increased risk. Our efforts address a great healthcare need, as they revealed new epidemiological knowledge of a vulnerable and understudied population. The results of this project reveal new insights into the epidemiological characteristics of prosopagnosia and its surrogate diagnoses, and demonstrate the feasibility of mining large clinical databases to identify rare clinical populations. Our results suggest the need for a more targeted diagnostic assessment of face perception abilities in populations under increased risk.

OBJECTIVES/GOALS: Clinical and translational science needs to address roadblocks to translational processes. We conducted a survey at two institutions, a private medical school and a large public university, to understand the frequency and distribution of barriers and roadblocks to research. METHODS/STUDY POPULATION: We reviewed the literature to compile a pool of barriers and roadblocks and convened a panel of relevant stakeholders to develop a 20-item questionnaire. Survey respondents were asked to select and prioritize the five leading clinical and translational roadblocks, provide information regarding their academic degrees and rank/position, complete open-ended items regarding their areas of research, and optionally add additional remarks in a comment box. The survey was disseminated in August 2022 via REDCap to faculty and staff with active research protocols at Baylor College of Medicine and the University of Houston. RESULTS/ANTICIPATED RESULTS: In total, 227 respondents completed the survey. Their disciplines were basic science (29.5%), translational research (52.9%), clinical research (55.5%), community-engaged research (9.7%), and educational research (9.7%). Respondents identified 1) lack of access to trained research coordinators, 2) lack of understanding about different resources that facilitate research, 3) complex regulatory environment and delays, 4) fragmented infrastructure for administrative and fiscal processes, and 5) inadequate funding for pilot projects to foster new research. Other roadblocks included lack of established community stakeholder partnerships, inadequate access to medical record data, and limited biostatistical support. In the comments, several respondents noted that all items included were important. DISCUSSION/SIGNIFICANCE: Research workforce recruitment/training was the highest priority followed by lack of access to information and administrative bottlenecks. We are building an online portal to increase awareness and simplify access to competency-based training and research services. Initiatives are underway to address other roadblocks.

OBJECTIVES/SPECIFIC AIMS: Voiding postponement is common cause of LUT dysfunction in which children void infrequently with large volumes. This condition is modeled in mice that are subjected to social stress who show decreased voiding frequency and increased voided volumes along with increases in corticotropin-releasing hormone (CRH) expression in Barrington’s nucleus (BN) (i.e., the pontine micturition center). Optogenetics is a technique to selectively stimulate cells or neurons of interest via light activated channel receptors [i.e., channel-2 rhodopsin (ChR2)]. Here we examined the effects of optogenetic manipulation of CRH BN neurons on the in vivo voiding phenotype and urodynamics in awake mice. We hypothesized that stimulating these neurons at higher frequencies (10–50 Hz) would lead to CRH-dependent alterations in voiding phenotype (i.e., larger voided volumes and longer intermicturition intervals. METHODS/STUDY POPULATION: Double transgenic mice expressing ChR2 in CRH cells were generated using the Cre-lox recombinase system and had fiberoptic probes implanted into BN at 8 weeks of age. The mice also underwent simultaneous catheter placement into the bladder for in vivo cystometry. In vivo cystometry before and during optogenetic stimulation at various frequencies was performed 5–7 days postoperatively. Saline was perfused at 10 µL/minute and baseline stable voiding cycles were established. Bladder capacity, threshold pressure, voiding pressure, and voided volume were recorded at baseline and at each optogenetic setting. In some mice, the protocol was repeated in the presence of CRH antagonist (NBI 30775). RESULTS/ANTICIPATED RESULTS: Fiberoptic stimulation (470 nm at 25 and 50 Hz) produced a significant rise in the intermicturition interval, bladder capacities and increased void volumes. This effect was especially pronounced in females in whom bladder capacity and intermicturition interval more than doubled at 50 Hz stimulation. Fluoroscopic images confirmed complete bladder emptying with each void. The increased bladder capacity at higher frequencies (25 and 50 Hz) was CRH-dependent as injection of a CRH antagonist (NBI 30775) blocked the optogenetic effect. Control non-double mice showed no effects from optogenetic stimulation. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results suggest that optogenetic stimulation of CRH-expressing neurons in BN at high frequency (25 and 50 Hz) inhibits micturition and recapitulates the voiding phenotype seen in socially stressed mice (large, infrequent voids). Lower frequencies of optogenetic stimulation (2 and 10 Hz) had no effects on cystometry parameters or voiding phenotype. In addition, females had a greater response to optogenetic stimulation compared with males with larger bladder capacities and longer intermicturition intervals. The changes in voiding phenotype seen were CRH dependent as blockage of the CRH receptor prevented changes in cystometry parameters with optogenetic stimulation. Further elucidation of these and other neural subpopulations in BN are warranted to understand micturition and how it may be manipulated in disease states such as voiding postponement and acute urinary retention.