Search Results (1,541)

Sleep disorders and stroke are intricately linked through a complex, bidirectional relationship. Sleep disturbances such as obstructive sleep apnea (OSA), insomnia, and restless legs syndrome (RLS) not only increase the risk of stroke but also frequently emerge as consequences of cerebrovascular events. OSA, in particular, is associated with a two- to three-fold increased risk of incident stroke, primarily through mechanisms involving intermittent hypoxia, systemic inflammation, endothelial dysfunction, and autonomic dysregulation. Conversely, stroke can disrupt sleep architecture and trigger or exacerbate sleep disorders, including insomnia, hypersomnia, circadian rhythm disturbances, and breathing-related sleep disorders. These post-stroke sleep disturbances are common and significantly impair rehabilitation, cognitive recovery, and quality of life, yet they remain underdiagnosed and undertreated. Early identification and management of sleep disorders in stroke patients are essential to optimize recovery and reduce the risk of recurrence. Therapeutic strategies include lifestyle modifications, pharmacological treatments, medical devices such as continuous positive airway pressure (CPAP), and emerging alternatives for CPAP-intolerant individuals. Despite growing awareness, significant knowledge gaps persist, particularly regarding non-OSA sleep disorders and their impact on stroke outcomes. Improved diagnostic tools, broader screening protocols, and greater integration of sleep assessments into stroke care are urgently needed. This narrative review synthesizes current evidence on the interplay between sleep and stroke, emphasizing the importance of personalized, multidisciplinary approaches to diagnosis and treatment. Advancing research in this field holds promise for reducing the global burden of stroke and improving long-term outcomes through targeted sleep interventions. Full article

Early weaning of piglets elicits weaning stress, which in turn induces oxidative stress and consequently impairs growth and development. Hydrogen-rich water (HRW), characterized by selective antioxidant properties, mitigates oxidative stress damage and serves as an ideal intervention. This study aimed to evaluate the effects of HRW on weaned piglets, specifically investigating its impact on growth performance, diarrhea incidence, antioxidant function, intestinal morphology, gut microbiota, and hepatic metabolites. The results demonstrate that HRW significantly increased the average daily feed intake and significantly reduced the diarrhea rate in weaned piglets. Analysis of serum oxidative stress indicators revealed that HRW significantly elevated the activities of total antioxidant capacity and total superoxide dismutase while significantly decreasing malondialdehyde concentration. Assessment of intestinal morphology showed that HRW significantly increased the villus height to crypt depth ratio in the duodenum, jejunum, and ileum. Microbial analysis indicated that HRW significantly increased the abundance of Prevotella in the colon. Furthermore, HRW increased the abundance of beneficial bacteria, such as Akkermansia, in the jejunum and cecum, while concurrently reducing the abundance of harmful bacteria like Escherichia. Hepatic metabolite profiling revealed that HRW significantly altered the metabolite composition in the liver of weaned piglets. Differentially abundant metabolites were enriched in oxidative stress-related KEGG pathways, including ABC transporters; pyruvate metabolism; autophagy; FoxO signaling pathway; glutathione metabolism; ferroptosis; and AMPK signaling pathways. In conclusion, HRW alleviates diarrhea and promotes growth in weaned piglets by enhancing antioxidant capacity. These findings provide a scientific foundation for the application of HRW in swine production and serve as a reference for further exploration into the mechanisms underlying HRW’s effects on animal health and productivity. Full article

Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension. By 2040, CKD is predicted to be the fifth-leading cause of years of life lost. Developing strategies to prevent CKD and to reduce its progression to kidney failure is thus of great public health significance. Hypertension is known to be both a cause and a consequence of kidney damage and an eminently modifiable risk factor. An increased risk of hypertension, especially among women, has been linked to chronic exposure to the ubiquitous food contaminant cadmium (Cd). The mechanism is unclear but is likely to involve its action on the proximal tubular cells (PTCs) of the kidney, where Cd accumulates. Here, it leads to chronic tubular injury and a sustained drop in the estimated glomerular filtration rate (eGFR), a common sequela of ischemic acute tubular necrosis and acute and chronic tubulointerstitial inflammation, all of which hinder glomerular filtration. The present review discusses exposure levels of Cd that have been associated with an increased risk of hypertension, albuminuria, and eGFR ≤ 60 mL/min/1.73 m² (low eGFR) in environmentally exposed people. It highlights the potential role of 20-hydroxyeicosatetraenoic acid (20-HETE), the second messenger produced in the kidneys, as the contributing factor to gender-differentiated effects of Cd-induced hypertension. Use of GFR loss and albumin excretion in toxicological risk calculation, and derivation of Cd exposure limits, instead of β₂-microglobulin (β₂M) excretion at a rate of 300 µg/g creatinine, are recommended. Full article

