ABSTRACT IMPACT: Our may suggest that delta hsTrop could be of prognostic value in patients with sepsis. OBJECTIVES/GOALS: - METHODS/STUDY POPULATION: We analyzed data of those presenting to the ED over an 18-month period with sepsis and at least one episode of hypotension after 1 liter of IV fluids. We performed a retrospective analysis using a cohort derived from modified inclusion and exclusion criteria from the CLOVERS study. The outcomes of patients found to have a delta (at least 6 pg/dL) in high sensitivity troponin T were compared to patients who did not have a delta or have a troponin level measured. We examined demographic and treatment characteristics of this cohort and the incidence of adverse outcomes were determined. We used multivariable logistic regression analysis to test the association of hsTrop and mortality. RESULTS/ANTICIPATED RESULTS: 778 patients met criteria to be included in the cohort. 279 patients had a change in high sensitivity troponins, an incidence of 35.9%. Patients with a delta were more likely to be older, male, and have a higher Charlson index than patients without a delta or those that had no troponin measured. They were also more likely to have a history of chronic lung disease, heart failure and hypertension. Change in high sensitivity troponins were associated with higher in-hospital mortality. When adjusted for age, gender, and Charlson Index, the association between a positive delta troponin and mortality remained statistically significant. DISCUSSION/SIGNIFICANCE OF FINDINGS: In patients with severe sepsis and septic shock, the presence of a positive or negative delta hsTrop at 2 hours is associated with increased mortality. Measurement of high sensitivity troponin early in the patient’s hospital course may have prognostic utility.

OBJECTIVES/GOALS: Sexism harms women’s well-being, affecting life satisfaction and self-doubt in complex ways (Shattell etal., 2008; Oswald etal., 2018). This study examines how hostile and benevolent sexist attitudes moderates the link between experiences of benevolent sexism, self-doubt, and life satisfaction in Latinx women. METHODS/STUDY POPULATION: Participants included 57 English-speaking Latinx women residing in the United States, with a mean age of 31.89 (SD=10.14) years. The majority (61.4%, n=35) identified as Mexican, and most identified as second generation or later (80.7%, n=46). Participants completed surveys assessing hostile and benevolent sexist attitudes (Glick & Fiske, 1996), self-doubt (Oleson etal., 2000), life satisfaction (Diener etal., 1985), and experiences with three aspects of benevolent sexism – protective paternalism (PP), heterosexual intimacy (HI), and complimentary gender differentiation (CGD) (Oswald etal., 2018). RESULTS/ANTICIPATED RESULTS: Moderation analyses were conducted to examine the moderating role of hostile and benevolent sexist attitudes between experiences of benevolent sexism (PP, HI, & CGD) and well-being measures (self-doubt and life satisfaction). An example finding revealed a significant interaction effect between benevolent sexist attitudes and experiences with CGD on satisfaction with lifeF(1,53)=8.34,p<.01. For participants who endorsed high benevolent sexist attitudes, experiences with CGD was associated with increased satisfaction with life (b=.78, p<.001), while the effect of experiences with CGD on life satisfaction was attenuated for those who endorsed low benevolent sexist attitudes (b=.30, p<.05). DISCUSSION/SIGNIFICANCE: These findings have important implications on the well-being of Latinx women as they indicate that those who reject sexist attitudes risk their well-being when confronted with benevolent sexism, unlike those who endorse to such beliefs, potentially gaining increased life satisfaction at the cost of embracing benevolent sexist behavior.

