Search Results (2,916)

Background/Objectives: Post-traumatic epileptogenesis is a frequent and clinically relevant consequence of traumatic brain injury (TBI), often contributing to worsened neurological and functional outcomes. In patients experiencing early post-injury seizures, rehabilitative strategies that support recovery while considering increased epileptogenic risk are needed. This case study explores the potential benefits of combining neurofeedback (NFB) with motor therapy on cognitive and motor recovery. Methods: A patient hospitalized for severe TBI who experienced an acute symptomatic seizure in the early post-injury phase underwent baseline quantitative EEG (qEEG), neuromotor, functional, and neuropsychological assessments. The patient then completed a three-week rehabilitation program (five days/week) including 30 sensorimotor rhythm (SMR) NFB sessions (35 min each) combined with daily one-hour motor therapy. qEEG and clinical assessments were repeated post-intervention and at 6-month follow-up. Results: Post-intervention qEEG showed significant reductions in Delta and Theta power, reflecting decreased cortical slowing and enhanced neural activation. Relative power analysis indicated reduced Theta activity and Alpha normalization, suggesting improved cortical stability. Increases were observed in Beta and High-beta activity, alongside significant reductions in the Theta/Beta ratio, consistent with improved attentional regulation. Neuropsychological outcomes revealed reliable improvements in global cognition, memory, and visuospatial abilities, mostly maintained or enhanced at follow-up. Depressive and anxiety symptoms decreased markedly. Motor and functional assessments demonstrated meaningful improvements in motor performance, coordination, and functional independence. Conclusions: Findings suggest that integrating NFB with motor therapy may support recovery processes and be associated with sustained neuroplastic changes in the early post-injury phase after TBI, a condition associated with elevated risk for post-traumatic epilepsy. Full article

With the intensification of global population aging, the co-morbidity rate of periodontitis and osteoporosis has significantly increased. The two are pathologically intertwined, forming a vicious cycle characterized by bone immunoregulatory dysfunction in the periodontal microenvironment, abnormal accumulation of reactive oxygen species (ROS), and disruption of bone homeostasis. Conventional mechanical debridement and anti-infective therapy can reduce the pathogen load, but in some patients, it remains challenging to achieve long-term stable control of inflammation and bone resorption. Furthermore, abnormal bone metabolism in the context of osteoporosis further weakens the osteogenic response during the repair phase, limiting the efficacy of these treatments. Bioinspired cell membrane-coated nanoparticles (CMNPs) have emerged as an innovative technological platform. By mimicking the biointerface properties of source cells—such as red blood cells, platelets, white blood cells, stem cells, and their exosomes—CMNPs enable targeted drug delivery, prolonged circulation within the body, and intelligent responses to pathological microenvironments. This review systematically explores how biomimetic design leverages the advantages of natural biological membranes to address challenges in therapeutic site enrichment and tissue penetration, in vivo circulation stability and effective exposure maintenance, and oxidative stress and immune microenvironment intervention, as well as functional regeneration supported by osteogenesis and angiogenesis. Additionally, we conducted an in-depth analysis of the key challenges encountered in translating preclinical research findings into clinical applications within this field, including issues such as the feasibility of large-scale production, batch-to-batch consistency, and long-term biosafety. This review lays a solid theoretical foundation for advancing the clinical translation of synergistic treatment strategies for periodontitis with osteoporosis and provides a clear research and development pathway. Full article

