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Abstract P3043: Circulating Omega-3 Polyunsaturated Fatty Acids and Early Type 2 Diabetes Risk Phenotypes: Longitudinal Analyses in the PROspective Metabolism and ISlet cell Evaluation (PROMISE) Cohort
Background: Literature on omega-3s and T2D risk has been heterogenous; however, most prior studies have used self-reported dietary intake or short-term supplementation regimens. Thus, further investigation is needed to assess longitudinal associations of circulating omega-3 with early T2D risk phenotypes. Objective: Assess longitudinal associations of circulating omega-3s with changes in insulin sensitivity (IS) and β-cell function (BCF) in the PROMISE cohort. Methods: Adults at-risk for T2D underwent four assessments over 9 years (n=472); blood samples were collected to determine insulin and glucose concentrations, and an OGTT was conducted. Baseline serum omega-3s (ALA, EPA, DPAn-3, DHA) were measured using gas chromatography-flame ionization detection. OGTT values were used to calculate validated IS (HOMA2-%S, ISI) and BCF (IGI/IR, ISSI-2) indices. Generalized estimating equations (GEE) analysis assessed the association between baseline omega-3s (mol%) with longitudinal change in IS and BCF indices after covariate adjustment. Results: Significant positive correlations were shown between EPA and DHA with IS measures (HOMA2-%S: EPA, r=0.18, DHA, r=0.23, all p<0.001; ISI: EPA, r=0.15, p<0.01, DHA, r=0.19, p<0.001) and between DHA and BCF indices (IGI/IR, r=0.14, p<0.01; ISSI-2, r=0.1, p<0.05). In adjusted GEE models, baseline EPA and DHA were positively associated with longitudinal change in IS (HOMA2-%S, p<0.001; ISI , p<0.01), and BCF (IGI/IR, p<0.05) ( Figure ) . Conclusions: Circulating omega-3s (specifically EPA and DHA) were positively associated with IS and BCF, which are important early T2D risk phenotypes. These findings add to growing evidence of the potential role omega-3s have in T2D primary prevention.
Abstract P1130: Patterns of Physical Activity from Midlife to Late Life: The Multi-Ethnic Study of Atherosclerosis (MESA)
Introduction: Physical activity (PA) is an important component of healthy aging, playing a key role in preserving mobility, preventing falls, and mitigating the risks of conditions like sarcopenia, osteoporosis, and cognitive impairment. Despite its importance, engagement in PA, particularly higher intensity exercise, tends to diminish as individuals age, yet there is limited understanding of the specific patterns and factors influencing this decline across diverse populations. The purpose of this study was to quantify patterns of PA change from midlife to older adulthood, by domain and intensity. Methods: Data are from 6,814 MESA participants (53% women, 39% White persons) who attended at least one exam. Participation in ten PA types or categories was measured by the MESA Typical Week PA Survey at each exam. To characterize the life-course, participant data from Exams 1-7 were grouped based on age categories (5-year age increments from <50 to ≥90 years). Participants reporting 0 min/week within the PA category determined non-participation in the respective category. Participation in PA categories was assessed for each intensity category (light, moderate, vigorous) for all activity categories, where appropriate. Findings are presented as heat maps. Results: Marked reductions in the endorsement of most PA types across increasing age groups was found, particularly in categories reflecting higher intensity sports and occupational activity categories (Figure). PA categories reflecting everyday lower intensity lifestyle activities, including television viewing, non-active commuting, and household chores, had a more stable endorsement over time. Walking, for both exercise and transportation, was common regardless of age. Conclusions: These findings present valuable insights into patterns of PA across an important life-course transition. Opportunities to further support the promotion of walking is needed to ensure adequate PA accumulation for health benefits in older adults.
Conformational free energy landscape of a glutamate transporter and microscopic details of its transport mechanism
Removing glutamate from the synaptic cleft is vital for proper function of the brain. Excitatory amino acid transporters mediate this process by uptaking the neurotransmitter from the synaptic cleft back to the cell after its release. The archaeal homolog, Glt Ph , an aspartate transporter from Pyrococcus horikoshii , presents the best structurally characterized model for this family of transporters. In order to transport, Glt Ph undergoes elevator-like conformational changes between inward-facing (IF) and outward-facing (OF) states. Here, we characterize, at an atomic level, the OF⇌IF transition of Glt Ph in different apo /bound states using a combination of ensemble-based enhanced sampling techniques, employing more than two thousand of coupled simulation replicas of membrane-embedded Glt Ph . The resulting free-energy profiles portray the transition of apo /bound states as a complex four-stage process, while sodium binding alone locks the structure in one of its states. Along the transition, the transport domain (TD) disengages from the scaffold domain (SD), allowing it to move as a piston sliding vertically with respect to the membrane during the elevator-like motion of TD. Lipid interactions with residues comprising the SD–TD interface directly influence the large-scale conformational changes and, consequently, the energetics of transport. Structural intermediates formed during the transition leak water molecules and may correlate to the uncoupled Cl − ion conductance observed experimentally in both prokaryotic and mammalian glutamate transporters. Mechanistic insights obtained from our study provide a structural framework for better development of therapeutic for neurological disorders.