OBJECTIVES/SPECIFIC AIMS: The Empower Lab was established in 2015 with the goal of providing students with hands-on research experience in sexual and gender-based violence and health. METHODS/STUDY POPULATION: The Empower Lab consists of 10–12 undergraduate, graduate, and medical students at a time. Students undergo a rigorous application process, and agree to volunteer 8 hours per week for at least 1 year. Students are assigned to teams, and learn research skills such as literature searches, systematic reviews, research question generation, study design, IRB procedures, database creation and management, data collection and analysis, oral and poster presentation, manuscript preparation, team collaboration and communication, advocacy, and leadership. Students start as research assistants, and can be promoted to team leader, and associate director of research. Students mentor and teach each other, and are supervised by the principal investigator (PI). A survey skill self-assessment is administered to lab members on entry to the lab, every 4–6 months, and upon exit. RESULTS/ANTICIPATED RESULTS: In total, 20 students have participated in the lab to date, and 12 are currently enrolled. Eighty percent of the lab members are women. The students are 45% undergraduates, 15% graduate (nursing, social work, public health), 20% medical students, and 10% not currently enrolled in school (gap year). Twenty students completed entry surveys, 11 students have completed interim surveys, and 5 students have completed exit surveys. Examination of current surveys indicates that students are gaining skills throughout the lab experience. Free-text feedback provided further insight. Currently, the lab has 5 IRB-approved studies actively recruiting participants, 4 manuscripts being written, and 3 studies in the development phase. Students have presented at three local and 2 national meetings to date. Changes have been made to the lab structure over time in order to provide clear expectations and feedback, and strengthen student performance. DISCUSSION/SIGNIFICANCE OF IMPACT: The Empower Lab is an innovative public health lab that provides opportunities for real-world research experience for students. The teamwork, collaboration, and structure of the lab permit mentoring, support, and teaching from peers, as well as from the PI. The Lab increases the PI’s productivity. Students are encouraged to develop and implement their own research ideas, further encouraging independence and initiative. Although the number of surveys is limited to date, they indicate improvement in skills and confidence among lab members. The predominance of women in the lab suggests that this is a strong model for recruitment and retention of women in STEM.

OBJECTIVES/GOALS: The impact of baseline BMI on glycemic response to group medical visits (GMV) and weight management (WM)-based interventions is unclear. Our objective is to determine how baseline BMI class impacts patient responses to GMV and interventions that combine WM/GMV. METHODS/STUDY POPULATION: We will perform a secondary analysis of Jump Start, a randomized, controlled trial that compared the effectiveness of a GMV-based low carbohydrate diet-focused WM program (WM/GMV) to traditional GMV-based medication management (GMV) on diabetes control. The primary and secondary outcomes will be change in hemoglobin A1c (HbA1c) and weight at 48 months, respectively. Study participants will be stratified into BMI categories defined by BMI 27-29.9kg/m2, 30.0-34.9kg/m2, 35.0-39.9kg/m2, and ≥40.0kg/m2. Hierarchical mixed models will be used to examine the differential impact of the WM/GMV intervention compared to GMV on changes in outcomes by BMI class category. RESULTS/ANTICIPATED RESULTS: Jump Start enrolled 263 overweight Veterans (BMI ≥ 27kg/m2) with type 2 diabetes. At baseline, mean BMI was 35.3 and mean HbA1c was 9.1. 14.5% were overweight (BMI 27–29.9) and 84.5% were obese (BMI ≥ 30). The proposed analyses are ongoing. We anticipate that patients in the higher BMI obesity classes will demonstrate greater reductions in HbA1c and weight with the WM/GMV intervention relative to traditional GMV. DISCUSSION/SIGNIFICANCE OF IMPACT: This work will advance the understanding of the relationship between BMI and glycemic response to targeted interventions, and may ultimately provide guidance for interventions for type 2 diabetes.

OBJECTIVES/SPECIFIC AIMS: The primary goal of this project is to verify findings from a murine prostatitis model in the human setting. METHODS/STUDY POPULATION: Methods include primary cell isolation and culture, FACS, adoptive transfer, 3D cell culture, histology, immunofluorescence, xenograft, and tissue recombination. The study population includes patients undergoing HoLEP or radical prostatectomy due to hyperplasia or adjacent bladder or prostate cancer. RESULTS/ANTICIPATED RESULTS: Having verified similar sensitivities to androgen receptor (AR) inhibitors between naive murine and human basal prostate stem cells, we anticipate that autoimmune inflammation in humans affects the response of basal prostate stem cells in a manner similar to the murine setting as well. This includes increased proliferation, increased differentiation, and decreased response to AR inhibitors. DISCUSSION/SIGNIFICANCE OF IMPACT: The identification of survival mechanisms used by basal prostate stem cells in an androgen deprived environment may give insight to the process by which prostate cancer becomes androgen independent. The effect of inflammation on proliferation, survival, and AR signaling in these cells may also provide information relevant to cancer initiation and progression.

