Browse Articles
Discover research articles across all indexed journals
Abstract P3175: Navigating Stroke Recovery: The Association of Insurance Coverage on Hospital Discharge Disposition in Rural versus Urban Settings in North Carolina
Introduction/Hypothesis: Hospital discharge disposition of stroke patients is influenced by various factors, including health status, recovery needs, and healthcare resource availability. Health insurance coverage as a proxy for access to post-stroke care may reveal disparities in discharge outcomes. We examined the association between insurance status and discharge outcomes for stroke patients in rural and urban North Carolina, emphasizing the importance of stratifying by rurality to explore potential differences in access to care. Methods: We obtained demographics, county of residence, insurance, admission date, and discharge disposition of adult patients with principal discharge diagnosis codes for stroke (ICD-10-CM I60.xx-I63.xx) from an inpatient database of hospitalizations from January 2019 to September 2020 across 115 NC hospitals. We categorized patient insurance status as Private, Self-pay, Medicare, Medicaid, or Other. We dichotomized discharge disposition to Home or Healthcare Facility. Multivariable logistic regression estimated associations between insurance and discharge outcomes, adjusting for age, sex, stroke type, and rurality. Separate models for rural and urban populations explored differences in discharge patterns. Results: Among 31,935 patients with a mean age of 69, 38% lived in rural counties, 50% were female, and 60% were discharged home. Medicaid (OR=0.64, 95% CI: 0.58-0.70) and Medicare (OR=0.75, 95% CI: 0.71-0.80) patients had lower odds, and Self-pay (OR=2.07, 95% CI: 1.83-2.35) patients had higher odds of being discharged home compared to patients with private insurance. Discharge outcomes based on insurance status were consistent across rural and urban subgroups. Conclusions: Insurance status is significantly associated with discharge outcomes, with Medicaid and Medicare patients less likely and Self-Pay patients more likely to be discharged home compared to private insurance, regardless of rurality. Understanding discharge dynamics can inform policies to improve access and equity in post-stroke care. Further research should explore discharge disparities for vulnerable patient groups.
Broken time-reversal symmetry in visual motion detection
Our intuition suggests that when a movie is played in reverse, our perception of motion at each location in the reversed movie will be perfectly inverted compared to the original. This intuition is also reflected in classical theoretical and practical models of motion estimation, in which velocity flow fields invert when inputs are reversed in time. However, here we report that this symmetry of motion perception upon time reversal is broken in real visual systems. We designed a set of visual stimuli to investigate time reversal symmetry breaking in the fruit fly Drosophila ’s well-studied optomotor rotation behavior. We identified a suite of stimuli with a wide variety of properties that can uncover broken time reversal symmetry in fly behavioral responses. We then trained neural network models to predict the velocity of scenes with both natural and artificial contrast distributions. Training with naturalistic contrast distributions yielded models that broke time reversal symmetry, even when the training data themselves were time reversal symmetric. We show analytically and numerically that the breaking of time reversal symmetry in the model responses can arise from contrast asymmetry in the training data, but can also arise from other features of the contrast distribution. Furthermore, shallower neural network models can exhibit stronger symmetry breaking than deeper ones, suggesting that less flexible neural networks may be more prone to time reversal symmetry breaking. Overall, these results reveal a surprising feature of biological motion detectors and suggest that it could arise from constrained optimization in natural environments.
Abstract MP25: The association between egg consumption, total serum cholesterol concentration, and cardiovascular disease incidence among American Indians: The Strong Heart Family Study
Prior studies suggest associations between egg consumption, serum cholesterol levels, subclinical atherosclerosis and cardiovascular diseases (CVD). However, existing evidence remains controversial and limited. This study aimed to investigate the association between egg consumption, serum cholesterol profiles, subclinical atherosclerosis incidence, and CVD incidence among American Indians. The Strong Heart Family Study (SHFS) is a multicenter, family-based, prospective cohort study of CVD among American Indian communities. We evaluated SHFS participants at the baseline between 2001 and 2003 (n=2147). Carotid ultrasounds were used to detect plaque at baseline and follow-up examinations between 2006 and 2009, with a median follow-up of 5.3 years (Q1, Q3: 4.8, 6.4 years). We identified 422 incident CVD events through 2022, with a median follow-up of 20.2 years (Q1, Q3: 16.6, 21.1 years). General linear mixed models were used to evaluate the association between egg consumption and changes in serum total cholesterol, triglycerides, LDL-C, and HDL-C levels. The analysis revealed very weak associations, with respective regression coefficients of -0.06, 0.0004, -0.02, and -0.05, and corresponding P-values of 0.005, 0.68, 0.05, 0.01. These findings suggested that egg consumption had minimal impact on serum cholesterol levels. Shared frailty proportional hazards models were used to assess the association between egg consumption and subclinical atherosclerosis or CVD. We did not find a significant association between egg consumption and the development of carotid plaque. After adjusting for age, study site, hypertension, diabetes, and total caloric intake, the hazards ratios for incident CVD in the 2 nd , 3 rd , and 4 th quartiles of egg consumption were 0.77(95%CI: 0.56-1.05; P: 0.1), 0.74 (95%CI: 0.55-0.98; P: 0.04), and 1.12 (95%CI: 0.8-1.49; P: 0.42), compared to those in the 1 st quartile. Participants in the 3 rd quartile had a significantly lower risk of developing CVD. This study found weak associations between egg consumption and serum cholesterol levels in the SHFS. Moderate egg consumption was associated with a significantly lower risk of developing CVD compared to the lowest consumption in this population. This association was not observed in the group with the highest egg consumption. Moderate egg consumption appeared to be a way for low-income communities to obtain essential nutrients, particularly proteins, without burdening on the cardiovascular system.
