Left Ventricular Wall Stress and Incident Heart Failure in Elderly Community-Dwelling Individuals.

Background: Greater left ventricular (LV) wall stress is associated with adverse outcomes among patients with prevalent heart failure (HF). Less is known about the association between LV wall stress and incident HF. Objectives: The purpose of the study was to identify clinical factors associated with wall stress and test the association between wall stress and incident HF. Methods: We studied 4,601 ARIC (Atherosclerosis Risk In Communities) study participants without prevalent HF who underwent echocardiography between 2011 and 2013. LV end systolic and diastolic wall stress (LVESWS, LVEDWS) were calculated from chamber and wall thickness, systemic blood pressure, and transmitral Doppler E/e' as a surrogate for LV end diastolic pressure. Incident HF was ascertained by International Classification of Diseases (ICD)-9/10 claims for hospitalized HF through December 31, 2016. We used Cox regression to test the association between wall stress and incident HF, adjusted for demographics, traditional cardiovascular risk factors, prevalent coronary artery disease and atrial fibrillation, creatinine, N-terminal pro-B-type natriuretic peptide, troponin, triglycerides, C-reactive protein, LV ejection fraction, and LV mass. Results: The cohort had a median age of 75 years and 58% women, with 18% identifying as Black. Median LVESWS and LVEDWS were 48.8 (25th-75th percentile: 39.3-60.1) and 18.9 (25th-75th percentile: 15.8-22.5) kdynes/cm2, respectively. LVESWS and LVEDWS were modestly related (rho = 0.30, P < 0.001). Over 4.6 years of median follow-up (156 HF events), each 1 kdyne/cm2 greater LVEDWS was significantly associated with higher risk of incident HF (HR: 1.03; 95% CI: 1.01-1.06), while LVESWS was not (HR: 1.00; 95% CI: 0.99-1.01). Conclusions: Among community-dwelling elderly individuals, greater LVEDWS is associated with a higher risk for incident HF.

Biplane 3D overlay guidance for congenital heart disease to assist cardiac catheterization interventions-A pilot study.

Cardiac catheterization for congenital heart disease (CHD) performed under fluoroscopic guidance still lacks definition and requires exposure to ionizing radiation and contrast agents, with most patients needing multiple procedures through their lifetime, leading to cumulative radiation risks. While fusion overlay techniques have been employed in the past to aid, these have been limited to a single plane, while interventions are traditionally performed under biplane fluoroscopy. We describe our initial experience performing cardiac catheterizations guided by an enhanced biplane GuideCCI system© (Siemens Healthcare, Germany) augmented by 3D magnetic resonance imaging and computed tomography modeling. Twenty-one children and young adults with CHD undergoing catheterization procedures between October 2019 and May 2021 were chosen based on their degree of complexity of cardiac anatomy. 3D stereolithography models were generated, overlayed, and displayed in real time, alongside angiographs in both planes on the screen during these procedures. We report successful implementation of this novel technology for performance of 26 interventions including stent placements, balloon dilations, vessel occlusion and percutaneous valve and transvenous pacemaker implantation all in patients with various complex cardiac anatomies. A statistically significant reduction in radiation and contrast use was noted for coarctation of the aorta stent angioplasty and transcatheter pulmonary valve replacement when compared with national benchmarks and local institutional metrics (with and without single plane overlay). No complications were encountered with the use of this technology. Use of a tracheal registration technique provided very good correlation in most cases. Operators preferred using biplane augmented catheterization over traditional fluoroscopy in patients with complex cardiac anatomy undergoing interventions.

Proteomic Risk Score of Increased Respiratory Susceptibility: A Multi-Cohort Study.