OBJECTIVES/GOALS: Surgical training is constrained by duty hour limits, bias, and a trial-and-error learning process. Surgeon skill variation is a healthcare system disparity that can impact patient outcomes. Incorporating validated, standardized assessment tools and machine learning (ML) algorithms may help to standardize and reduce bias in surgeon education. METHODS/STUDY POPULATION: To support assessment tool and ML algorithm development, we are curating an annotated video registry of neurosurgical procedures. Point-of-view video of resident and attending neurosurgeons performing craniotomies is recorded via an eye-tracking headset. A Delphi panel of neurosurgeons will review the video and determine which represent expert versus trainee performance. Neurosurgery attendings will be interviewed to provide descriptions of craniotomies which will be used to develop an assessment rubric. A Delphi panel will determine what rubric components should be maintained. New craniotomy videos will be viewed by attendings in a blinded fashion while completing the assessment rubric. An online feedback platform is being developed allowing residents to prospectively track assessment data. RESULTS/ANTICIPATED RESULTS: We anticipate development of an annotated, institutional video database featuring craniotomies performed by residents and attending neurosurgeons. Using a Delphi approach, we anticipate achieving consensus on which videos reflect expert versus trainee performance. We anticipate development of a novel craniotomy assessment rubric that is both valid and reliable. Our online feedback platform will allow prospective tracking of assessment data from multiple sources and enhanced transparency in the feedback process. The video registry and assessment data will enable development of novel ML algorithms able to recognize craniotomy segments and estimate operator skill. DISCUSSION/SIGNIFICANCE: Building a video registry of procedures, validated assessment tools, and a prototype feedback platform enables a pipeline for ML algorithm development. Together these tools will help to standardize and optimize resident education translating to earlier operative independence, improved patient safety, and reduced bias during surgical training.

OBJECTIVES/GOALS: Scholarly achievement metrics are essential for academic researchers since they are used for promotion and funding opportunities. Our objective was to create awareness among pilot project PIs about how these scholarly activities are evaluated and about the need for continuous auto-evaluation. METHODS/STUDY POPULATION: NIH-sponsored Clinical & Translational Research (CTR) infrastructure grants are a critical mechanism to increase scholarly activity. The Pilot Project Program Core (PPP) of The Alliance IDeA-CTR created a weighted metrics system to evaluate activities including presentations, publications, promotion, honors, & community service. We used the revised evidence-based medicine pyramid to develop the metric instrument. Pilot project PIs received the metric table and met quarterly with a PPP member to discuss progress. The top PIs were acknowledged during the Alliance Research Day with a platform presentation and a monetary award for research expenses or travel to scientific meetings. RESULTS/ANTICIPATED RESULTS: During our first 2 pilot project calls (2020-2022) the PPP funded 7 one-year pilot projects for ($50,000 each). We had a total of 10 PIs, 2 of the projects were MPI. Seven PIs were early or new stage investigators (ESI/NSI). Using the productivity award metric we had a total of 33 presentations, 10 publications, 12 events of community service, and 2 external grant funding. These are significant outcomes considering the pandemics impact on clinical & translational research. A total of 3 awards were given, one award per year for funding and an overall award. The activity was well received by the PIs who actively participated in the tracking of their scholarly activities using the metric. DISCUSSION/SIGNIFICANCE: Productivity metrics are crucial for the career development of ESI and NSI by raising awareness regarding the importance of scholarly activities in their career. This activity will help them track their productivity in an ongoing manner while becoming independent researchers.