Abstract 054: Prospective associations of pregnancy heavy metals and essential elements with women’s mid-life obesity risk: implications of folate supplementation as a possible intervention strategy to mitigate metal-related health effects
Background: Pregnancy is a critical period for women’s long-term cardiometabolic health, with women being particularly sensitive to environmental exposures. The effects of heavy metals and essential elements during pregnancy on long-term obesity risk are understudied. Cohort studies and trials suggest that folate may mitigate metal toxicity—a recent AHA Scientific Statement on metals identified this area of research as a critical gap and priority. Objective: 1) To investigate the associations of pregnancy levels of metals and elements with women’s mid-life obesity risk; and 2) to explore whether adequate pregnancy folate mitigates the obesogenic effects of metals. Methods: Project Viva is a pregnancy cohort enrolled in Eastern MA between 1999-2002 (median age: 32.9y). We measured (As, Ba, Cd, Cs, Hg, Pb) and elements (Cu, Mg, Mn, Se, Zn) in red blood cells and folate in plasma collected during the first trimester. At the Mid-Life visit (2017-2021; median age: 51.2y), we measured weight and height and defined obesity as BMI >30 kg/m 2 (reference: ≤30 kg/m 2 ). We examined associations of metals and elements with obesity using modified Poisson regression, adjusting for confounders ( Figure 1 footnote ). We used Bayesian kernel machine regression (BKMR) to assess the mixture effects of all metals, elements, and folate. Results: We followed 500 women (72% White, 11% Black) for a median of 18.1y (range: 17.5-20.8y). Cs and Cu were associated with a lower risk of obesity: per doubling, Cs and Cu were associated with 0.78 (95% CI: 0.63-0.97) and 0.71 (95% CI: 0.50-0.99) times the obesity risk, respectively. Mg, Se, and Zn were also associated with >10% lower obesity risk, though the 95% CIs crossed the null ( Figure 1 ). BKMR results confirmed consistent dose-response associations ( Figure 2 ). Although neither As nor folate was individually associated with obesity, they showed an interaction in association with obesity ( Figure 3 ): at lower folate levels, As was associated with a higher obesity risk, but as folate levels increased, the As-obesity association was attenuated and eventually became inverse. Conclusion: Optimal pregnancy levels of essential elements (e.g., Cu, Se, Mg, Zn) were associated with a lower risk of mid-life obesity, while adequate folate levels may counteract the obesogenic effects of As. Our study advances a research priority in the AHA Scientific Statement, suggesting folate as a potential intervention strategy to mitigate metal-related health effects.
Abstract P1021: Leadless Pacemakers: A Systematic Review on Superior Alternative for Cardiac Support in Post-Valvular Interventional Patients
Background: Around 10% of patients need a permanent pacemaker due to conduction issues in heart post-valvular interventions. The transvenous pacemaker has many complications compared to novel Leadless pacemaker(LPM) implantation. Objective: The main aim of this review is to compare the outcomes between conventional transvenous pacemakers and leadless pacemaker implantation after valvular intervention. Method: We conducted a comprehensive search of PubMed and ScienceDirect databases for relevant studies published between 2019 and 2024 using the keywords- pacemaker implantation and valvular intervention. Studies available in full text and in English language were included. After removing duplicates using the Rayyan tool, the remaining studies were screened and selected based on predefined inclusion criteria. Eligible studies included retrospective analyses of patients aged over 40 years, with indications for leadless pacemaker implantation such as atrial fibrillation, sick sinus syndrome, complete heart block, or complications following pacemaker implantation. Patients who had previously undergone implantations were excluded. We performed a qualitative synthesis of data to note the comparisons. Result: A total of 9 studies were included, comprising 10,776 patients, of whom 1121 underwent LPM implantation and 9655 received conventional transvenous pacemakers. Indications for LPM following valvular interventions included atrial fibrillation(n=24), complete heart block(n=20), bradycardia(n=26), high-degree atrioventricular (AV) block(n=30), and left bundle branch block(n=9). For conventional transvenous pacemakers, complete heart block(n=24) and high-degree AV block(n=7) were the primary indications. Compared to LPM, patients with conventional pacemakers reported more complications like pocket formation, pericardial effusion, pneumothorax, and infections, along with increased hospital stay duration. A few patients with LPM suffered from device-related complications like device dislodgement and device thrombus formation. Conclusion: The above findings suggest that while both the devices showed some device related risks, LPMs presented with fewer overall adverse outcomes, and thus, may be a safer alternative than conventional pacemakers. There is insufficient data on the use of LPM after valvular interventions. Further studies are required to fully assess the risks and benefits of LPM and their usage in patients of conduction abnormalities after valvular interventions.