Abstract P3173: Stroke Risk Associated with Atrial Fibrillation in the General Population: A Systematic Review and Bayesian Meta-Analysis
Objective: The contribution of atrial fibrillation (AF) to global stroke burden is not well described. This study synthesized available evidence using the Burden of Proof (BoP) methodology and a Meta-regression-Bayesian, Regularized, trimmed (MR-BRT) model, to provide a robust stroke risk estimate for the general population while accounting for multiple potential biases. Methods: We conducted a systematic review and Bayesian meta-analysis of population-based observational studies of AF and stroke, sourced from PubMed and EMBASE (1970-2024). To adequately capture potential global burden, all (paroxysmal, persistent/sustained, chronic and, unspecified) types of AF were considered as exposure and the study outcome was any types of incident (ischemic, hemorrhagic, or total) stroke. Relative risk (RR) assessments - hazard ratio, risk ratio, and odds ratio were extracted from published observational studies. Binary covariates were generated to identify potential systematic bias, including the representativeness, precision in exposure and outcome status determination, variations in definitions, and adjustment was made for confounders - age, sex, education, lifestyle factors, study design, and comorbidities. We used the MR-BRT model to estimate a conservative mean AF-stroke dichotomous risk function and the overall pooled mean RR, adjusting for study heterogeneity and publication bias. Results: Of 6,447 articles reviewed, 49 studies were included, with participants aged 18 to 99 and sample sizes ranging from 250 to 4.3 million. Individuals with AF had a 99% higher risk of stroke (RR 1.99, 95% uncertainty interval [UI]: 1.91, 2.08), with an increasing range of 92% to 108%, indicating a significant association despite study heterogeneity (γ). The most conservative estimate was 1.92 (95% UI: 1.90, 1.99). No publication bias was found based on the funnel plot analysis. Conclusion: This study quantifies the risk of all strokes in the general population due to any type of AF. Differences in age, comorbidities, and medication use (especially anticoagulants) across populations and the level of confounder adjustment may influence the observed risk. The BoP framework highlights the importance of synthesizing high-quality evidence to guide targeted interventions and health policy decisions aimed at reducing stroke globally. These findings support more aggressive AF management, particularly in lower-resource settings, as part of stroke prevention strategies to reduce stroke incidence.
Abstract P1022: Interatrial Septal Thickening as a Predictor of Atrial Fibrillation and Structural Heart Remodeling
Introduction: Lipomatous hypertrophy of the interatrial septum is characterized by adipose deposition in the interatrial septum (IAS). Although generally considered benign, its associations with arrhythmias and remodeling are not well understood and require further investigation. Understanding the role of IAS thickening in arrhythmogenesis and remodeling could improve detection and management. Hypothesis: We hypothesized that increased IAS thickness is associated with a higher prevalence of atrial fibrillation (AF), larger body surface area (BSA), interventricular septal thickness (IVS), coronary artery disease (CAD), and valvular disease. Methods: We conducted a retrospective analysis of 208 consecutive patients who underwent transesophageal echocardiography. IAS thickness was manually measured in the bicaval view by a trained physician at our academic center. IAS thickness was stratified into the groups <6 mm, 6-12 mm, and >12 mm. We analyzed variables including IVS thickness, valvular defects, electrocardiogram abnormalities, medications, and morbidities such as diabetes and hypertension. BMI and BSA were calculated. Chi-square and ANOVA were used to assess statistical significance (p < 0.05). Results: Among the 208 patients (mean age 60.5 years; 56% male), IAS thickening was significantly associated with increased BSA (p < 0.05), suggesting that body size and metabolic factors contribute to septal hypertrophy and structural heart changes. Patients with thicker IAS also had increased IVS thickness (p < 0.05), indicating that hypertrophic changes extend beyond the atrial septum to affect broader myocardial structures. IAS thickening was linked to CAD (p < 0.05) and mitral regurgitation (p < 0.05), suggesting that septal hypertrophy may serve as a marker for valvular pathology and atherosclerotic burden. AF was strongly correlated with increased IAS thickness (p < 0.05), reinforcing its link to electrical and structural heart remodeling. Conclusions: Increased IAS thickness may be associated with atrial arrhythmias, BSA, IVS thickness, CAD, and valvular dysfunction. Particularly in patients with cardiovascular risk factors, IAS thickening is linked to arrhythmias and structural heart changes. It may serve as a valuable marker for identifying at-risk patients and enabling earlier intervention to prevent adverse cardiac events. Larger studies are necessary to further explore these associations and deepen our understanding of IAS thickening’s clinical significance.
