ABSTRACT IMPACT: The UTMB Institute for Translational Sciences (ITS) seeks to advance the field of community engagement and facilitate competency in community-engaged and community-based participatory research as a means of expanding team science to integrate community involvement and to assist investigators in building relationships that enable them to contribute to community initiatives. OBJECTIVES/GOALS: The UTMB ITS recently implemented a new Community Health Small Grants program to promote and enhance community-campus partnerships. Our goal is to better translate science from discovery to clinical practice and public health through community-engaged research, education, and dissemination. METHODS/STUDY POPULATION: Applications were solicited from community and academic research partners. Community partners may include existing collaborative groups, community health centers, health departments, nonprofits, schools, social services agencies, practice-based research networks, or Community Advisory Boards. Academic partners may include faculty and/or students. The PI may be a community or academic partner. While this Grants Program will transition to the ITS Pilot Project Program, it will utilize a separate review process and scoring rubric focused on immediate and future community benefit, project feasibility, organizational fit, and other factors unique to community-based partnership projects. RESULTS/ANTICIPATED RESULTS: We received an enthusiastic response to our RFA, based upon a long-standing program of a sister CTSA hub. Proposals received include target populations representative of our most vulnerable’‘ children, the elderly, those lacking access to health care, and those for whom language is a barrier. One addresses the Institution’s and the CEC’s need to conduct community needs assessments to enable the implementation of evidence-based programs driven by data and metrics identified and developed by our communities. Each awarded proposal demonstrates a significant and sometimes critical need for the project. Partnerships are anticipated to have significant impacts on the community and its population. DISCUSSION/SIGNIFICANCE OF FINDINGS: We generate, test, and disseminate team science, education and best practices through stakeholder involvement. Our Community Health Small Grants program aims to involve community in our scientific teams and to involve academics in community-derived projects as well as foster relationships and trust.

