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.

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.

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.

Proteomics, Human Environmental Exposure, and Cardiometabolic Risk.

BACKGROUND: The biological mechanisms linking environmental exposures with cardiovascular disease pathobiology are incompletely understood. We sought to identify circulating proteomic signatures of environmental exposures and examine their associations with cardiometabolic and respiratory disease in observational cohort studies. METHODS: We tested the relations of >6500 circulating proteins with 29 environmental exposures across the built environment, green space, air pollution, temperature, and social vulnerability indicators in ≈3000 participants of the CARDIA study (Coronary Artery Risk Development in Young Adults) across 4 centers using penalized and ordinary linear regression. In >3500 participants from FHS (Framingham Heart Study) and JHS (Jackson Heart Study), we evaluated the prospective relations of proteomic signatures of the envirome with cardiovascular disease and mortality using Cox models. RESULTS: Proteomic signatures of the envirome identified novel/established cardiovascular disease-relevant pathways including DNA damage, fibrosis, inflammation, and mitochondrial function. The proteomic signatures of the envirome were broadly related to cardiometabolic disease and respiratory phenotypes (eg, body mass index, lipids, and left ventricular mass) in CARDIA, with replication in FHS/JHS. A proteomic signature of social vulnerability was associated with a composite of cardiovascular disease/mortality (1428 events; FHS: hazard ratio, 1.16 [95% CI, 1.08-1.24]; P=1.77×10-5; JHS: hazard ratio, 1.25 [95% CI, 1.13-1.38]; P=6.38×10-6; hazard ratioexpressed as per 1 SD increase in proteomic signature), robust to adjustment for known clinical risk factors. CONCLUSIONS: Environmental exposures are related to an inflammatory-metabolic proteome, which identifies individuals with cardiometabolic disease and respiratory phenotypes and outcomes. Future work examining the dynamic impact of the environment on human cardiometabolic health is warranted.

Human metabolic chambers reveal a coordinated metabolic-physiologic response to nutrition.

The emerging field of precision nutrition is based on the notion that inter-individual responses across diets of different calorie-macronutrient content may contribute to inter-individual differences in metabolism, adiposity, and weight gain. Free-living diet studies have been traditionally challenged by difficulties in controlling adherence to prescribed calories and macronutrient content and rarely allow a period of metabolic stability prior to metabolic measures (to minimize influences of weight changes). In this context, key physiologic measures central to precision nutrition responses may be most precisely quantified via whole room indirect calorimetry over 24-h, in which precise control of activity and nutrition can be achieved. In addition, these studies represent unique "N of 1" human crossover metabolic-physiologic experiments during which specific molecular pathways central to nutrient metabolism may be discerned. Here, we quantified 263 circulating metabolites during a ≈40-day inpatient admission in which up to 94 participants underwent seven monitored 24-h nutritional interventions of differing macronutrient composition in a whole-room indirect calorimeter to capture precision metabolic responses. Broadly, we observed heterogenous responses in metabolites across dietary chambers, with the exception of carnitines which tracked with 24-h respiratory quotient. We identified excursions in shared metabolic species (e.g., carnitines, glycerophospholipids, amino acids) that mapped onto gold-standard calorimetric measures of substrate oxidation preference and lipid availability. These findings support a coordinated metabolic-physiologic response to nutrition, highlighting the relevance of these controlled settings to uncover biological pathways of energy utilization during precision nutrition studies.

The Correlation Between Serum Fibroblast Growth Factor 21 and the Severity and Occurrence of Coronary Artery Disease.