RATIONALE: Accelerated decline in lung function is associated with incident COPD, hospitalizations and death. However, identifying this trajectory with longitudinal spirometry measurements is challenging in clinical practice. OBJECTIVE: To determine whether a proteomic risk score trained on accelerated decline in lung function can assess risk of future respiratory disease and mortality. METHODS: In CARDIA, a population-based cohort starting in young adulthood, longitudinal measurements of FEV1 percent predicted (up to six timepoints over 30 years) were used to identify accelerated and normal decline trajectories. Protein aptamers associated with an accelerated decline trajectory were identified with multivariable logistic regression followed by LASSO regression. The proteomic respiratory susceptibility score was derived based on these circulating proteins and applied to the UK Biobank and COPDGene studies to examine associations with future respiratory morbidity and mortality. MEASUREMENTS AND RESULTS: Higher susceptibility score was independently associated with all-cause mortality (UKBB: HR 1.56, 95%CI 1.50-1.61; COPDGene: HR 1.75, 95%CI 1.63-1.88), respiratory mortality (UKBB: HR 2.39, 95% CI 2.16-2.64; COPDGene: HR 1.83, 95%CI 1.33-2.51), incident COPD (UKBB: HR 1.84, 95%CI 1.71-1.98), incident respiratory exacerbation (COPDGene: OR 1.11, 95%CI 1.03-1.20), and incident exacerbation requiring hospitalization (COPDGene: OR 1.18, 95%CI 1.08-1.28). CONCLUSIONS: A proteomic signature of increased respiratory susceptibility identifies people at risk of respiratory death, incident COPD, and respiratory exacerbations. This susceptibility score is comprised of proteins with well-known and novel associations with lung health and holds promise for the early detection of lung disease without requiring years of spirometry measurements.

Choline Metabolites and 15-Year Risk of Incident Diabetes in a Prospective Cohort of Adults: Coronary Artery Risk Development in Young Adults (CARDIA) Study.

OBJECTIVE: The potential for choline metabolism to influence the development of diabetes has received increased attention. Previous studies on circulating choline metabolites and incident diabetes have been conducted in samples of older adults, often with a high prevalence of risk factors. RESEARCH DESIGN AND METHODS: Participants were from year 15 of follow-up (2000-2001) in the Coronary Artery Risk Development in Young Adults (CARDIA) Study (n = 3,133, aged 33-45 years) with plasma choline metabolite (choline, betaine, and trimethylamine N-oxide [TMAO]) data. We quantified associations between choline metabolites and 15-year risk of incident diabetes (n = 387) among participants free of diabetes at baseline using Cox proportional hazards regression models adjusted for sociodemographics, health behaviors, and clinical variables. RESULTS: Betaine was inversely associated with 15-year risk of incident diabetes (hazard ratio 0.76 [95% CI 0.67, 0.88] per 1-SD unit betaine), and TMAO was positively associated with 15-year risk of incident diabetes (1.11 [1.01, 1.22] per 1-SD unit). Choline was not significantly associated with 15-year risk of incident diabetes (1.05 [0.94, 1.16] per 1-SD). CONCLUSIONS: Our findings are consistent with other published literature supporting a role for choline metabolism in diabetes. Our study extends the current literature by analyzing a racially diverse population-based cohort of early middle-aged individuals in whom preventive activities may be most relevant.

Understanding and controlling the variables for stromal vascular fraction therapy.

In regenerative medicine, the isolation of mesenchymal stromal cells (MSCs) from the adipose tissue's stromal vascular fraction (SVF) is a critical area of study. Our review meticulously examines the isolation process of MSCs, starting with the extraction of adipose tissue. The choice of liposuction technique, anatomical site, and immediate processing are essential to maintain cell functionality. We delve into the intricacies of enzymatic digestion, emphasizing the fine-tuning of enzyme concentrations to maximize cell yield while preventing harm. The review then outlines the filtration and centrifugation techniques necessary for isolating a purified SVF, alongside cell viability assessments like flow cytometry, which are vital for confirming the efficacy of the isolated MSCs. We discuss the advantages and drawbacks of using autologous vs allogeneic SVF sources, touching upon immunocompatibility and logistical considerations, as well as the variability inherent in donor-derived cells. Anesthesia choices, the selection between hypodermic needles vs liposuction cannulas, and the role of adipose tissue lysers in achieving cellular dissociation are evaluated for their impact on SVF isolation. Centrifugation protocols are also analyzed for their part in ensuring the integrity of the SVF. The necessity for standardized MSC isolation protocols is highlighted, promoting reproducibility and successful clinical application. We encourage ongoing research to deepen the understanding of MSC biology and therapeutic action, aiming to further the field of regenerative medicine. The review concludes with a call for rigorous research, interdisciplinary collaboration, and strict adherence to ethical and regulatory standards to safeguard patient safety and optimize treatment outcomes with MSCs.