Cryo-EM meets crystallography: A model-independent view of the heteronuclear Mn <sub>4</sub> Ca cluster structure of photosystem II
Photosynthesis converts solar energy to chemical energy by splitting water molecules and carbon dioxide to produce oxygen and carbohydrates with an efficiency that engineers working on solar energy device can only dream of. Photosystem II (PSII) is the enzyme that catalyzes the light-driven oxidation of water that occurs during photosynthesis. This oxygen-producing reaction occurs in the Mn 4 Ca cluster found inside the enzyme’s oxygen-evolving center (OEC). Even though the structure and mechanism of action of the OEC have been intensively investigated for many decades, questions still remain about both. The Mn 4 Ca cluster stores the high-energy oxidizing equivalents required for water oxidation so that its own oxidation state depends on its chemical composition, i.e., the number of its oxygen ligands. The issue addressed here is the number of oxygen ligands associated with the Mn 4 Ca cluster after PSII has been exposed to two of the four flashes of light necessary for it to produce an oxygen molecule, PSII 2F. Comparisons of recently published cryo-EM maps and crystallographic OEC-omit maps described here reveal the OEC structure of PSII 2F contains only five internal oxygen ligands, and that the sixth O ligand identified earlier in PSII 2F crystal structures is an artifact caused by model bias. This finding should have a significant impact on our understanding of the mechanism of water oxidation that is catalyzed by PSII because it is incompatible with prevailing high valence paradigm (HVP) models for this process.
Abstract P3030: Associations of Co-Existing Hypertension and Diabetes with Mortality Risk in US Adults: A Prospective Analysis of the 1999-2018 National Health and Nutrition Examination Surveys
Introduction: Hypertension (HTN) and type 2 diabetes (T2D) prevalence is on the rise resulting in an increasing number of US adults living with multiple cardiometabolic morbidities. The association of co-existing HTN and T2D with mortality risk has not been quantified. Hypothesis: Co-existing HTN and T2D are associated with higher all-cause and cardiovascular mortality risk compared to having either condition alone or neither condition, and associations vary by sex, race and ethnicity. Methods: Participants were 48,727 adults from the 1999-2018 National Health and Nutrition Examination Surveys (NHANES). Blood pressure and glycemic indicators were used to categorize participants into 4 groups: 1) neither condition, 2) HTN only, 3) T2D only, 4) co-existing HTN and T2D. Mortality was ascertained using the National Death Index. Kaplan-Meier curves and multivariable Cox proportional hazards models evaluated associations with mortality. Results: Overall, 50.1% of participants had neither condition, 38.4% had hypertension alone, 2.8% had T2D alone, and 8.7% had both. During a median follow up of 9.2y, there were 7,734 total deaths, of which 2,013 were CVD deaths. Compared to having neither condition, co-existing HTN and T2D were associated with >2-fold and ~3-fold higher all-cause and CVD mortality risk (HR(95%CI): 2.46 (2.45, 2.47) and 2.97 (2.94, 3.00), respectively). Compared to having T2D or HTN only, co-existing T2D and HTN status was associated with up to 82% and 93% higher all-cause and CVD mortality risk. In stratified analyses, associations were stronger in females vs. males (p-interaction<0.01), and differential associations were observed by race and ethnicity (p-interaction<0.01) (Figure). Conclusions: The co-existence of HTN and T2D substantially increases all-cause and CVD mortality risk. Findings underscore the critical need for multilevel contextual interventions that address multiple cardiometabolic morbidities to extend lifespan and address chronic disease inequities in the US population.
