Search Results (5,537)

Background: Serum cystatin C is a promising biomarker for vascular risk, yet its nonlinear dose–response relationships and prognostic value in general populations remain unclear, particularly for stroke-specific outcomes. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted in 1999–2002 cycles. A total of 11,610 participants were included in the primary analysis examining the cross-sectional association between cystatin C and stroke morbidity, using multivariate logistic regression models and odds ratios (ORs). Analyses utilized complete-case data (n = 11,610 for morbidity; n = 11,598 for mortality). Subsequently, 11,598 adults were retained for mortality endpoint analyses, which focused on the longitudinal association between cystatin C and stroke mortality, using cause-specific weighted multivariable Cox models and ratios (HRs). Restricted cubic splines identified nonlinear thresholds, and piecewise regression quantified risk gradients. Models were adjusted for sociodemographic/clinical/behavioral confounders. Results: Serum cystatin C exhibited a nonlinear dose–response relationship with stroke morbidity (p for nonlinear < 0.001), with an inflection point at 1.24 mg/L; below this threshold, each 0.1 mg/L increase conferred 13.84-fold higher odds (95% CI: 7.11–27.03, p < 0.001). For mortality, nonlinear thresholds were identified at 1.24 mg/L for all-cause/cause-specific mortality (HR = 6.73–10.60 per 0.1 mg/L increase, p < 0.001) and 1.81 mg/L for stroke-specific mortality. Conversely, cerebrovascular mortality demonstrated a linear association (HR = 1.43 per 1 mg/L increase, p = 0.008), though cystatin C independently predicted risk (HR = 1.38/continuous, p = 0.034 in fully adjusted models). Conclusions: This study identifies serum cystatin C as an independent predictor after full adjustment of stroke morbidity and all-cause and cardio-cerebrovascular mortality. Consequently, cystatin C emerges as a dual-purpose biomarker for early vascular injury detection in subclinical populations and integrated mortality risk stratification. Future research should validate these thresholds in prospective neuroimaging-confirmed cohorts and investigate interventions targeting cystatin C pathways to optimize preventive strategies. Full article

Advancements in the medical field, particularly in cardiovascular diseases, have significantly improved the diagnosis, management, and prevention of life-threatening presentations and comorbidities. Despite this progress, cardiovascular diseases continue to place a substantial burden on healthcare systems, contributing to nearly 32% of all global deaths according to the World Health Organisation. A predominant complication arising from the treatment of cardiovascular diseases is cardiac ischaemia–reperfusion (I/R) injury, which occurs when blood supply is restored to the myocardium following a period of ischaemia, paradoxically resulting in further tissue damage. There are multiple factors involved in complex pathophysiology and complicated clinical outcomes. Although various therapeutic strategies have been explored to mitigate this injury, an optimal solution has yet to be identified. Therapeutic approaches such as pharmacological interventions and molecular therapy have shown promising prospects in this field. Ongoing research aims to address this unresolved issue, which continues to pose significant challenges for both patients and healthcare professionals. This review aims to explore the multitude of underlying mechanisms of ischaemia–reperfusion injury, and identify current knowledge gaps and new emerging therapeutic interventions. Full article

With the rapid advancement of industrial intelligence, ensuring occupational safety has become an increasingly critical concern. Among the essential personal protective equipment (PPE), safety helmets play a vital role in preventing head injuries. There is a growing demand for real-time detection of helmet chinstrap wearing status during industrial operations. However, existing detection methods often encounter limitations such as user discomfort or potential privacy invasion. To overcome these challenges, this study proposes a non-intrusive approach for detecting the wearing state of helmet chinstraps, inspired by the mechanosensory hair arrays found on spider legs. The proposed method utilizes multiple MEMS inertial sensors to emulate the sensory functionality of spider leg hairs, thereby enabling efficient acquisition and analysis of helmet wearing states. Unlike conventional vibration-based detection techniques, posture signals reflect spatial structural characteristics; however, their integration from multiple sensors introduces increased signal complexity and background noise. To address this issue, an improved adaptive convolutional neural network (ICNN) integrated with a long short-term memory (LSTM) network is employed to classify the tightness levels of the helmet chinstrap using both single-sensor and multi-sensor data. Experimental validation was conducted based on data collected from 20 participants performing wall-climbing robot operation tasks. The results demonstrate that the proposed method achieves a high recognition accuracy of 96%. This research offers a practical, privacy-preserving, and highly effective solution for helmet-wearing status monitoring in industrial environments. Full article