Clinical-transcriptional prioritization of the circulating proteome in human heart failure.

Given expanding studies in epidemiology and disease-oriented human studies offering hundreds of associations between the human "ome" and disease, prioritizing molecules relevant to disease mechanisms among this growing breadth is important. Here, we link the circulating proteome to human heart failure (HF) propensity (via echocardiographic phenotyping and clinical outcomes) across the lifespan, demonstrating key pathways of fibrosis, inflammation, metabolism, and hypertrophy. We observe a broad array of genes encoding proteins linked to HF phenotypes and outcomes in clinical populations dynamically expressed at a transcriptional level in human myocardium during HF and cardiac recovery (several in a cell-specific fashion). Many identified targets do not have wide precedent in large-scale genomic discovery or human studies, highlighting the complementary roles for proteomic and tissue transcriptomic discovery to focus epidemiological targets to those relevant in human myocardium for further interrogation.

Nonphotochemical quenching kinetics GWAS in sorghum identifies genes that may play conserved roles in maize and Arabidopsis thaliana photoprotection.

Photosynthetic organisms must cope with rapid fluctuations in light intensity. Nonphotochemical quenching (NPQ) enables the dissipation of excess light energy as heat under high light conditions, whereas its relaxation under low light maximizes photosynthetic productivity. We quantified variation in NPQ kinetics across a large sorghum (Sorghum bicolor) association panel in four environments, uncovering significant genetic control for NPQ. A genome-wide association study (GWAS) confidently identified three unique regions in the sorghum genome associated with NPQ and suggestive associations in an additional 61 regions. We detected strong signals from the sorghum ortholog of Arabidopsis thaliana Suppressor Of Variegation 3 (SVR3) involved in plastid-nucleus signaling. By integrating GWAS results for NPQ across maize (Zea mays) and sorghum-association panels, we identified a second gene, Non-yellowing 1 (NYE1), originally studied by Gregor Mendel in pea (Pisum sativum) and involved in the degradation of photosynthetic pigments in light-harvesting complexes. Analysis of nye1 insertion alleles in A. thaliana confirmed the effect of this gene on NPQ kinetics in eudicots. We extended our comparative genomics GWAS framework across the entire maize and sorghum genomes, identifying four additional loci involved in NPQ kinetics. These results provide a baseline for increasing the accuracy and speed of candidate gene identification for GWAS in species with high linkage disequilibrium.

Big data analytics and artificial intelligence aspects for privacy and security concerns for demand response modelling in smart grid: A futuristic approach.

Next generation electrical grid considered as Smart Grid has completely embarked a journey in the present electricity era. This creates a dominant need of machine learning approaches for security aspects at the larger scale for the electrical grid. The need of connectivity and complete communication in the system uses a large amount of data where the involvement of machine learning models with proper frameworks are required. This massive amount of data can be handled by various process of machine learning models by selecting appropriate set of consumers to respond in accordance with demand response modelling, learning the different attributes of the consumers, dynamic pricing schemes, various load forecasting and also data acquisition process with more cost effectiveness. In connected to this process, considering complex smart grid security and privacy based methods becomes a major aspect and there can be potential cyber threats for the consumers and also utility data. The security concerns related to machine learning model exhibits a key factor based on different machine learning algorithms used and needed for the energy application at a future perspective. This work exhibits as a detailed analysis with machine learning models which are considered as cyber physical system model with smart grid. This work also gives a clear understanding towards the potential advantages, limitations of the algorithms in a security aspect and outlines future direction in this very important area and fast-growing approach.

Psilocybin desynchronizes the human brain.

A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials1-4. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus5-8. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6-12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.

The subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose.