Fluidization and anomalous density fluctuations in 2D Voronoi cell tissues with pulsating activity
Cells not only can be motile by crawling but are also capable of nonmotility active motions like periodic contraction or pulsation. In this work, based on a Voronoi cell model, we show how this nonmotility activity affects the structure, dynamic, and density fluctuations of cellular monolayers. Our model shows that random cell pulsation fluidizes solid epithelial tissues into a hyperuniform fluid state, while pulsation synchronization inhibits the fluidity and causes a reverse solidification. Our results indicate this solidification is a Berezinskii–Kosterlitz–Thouless-type transition, characterized by strong density/dynamic heterogeneity arising from the annihilation of topological defects in the pulsating phase space. The magnitude and length scale of density heterogeneity diverge with the pulsating period, resulting in an opposite giant density fluctuation or anti-hyperuniformity. We propose a fluctuating hydrodynamic theory that can unify the two opposite anomalous fluctuation phenomena. Our findings can help to understand recent experimental observations in Madin-Darby canine kidney monolayers.
Abstract P2088: Impact Of Geographic Residence And Treatment Modality On Mortality Outcomes Among Adult Patients Diagnosed With Acute Myocardial Infarction
Background: In the United States, rural residents face unique challenges that affect their overall cardiovascular health and mortality including access to care for acute cardiovascular conditions. We assessed differences in mortality and mode of care among adult patients diagnosed with acute myocardial infarction (AMI) based on geographical residence. Methods: Using data from the Medicare Provider Analysis and Review files, we identified adult patients aged 45 and older who were diagnosed with AMI between 2015 and 2019. Cox-proportional hazards regression models were constructed to determine the association between patient’s geographic residence (rural vs. urban) on 30- and 90-day all-cause mortality. Results: A total of 868,955 adult patients diagnosed with AMI were included in this study. Twenty-six percent of the sample resided in rural areas. Among rural residents with AMI, 46% were managed invasively with either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery which was similar to 45% of urban residents. After controlling for age, race, sex, and comorbid conditions, rural residents had a higher risk of death compared to urban patients (aHR 1.04, p<0.001) at 30 and 90 days. In subgroup analyses, a similar pattern was observed among those who did not undergo invasive procedures (aHR 1.06, p<0.001), however, there was no differences in mortality at 30 days (aHR 0.99, p=0.30) and 90 days (aHR: 0.99, p=0.36) between rural and urban residents who were managed by PCI or CABG. Conclusion: Rural patients with AMI had a higher mortality risk than their urban counterparts, and this difference was driven by a higher death rate among those managed conservatively. Further investigation is needed to understand the underlying factors driving rural-urban disparities in mortality, particularly with non-invasive management of AMI.
Abstract P2006: Examining the Associations Between Resistance Exercise, Sleep, and Cardiometabolic Health in Young Black Women: Results from a 10-Week Randomized Controlled Trial
Introduction: Insufficient sleep, including short duration, poor efficiency, and high variability (night-to-night variation in sleep), is associated with increased cardiometabolic disease risk. Black adults are more likely to exhibit poor sleep in comparison to White adults, and Black women in particular are at high risk for poor cardiometabolic health. Effective strategies to attenuate these disparities are not well studied. Therefore, this study aimed to assess the impact of resistance exercise (RE) on sleep and cardiometabolic health in young Black women. Methods: 30 young Black women [25±4 yrs; body mass index (BMI)]: 30.3±9.5kg/m 2 ) completed a 10-week, twice weekly, supervised RE intervention. During pre and post-intervention visits we measured BMI, waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, triglycerides, and fasting blood glucose. We assessed objective sleep duration, efficiency, sleep timing standard deviation (SD), and midpoint using a Philips Actiwatch Spectrum PLUS watch. We measured self-reported sleep quality using the Pittsburgh Sleep Quality Index (PSQI). We assessed pre to post RE changes in variables of interest via t-tests (PSQI) or Wilcoxon Signed Rank tests (sleep duration, efficiency, timing SD, midpoint), and Spearman’s Rank Correlations to assess associations between baseline sleep metrics and cardiometabolic factors with α set to ≤ 0.05. Results: There were no differences in objective sleep measures from pre to post RE. In contrast, self-reported sleep quality improved after RE (PSQI global scores- pre: 5.5±2.1 vs. post: 4.6±1.6, p = 0.020). Regarding sleep and cardiometabolic health, higher sleep efficiency was associated with a lower BMI (r= -0.458, p = 0.013), WC (r= -0.445, p = 0.015), DBP (r= -0.489, p = 0.007), and glucose concentration (r= -0.433, p = 0.019). Higher sleep timing SD (i.e., bedtime) was correlated with higher fasting glucose concentration (r= 0.521, p = 0.013). Unexpectedly, increased sleep midpoint was associated with lower SBP (r= -0.615, p = 0.002) and DBP (r= -0.613, p = 0.002). Conclusion: Our data indicate that 10 weeks of RE improved self-reported, but not objective, sleep quality in young Black women. Pre-intervention sleep efficiency and variability were associated with select measures of cardiometabolic health. Future studies should promote strategies to increase consistent sleep habits to reduce the risks for cardiometabolic disease in Black women.