OBJECTIVES/SPECIFIC AIMS: (1) Evaluate safety of a novel influenza vaccination strategy in patients with plasma cell disorders. (2) Measure laboratory-confirmed influenza infection rates following a novel influenza vaccination strategy in patients with plasma cell disorders. (3) Evaluate clinical correlates of response following a novel influenza vaccination strategy in patients with plasma cell disorders. METHODS/STUDY POPULATION: We conducted a double-blind, randomized study over the 2015–16 flu season, comparing 2 doses of Fluzone® High-Dose influenza vaccination (separated by 30 d) to the current standard of care influenza vaccination. Patients were allocated to the experimental arm in 2:1 ratio compared with standard of care arm. Standard of care influenza vaccination was considered single age-based vaccination (standard dose for those <65 y and high dosefor those ≥65 y) and patients in this arm received a saline placebo injection at 30 days to assist in blinding. Eligibility criteria allowed any patient with a PCD and no contraindication to trivalent inactivated influenza vaccine. The primary endpoint was laboratory-confirmed flu infection rate. Protocol-driven surveillance screened patients for flu-like illnesses and performed laboratory testing for influenza until the end of the flu season in May 2016. Secondary endpoints include HAI titer serologic response rates, clinical correlates of protection from influenza infection, and exploratory studies of cell-mediated immunity through characterization of T cell subpopulations, cytokine profiles, and flu-specific T-cell responsiveness. RESULTS/ANTICIPATED RESULTS: In total, 122 plasma cell disorder patients were enrolled (97 with disease requiring therapy and 25 with asymptomatic gammopathy). Of those 48 patients received a single standard of care influenza vaccination and 74 patients received 2 doses of Fluzone® high-dose vaccine. Median age was 67 years (range 42–90). This 2-dose vaccination strategy was safely tolerated in all patients with no grade 2 adverse events attributed to vaccine. With close clinical follow-up, only 4% of patients receiving 2 vaccine doses developed laboratory confirmed influenza Versus 8.3% of those receiving single vaccine. When compared to the expected CDC influenza infection rate of 10%–15%, 1 sample, 2-tailed binomial testing revealed patients receiving 2 vaccines experienced a significantly lower rate of infection than the expected rate (p<0.05) whereas those receiving single vaccine showed no significant difference (p=0.38). DISCUSSION/SIGNIFICANCE OF IMPACT: This randomized study demonstrates that the 2 dose strategy of Fluzone® high-dose influenza vaccine is safely tolerated in patients with plasma cell disorders and associated with significantly less than expected laboratory-confirmed influenza infections. The results suggest that this novel vaccination strategy may have a clinical benefit in reducing influenza infections in plasma cell disorder patients and thus may have practice changing implications. Final analyses of serologic responses, clinical correlates of response, and cell-mediated immune correlates may provide valuable insights into in vivo “immune-competence” in patients with plasma cell disorders.

OBJECTIVES/GOALS: This study aimed to investigate the mechanistic effects of fish oil (âμ-3 fatty acids) or evening primrose oil (âμ-6 fatty acids) supplementation on platelet reactivity in postmenopausal women. METHODS/STUDY POPULATION: Postmenopausal women were recruited from the Ann Arbor community and the University of Michigan Medicine Center. All subjects were recruited under study protocols approved by the University of Michigan IRB between November 2015 and March 2017. We conducted a randomized, double-blind, two-period crossover trial, consisting of a 60-day supplementation period followed by a 14-day washout period in between and at the end of the study. Subjects were treated daily in random order with 2g of fish oil supplement and 2g of evening primrose oil. Blood was drawn at baseline, post-supplementation, and after washout. The effects of fatty acid supplementation on platelet aggregation, dense granule secretion and activation of basal integrin âºIIbÎ23 were assessed following supplementation and washout period. RESULTS/ANTICIPATED RESULTS: The study started with 90 postmenopausal women. A total of 78 subjects completed the study, with 12 subjects dropping out due to non-compliance and medical reasons. Supplementation with fish oil attenuated the thrombin receptor PAR4-induced platelet aggregation, whereas primrose oil supplementation attenuated aggregation mediated by PAR4 or collagen. Supplementation with âμ-3 or âμ-6 fatty acids decreased platelet dense granule secretion and attenuated basal levels of integrin âºIIbÎ23 activation. Post-washout following supplementation with primrose oil, the thrombin receptor PAR1-induced platelet aggregation was similarly attenuated. For either treatment, the observed effects post supplementation on dense granule secretion and basal integrin activation were sustained after the washout. DISCUSSION/SIGNIFICANCE: Postmenopausal women are at increased risk for a cardiovascular event due to platelet hyperactivity. This study indicates that supplementation with âμ-3 and âμ-6 fatty acids may offer significant protection for postmenopausal women against cardiovascular diseases and occlusive thrombotic events by reducing platelet reactivity.