Abstract P1084: Association of Body Composition and Incident Heart Failure and Heart Failure with Preserved Ejection Fraction and Heart Failure with Reduced Ejection Fraction in postmenopausal women
Background: As the US population ages, Heart Failure (HF) is reaching epidemic proportions, with heart failure with preserved ejection fraction (HFpEF) placing a particular burden on elderly women. While the association of obesity with the risk of heart failure is well established, the role of visceral adiposity and other measures of body composition have had limited research. Methods: A cohort of 10,527 postmenopausal women, mean age 63.3 (7.4) at baseline had DXA measures of VAT area ( cm 2 ), SAT area (cm 2 ), VAT/SAT ratio, Fat mass(kg), Lean mass (kg), % body fat and BMI (kg/m 2 ) and were followed for 16.7 years with 852 cases of incident HF . A sub-cohort of 3528 women were followed for the same period were evaluated for adjudicated HFpEF and HFrEF with 116 cases of HFpEF and 107 cases of HFrEF. We evaluate the association of the above body composition variables using multiple variable cox proportional hazards models (see tables below) .We also evaluated a comprehensive model including all sociodemographic and lifestyle variables as well as potential confounders/mediators of medical co-morbidities. Results: Both quartile and continuous measures of VAT, SAT, VAT/SAT ratio, Fat mass, lean mass, and BMI were associated with increased risk of HF and HFpEF with stronger associations with HFpEF but not HFrEF in our main model. The comprehensive model including potential mediators showed persistent but diminished associations for VAT, VAT/SAT ratio, Fat mass, Lean mass, and BMI but not SAT or %body fat. Time varying measures of VAT, VAT/SAT ratio showed persistent and stronger associations than baseline measures for HF and HFpEF but not HFrEF. Competing risk models for death and HF subtype when evaluating HFpEF or HFrEF showed similar but slightly attenuated results. Conclusion: Visceral Fat and VAT/SAT ratio, Fat mass, and Lean mass are associated with increased risk of HF and HFpEF but not HFrEF in this cohort of elderly women. Whether new treatments for weight loss that reduce visceral fat will reduce the risk of HF and HFpEF is worthy of future research.
Abstract P2028: Air Pollution Induces Atrial Fibrosis via CARD9-Mediated Immune Response
Background: Exposure to ambient fine particulate matter (PM) triggers systemic inflammation and is associated with atrial fibrosis (AF) and cardiac arrhythmia. The cytosolic adaptor caspase recruitment domain 9 (CARD9) is crucial for macrophage function and innate immune response. This study aimed to investigate the role of CARD9-dependent immune response in PM-induced macrophage-mediated inflammation and the detrimental effects of PM on the heart atrium, exploring the underlying mechanisms. Methods: Male C57BL/6 wild type (WT) mice (4-6 months old, n=8-12) and age- and sex-matched CARD9 knockout (CARD9 -/- ) mice (n=8-12) were intranasally exposed to PM for 1, 2, 7, 14, and 28 days. Serum levels of TNF-α, IL-1β, IL-6, and IL-10 were measured using ELISA. Total macrophage populations and M1/M2 subpopulations in bone marrow (BM) and blood were analyzed in mice with and without PM exposure. BM macrophages were cultured for 48 hours in M0, M1, or M2 medium to analyze their populations and cytokine production with or without PM exposure. Phosphorylated Akt (p-Akt), p-Erk, and Ankyrin-B levels were determined in atrial cardiomyocytes using immunoblotting. AF area was measured with Masson’s trichrome staining. Results: PM exposure significantly elevated serum levels of TNF-α, IL-1β, and IL-6 in WT mice within 24 hours, but not in CARD9-/- mice （Fig. 1). In CARD9-/- mice, PM exposure increased the M2 macrophage population and IL-10 levels compared to WT mice (Fig. 2), with similar findings observed in vitro using BM cells cultured in M0, M1, and M2 media. PM-induced AF was linked to reduced atrial p-Akt and Ankyrin-B levels, effects that were mitigated in CARD9-/- mice compared to WT mice (Fig.3). Conclusion: PM exposure-induced AF may be linked to an enhanced macrophage inflammatory response through CARD9-mediated reduction in IL-10 secretion, resulting in a decreased M2 macrophage polarization from M0 macrophage. This study outlines the underlying mechanism of air pollution-induced atrial arrhythmia and explores potential prevention strategies and treatments.
Abstract P3077: Pro-Enkephalin A and Risk of Incident Hypertension: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Introduction: Hypertension, a risk factor for cardiovascular disease and chronic kidney disease, poses a significant burden in the U.S, especially among Black U.S. adults. Higher pro-enkephalin A (PENK-A), a byproduct of endogenous opioid peptide processing and a novel marker for estimation of glomerular filtration rate, is associated with antihypertensive use and greater risk of stroke, heart failure, and renal dysfunction. Whether low PENK-A is a risk factor for incident hypertension is unknown. Hypotheses: We hypothesized that lower PENK-A will be associated with greater risk of incident hypertension. Methods: REGARDS cohort study enrolled 30,239 Black and White U.S adults aged ≥45 years, with an initial visit between 2003-2007 and a follow-up visit in 2013-2016. A race-sex stratified sample of 4,400 participants were randomly selected. Hypertension was defined with a blood pressure (BP) threshold of 140/90 mm Hg or use of antihypertensive medications. We excluded those with prevalent hypertension, missing model covariates, or missing PENK-A, resulting in an analytical population of 1,859 participants. Proportion of incident hypertension events were calculated by tertile of PENK-A. Modified Poisson regression estimated unadjusted and adjusted risk ratios (RR) of incident hypertension per 1-SD higher of log-transformed PENK-A. Results: Among 1,859 participants (mean [SD] age 62 [8] years, 51% female, and 36% Black race), median (IQR) follow up was 9.5 (8.7 to 10.0) years. Median (IQR) PENK-A was 59.7 (49.6-72.4) pmol/L. Hypertension developed in 35.4% of participants overall, (37.7% of tertile 1, 34.9% of tertile 2, and 33.7% of tertile 3 of PENK-A). However, there was no difference in RR of incident hypertension per 1-SD higher of log PENK-A in unadjusted (RR 0.96; 95% CI 0.90-1.02) or fully-adjusted models (RR 1.01; 95% CI 0.94-1.08). Restricted cubic splines depict no difference in RR of incident hypertension across the means of PENK-A levels relative to the median value ( Figure ). Conclusions: PENK-A was not associated with greater risk of incident hypertension in a contemporary cohort study. PENK-A does not appear to influence risk for stroke and heart failure through hypertension, but whether PENK-A modifies cardiovascular disease risk among persons with hypertension is unclear given its bidirectional role in the cardiorenal pathway.
