Search Results (623)

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, with hypercholesterolemia identified as a major, but modifiable risk factor. This review serves as the second part of a comprehensive analysis of dyslipidemia management. The first installment laid the groundwork by detailing the key pathophysiological mechanisms of lipid metabolism, the development of atherosclerosis, major complications of hyperlipidemia, and the importance of cardiovascular risk assessment in therapeutic decision-making. It also examined non-pharmacological interventions and conventional therapies, with a detailed focus on statins and ezetimibe. Building upon that foundation, the present article focuses exclusively on emerging pharmacological therapies designed to overcome limitations of standard treatment. It explores the mechanisms, clinical applications, safety profiles, and pharmacogenetic aspects of novel agents such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (alirocumab, evolocumab), small interfering RNA (siRNA) therapy (inclisiran), adenosine triphosphate–citrate lyase (ACL) inhibitor (bempedoic acid), microsomal triglyceride transfer protein (MTP) inhibitor (lomitapide), and angiopoietin-like protein 3 (ANGPTL3) inhibitor (evinacumab). These agents offer targeted strategies for patients with high residual cardiovascular risk, familial hypercholesterolemia (FH), or statin intolerance. By integrating the latest advances in precision medicine, this review underscores the expanding therapeutic landscape in dyslipidemia management and the evolving potential for individualized care. Full article

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by inattention, hyperactivity, and impulsivity, frequently observed in juvenile offenders. This systematic review explores the interplay between ADHD and juvenile delinquency, focusing on behavioural, psychological, and social dimensions. Following the PRISMA guidelines, a systematic literature review was conducted using EBSCO Discovery Service, Science Direct, PubMed, and snowballing techniques. Studies meeting specific inclusion criteria, including juvenile offenders diagnosed with ADHD and comparisons to non-offender or non-ADHD control groups, were analysed. The methodological quality of studies was assessed using the Joanna Briggs Institute appraisal tools. A total of 21 studies were included, highlighting significant associations between ADHD and juvenile delinquency. ADHD symptoms, especially impulsivity and emotional dysregulation, were linked to an earlier onset of offending and higher rates of property crimes. Comorbidities such as conduct disorder, substance use disorder, and depression exacerbated these behaviours. Sociodemographic factors like low education levels and adverse family environments were also critical modifiers. Early intervention and tailored treatment approaches were emphasised to address these challenges. The findings underscore the need for early diagnosis, individualised treatment, and integrative rehabilitation programmes within the juvenile justice system to mitigate long-term risks and promote social inclusion. Full article

Sarcopenia is a progressive age-related musculoskeletal disorder characterized by loss of muscle mass, strength, and physical performance, contributing to functional decline and increased risk of disability. Emerging evidence suggests that vitamin D (Vit D) plays a pivotal role in skeletal muscle physiology beyond its classical functions in bone metabolism. This review aims to critically analyze the relationship between serum Vit D levels and sarcopenia in older adults, focusing on pathophysiological mechanisms, diagnostic criteria, clinical evidence, and preventive strategies. An integrative narrative review of observational studies, randomized controlled trials, and meta-analyses published in the last decade was conducted. The analysis incorporated international diagnostic criteria for sarcopenia (EWGSOP2, AWGS, FNIH, IWGS), current guidelines for Vit D sufficiency, and molecular mechanisms related to Vit D receptor (VDR) signaling in muscle tissue. Low serum 25-hydroxyvitamin D levels are consistently associated with decreased muscle strength, reduced physical performance, and increased prevalence of sarcopenia. Although interventional trials using Vit D supplementation report variable results, benefits are more evident in individuals with baseline deficiency and when combined with protein intake and resistance training. Mechanistically, Vit D influences muscle health via genomic and non-genomic pathways, regulating calcium homeostasis, mitochondrial function, oxidative stress, and inflammatory signaling. Vit D deficiency represents a modifiable risk factor for sarcopenia and functional impairment in older adults. While current evidence supports its role in muscular health, future high-quality trials are needed to establish optimal serum thresholds and dosing strategies for prevention and treatment. An individualized, multimodal approach involving supplementation, exercise, and nutritional optimization appears most promising. Full article