Postmenopausal osteoporosis is estrogen-dependent and results in an imbalance between bone formation and resorption. The approved therapy is intended to reduce the risk and consequences of fractures, but still has a number of contraindications and associated adverse effects. Recently, oxytocin has been shown to have an anabolic effect on bone tissue, increasing the production of osteoblasts and inhibiting the activity of osteoclasts. Thus, this study aimed to examine the potential of oxytocin as a biomarker and therapeutic agent for postmenopausal osteoporosis. A PubMed search yielded 16 articles upon analysis of the inclusion and exclusion criteria. The results showed that, compared to women in the same age group without bone loss, those diagnosed with osteoporosis exhibited lower blood oxytocin levels, possibly related to a greater tendency towards fractures. The administration of oxytocin could be a promising strategy to enhance bone quality and, consequently, to reduce the incidence of fragility fractures; however, no human studies have been conducted regarding its use as a possible treatment. Thus, it is essential to increase the number of clinical trials in women with ovarian dysfunction and bone loss, in which oxytocin could become a viable therapeutic alternative. Full article

Insulin resistance (IR), a core component in the development of type 2 diabetes mellitus (T2DM), is increasingly recognized for its role in cardiovascular and pulmonary complications. This review explores the relationship between IR, right ventricular dysfunction (RVD), and decreased lung volume in patients with T2DM. Emerging evidence suggests that IR contributes to early structural and functional alterations in the right ventricle, independent of overt cardiovascular disease. The mechanisms involved include oxidative stress, inflammation, dyslipidemia, and obesity—factors commonly found in metabolic syndrome and T2DM. These pathophysiological changes compromise right ventricular contractility, leading to reduced pulmonary perfusion and respiratory capacity. RVD has been associated with chronic lung disease, pulmonary hypertension, and obstructive sleep apnea, all of which are prevalent in the diabetic population. As RVD progresses, it can result in impaired gas exchange, interstitial pulmonary edema, and exercise intolerance—highlighting the importance of early recognition and management. Therapeutic strategies should aim to improve insulin sensitivity and cardiac function through lifestyle interventions, pharmacological agents such as SGLT2 inhibitors and GLP-1/GIP analogs, and routine cardiac monitoring. These approaches may help slow the progression of RVD and its respiratory consequences. Considering the global burden of diabetes and obesity, and the growing incidence of related complications, further research is warranted to clarify the mechanisms linking IR, RVD, and respiratory dysfunction. Understanding this triad will be crucial for developing targeted interventions that improve outcomes and quality of life in affected patients. Full article

The extended operation of high-speed railways has led to an increased incidence of tunnel lining defects, with falling debris posing a significant safety threat. Within tunnels, single-train passage and trains-crossing events constitute the most frequent operational scenarios, both generating extreme aerodynamic environments that alter debris trajectories from free fall. To systematically investigate the aerodynamic differences and underlying mechanisms governing falling debris behavior under these two distinct conditions, a three-dimensional computational fluid dynamics (CFD) model (debris–air–tunnel–train) was developed using an improved delayed detached eddy simulation (IDDES) turbulence model. Comparative analyses focused on the translational and rotational motions as well as the aerodynamic load coefficients of the debris in both single-train and trains-crossing scenarios. The mechanisms driving the changes in debris aerodynamic behavior are elucidated. Findings reveal that under single-train operation, falling debris travels a greater distance compared with trains-crossing conditions. Specifically, at train speeds ranging from 250–350 km/h, the average flight distances of falling debris in the X and Z directions under single-train conditions surpass those under trains crossing conditions by 10.3 and 5.5 times, respectively. At a train speed of 300 km/h, the impulse of C_Fx and C_Fz under single-train conditions is 8.6 and 4.5 times greater than under trains-crossing conditions, consequently leading to the observed reduction in flight distance. Under the conditions of trains crossing, the falling debris is situated between the two trains, and although the wind speed is low, the flow field exhibits instability. This is the primary factor contributing to the reduced flight distance of the falling debris. However, it also leads to more pronounced trajectory deviations and increased speed fluctuations under intersection conditions. The relative velocity (CRV) on the falling debris surface is diminished, resulting in smaller-scale vortex structures that are more numerous. Consequently, the aerodynamic load coefficient is reduced, while the fluctuation range experiences an increase. Full article