OBJECTIVES/SPECIFIC AIMS: The objective of this research was to identify and evaluate published research articles that highlight the use of CTSA institutional websites as a research tool or data source for translational science research. METHODS/STUDY POPULATION: A multifaceted systematic search process was engaged for this literature review process using standard literature database searching, digital journal database searching, and pearl growing. All U.S. based studies and reports from 2006 through the present that addressed the application of websites of CTSA institutions for translational science purposes were included in this review. Identified articles were collected, organized, and analyzed using an excel spreadsheet. There were 2 different data collection and organization protocols, one for studies the other for reports. The first data collection protocol was for identified studies that used individual CTSA Institutional websites as a data source for a research topic. The organization processes for each relevant study article included a customized data extraction process that looked to identify a standard group of key elements from each study: (1) The study’s NCATS CTSA Goal. (2) The type of data searched in the CTSA institutional website. (3) The number of CTSA institutional websites searched. (4) The number of sites that had the needed data. (6) The outcomes reported from the research. The second data collection protocol was for identified reports that referenced single CTSA Institutional websites as performing a specific translational informatics functionality either as a portal to Clinical and Translational Science Award tools and resources or as a direct information source. The organizational process for each relevant report article also included a customized data extraction process that looked to identify a standard group of key elements from each report: (1) NCATS / CTSA Goal (2) Tool or Functionality Promoted (3) Description (4) Website used as portal or direct tool. (5) Target Audience. RESULTS/ANTICIPATED RESULTS: The studies were summarized using the standard group of key elements identified for data extraction and summarized in a table. In 5 of the 6 studies, researchers relied on CTSA member individual website content to mine necessary data. One (1) of the studies employed a mixed methods approach to data acquisition and only relied on CTSA member individual website content for CTSA institutions that did not respond to a user survey. One (1) study used a survey to learn about CTSA website content rather than review the websites. In 5 of the 6 studies, researchers reviewed individual CTSA websites for the purposes of determining the number or percentages of CTSA institutions had specific data. One (1) study instead reviewed the individual websites to develop a broader picture of what the CTSA Consortium offered as a group. The percentage of CTSA websites that had the needed data of the researchers ranged from 32% to 100%. The median and mean scores for CTSA websites having the needed data was 66% and 66.5% respectively. One study did not provide specific information for assessment. All 6 studies included research that fell within at least 2 categories of the 5 NCATS CTSA Goal topics. The category most investigated was translational research processes where 5 of the 6 studies investigated how CTSA websites looked to improve the quality and efficiency of translational research. Three (3) studies investigated how CTSA’s cultivated and trained the clinical and translational science workforce. Two (2) studies investigated how CTSA’s engaged patients and communities in the translational research process. Two (2) studies investigated how CTSA’s promoted the integration of underserved populations. One (1) study investigated ways the CTSA’s used their websites to advance the use of cutting-edge informatics. The outcomes reported included (1) the percentage CTSA individual websites that provided information regarding patient recruitment. (2) A list of generic services provided across the CTSA Individual website medium. (3) The number of CTSA individual website education and training programs. (4) The number and quality of informed consent forms presented online. (5) Investigational New Drug (IND) / Investigational Device Exemption (IDE) training methods for CTSA Investigators. (6) The percentage of KL2 Awards used by Child Health Investigators at CTSA Institutions. The reports (rn=9) were also summarized using the standard group of key elements identified for data extraction and summarized in a table. All six articles reported using their Institutional CTSA website as either a portal or a tool to promote clinical and translational science as outlined through NCATS goals. A CTSA website is used as a portal when it provides links to other sites, tools, or programs. A CTSA Website is used as a tool when it provides the functionality within its web design like providing an online application or database, or interactive training pages. In 8 of the 9 articles, authors reported on CTSA institutional website as either a translational informatics portal or providing informatics functionalities. Four (4) of the articles reported the use of their website for engagement, on either the collaborator or patient level, such as advocacy, education, or subject enrollment. Two (2) articles reported the use of their CTSA website for the cultivation and training of a clinical and translational science workforce. Four (4) articles reported on the use of their CTSA website for the purposes of increasing the quality and efficiency of translational research. None of the articles reported how their sites were used to promote the integration of underserved populations. All the reports identified a CTSA institutional website as a tool to leverage or disseminate CTSA capabilities and functionality. The access point and or warehousing of these capabilities was the CTSA institutional website. The target audience for these publications included researchers, clinical research administrators, IT programmers, community collaborators, and research subjects. The articles that reported on the use of CTSA institutional websites for clinical and translational functionality included topics such as: (1) the introduction of an informatics tool that searches clinical notes to identify clinical data for research. (2) the promotion of an online research subject advocacy program. (3) the introduction of an informatics tool portal that allows researchers flexible, efficient and effective means of collaboration and interaction with data. (4) the promotion of a team development project tool. (5) the introduction of a research participant registry and study promotion and education tool. (6) the promotion of an independent informatics tool registry that could connect to all CTSA websites. DISCUSSION/SIGNIFICANCE OF IMPACT: This research shows that CTSA institutional website functionality and content contributes to the CTSA body of research and the advancement NIH translational science goals.

OBJECTIVES/GOALS: We sought to examine: 1) variability in center acceptance patterns for heart allografts offered to the highest-priority candidates, 2) impact of this acceptance behavior on candidate survival, and 3) post-transplantation outcomes in candidates who accepted first rank offer vs. previously declined offer. METHODS/STUDY POPULATION: In this retrospective cohort study, the US national transplant registry was queried for all match runs of adult candidates listed for isolated heart transplantation between 2007-2017. We examined center acceptance rates for heart allografts offered to the highest-priority candidates and accounted for covariates in multivariable logistic regression. Competing risks analysis was performed to assess the relationship between center acceptance rate and waitlist mortality. Post-transplantation outcomes (patient survival and graft failure) between candidates who accepted their first-rank offers vs those who accepted previously declined offers were compared using Fine-Gray subdistribution hazards model. RESULTS/ANTICIPATED RESULTS: Among 19,703 unique organ offers, 6,302 (32%) were accepted for first-ranked candidates. After adjustment for donor, recipient, and geographic covariates, transplant centers varied markedly in acceptance rates (12%-62%) of offers made to first-ranked candidates. Lowest acceptance rate centers (<25%) associated with highest cumulative incidence of waitlist mortality. For every 10% increase in adjusted center acceptance rate, waitlist mortality risk decreased by 27% (SHR 0.73, 95% CI 0.67-0.80). No significant difference was observed in 5-year adjusted post-Tx survival and graft failure between hearts accepted at the first-rank vs lower-rank positions. DISCUSSION/SIGNIFICANCE OF IMPACT: Wide variability in heart acceptance rates exists among centers, with candidates listed at low acceptance rate centers more likely to die waiting. Similar post-Tx survival suggests previously declined allografts function as well as those accepted at first offer. Center-level decision is a modifiable behavior associated with waitlist mortality.