Background/Objectives: Childhood metabolic dysregulation exerts a profound influence on the development of obesity and metabolic diseases. The human gut microbiota, with highly personalized characteristics, plays an important role in host metabolism. However, the dynamics of gut microbial features during this developmental phase are still unclear. This longitudinal observational study collected 204 fecal samples and 153 blood samples from 51 children (aged 8.90 ± 0.78 years) at four timepoints over 52 weeks, aiming to identify dynamic changes in individual gut microbiota and underlying mechanistic interactions that predict measures of pediatric metabolic health. Methods: Fecal samples were subjected to 16S rRNA gene amplicon sequencing and short-chain fatty acid quantification. Serum samples were analyzed for biochemical tests. Dietary intake, physical activity, clinical phenotypes, early-life factors, and fecal characteristics were further assessed. Results: In the results, the fecal microbiota dynamics exhibit inter-individual variation among children, allowing classification into high- and low-stability subgroups based on intra-individual β-diversity variability. Children with low-stability microbiota had adverse blood lipid profiles (p < 0.05). Compared to the high-stability group, the low-stability microbiota demonstrated significant association with low dietary fiber and highly variable amino acid consumption (|r| > 0.3, q < 0.05). Low-stability microbiota exhibited marked fluctuations in Phocaeicola vulgatus, which was strongly linked to both blood triglycerides and lipoprotein(a) levels, as well as dietary fiber and amino acid intake. Baseline depletion of P. vulgatus and Faecalibacterium duncaniae, combined with the children’s physiological status, lifestyle behaviors, and early-life factors, predicted microbial stability classification (AUROC = 0.93). Conclusions: These findings suggested that the variation in the gut microbiota dynamics could be considered as a possible complementary biomarker to understand the individualized responses within dietary interventions aimed at improving metabolic health in childhood. Further well-designed intervention study is needed to define these observational associations. Full article

Emerging research indicates that neuronal activity is maintained by an architectural system of protons in a multi-scale fashion. Proton architecture is formed when organelles (such as mitochondria, endoplasmic reticulum, lysosomes, synaptic vesicles, etc.) are coupled together to produce dynamic energy domains. Techniques have been developed to visualize protons in neurons; recent advances include near-atomic structural imaging of organelle interfaces using cryo-tomography and nanoscale resolution imaging of organelle interfaces and proton tracking using ultra-fast spectroscopy. Results of these studies indicate that protons in neurons do not diffuse randomly throughout the neuron but instead exist in organized geometric configurations. The cristae of mitochondrial cells create oscillating proton micro-domains that are influenced by the curvature of the cristae, hydrogen bonding between molecules, and localized changes in dielectric properties that result in time-patterned proton signals that can be used to determine the metabolic load of the cell and the redox state of its mitochondria. These proton patterns also communicate to the rest of the cell via hydrated aligned proton-conductive pathways at the mitochon-dria-endoplasmic reticulum junctions, through acidic lipid regions, and through nano-tethered contact sites between mitochondria and other organelles, which are typically spaced approximately 10–25 nm apart. Other proton architectures exist in lysosomes, endosomes, and synaptic vesicles. In each of these organelles, the V-ATPase generates steep concentration gradients across their membranes, controlling the rate of cargo removal from the lumen of the organelle, recycling receptors from the surface of the membrane, and loading neurotransmitters into the vesicles. Recent super-resolution pH mapping has indicated that populations of synaptic vesicles contain significant heterogeneity in the amount of protons they contain, thereby influencing the amount of neurotransmitter released per vesicle, the probability of vesicle release, and the degree of post-synaptic receptor protonation. Additionally, proton gradients in each organelle interact with the cytoskeleton: the protonation status of actin and microtubules influences filament stiffness, protein–protein interactions, and organelle movement, resulting in the formation of localized spatial structures that may possess some type of computational significance. At multiple scales, it appears that neurons integrate the proton micro-domains with mechanical tension fields, dielectric nanodomains, and phase-state transitions to form distributed computing elements whose behavior is determined by the integration of energy flow, organelle geometry, and the organization of soft materials. Alterations to the proton landscape in neurons (e.g., due to alterations in cristae structure, drift in luminal pH, disruption in the hydration-structure of the cell, or imbalance in the protonation of cytoskeletal components) could disrupt the intracellular signaling network well before the onset of measurable electrical or biochemical pathologies. This article will summarize evidence indicating that proton–organelle interaction provides a previously unknown source of energetic substrate for neural computation. Using an integrated approach combining nanoscale proton energy, organelle interface geometry, cytoskeletal mechanics, and AI-based multiscale models, this article outlines current principles and unresolved questions related to the subject area as well as possible new approaches to early detection and precise intervention of pathological conditions related to altered intracellular energy flow. Full article