OBJECTIVES/GOALS: Preterm birth is the most common birth complication in the United States. To date, there are no effective public health strategies to reduce the burden of prematurity. Using geospatial information system (GIS) mapping, we identified the most salient risk factors of preterm birth across US counties targetable for future interventions. METHODS/STUDY POPULATION: Risk factors of preterm birth were identified from the perinatal health nonprofit organization, March of Dimes, and included factors such as obesity, smoking, insurance coverage and poverty. US 2013 county-level data on sociodemographic characteristics, behavioral risk factors and preterm birth were extracted and combined from the American Census, Center for Disease Control, and US Health Resources and Services Administration. Spatial autocorrelation and multivariate spatial regression were used to determine the risk factors most strongly associated with preterm birth. These models were adjusted for race, given well-documented race disparities for preterm birth. As a case-study comparison, we mapped risk factors in the two states with the highest and lowest proportion of preterm births in 2013. RESULTS/ANTICIPATED RESULTS: In our preliminary analysis, obesity was the factor most strongly associated with preterm birth (ß = 7.32, SE: 1.13, p<0.001) at the US county-level. Surprisingly, smoking was not found to be significantly associated with preterm birth. In 2013, Vermont had the lowest prevalence of preterm birth at 7.6% and Mississippi had the highest prevalence of preterm birth at 13.1%. Health insurance coverage and obesity were the two risk factors that differed between Vermont and Mississippi. The median proportion of uninsured individuals in Mississippi counties was four times higher than that of Vermont counties (26.3% vs 10.9%, p<0.01). Similarly, the median obesity prevalence in Mississippi counties was significantly higher than the median obesity prevalence in Vermont counties (38.8% vs. 25.2%). DISCUSSION/SIGNIFICANCE OF IMPACT: Public health efforts aimed at reducing obesity and increasing health insurance coverage may have the greatest impact at addressing the US burden of preterm birth. Further, geospatial mapping is a powerful analytic tool to identify regions in the US where preterm birth interventions would be most beneficial.

ABSTRACT IMPACT: This study establishes the association between childhood hypertension and health outcomes in early adulthood, identifying the need to understand blood pressure during early life for primary prevention of hypertension and cardiovascular disease. OBJECTIVES/GOALS: There is evidence that blood pressure level in early life can influence hypertension and other cardiovascular risk factors later in life. We examined whether hypertension before the age of 18 is associated with higher odds of obesity and hypertension after the age of 18. METHODS/STUDY POPULATION: We studied 19,367 children and adolescents from the Vanderbilt University Medical Center’s Synthetic Derivative, a de-identified version of the electronic medical record. Childhood hypertension was defined as systolic blood pressure (SBP) ≥130 mmHg or diastolic blood pressure (DBP) ≥80 mmHg at three or more outpatient visits before the age of 18. Obesity and hypertension in early adulthood were the primary outcomes. Obesity was defined as being above normal weight for adulthood height at age 30 based on the NIH’s body mass index tables. Hypertension was defined as SBP ≥130 mmHg or DBP ≥80 mmHg at three or more outpatient visits after the age of 18. Odds ratios and 95% confidence intervals (CIs) were computed from logistic regression models adjusted for demographics, medication use, and childhood weight. RESULTS/ANTICIPATED RESULTS: Most subjects were female (63%) and white (80%). During childhood, 17% of participants had hypertension. Approximately 58% of this group were obese at age 30, and 38% had hypertension as adults. Compared to females with no childhood hypertension, females with childhood hypertension had 1.35 times higher odds of being obese at age 30 (95% CI: 1.15, 1.58) and 3.56 times higher odds of having hypertension over the age of 18 (95% CI: 3.09, 4.09). Males with childhood hypertension, compared to males without, had 1.28 times higher odds of being obese at age 30 (95% CI: 1.08, 1.52) and 2.74 times higher odds of having hypertension over the age of 18 (95% CI: 2.35, 3.20). Associations between childhood hypertension, early adulthood obesity, and hypertension significantly differed by gender (p-for-interaction for both: <0.01). DISCUSSION/SIGNIFICANCE OF FINDINGS: Childhood hypertension is associated with obesity and hypertension in early adulthood. Understanding blood pressure levels in childhood and adolescence may help target efforts to reduce early adulthood cardiovascular risk factors.

