OBJECTIVES/GOALS: The spectrum of disease caused by SARS-CoV-2 ranges from asymptomatic detection to severe illness, with varying presentations by age. Therefore, we aimed to compare the clinical characteristics between children and adults with SARS-CoV-2. METHODS/STUDY POPULATION: From March 20, 2020, to August 18, 2021, we conducted SARS-CoV-2 surveillance in individuals from metropolitan Nashville, TN. Children with multisystem inflammatory syndrome were excluded. Analyses were restricted to individuals with SARS-CoV-2 infection confirmed by detection of viral RNA in nasal specimens using reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and/or by detection of serum IgG to the SARS-CoV-2 spike and nucleocapsid proteins using enzyme-linked immunosorbent assay (ELISA). Those with negative RT-qPCR results, but a positive ELISA within 4-6 weeks of symptom onset, were classified as SARS-CoV-2 positive. Clinical characteristics between children and adults were compared with Pearson’s chi square. Illness duration was compared using Kaplan Meier estimators. RESULTS/ANTICIPATED RESULTS: Overall, 426/826 (49%) individuals (children: 57 [13%); adults: 369 [87%]) were SARS-CoV-2 positive, with median ages of 12 and 41 years, respectively. Most individuals were female (54%) and white, non-Hispanic (79%). Compared to adults, children were more likely to be asymptomatic (children: 16% vs. adults: 5%; p=0.001). In contrast, symptomatic adults were more likely to report cough (71% vs. 56%), wheezing (21% vs. 8%), shortness of breath (45% vs. 19%), ageusia (67% vs. 23%), and anosmia (64% vs 27%) than symptomatic children (p<0.05). Mean illness duration was shorter in children than adults: 7 days (95% CI: 5.1, 8.9) vs. 14 days (95% CI: 12.4,15.0), respectively. A total of 5% (18/352) of adults reported symptoms lasting ? 4 weeks (range: 31-96 days), whereas all symptoms in children resolved by 31 days. DISCUSSION/SIGNIFICANCE: Overall, children with SARS-CoV-2 present with a shorter and milder disease course compared to adults. Further studies are needed to understand SARS-CoV-2 illness severity across the lifespan.

OBJECTIVES/GOALS: Cadmium is a widespread neurotoxic metal pollutant; however prior study results of Cd and later-life cognition are mixed. We investigated association of urinary cadmium on Alzheimer’s Disease (AD) mortality risk, accounting for key co-pollutants smoking and lead, in the presence of competing risks. METHODS/STUDY POPULATION: We included 5692 persons, 60 years old from the 1998-2018 National Health and Nutrition Examination Survey. Underlying cause of death was determined via linked 1999-2019 National Death Index data. Urinary cadmium (UCD) reflects prolonged exposure and was adjusted for creatinine. We used multiple imputation (5 iterations) to recapture substantial model observation drop-out (N=782). We used three Cox proportional hazard models to estimate hazard ratios (HR) and 95% confidence interval (CI) per unit increase in UCD and time to AD mortality: a competing risks model, a survey-weighted model, and a baseline model including neither, all adjusted for demographic characteristics, lead, and smoking. RESULTS/ANTICIPATED RESULTS: Follow-up ranged from 0 to 20.8 years (mean 8.2 years), with a total of 1,987 individuals deceased (14,232 person-years at-risk), including 88 individuals dying from AD. Mean UCD was 0.50 μg/g creatinine (standard error=0.01). In baseline and survey-weighted models fully adjusted for NHANES cycle, poverty income ratio, age, race/ethnicity, sex, marital status, education, smoking status, and blood lead levels, a per unit increase in UCD was associated with approximately twice the rate of AD mortality (baseline model HR: 1.92, 95% CI: 1.28, 2.89; survey-weighted model HR: 2.08, 95% CI: 1.42, 3.06). In the competing risks model, this association was attenuated (HR: 1.58, 95% CI 1.06 2.36). DISCUSSION/SIGNIFICANCE: Our study finds chronic cadmium exposure associated with AD mortality even after accounting for competing risks of AD mortality and confounding effects of cigarette smoking and lead exposure, strengthening the evidence that long-term cadmium exposure adversely affects later-life cognitive health.