OBJECTIVES/GOALS: The dominant complication of Systemic Sclerosis (SSc) is clinically severe and commonly fatal pulmonary fibrosis (PF). We sought to determine the downstream regulatory role of the basic Helix-Loop-Helix protein 40 (bHLHe40), in response to Insulin-like Growth Factor II (IGF-II) on Pro-Lysyl Oxidase cleavage products. METHODS/STUDY POPULATION: We examined the response of primary pulmonary fibroblasts cultured from the lungs of control donors and SSc lung explants to IGF-II as well as human recombinant Lysyl Oxidase Propeptide (LOX-PP). In addition, we utilized an experimentally-induced model of lung fibrosis with intratracheal bleomycin administration. We used qPCR and immunoblotting to quantify mRNA and protein levels, respectively. We used sequence-specific small-interfering RNA to silence targeted genes. Immunoblots were quantified in ImageJ (NIH) and statistical analyses were performed in GraphPad Prism. RESULTS/ANTICIPATED RESULTS: IGF-II regulates levels of Pro-LOX, active LOX, and LOX-PP, as well as isoforms of proteases Bone Morphogenetic Protein 1 (BMP1) and Tolloid-like 1 (TLL1). The transcription factorbHLHe40 localizes to the nucleus in response to IGF-II. bHLHe40 silencing downregulated TLL1, abrogating the enzymatic cleavage of Pro-LOX. SSc lungs have higher baseline levels of the total (N-glycosylated/unglycosylated) LOX-PP than normal lung tissues, and baseline levels of LOX-PP correlated with TLL1 Isoform 2 in SSc lungs. LOX-PP contributes to the development and progression of SSc-PF by mediating changes consistent with the extracellular matrix deregulation implicated in SSc-PF: elevated levels of Collagen 3A1 (COL3A1), Fibronectin-1 (FN1), and Plasminogen Activator Inhibitor-1 (PAI1). DISCUSSION/SIGNIFICANCE: Our findings indicate that bHLHe40, TLL1, and LOX-PP may serve as targets of therapeutic intervention to stop the progression of SSc-PF. Since activation of common fibrotic pathways are involved in different diseases characterized by lung fibrosis such as IPF, our findings may have wider implications for lung fibrosis associated with other diseases.

ABSTRACT IMPACT: This work will inform the need for more trauma-informed approaches to violence screenings among marginalized populations by health care providers. OBJECTIVES/GOALS: Female sex workers (FSW) experience high rates of intimate partner violence (IPV) which may have negative reproductive health consequences. Routine IPV screening by healthcare providers (HCP) is recommended. This study examines how FSW experience IPV assessments by HCP. METHODS/STUDY POPULATION: This qualitative descriptive study is nested within EMERALD, a longitudinal cohort study of street-based FSW. EMERALD assesses a structural community-level intervention on HIV and STI risks among FSW. Participants were recruited for EMERALD using time-location sampling to identify a sampling frame of venues and times where sex work is likely to occur. Inclusion criteria for this qualitative study include: participating in EMERALD, age 18-49, and willingness to participate in one phone interview. Twenty-two semi-structured individual qualitative interviews were conducted. Two coders, using thematic analysis, applied deductive codes and inductive coding to identify themes. RESULTS/ANTICIPATED RESULTS: Three themes emerged from participant interviews regarding IPV screening. Inconsistent screening practices: Despite frequent reproductive health visits among participants, many women did not recall IPV screening by a HCP. Stigma as a barrier to disclosure: Women described feeling judged by HCP regarding their frequency of visits for reproductive concerns, sex work, and substance use and did not trust disclosing violence to HCP. Transactional health encounters: During visits, HCP were focused on addressing women’s immediate concerns; if the HCP did ask about IPV women felt the questions were asked part of a required protocol and not driven by a concern to deeply understand their lives. DISCUSSION/SIGNIFICANCE OF FINDINGS: FSW described inconsistent IPV screening practices by HPC. Participants expressed feeling stigmatized by HCP and that encounters with HCP did not foster trust for women to disclose IPV experiences. There is a need for HPC training in universal IPV screening focused on relationship and trust building to facilitate disclosure.

