Search Results (10,194)

Type 1 diabetes (T1DM) is associated with elevated cardiovascular (CV) risk, often exacerbated by the rising prevalence of obesity. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce CV risk in type 2 diabetes, but their role in T1DM is less well-defined. This umbrella review synthesizes evidence from systematic reviews, meta-analyses, and Mendelian Randomization (MR) studies to evaluate the metabolic efficacy and safety of GLP-1 RAs in T1DM. Adjunctive therapy, particularly with liraglutide and exenatide, was associated with clinically meaningful weight reduction (mean difference: −4.35 kg to −5.1 kg) and lower total daily insulin doses. HbA1c reductions were statistically significant but modest (0.2–0.3%), with no improvement in Time in Range. Secondary benefits included lower systolic blood pressure. Safety data were mixed: the risk of severe hypoglycemia was not increased, whereas Time Below Range and gastrointestinal adverse events were more frequent. Evidence on diabetic ketoacidosis (DKA) was inconsistent across studies. Overall, GLP-1 RAs improve weight and reduce insulin requirements in T1DM, potentially mitigating indirect CV risk factors; however their direct cardiovascular benefits remain unproven in the absence of dedicated outcome trials. Full article

Background: Cardiorenal syndrome (CRS) arises from interconnected cardiovascular, renal, and metabolic dysfunction driven by shared risk factors such as hypertension, diabetes, and obesity. Cardiac rehabilitation (CR) is a multidisciplinary intervention; however, its impact on CRS risks remains unclear. Methods: This retrospective cohort study analyzed electronic medical record data from 394 participants enrolled in a three-month CR program. Baseline and post-program measures included functional capacity, cardiometabolic risk factors, and psychosocial outcomes. Results: Participants (mean age 62.44 ± 12.15 years; 66.8% male) had a high burden of CRS risk factors, including hypertension (85.8%), diabetes (60.6%), and obesity (57.8%). Significant improvements were observed in functional capacity (6 min walk distance increased by 213 m, p < 0.001), muscular strength, flexibility, and psychosocial outcomes (anxiety, depression, perceived health; all p < 0.001). In contrast, changes in CRS risk factors were modest: fasting blood glucose decreased slightly (p = 0.043), while HbA1c, body fat, and cholesterol showed no significant change. Systolic blood pressure and body weight increased significantly. Cardiac rehabilitation improves functional and psychosocial outcomes but demonstrates limited short-term impact on CRS risk factors. Conclusions: These findings suggest CR may serve as an initial platform for CRS risk modification but requires integration with comprehensive cardio–renal–metabolic management strategies. Full article

Background: Blood flow restriction (BFR) training induces morphological and neuromuscular adaptations using low-intensity exercise (20–40% 1RM), offering a reduced mechanical load alternative to traditional high-load resistance training. Safe and effective implementation, however, requires a clear understanding of physiological mechanisms, contraindications, and pressure determination methodologies. In this three-part series, we provide a comprehensive review of BFR for athletic populations and provide strength and conditioning coaches with a structured framework for screening, safety, and methodological considerations to support BFR integration in high-performance settings. Methods: A narrative review of the literature examining BFR safety, contraindication screening, adverse event reporting, and occlusion pressure determination was conducted using a PubMed and MEDLINE search. Search terms included combinations of (“blood flow restriction” OR “BFR” OR “occlusion training” OR “KAATSU”) AND (“safety” OR “contraindications” OR “risk stratification”) AND (“arterial occlusion pressure” OR “limb occlusion pressure” OR “occlusion pressure” OR “Doppler” OR “handheld Doppler” OR “pulse oximetry” OR “cuff width” OR “capillary refill time” OR “monitoring”). Studies examining contraindication screening systems, arterial occlusion pressure calculation methods, and real-time monitoring protocols were evaluated. Primary considerations included risk stratification frameworks, pressure determination accuracy, and control parameter validation for ensuring vascular safety during application. Results: Risk stratification systems can effectively identify absolute and relative contraindications requiring medical clearance prior to BFR use. Epidemiological data indicate that adverse events are transient and non-serious, while serious events appear rare when evidence-informed protocols are applied. Doppler-based assessment remains a criterion approach for determining inflation pressure, although validated estimation methods using limb circumference and systolic blood pressure offer a pragmatic and comparable alternative for applied environments. Inflation pressures of 50–80% arterial occlusion, adjusted for cuff width, produce effective and safe stimulus. Real-time monitoring through capillary refill time, pulse strength palpation, and skin coloration can support iterative pressure optimization and help identify excessive restriction pressures. Conclusions: BFR implementation in athletic populations requires systematic screening protocols, individualized inflation pressure determination using validated methods, and real-time monitoring parameters. These foundations provide the essential safety infrastructure required before progressing to specific training applications across resistance, cardiovascular, and other performance and rehabilitation modalities. Full article

