Search Results (7,543)

Objectives: This systematic review examined studies combining transcranial direct current stimulation (tDCS) with virtual reality (VR) in healthy or non-clinical populations. The aim was to evaluate whether active tDCS provides additional benefits when delivered during VR-based tasks or interventions aimed at improving behavioral abilities. Methods: Following PRISMA guidelines, a comprehensive search of electronic databases (2000–September 2025) identified randomized and non-randomized studies employing simultaneous tDCS and VR in healthy individuals. Studies reporting psychological or cognitive quantitative outcomes were included. Risk of bias was assessed using RoB-2 and ROBINS-I tools. Results: Twelve studies met inclusion criteria. The included studies were highly heterogeneous in terms of sample size, VR systems, stimulation parameters, targeted cortical regions, outcome measures, and control conditions. Most designs compared active tDCS during VR with sham tDCS during the same VR exposure. Therefore, the available evidence mainly addresses whether tDCS adds value to VR-based procedures, rather than whether tDCS and VR exert independent or synergistic effects. Some studies reported favorable between-group effects on emotional control or skill acquisition. However, in other cognitive domains both active and sham/control VR groups improved, suggesting that VR training or exposure itself may have contributed substantially to the observed changes. Moreover, small sample sizes, multiple outcome testing, and limited correction for multiple comparisons reduce confidence in borderline findings. Conclusions: Current evidence suggests that active tDCS may incrementally enhance selected VR-based outcomes in healthy populations, particularly in emotional control and skill-learning domains. However, the literature does not yet support strong claims of synergistic interaction between tDCS and VR. Future studies should use adequately powered factorial designs including VR-only, tDCS-only, combined, and sham/no-intervention conditions to disentangle independent, additive, and interaction effects. Full article

Background/Objectives: Atopic dermatitis (AD) and food allergy (FA) frequently coexist in the concept of atopic march; however, their combined associations with psychological problems remain poorly understood. This study aimed to investigate the associations of AD and FA with psychological outcomes at age 7 and evaluate whether respiratory allergies account for part of these associations. Methods: We enrolled 1577 children aged 7 years from the Panel Study of Korean Children. The Korean version of the Child Behavior Checklist was used to assess psychological and behavioral problems. Multivariable regression and parallel mediation analyses were used to evaluate independent and interactive associations. Results: AD and FA were associated with psychological and behavioral problems, most consistently with somatic problems on the Diagnostic and Statistical Manual of Mental Disorders (DSM)-oriented scale. These associations were more pronounced in children with comorbid AD and FA than in those with single allergies. Among the 9 children with concurrent AD and FA, an interaction between the two conditions on somatic problems was observed (P for interaction = 0.033). The comorbid group showed higher eosinophil counts and total IgE levels, but no differences in SCORAD indices or C-reactive protein levels. Mediation analysis identified a direct association of AD with somatic problems (B = 1.062; 95% CI, 0.601–1.562), with a portion accounted for by allergic rhinitis (AR) (B = 0.656; 95% CI, 0.306–1.241). Conclusions: Comorbid AD and FA were associated with higher odds of somatic problems than either condition alone in 7-year-old children, with a portion of the AD association accounted for by AR. Because exposures and outcomes were assessed concurrently, these associations are exploratory and hypothesis-generating rather than causal. Clinical attention may be warranted for children with both AD and FA. Full article

The growing demand for rare earth elements (REEs), heavy metals (HMs) and precious metals (PMs) has intensified interest in sustainable recovery strategies from secondary resources, including mining residues, industrial effluents and waste electrical and electronic equipment (WEEE). These streams represent exposure interfaces, because soluble and bioavailable metal species may persist, bioaccumulate and contribute to oxidative stress, genotoxicity, carcinogenic outcomes and chronic systemic effects. This systematic review, conducted following PRISMA guidelines, evaluates the thermoacidophilic red microalga Galdieria spp. as an extremophilic platform for metal bioremediation, recovery and upstream risk reduction. Galdieria spp. combines tolerance to low pH, elevated temperature and high metal loads with rapid surface biosorption and, in living biomass, slower intracellular sequestration and detoxification. Its interaction with REEs, PMs and toxic HMs is mediated by cell-wall functional groups, extracellular polymeric substances, redox-active processes and metabolic flexibility shaped partly by horizontal gene transfer (HGT). The review discusses matrix complexity and adsorption–desorption cycles, highlighting their implications for real industrial streams. Overall, Galdieria spp. emerges as a robust extremophilic bio-interface for selective metal recovery, hazardous waste mitigation, circular-economy biorefinery models and prevention of metal-associated risks to environmental and human health, while current scale-up limitations and process-oriented research priorities are identified. Full article

