Search Results (3,408)

This study aimed to identify metabolomic biomarkers for diabetes progression and validate their response to lifestyle intervention. A two-phase design was employed: first, untargeted metabolomics distinguished normoglycemic, prediabetic (PDM), and diabetic (DM) individuals, identifying 1,5-anhydroglucitol (1,5-AG) as the most significant biomarker for differentiating PDM from DM (apparent AUC = 0.97, 95% CI: 0.95–1.00; corrected AUC = 0.94, 95% CI: 0.83–1.00; q < 0.001). Second, in a 3-month randomized controlled trial involving 300 adults with PDM, the combined diet and exercise intervention significantly improved fasting blood glucose and glycated hemoglobin levels, while concurrently elevating serum 1,5-AG levels compared with the control group, though it did not yield significant improvements in other cardiovascular disease-related risk factors including body mass index, waist circumference, systolic blood pressure, and diastolic blood pressure. The intervention also showed a trend toward reduced diabetes incidence. Integrated analysis establishes 1,5-AG as a sensitive biomarker of dysglycemia that is responsive to lifestyle modification, supporting its potential as a mechanistic tool for monitoring intervention efficacy in diabetes prevention. Full article

Introduction: Primary Sjögren’s (pSS) is an autoimmune disease that affects several organs, especially the heart, and raises cardiovascular risk. Investigating the associations of hemoglobin-to-red cell distribution width (RDW) ratio (HRR), vitamin D status, and cardiac function could provide valuable insights and biomarkers regarding early cardiovascular risk in patients with pSS. Method: This cross-sectional study involved 61 patients diagnosed with pSS based on ACR/EULAR criteria. Data on demographics, hematological (Hb, RDW), echocardiography, and serum vitamin D levels were collected. Echocardiograms were conducted by trained cardiologists following established guidelines, while vitamin D levels were measured using ELISA. Statistical analyses, including univariate linear regression, were performed with SPSS in order to identify whether HRR tertiles were related to cardiac function and vitamin D status. Results: A study of 61 pSS patients (mean age 59.8 years, 89% female) revealed that patients with a lower hemoglobin-to-RDW ratio (HRR ≤ 0.98) had significantly higher pulmonary artery pressures (PAPs) and lower values for the tricuspid annular plane systolic excursion (TAPSE)/PAPs ratio, contributing to poor right heart function. These associations were particularly strong in patients with insufficient levels of vitamin D (<30 ng/mL), while differences in other echocardiographic parameters remained nonsignificant between HRR groups. Conclusions: These findings underscore the clinical value of HRR as a composite biomarker that reflects the interplay between anemia, inflammation, and cardiovascular health in primary Sjögren’s disease. They also suggest that vitamin D status may be an important therapeutic consideration to mitigate cardiopulmonary risks in this population. Full article

Background: Autism Spectrum Disorder (ASD) involves social, emotional, and behavioral challenges, and conventional therapies show limited effectiveness. Aims: To evaluate the effect of Yoga Therapy (YT) on neurophysiological regulation and behavioral functioning in individuals with ASD. Methods: Thirty-six autistic individuals, aged 6 to 25 years and with Childhood Autism Rating Scale (CARS) scores above 15, were randomly assigned to yoga (YG) and control (CG) groups. YG received 60 min YT sessions twice weekly for six months alongside a regular school routine, while CG followed only a regular school routine. Handgrip strength (HGS), visual reaction time (VRT), systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR), and CARS scores were assessed at pre-, mid-, and post-intervention. Repeated measures ANOVA and Pearson’s correlation were used for statistical analysis. Results: The study showed an increase in HGS (Δ = 3.27 kg) and a reduction in VRT (Δ = −523.86 ms) with a marked decrease in total CARS score (Δ = −5.67), p < 0.01 in YG. There was a mild, non-significant reduction in cardiovascular (CV) dysfunction in YG, while CG showed no significant changes across all measures. Conclusion: Biweekly YT sessions over six months enhanced neurophysiological regulation, improving sensorimotor integration and accelerating cognitive, emotional, and behavioral outcomes in individuals with ASD. Full article