OBJECTIVES/SPECIFIC AIMS: Our objective was to compare the proteomics of HDL between youth with T1DM and healthy controls (HC). METHODS/STUDY POPULATION: We did chromatography-based HDL purification and SWATH-MS-based proteomic quantitation. Proteomic alterations of HDL fractions and their association with glycemic control was examined. Study population: 26 patients with T1DM and 13 HC. RESULTS/ANTICIPATED RESULTS: We quantified 78 proteins in isolated HDL, using mass spectrometry and label-free SWATH quantification. Youth with T1DM had significantly higher protein levels of A1BG (P = 0.008), A2AP (P = 0.0448), APOA4 (P = 0.0366), CFAH (P = 0.0476), FHR2 (P = 0.0005), ITIH4(P = 0.01), PGRP2 (P = 0.0167) and lower levels of ALBU (P = 0.0164) and CO3 (P = 0.019) compared to HC. A1BG (r=0.541, P<0.001) and ITIH4 (r=0.357, P = 0.026) were significantly positively correlated with HbA1c. DISCUSSION/SIGNIFICANCE OF IMPACT: Youth with T1DM have proteomic alterations of their HDL compared to HC, despite similar concentration of HDL cholesterol, that might affect the cardioprotective mechanisms of HDL. Future efforts should focus on investigating the role of these HDL associated proteins in regard to HDL function and their role in CVD risk in patients with T1DM.

OBJECTIVES/SPECIFIC AIMS: A hallmark of progressive HIV-1 infection is the massive activation and depletion of the gut barrier protective CD4 T helper subsets (Th17 and Th22) in the intestinal mucosa. The loss of these cells is thought to contribute to microbial translocation and systemic immune activation that occurs during chronic infection. In addition to the loss of protective Th subsets, we previously showed that chronically HIV-1 infected individuals have an altered colonic mucosal microbiome, which is in part characterized by a lower relative abundance of bacteria that produce the short-chain fatty acid butyrate in conjunction with increased relative abundance of gram-negative pathobionts. This dysbiosis was linked to markers of mucosal and systemic immune activation in these individuals. Following up on these clinical observations, we sought to understand how a loss of butyrate might contribute to HIV-associated inflammation. Initial studies showed that the addition of butyrate to cultured lamina propria mononuclear cells (LPMC) resulted in decreased pathobiont-driven gut T cell activation, HIV-1 infection levels and production of IL-17 and IFNy. Since the gut barrier protective Th17 and Th22 subsets are preferentially infected and depleted, which is critical to HIV-1 pathogenesis, we wanted to determine the mechanism by which butyrate modulates activation of these important Th subsets in the gut. METHODS/STUDY POPULATION: Total LPMCs or purified LP CD4 T cells were isolated from human jejunal tissue (n=3–6), labeled with CFSE and cultured with TCR/CD28 beads to mimic APC driven T cell activation, with the addition of butyrate at physiologic doses(0–2 mM). Four days after culture, secreted cytokine(IL-17 and IFNy) levels were measured by ELISA. Cells were then short-term (4 hr) mitogenically stimulated (PMA/Ionomycin) in the presence of a golgi transport inhibitor. Total CD4 T cell activation (CD38+/HLA-DR+, CD25+), proliferation (CFSElow), and frequencies of intracellular cytokines were measured by multi-color flow cytometry. Paired t-tests were performed to determine statistical significance. RESULTS/ANTICIPATED RESULTS: Butyrate inhibited LP CD4 T cell activation (p=0.013) and proliferation (p=0.015) within total LPMCs stimulated with TCR/CD28 beads in a dose-dependent manner, with significant activity starting at 0.125 mM. Quantification of total secreted cytokines revealed that butyrate significantly decreased both IL-17 and IFNy production after 4 days of culture at 0.0625 mM and 0.25 mM of butyrate, respectively. Assays using purified LP CD4 T cells demonstrated that butyrate directly decreased LP CD4 T cell activation, proliferation and cytokine production in response to TCR/CD28 stimulation. Studies on specific T helper subsets revealed that butyrate inhibited proliferation of Th17 cells at lower concentrations (IC50:0.147 mM) compared with Th1 (IC50:0.229 mM) and Th22 (IC50:0.258 mM) and Th non-IL-22/IL-17/IFNy producing (IC50:2.14 mM) subsets. In addition, it appeared there was a paradoxical increase of HIV-1 infection levels at lower concentrations of butyrate (0.125 mM). DISCUSSION/SIGNIFICANCE OF IMPACT: The addition of butyrate to activated LP CD4 T cells decreases TCR-mediated activation in a dose-dependent manner, and butyrate acts directly on purified LP CD4 T cell populations independent of other cell populations. Butyrate differentially inhibited the proliferation of Th17, Th1, and Th22 subsets, with Th17 cells being the most sensitive to butyrate but increased the infection levels of all T helper subsets at low concentrations. Further studies are needed to determine the mechanism of butyrate’s actions on LP Th cells and the sensitivity of Th17 cells to the inhibitory effects of butyrate. These results could help direct targeted manipulation of the colonic microbiome of HIV-1 infected individuals to help resolve inflammation and limit the impact of the infection in the gut mucosa and systemically.