Background/Objectives: Uncontrolled hypertension (UH), defined as markedly elevated blood pressure without acute target organ damage, is a clinically relevant condition in which psychological burden remains poorly characterized. We aimed to assess the psychological burden of patients with UH and compare it with that of outpatient hypertensive (HTN) and normotensive (NT) individuals. Methods: In this multicenter cross-sectional study, 191 patients with UH, 56 with HTN, and 89 NT individuals were enrolled across six Italian hospitals. Participants completed validated self-report scales assessing anxiety, depressive symptoms, and psychological distress (HADS), perceived stress (PSS-10), and Type D personality traits (DS-14). Statistical analyses included nonparametric group comparisons and multivariable logistic regression with bootstrap resampling. Results: UH patients showed significantly higher levels of anxiety, depressive symptoms, and psychological distress than both control groups (all p < 0.001). Clinically relevant anxiety was observed in 41.9% of UH patients, compared with 25.0% of HTN and 19.1% of NT participants; depressive symptoms were present in 34.6%, 19.6%, and 12.4%, respectively, and psychological distress in 38.7%, 23.2%, and 14.6%, respectively. Perceived stress was higher in UH than in NT individuals (p < 0.001), as were overall Type D personality traits (p = 0.016). In multivariable analysis, higher heart rate, smoking, depressive symptoms, dyslipidemia, and prior hypertension were independently associated with UH vs. HTN. Conclusions: UH patients exhibit a substantial psychological burden. In this Italian sample, screening for anxiety and depression in patients with UH should be considered in routine clinical practice. Full article

Neonatal infections remain a leading cause of morbidity and mortality worldwide, particularly among preterm and low-birth-weight infants and in low- and middle-income countries. This burden has intensified with the global increase in multidrug-resistant (MDR) bacteria, especially in neonatal intensive care units, where prolonged hospitalization, invasive interventions, and exposure to broad-spectrum antibiotics promote colonization, transmission, and invasive infection. In this narrative review, we explore the epidemiology and microbiological characteristics of MDR bacterial infections in newborns, alongside their associated risk factors, diagnostic challenges, treatment outcomes, and prevention strategies. Across different settings, Gram-negative pathogens, particularly Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii, account for a substantial proportion of severe neonatal infections, whereas methicillin-resistant Staphylococcus aureus remains important in selected units. The risk of MDR infection is driven by a complex interplay of factors, ranging from maternal and perinatal exposures to the inherent immunological vulnerability of newborns, hospital-based transmission, antibiotic selection pressure, and structural deficiencies in healthcare infrastructure. Diagnosis remains challenging because clinical presentations are nonspecific and culture-based methods are constrained by low blood volumes, prior antimicrobial exposure, and delayed turnaround times. Treatment is increasingly complicated due to resistance to standard empirical regimens, substantial regional variation in susceptibility profiles, and limited neonatal pharmacokinetic and safety data for reserve agents. Current evidence mainly supports surveillance-informed empirical therapy, susceptibility-guided treatment adjustment, antimicrobial stewardship, and strict infection prevention measures. Future progress will require neonatal-specific clinical trials, harmonized surveillance systems, stronger molecular epidemiology, and more equitable access to microbiological diagnostics and effective treatment. Full article

Blood pressure monitoring is important for overall health assessment, yet traditional cuff-based methods are intrusive and unsuitable for continuous monitoring. This paper proposes a contactless approach for blood pressure estimation from facial videos using a bidirectional Mamba-based architecture with uncertainty quantification. Our method processes 64-frame video segments through a hierarchical 3D convolutional encoder to extract spatiotemporal features, then applies bidirectional state-space modeling to capture temporal dynamics efficiently. The model was evaluated on the Vitals for Vision (V4V) dataset, achieving mean absolute errors of 13.15 mmHg for systolic and 9.56 mmHg for diastolic blood pressure, outperforming prior methods while requiring significantly fewer computational resources than attention-based approaches. While these results do not meet clinical-grade diagnostic standards, they demonstrate the feasibility of contactless blood pressure estimation for non-clinical applications such as wellness monitoring, preliminary health screening, and continuous remote observation, where unobtrusive and computationally efficient monitoring is desirable. Full article