Background/Objectives: Methamphetamine (METH), a potent psychostimulant, exerts harmful effects on the vascular system by promoting oxidative stress, inflammation, and endothelial injury. While its impact on the blood–brain barrier is well documented, its influence on the retinal microvasculature remains less understood. This study investigated the effects of METH on syndecan-1 expression and endothelial function in primary rat retinal microvascular endothelial cells (RRMECs) and isolated ophthalmic arteries. Methods: We assessed METH-induced changes in mRNA and protein expression levels of syndecan-1, matrix metalloproteinase (MMP)-2, and MMP-9. Endothelial function was evaluated using scratch migration assays and trans-endothelial electrical resistance (TEER) measurements. The mechanistic involvement of MMP-9 and trace amine-associated receptor 1 (TAAR-1), a known receptor for METH, was examined using selective pharmacological inhibitors. Results: METH exposure significantly decreased syndecan-1 expression and increased MMP-9 levels. These changes were accompanied by impaired endothelial migration and reduced TEER in RRMECs. Similar findings were confirmed in cultured ophthalmic arteries, reinforcing the translational relevance of our in vitro results. Inhibition of MMPs restored syndecan-1 expression and rescued endothelial function. Furthermore, TAAR-1 antagonism protected against syndecan-1 degradation, reduced MMP-9 upregulation, and improved endothelial migration and barrier resistance. Conclusions: Our findings suggest that METH induces loss of syndecan-1 and retinal vascular integrity by promoting TAAR-1–mediated MMP-9 upregulation. Targeting the TAAR-1/MMP-9 axis may offer a promising therapeutic strategy for preventing METH-induced microvascular damage in the retina. Full article

Excessive stress disrupts cardiac homeostasis via complex and multifactorial mechanisms, resulting in cardiac dysfunction, cardiovascular disease, or even sudden cardiac death, yet the underlying molecular mechanisms remain poorly understood. Accordingly, we aimed to elucidate how stress induces calcium dysregulation and contributes to cardiac dysfunction and injury through the nuclear receptor subfamily 3 group c member 1 (NR3C1)/Glomulin (GLMN)/FK506-binding protein 12.6 (FKBP12.6) signaling pathway. Using mouse models of acute and chronic restraint stress, we observed that stress-exposed mice exhibited reduced left ventricular ejection fraction, ventricular wall thickening, elevated serum and myocardial cTnI levels, along with pathological features of myocardial ischemia and hypoxia, through morphological, functional, and hormonal assessments. Using transmission electron microscopy and Western blotting, we found that stress disrupted mitochondrial quality control in cardiomyocytes, evidenced by progressive mitochondrial swelling, cristae rupture, decreased expression of fusion proteins (MFN1/OPA1) and biogenesis regulator PGC-1α, along with aberrant accumulation of fission protein (FIS1) and autophagy marker LC3. At the cellular level, ChIP-qPCR and siRNA knockdown confirmed that stress activates the glucocorticoid receptor NR3C1 to repress its downstream target GLMN, thereby preventing FKBP12.6 ubiquitination and degradation, resulting in calcium leakage and overload, which ultimately impairs mitochondrial quality control and damages cardiomyocytes. In conclusion, our findings reveal that stress induces myocardial damage through NR3C1/GLMN-mediated FKBP12.6 ubiquitination, disrupting calcium homeostasis and mitochondrial quality control, and lay a theoretical foundation for dissecting the intricate molecular network of stress-induced cardiomyopathy. Full article

This study aimed to monitor internal load, well-being, and recovery status in U16 male water polo players during a congested competitive period. Fourteen athletes from an Italian club played 12 matches (seven friendly, five official) over 7 days. The internal match load was measured using the session-RPE method (s-RPE). Perceived enjoyment was measured with the Enjoyment Likert Scale (ENJ), while recovery and well-being were evaluated using the Perceived Recovery Scale (PRS) and the Hooper Index (HI), respectively. No significant main effects were found on s-RPE, PRS, and HI considering friendly and official matches. However, ENJ was significantly higher during official matches (p < 0.005). PRS values were significantly affected by daytime matches (p < 0.005), with better perceived recovery reported for morning matches. Linear mixed model analysis revealed significant associations between s-RPE and HI (p = 0.001), the fatigue item (p = 0.001), and the PRS (p = 0.004). These results suggest that as internal load increases, players experience higher fatigue and report lower recovery and well-being scores. Employing simple, non-invasive tools like the RPE, PRS, and HI can help coaches and support staff to identify early signs of overtraining or insufficient recovery, allowing for more individualized load management and injury prevention in youth water polo athletes. Full article