OBJECTIVES/GOALS: We will use a novel syngeneic model of prostate cancer to examine impairments and uncover potential changes in inflammatory signaling in the brains of animals with and without tumors. We will then investigate the interaction between peripheral tumor, age, and chemotherapy on cognitive impairments and any accompanying neuroinflammation METHODS/STUDY POPULATION: Male Copenhagen rats (aged 3 or 10 months) were subjected to tumor fragment implantation (Dunning R2237G cells) or sham surgery. Once tumors were palpable, animals received either docetaxel (4.5mg/kg, intraperitoneal) or it’s vehicle once every other day for 5 days (3 injections total) followed by a two-week recovery period. During this time, TNFa and IL-6 was quantified in plasma samples obtained once per week for two weeks. Hippocampal-mediated visuospatial and working memories were assessed using the novel object task and percent alternation in a y-maze, respectively. Afterwards, trunk blood and hippocampal tissue were isolated. TNFa and IL-6 protein was quantified in plasma. Hippocampal tissue was probed for markers of neuroinflammation, including increases in TNFa, IL-6, and reactive microglia RESULTS/ANTICIPATED RESULTS: The presence of a tumor alone produces deficits in hippocampal-mediated visuospatial memory and working memory regardless of treatment and persistent elevations in TNFa and IL-6 in plasma. Docetaxel administration also produces impairments in hippocampal-mediated visuospatial memory, but not in working memory. We anticipate these cognitive impairments will be accompanied by hippocampal neuroinflammation. We expect age and docetaxel chemotherapy to exacerbate working memory deficits and markers in hippocampal neuroinflammation, including increases in TNFa, IL-6 and reactive microglia DISCUSSION/SIGNIFICANCE: This study will provide insight into the interaction between tumor, age, and chemotherapy in impairments in visuospatial memories. This model provides a substrate upon which interventions can be tested to ensure the efficacy of the cancer treatment is maintained when treating these cognitive impairments.

ABSTRACT IMPACT: The impact of this study is to encourage health professionals to screen for violent experiences as potential risk factors for CVD and adapt interventions from the non-abused in children as in adults. OBJECTIVES/GOALS: This study aims to assess the relationship between child sexual abuse and cardiovascular risk factors (CVDRF) that present in children. The objectives will provide the prevalence of CVDRF, their association with types of sexual victimization, and a score to assess the impact. METHODS/STUDY POPULATION: This study is a chart review, cross-sectional study. The Puerto Rico Health Justice Center (PRHJC) is a forensic, transdisciplinary, victim-centered, trauma-informed, and evidence-based service. The demographic variables collected are age, sex; the cardiovascular risk factors variables include a level of physical activity, tobacco exposure/alcohol, vital signs (blood pressure, BMI), lipid profile, and C-reactive protein. Sexual violence variables are the type of victimization (sexual assault, sexual molestation), the number of victimizations, and the relationship with the offender. RESULTS/ANTICIPATED RESULTS: A previous study, which examined types of evidence related to the prosecution of sexual violence cases, found that among female victims, 54% was a victim of sexual assault, and 59% had at least one health concern. The study’s hypothesis includes that older and female victims have a higher prevalence of cardiovascular disease risk factors. Also, children victims of sexual assault will have more cardiovascular risk factors than victims of sexual molestation. The age group, sex, number of victimizations, and relationship with the offender will also impact the relationship between the type of victimization and cardiovascular risk factors. DISCUSSION/SIGNIFICANCE OF FINDINGS: Early identification of child sexual abuse is needed to prevent long-term health impacts. The study’s results will be significant in developing clinical guidelines for health care providers to identify child sexual abuse as a predictor of cardiovascular risk factors and encourage victim advocates to identify cardiovascular risk factors.