The manuscript examines the cause-and-effect relationships of fires in the Republic of Serbia over a fifteen-year period, primarily from the aspect of human safety. For this purpose, numerical variables describing the number of injuries and deaths in fires were introduced, on which various analysis and modeling techniques were implemented, which can be viewed in the context of data mining (DM). First, for both observed variables, stochastic modeling of their temporal dynamics was analyzed, and subsequently, cluster analysis of the values of these variables was performed using two different methods. Finally, by interpreting these variables as outputs (objectives) for the classification problem, several decision trees were formed that describe the influence and relationship of different fire causes on situations in which injuries or human casualties occur or not. In that way, several different types of fires have been identified, including rare but deadly incidents that require urgent preventive measures. Key risk factors such as fire cause, location, season, etc., have been found to significantly influence human casualties. These findings provide practical insights for improving fire protection policies and emergency response. Through such a comprehensive analysis, it is believed that some important results have been obtained that precisely describe the specific relationships between the causes and consequences of fires occurring in the Republic of Serbia. Full article

The improvement of environmental conditions has become a priority for governments and legislators. New electrified mobility systems are increasingly present in our environment, as they enable the reduction of polluting emissions. Electric vehicles (EVs) are one of the fastest-growing alternatives to date, with exponential growth expected over the next few years. In this article, the various charging modes for EVs are explored, and the risks associated with charging technologies are analysed, particularly for charging systems in high-power DC with Lithium battery energy storage, given their long market deployment and characteristic behaviour. In particular, the Arc Flash (AF) risk present in high-power DC chargers will be studied, involving numerous simulations of the charging process. Subsequently, the Incident Energy (IE) analysis is carried out at different specific points of a commercial high-power ‘Mode 4’ charger. For this purpose, different analysis methods of recognised prestige, such as Doan, Paukert, or Stokes and Oppenlander, are applied, using the latest version of the ETAP^® simulation tool version 22.5.0. This study focuses on quantifying the potential severity (consequences) of an AF event, assuming its occurrence, rather than performing a probabilistic risk assessment according to standard methodologies. The primary objective of this research is to comprehensively quantify the potential consequences for workers involved in the operation, maintenance, repair, and execution of tasks related to EV charging systems. This analysis makes it possible to provide safe working conditions and to choose the appropriate and necessary personal protective equipment (PPE) for each type of operation. It is essential to develop this novel process to quantify the consequences of AF and to protect the end users of EV charging systems. Full article

Obesity is a growing global health concern with widespread impacts on physical, psychological, and social well-being. Clinically, it is a major driver of type 2 diabetes (T2D), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), and cancer, reducing life expectancy by 5–20 years and imposing a staggering economic burden of USD 2 trillion annually (2.8% of global GDP). Despite its significant health and socioeconomic impact, earlier obesity medications, such as fenfluramine, sibutramine, and orlistat, fell short of expectations due to limited effectiveness, serious side effects including valvular heart disease and gastrointestinal issues, and high rates of treatment discontinuation. The advent of glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, tirzepatide) has revolutionized obesity management. These agents demonstrate unprecedented efficacy, achieving 15–25% mean weight loss in clinical trials, alongside reducing major adverse cardiovascular events by 20% and T2D incidence by 72%. Emerging therapies, including oral GLP-1 agonists and triple-receptor agonists (e.g., retatrutide), promise enhanced tolerability and muscle preservation, potentially bridging the efficacy gap with bariatric surgery. However, challenges persist. High costs, supply shortages, and unequal access pose significant barriers to the widespread implementation of obesity treatment, particularly in low-resource settings. Gastrointestinal side effects and long-term safety concerns require close monitoring, while weight regain after medication discontinuation emphasizes the need for ongoing adherence and lifestyle support. This review highlights the transformative potential of incretin-based therapies while advocating for policy reforms to address cost barriers, equitable access, and preventive strategies. Future research must prioritize long-term cardiovascular outcome trials and mitigate emerging risks, such as sarcopenia and joint degeneration. A multidisciplinary approach combining pharmacotherapy, behavioral interventions, and systemic policy changes is critical to curbing the obesity epidemic and its downstream consequences. Full article