Background: Freeze tolerance is an uncommon but highly effective strategy that allows certain vertebrates to survive prolonged exposure to subzero temperatures in a frozen, ischemic state. While past studies have characterized the metabolic and biochemical adaptations involved, including cryoprotectant accumulation and metabolic rate suppression, the contribution of post-transcriptional gene regulation by microRNAs (miRNAs) remains largely unexplored. This study investigated freeze-responsive miRNAs in cardiac tissue of the gray tree frog, Dryophytes versicolor, to better understand the molecular mechanisms that support ischemic survival and tissue preservation. Methods: Adult frogs were subjected to controlled freezing at −2.5 °C, and cardiac tissue was collected from frozen and control animals. Total RNA was extracted and analyzed via small RNA sequencing to identify differentially expressed miRNAs, followed by target gene prediction and KEGG pathway enrichment analysis. Results: A total of 3 miRNAs were differentially expressed during freezing, with significant upregulation of miR-93-5p and let-7b-5p and downregulation of miR-4485-3p. Predicted targets of upregulated miRNAs included genes involved in immune signaling pathways (e.g., cytokine–cytokine receptor interaction), steroid hormone biosynthesis, and neuroactive ligand–receptor interaction, suggesting suppression of energetically costly signaling processes. Downregulation of miRNAs targeting cell cycle, insulin signaling, and WNT pathways indicates possible selective preservation of cytoprotective and repair functions. Conclusion: Overall, these results suggest that D. versicolor employs miRNA-mediated regulatory networks to support metabolic suppression, maintain essential signaling, and prevent damage during prolonged cardiac arrest. This work expands our understanding of freeze tolerance at the molecular level and may offer insights into biomedical strategies for cryopreservation and ischemia–reperfusion injury. Full article

Globally, cardiovascular diseases represent a major cause of morbidity and mortality, despite the availability of preventive, diagnostic, and therapeutic measures in contemporary allopathic medicine. In accordance with their ethnomedical applications, herbal medicines may offer valuable options for the prevention, treatment, and management of cardiovascular disorders. Considering that cardioprotective effects are associated with antioxidant mechanisms, and that our knowledge of the antioxidant properties of polyphenolic compounds, as well as of the effects of Melilotus species on the heart, is limited, the present study aimed to evaluate the cardioprotective potential of hydroalcoholic extracts of M. officinalis and M. albus aerial parts. The extracts were evaluated for total phenolic content (TPC), total flavonoid content (TFC), and total coumarin content (TCC) by spectrophotometric methods and by LC-MS/MS. The effect of pretreatment with Melilotus sp. extracts on the isoprenaline-induced infarct-like lesion in rats was evaluated by ECG monitoring and the assessment of serum oxidative stress markers and serum cardiac injury markers. Various polyphenolic compounds were identified by LC-MS/MS in M. officinalis and M. albus aerial parts: catechin, syringic acid, protocatechuic acid, and vanillic acid. Gallic acid and chlorogenic acid were found only in M. officinalis. The extracts showed good in vivo antioxidant activity: M. officinalis and M. albus extracts induced a significant decrease in the levels of oxidative stress index (OSI) and total oxidant status (TOS), while pre-treatment with M. albus extract induced a significant reduction in nitric oxide production, and pretreatment with M. officinalis increased total thiols (SH) levels. In the same way, ECG and cardiac injury markers were also improved. These results show that M. officinalis and M. albus extracts may exert cardioprotective effects against myocardial ischemia by reducing oxidative stress. Full article

Background: Body composition assessment is important in professional football as a measure of overall adaptation of the athlete to the training demand and calorie intake. However, it is operator-dependent, relying on subject positioning and the focus angle of the X-rays. In addition, the usual appendicular lean mass index (ALMI) does not include the pelvitrochanteric muscles, which are often implicated in athlete injuries. Methods: Three independent operators compared the reproducibility of dual-energy X-ray absorptiometry (DEXA) including pelvi-trochanteric muscle mass in twenty professional football players, using the standard and a new method. Results: Mean age, weight, and height of the footballers were 25.9 ± 4.9 years, 79.4 ± 9.4 kg, and 1.83 ± 0.09 m. Using the standard method, the ALMI was 9.28 ± 0.62, 9.20 ± 0.65, and 9.13 ± 0.64 kg/m² for the first, second and third operator, respectively. When including the pelvi-trochanteric muscles, the ALMI values were 11.90 ± 0.66, 11.84 ± 0.63, and 11.83 ± 0.65 kg/m² for the three operators. The difference between the two methods was significant (p < 0.001). The mean inter-operator difference was similar regardless of the method used (0.099 ± 0.06 kg/m²). The intraclass correlation coefficients (ICC) (A,1) were 0.949 [0.881; 0.979] for the standard method and 0.977 [0.951; 0.990] for the new method. The ICC (C,1) was 0.960 [0.918; 0.983] for the standard method and 0.979 [0.957; 0.991] for the new method. Conclusions: Thus, both new and conventional methods showed excellent reproducibility. However, reproducibility and inter-operator variability were better with the adjustment of the new scan lines. Moreover, the inclusion of a larger gluteal and adductors muscle mass was easy to achieve, providing additional information that could potentially be useful for early diagnosis and/or prevention of future muscular injuries in elite athletes. Full article