This study explores the potential of educational game design as a pedagogical strategy for teaching Mathematics in lower secondary education, addressing persistent challenges related to students’ motivation and engagement with the subject. The research focuses on the creation and implementation of a game, CriaMat, an ideation tool developed to support students in designing their own mathematical games. A qualitative approach was adopted, structured as a case study conducted in four classes and involving a total of 50 students. Data collection followed a mixed-methods strategy, combining participant observation, document analysis, and questionnaire-based inquiry, each applied during different phases of the intervention. The results indicate a positive reception of the approach, particularly in terms of student engagement, collaboration, and perceived learning. Analysis of the games produced demonstrates students’ ability to create functional games that integrate the knowledge and skills developed throughout the process. The findings also suggest that learning to design games was perceived as a valuable strategy for engaging with and consolidating mathematical content, while simultaneously providing a privileged context for developing essential competencies—such as critical thinking, creativity, and problem-solving—aligned with the national competency framework for compulsory education. The study does not aim to measure learning gains, but rather to explore students’ perceptions and experiences of learning mathematics through the process of game creation. Full article

Chronic diseases disproportionately impact Indigenous peoples in Australia, with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) representing leading causes of morbidity and mortality. Despite evidence supporting community-based exercise interventions for T2DM management, no culturally adapted programs utilizing wearable technology have been co-designed specifically with Indigenous Australian communities. This study protocol aims to determine if wearable-based exercise interventions can effectively prevent CVD development and manage T2DM progression in Indigenous Australians through culturally safe, community-led approaches. The PrIDE study protocol describes a mixed-methods translational research design incorporating Indigenous and Western methodologies across three phases: (1) co-designing culturally adapted exercise programs and assessment tools, (2) implementing interventions with wearable monitoring, and (3) conducting evaluation and scale-up assessment. Sixty-four Indigenous Australian adults with T2DM will be recruited across remote, rural/regional sites to self-select into either individual or group exercise programs using the Withings ScanWatch 2. Primary outcomes include cardiovascular risk factors, physical fitness, and health self-efficacy measured using culturally adapted tools. Indigenous governance structures will ensure cultural safety and community ownership throughout. The PrIDE protocol presents a novel approach to improving health equity while advancing understanding of wearable technology integration in Indigenous healthcare, informing future larger-scale trials and policy development. Full article

Background/Objectives: The transition to higher education is a critical phase of human development that makes adolescents and young adults particularly vulnerable to mental health problems, such as depression, anxiety, and stress. This study aimed to evaluate the psychometric properties of the Portuguese version of the Depression, Anxiety and Stress Scale-21 Items (DASS-21) among first-year undergraduate nursing students. Methods: A methodological study was conducted with 225 undergraduate nursing students, aged 17 to 18 years, from a higher education institution in central Portugal. Data were collected using the Google Forms platform. Confirmatory factor analysis was conducted to test three competing models: a single-factor model, a three-factor correlated model, and a second-order factor model. Reliability was assessed using composite reliability, and validity was evaluated using average variance extracted and the Fornell–Larcker criterion for discriminant validity. Results: Factor analyses revealed that the three-factor correlated model fit the data best overall, showing superior fit indices compared to the competing models (χ²/df = 2.37; CFI = 0.90; and RMSEA = 0.08; TLI = 0.88 and SRMR = 0.04). Composite reliability was high across all tested models, ranging from 0.84 to 0.94. The analysis of score distributions by category revealed a high prevalence of severe or extremely severe symptoms of anxiety, stress, and, to a lesser extent, depression. A statistically significant association was found between higher symptom severity and prior familiarity with mental illness. Conclusions: The DASS-21 proved to be a valid and reliable instrument for assessing psychological distress in higher education students. These findings underscore the urgent need for mental health programs in higher education institutions that focus on early detection and intervention, particularly for students initiating their studies and those with a history of mental health problems. Full article