Introduction: Distress during pediatric magnetic resonance imaging (MRI) neuroimaging can compromise scan quality and negatively impact children’s experiences. This review aimed to systematically synthesize biomarkers and psychological factors associated with distress in children, adolescents, and young adults undergoing neuroimaging. Methods: This systematic review was conducted according to PRISMA and AMSTAR-2 guidelines and preregistered in OSF. A systematic search was performed in six electronic databases, including observational articles published between 2000 and 2025 that assessed distress during MRI and functional MRI (fMRI). Data extraction and risk of bias assessment (QUIPS tool) were performed independently by two reviewers. Results: Ten studies (n = 558) examining distress during neuroimaging were included in this review. Distress was assessed through subjective self- and parent-reports, objective physiological measures, and qualitative interviews. Overall, distress levels were low to moderate; most participants tolerated scans well, though younger age, male sex, parental anxiety, procedure length, and chronic illness were associated with greater discomfort. Noise, immobility, and boredom emerged as the most frequent triggers, while strategies such as distraction, age-appropriate information, and reducing waiting times were perceived as helpful. Among participants with cancer, scan-related anxiety was closely linked to fear of recurrence and perceived stress. Risk of bias across studies was moderate to high, particularly in domains of attrition and statistical reporting. Conclusions: Distress during scanning is driven by anticipatory and parental anxiety, procedure length, and chronic illness. Biomarkers (e.g., cortisol, blood pressure) showed inconsistent links with subjective distress, highlighting the need for integrated measures. Full article

Blood pressure is a central marker of cardiovascular risk, but continuous monitoring remains difficult because cuff-based measurements are intermittent and uncomfortable. Photoplethysmography (PPG) is already ubiquitous in wearables and can, in principle, enable cuffless blood pressure estimation from a single optical signal. However, many deep learning approaches that perform well in floating-point are impractical for microcontroller-class devices, where memory budgets, latency, and integer-only arithmetic constrain what can be deployed. A key open question is which neural architectures retain accuracy after full-integer quantization, rather than only under desktop inference. Here, we show an end-to-end, microcontroller-oriented evaluation framework that benchmarks multiple 1D convolutional models for cuffless systolic and diastolic pressure estimation from single-channel PPG, jointly optimizing estimation error, model footprint, and quantization robustness. We find that floating-point accuracy alone is a poor predictor of deployability: some lightweight CNNs exhibit substantial performance drift after INT8 conversion, whereas a compact residual 1D CNN preserves its predictions with near-identical error statistics after integer quantization. We then deploy the selected integer-only model on an STM32N6 microcontroller using an industrial toolchain and confirm that on-device inference maintains low bias and limited error dispersion while meeting real-time constraints for continuous operation. These results highlight architecture-dependent quantization stability as a critical design dimension for sensor-edge intelligence and support the feasibility of fully on-device cuffless blood pressure monitoring without multimodal sensing or cloud processing. Full article

Hypertension affects approximately 1.4 billion people worldwide. It is worth noting that it is also found in approximately 4% of children, with about half of pediatric patients having primary hypertension. Despite its widespread prevalence, the pathogenesis of primary hypertension remains poorly understood. Among the many hypotheses, research into epigenetic factors, primarily microRNA, has gained momentum in recent years. The role of microRNA is to bind to mRNA and thus influence protein translation. It is postulated that the main sites where microRNA influences blood pressure are the vascular wall, vascular smooth muscle cells, and the kidney. Many microRNAs have been identified whose importance in primary hypertension development has been demonstrated in experimental and human studies. This article discusses in detail the significance of microRNA-16, -21, -27a, -27b, -133a, and -145. It presents the current state of knowledge, as well as the challenges, limitations, and uncertainties regarding the use of these fascinating molecules as biomarkers and in potential therapy. MicroRNAs are an extremely promising area of research into the pathogenesis of primary hypertension. However, we still do not know whether they will prove to be a promising biomarker of primary hypertension. Full article