Background: Prosthetic joint infection (PJI) following total shoulder arthroplasty (TSA) is a rare but clinically relevant complication, largely attributable to the distinctive shoulder skin microbiome, predominantly composed of Cutibacterium acnes and coagulase-negative staphylococci (CoNS), which are considered low-virulence pathogens. Standard skin disinfection protocols do not completely prevent bacterial infiltration into the surgical field; therefore, the World Health Organization (WHO) recommends the use of intraoperative irrigation to reduce the risk of shoulder PJIs. Recently, the use of povidone–iodine (PVI) irrigation has been shown to significantly reduce both bacterial load and diversity after TSA; however, its activity against C. acnes remains suboptimal. Therefore, the aim of this study was to evaluate improved in vitro disinfection protocols by combining PVI and hydrogen peroxide for use as intraoperative irrigation in shoulder arthroplasty, which is characterized by a distinctive microbiome. Methods: In vitro broth dilution assays and time-kill experiments were performed to test PVI and H₂O₂, alone or in combination, against CoNS, Staphylococcus aureus, and Escherichia coli as representative aerobic bacteria, and against C. acnes as an anaerobic pathogen. Results: The results revealed that, when used alone, PVI exerted a more pronounced bactericidal effect against staphylococci, whereas H₂O₂ was more effective against C. acnes, even at a high bacterial inoculum, although at cytotoxic concentrations, particularly for PVI. Notably, when the disinfectants were used in combination, bacterial killing was achieved against all the tested pathogens, starting from short exposure times, mainly 3 min, and at low concentrations. Moreover, the antiseptics significantly reduced mature biofilm, although complete eradication was not achieved. Conclusions: A targeted irrigation protocol to prevent shoulder PJI can be achieved by combining PVI and H₂O₂ at non-toxic concentrations and for short exposure times that do not interfere with operating room costs or increase the risk of infection. Full article

Occupational cholangiocarcinoma among printing workers in Japan has raised concern regarding the carcinogenic hazards of chlorinated organic solvents, particularly 1,2-dichloropropane (1,2-DCP) and dichloromethane (DCM). Because workers were often exposed to multiple solvents, this study examined whether DCM modifies 1,2-DCP-associated hepatocellular tumor development in mice. Male C3H/HeN mice were administered a corn oil vehicle, 1,2-DCP alone at 500 mg/kg bw, or 1,2-DCP and DCM at 500 mg/kg bw each by oral gavage twice weekly for 52 weeks. Combined exposure significantly increased the incidence of hepatocellular adenomas (HCAs) compared with both the vehicle control and 1,2-DCP-alone groups. Tumor multiplicity was also significantly higher in the 1,2-DCP + DCM group than in the 1,2-DCP-alone group. HCAs from the 1,2-DCP + DCM group showed increased cell proliferative activity, 29 uniquely altered differentially expressed genes, significant upregulation of Gpc3 and Igfbp1, and downregulation of Dcn, consistent with altered tumor-associated molecular features. Canonical pathway analysis indicated suppression of xenobiotic metabolism, bile acid metabolism, and peroxisomal function in treatment-associated HCAs. These findings indicate that DCM co-exposure enhanced 1,2-DCP-associated hepatocellular tumor development and altered tumor-associated molecular features in mice, highlighting the importance of considering combined solvent exposure in chemical carcinogenic risk assessment. Full article