Background/Objectives: Recent studies linked a diet rich in ultra-processed foods (UPFs) with depression and diabetes. Although common risk factors, such as aging, are defined for both diseases, how UPFs are associated with the bidirectional relationship between them is not known. This study aimed to investigate whether UPF intake modifies the association between depression and diabetes within the Brazilian adult population. Methods: This cross-sectional analysis utilized data from the 2019 Brazilian National Health Survey, involving over 87,000 adults (aged 18–92 years). Participants provided self-reported data on diabetes and depression diagnoses, dietary habits (assessed by qualitative FFQ), as well as demographic, and socioeconomic variables. Multivariate logistic regression models were used to evaluate the associations, employing two classification methods—UPF1 and UPF2—based on different thresholds of weekly consumption, for high/low UPF intake. Analyses were stratified by age groups to identify variations in associations. Results: There was a significant association between depression and diabetes, especially among participants with high UPF consumption. Models adjusted by demographic characteristics, as well as meat and vegetable consumptions, demonstrated elevated odds ratios (ORs) for diabetes among individuals with depression consuming high levels of UPF, compared to those with a low UPF intake (OR: 1.258; 95% CI: 1.064–1.489 for UPF1 and OR: 1.251; 95% CI: 1.059–1.478 for UPF2). Stratified analysis by age further amplified these findings, with younger individuals showing notably stronger associations (non-old adult group OR: 1.596; 95% CI: 1.127–2.260 for UPF1, and OR: 6.726; 95% CI: 2.625–17.233 for UPF2). Conclusions: These findings suggest that high UPF intake may influence the relationship between depression and diabetes, especially in younger adults. Future longitudinal studies are warranted to establish causality, investigate underlying biological mechanisms, and examine whether improving overall nutrient intake through dietary interventions can reduce the co-occurrence of depression and diabetes. Full article

Background: Environmental exposures, such as per- and polyfluoroalkyl substances (PFAS), in conjunction with social and behavioral factors, can significantly impact liver health. This research investigates the combined effects of PFAS (perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), alcohol consumption, smoking, income, and education on liver function among the U.S. population, utilizing data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES). Methods: PFAS concentrations in blood samples were analyzed using online solid-phase extraction combined with liquid chromatography–tandem mass spectrometry (LC-MS/MS), a highly sensitive and specific method for detecting levels of PFAS. Liver function was evaluated using biomarkers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total bilirubin, and the fatty liver index (FLI). Descriptive statistics and multivariable linear regression analyses were employed to assess the associations between exposures and liver outcomes. Bayesian Kernel Machine Regression (BKMR) was utilized to explore the nonlinear and interactive effects of these exposures. To determine the relative influence of each factor on liver health, Posterior Inclusion Probabilities (PIPs) were calculated. Results: Linear regression analyses indicated that income and education were inversely associated with several liver injury biomarkers, while alcohol use and smoking demonstrated stronger and more consistent associations. Bayesian Kernel Machine Regression (BKMR) further highlighted alcohol and smoking as the most influential predictors, particularly for GGT and total bilirubin, with posterior inclusion probabilities (PIPs) close to 1.0. In contrast, PFAS showed weaker associations. Regression coefficients were small and largely non-significant, and PIPs were comparatively lower across most liver outcomes. Notably, education had a higher PIP for ALT and GGT than PFAS, suggesting a more protective role in liver health. People with higher education levels tend to live healthier lifestyles, have better access to healthcare, and are generally more aware of health risks. These factors can all help reduce the risk of liver problems. Overall mixture effects demonstrated nonlinear trends, including U-shaped relationships for ALT and GGT, and inverse associations for AST, FLI, and ALP. Conclusion: These findings underscore the importance of considering both environmental and social–behavioral determinants in liver health. While PFAS exposures remain a long-term concern, modifiable lifestyle and structural factors, particularly alcohol, smoking, income, and education, exert more immediate and pronounced effects on hepatic biomarkers in the general population. Full article