OBJECTIVES/GOALS: We conducted interviews with investigators, clinicians, and health system and health agency leaders to assess regional educational needs in implementation and improvement science, including content (knowledge and skill), format, experiential learning, and mentoring, to identify barriers and guide planning. METHODS/STUDY POPULATION: Five CTSAs in the University of California Biomedical Research Acceleration, Integration, & Development consortium (UC BRAID) plus a fifth affiliated CTSA developed a common protocol and interviewed 31 California-based learners (current fellows, early and mid-career investigators, clinicians, and health agency personnel) and system leaders from health care and health agencies. Interviews focused on impact goals, educational needs in dissemination, implementation, and improvement (DII) science, challenges in DII research, preferred learning formats, desired proficiencies and skills, and barriers such as cost, time, awareness, terminology, and suitability and availability of training. A rapid review of literature identified potential domains of knowledge and skills for a proposed curriculum. RESULTS/ANTICIPATED RESULTS: Areas of emphasis varied among interviewees; identified learning needs differed between traditional research perspectives (emphasizing areas such as partner engagement, grant writing, frameworks, study design) and applied perspectives (emphasizing areas such as managing change, complex systems, learning system capacity). Learners had a range of preferences; most interviewees desired formats that are longitudinal, experiential, applied, cooperative, and affordable. Variation in knowledge of, and interpretations of, DII terms and goals limited the ability of some interviewees to specify educational needs. A synthesis reveals areas for potential future co-development and networked approaches to regional training and capacity enhancement. DISCUSSION/SIGNIFICANCE OF IMPACT: In response to a rapidly changing health landscape, our academic health systems are developing capabilities to improve care for their populations. Our work informs the training and education needs that are critical to translation at a system-wide level. Regional convenings can raise awareness while translational programs fill educational gaps.

OBJECTIVES/GOALS: The purpose of this study is to identify and quantitatively describe environmental barriers to community engagement and activity participation for adults with stroke and low income. Repeated electronic surveys collected in real time will reduce recall bias and improve characterization of barriers. METHODS/STUDY POPULATION: 20-30 community-dwelling adults with stroke and low income will be recruited for this pilot study. Inclusion criteria: > 1 month post stroke and evidence that they have the vision, literacy, and cognitive capacities to answer survey questions on a smart device. Exclusion criteria: severe aphasia, severe mental illness or substance abuse within 3 months, and ataxia. Participants will complete standardized assessments of daily activities, engagement in and perceptions about community activities, social support, and perceived environmental barriers. Participants then complete four surveys per day for 14 days using an app on an iPod Touch, reporting activities attempted and barriers encountered. RESULTS/ANTICIPATED RESULTS: This is the first study of this kind and is a work in progress. We anticipate that the environmental barriers reported will include physical (e.g. built structures, climate, and natural terrain), social (e.g. support or lack thereof; stigma), political (e.g. access to transportation; healthcare services), and technological barriers (e.g. difficulties with personal equipment and/or technologies such as elevators, ticket kiosks, etc.). DISCUSSION/SIGNIFICANCE OF IMPACT: An increased understanding of the barriers facing community-dwelling adults with stroke and low income will facilitate the development of culturally-appropriate and more accessible self-management programs to help this population re-engage in their communities and return to pre-stroke activities.