Background/Objectives: Under general anesthesia, maintaining patients’ blood pressure (BP) is important to prevent organ ischemia. When bleeding occurs, it is sometimes difficult to increase BP with boluses of fluids or transfusions, and vasoconstrictors must be administered. This study investigated circulatory dynamic changes in patients who bled during surgery and were administered phenylephrine, particularly left ventricular end-diastolic volume (EDV), effective arterial elastance (Ea), and left ventricular end-systolic elastance (Ees), calculating each value from the left ventricular–arterial coupling (Ees/Ea). Methods: We calculated Ees/Ea using electrocardiograms, arterial pressure waveforms, and phonocardiograms using an esophageal stethoscope. We investigated the changes in patients’ EDV, Ea, and Ees during two periods: phenylephrine administration and after BP elevation. Results: The seven participants comprised three men and four women. Between the two periods, linear mixed-model analysis revealed that mean arterial pressure (MAP), Ea, and Ees significantly increased over time (MAP; β = 8.7, p < 0.01, Ea; β = 0.22, p < 0.05, Ees; β = 0.73, p < 0.05), while no significant changes were observed in other parameters such as heart rate and EDV. Conventional parameters demonstrated that stroke volume variation significantly decreased (β = −2.0, p = 0.01), systemic vascular resistance index significantly increased (β = 200, p < 0.01), while no significant change was observed in cardiac index (β = −0.03, p = 0.7). In patients administered phenylephrine due to BP decrease from bleeding, significant changes in afterload and cardiac contractility occurred without changes in preload. Conclusions: Our noninvasive method for calculating EDV, Ea, and Ees can be valuable for monitoring hemodynamics under anesthesia. Full article

The quality of high-density lipoproteins (HDLs) is characterized by lipid and protein composition, oxidation and glycation extent, and particle size, while the quantity of HDL-C is just the cholesterol amount in HDL. The inverse association between HDL-C and cardiovascular disease (CVD) and hypertension has been well established; however, the U-shaped mortality risk observed from HDL-C underscores that HDL quality and function are equally important. The present cross-sectional study assessed the correlations of serum lipid and glucose profiles, and low-density lipoprotein (LDL) and HDL characteristics, with blood pressure (BP) distribution in ordinary middle-aged Korean participants (n = 50; mean age 47.0 ± 11.7 years; males: n = 25, 49.2.0 ± 11.7 years; females: n = 25, 44.8 ± 11.5 years), with particular focus on HDL quality and its antioxidant capacity. This study observed that serum elevated triglyceride (TG) and glucose levels were directly proportional to elevated systolic BP (SBP) and diastolic BP (DBP), whereas serum total cholesterol (TC), LDL-C, and HDL-C were not correlated with BP. However, HDL-C/TC (%) was negatively associated with SBP (p = 0.036), while TG/HDL-C and glucose/HDL-C ratios were positively associated with both SBP and DBP, suggesting that TG and glucose proportions relative to HDL-C are probable predictors of hypertension. Elevations of TG, oxidation, and glycation in LDL were positively associated with elevations of BP, whereas LDL particle size was negatively correlated with BP. Similarly, elevations of TG and glycation in HDL₂ and HDL₃ were positively correlated with elevations of BP, while the particle size of HDL₂ was negatively correlated with BP. The heightened HDL₂-associated paraoxonase (PON) activity and ferric ion reduction ability (FRA) negatively correlated with LDL oxidation and particle size, whereas elevated HDL₃-associated PON and FRA activities were inversely related to LDL glycation. An enhanced glycation in HDL₂ was negatively correlated with HDL₂-associated PON activity and FRA, while an increase in HDL₂ particle size was only dependent on the associated PON activity but not on FRA. In conclusion, observational outcomes demonstrated that improved HDL quality and functionality (characterized by large particle size, reduced glycation, and higher FRA and PON activities) were inversely correlated with LDL oxidation, glycation, particle shrinkage, and the risk of hypertension. Full article