OBJECTIVES/GOALS: Congenital anomalies (CAs) affect 3% of live births, yet the cause of 80% of CAs is unknown and for the 20% with an identified cause, variability in penetrance suggests additional risk drivers exist. Our method for identifying and categorizing CAs in electronic health record (EHR) linked biobank databases can expand and improve CA etiologic research. METHODS/STUDY POPULATION: We identified individuals with CAs in three groups: 1. Those with at least one CA 2. Those with multiple CAs (MCA), those with two or more ‘major’ CAs, and 3. Those with CAs in a specific organ system. We also created a novel quantitative approach, using phenome-wide association studies (pheWAS), for determining CA-associated genetic disease billing codes in order to separate individuals that have a known genetic cause for their CAs from those with idiopathic CAs. We updated CA phecodes, aggregates of clinical billing codes, which we used to identify CA cases in Vanderbilt’s EHR-linked biobank database, BioVU. We create a new phecode, ‘All CAs’, for researchers to quickly identify all individuals with at least one CA. We evaluate the definition of MCA using pheWAS analyses to compare ‘minor’ vs ‘major’ CA. RESULTS/ANTICIPATED RESULTS: The new CA phecode nomenclature includes 5.8 times more codes for CAs compared with the previous version (365 vs 56), improving granularity. 85 (19.7%) CA-associated genetic disease billing codes were identified through literature review. PheWAS analyses revealed an additional 16 (3.7%) genetic disease billing codes with one or more significant (p< 2.75 x10-5) association with CA-related phecodes. Identifying CA-associated genetic disease billing codes allows researchers to differentiate between idiopathic CAs and those that have a known genetic cause. PheWAS analyses of individuals with previously considered “minor” CAs showed many associated severe health problems, revealing that the differentiation between “minor” vs “major” CAs when identifying individuals with MCA in the EHR is arbitrary. DISCUSSION/SIGNIFICANCE: Our CA identification method is scalable for the growing number of EHR-linked biobanks. Differentiating between idiopathic CAs from those with known causes will increase power in studies discovering additional genetic drivers of CAs. Our novel method allows for expansion and acceleration of CA epidemiological research in EHR-linked biobank data.

OBJECTIVES/SPECIFIC AIMS: Our research hypothesis is that resting state fMRI (rsfMRI) data can be used to identify regions of the brain which are associated with cognitive decline in patients – thereby providing a tool by which to characterize AD progression in patients. METHODS/STUDY POPULATION: We used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to analyze Mini-Mental State Examination (MMSE) questionnaire scores from 14 patients diagnosed with AD at two measurement occasions. RsfMRI data was available at the first of these occasions for these patients. These rsfMRI data were summarized into 264 node-based graph theory measures of clustering coefficient and eigenvector centrality. To address our research hypothesis, we modeled changes in patient MMSE scores over time as a function of these rsfMRI data, controlling for relevant confounding factors. This model accounted for the high-dimensionality of our predictor data, the longitudinal nature of the outcome, and our desire to identify a subset of regions in the brain most associated with the MMSE outcome. RESULTS/ANTICIPATED RESULTS: The use of either the clustering coefficient or eigenvector centrality rsfMRI predictors in modeling MMSE scores for patients over time resulted in the identification of different subsets of brain regions associated with cognitive decline. This suggests that these predictors capture different information on patient propensity for cognitive decline. Further work is warranted to validate these results on a larger sample of ADNI patients. DISCUSSION/SIGNIFICANCE OF IMPACT: We conclude that different rsfMRI graph theory measures capture different aspects of cognitive function and decline in patients, which could be a future consideration in clinical practice.