Structural basis of SARS-CoV-2 polymerase inhibition by nonnucleoside inhibitor HeE1-2Tyr
Targeting the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with small molecules is a promising therapeutic strategy against COVID-19, but potent and safe inhibitors are lacking. HeE1-2Tyr, a nonnucleoside inhibitor of Dengue virus RdRp, was also shown to inhibit SARS-CoV-2 RdRp in vitro and to have antiviral activity in cells, but the underlying mechanism remains unclear. Here, we elucidate the molecular mechanism of HeE1-2Tyr-mediated SARS-CoV-2 RdRp inhibition. Biochemical assays confirm that HeE1-2Tyr inhibits RdRp with an IC 50 of 5 µM and show that it competes with RNA binding to RdRp in vitro. Structural analysis using cryo-EM reveals that a stack of three HeE1-2Tyr molecules binds to the RNA binding site of RdRp. The identification of the conserved HeE1-2Tyr binding site and its intriguing inhibition mechanism of three stacked molecules that outcompete RNA may facilitate further development of pan-corona nonnucleoside inhibitors.
Abstract P3050: Diabetes Incidence Before and After the COVID-19 Pandemic Shelter-in-Place Mandate in Adults with Prediabetes
Background: We evaluated changes in type 2 diabetes (T2D) incidence associated with onset of the COVID-19 pandemic shelter-in-place (SIP) mandate; and if changes were greater among public (Medicaid) vs. commercially insured patients, and Asian, Black, and Hispanic vs. White patients, who have greater T2D risks. Methods: We examined electronic health records of 323,609 adults ages ≥18-89 years with BMI ≥25 (≥23 if Asian) and prediabetes (fasting glucose 100-125 mg/dL, or A1c 5.7-6.4%) from 1-1-2019 to 12-31-2021, at Kaiser Permanente Northern California. We defined T2D as having one inpatient discharge diagnosis or any of the following two within 24 months: A1c ≥6.5%, fasting glucose ≥126 mg/dl, random glucose ≥200 mg/dl, 2-hour 75-g oral glucose tolerance test ≥200 mg/dl, outpatient diagnosis code, and/or filled T2D medication. In a sub-analysis, we used only the first positive lab test in the T2D range. Using an interrupted time-series analysis, we evaluated whether an increase in T2D incidence was associated with the start of the pandemic SIP mandate (March 2020). The analysis was operationalized by fitting segmented linear regression models using generalized least squares, accounting for autocorrelation, and with monthly cases per 10,000 patients as the outcome. Results: In the 10 months before the pandemic SIP mandate, the average monthly T2D incidence was 12.2 cases (and 268 lab positivity cases) per 10,000 patients with stable trends. At the start of the SIP mandate, there was a nonsignificant steady increase in the monthly incidence of 0.8 (95% CI: -0.2,1.8) cases/month which persisted through 2021. There was also a steady and significant increase in the monthly lab positivity incidence rate of 8 (1, 16) cases/month, which persisted through 2021. In stratified analyses of lab positivity changes, the rate increase was similar across insurance types. However, compared to White patients, at the start of the SIP mandate, there was an immediate significantly greater increase in lab positivity of 104 (75, 133) cases/month for Hispanic patients, followed by an increase in monthly incidence that continued through 2021. There were no differences between Asian or Black and White patients. Conclusion: The COVID-19 pandemic and SIP mandate were associated with a steady increase in the T2D lab positivity rate among adults with prediabetes that persisted through 2021. The increase was larger among Hispanic compared to White patients, reflecting disparities.