Objectives: Prediabetes is characterized by elevated blood glucose levels associated with insulin resistance, increasing the risk of progression to type 2 diabetes mellitus (T2DM) and cardiovascular disease. High-intensity interval training (HIIT) has emerged as an effective non-pharmacological strategy to improve insulin sensitivity and cardiorespiratory fitness. This study aimed to analyze the effects of HIIT alone or combined with a hypocaloric diet on metabolic and cardiorespiratory parameters in individuals with prediabetes. Methods: A controlled, longitudinal, single-blind intervention study enrolled 68 adults with prediabetes (mean age 42.22–46.60 years; 73.5% women) and randomized them to HIIT plus hypocaloric diet (n = 23), HIIT only (n = 23), or hypocaloric diet only (n = 22) for 13 weeks, with pre/post assessments of glucose, VO₂max, blood pressure, FINDRISC. Results: Significant post-intervention differences were observed among groups in body mass index (p = 0.049), VO₂max (p < 0.001), fasting glucose (p < 0.001), systolic blood pressure (p < 0.001), and diabetes risk (p = 0.038), with the greatest improvements consistently observed in Group A. In Group A, fasting glucose decreased from 111.94 to 91.28 mg/dL (−20.66 mg/dL; −18.5%), VO₂max increased from 21.27 to 24.02 mL·kg⁻¹·min⁻¹ (+2.75; +12.9%), and systolic blood pressure decreased from 163.56 to 150.13 mmHg (−13.43 mmHg; −8.2%). No significant between-group differences were found for body weight (p = 0.271) or waist circumference (p = 0.174). Conclusions: HIIT combined with a hypocaloric diet is an effective and safe strategy for managing prediabetes, producing superior improvements in cardiorespiratory fitness, glycemic control, and reduction in diabetes risk compared with either intervention alone. Full article

Background/Objectives: Insulin resistance and ambulatory blood pressure monitoring (ABPM) abnormalities represent distinct but interrelated pathways contributing to cardiovascular risk. The triglyceride–glucose (TyG) index reflects metabolic burden, whereas arterial load—captured through arterial stiffness, blood pressure variability, and morning surge—reflects hemodynamic instability. Whether the coexistence of these domains identifies a particularly high-risk ambulatory phenotype remains unclear. To evaluate the independent and combined effects of metabolic burden (TyG) and arterial load on circadian blood pressure pattern and short-term systolic blood pressure variability. Methods: This retrospective cross-sectional study included 294 adults who underwent 24 h ABPM. Arterial load was defined using three ABPM-derived indices (high AASI, high SBP-ARV, high morning surge). High metabolic burden was defined as TyG in the upper quartile. The “double-high” phenotype was classified as high TyG plus high arterial load. Primary and secondary outcomes were non-dipping pattern and high SBP variability. Multivariable logistic regression and Firth penalized models were used to assess independent associations. Predictive performance was evaluated using ROC analysis. Results: The double-high phenotype (n = 15) demonstrated significantly higher nighttime SBP, reduced nocturnal dipping, and markedly elevated BP variability. It was the strongest independent predictor of non-dipping (adjusted OR = 42.0; Firth OR = 11.73; both p < 0.001) and high SBP variability (adjusted OR = 41.7; Firth OR = 26.29; both p < 0.001). Arterial load substantially improved model discrimination (AUC = 0.819 for non-dipping; 0.979 for SBP variability), whereas adding TyG to arterial load produced minimal incremental benefit. Conclusions: The coexistence of elevated TyG and increased arterial load defines a distinct hemodynamic endotype characterized by severe circadian blood pressure disruption and exaggerated short-term variability. While arterial load emerged as the principal determinant of adverse ambulatory blood pressure phenotypes, TyG alone demonstrated limited discriminative capacity. These findings suggest that TyG primarily acts as a metabolic modifier, amplifying adverse ambulatory blood pressure phenotypes predominantly in the presence of underlying arterial instability rather than serving as an independent discriminator. Integrating metabolic and hemodynamic domains may therefore improve risk stratification and help identify a small but clinically meaningful subgroup of patients with extreme ambulatory blood pressure dysregulation. Full article