Dietary patterns have been identified as one of the most important modifiable risk factors for several non-communicable diseases, inextricably linked to the health span of older people. Poor dietary choices may act as triggers for immune responses such as aggravated inflammatory reactions and oxidative stress contributing to the pathophysiology of several ageing hallmarks. Novel dietary interventions are being explored to restore gut microbiota balance and promote overall health in ageing populations. Probiotics and, most recently, postbiotics, which are products of probiotic fermentation, have been reported to modulate different signalling biomolecules involved in immunity, metabolism, inflammation, and oxidation pathways. This review presents evidence-based literature on the effects of postbiotics in promoting healthy ageing and mitigating various age-related diseases. The development of postbiotic-based therapeutics and diet-based interventions within a personalised microbiota-targeted approach is proposed as a possible direction for improving health in the elderly population. Despite growing evidence, the data regarding their exact mechanistic pathways for antioxidant and immunomodulating activities remain largely unexplored. Expanding our understanding of the mechanistic and chemical determinants of postbiotics could contribute to disease management approaches, as well as the development of and optimisation of biotherapeutics. Full article

Hypercholesterolemia is a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD), affecting a significant proportion of the adult population worldwide. This narrative review provides a comprehensive and up-to-date overview of hyperlipidemia management, spanning from epidemiological trends and underlying pathophysiological mechanisms to the limitations of conventional therapies such as statins and ezetimibe. Particular emphasis is placed on cardiovascular risk assessment, current stratification tools, and international guideline-based interventions. The present paper, focusing primarily on the biological mechanisms of dyslipidemia and the clinical use of traditional lipid-lowering agents, serves as the first part of a two-part series, preceding a forthcoming review of novel pharmacological approaches. Our data synthesis is based on a structured literature search conducted across Google Scholar, PubMed, and Scopus, including studies published up to June 2025. The review also includes aspects related to non-pharmacological strategies, pharmacoeconomic considerations, and pharmacogenetic influences on treatment response. Ultimately, this work aims to equip clinicians with evidence-based, nuanced insights essential for optimizing lipid management and reducing cardiovascular risk, while setting the foundation for understanding how emerging therapies may overcome current therapeutic limitations. Full article

Children and adolescents with type 1 diabetes (T1D) often experience abnormalities in bone health. Studies have consistently demonstrated that youth with T1D have lower bone mineral density (BMD) compared to their healthy peers. Additionally, children with T1D show impaired bone microarchitecture and reduced bone turnover. These factors collectively contribute to an increased risk of fractures across the life span of this population. To optimize bone accrual and reduce fracture risk, several strategies can be employed during childhood and adolescence. First, maintaining good glycemic control is critical, as poor glycemic control has been associated with lower BMD and an increased risk of fractures. Second, specific nutritional recommendations can help improve bone health, including a balanced diet, adequate calcium and vitamin D intake, and careful monitoring of both macronutrient and micronutrient intake. Third, regular physical activity plays a vital role. A systematic review and meta-analysis have shown that youth with T1D are generally less physically active, more sedentary, and have lower cardiorespiratory fitness levels than their non-diabetic peers. This review emphasizes targeted strategies aimed at optimizing skeletal health in the pediatric population with T1D, with a particular focus on the critical roles of glycemic control, nutritional adequacy, and regular physical activity. These modifiable factors may contribute to the reduction of fracture risk across the life span in individuals with T1D. Full article

Background: Non-syndromic orofacial clefts (NSOFCs) are one of the common congenital malformations in Vietnam, with 1.4 per 1000 live births, with notable sex differences in occurrence. This case–control study aims to investigate potential sex-specific interactions of WNT3 and NOG polymorphisms across NSOFC subtypes in a Vietnamese population. Methods: A total of 720 participants were separated into 4 groups with a male/female ratio of 1:1 (160 individuals with cleft lip and palate (NSCLP), 160 with cleft lip only (NSCLO), 160 with cleft palate only (NSCPO), 240 healthy controls). Two single-nucleotide polymorphisms (SNPs), rs3809857 and rs227731, were genotyped by using the StepOnePlus Real-Time PCR System. Results: The most significant findings were found in the male NSCLO group under a recessive model of WNT3 rs3809857 after applying Bonferroni correction, as a five-fold protective factor with OR = 0.18 (95% confidence interval: 0.05–0.64, p = 0.0033). Additionally, the weak or moderate protective association between rs3809857 and male NSCLP was found with p < 0.05 under the dominant model. However, there were no significant findings in the female NSOFC subtypes associated with WNT3. Conversely, NOG rs227731 results showed a weak increased risk in female NSCLO and NSCPO with p < 0.05. Conclusion: this study identified the critical role of WNT3 rs3809857 in reducing NSCLO risk in males. These findings support the potential influence of sex as a modifying factor in the genetic susceptibility to non-syndromic orofacial clefts. Full article