BACKGROUND: The burden of cardiovascular diseases (CVDs) is increasing worldwide with CVD being one of the leading causes of death, including atherosclerosis, myocardial infarction, cardiomyopathy, and heart failure (HF). Fibroblast growth factor 21 (FGF21) is an endocrine hormone that regulates carbohydrate and lipid metabolism. It exerts direct effects on the cardiovascular system and can serve as an early indicator of CVDs. FGF21's therapeutic properties include reducing obesity, dyslipidaemia, and hyperglycemia, which can help treat metabolic disorders, autophagy, and apoptosis. Atherosclerosis is developed due to chronic inflammatory conditions, and the immune system's reaction to oxidized lipoproteins is mainly responsible for the development of atherosclerosis. FGF21's precise role in the pathogenesis of coronary artery disease (CAD) remains elusive.  Aim: This study aimed to assess the role of FGF21 in predicting the severity and magnitude of CAD in individuals diagnosed with stable angina pectoris (SAP). MATERIALS AND METHODS: A prospective cross-sectional study was conducted on 110 consecutive patients with SAP reported to the cardiology department of the Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, India. They were divided into two groups based on coronary angiography findings. Control groups included patients not showing any atherosclerotic lesions and case groups with atherosclerotic lesions. The SYNTAX score is a grading system that measures the location and complexity of coronary arteries using anatomical principles. The Gensini score assessment technique was employed to determine the severity of CAD. We compared serum FGF21 levels,left ventricular ejection fraction (LVEF), and inflammatory biomarker C-reactive protein (CRP) levels between the two groups. Moreover, we examined the correlation between the serum FGF21 level and the SYNTAX and Gensini scores. The statistical analysis was done using Version 23.0 of SPSS Statistics. P-values below 0.05 were considered statistically significant. RESULTS: The study found that the case group had a higher average age and a higher proportion of male patients. The case group had considerably higher levels of FGF21 (166.59 ± 94.49791 pg/mL) compared to the control group (54.13 ± 48.467 pg/mL) (p=0.034). The LVEF exhibited a significant difference between the case and control groups, with mean values of 50.3056 ± 7.8242% and 56.078 ± 5.3987%, respectively (p=0.031). CRP levels were comparable in both groups. The case group had mean values of SYNTAX and Gensini scores of 23.19±7.43 and 50.03±27.30, respectively. We found that there was no statistically significant association between the risk assessments for CAD severity and the levels of serum FGF21 (correlation coefficient r=0.14070, p>0.05, and r=0.206415, p>0.05, respectively) Conclusions: FGF21 is gaining recognition as a prospective addition to the FGF family, potentially playing a significant role in cardiovascular disease, particularly atherosclerosis. A statistically significant difference was seen in the serum FGF21 levels between the case and control groups, indicating that it can help in the diagnosis of CAD. However, there was no apparent correlation found between the serum FGF21 levels and the SYNTAX and Gensini scores. The role of FGF21 in the development of atherosclerosis and whether FGF21 could serve as a reliable marker need to be studied further.

Differences in Cardiometabolic Proteins in Pregnancy Prioritize Relevant Targets of Preeclampsia.

BACKGROUND: Preeclampsia is a hypertensive disorder of pregnancy characterized by widespread vascular inflammation. It occurs frequently in pregnancy, often without known risk factors, and has high rates of maternal and fetal morbidity and mortality. Identification of biomarkers that predict preeclampsia and its cardiovascular sequelae before clinical onset, or even before pregnancy, is a critical unmet need for the prevention of adverse pregnancy outcomes. METHODS: We explored differences in cardiovascular proteomics (Olink Explore 384) in 256 diverse pregnant persons across 2 centers (26% Hispanic, 21% Black). RESULTS: We identified significant differences in plasma abundance of markers associated with angiogenesis, blood pressure, cell adhesion, inflammation, and metabolism between individuals delivering with preeclampsia and controls, some of which have not been widely described previously and are not represented in the preeclampsia placental transcriptome. While we observed a broadly similar pattern in early (<34 weeks) versus late (≥34 weeks) preeclampsia, several proteins related to hemodynamic stress, hemostasis, and immune response appeared to be more highly dysregulated in early preeclampsia relative to late preeclampsia. CONCLUSIONS: These results demonstrate the value of performing targeted proteomics using a panel of cardiovascular biomarkers to identify biomarkers relevant to preeclampsia pathophysiology and highlight the need for larger multiomic studies to define modifiable pathways of surveillance and intervention upstream to preeclampsia diagnosis.