OBJECTIVES/GOALS: 1. Identify candidate AN-SAD-causing variants. 2. Estimate the variant effect size of and genotypic relative risk for arrhythmias and AN-SAD. METHODS/STUDY POPULATION: We performed whole genome sequencing (WGS) on 59 Thoroughbred AN-SAD cases and 58 controls. WGS was mapped and variants identified using a modified version of the Genome Analysis Toolkit best practices. Variants will be selected based on case-control analysis using SnpSift and presence in candidate genes. The top 400 candidate AN-SAD-causing variants will be selected based on being common in cases and rare or absent in controls, and uncommon (allele frequency less than 10%) in a catalog of genetic variation for the horse. The 400 variants will be genotyped in our cohort of 1,200 racehorses to determine variant effect size and genotypic relative risk. RESULTS/ANTICIPATED RESULTS: 17,182,003 variants were identified. 230 variants had significantly different allele frequencies (AF) between cases and controls (SnpSift). 723 high and 4,824 moderate impact variants were identified in 1,072 candidate genes. 3,681 variants were present at an AF 10% in the equine variant catalog. Variant effect prediction is ongoing to select the final 400 variants. Cardiac phenotyping (cardiac auscultation and ECG before, during, and after exercise) was performed on 790 racehorses and we will have 1,200 racehorses with cardiac phenotypes and/or AN-SAD. We will genotype the top 400 candidate AN-SAD-causing variants in these 1,200 horses to identify variants of large effect size. DISCUSSION/SIGNIFICANCE: Identification of candidate AN-SAD variants in a spontaneous animal model can facilitate interpretation of candidate variants in humans and horses. This project will provide further support for the racehorse AN-SAD model and will support future work exploring the genetic and environmental risk factors contributing to AN-SAD in this animal model.

OBJECTIVES/GOALS: Neuropsychiatric disorders classified as synaptopathies are marked by a glutamate-associated hypofrontality which impacts decision making and impulsivity. We hypothesized that behavioral efficacy of the psychoplastogen ketamine is mediated in part through lasting promotion of markers of synaptic strength in corticoaccumbens circuit. METHODS/STUDY POPULATION: Male, Sprague-Dawley rats received an intraperitoneal (i.p.) injection of saline, single ketamine (10 mg/kg; 1x/day), or repeated ketamine (10 mg/kg; 1x/day for three days). Twenty-four hrs following the dosing regimen, animals were euthanized, and brains dissected to harvest corticoaccumbens structures including the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAc). mRNA was extracted and converted to cDNA. Levels of brain derived neurotrophic factor (BDNF) exon II mRNA were quantified using reverse transcriptase polymerase chain reaction (RT-PCR); cyclophilin A (PPIA) was used as a loading control. Gene expression differences in ketamine-treated rats were identified versus saline-treated rats. BDNF protein levels were quantified using capillary-electrophoresis immunoblotting. RESULTS/ANTICIPATED RESULTS: Repeated, but not single, ketamine administration decreased mPFC, but increased NAc, BDNF exon II mRNA levels versus saline (p<0.05). Single and repeated ketamine administration increased NAC BDNF protein (p<0.05), while both dosing paradigms induced a trend towards an increase in mPFC BDNF levels. DISCUSSION/SIGNIFICANCE: We discovered a dosing regimen-dependent and sustained effects of ketamine administration on BDNF levels in the rodent brain. Taken together, ketamine-mediated BDNF levels may sustain synaptic strengthening mechanisms supporting future investigation into the utility of ketamine for diseases characterized by synaptopathies.

OBJECTIVES/GOALS: Current COVID-19 rapid molecular tests require cartridge-reader detection, expensive circuitry, and complex microfluidics making the most accurate tests unavailable to the masses. Here we present a rapid molecular diagnostic leveraging isothermal amplification and paper-based microfluidics for a low-cost ultra-sensitive COVID-19 assay. METHODS/STUDY POPULATION: We designed a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of SARS-CoV-2 and bacteriophage MS2 RNA. RT-RPA is a sequence specific, ultrasensitive, rapid isothermal DNA amplification technique that is well suited to home based testing due to its rapid assay time, robustness, ease of use, and readout options. RT-RPA reagents are added to a tube and incubated at 39°C in a fluorometer. Realtime fluorometer data gives results in under 15 minutes. This assay also provides visual detection via lateral flow readout with results in 23 minutes. RESULTS/ANTICIPATED RESULTS: We have developed a rapid multiplexed nucleic acid amplification assay with an internal process control for SARS-CoV-2 using single-pot RT-RPA. We screened 21 primer combinations to select primers that demonstrated excellent performance and target specificity against common respiratory viruses. We demonstrate the ability to multiplex SARS-CoV-2 and MS2 detection, utilizing MS2 as an internal process control for lysis, reverse transcription, amplification, and readout. We show duplexed detection using both fluorescence readout and visual readout using lateral flow strips. Duplexed fluorescence detection shows a limit of detection of 25 copies per reaction. Duplexed lateral flow readout shows a limit of detection of 50 copies per reaction DISCUSSION/SIGNIFICANCE: We developed a duplexed RT-RPA assay for SARS-CoV-2 with fluorescence or lateral flow readout. Our assay does not re-quire expensive reader, circuity, or fluid handling. The low material cost, temperature, and robustness make it ideal for a more accurate home-based COVID-19 diagnostic.