Metabolic dysfunction-associated fatty liver disease (MAFLD), a recently proposed term to replace non-alcoholic fatty liver disease (NAFLD), emphasizes the critical role of metabolic dysfunction and applies broader diagnostic criteria. Diagnosis of MAFLD requires evidence of hepatic steatosis combined with obesity, type 2 diabetes mellitus, or other metabolic dysregulation conditions, all of which significantly elevate the risk of chronic kidney disease (CKD). This review discusses the pathological mechanisms of lipid accumulation and insulin resistance in MAFLD and CKD, highlighting their mechanistic connections. Specifically, ectopic fat accumulation triggered by metabolic reprogramming, oxidative stress and inflammation induced by energy overload, modified lipids, uremic toxins, and senescence, as well as insulin resistance pathways activated by pro-inflammatory factors and lipotoxic products, collectively exacerbate simultaneous hepatic and renal injury. Moreover, interactions among hyperinsulinemia, the sympathetic nervous system, the renin–angiotensin system (RAS), and altered adipokine and hepatokine profiles further amplify insulin resistance, ectopic lipid deposition, and systemic damage. Finally, the review explores potential therapeutic strategies targeting lipid metabolism, insulin sensitivity, and RAS activity, which offer promise for dual-organ protection and improved outcomes in both hepatic and renal systems. Full article

Approximately 18% of U.S. children experience cognitive and behavioral challenges, with both genetic and environmental contributors. We examined if household insecticides, particularly those used in and around the home and on pets, are associated with neurodevelopmental changes. Data were from children aged 24–60 months in the CHARGE study with the following classifications: autism spectrum disorder (ASD, n = 810), developmental delay (DD, n = 192), and typical development (TD, n = 531). Exposure to indoor, outdoor, and pet insecticides was reported for the period from three months pre-conception to the second birthday. Cognitive and adaptive functioning were assessed using the Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales. Linear regression was used to evaluate associations by diagnostic group, adjusting for confounders. Flea/tick soaps, shampoos, and powders used during year two were significantly associated with lower cognitive and adaptive scores in children with ASD after FDR correction. Flea/tick skin treatments in early pregnancy were associated with reduced scores in the DD group, though not significant after correction, especially when used with high frequency. No associations were observed in TD children. These findings underscore the need to examine early-life exposure to non-agricultural insecticides as modifiable risk factors for neurodevelopment. Full article

Objective: Our objective was to investigate the short-term effects of ambient ozone (O₃) meteorological factors and their interactions on hospitalizations for cerebral infarction in Zhengzhou, China. Methods: Daily data on air pollutants, meteorological factors, and hospitalization of cerebral infarction patients were collected from 1 January 2019 to 31 December 2023 in Zhengzhou, China. A generalized additive model was constructed to evaluate the association between ambient O₃ levels and hospitalization for cerebral infarction. A distributed lag non-linear model was applied to capture lagged and non-linear exposure effects. We further examined the modifying roles of temperature, humidity, wind speed, and atmospheric pressure, and conducted stratified analyses by sex, age, and season. Results: O₃ exposure was significantly associated with increased cerebral infarction risk, particularly during the warm season. A bimodal temperature-lag pattern was observed, as follows: moderate temperatures (10–20 °C) were associated with immediate effects, while cold (<10 °C) and hot (>30 °C) temperatures were linked to delayed risks. The association of O₃ and hospitalizations for cerebral infarction appeared stronger under high humidity, low wind speed, and low atmospheric pressure. Conclusions: Short-term O₃ exposure and adverse meteorological conditions are jointly associated with an elevated risk of cerebral infarction. Integrated air quality and weather-based warning systems are essential for targeted stroke prevention. Full article