Targeted Proteomics Reveals Functional Targets for Early Diabetes Susceptibility in Young Adults.

BACKGROUND: The circulating proteome may encode early pathways of diabetes susceptibility in young adults for surveillance and intervention. Here, we define proteomic correlates of tissue phenotypes and diabetes in young adults. METHODS: We used penalized models and principal components analysis to generate parsimonious proteomic signatures of diabetes susceptibility based on phenotypes and on diabetes diagnosis across 184 proteins in >2000 young adults in the CARDIA (Coronary Artery Risk Development in Young Adults study; mean age, 32 years; 44% women; 43% Black; mean body mass index, 25.6±4.9 kg/m2), with validation against diabetes in >1800 individuals in the FHS (Framingham Heart Study) and WHI (Women's Health Initiative). RESULTS: In 184 proteins in >2000 young adults in CARDIA, we identified 2 proteotypes of diabetes susceptibility-a proinflammatory fat proteotype (visceral fat, liver fat, inflammatory biomarkers) and a muscularity proteotype (muscle mass), linked to diabetes in CARDIA and WHI/FHS. These proteotypes specified broad mechanisms of early diabetes pathogenesis, including transorgan communication, hepatic and skeletal muscle stress responses, vascular inflammation and hemostasis, fibrosis, and renal injury. Using human adipose tissue single cell/nuclear RNA-seq, we demonstrate expression at transcriptional level for implicated proteins across adipocytes and nonadipocyte cell types (eg, fibroadipogenic precursors, immune and vascular cells). Using functional assays in human adipose tissue, we demonstrate the association of expression of genes encoding these implicated proteins with adipose tissue metabolism, inflammation, and insulin resistance. CONCLUSIONS: A multifaceted discovery effort uniting proteomics, underlying clinical susceptibility phenotypes, and tissue expression patterns may uncover potentially novel functional biomarkers of early diabetes susceptibility in young adults for future mechanistic evaluation.

Approach towards surveillance-based diagnosis of acute respiratory illness in India: Expert recommendations.

BACKGROUND: Emerging infectious diseases, often zoonotic, demand a collaborative "One-Health" surveillance approach due to human activities. The need for standardized diagnostic and surveillance algorithms is emphasized to address the difficulty in clinical differentiation and curb antimicrobial resistance. OBJECTIVE: The present recommendations are comprehensive diagnostic and surveillance algorithm for ARIs, developed by the Indian Council of Medical Research (ICMR), which aims to enhance early detection and treatment with improved surveillance. This algorithm shall be serving as a blueprint for respiratory infections landscape in the country and early detection of surge of respiratory infections in the country. CONTENT: The ICMR has risen up to the threat of emerging and re-emerging infections. Here, we seek to recommend a structured approach for diagnosing respiratory illnesses. The recommendations emphasize the significance of prioritizing respiratory pathogens based on factors such as the frequency of occurrence (seasonal or geographical), disease severity, ease of diagnosis and public health importance. The proposed surveillance-based diagnostic algorithm for ARI relies on a combination of gold-standard conventional methods, innovative serological and molecular techniques, as well as radiological approaches, which collectively contribute to the detection of various causative agents. The diagnostic part of the integrated algorithm can be dealt at the local microbiology laboratory of the healthcare facility with the few positive and negative specimens shipped to linked viral disease research laboratories (VRDLs) and other ICMR designated laboratories for genome characterisation, cluster identification and identification of novel agents.

Heart failure with improved ejection fraction: Beyond diagnosis to trajectory analysis.