Rockfalls, among the most common natural disasters, pose risks such as traffic congestion, casualties, and substantial property damage. Guizhou Province, with China’s fourth-longest highway network, features mountainous terrain prone to frequent rockfall incidents annually. Consequently, assessing highway rockfall risks in Guizhou Province is crucial for safeguarding the lives and travel of residents. This study evaluates highway rockfall risk through three key components: susceptibility, hazard, and vulnerability. Susceptibility was assessed using information content and logistic regression methods, considering factors such as elevation, slope, normalized difference vegetation index (NDVI), aspect, distance from fault, relief amplitude, lithology, and rock weathering index (RWI). Hazard assessment utilized a fuzzy analytic hierarchy process (AHP), focusing on average annual rainfall and daily maximum rainfall. Socioeconomic factors, including GDP, population density, and land use type, were incorporated to gauge vulnerability. Integration of these assessments via a risk matrix yielded comprehensive highway rockfall risk profiles. Results indicate a predominantly high risk across Guizhou Province, with high-risk zones covering 41.19% of the area. Spatially, the western regions exhibit higher risk levels compared to eastern areas. Notably, the Bijie region features over 70% of its highway mileage categorized as high risk or above. Logistic regression identified distance from fault lines as the most negatively correlated factor affecting highway rockfall susceptibility, whereas elevation gradient demonstrated a minimal influence. This research provides valuable insights for decision-makers in formulating highway rockfall prevention and control strategies. Full article

Alzheimer’s disease (AD) is one of the main causes of dementia, with an exponential increment in its incidence as years go by. However, since pathophysiological mechanisms are complex and multifactorial, therapeutic strategies remain inconclusive and only provide symptomatic relief to patients. In order to solve this problem, new strategies have been investigated over recent years for AD treatment. This field has been reborn due to epidemiological and preclinical findings that demonstrate the fact that omega-3 polyunsaturated fatty acids (ω-3 PUFAs) can be promising therapeutic agents because of their anti-inflammatory, antioxidant, and neurogenic-promoting activities, thus allowing us to classify these molecules as neuroprotectors. Similarly, ω-3 PUFAs perform important actions in the formation of characteristic AD lesions, amyloid-β plaques (Aβ) and neurofibrillary tangles, reducing the development of these structures. Altogether, the aforementioned actions hinder cognitive decline and possibly reduce AD development. In addition, ω-3 PUFAs modulate the inflammatory response by inhibiting the production of pro-inflammatory molecules and promoting the synthesis of specialised pro-resolving mediators. Consequently, the present review assesses the mechanisms by which ω-3 PUFAs can act as therapeutic molecules and the effectiveness of their use in patients. Clinical evidence so far has shown promising results on ω-3 PUFA effects, both in animal and epidemiological studies, but remains contradictory in clinical trials. More research on these molecules and their neuroprotective effects in AD is needed, as well as the establishment of future guidelines to obtain more reproducible results on this matter. Full article

Congenital hypothyroidism (CH) is one of the major preventable causes of intellectual disability. This study evaluates the incidence of CH through a newborn screening (NBS) program in eastern Morocco. A descriptive cross-sectional design was used and heel prick blood samples were collected on blotting paper to measure Thyroid-Stimulating Hormone (TSH) using an immunofluorimetric assay. 4062 newborns were screened (51.3% male, 48.7% female). TSH levels significantly varied by age: newborns sampled before 24 h had a higher median TSH (3.7 µU/mL [0.10–28.90]) compared to those sampled at 24 h or more (2.1 µU/mL [0.10–32.30]; p < 0.001). Using age-specific cut-off values, 18 suspected CH cases were recalled (recall rate: 0.44%). Among the 16 cases who completed confirmatory testing, 4 had transient hyperthyrotropinemia (HTT), characterized by mildly abnormal serum TSH and T4 levels that normalized spontaneously after few months without treatment. Three cases were diagnosed with CH confirmed at birth with markedly elevated serum TSH concentrations and significantly reduced T4 levels. Consequently, the birth prevalence of CH confirmed at birth was 1:1354 live births. The median preanalytical delay was 6 days (IQR: 3–12) and the TSH result turnaround was 8 days (IQR: 5–15), potentially affecting timely intervention. This first report from eastern Morocco confirms the relevance of neonatal screening but highlights delays that must be addressed to enhance early diagnosis and management. Full article