Diabetes complications may increase frailty rates among the elderly, leading to falls, immobility, dependency, hospitalizations, and death. The study aimed to assess any association between frailty status and glycaemic control among older adults with type 2 diabetes mellitus at Kenyatta National Hospital, Kenya. We conducted a cross-sectional study of 430 older individuals aged 60+ years with type 2 diabetes at a specialized diabetes clinic using a modified FRAIL scale. Mean age was 69.1 years; 65.7% were female and 76.2% completed primary school. Frailty prevalence was 3.8%, pre-frailty constituted 24.3%, and robust/non-frail comprised 71.9%. It was associated with age, social status, health knowledge, duration of DM, blood pressure, body mass index, high-density lipoprotein-C, and renal failure. Mean fasting plasma glucose (FPG) was 8.7 mmol/L, with 60% having FPG > 7 mmol/L; mean glycated haemoglobin (HbA1C) was 8.0%, with 41% having HbA1C > 8%. Glycaemic control was correlated with number of medications, blood pressure, and lipidaemia, but not age, sex, or social status. No correlation was found between frailty and glycaemic control: frailty versus FPG (r = 0.038, p = 0.459; χ² = 0.699, p = 0.705) and HbA1C (r = −0.009, p = 0.877; χ² = 0.046, p = 0.977). Low frailty prevalence was noted, with no association to glycaemic control. Our findings provide evidence for conducting frailty assessments in chronic disease care. Full article

Background/Objectives: Sphingosine-1-phosphate (S1P) is implicated in glycemic control. However, its circulating levels and clinical significance in type 2 diabetes mellitus (T2DM) remain controversial. We assessed plasma S1P levels in T2DM patients, its associations with metabolic parameters and complications, and explored its biomarker potential and non-linear (U-/J-shaped) relationships. Methods: This cross-sectional study enrolled 140 patients with T2DM and 63 matching healthy controls. Plasma S1P was measured by competitive ELISA. Statistical analyses included comparisons, correlation, ROC analysis, multivariable logistic regression, and quadratic/spline regression for U-shaped relationships. Results: Plasma S1P was significantly elevated in T2DM patients [1256.7 (149.4–1510.0) ng/mL] compared to controls [1075.1 (202.0–1510.0) ng/mL; p < 0.001]. S1P correlated positively with age, disease duration, HbA1c, insulin resistance, TyG index, triglycerides, systolic blood pressure, and negatively with HDL-C. Patients with complications had higher S1P than those without (p = 0.001), with progressive increases from retinopathy to nephropathy to mixed complications. Insulin-treated patients exhibited the highest S1P levels (p < 0.001). ROC analysis showed moderate diagnostic accuracy (AUC = 0.724). S1P is an independent associated factor with complications (OR = 1.18 per 100 ng/mL, p = 0.003). Non-linear analysis revealed a U-shaped relationship with HDL-C (optimal S1P: 1100–1350 ng/mL) and a J-shaped relationship with complication risk (threshold ~1250 ng/mL). Conclusions: Plasma S1P is elevated in T2DM and correlates with disease severity, glycemic control, insulin resistance, and complications. S1P demonstrates moderate biomarker potential and exhibits non-linear U-/J-shaped relationships with metabolic parameters, suggesting an optimal therapeutic window of 1100–1280 ng/mL. These findings support S1P as a marker of cumulative disease burden and a potential therapeutic target. Full article

Zinc-α2-glycoprotein (ZAG) is a novel adipokine with a plethora of functions meaningful for the regulation of adipose tissue and insulin sensitivity. Despite research, the role of ZAG in the course of childhood obesity is not fully understood. The aim of this study is to investigate whether the levels of ZAG can be used as a predictive or monitoring biomarker of adolescent obesity. Secondly, to determine the cut-off value of ZAG in blood serum in adolescents with obesity. The study included a group of 77 adolescent patients, including 59 obese patients, and 18 without obesity as healthy control subjects. All study participants had their biochemical parameters assessed by a certified medical laboratory. The recommendations of the Polish Society of Hypertensions were used to assess the blood pressure measurements in each group. ELISA enzyme immunoassays (R&D Systems, Minneapolis, MN, USA) were used to detect serum levels of ZAG. Our study showed that obese children and adolescents have significantly higher body mass, cholesterol, LDL-cholesterol, triglycerides (TG), systolic blood pressure (SBP) and diastolic blood pressure (DBP), but lower serum ZAG levels compared to the healthy control subjects. Furthermore, in our study, we found that median ZAG values were comparable between females and males within the same obesity category (median female ZAG level: 2.84, median male ZAG level: 2.89) and healthy control participants (median female ZAG level: 5.20, median male ZAG level: 4.99). Serum ZAG concentrations were significantly lower in obese participants (2.86 ± 0.40 mg/L) than in the control group (5.10 ± 0.74 mg/L; p < 0.001). The multivariable Firth’s logistic regression model, incorporating the selected factors, revealed a significant association between obesity and ZAG. ROC curve analysis indicated strong discriminatory ability of ZAG for identifying obesity, with a proposed cut-off value of 3.62 mg/L. Circulating ZAG level is significantly reduced in children and adolescents with obesity. An important finding of our study is the detection of a cutoff value for serum ZAG levels. Furthermore, the use of the Least Absolute Shrinkage and Selection Operator (LASSO) model can be considered a valuable contribution to defining ZAG as an independent factor associated with obesity. Full article