The ability of research networks and individual institutions to effectively and efficiently prepare, respond, and adapt to emergent challenges is essential for the biomedical research enterprise. At the beginning of 2021, a special Working Group was formed by individuals in the Clinical and Translational Science Award (CTSA) consortium and approved by the CTSA Steering Committee to explore “Adaptive Capacity and Preparedness (AC&P) of CTSA Hubs.” The AC&P Working Group took a pragmatic Environmental Scan (E-Scan) approach of utilizing the diverse data that had been collected through existing mechanisms. The Local Adaptive Capacity framework was adapted to illustrate the interconnectedness of CTSA programs and services, while exposing how the demands of the pandemic forced them to quickly pivot and adapt. This paper presents a synopsis of the themes and lessons learned that emerged from individual sections of the E-Scan. Lessons learned from this study may improve our understanding of adaptive capacity and preparedness at different levels, as well as help strengthen the core service models, strategies, and foster innovation in clinical and translational science research.

OBJECTIVES/GOALS: The ITHS TL1 program is designed to grow trainees’ competence and knowledge in translational research. Our objective is to expand the program to the 5-state Washington, Wyoming, Alaska, Montana, and Idaho (WWAMI) region by establishing a TL1 cohort at Montana State University (MSU). METHODS/STUDY POPULATION: Interdisciplinary training at the predoctoral level is ideal for preparing the future translational workforce. At this stage in their training, they have developed disciplinary expertise but have not yet narrowed their specializations. By expanding the TL1 program to include both University of Washington (UW) and MSU we are amplifying the robust academic research networks of both institutions, particularly programs in rural health equity, rural and tribal populations, and emerging infectious diseases. Using a collaborative, online educational model we will bring together trainees in a multi directional, joint training effort utilizing existing and emerging collaborations. RESULTS/ANTICIPATED RESULTS: The anticipated outcome is to create a single program by bringing together a cohort of scholars from various disciplines spanning the translational science spectrum, with diverse types of research experience which enables them to learn from each other in a diverse setting. This will allow the program to more effectively grow trainee’s competencies and knowledge in multidisciplinary translational research methodology, as well as build skills in team science and cross-disciplinary communication. DISCUSSION/SIGNIFICANCE: If successful, the ITHS TL1 program will prepare translational scientists with an awareness of diverse perspectives and contemporary research challenges. This would benefit the 5 state WWAMI region, which covers 27% of the total land mass of the US.

OBJECTIVES/SPECIFIC AIMS: We sought to investigate the role of the host microbiome during severe, acute respiratory infection (ARI) to understand the drivers of both acute clinical pathogenesis. METHODS/STUDY POPULATION: Nasopharyngeal swabs comprised of mixed cell populations at the active site of infection were collected from 192 hospitalized pediatric patients with ARI. We combined comprehensive respiratory virus detection and virus genome sequencing with 16S rRNA gene sequencing to evaluate the microbial content of the airway during ARI. This data was coupled with 11 clinical parameters, which were compiled to create a clinical severity score. The microbiome profiles were assessed to determine if clinical severity of infection, and/or specific virus was associated with increased clinical severity. RESULTS/ANTICIPATED RESULTS: We identified 8 major microbiome profiles classified by dominant bacterial genus, Moraxella, Corynebacterium, Staphylococcus, Haemophilus, Streptococcus, Alloiococcus, Schlegelella, and Diverse. Increased clinical severity was significantly associated with microbiome profiles dominated by Haemophilus, Streptococcus, and Schlegelella, whereas Corynebacterium and Alloiococcus were more prevalent in children with less severe disease. Independent of the microbial community, more than 60% of patients with the highest clinical severity were infected with either respiratory syncytial virus or rhinovirus. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that individually and in combination, both virus and microbial composition may drive clinical severity during acute respiratory viral infections. It is still unclear how the complex interplay between virus, bacterial community, and the host response influence long-term respiratory impacts, such as the development of asthma. Nonetheless, during ARIs therapeutic interventions such as antibiotics and probiotics may be warranted in a subset of patients that are identified to have both a virus and microbiome profile that is associated with increased pathogenesis to limit both acute and long-term phenotypes.