Abstract P1120: Association Between Depression and Movement Behaviors with Risk of Mortality among people with Arthritis: The National Health and Nutrition Examination Survey (NHANES) 2007-2016
Arthritis is a chronic inflammatory disease characterized by joint pain, swelling and limited range of motion. Depression is prevalent among individuals with arthritis and is associated with increased risks of health conditions and mortality. P hysical activity (PA) is a strong predictor of lower mortality and can serve as a protective factor against both depression and arthritis. This study aimed to examine the associations between depression, moderate to vigorous PA (MVPA) and sedentary behavior (SB) with all-cause mortality among individuals with arthritis. Methods: We included 5129 participant aged ≥ 40 years from NHANES 2007-2016. The death records through 2019 were ascertained. Depression was assessed using Patient Health Questionnaire (PHQ9) and categorized into depressed and not depressed groups. MVPA and SB were measured using the Global Physical Activity Questionnaire (GPAQ). Individuals with no leisure time MVPA were classified as inactive and those with ≥ 8 hours of daily sitting were considered sedentary. To investigate joint associations, participants were grouped based on depression status and MVPA or sedentary status. Weighted multivariate Cox regression models adjusted for age (Model 1) and additional covariates (Model 2) were used to examine the associations of depression, MVPA and SB with mortality (Table). Results: Over 8 ± 3 years of follow-up,1247 (24%) participants died. Compared to active group without depression, inactive groups with and without depression had 1.98 (95% CI: 1.56-2.47) and 1.52 (95% CI: 1.25-1.84) times risk of mortality, respectively (Table). Compared to the non-sedentary group without depression, sedentary groups with and without depression had 1.92 (95% CI: 1.62-2.28) and 1.40 (95% CI: 1.16-1.70) times risk of mortality (Table). Conclusion: Depression, MVPA and SB, were independently and jointly associated with all-cause mortality among people with arthritis. Being more active and less sedentary may help lower the risk of mortality in this population.
Abstract P2107: Sex-Specific Associations of Plasma Proteins with HF Risk: The Atherosclerosis in Communities (ARIC) Study
Introduction: Heart failure (HF) epidemiology and pathophysiology differ by sex. Large scale plasma proteomics offers promise to provide insight into biologic mechanisms underlying sex-based differences, but limited data is available. Hypothesis: A subset of circulating proteins will differentially associate with incident HF in women compared to men. Methods: We examined 10983 participants in the community-based ARIC cohort study who attended study Visit 2 (1990-92), were free of HF, and had aptamer-based proteomic measurements (SomaLogic; 4955 aptamers corresponding to 4715 unique proteins). We used multivariable Cox regression to test the association of plasma proteins with HF. Models were adjusted for age, BMI, eGFR, Black race, smoking status, visit center, CHD, diabetes, and hypertension, and included sex interaction terms with protein measurement and all other model covariates except visit center. For proteins with a significant sex*protein interaction after FDR correction for multiple testing (FDR corrected p<0.05), we fit stratified models for men and women and fit interaction models to test for differential associations of protein measures with HF risk factors by sex. Results: Among 4935 men (mean age 57±6 years, 20% Black race) and 6048 women (57±6 years, 25% Black race), 369 and 298 incident HF events occurred over 10-year follow-up respectively. Effect modification of sex on the association of protein level with incident HF was observed for 9 proteins, all of which were significantly associated with HF in women, while 3 showed directionally opposite associations with HF in men in stratified models (Figure). In addition to known sex hormones (CGA/LHB), the proteins reflected processes related to inflammation, including immune regulation (RPS19) and TGF-beta signaling (SMAD3, WWP1); purine and cellular energy metabolism (ADSL, PPP1R2); and wound healing (MCF2L). ADSL was also more strongly associated with BMI among women than men. ADSL is expressed in adipose, cardiac, and skeletal muscle tissues, and has shared pQTLs with eQTLs in these tissues. Conclusions: High throughput proteomics identifies circulating proteins differentially related to HF risk in women versus men. These findings highlight potential differential roles for specific inflammatory pathways and alterations in cellular metabolism to HF development in women. Further studies of ADSL as potentially linking obesity, metabolic dysfunction, and HF in women are warranted.
