Search Results (32,490)

Background: Blood pressure elevation in children is an important health concern. The extent to which hypertension is diagnosed in German pediatric practices is not yet known. The aim of this study is, therefore, to examine the prevalence of hypertension diagnosis in children and adolescents treated in pediatric practices, as well as the factors associated with hypertension in this population. Methods: This retrospective case–control study used electronic medical records from 258 primary care pediatricians in Germany and included children and adolescents aged 0–17 years with an initial documented diagnosis of primary hypertension between January 2005 and December 2023. Hypertension patients were matched 1:5 with non-hypertension patients by age and sex. Conditional multivariable logistic regression models were used to estimate the association of chronic diseases and therapies with a risk of hypertension. Results: After 1:5 matching, the present study included 7482 children and adolescents with hypertension, and 37,410 controls without hypertension. The average prevalence of hypertension was 0.12% and the incidence was 1.24 cases per 1000 person-years, both increasing with age. In the multivariable regression analysis, a significant positive association was observed between hypertension and ten disorders including obesity (odds ratio, OR: 6.91; 95% confidence intervals, CI: 6.28–7.60), type 1 diabetes mellitus (OR: 2.85; 95% CI: 2.13–3.82), dyslipidemia (OR: 1.99; 95% CI: 1.46–2.72), chronic bronchitis (OR: 1.63; 95% CI: 1.39–1.90), hypothyroidism (OR: 1.62; 95% CI: 1.30–2.02), migraine (OR: 1.52; 95% CI: 1.17–1.98), ADHD (OR: 1.45; 95% CI: 1.28–1.65), scoliosis (OR: 1.40; 95% CI: 1.13–1.73), chronic rhinitis (OR: 1.31; 95% CI: 1.14–1.50), and reaction to severe stress and adjustment disorders (OR: 1.31; 95% CI: 1.04–1.65). Furthermore, paracetamol prescription was positively associated with hypertension risk (OR: 1.68; 95% CI: 1.41–2.00). Conclusions: The significant associations between hypertension and chronic disorders, particularly obesity, underscore the need for early prevention strategies. Prospective studies are needed to confirm these associations. Similarly, pathophysiological and mechanistic explanations for the associations identified need to be explored and verified in properly designed studies. Full article

To better understand diabetic nephropathy (DN), developing accurate animal models is crucial. Current models often fail to fully mimic human DN, showing only mild albuminuria, glomerular hypertrophy, and limited mesangial matrix expansion. Our study aims to develop a more robust model by combining streptozotocin (STZ)-induced diabetes with a high-protein diet (HPD). We divided C57Bl/6J mice into three groups: control, STZ with a standard diet (STZ-SD), and STZ with a HPD (45 kcal% protein) (STZ-HPD) for 12 weeks. Renal function was evaluated using the urinary albumin-to-creatinine ratio, and kidney tissues were analyzed for histological and molecular changes. The STZ-HPD group showed significantly higher albuminuria and more severe glomerular and tubular damage compared to the control and STZ-SD groups. These changes were accompanied by increased inflammatory and oxidative stress markers, highlighting the harmful effects of high-protein intake on renal injury. Our findings suggest that the STZ-HPD model could be a valuable tool for studying DN pathophysiology and evaluating therapeutic interventions, providing a new approach for preclinical research. Full article

Chronic wounds present a large burden to our healthcare system and are typically marked by a failure to transition out of the inflammatory phase of wound healing. Venous leg ulcers (VLUs) represent the largest portion of chronic wounds. A pilot study of eleven (11) patients with VLUs seen over a 12-week period was undertaken utilizing RNA sequencing of wound biopsies and plasma cytokine levels to determine if biomarkers could be identified that would distinguish between wounds which heal versus those that do not. Chronic wounds were found to have increased expression of genes relating to epithelial-to-mesenchymal transition (EMT), cartilage and bone formation, and regulation of apical junction. Plasma cytokine levels showed predictive potential for IL-15 and RANTES, which were found to increase over time in patients with healed wounds. Further research is needed to validate these biomarkers as well as additional study of other chronic wound models, such as diabetic foot ulcers (DFUs). Full article