Repeated UV exposure, air pollution, and toxins promote skin oxidative stress. ROS destroy macromolecules, changing cellular mechanisms and signaling cascades. Inflammation and injury to skin cells degrade function and accelerate aging, causing wrinkles, firmness loss, and dermatological disorders. Gymnema inodorum (GI) contains phytochemical antioxidants such polyphenols and triterpenoids that lower ROS and strengthen skin. GI extracts (GIEs) have never been examined for their effects on dermal skin fibroblasts’ oxidative stress and intracellular cytoprotective mechanisms. In this study, GIEs were prepared as a water extract (GIE0) and ethanol extracts with concentrations ranging from 20% to 95% v/v (GIE20, GIE40, GIE60, GIE80, and GIE95). These extracts were assessed for phytochemical content, antioxidant capacity, and free radical scavenging efficacy. The results were compared to a commercially available native Gymnema extract (NGE) obtained from Gymnema sylvestre. During principal component analysis (PCA), the most effective extracts were identified and subsequently evaluated for their ability to mitigate oxidative stress in fibroblasts. Cytoprotective effects of GIE and NGE against H₂O₂-induced human dermal fibroblast injury were investigated by cell viability, intracellular ROS production, and signaling pathways. GIE0, GIE80, GIE95, and NGE were the best antioxidants. By preserving ROS balance and redox homeostasis, GIE and NGE reduce fibroblast inflammation and oxidative stress-induced damage. Decreased ROS levels reduce MAPK/AP-1/NF-κB and PI3K/AKT/NF-κB signaling pathways, diminishing inflammatory cytokines. In conclusion, GIE and NGE have antioxidant and anti-inflammatory capabilities that can reduce H₂O₂-induced fibroblast oxidative stress and damage, thereby preventing skin aging and targeting cancer-associated fibroblasts. Full article

Doxorubicin (DOX) is an anthracycline chemotherapeutic agent that is clinically limited by doxorubicin-induced cardiotoxicity (DIC), with ferroptosis and apoptosis identified as key mechanisms. As an antioxidant enzyme, GPX4 undergoes ubiquitin-mediated degradation during myocardial ischemia–reperfusion injury; however, the role of its ubiquitination in DIC remains unclear. This study revealed that GPX4 undergoes ubiquitinated degradation during DIC, exacerbating ferroptosis and apoptosis in cardiomyocytes. NEDD4L was found to interact with GPX4, and its expression was upregulated in DOX-treated mouse myocardial tissues and cardiomyocytes. NEDD4L knockdown alleviated DIC, as well as ferroptosis and apoptosis in cardiomyocytes. Mechanistically, NEDD4L recognizes GPX4 through its WW domain and mediates K48-linked ubiquitination and degradation of GPX4 under DOX stimulation via its HECT domain. Knockdown of NEDD4L reduced DOX-induced GPX4 ubiquitination levels and subsequent degradation. Notably, while NEDD4L knockdown mitigated DOX-induced cell death, concurrent GPX4 knockdown attenuated this protective effect, indicating that GPX4 is a key downstream target of NEDD4L in regulating cardiomyocyte death. These findings identify NEDD4L as a potential therapeutic target for preventing and treating DIC. Full article