OBJECTIVES/SPECIFIC AIMS: The serotonin receptor 6 (5-HT6) is a potential therapeutic target given its distribution in brain regions that are important in depression, anxiety, and cognition. This study sought to investigate the effects of age on 5-HT6 receptor availability using 11C GSK215083, a PET ligand with affinity for 5-HT6 in the striatum and 5-HT2A in the cortex. METHODS/STUDY POPULATION: In total, 28 healthy male subjects (age range: 23–52 years) were scanned with 11C-GSK215083 on the HR+PET scanner. Time-activity curves in regions-of-interest were fitted with multilinear analysis-1 method. Binding potentials (BPND) were calculated using cerebellum as the reference region and corrected for partial volume effects. RESULTS/ANTICIPATED RESULTS: In 5-HT6 rich areas, regional 11C-GSK215083 displayed a negative correlation between BPND and age in the caudate (r=−0.41, p=0.03) (14% change per decade), and putamen (r=−0.30, p=0.04) (11% change per decade), but not in the ventral striatum and pallidum. Negative correlation with age was also seen in cortical regions (r=−0.41, p=0.03) (7% change per decade), consistent with the literature on 5-HT2A availability. DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first in vivo study in humans to examine the effect of age on 5-HT6 receptor availability. The study demonstrated a significant age-related decline in 5-HT6 availability (BPND) in the caudate and putamen.

OBJECTIVES/GOALS: Suicide is a growing public health problem with the rate of suicide increasing 33% since 1999. Physicians are not immune to this growing problem. Physicians represent a unique population that has been understudied with respect to suicide. The aim of the study is to investigate risk factors unique to physicians compared to the general population. METHODS/STUDY POPULATION: Using data from the National Violent Death Reporting System, a nationwide CDC database which aggregates information on violent deaths, we extracted demographic and circumstantial data on 172,135 suicide decedents ≥ 25 years old in participating states from 2003-2017. Of these, we found complete information regarding demographics, occupation, and circumstance for 160,159 suicide decedents. We separated suicide decedents by physician-status and compared 795 physicians to 159,364 non-physician decedents using chi-squared test. We then used multivariate logistic regression to examine differences in suicide method and circumstance by physician-status status, controlling for age, sex, and race. RESULTS/ANTICIPATED RESULTS: Compared to non-physicians, physicians were more likely to be male (84.5% vs 77.3%, p<0.001) and older (45.1% ≥65 vs. 17.8%, p<0.001). Controlling for demographics, physicians were less likely to complete suicide by firearm (aOR=0.60, 95%CI=0.51-0.71) but were more likely to suicide by overdose (aOR=1.41, 95%CI=1.13-1.77) or cutting (aOR=2.81, 95%CI=2.03-3.88). Physicians were more likely to have job related stressors (aOR=2.24, 95%Cl=1.83-2.74) and legal problems (aOR=2.34, 95%Cl=1.70-3.21). Physicians were also more likely to leave a suicide note (aOR=1.48, 95%Cl=1.26-1.73) but were less likely to be intoxicated on alcohol at time of death (aOR=0.76, 95%Cl=0.62-0.93). Physicians were no different than non-physicians in terms of financial or relational stressors. DISCUSSION/SIGNIFICANCE: Physicians are more likely to be male and older. Given their medical training, overdose and cutting may be more accessible and lethal methods for physicians. Physicians are more likely to leave a suicide note and less likely to be intoxicated, which may imply less impulsivity. Job stressors and legal problems may also contribute to physician suicide.