Objectives/Goals: Evaluate the impact of intrauterine growth restriction (IUGR) on neonatal brain development using magnetoencephalography (MEG) and correlate findings with NICU Network Neurobehavioral scale (NNNS) scores at 1 month Methods/Study Population: In this prospective cohort study, we will enroll 30 participants, consisting of 15 neonates diagnosed with IUGR and 15 healthy controls, matched by gestational age, from the University of Arkansas for Medical Sciences. We will perform MEG scans at three key developmental stages: during fetal life, at 1 month, and at 3 months of age and a Bayley IV exam at 12 months of age. The NNNS assessments will be conducted at the 1-month visit to evaluate neurobehavioral outcomes. All MEG data will be synchronized with clinical evaluations and maternal health records to ensure comprehensive analysis. Results/Anticipated Results: We anticipate that the study will reveal significant differences in brain maturation and neural activity patterns between IUGR-affected infants and healthy controls. Specifically, we expect to find altered neural connectivity and delayed maturation in the delta and theta frequency bands during the early neonatal period in the IUGR group. These anticipated neuroimaging findings will be correlated with NNNS scores to assess functional implications of the observed brain activity differences. If our hypotheses are confirmed, the study will provide robust biomarkers for early identification of neurodevelopmental delays in IUGR-affected infants, paving the way for targeted early interventions. Discussion/Significance of Impact: This study could significantly enhance early detection and intervention strategies for IUGR, potentially reducing long-term neurodevelopmental challenges and improving clinical outcomes

Objectives/Goals: Tacrolimus (TAC) is an immunosuppressant used after hematopoietic stem cell transplant (HSCT). Recently, TAC was found to be metabolized to a novel, less active metabolite by common gut microbiota. Our objective is to determine a microbiome signature that influences oral TAC pharmacokinetic (PK) and to develop a clinical tool to select the TAC dose. Methods/Study Population: This is an observational IRB approved microbiome-pharmacogenomic study using banked biospecimens and clinical data, TAC dose, and PK information from the electronic health record. Adult HSCT patients with pre-transplant DNA and stool specimens were included in this analysis if they received TAC in the first 100 days post-HSCT. A global diversity array was used for DNA pharmacogenomic (PGx) genotyping, and metagenomic shotgun sequencing was used for stool microbiome analysis. Spearman correlation will be used to identify potential stool microbiota associated with TAC PK. TAC trough concentrations at steady state will be modeled using nonlinear mixed effects (NLME) modeling to identify potential genetic and microbiota covariates that influence TAC clearance. Results/Anticipated Results: We identified 53 eligible patients who had available DNA and 90 stool samples. The majority (n = 49, 92.5%) were of European ancestry. These patients had 920 (oral  =  622, IV infusion  =  298) TAC trough blood concentrations. We expect that patients who have high abundance of bacteria that metabolize or reduce the absorption of TAC will have lower blood concentrations and will require a higher IV to oral dose conversion ratio than those with lower abundance. Those patients will also require higher oral TAC daily doses. Low stool microbial diversity is expected to be associated with high oral TAC trough intra-patient variability in the first 100 days post-transplant. In the NLME model, PGx when combined with potential bacterial signature will better explain variability in TAC clearance. Discussion/Significance of Impact: Combining PGx and microbiome biomarkers will provide a better understanding of the factors influencing TAC PK and lead to models for individualized dosing. To our knowledge, this is the first study to investigate the combined influence of microbiome and PGx on drug PK. The study is limited to the availability of samples in the biobank.