The backbone of maritime transportation has always been the successful execution of ship operations. However, the human factor has proven to be a weak point in the system. To reduce and mitigate it, a regulatory framework and consequently a safety system for ship barriers were created and implemented with this goal in mind. The expected result of these measures was the creation of a resilient maritime transport system. Nevertheless, the available statistics show that most of the reported accidents and incidents occurred during ship operation, with the human factor as the main cause. Therefore, it is useful to investigate whether the regulatory framework can influence the safety system of ship barriers. Therefore, the objectives of the study are as follows: (a) to investigate and determine the regulatory safety requirements and the elements related to the ship barrier system, and (b) to investigate the influence of the regulatory safety requirements on the elements related to the ship barrier system. From the data obtained and the analyses performed, seven factors emerged. Four of them were related to the regulatory requirements and three to the shipboard barrier system, a basis for the presented models. Several important findings were obtained that have theoretical and practical implications and further highlight the importance and potential undesirable side effects of the provisions of the current regulatory framework. Full article

Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy with rising incidence and poor prognosis. TP53, previously identified as the most frequently mutated gene in EAC in our studies, plays a central role in tumor suppression and regulation. However, the metabolic consequences of TP53 mutations in EAC remain largely uncharacterized. We metabolically profiled three TP53-mutant EAC cell models (OE33, OE19, and FLO1) representing progressive stages of tumor differentiation and harboring distinct TP53 alterations. Our analyses revealed different metabolic phenotypes associated with TP53 status. OE33 cells predominantly use glycolytic metabolism but display limited adaptability to environmental changes, possibly due to a higher differentiation state. FLO1 cells exhibit a strong glycolytic dependence, elevated lactate production, and robust proliferation under acidic conditions, consistent with an aggressive and metastatic phenotype. OE19 cells preferentially utilize oxidative phosphorylation, demonstrated by resilience to glucose and glutamine deprivation, and ROS accumulation. These findings highlight the metabolic plasticity of EAC and suggest that TP53 mutation type might influence bioenergetic dependencies. Targeting these metabolic vulnerabilities may offer novel therapeutic avenues for personalized treatment in EAC. Full article

Background/Objectives: Adequate vitamin D levels are essential for various physiological functions, including cell growth, immune modulation, metabolic regulation, DNA repair, and overall health span. Despite its proven cost-effectiveness, widespread deficiency persists due to inadequate supplementation and limited sunlight exposure. Methods: This systematic review (SR) examines the relationship between vitamin D and the reduction of cancer risk and mortality, and the mechanisms involved in cancer prevention. This SR followed the PRISMA and PICOS guidelines and synthesized evidence from relevant studies. Results: Beyond genomic actions via calcitriol [1,25(OH)₂D]-receptor interactions, vitamin D exerts cancer-protective effects through mitigating inflammation, autocrine, paracrine, and membrane signaling. The findings reveal a strong inverse relationship between serum 25(OH)D levels and the incidence, metastasis, and mortality of several cancer types, including colon, gastric, rectal, breast, endometrial, bladder, esophageal, gallbladder, ovarian, pancreatic, renal, vulvar cancers, and both Hodgkin’s and non-Hodgkin’s lymphomas. While 25(OH)D levels of around 20 ng/mL suffice for musculoskeletal health, maintaining levels above 40 ng/mL (100 nmol/L: range, 40–80 ng/mL) significantly lowers cancer risks and mortality. Conclusions: While many observational studies support vitamin D’s protective role in incidents and deaths from cancer, some recent mega-RCTs have failed to demonstrate this. The latter is primarily due to critical study design flaws, like recruiting vitamin D sufficient subjects, inadequate dosing, short durations, and biased designs in nutrient supplementation studies. Consequently, conclusions from these cannot be relied upon. Well-designed, adequately powered clinical trials using appropriate methodologies, sufficient vitamin D₃ doses, and extended durations consistently demonstrate that proper supplementation significantly reduces cancer risk and markedly lowers cancer mortality. Full article