The extreme temperature cycling (−196 °C to 125 °C) and intense ultraviolet radiation on the lunar surface pose significant degradation risks to polymeric materials and their fibrous reinforcements. This work presents a comparative durability assessment between basalt fiber fabric and basalt rock powder after accelerated cyclic thermal shock treatments and UV exposure, aiming to establish a fundamental durability database for basalt fibers as candidate reinforcements for future polymer-matrix composites in lunar exploration. Multiscale characterizations reveal that regardless of the number of treatment cycles, the fiber surface morphology remains intact without cracking or etching. X-ray diffraction and Fourier-transform infrared spectroscopy confirm that the amorphous silicate network of the basalt fibers is well preserved, with no thermally induced recrystallization or compositional alteration. Thermogravimetric analysis further demonstrates that the treated fabrics retain the inherent thermal stability of pristine basalt, indirectly evidencing structural integrity. Importantly, the tensile strength of basalt yarns does not exhibit a cycle-dependent degradation trend, and the K/S colorimetric values remain stable even under combined thermal and UV exposure. Collectively, these findings confirm that basalt fiber fabric possesses exceptional resistance to lunar-mimetic aggressive environments, and its durability is comparable to that of natural basalt rock. Full article

The nanoscale surface topography and microhardness of additive and subtractive dental polymers were evaluated following exposure to environmental challenges. The study examined two 3D-printed resins (Saremco and Voco) and two milled CAD/CAM blocks (Vita Enamic and Tetric). Specimens were allocated to control or experimental groups and subjected to hydrothermal ageing (thermocycling), in vitro mechanical wear, or a combined protocol involving wear followed by thermal ageing. Surface microtopography was analysed both quantitatively and qualitatively using atomic force microscopy (AFM), while structural stability was assessed through surface microhardness testing. Statistical significance was determined using matrix comparisons (p < 0.05). Milled monolithic blocks demonstrated a dense, uniform baseline topography, whereas 3D-printed resins exhibited structural heterogeneity attributed to their layer-by-layer photocuring process. Saremco maintained polymer network stability under thermal stress (p = 0.1878), while Voco was highly susceptible to hydrothermal swelling and early matrix plasticization (p = 0.0084). The combined protocol of wear and thermal ageing resulted in advanced structural breakdown in all groups (p < 0.001). Industrial subtractive blocks exhibited greater resistance to oral environmental stresses. The ceramic framework of Vita Enamic limited polymer domain collapse, whereas Tetric experienced accelerated inter-layer delamination and embrittlement. The combined protocol of wear followed by thermal ageing resulted in significant and uniform degradation of surface microhardness and topographic roughness in all tested groups. Nevertheless, the additively manufactured resins demonstrated substantial structural integrity and exhibited low volumetric wear rates. Full article

This study analyzes trends in 18 temperature- and precipitation-related indices recommended by the Expert Team on Climate Change Detection and Indices (ETCCDI) across mainland Portugal over the most recent 46-year complete period (1980–2025), using ERA5-Land reanalysis data. Prior to the computation of the indices, daily ERA5-Land extreme temperature and precipitation data were validated against ground-based observations, showing good agreement and confirming the suitability of the reanalysis dataset for assessing climate extremes at the national scale. The results reveal a consistent and statistically significant warming signal across the study area, with the strongest increases observed in southern and inland regions. The frequency of extreme heat events has intensified markedly since the early 2000s. In contrast, precipitation-related indices display high spatial variability and trends with limited statistical significance, reflecting both genuine climatic heterogeneity and the inherent challenges of reproducing rainfall extremes in complex terrain using reanalysis data. The combined interpretation highlights an emerging climatic asymmetry—robust and spatially coherent warming versus localized and uncertain precipitation trends—underscoring distinct regional vulnerabilities. The findings provide actionable insights for climate services, supporting the design of region-specific adaptation strategies in Portugal, especially the need to address increasing heat stress in southern regions and the growing exposure to short-duration heavy rainfall in northern areas. Full article