Left ventricular (LV) systolic dysfunction represents a highly treatable cause of heart failure (HF). A substantial proportion of patients with HF with reduced ejection fraction (EF;HFrEF) demonstrate improvement in LV systolic function (termed HF with improved EF [HFimpEF]), either spontaneously or when treated with guideline-directed medical therapy (GDMT). Although it is a relatively new HF classification, HFimpEF has emerged in recent years as an important and distinct clinical entity. Improvement in LVEF leads to decreased rates of mortality and adverse HF-related outcomes compared to patients with sustained LV systolic dysfunction (HFrEF). While numerous clinical and imaging factors have been associated with HFimpEF, identification of which patients do and do not improve requires further investigation. In addition, patients improve at different rates, and what determines the trajectory of HFimpEF patients after improvement is incompletely characterized. A proportion of patients maintain improvement in LV systolic function, while others experience a recrudescence of systolic dysfunction, especially with GDMT discontinuation. In this review we discuss the contemporary guideline-recommended classification definition of HFimpEF, the epidemiology of improvement in LV systolic function, and the clinical course of this unique patient population. We also offer evidence-based recommendations for the clinical management of HFimpEF and provide a roadmap for future directions in understanding and improving outcomes in the care of patients with HFimpEF.

Implications of metabolism on multi-systems healthy aging across the lifespan.

Aging is increasingly thought to involve dysregulation of metabolism in multiple organ systems that culminate in decreased functional capacity and morbidity. Here, we seek to understand complex interactions among metabolism, aging, and systems-wide phenotypes across the lifespan. Among 2469 adults (mean age 74.7 years; 38% Black) in the Health, Aging and Body Composition study we identified metabolic cross-sectionally correlates across 20 multi-dimensional aging-related phenotypes spanning seven domains. We used LASSO-PCA and bioinformatic techniques to summarize metabolome-phenome relationships and derive metabolic scores, which were subsequently linked to healthy aging, mortality, and incident outcomes (cardiovascular disease, disability, dementia, and cancer) over 9 years. To clarify the relationship of metabolism in early adulthood to aging, we tested association of these metabolic scores with aging phenotypes/outcomes in 2320 participants (mean age 32.1, 44% Black) of the Coronary Artery Risk Development in Young Adults (CARDIA) study. We observed significant overlap in metabolic correlates across the seven aging domains, specifying pathways of mitochondrial/cellular energetics, host-commensal metabolism, inflammation, and oxidative stress. Across four metabolic scores (body composition, mental-physical performance, muscle strength, and physical activity), we found strong associations with healthy aging and incident outcomes, robust to adjustment for risk factors. Metabolic scores for participants four decades younger in CARDIA were related to incident cardiovascular, metabolic, and neurocognitive performance, as well as long-term cardiovascular disease and mortality over three decades. Conserved metabolic states are strongly related to domain-specific aging and outcomes over the life-course relevant to energetics, host-commensal interactions, and mechanisms of innate immunity.

Branched-chain amino acids and type 2 diabetes: a bidirectional Mendelian randomization analysis.

OBJECTIVE: Genetic studies have suggested that the branched-chain amino acids (BCAAs) valine, leucine, and isoleucine have a causal association with type 2 diabetes (T2D). However, inferences are based on a limited number of genetic loci associated with BCAAs. METHODS: Instrumental variables (IVs) for each BCAA were constructed and validated using large well-powered data sets and their association with T2D was tested using a two-sample inverse-variance weighted Mendelian randomization approach. Sensitivity analyses were performed to ensure the accuracy of the findings. A reverse association was assessed using instrumental variables for T2D. RESULTS: Estimated effect sizes between BCAA IVs and T2D, excluding outliers, were as follows: valine (ß = 0.14 change in log-odds per SD change in valine, 95% CI: -0.06 to 0.33, p = 0.17), leucine (ß = 0.15, 95% CI: -0.02 to 0.32, p = 0.09), and isoleucine (ß = 0.13, 95% CI: -0.08 to 0.34, p = 0.24). In contrast, T2D IVs were positively associated with each BCAA, i.e., valine (ß = 0.08 per SD change in levels per log-odds change in T2D, 95% CI: 0.05 to 0.10, p = 1.8 × 10-9 ), leucine (ß = 0.06, 95% CI: 0.04 to 0.09, p = 4.5 × 10-8 ), and isoleucine (ß = 0.06, 95% CI: 0.04 to 0.08, p = 2.8 × 10-8 ). CONCLUSIONS: These data suggest that the BCAAs are not mediators of T2D risk but are biomarkers of diabetes.