Abstract P3170: Identifying moderate to severe food insecurity among hypertensive patients in a low and middle-income Caribbean country
Introduction: The Caribbean is experiencing a high burden from food insecurity (FI) and cardiovascular disorders including hypertension. Hypertensive patients with FI need to be easily identified to address social and dietary factors that may worsen blood pressure control and result in adverse health outcomes. In this study we evaluated the ability of single questions from the Latin American and Caribbean Food Security Scale (ELCSA) to identify patients with moderate to severe FI. Hypothesis: We hypothesized that a single question from the ELCSA could be used to screen for moderate to severe FI in adults during a routine clinical encounter Methods: The Addressing Blood Pressure Control using Dietary Approaches (ABCD) study was a cross-sectional study of hypertensive outpatients from a semi-private hospital referral specialist clinic and a government-run primary care facility in Jamaica. The ELCSA scale (excluding questions about children/adolescents) was administered by trained interviewers to all participants. Those with a score of 0 were categorized as food secure, 1-3 mild FI, and ≥ 4 as moderate to severe FI. We calculated the sensitivity, specificity, and positive predictive value of each ELCSA question to evaluate its ability to identify patients with moderate to severe FI. Results: Of the 257 patients interviewed (28% male, 50% over 65 years), 35% had moderate to severe FI. The three questions that best identified these patients were asking whether (i) they or any adult in the home ate less food than what was needed because there was not enough food (sensitivity 79%, specificity 88%), (ii) if the home ran out of food at any time (sensitivity 80%, specificity 87%), and (iii) if they were worried about running out of food (sensitivity 75%, specificity – 88%). All three questions had a positive predictive value over 78%. Conclusion: The inclusion of a single item on food availability during clinical encounters could identify most patients with moderate to severe FI and provides a practical approach to FI screening for Jamaican clinicians. Caribbean clinicians should be encouraged to screen for FI to address this important social determinant of health.
Abstract P2032: Associations of Volatile Organic Compound Metabolites with Urinary Catecholamines: A Cross-Sectional Study with Green Heart Louisville
Volatile organic compounds (VOCs) are ubiquitous gaseous chemicals present in indoor and outdoor air. These compounds are emitted from several sources such as automobiles, paints, and household items. Human exposures are frequent and expected to increase with climate change. VOC exposures have been linked to negative cardiometabolic effects; however, the underlying mechanisms by which they impact cardiovascular function remain unknown. Exposure to VOCs may stimulate sympathetic nervous system activity. Thus, we aim to investigate the association of urinary VOC metabolites with levels of catecholamines as a biomarker of sympathetic activation. Participants (n=806, age 25-70) were recruited between 2018-2021 from low- to middle-income neighborhoods in Louisville, KY. Clean catch, spot urine samples were obtained during an in-person study visit. Urinary samples were used to quantify metabolites of VOCs and catecholamines using UPLC-MS/MS. The associations of log-transformed, creatinine standardized urinary constituents were examined using adjusted multivariable linear regression models for individual metabolites and quantile-based g computation for overall mixture models. Final models were adjusted for relevant demographic factors, stress, smoking status, medication use, and urine collection time. Detectable levels of acrylamide, acrolein, 1,3-butadiene, crotonaldehyde, N, N-dimethylformamide, propylene oxide, styrene, toluene, and xylene metabolites were present in >80% of urinary samples. In adjusted models, higher concentrations of most VOC metabolites, other than BMA (a metabolite of toluene), were associated with higher levels of urinary catecholamines (p<0.001). Specifically, a 10% increase in 11 individual VOC metabolites was associated with 1.2% to 2.4% higher epinephrine, 0.7% to 1.4% higher norepinephrine, and 0.7% to 1.5% higher dopamine levels. A quartile increase in the overall VOC metabolite mixture was associated with 57% higher epinephrine (95%CI = 41, 76%; p<0.001), 37% higher norepinephrine (95%CI=28, 48%; p<0.001), and 40% dopamine levels (95%CI=31, 48%; p<0.001). Our results suggest that exposure to these ubiquitous volatile compounds is associated with an increase in sympathetic stimulation. Mixture analysis further demonstrated potential additive effects of VOC exposures on autonomic modulation. Hence, an elevated sympathetic tone may in part be responsible for the negative cardiometabolic outcomes related to increased VOC exposure.