Background/Objectives: Individuals with Autism Spectrum Disorder (ASD) often exhibit low dietary diversity due to Food Selectivity (FS), leading to various forms of malnutrition, such as obesity and/or micronutrient deficiencies. The main objective of the AUT-MENU project is to improve meal acceptance among individuals with ASD. A secondary goal is to evaluate the effectiveness of a nutrition education course for parents of enrolled participants to reduce FS. Methods: The study is a bicentric intervention conducted in three care centers (Northern area, Pavia and Milan) and one secondary school (Southern area, Rome), involving individuals with ASD aged 3 to 35 years. The study consists of an observational phase (T0) and an intervention phase (T1). At T0, biographical data, clinical characteristics, and dietary patterns of participants are collected. Based on T0 findings and existing nutritional recommendations for ASD individuals, targeted menus are developed and tested. At T1, the same assessment tools used at T0 will be applied to evaluate intervention effects. Additionally, a nutrition education course for caregivers will be implemented between T0 and T1, with a pre- and post-course knowledge questionnaire to assess its effectiveness. Results: This paper reports the results from the care centers in the Northern Area. Conclusions: Menu adaptations, developed according to individual preferences and nutritional guidelines, did not significantly modify food consumption but were well tolerated, allowing for an improvement in the nutritional profile of meals without reducing acceptability. These findings support the feasibility of implementing tailored menu strategies in collective catering for individuals with ASD. Full article

Background: Metabolomic profiling can uncover metabolic differences among seemingly healthy children, providing opportunities for personalized medicine and early detection of risk biomarkers for future metabolic disorders. This study aimed to identify and internally validate metabotypes in apparently healthy schoolchildren using targeted serum metabolomics and to assess the external validity of this metabotype classification tool in two separate groups of children. Methods: Data from schoolchildren aged 6–11 years were analyzed in two phases. In the first phase, we developed and validated a classification tool using targeted serum metabolomics in healthy children. Metabotypes were identified through unsupervised clustering with a self-organizing map, followed by assessment of cluster stability and classification accuracy. In the second phase, we tested the tool’s consistency by applying it to two additional groups: the same children from phase 1 after a 10-month physical activity intervention, and a separate group diagnosed with metabolic syndrome. Results: Three metabotypes were identified in healthy children: METBA (balanced profile), METLI (high lipid and glucose levels), and METAA (high amino acid levels). Internal validation showed strong cluster stability (ARI = 0.79) and high classification accuracy (0.95). After the intervention, 55% of children were reclassified, indicating diverse metabolic responses to physical activity. Among children with metabolic syndrome, 83% were classified as METLI and 13% as METAA. Conclusions. This tool revealed serum metabolomic diversity, enabling classification of healthy children into three distinct metabotypes. It also detects changes in metabotype classification associated with a physical activity intervention and identifies the majority of children diagnosed with metabolic syndrome within two groups. This supports the potential use of metabotypes as biomarkers and eventually for personalized interventions. Full article