ABSTRACT IMPACT: Optimization of primary septal-hippocampal co-cultures facilitates studying central cholinergic synapse formation and dysfunction OBJECTIVES/GOALS: Septal cholinergic innervation to the hippocampus is critical for normal learning and memory and is severely degenerated in Alzheimer’s disease. To understand the molecular events underlying this loss, we optimized a primary septal-hippocampal co-culture system that facilitates the study of central cholinergic synapses. METHODS/STUDY POPULATION: We developed an optimized in vitro septal-hippocampal co-culture system modified from previously published protocols. Briefly, hippocampal and septal tissue were harvested from embryonic day 19 (E19) Sprague-Dawley rats, digested with 0.1% trypsin, and an equal number of cells from each region plated onto coverslips coated with poly-D-lysine and laminin at a final density of 300 cells/mm2. We use immunostaining with validated primary antibodies and a fluorescent binding assay, together with confocal microscopy, to determine the structure of cholinergic synapses that are 1) native, 2) mammalian, 3) CNS derived, 4) comprised of physiological synaptic partners, and 5) developmentally mature. RESULTS/ANTICIPATED RESULTS: After DIV21, co-cultures maintained a healthy morphology. A subpopulation of neurons strongly expressed the cholinergic markers vesicular ACh transporter (vAChT), choline acetyltransferase (ChAT), and the high-affinity choline transporter (ChT1), whereas most neurons lacked vAChT expression and were presumably glutamatergic or GABAergic. The percentage of cholinergic neurons attained in the co-culture is ˜5-7%. The size of these cholinergic neurons is strikingly similar to that reported for BFCNs in the intact brain (mean 30μm, range 18-43μm). All sampled cholinergic neurons (28/28 neurons) also expressed molecular machinery necessary for GABA release. Staining for a cholinergic postsynaptic marker shows that 63% of the contacts made with are synaptic. DISCUSSION/SIGNIFICANCE OF FINDINGS: Primary septal-hippocampal co-cultured neurons have not been exploited extensively in the field, perhaps due to the difficulty in maintaining such cultures for extended periods. Here, we optimized an in vitro septal-hippocampal co-culture system, a powerful tool to comprehensively analyze central cholinergic synapse formation and dysfunction.

OBJECTIVES/GOALS: Multiple induction agents can facilitate rapid sequence intubation (RSI) in management of refractory status epilepticus (rSE), many which have anti-seizure properties. We examine the anti-seizure efficacy and safety of induction agents used during RSI in the management of rSE. METHODS/STUDY POPULATION: We conducted a single-center retrospective review of patients admitted to the neuro-ICU intubated for management of rSE. Propofol, ketamine and benzodiazepines were considered anti-seizure medication (ASMs), etomidate was not. Patients were treated with propofol or midazolam following intubation. Our primary outcome was clinical or electrographic recurrence of SE within 12 hours of intubation. Exploratory outcomes included time to recover command following, duration of mechanical ventilation (MV) and complications related to intubation. We used multivariable logistical regression to evaluate outcomes between patients induced with ASMs and etomidate. A Fisher exact test was used to compare rSE cessation in a subset of patients with continuous electroencephalography (cEEG) at the time of intubation. RESULTS/ANTICIPATED RESULTS: We identified 149 induced for RSI in management of rSE: 88 patients intubated using ASMs (propofol,n=56; ketamine,n=14; benzodiazepines,n=18) and 61 patients intubated with etomidate. Forty-one patients had recurrence (29.9% ASMS, 24.6% etomidate). The induction agent was not associated with recurrence of SE, time to command following, or duration of MV. Twenty-seven patients had cEEG monitoring at the time of intubation. Sixteen of the 22 patients induced with ASMs had cessation of rSE with induction, while 1 of 5 intubated with etomidate had cessation (Fisher exact test, p=0.047). There were 34 patients with post-induction hypotension (22.9% ASMs, 22.9% etomidate (Fisher exact test, p=1)). DISCUSSION/SIGNIFICANCE: Induction with an anti-seizure medication during intubation was more likely to halt rSE, but did not decrease the likelihood of clinical or electrographic recurrence of rSE and may not affect time to recovery of command following or duration of MV.