Abstract 019: Association Of Sleep Irregularity And Variability With Leptin And Adiponectin Levels In Adolescents
Introduction: Hormone fluctuations and circadian rhythms, including the sleep-wake cycle, are reciprocally associated. Lipid and glucose metabolism pace depend on leptin and adiponectin levels. Alignment of the sleep-wake cycle is associated with optimal sleep duration and metabolic regulation. Therefore, deviations in sleep timing and duration resulting from circadian misalignment, which is highly prevalent in adolescents, are potentially impacting this association. Hypothesis: Objective metrics of sleep timing and duration are associated with adiponectin and leptin levels in adolescents. Methods: We assessed 344 adolescents from the Penn State Child Cohort [16.2 (2.2) years; 44.4% female; 21.5% racial/ethnic minority], of whom 215 were evaluated while in school and 129 while on break. All subjects had a minimum of 3-nights of at-home actigraphy and 9-hour in-lab polysomnography. Sleep midpoint (SM) was calculated as the central point of the sleep period, while sleep irregularity (SI) and sleep variability (SV) as the intra-individual standard deviation of the SM and total sleep time, respectively. Adiponectin and leptin levels were assayed via ELISA from blood samples. Linear regression models adjusted for sex, race/ethnicity, age, apnea/hypopnea index, BMI percentile, and SES. Results: Greater SI and SV while attending school were associated with lower log-adiponectin levels (B=-0.155, SD=0.057, p=0.007 and B=-0.127, SD=0.054, p=0.021, respectively). SM was not significantly associated with either log-leptin or log-adiponectin levels. Conclusions: Increased irregularity and variability in the timing and duration of sleep during the academic year affect glucose and fatty acid control mechanisms in adolescents. Our findings further support targeting sleep from a multidimensional standpoint to better prevent its impact on cardiometabolic health. Support: National Institutes of Health (R01HL136587, UL1TR000127)
Allosteric inhibition of the IZUMO1–JUNO fertilization complex by the naturally occurring antisperm antibody OBF13
Sperm IZUMO1 binds to egg JUNO, and this interaction is essential for mammalian fertilization. Isolated from a female mouse immunized with syngeneic sperm, the antisperm antibody OBF13 recognizes IZUMO1 and inhibits murine fertilization. How OBF13 interferes with sperm–egg interactions was unknown. Here, we present the X-ray crystal structure of IZUMO1 in complex with OBF13. OBF13 binds to the apex of the four-helix domain of IZUMO1, distant from the JUNO-binding site. Our crystal structure of OBF13-bound IZUMO1 resembles apo-IZUMO1 and differs from the structure of IZUMO1 in complex with JUNO. We identify that OBF13 carries a low level of somatic hypermutation, and through deep mutational scanning, we engineer an affinity-enhanced OBF13 variant. This OBF13 variant single-chain fragment variable decreases the apparent affinity of IZUMO1 for membrane-bound murine JUNO and blocks the binding of acrosome-reacted sperm to eggs, thereby preventing fertilization. We propose allostery between the OBF13 epitope and the JUNO-binding site. OBF13 inhibits a conformational change in IZUMO1, preventing fusion-competent sperm from adhering to murine eggs during fertilization. Surprisingly, murine IZUMO1 binds to hamster JUNO with an affinity ~20-fold higher than to murine JUNO. The decreased affinity caused by OBF13 of murine IZUMO1 for hamster JUNO is sufficient for murine sperm to bind to and fuse with hamster eggs. Our studies provide a structural and mechanistic framework for species-specific, allosteric inhibition of IZUMO1 by a naturally occurring antisperm antibody and offer insights into the development of immunocontraceptives.
Abstract 015: Sleep Health and Cardiometabolic Risk in Health Care Workers: The role of heart rate and heart rate variability
Purpose: Despite strong evidence linking poor sleep with cardiometabolic risk, underlying mechanisms are poorly understood, limiting interventions to improve sleep&cardiometabolic health. Higher heart rate (HR) and lower HR variability (HRV) are associated with worse cardiometabolic health and may be affected by sleep. We determined associations between multidimensional sleep health, HR, and HRV among healthcare workers (HCW) from federally qualified health centers (FQHCs) in Louisiana. Methods: Eighty HCW wore wrist-worn sensors capturing sleep onset, wake, HR, and HRV for 6 weeks. Four dimensions of sleep health were measured: regularity was assessed as the standard deviation (SD) of midpoints of all nighttime sleep periods for a participant; “irregular”=SD >60 minutes. Timing was assessed using participants’ mean sleep midpoint; “poor timing”=midpoint not between 1am&3am. Efficiency was calculated as % of time in bed spent asleep; “inefficient”=mean efficiency across nights <85%. Duration was calculated as time between first sleep onset after 8pm&last wake, minus time spent awake during the night; “insufficient”=mean duration <7 hours. Dichotomized regularity, timing, efficiency&duration were summed; multidimensional “poor sleep”=score ≥2. HR (beats/minute) and HRV (root mean square of successive differences between beats) were measured every 5 minutes. Multivariable linear regression estimated differences in HR and HRV across each sleep metric, adjusting for age and mental health/sleep medications. Results: 74 participants recorded sleep data: 90% women, 41% Black, mean age 45.6 (SD 11.5) years; 36% were taking mental health/sleep medications. Sixty-eight had ≥7 nights of sleep data&complete medication data. Among those, inefficient sleep and insufficient sleep duration were associated with 6.6 (95% CI 0.6, 12.7) and 4.0 (95% CI 0.0, 7.9) higher HR in the 2 hours before wake, respectively. “Poor sleep” was associated with 4.6 (95% CI 0.8, 8.5) higher HR. Irregular sleep and poor timing were not associated with HR. No sleep metrics were associated with HRV in the period spanning the hour before&hour after wake. Conclusion: Louisiana FQHC HCWs with inefficient sleep and insufficient sleep duration had higher mean HR in the 2 hours before wake. Sleep was not associated with HRV, which may be less sensitive to short term change. Further research is needed in larger samples to determine mechanisms linking poor sleep to cardiometabolic risk.