Background: Socioeconomic factors significantly influence health outcomes in older adults, yet their impact on specific aspects of mobility remains unclear. This study investigates the relationship between area-level socioeconomic disadvantage and mobility health in older adults. Methods: We conducted a cross-sectional study of 110 community-dwelling older adults recruited and collected using voluntary response sampling at eight health fairs across rural Southeast Alabama in 2022–2024 (60 ± 16 years, 80% female). Area-level socioeconomic status was measured using the Area Deprivation Index (ADI), a validated composite measure of neighborhood disadvantage. Mobility was assessed using the Instrumented Timed Up and Go (iTUG) test and the Instrumented Five Times Sit-to-Stand (i5TSTS) test. Kruskal–Wallis tests and general linear models in SAS 9.4 analyzed the relationship between ADI and mobility measures. Results: Higher ADI scores were significantly associated with poorer performance on the i5TSTS test (p = 0.0004). While overall iTUG duration did not differ significantly across ADI groups, the sit-to-stand phase of the iTUG showed a significant relationship with ADI (p = 0.0026). These associations remained significant after adjusting for age, weight, race, and education level. Conclusions: These findings suggest that neighborhood context plays a crucial role in mobility health, particularly in functions related to postural transitions. Clinicians should consider area-level disadvantage when screening for mobility limitations and may need to prioritize sit-to-stand interventions for patients living in high-deprivation areas. Full article

Objectives: Glaucoma is an age-related neurodegenerative disease, characterized by retinal ganglion cell loss and progressive visual field deterioration. Beyond intraocular pressure (IOP), vascular and metabolic dysregulation contributes to optic nerve head (ONH) ischemia and neuronal vulnerability. Nutritional factors with antioxidative and vasodilatory properties may help preserve ocular perfusion. This study investigated the acute and subacute effects of a single dose of a dietary supplement containing red ginger extract (Zingiber officinale var. rubra), lutein, and vitamin B6 on ONH blood flow in patients with open-angle glaucoma (OAG). Methods: A retrospective self-controlled study was conducted at Tohoku University Hospital between August 2023 and March 2025. ONH blood flow was quantified using a laser speckle flowgraphy (LSFG) baseline one hour after and one month after continuous oral supplementation in patients with OAG. Systemic parameters, ocular biometry, and concomitant glaucoma medications were recorded in medical charts. Relative mean blur rate (MBR) changes were analyzed using a linear mixed-effects model, accounting for repeated measures and inter-eye correlations. Results: Nineteen glaucoma patients (38 eyes) were included in the acute phase and 13 patients (26 eyes) completed the one-month follow-up. After adjusting for age and sex, a single oral dose of red ginger extract significantly increased the relative MBR at 1 h (106.9 ± 3.1%; p < 0.05), and this enhancement increased after 1 month of continuous intake (115.4 ± 6.7%; p < 0.05). Greater ONH perfusion was particularly prominent in eyes with shorter axial length. Conclusions: Oral supplementation was associated with acute and short-term increases in ONH blood flow in glaucomatous eyes. Although this study was a retrospective study without a placebo-controlled comparison group, our findings offer hypothesis-generating evidence that nutritional interventions may support ocular perfusion alongside conventional glaucoma management. Future prospective randomized controlled trials are required to confirm these associations. Full article

The pervasive misuse of Duty-Free Quota Abuse Smuggling has seriously undermined fiscal and market order. This study breaks through the traditional model’s assumption of complete rationality and establishes a Multi-Phase Dynamic Decision-Making Model for Duty-Free Quota Abuse Smuggling Chain System, incorporating the risk avoidance preference of illegal actors to analyze strategic interactions within the smuggling chain system. Through theoretical deduction and simulation experiments, the evolution of the system during the decision-making phases of Decentralized Profit-Seeking, Localized Collusive, and Collaborative Profit-Seeking was analyzed, and key intervention points were identified. The study results indicate that smuggling chains will continuously gravitate toward localized collusive; the risk avoidance of illegal actors suppresses local alliance benefits and shortens accumulation cycles; strengthening cost constraints reduces the overall level of smuggling in the system, with Quota Sellers being the most sensitive. Therefore, we propose hierarchical regulation, credit supervision, and differentiated law enforcement to precisely target smuggling chains. Full article