Abstract P1050: Associations between Food Insecurity Trajectories in Youth and Overweight and Obesity Status in Young Adulthood
Background: Obesity is influenced by socioeconomic factors such as food insecurity (FI) over the life course. Little is known about longitudinal experiences of FI in childhood and adolescence and how these experiences relate to overweight and obesity status in adulthood. Objective: Our study aimed to investigate FI trajectories throughout youth and their associations with weight status in young adulthood. We hypothesized that trajectories indicating FI in childhood and adolescence would be associated with increased odds of being overweight and obese in young adulthood and that these associations would differ by extreme poverty status in adulthood. Methods: We used data from the Future of Families and Child Wellbeing Study, a longitudinal sample of children born in large U.S. cities between 1998-2002. We used group-based trajectory modeling to identify distinct FI trajectories from ages 3 to 15, based on survey questions approximating Hunger Vital Sign at ages 3, 5, 9, and 15. Overweight and obese status were defined using self-reported weight and height at age 22. Associations between FI trajectory and weight status were assessed using multivariate logistic regression, adjusting for relevant covariates. We stratified adjusted analyses by extreme poverty or not at age 22. Results: Of the total sample (n = 4,296), 12.2% identified as non-Hispanic White, 48.1% as female. Three distinct FI trajectories in youth were identified: 51.3% were food secure, 13.2% were food insecure, and 35.5% transitioned from food insecure-to-secure (Figure). Mean body mass index at age 22 was 27.6 (standard deviation 8.0). In adjusted analyses, young adults in the food insecure-to-secure group had higher odds of being overweight (OR 1.23, 95% CI [1.01-1.51]) compared to those in the food secure group. When stratified by poverty status, among young adults not in extreme poverty, those who were food insecure-to-secure had higher odds of being overweight (OR 1.34 95% CI [1.03-1.75]) and obese [OR 1.50, 95% CI [1.14-1.98]) compared to those who were food secure. These associations were not significant for those in extreme poverty. Conclusions: Young adults who transitioned from being food insecure to secure, particularly those not in extreme poverty, are vulnerable to having high weight status, highlighting the importance of supporting early childhood food security.
A horizontally transferred bacterial gene aids the freezing tolerance of Antarctic bdelloid rotifers
Bdelloid rotifers are well known for their abilities to survive long periods of freezing as well as acquire foreign genes. Recently sequenced genomes of some bdelloid rotifers in England were found to encode several proteins similar to ice-binding proteins (IBPs) that are usually associated with freeze–thaw tolerance. Here, I describe bdelloid rotifers inhabiting an algal patch in Antarctica that have multiple homologs of these genes. Structures of the proteins predicted by AlphaFold show that they are well designed for ice-binding and a recombinant protein made for one of them showed strong ice-binding activity. The existence of multiple copies of these proteins is another characteristic of IBPs. Furthermore, multiple bdelloid rotifers in the algal patch were revived in less than an hour after storage at −25 °C for 24 y, an apparent record for laboratory-controlled studies. Several characteristics of these genes point to bacteria as their source: sequence homology, absence of introns, and a structural peculiarity so far found only in bacteria. The remarkable freezing tolerance of bdelloid rotifers can thus be at least partially attributed to horizontally acquired bacterial genes encoding IBPs.
Abstract P3085: Influence of the 5-minute Rest Period on Home Blood Pressure Monitoring in Postpartum Women
Introduction: Home blood pressure (BP) monitoring is a practical approach for out-of-office measurement, allowing confirmation of elevated BP outside of the clinic setting. Patients are instructed to complete a 5-minute seated rest prior to home BP measurements for accuracy; however, compliance with this rest period and its impact on home BP readings remain unknown. Hypothesis: We hypothesize (1) participants would not consistently complete the 5-minute rest prior to home BP measurements, and (2) readings following the 5-minute rest would be significantly lower and have higher consistency within measurements compared to non-compliant readings. Methods: Participants were postpartum women (3 months after delivery; n = 40) enrolled in the multi-site Postpartum 24/7 pilot cohort study. Participants were instructed to assess BP twice on two occasions (morning and night) for 7 days using the Omron 5 series BP monitor, with 5 minutes of quiet, seated rest before the first measurement. A thigh-worn activPAL3 micro was concurrently used to assess compliance with the 5-minute rest. Given 1-minute epoch lengths from the BP monitor data, we defined compliance as readings with at least 4 minutes of continuous sitting from the activPAL3 before the BP reading. The compliance rate was the percentage of compliant measurements. The random and fixed effects of the 5-minute rest and intraclass correlation coefficients (ICC) of BP readings were calculated using a linear mixed model. Results: Participants (mean age: 30.6 ± 4.2 years; mean body mass index: 28.7 ± 6.6 kg/m 2 ) had 1,034 BP readings, with an average of 25.9 of 28 (92.5%) requested readings per person. Of these, 47.2% of BP readings were considered compliant with the 5-minute rest. Systolic BP was significantly lower by -2.83 mmHg (95% CI: -4.21, -1.47) in rest-compliant readings compared to non-compliant readings, though diastolic BP was similar. ICCs for rest-compliant systolic and diastolic BP readings were 0.708 and 0.690, respectively, suggesting moderate consistency; the corresponding ICCs for non-compliant readings were lower at 0.598 for systolic and 0.581 for diastolic BP. Conclusions: Participants were able to complete most home BP readings but with low compliance with the 5-minute rest period, which affected systolic BP values and overall BP consistency. Future research should assess rest compliance rates in more general populations and its impact on clinical decision-making and outcomes.