High-velocity oxy-fuel (HVOF)-sprayed NiCrBSi coatings containing 0, 10, 30, and 50 wt.% WC-Co were evaluated on AZ91D magnesium alloy to determine how the discrete reinforcement level affects surface topography, phase constitution, Vickers microhardness, dry-sliding friction, mass loss, and wear-track microchemistry. As-sprayed surfaces were characterized by three-dimensional profilometry; coating cross-sections and worn surfaces by optical microscopy and SEM/EDS; phase constitution by XRD; and mechanical response by HV_0.1 indentation. Dry-sliding tests were performed at 10, 30, and 50 N over 100–1000 m. Increasing WC-Co content raised Sa from 8.8 ± 0.3 to 13.0 ± 0.5 µm and Vickers microhardness from 776 ± 4 to 959 ± 5 HV_0.1. XRD indicated a γ-Ni-based matrix containing boride/carbide constituents, while WC, W₂C, and Co became increasingly prominent in the reinforced coatings. Boride assignments are based on diffraction evidence, whereas B and C EDS signals were treated semi-quantitatively. The 50 wt.% WC-Co coating exhibited the lowest mass loss and mean coefficient of friction at every load. Its mean friction coefficients were 0.31, 0.35, and 0.41 at 10, 30, and 50 N, corresponding to reductions of 40.1%, 38.9%, and 36.2% relative to AZ91D. At 1000 m, its mass-normalized wear rate indices were 9.0 × 10⁻⁴, 4.0 × 10⁻⁴, and 5.3 × 10⁻⁴ mg N⁻¹ m⁻¹, respectively. Post-wear mapping showed the largest field-scale W-Co-rich fraction in the 50 wt.% coating; however, isolated spectra containing more than 94 wt.% Mg are compatible with local coating penetration/substrate exposure and/or Mg-rich debris. The 50 wt.% composition therefore provided the best combined response among the four tested levels, while intermediate compositions are required to identify a continuous-composition optimum. Full article

Background: Isoniazid (INH) remains a cornerstone of tuberculosis (TB) prevention and treatment, administered either as monotherapy or in combination with rifamycin-containing regimens. In this study, the preventive regimens analyzed included 6 months of daily INH monotherapy (6H), 3 months of daily INH plus rifampicin (3HR), and 3 months of twice-weekly INH plus rifapentine (3H2P2). Despite the adoption of shorter-course regimens, substantial inter-individual variability (IIV) in INH exposure persists, potentially impacting both therapeutic efficacy and toxicity. A quantitative, regimen-specific characterization of INH pharmacokinetics is therefore critical to support model-informed dosing strategies. Methods: Population pharmacokinetic models were developed separately for INH administered as 6H, 3HR, and 3H2P2. The models characterized absorption, clearance, and IIV of INH, while accounting for co-administered rifamycin. The effects of N-acetyltransferase 2 (NAT2) acetylator phenotype and relevant clinical covariates were systematically evaluated. Model performance was assessed using goodness-of-fit diagnostics, posterior predictive checks, and visual predictive checks. Population pharmacokinetic models were developed using a Bayesian nonlinear mixed-effects framework implemented in Stan through CmdStanR version 0.9.0, with additional data processing, statistical summaries, and visualization performed using R version 4.2.3. Results: INH pharmacokinetics were adequately described by regimen-specific models, revealing distinct differences in absorption and variability across regimens. Typical INH apparent oral clearance (CL/F) estimates were 21.83 L/h for 6H, 26.32 L/h for 3HR, and 25.98 L/h for 3H2P2. NAT2 phenotype was a major determinant of INH clearance across regimens: compared with intermediate acetylators, slow acetylators showed 35.4% lower CL/F, whereas fast acetylators showed 48.4% higher CL/F, indicating higher INH exposure in slow acetylators and lower exposure in fast acetylators. Body weight also influenced INH pharmacokinetics. Co-administration with rifampicin or rifapentine influenced INH pharmacokinetics in a manner consistent with reduced exposure in rifamycin-containing regimens, particularly among fast acetylators. Conclusions: Regimen-specific population pharmacokinetic modeling elucidated clinically relevant differences in INH exposure across commonly used preventive and treatment regimens. These findings highlight the importance of accounting for regimen- and genotype-specific effects when optimizing INH dosing and provide a quantitative framework for future model-informed precision dosing approaches in TB care. Full article