Background: Persistent low-grade inflammation has been proposed as part of the biological mechanisms underlying post-COVID condition (PCC), which can result in laboratory tests abnormalities. However, the accuracy of routine laboratory tests for the diagnosis and follow-up of PCC is still under discussion. Methods: Patients with SARS-CoV-2 infection enrolled in the prospective, multinational ORCHESTRA cohort study, which included both European and non-European countries, were followed up for 18 months after acute infection. Blood test results were collected at acute infection and at 6, 12, and 18 months. A multivariable analysis was performed to estimate the relationship between the alterations of biochemical markers and the presence of four distinct PCC phenotypes, identified previously through a principal component analysis—respiratory (RESc), chronic pain (CPc), chronic fatigue (CFc), and neurosensorial (NSc)—during follow-up. Furthermore, this study investigated the correlation between biochemical parameters measured during the acute phase and the subsequent development of PCC. Finally, the relationship between the severity of the acute infection and biochemical abnormalities observed during follow-up was assessed. Results: The cohort included 4587 patients, 58% male, with a mean age of 58.7 (±15.5) years. A robust multivariable analysis demonstrated that, compared to controls, patients with PCC, and in particular those in the RESc cluster, presented higher mean C-reactive protein (CRP) levels at the 12- and 18-month follow-up (p-value = 0.01). In each follow-up, CRP values in patients with PCC and RESc were above 3 mg/L, corresponding to those observed in low-grade inflammation (3–10 mg/L). The severity of COVID-19 acute infection was associated with increased levels of CRP, ferritin and LDH during follow-up (p < 0.001). Biochemistry abnormalities detected during the early stages of acute COVID-19 did not correlate with an increased risk of developing PCC and its phenotypes. Conclusions: In patients with the RESc PCC phenotype, identified through a principal component analysis, blood test abnormalities consistent with prolonged and sustained low-grade inflammation can be detected up to 18 months after acute infection, supporting its role in the pathogenesis of PCC. Based on these results, trials on anti-inflammatory drugs, together with symptom-tailored interventions for patients with RESc, should be planned to prove their effectiveness in managing PCC and improving patient outcomes. Full article

This paper presents a validated, data-driven framework for the sustainable rehabilitation of corrosion-damaged marine infrastructure, demonstrated through a comprehensive study on a historic coastal structure. The implemented three-phase methodology—integrating advanced condition assessment, evidence-based intervention design, and rigorous performance validation—successfully addressed severe chloride-induced deterioration. Diagnostic quantification revealed that 30% of the primary substructure was severely compromised, with chloride concentrations reaching 1.94% by weight (970% above the corrosion threshold) and half-cell potential mapping confirming a >90% probability of active corrosion in critical elements. Guided by this data, a synergistic intervention combining galvanic cathodic protection, high-performance coatings, and structural strengthening was deployed. Post-repair validation confirmed exceptional outcomes: a complete electrochemical repassivation (potential shift from −385 mV to −185 mV), a 97.3% reduction in chloride diffusion rates, a 250% increase in surface resistivity, and the restoration of structural capacity to 115% of design specifications. The framework achieved a 65% reduction in projected lifecycle costs while establishing a new paradigm for preserving marine infrastructure through evidence-based, multi-mechanism strategies that ensure long-term durability and economic viability. Full article

Wastewater management plays a critical role in advancing the circular economy, as wastewater is increasingly considered a recoverable resource rather than a waste product. This paper reviews physical, chemical, biological, and combined treatment methodologies, highlighting a lack of a holistic framework in current research which includes both the operational phases of wastewater treatment and proper risk analysis tools. To address this gap, an innovative methodological framework for wastewater recovery and risk management within an integrated logistic–production process is proposed. The framework is structured in five steps: description of the logistic–production process, hazard identification, risk assessment through the Failure Modes, Effects, and Criticality Analysis (FMECA), prioritization of interventions using the Action Priority (AP) method, and definition of corrective actions. The application of the proposed methodology can optimize the usage of available resources across various sectors while minimizing waste products, thus supporting environmental sustainability. Furthermore, political, economic and social implications of adopting the proposed approach in the field of energy transition are discussed. Full article