Abstract P1055: Anxiety, Stress, Emotional Difficulties and Behavioral Cardiovascular Health in Childhood: The Young Hearts Study
Background: Psychosocial factors in childhood, such as emotional and behavioral difficulties, contribute to long-term cardiovascular health (CVH). However, limited research has explored the relationship between these difficulties and childhood CVH. Methods: This cross-sectional analysis includes participants aged 2-18 (N = 6,892) from the Young Hearts cohort with complete behavioral CVH (bCVH) and Strengths and Difficulties Questionnaire (SDQ) data. SDQ scores included the Total Difficulties Score (TDS), measuring emotional and behavioral difficulties, and the Prosocial Behavior Score (PBS), reflecting empathy and cooperation. We calculated bCVH scores using the Life’s Essential 8 metrics (diet, exercise, nicotine exposure, sleep, and BMI). Linear regression was used to assess associations between TDS, PBS, and bCVH, adjusting for age, sex, race/ethnicity, parental education, financial stability, food security, and health insurance status. Results: The sample had a mean age of 8.7, 48% female, 46% non-Hispanic White, 28% Hispanic, and 15% non-Hispanic Black. Higher TDS was associated with lower bCVH (-1.91; 95% CI -2.27, -1.56), while higher PBS was linked to better bCVH (1.75; 95% CI 1.41, 2.1), and physical activity largely contributed to these differences (Figure 1). Conclusion: Psychosocial difficulties and prosocial behaviors have a strong association with physical activity, making it a potential intervention target for improving childhood CV outcomes. Enhancing prosocial behaviors through interventions like social-skills training may further support both psychosocial well-being and cardiovascular health in children.
MUC5AC filaments illuminate the structural diversification of respiratory and intestinal mucins
Secreted mucins are multimegadalton glycoprotein polymers that share the function of protecting mucosal tissues but diversified for activities in different organs of the body. Structural studies of secreted mucins are complicated by the enormous sizes, flexibility, and complex supramolecular assembly modes of these glycoproteins. The two major respiratory mucins are MUC5AC and MUC5B. Here, we present structures of a large amino-terminal segment of MUC5AC in the form of helical filaments. These filaments differ from filamentous and tubular structures observed previously for the intestinal mucin MUC2 and the partial mucin homolog VWF. Nevertheless, the MUC5AC helical filaments support the proposed mechanism, based on MUC2 and VWF, for how noncovalent interactions between mucin monomers guide disulfide crosslinking to form polymers. The high-resolution MUC5AC structures show how local and limited changes in amino acid sequence can profoundly affect higher-order assembly while preserving the overall folds and polymerization activity of mucin glycoproteins. Differences in supramolecular assembly are likely to be functionally significant considering the divergence of mechanical properties and physiological requirements between respiratory and intestinal mucins. Determining the high-resolution structures of respiratory mucins provides a foundation for understanding the mechanisms by which they clean and protect the lungs. Moreover, the MUC5AC structure enables visualization of the sites of human amino acid sequence variation and disease-associated mutations.