This study aims to deepen the understanding of the spatiotemporal evolution of the Extreme Precipitation Index in the YRD, evaluating the comprehensive flood disaster risk across the region. Existing studies have rarely incorporated the frequency, duration, and intensity of extreme precipitation events as indicators of the hazard of causative factors into comprehensive flood risk assessments. Using daily precipitation records from 107 national meteorological stations spanning 1960–2024, this study employs four extreme precipitation indices recommended by the ETCCDI (PREPTOT, CWD, R95p, and Rx1day) to examine the spatiotemporal characteristics of extreme precipitation in the YRD, one of China’s most densely populated and economically significant regions. Furthermore, a comprehensive flood risk assessment framework encompassing the hazard of causative factors, the sensitivity of disaster-forming environments, the vulnerability of disaster-affected entities, and disaster prevention capabilities is constructed. Based on this framework, an integrated Analytic Hierarchy Process–Entropy Weight method is adopted to evaluate Flood Risks in the YRD. The results showed that: (1) during the period 1960—2024, only the Extreme Precipitation Index (R95p) exhibited a significant upward trend, increasing at a rate of 1.7 mm/10a, whereas PREPTOT, CWD, and Rx1day showed slight declining trends. Nevertheless, all four indices displayed pronounced oscillatory characteristics, characterized by recurring “decrease—increase” cycles over time. (2) In terms of spatial distribution, PREPTOT and R95p exhibited a clear south-to-north gradient pattern, while CWD and Rx1day demonstrated a multicentric distribution. This pattern highlights the combined influence of typhoon landfall frequency and topographic conditions on extreme precipitation across the southern YRD. (3) The Flood Risks in the YRD exhibited a distinct spatial pattern characterized by higher risk levels in the east than in the west and in the south than in the north. Areas classified as moderate-to-high risk accounted for 48.6% of the total study area, with high-risk zones primarily concentrated in the Shanghai—Hangzhou—Ningbo corridor. These findings suggest that Flood Risks in the YRD are not driven by a single factor; rather, they result from the complex interactions among extreme precipitation, topographic and geomorphological conditions, levels of social exposure, and regional buffering capacities. Consequently, under the increasingly frequent occurrence of extreme precipitation events, flood management strategies that rely predominantly on static engineering measures are becoming insufficient. Greater emphasis should therefore be placed on enhancing the resilience of urban lifeline infrastructure, improving high-resolution forecasting and early-warning capabilities for extreme precipitation, and establishing dynamic warning-release mechanisms based on risk thresholds. Such measures are essential for effectively mitigating regional flood risks. Full article

Conventional poly(vinyl alcohol) (PVA) hydrogels struggle to integrate the mechanical robustness, thermal management, and fire safety demanded by extreme environments. To overcome this, we fabricate a multifunctional hydrogel via a synergistic strategy combining freeze–thawing and citrate-driven Hofmeister salting-out. Kosmotropic citrate ions aggressively strip polymer hydration shells, driving intense intermolecular hydrogen bonding, elevated crystallinity, and severe network densification. Consequently, the optimized cit@PVA hydrogel exhibits a balanced mechanical performance, achieving a tensile strength of 1.31 MPa and an elongation at break of approximately 150%. The citrate-induced network densification not only reinforces the mechanical integrity of the hydrogel but also regulates its thermal transport characteristics. Benefiting from the dense polymer framework and intrinsic infrared-active chemical structures, the cit@PVA hydrogel demonstrates excellent thermal management capability, including effective high-temperature thermal insulation and high mid-infrared emissivity (~85%) for passive radiative cooling. Furthermore, the incorporated citrate shifts the degradation pathway toward catalytic charring, rapidly forming a dense carbonaceous shield to completely prevent burn-through during direct flame exposure. This scalable structural design overcomes traditional performance limitations, creating resilient soft materials for advanced flexible electronics and smart protective wearables. Full article