Objectives: Cardiorenal syndrome (CRS) is a complex disorder characterized by concurrent dysfunction of the heart and kidneys, with their detrimental effects perpetuating a bidirectional cycle. This study aimed to examine the clinical and hemodynamic factors associated with changes in renal function in patients with pulmonary hypertension (PH) secondary to chronic heart failure (HF). Methods: A total of 108 patients with HF were evaluated using right-heart catheterization. Results: 75 patients (69.4%) were diagnosed with PH. The mean baseline estimated GFR (beGFR) was similar in noPH (64 ± 21 mL/min/1.73 m²) and PH group (63 ± 23 mL/min/1.73 m²) (p = 0.71). After a median follow-up of 7 months, the last eGFR (leGFR) in the noPH and PH groups was comparable (49 ± 24 vs. 52 ± 25 mL/min/1.73 m² respectively; p = 0.62). However, in the PH group, for patients with baseline Cr (bCr) < 1.5 mg/dL, the reduction in eGFR showed a graded inverse relationship to serum creatinine, as compared with bCr ≥ 1.5 mg/dL, for whom beGFR and leGFR demonstrated large overlap. In a multivariable regression analysis, the primary independent predictors of leGFR were baseline creatinine, age, diabetes mellitus, left ventricular ejection fraction below 45%, and use of mineralocorticoids antagonists. The model explained 66% of the variance in leGFR. Conclusions: In a cohort of left HF and PH, an inverse non-linear and graded association between the baseline serum creatinine levels and the variation in estimated GFR was demonstrated, contrary to those without PH, for whom this relationship was linear and constant. The distinct patterns of GFR decline influenced by age, low ejection fraction, diabetes, and mineralocorticoid underscore the need for individualized treatment strategies. Full article

The interplay between gut microbiota and retinal health, known as the gut-–retina axis, has gained increasing attention in recent years. Short-chain fatty acids (SCFAs), metabolites produced by gut microbiota, have been identified as key mediators of gut–retina communication. This systematic review explores the role of SCFAs in retinal health and their potential impact on the development and progression of retinal diseases, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma. A literature search was conducted across multiple databases, including PubMed, Google Scholar, and Science Direct, to identify studies published between 2014 and December 2024. Studies were included if they investigated the effects of SCFAs on retinal structure, function, or disease pathogenesis in animal models or human subjects. The review included 10 original articles spanning both preclinical and clinical studies. Evidence suggests that SCFAs play a crucial role in maintaining retinal homeostasis through anti-inflammatory and neuroprotective mechanisms. Dysbiosis of the gut microbiota, leading to altered SCFA production, was associated with increased retinal inflammation, oxidative stress, and vascular dysfunction. Furthermore, reduced SCFA levels were linked to the progression of retinal diseases, such as diabetic retinopathy and age-related macular degeneration. Modulation of gut microbiota and SCFA levels through dietary interventions or probiotics may represent a novel therapeutic strategy for preventing or managing retinal diseases. Further research is needed to elucidate the precise molecular mechanisms underlying SCFA-mediated retinal protection and to evaluate the efficacy of targeted therapies in clinical settings. Full article

The life stage between the ages of 30–45 years for women is critical, given the competing demands of occupational advancement, intimate partner relationships, and childcare responsibilities. Cardiovascular disease (CVD) is the leading cause of death among women in the US, which is experienced inequitably by race/ethnicity/nativity and socioeconomic status and is embedded within geographic contexts. The objective of the current study was to examine social inequities in pre-pregnancy risk factors for cardiovascular disease. We analyzed 16 years of geocoded natality data in Texas (N = 2,089,588 births between 2005 and 2020 to mothers aged 30–45 years) linked with census tract- and county-level data. Dependent variables included pre-pregnancy diabetes, hypertension, obesity, and smoking. Independent variables included individual-level race/ethnicity/nativity and educational attainment, tract-level poverty and racial/ethnic concentrations, and county-level urban/rural status, with controls for other sociodemographic characteristics and time trend. Two-level, random intercept hierarchical generalized logistic models were used to estimate associations and model fit. Significant social inequities at the individual-, tract-, and county-levels in each risk factor were found. For example, tract-level variables had substantial and significant association with the four CVD risk factors, ranging from 13% to 72% higher odds in adjusted models. For all four risk factors, the more rural the county of residence was, the higher the odds of having the risk factor (24% to 256% higher odds). Individual-level social inequalities by race/ethnicity/nativity (ORs ranging from 0.04 to 2.12) and education (ORs ranging from 1.25 to 5.20) were also observed. Enhancing our understanding of this important period of life may enable policy and interventions to better support women through this critical life stage. Full article

