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: The objective of this study was to evaluate whether exposure to air pollution (PM 2.5) and neighborhood deprivation are associated with prostate cancer risk among men in Baltimore and to determine if social and environmental factors jointly influence disparities in prostate cancer occurrence among men. Methods/Study Population: This case–control study was conducted in the Greater Baltimore area between January 2005 and January 2016. Participants included 617 men with prostate cancer and 852 controls without prostate cancer of African and European descent. Individual data on demographics, smoking, BMI, income, and education were collected through chart review. Residential addresses were linked to neighborhood deprivation index (NDI) and average fine particulate matter (PM₂.₅) levels for 2010 using geospatial data. Logistic regression models were used to estimate associations between PM₂.₅, NDI, and odds of prostate cancer, adjusting for race, smoking, income, education, and BMI. All analyses were conducted using complete-case data. Results/Anticipated Results: In complete-case logistic regression of prostate cancer case status (n = 1,856), unadjusted PM₂.₅ (per 1 µg/m³) was positively associated with odds of prostate cancer (unadjusted OR for developing prostate cancer per 1 µg/m³ = 1.35; p = 0.014). After multivariable adjustment for neighborhood deprivation index (NDI), race, smoking, income, education, and BMI, the association between PM₂.₅ and case status was attenuated and not statistically significant (adjusted OR per 1 µg/m³ = 0.78; 95% CI 0.59–1.04; p = 0.088). By contrast, NDI was associated with higher odds of developing prostate cancer in adjusted models: adjusted OR per 1-unit increase in NDI was 1.15 (95% CI 1.09–1.21; p < 0.001). Using a standardized effect, the adjusted OR per 1 SD increase in NDI was 1.41 (95% CI 1.23–1.61). Discussion/Significance of Impact: Neighborhood deprivation was significantly associated with higher odds of prostate cancer, independent of race, smoking, income, education, and BMI. PM₂.₅ showed no independent association after adjustment, suggesting socioeconomic context may underlie observed disparities in prostate cancer incidence.

Objectives/Goals: Mathematical models of airborne virus transmission lack supporting field and clinical data such as viral aerosol emission rates and airborne infectious doses. Here, we aim to measure inhalation exposure to influenza aerosols in a room shared with persons with community-acquired influenza and estimate the infectious dose via inhalation. Methods/Study Population: We recruited healthy volunteer recipients and influenza donors with polymerase chain reaction (PCR)-confirmed community-acquired infection. On admission to a hotel quarantine, recipients provided sera to determine baseline immunity to influenza virus, and donor infections were confirmed by quantitative real-time polymerase chain reaction. Donors and recipients were housed in separate rooms and interacted in an “event room” with controlled ventilation (0.2 – 0.5 air changes/hour) and relative humidity (20–40%). We collected ambient bioaerosol exposure samples using NIOSH BC-251 samplers. Donors provided exhaled breath samples collected by a Gesundheit-II (G-II). We analyzed aerosol samples using dPCR and fluorescent focus assays for influenza A and sera by hemagglutinin inhibition assay (HAI) against donor viruses and vaccine strains. Results/Anticipated Results: Among two cohorts (24b and 24c), we exposed 11 recipients (mean age: 36; 55% female) to 5 donors (mean age: 21; 80% female) infected with influenza A H1N1 or H3N2. Eight G-II and two NIOSH bioaerosol samples (1–4 µm and ≥4 µm) were PCR positive. We cultured virus from one G-II sample. Based on previous literature, we hypothesized that ~50% of immunologically naïve people (HAI Discussion/Significance of Impact: We demonstrated that it is feasible to recruit donors with community-acquired influenza and expose recipients to measurable virus quantities under controlled conditions. However, baseline immunity was high among volunteers. Our work sets the stage for designing studies with increased sample sizes comprising immunologically naïve volunteers.

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/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/Goals: A sample of 1,073 hypertensive adults in Bangladesh showed unusually high rates of hypokalemia. We analyzed sociodemographic and clinical factors – including age, sex, weight, body mass index, blood pressure, creatinine clearance, and urine protein concentration – to identify key predictors of hypokalemia. Methods/Study Population: A cross-sectional analysis was conducted on 1,073 hypertensive adults from the OK study in Dhaka, Bangladesh (2022–2023). Hypertension was defined as blood pressure >140/90 mmHg, and none of the participants were on any antihypertensive medication prior to the study. Hypokalemia was defined as serum potassium Results/Anticipated Results: The prevalence of hypokalemia was 21.5%. In univariate analysis, age (OR 0.975, 95% CI [0.959, 0.990], p  =  0.00189), systolic blood pressure (OR 1.02, 95% CI [1.00, 1.03], p  =  0.00568) and diastolic blood pressure (OR 1.03, 95% CI [1.01, 1.04], p  =  0.000272) were significantly associated with hypokalemia. In multivariate analysis, age (OR 0.961, 95% CI [0.936, 0.985], p  =  0.00167) remained significant, and creatinine clearance (OR 0.986, 95% CI [0.974, 0.999], p  =  0.0386) became significant. BMI, weight, systolic and diastolic blood pressure, sex, and urine protein concentration were not significant. Discussion/Significance of Impact: In the multivariate analysis, age and creatinine clearance was statistically significant; however, their effect sizes were small and unlikely to be clinically meaningful. The underlying reasons for the high prevalence of hypokalemia in this population remain unclear, warranting further investigation to identify contributing factors.

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/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.

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/Goals: To quantify the association between proximity to harm-reduction vending machines and recurrent nonfatal overdose using recurrent-event survival models, estimate effects on time to reoverdose and hazard, and identify modifiable predictors to guide machine sitting. Methods/Study Population: Retrospective cohort of Milwaukee County nonfatal overdoses, Jan 2018 to Dec 2023 (28,108 events; 20,300 people). Records were geocoded, deduplicated, linked within person, and tagged as single or recurrent. Exposure: residence or event within a 30 min walk of a harm-reduction vending machine. Recurrence summarized with Kaplan-Meier curves and mean cumulative function. An interrupted time series (ITS) assessed pre- vs post-HRVM expansion. For inference, we compared Andersen-Gill, Prentice-Williams-Peterson, and Cox ML models, selecting AG gap time. Covariates: age, sex, race, jurisdiction, location type, disposition, proximity. Assumptions checked; hazards reported with 95% CIs. Results/Anticipated Results: 2018 to 2023: 28,108 nonfatal overdoses among 20,300 people; 3,803 had repeats (11,611 events). Inter-event times shortened with each recurrence. Kaplan–Meier for first to second overdose showed small, consistent separation favoring those within 30 min of HRVMs; mean cumulative functions rose more slowly near HRVMs. The selected Andersen–Gill gap-time model found no meaningful short-term effect of proximity (aHR ≈ 1.03, 95% CI 1.00–1.06). Younger age and public or commercial locations predicted faster recurrence. County ITS suggested stabilization after HRVM expansion without a clear early reduction. Discussion/Significance of Impact: Early HRVM rollout yields small reductions in cumulative recurrence without a meaningful short-term hazard change. Results support MOUD linkage and mobile outreach targeting younger people and public settings. The recurrent-event and ITS framework is generalizable for sitting and monitoring.

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.

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.