As the leading cause of global mortality, cardiovascular diseases demand improved and innovative strategies for early detection and risk assessment to enhance prevention and timely treatment. This comprehensive review examines the potential of combining high-sensitivity cardiac troponins (hs-cTns) and homocysteine (Hcy) as complementary biomarkers for enhanced cardiovascular risk prediction. hs-cTn assays have revolutionized cardiovascular diagnostics by enabling the detection of minimal myocardial injury, improving early diagnosis of acute coronary syndrome, and providing robust prognostic information in both symptomatic and asymptomatic populations. Hcy, while established as a marker of vascular dysfunction, presents an interpretative challenge due to multiple confounding factors and inconsistent therapeutic responses. Emerging evidence demonstrates significant correlations between elevated Hcy and troponins across various clinical conditions, suggesting that their combined assessment—reflecting both myocardial injury and vascular dysfunction—may improve cardiovascular risk stratification. While initial findings are promising, additional studies are required to validate the clinical value of the combined marker approach. Future development of personalized interpretation algorithms, and multi-marker panels incorporating these biomarkers, may significantly advance cardiovascular medicine and enable more effective population-specific risk management strategies. Full article

Spinal cord injury (SCI) profoundly affects motor–sensory functions, reducing mobility and quality of life. Robotic exoskeletons offer a promising solution to support gait training, improve mobility, and prevent secondary complications. Existing research predominantly focuses on complete SCI, with limited exploration of long-term effects and tailored training for incomplete SCI. This study investigates device-based outcomes of personalized exoskeleton gait training in 33 individuals with incomplete SCI, with different lesion levels: cervical, thoracic, and lumbar. Participants underwent up to 39 sessions of gait training with a commercially available lower limb exoskeleton. Session parameters, including duration, intensity, and modality, were tailored to each individual’s clinical needs as determined by a medical team. Analysis focused on endurance, performance on the device, and patient-reported outcomes related to walking fluidity, safety, and satisfaction. Results showed overall improvement in endurance and performance, with the most significant gains observed in participants with thoracic-level injuries. All participants reported increased perceived safety, walking fluidity, and high satisfaction with the training. These findings support the potential of personalized exoskeleton training to enhance outcomes and experiences for individuals with incomplete SCI. The difference in improvement between lesion levels highlights the need for customized approaches to address the diverse clinical conditions within this population. Full article

Background: Circus arts are gaining popularity across the globe and lifespan. Despite growing participation rates, there is limited high-quality evidence describing the physical therapy evaluation and management of injury within this population. The purpose of this scoping review was to identify and summarize evidence related to the injury characteristics and management of circus artists. Methods: With a research librarian, computerized searches were developed and performed using online databases (PubMed, CINAHL, Scopus, SPORTDiscus and Cochrane), gray literature and non-medical databases. Two authors independently voted on article inclusion with a third author blinded to previous voting used in case of conflict. Concept mapping identified five primary themes related to circus injuries and physical therapy treatment. Data was extracted from each article based on content relevant to the classification. Results: In total, 1095 titles were retrieved from electronic searches, of which 49 studies were included. Overall, 20 studies related to injury characteristics, 10 to risk factors, 9 to each psychosocial variables and interventions, and 8 to screening. Acrobats with required ground elements were the most commonly injured discipline, particularly at the shoulder, ankle and spine. Intrinsic and extrinsic risk factors were identified and numerous psychosocial and lifestyle contributing factors were reported. Literature guiding treatment is limited. Conclusions: This scoping review mapped and synthesized evidence related to the evaluation and management of circus artist injuries. While injury patterns and characteristics are generally understood, the treatment of this population is poorly described. Clear gaps in screening, injury prevention strategies, and interventions for this group were identified. Full article

Background: Firearm-related injuries are the leading cause of death among children and adolescents (ages 1 to 19 years) in the United States. Access to and carrying firearms are key risk factors for violence and adolescent firearm use. This study examines the association between family conflict and adolescent gun carrying in Los Angeles County, and the extent to which household and neighborhood contexts contribute to adolescent gun carrying. Methods: We use cross-sectional multilevel data from adolescents ages 12–17 years in the Los Angeles Family and Neighborhood Study, conducted in 2002, to fit a series of generalized linear mixed models to examine the association between family conflict (scale range: 0–2) and adolescent gun carrying. Models include random effects to examine the contributions of household and neighborhood contexts on the outcome measure. Results: After controlling for demographic characteristics, gang involvement, substance use, and household and neighborhood contexts, adolescent experiences of family conflict remain positively associated with adolescent gun carrying behavior (OR = 3.45, p = 0.043). Random effects estimates indicate that a relatively large amount of variation in adolescent gun carrying is explained by household and neighborhood contexts: 23% and 24%, respectively. Conclusions: Multilevel family and community-level interventions, with an emphasis on family violence, are necessary components of prevention strategies to reduce high rates of firearm-related mortality among US adolescents. Full article