We aimed to develop a multiple logistic regression model for predicting the occurrence of metabolic syndrome (MetS) using homeostasis model assessment of insulin resistance (HOMA-IR) levels, gender, age, and Diabetes Mellitus (DM) status, and to evaluate its predictive accuracy. Data from 6134 participants in the 2019 Korea National Health and Nutrition Examination Survey were analyzed. MetS was diagnosed using the Adult Treatment Panel III criteria. A logistic regression model was developed based on the regression coefficients of each variable. Model performance was evaluated through a receiver operating characteristic analysis, revealing an overall area under the curve (AUC) of 0.819, a sensitivity of 80%, and a specificity of 68.9%. Age-specific analysis showed that the model’s predictive power was highest among those aged 20–29 years (AUC: 0.864). Conversely, the AUC progressively decreased in individuals aged ≥50 years, indicating reduced predictive power in older adults. These findings suggest the importance of adopting a multidimensional approach that considers HOMA-IR, age, gender, and DM status for predicting MetS. The developed prediction model can be used as a valuable tool for the early diagnosis of MetS and the development of tailored MetS prevention programs. It also provides foundational data for shaping public health policies related to MetS. Full article

Background: Metabolic syndrome is a complex disorder characterized by the coexistence of multiple risk factors, including dysglycemia, hypertension, dyslipidemia, and visceral obesity. Both metabolic syndrome and diabetes mellitus are closely associated with the onset of microvascular complications such as retinopathy, polyneuropathy, and nephropathy. Methods: This narrative review analyzed 137 studies published up to 2025, retrieved from PubMed and Crossref databases. The objective was to identify and evaluate potential biomarkers that could facilitate the early detection of microvascular complications in patients with metabolic syndrome. Results: Several biomarkers demonstrated a strong correlation with microvascular complications in individuals with metabolic syndrome. These findings suggest their potential role in early diagnosis and risk assessment. Conclusions: The identification of reliable biomarkers may enhance early detection and targeted interventions for microvascular complications in metabolic syndrome. Further research is essential to validate these markers and establish their clinical applicability in routine medical practice. Full article

Background/Objectives: Our lab has previously reported that Grifola frondosa (maitake mushroom) GF5000 has antidiabetic potential owing to its ability to improve insulin resistance. This study aimed to gain insight into the system-level hypoglycemic mechanisms of GF5000 using transcriptomics, proteomics, and network pharmacology. This study provides new insights into the hypoglycemic mechanisms of GF5000, identifying key molecular targets involved in mitigating insulin resistance in T2DM. Methods: Liver protein and gene expression in normal control (NC), diabetic control (DC), and GF5000-treated (GF5000) rats were analyzed via iTRAQ and RNA-seq. The relationships between differentially expressed genes (DEGs), differentially expressed proteins (DEPs), and type 2 diabetes (T2DM) disease targets were studied using Metascape and the Cytoscape GeneMANIA plug-in. Results: One hundred and fifty-two DEGs and sixty-two DEPs were identified; twenty DEGs/DEPs exhibited the same trend in mRNA and protein expression levels when comparing the GF5000 vs. DC groups. The Metascape analysis revealed that the T2DM disease targets included four DEGs—Gck, Scd, Abcb4, and Cyp3a9—and two DEPs—glucokinase and acetyl-CoA carboxylase 2. A Cytoscape–GeneMANIA analysis of thirteen DEGs/DEPs related to T2DM showed that Apoa1/Apolipoprotein A-I, Gckr/glucokinase regulatory protein, and Gck/glucokinase had the highest connectivity and centrality in the topological network. The qPCR results confirmed that GF5000 increased the mRNA expression of GCK in GCK-knockdown HepG2 cells. Conclusions: These results provide theoretical evidence for the use of GF5000 as a potential active nutritional ingredient for the prevention and treatment of T2DM. Our findings suggest that GF5000 targets multiple pathways implicated in T2DM, offering a multi-faceted approach to disease management and prevention. Full article