Rheumatoid arthritis (RA) is a progressive and systemic autoimmune disease, characterized by a chronic inflammatory process, affecting the lining of the synovial joints, many body organs/systems, and blood vessels. Its pathological hallmarks are hyperplasic synovium, bone erosion, and progressive joint destruction. Rheumatoid arthritis affects over 20 million people, with a worldwide prevalence of 0.5–1.0%, exhibiting gender, ethnic, and geographical differences. The progressive disability severely impairs physical motion and quality of life and is finally leading to a shortened life span. The pathogenesis of RA is a complex and still poorly understood process in which genetic and environmental factors are principally associated. Current treatment mostly relies on conventional/non-biological disease-modifying anti-rheumatic drugs (cDMARDs), analgesics, non-steroidal anti-inflammatory drugs, glucocorticoids, steroids, immunosuppresants, and biologic DMARDs, which only control inflammation and pain. Along with side effects (drug toxicity and intolerance), these anti-rheumatic drugs possess limited efficacy. Therefore, the discovery of novel multi-target therapeutics with an improved safety profile that function as inhibitors of RA-linked signaling systems are in high demand, and this is in the interest of both patients and clinicians. Plant-derived extracts, nutritional supplements, dietary medicine, and molecules with anti-inflammatory activity represent promising adjuvant agents or alternatives for RA therapeutics. This review not only aims to discuss the basic features of RA pathogenesis, risk factors, and signaling pathways but also highlights the research progress in pre-clinical RA in in vitro and in vivo models, revealing new avenues in the management of the disease in terms of comprehensive multidisciplinary strategies originating from medicinal plants and plant-derived molecules. Full article

Aging is a major non-modifiable risk factor for cardiovascular disease (CVD), in part due to its detrimental effects on vascular endothelial function. Dietary interventions, including those rich in plant-based components or following dietary patterns such as the Mediterranean Diet, have been shown to improve endothelial function in older adults, assessed via brachial artery flow-mediated dilation (FMD). However, it is well recognized that FMD responses to dietary interventions often show considerable variability among individuals. This variability presents a major challenge to translating findings into effective, population-level guidance highlighting the need for more tailored approaches for CVD risk prevention. Thus, to advance these precision nutrition approaches, research must move beyond the overall group mean effects and begin to investigate the factors driving this variability. This narrative review summarizes current evidence on nutritional interventions that improve endothelial function with aging, highlights potential contributors to individual response variability, and outlines future research directions to reduce this variability to enhance clinical relevance and advance precision nutrition for the aging population. Full article

Equine asthma is a chronic respiratory disease characterised by neutrophilic inflammation, airway hyperresponsiveness, and impaired pulmonary function. Obesity, increasingly prevalent among domestic horses, has been identified as a potential risk factor for exacerbating inflammatory conditions. This study aimed to explore whether obesity modifies neutrophil metabolism and inflammatory responses in horses affected by asthma. Six asthmatic horses in clinical remission were categorised into two groups: obese and non-obese, based on body condition score. Serum levels of interleukin-1β (IL-1β) and peripheral blood neutrophil counts were significantly higher in obese horses, indicating a heightened systemic inflammatory state. Neutrophils from obese horses displayed a stronger oxidative burst following zymosan stimulation and elevated IL-1β gene expression in response to lipopolysaccharide, suggesting a hyperinflammatory phenotype. Metabolomic profiling of neutrophils identified 139 metabolites, with notable differences in fatty acids, branched-chain amino acids, and tricarboxylic acid (TCA) cycle intermediates. Pathway enrichment analysis revealed significant alterations in fatty acid biosynthesis, amino acid metabolism, and glutathione-related pathways. Elevated levels of itaconate, citraconic acid, and citrate in obese horses indicate profound metabolic reprogramming within neutrophils. These results suggest that obesity promotes a distinct neutrophil phenotype marked by increased metabolic activity and heightened responsiveness to inflammatory stimuli. This altered profile may contribute to the persistence or worsening of airway inflammation in asthmatic horses. The findings underscore the importance of addressing obesity in the clinical management of equine asthma and open avenues for further research into metabolic-targeted therapies in veterinary medicine. Full article