Background/Objective: Status epilepticus (SE) is a life-threatening condition that requires immediate response to effectively control. Although benzodiazepines are the first-line treatment against SE, when treatment is delayed, benzodiazepine pharmacoresistance develops. In preclinical models of benzodiazepine refractory SE, the addition of antiseizure medications (ASMs) as adjunct to midazolam to reduce neuronal excitability and enhance inhibitory function is essential to protect against the neurodegeneration and epileptogenesis that follows prolonged seizure. Brivaracetam is a recently FDA-approved ASM to treat partial onset seizures in pediatric and adult patients as a monotherapy or adjunct therapy. We evaluated the potential of brivaracetam as monotherapy or in combination with midazolam and ketamine for efficacy against organophosphorus nerve agent (OPNA)-induced refractory SE in rats. Methods: Adult male rats were exposed to a seizure-inducing dose of soman and treated with atropine sulfate and the oxime asoxime chloride one minute after soman exposure and with brivaracetam alone or in combination with midazolam and ketamine 40 min after seizure onset. Multiple metrics of protection such as seizure severity, spontaneous recurrent seizure (SRS), neuronal loss, and neuroinflammation were evaluated. Results: Although brivaracetam monotherapy resulted in 100% survival, protection from the development of SRS and neurodegeneration only occurred when brivaracetam was administered as an adjunct to ketamine and midazolam. Initial seizure severity was also reduced by the combination of brivaracetam–midazolam–ketamine over monotherapy. Conclusions: Although further research is needed to determine optimal drug combinations, these preclinical findings provided further evidence that simultaneous polytherapy with ASMs improves OPNA-induced seizure outcomes. Full article

Background: Diets high in fat and carbohydrates, like fructose, trigger colon inflammation, increase intestinal permeability, and drive dysbiosis. However, the effects of obesogenic diets on gut microbiota, including Clostridium and Bacteroides, remain unknown. Understanding how these diets damage the colon is critical. Methods: Using a controlled preclinical obesity model, we compared the effects over time of High-Fat Diet (HFD), High-Fructose Diet (HFrD), and their combination (HFHFrD). Diet-induced dysbiosis was assessed at 4 and 8 weeks via qPCR using primers specific to bacterial phyla and species. In addition, intestinal inflammation, atrophy, and mucin production were evaluated by digital pathology after 8 weeks of diet exposure. Results: both HFrD and HFHFrD mice exhibited marked intestinal inflammation, atrophy, and damage, alongside altered production of neutral and mixed mucins. HFD-fed mice displayed a 15-fold surge in Clostridium/Bacteroides ratio at 4 weeks. At 8 weeks, HFrD-fed mice showed a striking 10-fold rise in microbial relative abundance compared to the other diets. Both HFrD and HFHFrD triggered an early increase in Bacteroides species, but significance emerged only at 8 weeks. Conclusions: Although all obesogenic diets induced inflammation, atrophy, epithelial damage, and altered mucin patterns, HFrD and HFHFrD caused pronounced disruptions to barrier function and dysbiosis. Critically, HFD consistently raised the Firmicutes/Bacteroidetes ratio at 4 and 8 weeks, while the Clostridium/Bacteroides ratio spiked only at 4 weeks. Obesogenic diets fundamentally shifted microbial load and diversity. Therefore, bacterial ratios, such as Clostridium/Bacteroides, may signal dysbiosis and tissue damage from obesogenic diets, but further research is required for confirmation. Full article

Urban areas are increasingly exposed to heat stress under climate change due to rising temperatures, ageing populations, and increasing population density in cities. This study assesses current and future heat-stress risk in Vilnius, Lithuania, using the Humidex index and the CLIMADA risk modelling framework. Historical heat-stress conditions are analysed using observational meteorological data, while future conditions are evaluated using five CMIP6 climate models under SSP2-4.5 and SSP5-8.5 climate scenarios for the mid and late 21st century. The risk assessment combines high-resolution Humidex-based hazard data, gridded population exposure, and age-specific vulnerability functions. In addition to temporal Humidex trend analysis, CLIMADA is used to estimate spatially explicit Expected Annual Impact and population-normalised impact indicators. The frequency of heat-induced stress has increased significantly—the number of days when the Humidex index was ≥30 has risen by 5.6 days per decade. It is projected that by the end of the century, the proportion of such warm-season days (April–October) will increase from 13.1% to 25.8% under the SSP2-4.5 scenario and to 41.6% under the SSP5-8.5 scenario. Spatial impact maps identify areas with elevated total and population-normalised heat-stress burden, while age-specific results show higher impacts among residents aged ≥ 65 years. Cumulative heat-stress burden, expressed as Expected Annual Impact, could increase by approximately 1.8–11.4 times. The framework provides a spatially consistent and age-sensitive approach for assessing urban heat-stress risk and supporting local climate adaptation planning. Full article