OBJECTIVES/GOALS: Platform trials gain efficiency by sharing placebo controls among different study arms. However, the varying routes of administration make it unclear whether participants exposed to different placebos have similar outcomes. As such, we seek to compare outcomes between participants receiving tablet and inhaler placebos in the ACTIV-6 trial. METHODS/STUDY POPULATION: ACTIV-6 is a large, decentralized platform trial exploring repurposed drugs for the treatment of adults with mild to moderate COVID-19. Enrolled participants were randomly assigned to a study arm vs. placebo and then mailed the study drug. They were monitored until symptom resolution or Day 28. Here, we compare outcomes for control participants contributing to the fluticasone furoate study arm, in which 251 were assigned to a tablet placebo and 370 an inhaler placebo. Time to sustained recovery and time to resolution of individual symptoms are compared between groups using Kaplan-Meier curves and unadjusted log-rank tests. A step-down procedure is applied to control the false discovery rate. RESULTS/ANTICIPATED RESULTS: Control participants assigned to tablet placebos had shorter time to sustained recovery (adjusted hazard ratio (HR) 1.34 (95% CI 1.11, 1.62)). When examining each of the eleven individually reported symptoms on study Day 14, nasal symptoms (adjusted odds ratio (OR) 0.44 (0.27, 0.72), p<0.01), dyspnea (OR 0.44 (0.22, 0.87), p = 0.02), and cough (OR 0.54 (0.35, 0.83), p<0.01) were identified as symptoms in which the tablet-placebo group performed notably better than those who received inhaler-placebos. In the follow-up, longitudinal analysis, we anticipate similar results. DISCUSSION/SIGNIFICANCE: Among ACTIV-6 control participants, those receiving a tablet placebo had a significantly shorter time to sustained recovery than those receiving an inhaler placebo. Platform trials using shared controls should consider efficiency in the context of the additional variability when sharing controls with a different route of administration.

OBJECTIVES/SPECIFIC AIMS: Retinitis pigmentosa (RP) is a hereditary retinal degeneration disease that affects ~1 in 4000 individuals globally, and there are currently no effective treatment options available. In order to identify potential drug treatments, we optimized our existing a behavioral assay around a transgenic zebrafish carrying a truncated human rhodopsin transgene [Tg(rho:Hsa.RH1_Q344X)]. This line was also crossed with the Tg(-3.7rho:EGFP) reporter for rod visualization. The Q344X larvae experiences significant rod photoreceptor death by 7 days postfertilization (dpf) (Nakao et al., 2012). METHODS/STUDY POPULATION: To assess the vision of the Q344X zebrafish, the VMR assay was run under a dim-light condition based on recorded rod b-waves in larval fish (Moyano et al., 2013) and the minimum cone activation threshold in mice (Cachafeiro et al., 2010). Specifically, Q344X and control larvae at 7 dpf were placed into a 96-well plate and acclimated to a dim-light source (1.802e-05 μ W/cm2 at 500 nm) for 1 hour. The VMR was tracked and quantified during light offset. The total distance traveled was averaged and analyzed at 1 second poststimulus. Retinas were dissected from Q344X and control larvae and whole-mounted to validate the rod degeneration in the Q344X model. RESULTS/ANTICIPATED RESULTS: We found that the Q344X larvae displayed an attenuated VMR (0.121±0.041 cm) to the dim-light offset as compared with the control larvae (0.2751±0.038 cm) (two-sample t-test; p-value=4.619e-14, n=19). Analysis of whole-mounted retinae indicated significant rod degeneration at 7 dpf compared with controls (control: 87 rods/retina, Q344X: 9.3 rods/retina, Welch two-sample t-test, p-value=1.4e4). It is unlikely that the cones of the zebrafish contributed to this VMR since the light intensity of the assay was below the cone detection threshold of mice. As the only apparent difference between the 2 groups of larvae is significant rod degeneration, it can be concluded that the behavioral phenotype was a result of the degeneration. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that the attenuated Q344X VMR is a result of the rod photoreceptor death. This behavioral phenotype can be taken advantage of to develop a drug screening assay. Future steps will screen chemical libraries to identify compounds that ameliorate the rod degeneration. Compounds that prevent degeneration are expected to result in a significant increase in locomotion in response to the dim visual stimulus.