Abstract P1035: The Association between PREVENT 10-Year Overall Cardiovascular Disease Risk and Incident Fractures in Postmenopausal Women
Background: This study aimed to estimate the association between cardiovascular disease (CVD) risk and incident fracture in postmenopausal women. Methods: The study included data from women without a history of CVD enrolled in the Women’s Health Initiative, who had available CVD biomarker information at baseline necessary to compute a 10-year overall CVD risk using the PREVENT equation. Outcomes included self-reported any clinical, major osteoporotic (MOF-hip, spine, wrist, shoulder), and hip fractures. Women reporting anti-osteoporosis medications at baseline and pathologic fractures during follow-up were excluded. Hierarchical multivariable Cox proportional hazard models assessed the association of CVD risk with fracture and if the association was modified by race and ethnicity or body mass index (BMI). Results: Our study comprised 21,300 women (age: 63.7±7.3 years; non-Hispanic (NH) White: 48%; NH-Black: 33%). The mean 10-year overall CVD risk score was 9.3 ± 5.7, with 5,370 (25.2%), 4,169 (19.6%), 10,661 (50.0%), and 1,100 (5.2%) participants in the low (<5.0%), borderline (5.0-7.4%), intermediate (7.5-19.9%, and high ≥20.0%) categories, respectively. A total of 9,399, 5,104, and 1,769 clinical, MOF, and hip fracture cases were reported over a mean follow-up of 17.1 ± 6.7 years. After full covariate adjustment (Model 4) and adjustment for factors significantly associated with fracture from stepwise modeling (Model 5), women with intermediate- and high- overall CVD risk scores had significantly higher risk for all fracture types, particularly hip fracture [Model 5 HR (95% CI) - intermediate: 2.43 (1.53, 3.87); high: 3.56 (2.01, 6.15)] (Table). Neither race and ethnicity nor BMI modified the association between overall CVD risk and fracture. Conclusion: In postmenopausal women, higher CVD risk scores significantly associated with a higher risk of incident fractures. Future studies assessing if management of CVD aids in fracture prevention in high-risk CVD populations based on PREVENT score is warranted.
Abstract P1136: Fetal C-Reactive Protein rs1205 Genotype Associated with Maternal Pre-eclampsia
Introduction: Maternal variants including C-Reactive Protein, CRP rs1205 have previously been associated with risk of pre-eclampsia (PE). These findings were replicated in two non-American Indian populations. The rs1205 T allele is associated with reduced serum levels of CRP. Our objective was to determine if the fetal rs1205 genotype contributed to maternal risk of PE independent of maternal rs1205 genotype. Methods: Only offspring of both case and control mothers heterozygous for rs1205 were enrolled, thus controlling for maternal genetic influence at this locus. Offspring were then genotyped for rs1205 by TaqMan assay. Association was assessed by chi-square and multivariate logistic regression. Results: Offspring of 35 of 45 normal pregnancies and 12 of 23 PE pregnancies exhibited the rs1205 T allele dominant genotype (Pearson chi square p=0.031). Multivariate logistic regression analysis adjusted for maternal age, nulliparity and BMI demonstrates an odds ratio of 0.255, p=0.032, 95% CI 0.073-0.891 for the fetal, T-dominant genotype. Discussion: Among 68 women, heterozygous for the rs1205 allele, both chi-square and multivariate adjusted logistic analysis show reduced risk of PE among pregnancies with fetal T allele dominant genotypes. This is consistent with previous findings of reduced risk associated with this maternal genotype, and with a pathophysiologic model wherein less placental CRP expression reduces risk of PE.
A WRKY transcription factor confers broad-spectrum resistance to biotic stresses and yield stability in rice
Plants are subject to attack by diverse pests and pathogens. Few genes conferring broad-spectrum resistance to both insects and pathogens have been identified. Because of the growth–defense tradeoff, it is often challenging to balance biotic stress resistance and yield for crops. Here, we report that OsWRKY36 suppresses the resistance to insects and pathogens via transcriptional repression of Phenylalanine Ammonia Lyases ( PALs ), a key enzyme in phenylpropanoid pathway in rice. Knocking out OsWRKY36 causes elevated lignin biosynthesis and increased sclerenchyma thickness of leaf sheath, leading to enhanced resistance to multiple pests and pathogens. Additionally, loss of OsWRKY36 also derepresses the transcription of Ideal Plant Architecture 1 ( IPA1 ) and MONOCULM2 ( MOC2 ), resulting in increased spikelet number per panicle and tiller number. These findings provide mechanistic insights into biotic stress tolerance in rice and offer a promising strategy to breed rice cultivars with broad-spectrum resistance to insects and pathogens while maintaining stable yield.