Background: Lower socioeconomic status (SES) has been associated with increased mortality from coronary heart disease. This excess risk, relative to affluent patients, may be due to a combination of more adverse cardiovascular-risk factors, inequalities in access to cardiac investigations, longer waiting times for cardiac revascularisation and lower use of secondary prevention drugs. We sought to investigate whether socio-economic status influenced long-term all-cause mortality after PCI in a large metropolitan city (London), which serves a population of 11 million people with a mixed social background over a 10-year period. Methods: We conducted an observational cohort study of 123,780 consecutive PCI procedures from the Pan-London (United Kingdom) PCI registry. This data set is collected prospectively and includes all patients treated between January 2005 and December 2015. The database includes PCI performed for stable angina and ACS (ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina). Patient socio-economic status was defined by the English Index of Multiple Deprivation (IMD) score, according to residential postcode. Patients were analysed by quintile of IMD score (Q1, least deprived; Q5, most deprived). Median follow-up was 3.7 (IQR: 2.0–5.1) years and the primary outcome was all-cause mortality. Results: The mean age of the patients was 64.3 ± 12.1 years and 25.2% were female. A total of 22.4% of patients were diabetic and 27.3% had a history of previous myocardial infarction. The rates of long-term all-cause mortality increased progressively across quintiles of IMD score, with patients in Q5 showing significantly higher long-term mortality rates compared with patients in Q1 (p = 0.0044). This persisted following the inclusion of a propensity score in the proportional hazard model as a covariate (HR for Q5 compared to Q1: 1.15 [95% CI: 1.10–1.42]). Conclusions: This study has demonstrated that low SES is an independent predictor of adverse clinical outcomes following PCI in the large, diverse metropolitan city of London. There clearly are inequalities in cardio-vascular risk factors, time to access to medical treatment/PCI, access to complex imaging and devices during PCI, access to secondary prevention after PCI, and even race differences. Hence, attention to reducing the burden of cardiovascular risk factors and improving primary prevention, particularly in patients with lower SES, is required. Full article

The literature has identified several common acute and chronic complications associated with periodontal health during pregnancy, such as gingivitis, recession, periodontitis, and changes in systemic health, such as gestational diabetes, which may act as additional risk factors for chronic periodontal disease. Are the general public and health care providers aware of the potential risks of systemic and intrauterine inflammation caused by bacteria from the oral microbiota entering the bloodstream through inflamed gingival tissue and affecting the fetoplacental unit, leading to complications, such as preterm birth and reduced prenatal growth? A questionnaire-based survey, conducted between January 2023 and June 2023, aimed to assess patients’ personal oral hygiene practices and their understanding of the link between pregnancy and periodontal health. A total of 826 people completed a questionnaire for this study. The majority of women surveyed (86.9%) were not pregnant, but 77.7% had at least one child. The majority of women believed in good oral hygiene during pregnancy but lacked knowledge about how oral care can affect pregnancy outcomes. Full article

Kidney disease is a global health concern, impacting a substantial part of the overall population and contributing to high morbidity and mortality rates. The initially diagnosed phases of kidney disease are often present without noticeable indications, leading to delayed diagnosis and treatment. Therefore, early detection is crucial to reducing complications and improving the lives of those impacted. However, the performance of previous automated approaches has often been hindered by suboptimal feature selection and algorithms’ “black-box” nature, which adversely affect their interpretability and clinical applicability. This paper aims to address these limitations by creating an effective machine-learning-based approach that integrates ant colony metaheuristic optimization algorithms for feature selection and explainable artificial intelligence techniques such as SHAP and LIME for model interpretation. The ant colony optimization method identified the most relevant feature subsets using a clinical dataset, reducing model complexity while preserving predictive accuracy. Performance evaluation shows that the extra trees classifier, when using optimized selected features, achieved the highest performance with an accuracy of 97.70% and an area under the curve of 99.55%, outperforming previous models trained on raw and complete processed feature sets. To enhance interpretability, the SHAP and LIME explainable techniques were employed, providing detailed insights into the contribution of key features such as TimeToEventMonths, HistoryDiabetes, and Age. This comprehensive framework, combining advanced feature selection with explainable models, improves clinical decision-making and fosters trust in machine learning applications for healthcare. Full article