Abstract P3129: Epigenetic gestational age predicts subclinical atherosclerosis measures from childhood through adulthood
Objective: Atherosclerosis, an aging-related disease, may begin developing in childhood. Epigenetic age is known to predict biological aging accurately, and epigenetic gestational age can predict biological maturity at birth. However, the association of biological aging at birth with atherosclerosis in later life remains unknown. We aim to examine the association of epigenetic gestational age with subclinical measures of atherosclerosis at ages 11 to 24 and their changes over time. Methods: In the Southern California Children’s Health Study, DNA methylation from newborn bloodspots of 242 participants was analyzed using the Infinium 450K array. We calculated epigenetic gestational ages with the Knight and Bohlin algorithms. Intrinsic Epigenetic Gestational Age Deceleration (IEGAD), indicating developmental immaturity at birth, was derived by regressing epigenetic age on clinical gestational age, adjusted for cell composition. Subclinical measures of atherosclerosis, including carotid intima-media thickness (CIMT) and carotid distensibility, were obtained from ultrasound images from all participants in childhood (mean age: 11.3 years, SD: 0.6) in 2007, and repeatedly obtained from a subset of 54 participants again in adulthood (mean age: 24.2 years, SD: 1.6) between 2019 and 2022. Associations between each IEGAD and subclinical atherosclerosis measures, including their changes over time, were evaluated using linear regression, adjusting for sex, race, birthweight, age and body mass index at time of ultrasound, maternal age at delivery, and maternal pregnancy complications. Results: Knight IEGAD (mean: -0.05, SD = 1.1) and Bohlin IEGAD (mean: -0.03, SD=0.78) was moderately correlated (Pearson r = 0.67, P<0.001). Each week increase in Bohlin EEGAD was associated with higher adult CIMT (β = 34.9 µm, 95% CI: 1.63, 68.2) and with more CIMT thickening from childhood to adulthood (β = 2.2 µm/year, 95% CI: 0.05, 4.36). Similarly, each week increase in Knight IEGAD was associated with reduced arterial elasticity, as measured by lower carotid distensibility, in both childhood (β = -3.22, 95% CI: -0.78, -5.67) units (10 −6 ×m 2 /Newtons) and adulthood (β = -1.99, 95% CI: -0.36, 4.34), and an annual reduction of 0.40 (-0.14, 0.94) unit/year from childhood to adulthood. Conclusion: Developmental immaturity at birth, as indicated by epigenetic gestational age, is associated with adverse subclinical atherosclerosis markers from childhood to adulthood.
Abstract MP05: Consuming Pecans as a Snack Improves Lipids/Lipoproteins Compared to Usual Diet in Adults at Increased Risk for Cardiometabolic Diseases: A Randomized Controlled Trial
Background: Nut intake is associated with lower risk of cardiometabolic diseases through reductions in low density lipoprotein cholesterol (LDL-C) and triglycerides and improvements in measures of glycemic control. The cardiometabolic effects of pecan consumption have been less studied in comparison with other nuts. Objectives: The aim of this trial was to examine how substitution of usual snack foods with 57 g/day of pecans affects lipids and lipoproteins and measures of glycemic control compared to continuing usual dietary intake after 12-weeks in individuals at increased risk for cardiometabolic diseases. Methods: A 12-week single-blinded, parallel, randomized controlled trial was conducted. Adults with overweight or obesity and with ≥1 criterion for metabolic syndrome who were free from cardiovascular disease and type 2 diabetes were included. Participants were provided with 57 g/day of pecans and instructed to replace the snacks usually consumed with the provided pecans. The control group was instructed to continue consuming their usual intake. Lipids/lipoproteins and glycemic outcomes (i.e., fasting plasma glucose, hemoglobin A1C and insulin) were measured over two days approximately 24 hours apart at baseline and after 12 weeks. The between-group difference in the change from baseline for each outcome was evaluated by linear regression with adjustment for the baseline value, age, sex and body mass index. Results: In total, 138 participants (46 ± 13 years, 29.8 ± 3.7 kg/m 2 ; 59% female) were randomized. Both groups had 69 participants. Compared to the usual diet group, pecan intake reduced total cholesterol (-8.1 mg/dL; 95% CI -14.5, -1.7), LDL-C (-7.2 mg/dL; 95% CI -12.3, -2.1), non-HDL-C (-9.5 mg/dL; 95% CI -15.3, -3.7), and triglycerides (-16.4 mg/dL; 95% CI -30.0, -2.9) from baseline to 12 weeks. No between-group differences were observed for high-density lipoprotein cholesterol (HDL-C) or measures of glycemic control. Conclusions: Replacing usual snacks with 57 g/day of pecans for 12 weeks improved lipids and lipoproteins in adults at increased risk for cardiometabolic diseases.