Navigating the research domain at an academic medical center can be challenging, even for seasoned investigators. To address this, Duke University launched two initiatives: (1) a research navigation “hotline” to provide brief assistance with a variety of research questions; and (2) researcher onboarding and consultation, a one-to-one tailored offering to ensure that researchers are equipped to navigate research resources and processes effectively. The services are provided by the myRESEARCHnavigators (MRN) team, funded by Duke’s CTSA. The diverse scientific backgrounds of the six team members align well with those of the research community, allowing for a good match between the researcher and MRN team member. The MRN team answers approximately 30 questions per month, and has provided consultations to almost 400 researchers. Both services receive high satisfaction ratings (4 or 5 stars [out of 5 stars] given to 90% of hotline answers, and 99% of researcher onboarding/consultation sessions). As of July 2019, the School of Medicine has determined that the consultations are critical to their mission and have made them a requirement for new research faculty. The team will continue marketing both services to encourage adoption.

Given the rapidly progressing coronavirus disease 2019 (COVID-19) pandemic, this report on a US cohort of 54 COVID-19 patients from Stanford Hospital and data regarding risk factors for severe disease obtained at initial clinical presentation is highly important and immediately clinically relevant. We identified low presenting oxygen saturation as predictive of severe disease outcomes, such as diagnosis of pneumonia, acute respiratory distress syndrome, and admission to the intensive care unit, and also replicated data from China suggesting an association between hypertension and disease severity. Clinicians will benefit by tools to rapidly risk stratify patients at presentation by likelihood of progression to severe disease.

When the emergency committee of the World Health Organization declared that the outbreak of COVID-19 meets the criteria of a “Public Health Emergency of International Concern” on January 30th, 2020, no one could ever imagine how soon it will spread globally, and a health crisis would turn to a social crisis that affects everything including higher education. However, during this uncertainty, Tehran University of Medical Sciences (TUMS) tried to respond quickly. In this study, we explain how a nerve center has helped TUMS respond to this crisis and ensure safety to keep key operations going, and set up a functional decision-making system for the future. We also share perspectives on the critical issues, the challenges ahead, and the opportunities emerging in the “new normal.”

OBJECTIVES/GOALS: Super refractory status epilepticus (SRSE) is associated with high mortality, often due to withdrawal of life sustaining therapy (WLST) based on perceived poor neurological prognosis. Factors influencing decision making are underreported and poorly understood. We surveyed clinicians who treat SRSE to identify factors that influence WLST. METHODS/STUDY POPULATION: Health care providers (HCP), including physicians, pharmacists, and advanced practice providers, who treat SRSE answered a 51-question survey on respondent demographics, institutional characteristics and SRSE management that was distributed though professional societies. Respondents described approaches to prognostication and rated the importance of clinical factors in the management of two hypothetical clinical cases followed by their prediction of recovery potential for the same two cases. Neurointensivists and other HCP responses were compared using descriptive statistics to differentiate group characteristics; a p-value <0.05 was considered significant. Logistical regression models were employed to identify associations between clinician specific factors and prognostication. RESULTS/ANTICIPATED RESULTS: One-hundred and sixty-four respondents were included in the analysis. Compared to other HCPs (neurologists, epileptologists, neurosurgeons, other intensivists; n=122, 74%), neurointensivists (n=42, 26%) [Odds ratio (OR) 0.3, 95% confidence interval (CI) 0.14-0.68), p=.004)] were less likely to use prognostic severity scores and were less likely to prognosticate likelihood of good functional recovery (OR: 0.28 (95% CI: 0.13-0.62), p=.002) compared to non-neurointensivist HCPs, controlling for potential confounders including professional degree, years of experience, country of practice, and annual volume of SRSE cases. There was, however, significant overlap in factors deemed necessary for determining futility in care escalation. DISCUSSION/SIGNIFICANCE: Neurointensivists value similar clinical factors to other HCPs when evaluating medical futility in SRSE but are less likely to predict definitive outcomes. Pending final survey results, future studies aimed at understanding why neurointensivists may be less likely to decisively prognosticate (i.e. avoiding nihilism) in SRSE may be warranted.