Background/Objectives: The pathogenesis of diabetic kidney disease (DKD) is complex and multifactorial. Because of its complications and reduced number of diagnostic biomarkers, it is important to explore new biomarkers with possible roles in the early diagnosis of DKD. Our study aims to investigate the pattern of previously identified metabolites and their association with biomarkers of endothelial dysfunction, proximal tubule (PT) dysfunction, and podocyte injury. Methods: A total of 110 participants, comprising 20 healthy individuals and 90 patients divided in three groups were enrolled in the study: normoalbuminuria, microalbuminuria, and macroalbuminuria. Untargeted and targeted metabolomic methods were employed to assess urinary and serum biomarkers, as well as indicators of endothelial dysfunction, podocyte damage, and PT dysfunction through ELISA techniques. Results: Our research uncovered specific metabolites that exhibit varying levels across different sub-groups. Notably, glycine serves as a distinguishing factor between group C and the normoalbuminuric group. Furthermore, glycine is correlated with endothelial markers, especially VCAM. We observed a gradual decrease in kynurenic acid levels from group C to group P3; this biomarker also demonstrates an inverse relationship with both p-selectin and VCAM. Additionally, tryptophan levels decline progressively from group C to group P3, accompanied by a negative correlation with p-selectin and VCAM. Urinary tiglylglycine also differentiates among the patient groups, with concentrations decreasing as the condition worsens. It shows a strong positive correlation with nephrin, podocalyxin, KIM1, and NAG. Conclusions: In conclusion, glycine, tiglylglycine, kynurenic acid and tryptophan may be considered putative biomarkers for early diagnosis of DKD and T2DM progression. Full article

Background/Objectives: The current standard of care for assessing chronic kidney disease complicating diabetes (DKD) includes measurement of estimated glomerular filtration rate (eGFR) and urinary albumin:creatinine ratio (uACR) but both tests have limitations. The present study compared the biomarker-based Promarker^®D test with conventional biochemical measures for predicting future kidney function decline in adults with type 2 diabetes (T2D). Methods: Baseline concentrations of apolipoprotein A-IV, CD5 antigen-like protein and insulin-like growth factor binding protein 3 were combined with age, serum HDL cholesterol and eGFR to generate PromarkerD risk scores for incident DKD/eGFR decline ≥ 30% (the primary endpoint) in 857 adults with T2D (mean age 65.4 years, 54% males). Logistic regression modelling was used to compare the association of (i) PromarkerD, (ii) eGFR, (iii) uACR, and (iv) eGFR plus uACR with this outcome during 4 years of follow-up. Results: Study participants were classified by PromarkerD as low (63%), moderate (13%), or high risk (24%) for kidney function decline at baseline. Over a mean 4.2 years, 12.5% developed the primary endpoint. PromarkerD scores showed significantly higher predictive performance (area under the receiver operating characteristic curve (AUC) 0.88 (95% confidence interval (CI) 0.85–0.91)) compared to conventional biochemical measures (AUC = 0.63–0.82). There was a progressive increase in risk with moderate and high risk by PromarkerD exhibiting greater odds of the primary endpoint compared to those at low risk (odds ratios (OR) (95% CI) 8.11 (3.99–16.94) and 21.34 (12.03–40.54), respectively, both p < 0.001). Conclusions: PromarkerD more accurately identifies adults with T2D at risk of kidney function decline than current usual care biochemical tests. Full article

The mineralocorticoid receptor (MR) is a steroid hormone receptor that plays a key role in regulating sodium and water homeostasis and blood pressure. MR antagonists are a guideline recommended for therapy for the treatment of hypertension and cardiovascular disease but can cause hyperkalaemia. Modelling was performed for binding of the endogenous ligands aldosterone and cortisol and MR antagonist spironolactone to the ligand binding domain (LBD) of the MR. A molecular docking screen of compounds that were structurally similar to known antagonists was performed, leading to the identification of two novel compounds, C79 and E67. Molecular dynamics (MD) assessed the dynamic interactions with C79, E76, endogenous ligands, and spironolactone with the MR ligand binding domain (LBD). Analysis of the protein backbone showed modest changes in the overall structure of the MR LBD in response to binding of antagonists, with movement in helix 12 consistent with previous observations. All ligands tested maintained stable binding within the MR LBD throughout the simulations. Hydrogen bond formation played a more prominent role in the binding of endogenous ligands compared to antagonists. MM-PBSA binding free energy calculations showed that all ligands had similar binding affinities, with binding facilitated by key residues within the binding site. The novel antagonists demonstrated similar binding properties to spironolactone, warranting further evaluation. This study provides insights into the molecular mechanisms of MR activation and inhibition, which can aid in the development of novel therapeutic strategies for cardiovascular diseases. Full article