Feasibility and safety of bipolar radiofrequency track cautery during percutaneous image-guided abdominal biopsy procedures.

PURPOSE: The purpose of this study was to assess the feasibility and safety of using a bipolar radiofrequency track cautery device during percutaneous image-guided abdominal biopsy procedures in at-risk patients. METHODS: Forty-two patients (26-79 years old; female 44%) with at least one bleeding risk factor who underwent an abdominal image-guided (CT or US) biopsy and intended bipolar radiofrequency track cautery (BRTC) were retrospectively studied. An 18G radiofrequency electrode was inserted through a 17G biopsy introducer needle immediately following coaxial 18G core biopsy, to cauterize the biopsy track using temperature control. Bleeding risk factors, technical success, and adverse events were recorded. RESULTS: BRTC was technically successful in 41/42 (98%) of procedures; in one patient, the introducer needle retracted from the liver due to respiratory motion prior to BRTC. BRTC following percutaneous biopsy was applied during 41 abdominal biopsy procedures (renal mass = 12, renal parenchyma = 10, liver mass = 9, liver parenchyma = 5, splenic mass or parenchyma = 4, gastrohepatic mass = 1). All patients had one or more of the following risk factors: high-risk organ (spleen or renal parenchyma), hypervascular mass, elevated prothrombin time, renal insufficiency, thrombocytopenia, recent anticoagulation or anticoagulation not withheld for recommended interval, cirrhosis, intraprocedural hypertension, brisk back bleeding observed from the introducer needle, or subcapsular tumor location. No severe adverse events (grade 3 or higher) occurred. Two (2/41, 5%) mild (grade 1) bleeding events did not cause symptoms or require intervention. CONCLUSION: Bipolar radiofrequency track cautery was feasible and safe during percutaneous image-guided abdominal biopsy procedures. IRB approval: MBG 2022P002277.

Choline metabolites and incident cardiovascular disease in a prospective cohort of adults: Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND: The potential role for choline metabolite trimethylamine N-oxide (TMAO) in cardiovascular disease (CVD) has garnered much attention, but there have been limited data from diverse population-based cohorts. Furthermore, few studies have included circulating choline and betaine, which can serve as precursors to TMAO and may independently influence CVD. OBJECTIVE: We quantified prospective associations between 3 choline metabolites and 19-y incident CVD in a population-based cohort and tested effect modification of metabolite-CVD associations by kidney function. METHODS: Data were from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a prospective cohort with recruitment from 4 US urban centers (year 0: 1985-1986, n = 5115, ages 18-30). The analytic sample included 3444 White and Black males and females, aged 33 to 45, who attended the year 15 follow-up exam and did not have prevalent CVD. TMAO, choline, and betaine were quantitated from stored plasma (-70°C) using liquid-chromatography mass-spectrometry. Nineteen-year incident CVD events (n = 221), including coronary heart disease and stroke, were identified through adjudicated hospitalization records and linkage with the National Death Register. RESULTS: Plasma choline was positively associated with CVD in Cox proportional hazards regression analysis adjusted for demographics, health behaviors, CVD risk factors, and metabolites (hazard ratio: 1.24; 95% CI: 1.09, 1.40 per standard deviation-unit choline). TMAO and betaine were not associated with CVD in an identically adjusted analysis. There was statistical evidence for effect modification by kidney function with CVD positively associated with TMAO and negatively associated with betaine at lower values of estimated glomerular filtration rate (interaction P values: 0.0046 and 0.020, respectively). CONCLUSIONS: Our findings are consistent with a positive association between plasma choline and incident CVD. Among participants with lower kidney function, TMAO was positively, and betaine negatively, associated with CVD. These results further our understanding of the potential role for choline metabolism on CVD risk.