OBJECTIVE: The objective of this study was to identify the transcriptional landscape of insulin resistance (IR) in subcutaneous adipose tissue (SAT) in humans across the spectrum of obesity. METHODS: We used SAT RNA sequencing in 220 individuals with metabolic phenotyping. RESULTS: We identified a 35-gene signature with high predictive accuracy for homeostatic model of IR that was expressed across a variety of non-immune cell populations. We observed primarily "protective" IR associations for adipocyte transcripts and "deleterious" associations for macrophage transcripts, as well as a high concordance between SAT and visceral adipose tissue (VAT). Multiple SAT genes exhibited dynamic expression 5 years after weight loss surgery and with insulin stimulation. Using available expression quantitative trait loci in SAT and/or VAT, we demonstrated similar genetic effect sizes of SAT and VAT on type 2 diabetes and BMI. CONCLUSIONS: SAT is conventionally viewed as a metabolic buffer for lipid deposition during positive energy balance, whereas VAT is viewed as a dominant contributor to and prime mediator of IR and cardiometabolic disease risk. Our results implicate a dynamic transcriptional architecture of IR that resides in both immune and non-immune populations in SAT and is shared with VAT, nuancing the current VAT-centric concept of IR in humans.

Placental biophysical model for prediction of early onset fetal growth restriction in first and second trimester of pregnancy: A prospective cohort study.

INTRODUCTION: To assess the placental biometry, placental biomarkers and uterine artery Doppler in each trimester of pregnancy for prediction of early-onset fetal growth restriction (EO FGR). METHODS: In this prospective cohort study placental biometry; biomarkers PAPP-A, sFLT-1, and PlGF along with the uterine artery blood flow evaluation was done serially at 11-14, 20-24 and 28-32 weeks of gestation. The above parameters were compared between women with early onset FGR and controls. RESULTS: Out of 1008 fully followed cases, the small for gestational age fetuses were 227/1008 (22.5 %), and EO FGR were 84/1008(8.3 %).The placental length, volume, and PlGF levels were significantly lower, whereas the uterine artery PI(Ut PI) was significantly higher at all time points among cases. The sFLT-1 level showed a significant increase among cases, whereas it decreased among controls from the first to the second trimester. The detection rate using PV/UtA PI was 60 % in the first trimester and 66.7 % in the second trimester at 30 % FPR. CONCLUSION: The PV/Ut PI in first and the second trimester was a good marker for the prediction of pregnancies at increased risk of developing EO FGR.

Genomic co-localization of variation affecting agronomic and human gut microbiome traits in a meta-analysis of diverse sorghum.

Substantial functional metabolic diversity exists within species of cultivated grain crops that directly or indirectly provide more than half of all calories consumed by humans around the globe. While such diversity is the molecular currency used for improving agronomic traits, diversity is poorly characterized for its effects on human nutrition and utilization by gut microbes. Moreover, we know little about agronomic traits' potential tradeoffs and pleiotropic effects on human nutritional traits. Here, we applied a quantitative genetics approach using a meta-analysis and parallel genome-wide association studies of Sorghum bicolor traits describing changes in the composition and function of human gut microbe communities, and any of 200 sorghum seed and agronomic traits across a diverse sorghum population to identify associated genetic variants. A total of 15 multiple-effect loci (MEL) were initially found where different alleles in the sorghum genome produced changes in seed that affected the abundance of multiple bacterial taxa across 2 human microbiomes in automated in vitro fermentations. Next, parallel genome-wide studies conducted for seed, biochemical, and agronomic traits in the same population identified significant associations within the boundaries of 13/15 MEL for microbiome traits. In several instances, the colocalization of variation affecting gut microbiome and agronomic traits provided hypotheses for causal mechanisms through which variation could affect both agronomic traits and human gut microbes. This work demonstrates that genetic factors affecting agronomic traits in sorghum seed can also drive significant effects on human gut microbes, particularly bacterial taxa considered beneficial. Understanding these pleiotropic relationships will inform future strategies for crop improvement toward yield, sustainability, and human health.

Clusters of multidimensional exercise response patterns and estimated heart failure risk in the Framingham Heart Study.