The present review focuses on the particulars of the hemodynamic assessment of patients with Takotsubo syndrome (TTS), i.e., blood pressure, cardiac output, systemic vascular resistance, left ventricular ejection fraction, left ventricular–arterial coupling (VAC), left ventricular end-diastolic pressure (LVEDP), and their importance in the management of patients with TTS, and the unraveling of its pathophysiology. In addition, the review discusses the discrepancies noted in the reported literature on the LVEDP and the left VAC, speculating as to the underlying reasons, and providing recommendations. Full article

IgA nephropathy is the most common primary glomerulonephritis worldwide and a leading cause of chronic kidney disease and kidney failure, with geographic and ancestral variation and a course ranging from asymptomatic urinary abnormalities to progressive loss of kidney function. This narrative review links the multi-hit model to risk stratification, biomarkers, current management, and emerging therapies, and highlights implementation gaps. Risk assessment is longitudinal, prioritizing proteinuria and estimated glomerular filtration rate trajectories and integrating Oxford MEST-C, prediction tools, and biomarker and multi-omics approaches, while recognizing limitations in histologic reproducibility and model calibration. Current management is anchored in optimized supportive care aimed at sustained proteinuria reduction and kidney protection, including intensive blood pressure control with maximal tolerated renin–angiotensin system blockade, dietary sodium restriction and lifestyle measures, and sodium–glucose co-transporter 2 inhibitors for eligible patients. For selected higher-risk patients with persistent proteinuria despite optimized supportive care, immunomodulatory strategies are discussed, including systemic corticosteroids and targeted-release budesonide (Nefecon), emphasizing structured toxicity risk mitigation and cautioning against assuming interchangeability among alternative oral budesonide formulations. Emerging therapies are organized around mechanism-aligned targets across the BAFF/APRIL axis, complement pathways, and endothelin-based approaches, with growing interest in sequencing and combination regimens layered on supportive care. Key gaps include reliance on surrogate endpoints, limited long-term durability and safety data, and uneven evidence for special populations. Full article

Euphorbia tirucalli, commonly known as Aveloz, is widely used in Brazilian folk medicine for its purported antibacterial, antiviral, and antitumoral properties. However, scientific evidence regarding its systemic in vivo effects, particularly on the cardiovascular system, remains limited. This study investigated the impact of oral E. tirucalli latex ingestion on cardiac hemodynamics and associated molecular alterations in normotensive Wistar rats. Animals received water (control) or E. tirucalli latex (13.47 mg/kg) by oral gavage for 15 days. Hemodynamic parameters were assessed through noninvasive blood pressure monitoring and direct measurements of left ventricular systolic (LVSP) and end-diastolic pressures (LVEDP), cardiac cycle duration, rates of pressure development (dP/dt_max and dP/dt_min), and the left ventricular relaxation constant (Tau). Oxidative stress and inflammation were evaluated by plasma advanced oxidation protein products (AOPP) and myeloperoxidase (MPO), respectively, while reactive oxygen species production and apoptosis were analyzed in isolated cardiomyocytes. Although systemic blood pressure remained unchanged, E. tirucalli increased LVSP, LVEDP, cardiac cycle duration, and dP/dt_max, while reducing Tau. These alterations were accompanied by elevated AOPP and MPO levels, increased cardiomyocyte hydrogen peroxide, and higher rates of early apoptosis, indicating that E. tirucalli latex alters cardiac hemodynamics and promotes oxidative and inflammatory cardiac injury. Full article