Mitochondrial dysfunction contributes to impaired myocardial energetics and performance in heart failure with preserved ejection fraction (HFpEF). Elamipretide (Ela) enhances mitochondrial bioenergetics in preclinical models, yet its relevance in HFpEF remains unclear. This study examined the effects of Ela on cardiac mitochondrial function, structure, and cardiovascular performance in a rodent HFpEF model. Female obese ZSF1 rats received vehicle or Ela for 12 weeks, with age-matched lean rats as controls. Cardiac function and hemodynamics were assessed by echocardiography and pressure–volume analysis. Mitochondrial respiration was measured in permeabilized fibers and ultrastructure evaluated by transmission electron microscopy. Molecular and histological analyses included cardiolipin lipidomics and mRNA/protein profiling of hypertrophic, fibrotic, and inflammatory markers. Ela modestly improved complex I and II respiration, whereas mitochondrial ultrastructure, cardiolipin composition, and tafazzin expression were unchanged. Diastolic dysfunction persisted, reflected by unchanged E/é, ventricular stiffness factor β, and titin phosphorylation. Compared to untreated HFpEF, systolic performance showed a mild decline, with small reductions in LV ejection fraction and end-systolic elastance. Accordingly, cardiac remodeling, including hypertrophy, fibrosis, and inflammatory activation, remained unaltered. Vascular stiffness slightly increased, while carotid reactivity and morphology were preserved. In conclusion, despite enhanced mitochondrial respiration following Ela treatment, no functional or structural benefits were observed in experimental HFpEF, suggesting limited therapeutic efficacy once HFpEF is established. Full article

Background/Objectives: Hypertension control remains a global challenge. Evidence on the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and blood pressure (BP) control in older Mediterranean populations is limited. We aimed to assess this association in Spanish older adults. Methods: This cross-sectional analysis included 371 participants (69 ± 9 years). Dietary intake was assessed using a validated 146-item food frequency questionnaire (FFQ), and DASH diet adherence was categorized as low, medium, or high. Multivariable logistic regression models were used to examine associations with BP control. Results: Among participants with hypertension (n = 218), 52.8% achieved adequate BP control and consumed significantly more low-fat dairy products (+56%) and less sodium (−11%) than those with uncontrolled BP. The low adherence group had lower proportion of participants with controlled BP (21%) than the medium and high adherence groups (36% and 39%, respectively) (p < 0.05). Across increasing DASH diet adherence categories, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 4–5 mmHg and 3–4 mmHg lower, respectively. Medium adherence to the DASH diet was independently associated with substantially lower odds of uncontrolled BP (OR = 0.37; 95% CI: 0.16–0.82; p = 0.015). High adherence showed a similar magnitude of association but did not reach statistical significance. Conclusions: In this cohort of older Spanish adults, moderate adherence to the DASH diet was associated with meaningful improvements in BP control, suggesting that achievable, intermediate levels of DASH diet adherence may be sufficient to improve hypertension management in real-world settings. Longitudinal studies are needed to confirm causality and long-term cardiovascular benefits. Full article

Background: The management of spontaneous intracerebral hemorrhage (ICH) has centered around controlling blood pressure in order to prevent hematoma expansion (HE). Rate-pressure product (RPP) has emerged as a hemodynamic marker that accounts for heart rate (HR) and systolic blood pressure (SBP), both of which are crucial in modifying shear stress to the vasculature. We hypothesized that RPP in the pre-hospital hyperacute phase is positively associated with initial hematoma volume and HE. Methods: We analyzed 263 patients with primary ICH from the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) study with initial and interval neuroimaging. RPP was calculated as the product of HR and SBP in pre-hospital and pre-treatment phases, stratified into quintiles. HE was defined by volume expansion of >6 mL or >33% from baseline volume on repeat neuroimaging performed within 48 h of the first scan. The primary outcome was the initial hematoma volume by quintiles of hyperacute RPP. The secondary outcome was the occurrence of HE across RPP quintiles. Multivariable logistic regression was used to assess the degree to which RPP affects HE. Results: Of the 263 patients analyzed, 116 (44%) had HE. The proportion of patients with HE or the initial hematoma volume was not statistically significant across RPP quintiles overall. HE was significantly more common in female patients or patients on anticoagulation. Conclusions: Elevated RPP was not associated with increased initial hematoma volume or subsequent HE in the hyperacute period after spontaneous ICH. Future research is necessary to determine the clinical importance of RPP as a biomarker in the clinical outcome of ICH. Full article