AIMS: New tools are needed to identify heart failure (HF) risk earlier in its course. We evaluated the association of multidimensional cardiopulmonary exercise testing (CPET) phenotypes with subclinical risk markers and predicted long-term HF risk in a large community-based cohort. METHODS AND RESULTS: We studied 2532 Framingham Heart Study participants [age 53 ± 9 years, 52% women, body mass index (BMI) 28.0 ± 5.3 kg/m2, peak oxygen uptake (VO2) 21.1 ± 5.9 kg/m2 in women, 26.4 ± 6.7 kg/m2 in men] who underwent maximum effort CPET and were not taking atrioventricular nodal blocking agents. Higher peak VO2 was associated with a lower estimated HF risk score (Spearman correlation r: -0.60 in men and -0.55 in women, P < 0.0001), with an observed overlap of estimated risk across peak VO2 categories. Hierarchical clustering of 26 separate CPET phenotypes (values residualized on age, sex, and BMI to provide uniformity across these variables) identified three clusters with distinct exercise physiologies: Cluster 1-impaired oxygen kinetics; Cluster 2-impaired vascular; and Cluster 3-favourable exercise response. These clusters were similar in age, sex distribution, and BMI but displayed distinct associations with relevant subclinical phenotypes [Cluster 1-higher subcutaneous and visceral fat and lower pulmonary function; Cluster 2-higher carotid-femoral pulse wave velocity (CFPWV); and Cluster 3-lower CFPWV, C-reactive protein, fat volumes, and higher lung function; all false discovery rate < 5%]. Cluster membership provided incremental variance explained (adjusted R2 increment of 0.10 in women and men, P < 0.0001 for both) when compared with peak VO2 alone in association with predicted HF risk. CONCLUSIONS: Integrated CPET response patterns identify physiologically relevant profiles with distinct associations to subclinical phenotypes that are largely independent of standard risk factor-based assessment, which may suggest alternate pathways for prevention.

Proteomic analysis of cardiorespiratory fitness for prediction of mortality and multisystem disease risks.

Despite the wide effects of cardiorespiratory fitness (CRF) on metabolic, cardiovascular, pulmonary and neurological health, challenges in the feasibility and reproducibility of CRF measurements have impeded its use for clinical decision-making. Here we link proteomic profiles to CRF in 14,145 individuals across four international cohorts with diverse CRF ascertainment methods to establish, validate and characterize a proteomic CRF score. In a cohort of around 22,000 individuals in the UK Biobank, a proteomic CRF score was associated with a reduced risk of all-cause mortality (unadjusted hazard ratio 0.50 (95% confidence interval 0.48-0.52) per 1 s.d. increase). The proteomic CRF score was also associated with multisystem disease risk and provided risk reclassification and discrimination beyond clinical risk factors, as well as modulating high polygenic risk of certain diseases. Finally, we observed dynamicity of the proteomic CRF score in individuals who undertook a 20-week exercise training program and an association of the score with the degree of the effect of training on CRF, suggesting potential use of the score for personalization of exercise recommendations. These results indicate that population-based proteomics provides biologically relevant molecular readouts of CRF that are additive to genetic risk, potentially modifiable and clinically translatable.

Association of Smartwatch-Based Heart Rate and Physical Activity With Cardiorespiratory Fitness Measures in the Community: Cohort Study.

BACKGROUND: Resting heart rate (HR) and routine physical activity are associated with cardiorespiratory fitness levels. Commercial smartwatches permit remote HR monitoring and step count recording in real-world settings over long periods of time, but the relationship between smartwatch-measured HR and daily steps to cardiorespiratory fitness remains incompletely characterized in the community. OBJECTIVE: This study aimed to examine the association of nonactive HR and daily steps measured by a smartwatch with a multidimensional fitness assessment via cardiopulmonary exercise testing (CPET) among participants in the electronic Framingham Heart Study. METHODS: Electronic Framingham Heart Study participants were enrolled in a research examination (2016-2019) and provided with a study smartwatch that collected longitudinal HR and physical activity data for up to 3 years. At the same examination, the participants underwent CPET on a cycle ergometer. Multivariable linear models were used to test the association of CPET indices with nonactive HR and daily steps from the smartwatch. RESULTS: We included 662 participants (mean age 53, SD 9 years; n=391, 59% women, n=599, 91% White; mean nonactive HR 73, SD 6 beats per minute) with a median of 1836 (IQR 889-3559) HR records and a median of 128 (IQR 65-227) watch-wearing days for each individual. In multivariable-adjusted models, lower nonactive HR and higher daily steps were associated with higher peak oxygen uptake (VO2), % predicted peak VO2, and VO2 at the ventilatory anaerobic threshold, with false discovery rate (FDR)-adjusted P values <.001 for all. Reductions of 2.4 beats per minute in nonactive HR, or increases of nearly 1000 daily steps, corresponded to a 1.3 mL/kg/min higher peak VO2. In addition, ventilatory efficiency (VE/VCO2; FDR-adjusted P=.009), % predicted maximum HR (FDR-adjusted P<.001), and systolic blood pressure-to-workload slope (FDR-adjusted P=.01) were associated with nonactive HR but not associated with daily steps. CONCLUSIONS: Our findings suggest that smartwatch-based assessments are associated with a broad array of cardiorespiratory fitness responses in the community, including measures of global fitness (peak VO2), ventilatory efficiency, and blood pressure response to exercise. Metrics captured by wearable devices offer a valuable opportunity to use extensive data on health factors and behaviors to provide a window into individual cardiovascular fitness levels.