Metabolomic characterization of vigor to frailty among community-dwelling older Black and White men and women.

Older women and Black individuals are more likely to experience frailty. A metabolomic characterization of frailty may help inform more effective interventions aimed at improving health, reducing disparities, and preventing frailty with aging. We sought to identify metabolites and pathways associated with vigor to frailty and determine whether associations differed by sex and/or race among n = 2189 older Black and White men and women from the Health, Aging, and Body Composition (Health ABC) study. Fasting plasma metabolites were measured using liquid chromatography-mass spectrometry. Vigor to frailty was based on weight change, physical activity, gait speed, grip strength, and usual energy. We used linear regression of a single metabolite on vigor to frailty, adjusting for age, sex, race, study site, and multiple comparisons using a Bonferroni correction. Among 500 metabolites, 113 were associated with vigor to frailty (p < 0.0001). Associations between metabolites and vigor to frailty did not differ significantly by race and/or sex. Lower amino acids, glycerophospholipids, sphingolipids, and dehydroepiandrosterone sulfate and higher acylcarnitines, fatty acids, amino acid derivatives, organic acids, carbohydrates, citric acid cycle metabolites, and trimethylamine oxide were associated with frailer scores. Pathway analyses identified the citric acid cycle as containing more frailty-associated metabolites than expected by chance (p = 0.00005). Calories and protein intake did not differ by vigor to frailty. Frailer Health ABC participants may have lower utilization of energy pathways, potentially as a result of less demand and less efficient utilization of similar amounts of nutrients when compared to more vigorous participants.

Comparing the Efficacy of Paracetamol, Ibuprofen, and a Combination of the Two Drugs in Relieving Pain and Fever in the Pediatric Age Group: A Prospective Observational Study.

Introduction Fever and pain are common afflictions in the pediatric population, prompting the use of paracetamol and ibuprofen as primary treatment options. However, a comprehensive understanding of their comparative efficacy, safety profiles, and potential combined use remains crucial for informed clinical decision-making. In this prospective observational study, we aimed to delve into these aspects, shedding light on the optimal management strategies for fever and pain in pediatric patients. Methodology A total of 108 children were enrolled and categorized into three groups, namely, paracetamol monotherapy, ibuprofen monotherapy, and a combination of both drugs. Axillary temperature monitoring and assessment of pain on the Face, Legs, Activity, Cry, and Controllability (FLACC) scale/Visual Analog Scale (VAS) were employed as critical indicators. Concurrently, associated symptoms encompassing discomfort, activity levels, and appetite were meticulously recorded. To ensure safety, laboratory parameters including serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum creatinine, platelet count, and stool for occult blood were closely monitored before and after drug administration. The study duration spanned 48 hours post-initiation of the initial drug dose. Results A total of 108 pediatric cases were included in the study, spanning ages from six months to 18 years. Among them, the majority fell within the age group of six months to five years (n = 77). Participants were categorized based on the duration of fever, with 81 cases having a fever lasting more than 24 hours and 27 cases having a fever lasting less than 24 hours. The majority of cases presented with temperatures ranging from 38°C to 39°C. Comparison of drug efficacy in defervescence within the first four hours revealed that paracetamol alone took significantly longer than ibuprofen monotherapy or the paracetamol and ibuprofen combination (p = 0.026). In terms of the onset of effect, the paracetamol and ibuprofen combination showed comparable efficacy to ibuprofen alone. Regarding the total time without fever in 48 hours, significant differences were observed among the three drug regimens (p = 0.001 by the one-way analysis of variance (ANOVA) test). Paracetamol and ibuprofen were superior to paracetamol alone (p < 0.001) and ibuprofen alone (p = 0.014), while paracetamol alone and ibuprofen alone exhibited similar efficacy (p = 0.197). Based on the laboratory results as well as the clinical profile observed over 48 hours, we confirm safety based on this study. The combination of paracetamol and ibuprofen showed enhanced effectiveness in fever and pain relief. Conclusion This study demonstrates the favourable efficacy of paracetamol, ibuprofen, and their combination in the pediatric population. The combination of paracetamol and ibuprofen showed enhanced effectiveness in fever and pain relief, with minimal adverse effects and no significant derangements in biochemical parameters. This study thus contributes valuable insights to optimize the therapeutic approach to fever and pain in pediatric patients.