OBJECTIVES/SPECIFIC AIMS: Our objective is to understand the influence of the features comprising metabolic syndrome (central obesity, raised fasting plasma glucose, triglycerides, blood pressure, and decreased HDL cholesterol) on brain structure in men and women. With the understanding that MetS is a strong predictor of gray matter volume loss in specific brain regions, in this study we sought to quantify the influence of each of the metabolic syndrome biometric variables on the structures involved in the neural signature of metabolic syndrome. METHODS/STUDY POPULATION: We conducted multiple linear regression analyses on a cross-sectional sample of 800 individuals from the Genetics of Brian Structure (GOBS) image archive (352 men and 448 women). GOBS is an offshoot of the San Antonio Heart Study involving an extended pedigree of Mexican Americans from the greater San Antonio area. Its goal is to localize, identify, and characterize genes/quantitative trait loci associated with variations in brain structure and function (Winkler, 2010). The archive has continuously added participants from approximately 40 families since 2006. Neuroanatomic (T1-weighted MRI scans obtained on a Siemens 3T scanner and processed using FSL), neurocognitive, and biometric phenotypes have been obtained for each subject (including blood lipids). Linear regressions were run using SPSS and incorporated biometric and gray matter volume values obtained from 800 GOBS participants. RESULTS/ANTICIPATED RESULTS: Linear regressions incorporating metabolic syndrome variables as dependent variables and gray matter volume from regions involved in the neural signature of metabolic syndrome as predictors show significant predictive patterns that are largely similar between men and women, with some differences. Another linear regression conducted with gray matter volume from the neural signature of metabolic syndrome as the dependent variable and metabolic syndrome variables as predictors show that waist circumference and triglycerides are the greatest predictors of gray matter volume loss in men, and fasting plasma glucose and waist circumference are the greatest predictors of gray matter volume loss in women. DISCUSSION/SIGNIFICANCE OF IMPACT: Significant sex differences in the relationships between metabolic syndrome variables and gray matter volume changes between brain regions comprising the neural signature of metabolic syndrome were identified. waist circumference, fasting plasma glucose, and triglycerides are the most reliable predictors of gray matter volume loss. The variance in gray matter volume of the neural signature of metabolic syndrome in men is more significantly explained by waist circumference and triglycerides (when accounting for age) and in women is more significantly explained by waist circumference and fasting plasma glucose (when accounting for age). A model of metabolic syndrome that emphasizes a risk of neurodegeneration should focus on waist circumference for both men and women and weigh the remaining variables accordingly by sex (triglycerides in men and fasting plasma glucose in women).

Objectives/Goals: Our research goal is to translate medical guidelines for adolescent-centered contraceptive counseling into improved clinical practice. Here, we describe the process of co-designing a training program for adolescent-serving primary care clinicians with teen, caregiver, and clinician advisory boards. Methods/Study Population: We recruited teens, caregivers, and clinicians residing in North Carolina to participate in three virtual advisory boards separated by role. Eligible teen advisors were assigned female at birth and 15–19 years old; eligible clinicians provided care for teen patients; and all groups were purposively sampled to reflect diverse identities and experiences. At each advisor meeting, we used human-centered design techniques to elicit participant priorities, generate training content and engagement strategies, and obtain feedback on the final training program. We conducted a focus group at our final meetings and used rapid qualitative analysis to understand our advisors’ experiences participating in program co-development. Results/Anticipated Results: We partnered with 20 advisors with diverse identities across geographic location, race and ethnicity, sexuality, and experiences with disability. During 15 meetings from January to May 2024 (five with each advisor group), we developed a 3-hour virtual, synchronous training for adolescent-serving primary care providers to improve their contraceptive counseling skills. The curriculum includes five interactive modules and a resource toolkit. Advisors described motivations to participate (e.g., chance to share their perspective, desire to make change), positive experiences with the advisory boards (e.g., opportunities to learn, to connect with others), and opportunities for improvement (e.g., better technology orientation). Discussion/Significance of Impact: We describe developing a successful longitudinal partnership with three community advisory boards and co-creating a training program that incorporates community-led priorities and perspectives, including youth. This approach can be adapted for other clinician training programs seeking to center community voices.