Decreased postpartum exercise capacity after a diagnosis of pre-eclampsia: Implications for CVD risk prediction.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with increased long-term risk for cardiometabolic risk factors (chronic hypertension [HTN], obesity, diabetes) and heart failure. Exercise capacity is a known predictor of heart failure in patients with normal resting cardiac filling pressures. In this prospective observational cohort study, we sought to identify predictors of reduced postpartum exercise capacity in participants with normotensive vs preeclamptic pregnancies. METHODS: Preeclampsia (PreE) and normotensive subjects were enrolled to undergo bedside echocardiography within 48 hours of delivery, and rest/exercise echocardiography 12 weeks postpartum. RESULTS: Recruited subjects (n = 68) were grouped according to their blood pressure as: a) normotensive pregnancy n = 15; b) PreE with normotensive postpartum (PreE-Resolved, n = 36); c) PreE with persistent postpartum HTN (PreE-HTN, n = 17). At enrollment, a significantly higher percentage of subjects in the PreE-HTN group were Black. Compared to normotensive and PreE-Resolved subjects, those with PreE-HTN demonstrated higher resting systolic blood pressure (SBP, 112 [normotensive] vs 112 [PreE-Resolved] vs 134 [PreE-HTN], P < .001) and diastolic blood pressure (DBP, 70.0 vs 72.5 vs 85.0, P < .001), and significantly less postpartum weight loss (9.6% vs 13.6% vs 3.8%, P < .001). Following Bruce protocol stress testing, PreE-HTN subjects demonstrated achieved significantly lower exercise duration (10.4 vs 10.2 vs 7.9 minutes, P = .001). Subjects with PreE-HTN also demonstrated evidence of exercise-induced diastolic dysfunction as assessed by peak exercise lateral e' (18.0 vs 18.0 vs 13.5, P = .045) and peak exercise tricuspid regurgitation velocity (TR Vm, 2.4 vs 3.0 vs 3.1, P = 0.045). Exercise duration was negatively associated with gravidity (R = -0.27, P = .029) and postpartum LV mass index (R = -0.45, P < .001), resting average E/e' (R = -0.51, P < .001), BMI (R = -0.6, P < .001) and resting SBP (R = -0.51, P < .001). CONCLUSIONS: Postpartum exercise stress testing capacity is related to readily available clinical markers including pregnancy factors, echocardiographic parameters and unresolved cardiometabolic risk factors.

Metabolic liability for weight gain in early adulthood.

While weight gain is associated with a host of chronic illnesses, efforts in obesity have relied on single "snapshots" of body mass index (BMI) to guide genetic and molecular discovery. Here, we study >2,000 young adults with metabolomics and proteomics to identify a metabolic liability to weight gain in early adulthood. Using longitudinal regression and penalized regression, we identify a metabolic signature for weight liability, associated with a 2.6% (2.0%-3.2%, p = 7.5 × 10-19) gain in BMI over ≈20 years per SD higher score, after comprehensive adjustment. Identified molecules specified mechanisms of weight gain, including hunger and appetite regulation, energy expenditure, gut microbial metabolism, and host interaction with external exposure. Integration of longitudinal and concurrent measures in regression with Mendelian randomization highlights the complexity of metabolic regulation of weight gain, suggesting caution in interpretation of epidemiologic or genetic effect estimates traditionally used in metabolic research.

Evaluation of potential increase in photosynthetic efficiency of cassava (Manihot esculenta Crantz) plants exposed to elevated carbon dioxide.