Eicosanoid and eicosanoid-related inflammatory mediators and exercise intolerance in heart failure with preserved ejection fraction.

Systemic inflammation has been implicated in the pathobiology of heart failure with preserved ejection fraction (HFpEF). Here, we examine the association of upstream mediators of inflammation as ascertained by fatty-acid derived eicosanoid and eicosanoid-related metabolites with HFpEF status and exercise manifestations of HFpEF. Among 510 participants with chronic dyspnea and preserved LVEF who underwent invasive cardiopulmonary exercise testing, we find that 70 of 890 eicosanoid and related metabolites are associated with HFpEF status, including 17 named and 53 putative eicosanoids (FDR q-value < 0.1). Prostaglandin (15R-PGF2α, 11ß-dhk-PGF2α) and linoleic acid derivatives (12,13 EpOME) are associated with greater odds of HFpEF, while epoxides (8(9)-EpETE), docosanoids (13,14-DiHDPA), and oxylipins (12-OPDA) are associated with lower odds of HFpEF. Among 70 metabolites, 18 are associated with future development of heart failure in the community. Pro- and anti-inflammatory eicosanoid and related metabolites may contribute to the pathogenesis of HFpEF and serve as potential targets for intervention.

Arterial Stiffness and Cardiorespiratory Fitness Impairment in the Community.

Background During exercise, a healthy arterial system facilitates increased blood flow and distributes it effectively to essential organs. Accordingly, we sought to understand how arterial stiffening might impair cardiorespiratory fitness in community-dwelling individuals. Methods and Results Arterial tonometry and maximum effort cardiopulmonary exercise testing were performed on Framingham Heart Study participants (N=2898, age 54±9 years, 53% women, body mass index 28.1±5.3 kg/m2). We related 5 arterial stiffness measures (carotid-femoral pulse wave velocity [CFPWV]: a measure of aortic wall stiffness; central pulse pressure, forward wave amplitude, characteristic impedance: measures of pressure pulsatility; and augmentation index: a measure of relative wave reflection) to multidimensional exercise responses using linear models adjusted for age, sex, resting heart rate, habitual physical activity, and clinical risk factors. Greater CFPWV, augmentation index, and characteristic impedance were associated with lower peak oxygen uptake (VO2; all P<0.0001). We observed consistency of associations of CFPWV with peak oxygen uptake across age, sex, and cardiovascular risk profile (interaction P>0.05). However, the CFPWV-peak oxygen uptake relation was attenuated in individuals with obesity (P=0.002 for obesity*CFPWV interaction). Higher CPFWV, augmentation index, and characteristic impedance were also related to cardiopulmonary exercise testing measures reflecting adverse O2 kinetics and lower stroke volume and peripheral O2 extraction but not to ventilatory efficiency, a prognostic measure of right ventricular-pulmonary vascular performance. Conclusions Our findings delineate relations of arterial stiffness and cardiorespiratory fitness in community-dwelling individuals. Future studies are warranted to evaluate whether the physiological measures implicated here may represent potential targets for improving cardiorespiratory fitness in the general population.