Thiazides are among the most efficacious and commonly used drugs for the treatment of hypertension. The nanomolar stabilizer N3SA binds specifically to the recently discovered thiazide-binding site of the membrane target NAPE-PLD, showing sustained arterial blood pressure-lowering effects and vasodilation in spontaneous hypertensive rats (SHRs). To further support the relation between stabilizers anchored to NAPE-PLD and their beneficial effects on hypertension, we selected compound analogues of N3SA with chemical modifications at the three target-interacting sulfonic groups, including the drug Suramin. Each compound was injected i.v in an adult SHR (systolic blood pressure of 217 ± 5 mmHg) to evaluate the frequency components contribution to cerebral and peripheral arteriolar vasomotion. We visualized the pial and rectus femoral muscle microcirculation by Epi-illumination, measuring changes in the rhythmic arteriolar diameter. Findings showed that the minor structural differences in compounds correlated with the contribution of the six different frequency components affecting the arterial tone, as well as their vasodilatory effects, in both cerebral and femoral muscle arterioles. These results provide evidence that the spectra analysis of the regulation mechanisms of vascular tone and arterial blood pressure can accurately reflect the structure–activity correlations of different analogues of an antihypertensive compound. Full article

Pediatric obesity is a growing public health concern, significantly increasing the risk of metabolic and cardiovascular comorbidities. Background/Objectives: This study aims to explore the burden of obesity, its associated comorbidities, and resting metabolic rate (RMR) assessed by indirect calorimetry among children and adolescents in a cohort of 223 participants from Nord-East of Romania. Methods: A cross-sectional study was conducted among 223 children and adolescents (aged 4–18 years) who were diagnosed with obesity at Saint Mary Emergency Children’s Hospital Iași. Anthropometric measurements, clinical assessment, and biochemical parameters were recorded. RMR was measured by indirect calorimetry, using the Fitmate Pro Metabolic Technology (Cosmed, Rome, Italy), under a stable environment for 15 min, following a fasting period of minimum 6–8 h. Data were analyzed using SPSS 22.0, applying descriptive statistics and Pearson correlations. Results: A total of 223 participants were included in the analysis, with a mean age of 12.03 ± 3.32 years (range 4–17 years) and a mean body mass index (BMI) of 31.21 ± 5.84 kg/m². The average RMR was 1687.5 ± 425.5 kcal/day, with higher values in males compared with females. RMR showed significant positive correlations with age (r = 0.60), BMI (r = 0.51), waist circumference (r = 0.67), and fat mass measured with a three-site formula technique (r = 0.51) and systolic (r = 0.45) and diastolic blood pressure (r = 0.19), all with p < 0.001. A weak inverse correlation was observed between RMR and the fitness index (r = −0.24, p < 0.001), indicating an association between lower fitness scores and higher RMR values. RMR showed no significant correlation with fasting glucose or lipid levels, indicating that metabolic rate was more influenced by body composition than by biochemical markers. Conclusions: Pediatric obesity is strongly linked to multiple comorbidities, emphasizing the need for early detection and targeted interventions. Higher BMI and central adiposity were associated with increased RMR. Indirect calorimetry provides valuable insights into the metabolic profile of children with obesity and can inform individualized management strategies. Full article

Background: The differentiation of pheochromocytoma (PCC) from other adrenal lesions, particularly in incidentalomas with non-benign radiological characteristics (size > 4 cm or density > 10 HU), remains a clinical challenge. The study aimed to develop and validate an interpretable machine learning (ML) model for pairwise differentiation of PCC from adrenocortical carcinomas (ACCs) and non-functioning adrenal adenomas (NAAs) and to identify the most important clinical features. Methods: We analyzed a dataset of 50 clinical, laboratory, and radiological parameters from 123 patients with histologically verified adrenal tumors (63 PCC, 30 ACC, 30 NAA). Four classifiers—Logistic Regression (LR), Random Forest (RF), Linear Discriminant Analysis (LDA), and Extreme Gradient Boosting (XGBoost)—were trained for binary classification tasks (PCC vs. ACC, PCC vs. NAA, ACC vs. NAA) using a robust nested stratified cross-validation pipeline to ensure generalizability and avoid overfitting. Results: All four models showed strong predictive performance, with discrimination (AUC) more than 0.8. Our analysis, based on the interpretable LR model, identified the key discriminators differentiated PCC from both ACC and NAA: maximum systolic blood pressure, grade 3 hypertension, headache, palpitation, tachycardia, male sex, and concomitant gastric and duodenal ulcers. In contrast, lower back pain and general weakness were strong signs of lower probability of PCC. The tumor density specifically differentiated PCC from NAA, whereas tumor size was an important marker for distinguishing PCC and ACC. Conclusions: We developed robust ML models capable of accurately differentiating PCC from other adrenal tumors in complex cases. The models provide a clinically actionable tool for pre-surgical decision support. Furthermore, the identification of key discriminative features enhances the clinical understanding of PCC and facilitates its differential diagnosis prior to histological verification. Full article