Cassava (Manihot esculenta Crantz), an important tropical crop, is affected by extreme climatic events, including rising CO2 levels. We evaluated the short-term effect of elevated CO2 concentration (ECO2 ) (600, 800 and 1000ppm) on the photosynthetic efficiency of 14 cassava genotypes. ECO2 significantly altered gaseous exchange parameters (net photosynthetic rate (P n ), stomatal conductance (g s ), intercellular CO2 (C i ) and transpiration (E )) in cassava leaves. There were significant but varying interactive effects between ECO2 and varieties on these physiological characteristics. ECO2 at 600 and 800ppm increased the P n rate in the range of 13-24% in comparison to 400ppm (ambient CO2 ), followed by acclimation at the highest concentration of 1000ppm. A similar trend was observed in g s and E . Conversely, C i increased significantly and linearly across increasing CO2 concentration. Along with C i , a steady increase in water use efficiency [WUEintrinsic (P n /g s ) and WUEinstantaneous (P n /E )] across various CO2 concentrations corresponded with the central role of restricted stomatal activity, a common response under ECO2 . Furthermore, P n had a significant quadratic relationship with the ECO2 (R 2 =0.489) and a significant and linear relationship with C i (R 2 =0.227). Relative humidity and vapour pressure deficit during the time of measurements remained at 70-85% and ~0.9-1.31kPa, respectively, at 26±2°C leaf temperature. Notably, not a single variety exhibited constant performance for any of the parameters across CO2 concentrations. Our results indicate that the potential photosynthesis can be increased up to 800ppm cassava varieties with high sink capacity can be cultivated under protected cultivation to attain higher productivity.

Population-level gene expression can repeatedly link genes to functions in maize.

Transcriptome-wide association studies (TWAS) can provide single gene resolution for candidate genes in plants, complementing genome-wide association studies (GWAS) but efforts in plants have been met with, at best, mixed success. We generated expression data from 693 maize genotypes, measured in a common field experiment, sampled over a 2-h period to minimize diurnal and environmental effects, using full-length RNA-seq to maximize the accurate estimation of transcript abundance. TWAS could identify roughly 10 times as many genes likely to play a role in flowering time regulation as GWAS conducted data from the same experiment. TWAS using mature leaf tissue identified known true-positive flowering time genes known to act in the shoot apical meristem, and trait data from a new environment enabled the identification of additional flowering time genes without the need for new expression data. eQTL analysis of TWAS-tagged genes identified at least one additional known maize flowering time gene through trans-eQTL interactions. Collectively these results suggest the gene expression resource described here can link genes to functions across different plant phenotypes expressed in a range of tissues and scored in different experiments.

Life's Essential 8 Cardiovascular Health Score and Cardiorespiratory Fitness in the Community.

BACKGROUND: The relation of cardiorespiratory fitness (CRF) to lifestyle behaviors and factors linked with cardiovascular health remains unclear. We aimed to understand how the American Heart Association's Life's Essential 8 (LE8) score (and its changes over time) relate to CRF and complementary exercise measures in community-dwelling adults. METHODS AND RESULTS: Framingham Heart Study (FHS) participants underwent maximum effort cardiopulmonary exercise testing for direct quantification of peak oxygen uptake (V̇O2). A 100-point LE8 score was constructed as the average across 8 factors: diet, physical activity, nicotine exposure, sleep, body mass index, lipids, blood glucose, and blood pressure. We related total LE8 score, score components, and change in LE8 score over 8 years with peak V̇O2 (log-transformed) and complementary CRF measures. In age- and sex-adjusted linear models (N=1838, age 54±9 years, 54% women, LE8 score 76±12), a higher LE8 score was associated favorably with peak V̇O2, ventilatory efficiency, resting heart rate, and blood pressure response to exercise (all P<0.0001). A clinically meaningful 5-point higher LE8 score was associated with a 6.0% greater peak V̇O2 (≈1.4 mL/kg per minute at sample mean). All LE8 components were significantly associated with peak V̇O2 in models adjusted for age and sex, but blood lipids, diet, and sleep health were no longer statistically significant after adjustment for all LE8 components. Over an ≈8-year interval, a 5-unit increase in LE8 score was associated with a 3.7% higher peak V̇O2 (P<0.0001). CONCLUSIONS: Higher LE8 score and improvement in LE8 over time was associated with greater CRF, highlighting the importance of the LE8 factors in maintaining CRF.