The effect of salt additives on the glycine crystallization pathway revealed by studying one crystal nucleation at a time
Molecular-level understanding of the early stage of crystallization remains a significant challenge. For a wide range of fundamental research and applications, it is of great importance to understand the mechanism of crystal polymorph selections in different solvents or in the presence of additives. We studied glycine crystallization in aqueous solution with or without the addition of sodium chloride (NaCl), one crystal nucleation at a time, using the recently developed single-crystal nucleation spectroscopy (SCNS). It has been reported that glycine forms γ-glycine when salt is added to aqueous solution, and the mechanism has been considered as a classical nucleation where γ-glycine forms directly as a crystal nucleus. Our study shows that metastable polymorph β-glycine forms first in aqueous solution both with or without NaCl through a nonclassical nucleation pathway. NaCl can stabilize the metastable β-glycine over several hours and also prevent it from converting to α-glycine. Eventually γ-glycine nucleates on the surface of β-glycine and then grows while dissolving the mother β-glycine. The crystal habit of β-glycine suggests that the stabilization by NaCl occurs at its polar face. SCNS provides crucial information to accelerate the investigation of the early stage of crystallization toward the rational control of polymorphisms.
Abstract P3101: Predictive Modeling of Glycemic Variability and its Association with Metabolic Health: A Precision Nutrition Approach Using Korean National Data
The global burden of metabolic diseases, particularly diabetes and hyperglycemia, presents ongoing challenges for effective treatment and management. Conventional glycemic control strategies may not be suitable for healthy individuals and those with prediabetes. To enhance the personalized characterization of glycemic variability (GV), which reflects long-term glycemic trends rather than short-term responses to individual meals, this study developed a predictive model for Time in Range (TIR). This model enables monitoring of metabolic effects associated with lifestyle choices without the need for a continuous glucose monitoring system (CGMS). To estimate TIR, we applied a backward elimination linear regression model to optimize predictions based on lifestyle factors such as physical activity, sleep, stress, and dietary intake from 48 CGMS clinical study participants. The model showed a strong correlation between predicted TIR and actual metrics (R = 0.743, p < 0.001). Using data from 24,564 adults from the Korean National Health and Nutrition Examination Survey, we confirmed the association between predicted TIR values and metabolic health indicators. The results demonstrated a significant association between predicted TIR and reduced risk of metabolic diseases, particularly hypertension (Q1 vs. Q5: OR = 0.87; 95% CI = 0.79–0.95) and hypercholesterolemia (Q1 vs. Q5: OR = 0.82; 95% CI = 0.73–0.92). These findings may contribute to the development of precision nutrition-based healthcare for personalized prevention and management of metabolic diseases.
Abstract P1047: Pre- and Perinatal Determinants of Cardiovascular Health Trajectories Across Childhood and Adolescence
Introduction: The American Heart Association put forth the Life’s Essential 8 construct to assess cardiovascular health (CVH) status based on 8 health and behavioral factors. However, few studies have identified early-life determinants of CVH trajectories from childhood to adolescence, important life stages during which health behaviors and disease precursors are established. We sought to address this research gap in Project Viva, a prospective pre-birth cohort in Boston. Methods: We included 1,338 children with data on ≥3 CVH metrics in early childhood (median age 3.2y; range 2.8–6.2y) or ≥4 metrics in mid-childhood (7.7y; 6.6–10.9y), early adolescence (13.0y; 11.9–16.6y), or late adolescence (17.5y; 15.4–20.1y). We derived CVH score (range 0-100 points) at each life stage and used segmented mixed-effect models to estimate three CVH trajectory parameters: timing of inflection point when CVH score declines; slope before and after the inflection. Linear regression models evaluated associations of pre- and perinatal factors with each trajectory parameter, adjusting for maternal sociodemographic characteristics at enrollment. Results: The mean (SD) CVH score was 82.7 (8.4) in early childhood, 84.3 (8.2) in mid-childhood, 82.2 (9.7) in early adolescence, and 74.2 (11.4) in late adolescence. Estimated age of inflection when CVH score declined was 10.2y (0.7) for males and 10.0y (0.6) for females. Prepregnancy overweight or obesity (vs. healthy or under-weight), smoking during pregnancy (vs. never), and being weaned or formula-fed (vs. breastfeeding) in the first 6 months were each associated with persistently lower CVH from childhood to adolescence. Prepregnancy obesity (vs. healthy- or under-weight) was associated with later inflection (β 0.1y; 95% CI 0.0, 0.2) and slower subsequent CVH score decline (0.2 points/y; 0.1, 0.4). Gestational hypertension or preeclampsia (vs. normal blood pressure) was associated with faster CVH score gain before inflection (0.3 points/y; 0.1, 0.5), earlier timing of inflection (-0.1y; -0.2, 0.0), and faster CVH score decline (-0.3 points/y; -0.5, -0.1), while smoking during pregnancy (vs. never) was associated with later inflection (0.2y, 0.1, 0.3). Conclusions: This study provides insights into potentially modifiable pre- and perinatal factors of CVH trajectory across childhood and adolescence. Future work should examine whether early-life interventions addressing these factors would be effective in optimizing CVH in children.