Background: Prolonged sitting has been associated with adverse cardiovascular and neuromuscular responses; however, the temporal onset of these acute physiological changes remains unclear. This study aimed to determine the acute effects of prolonged sitting on blood flow, blood pressure, and muscle activity. Methods: A non-controlled clinical trial was conducted with 21 healthy adults (22.5 ± 1.60 years), both male and female. Participants remained seated continuously for three hours, with data collected every 20 min, including infrared thermography, blood pressure, and electromyographic activity. Skin temperature was measured using infrared thermography on the calf region of both legs, and the mean temperature was analyzed. Systolic and diastolic blood pressure were measured using an oscillometric device, and mean arterial pressure was subsequently calculated. Muscle activity was assessed through surface electromyography, using median frequency and root mean square values. Statistical analysis was performed using the Friedman test and the Durbin–Conover post hoc test, along with a subjective trend analysis of each variable over time. Results: A significant reduction was observed in both calf skin temperature and median frequency after 60 min of uninterrupted sitting (p < 0.05). Mean and systolic blood pressure exhibited an increasing trend after 160 min (p < 0.05). Conclusions: The exposure–response data from this study may contribute to the planning of future interventions aimed at refining recommendations for breaking up prolonged sitting periods. Full article

Individuals born after intrauterine growth restriction (IUGR) are at increased risk of long-term cardiovascular complications, including elevated blood pressure, endothelial dysfunction, and arterial stiffness. Endothelial progenitor cells (EPCs), particularly endothelial colony-forming cells (ECFCs), play a critical role in maintaining vascular homeostasis. Previously, Simoncini et al. observed that in a rat model of IUGR, six-month-old males exhibited elevated systolic blood pressure (SBP) and microvascular rarefaction compared with control (CTRL) rats. These vascular alterations were accompanied by reduced numbers and impaired function of bone marrow-derived ECFCs, which were associated with oxidative stress and stress-induced premature senescence (SIPS). In contrast, IUGR females of the same age and from the same litter did not exhibit higher SBP or microvascular rarefaction, raising the question of whether ECFC dysfunction in IUGR female rats can be present without vascular alterations. So, we investigated ECFCs isolated from six-month-old female IUGR offspring (maternal 9% casein diet) and CTRL females (23% casein diet). To complete the vascular assessment, we performed in vivo and in vitro investigations. No alteration in pulse wave velocity (measured by echo-Doppler) was observed; however, IUGR females showed decreased aortic collagen and increased elastin content compared with CTRL. Regarding ECFCs, those from IUGR females maintained their endothelial identity (CD31⁺/CD146⁺ ratio among viable CD45⁻ cells) but exhibited slight alterations in progenitor marker expression (CD34) compared with those of CTRL females. Functionally, IUGR-ECFCs displayed a delayed proliferation phase between 6 and 24 h, while their ability to form capillary-like structures remained unchanged, however their capacity to form capillary-like structures was preserved. Regarding the nitric oxide (NO) pathway, a biologically relevant trend toward reduced NO levels and decreased endothelial nitric oxide synthase expression was observed, whereas oxidative stress and SIPS markers remained unchanged. Overall, these findings indicate that ECFCs from six-month-old female IUGR rats exhibit only minor functional alterations, which may contribute to vascular protection against increase SBP, microvascular rarefaction, and arterial stiffness. Full article