Search Results (309,028)

Background: Vitamin B12 deficiency is a recognized but frequently under-integrated cause of global developmental delay (GDD) in infancy and early childhood. Early diagnosis is critical because neurological impairment may be partially or completely reversible with timely treatment. Objective: This narrative review aims to synthesize current evidence on the role of vitamin B12 deficiency in the diagnostic evaluation of GDD, with a focus on clinical phenotype, risk factors, biomarkers, treatment outcomes, and practical integration into contemporary diagnostic algorithms. Methods: A structured, non-systematic search of PubMed/MEDLINE, Embase, and Web of Science was performed to identify clinical studies, case series, reviews, and guideline documents addressing pediatric vitamin B12 deficiency and neurodevelopmental delay. Results: Vitamin B12 deficiency in early childhood is most commonly associated with maternal deficiency and exclusive breastfeeding without adequate supplementation. Evidence from recent clinical and observational studies indicates that vitamin B12 deficiency may present with nonspecific neurological symptoms, including developmental regression, hypotonia, and feeding difficulties. Incorporating vitamin B12 assessment—using serum vitamin B12, holotranscobalamin, methylmalonic acid, and homocysteine—into early diagnostic algorithms for GDD may facilitate timely identification of a treatable cause of neurodevelopmental impairment. The proposed diagnostic framework emphasizes early biochemical evaluation in infants with unexplained developmental delay, thereby supporting prompt treatment during a critical window of neurological reversibility. Conclusions: Targeted assessment of vitamin B12 status in children with GDD, together with evaluation of maternal status, represents a clinically relevant approach to identifying a potentially preventable and treatable cause of neurodevelopmental impairment. Integration of functional biomarkers into diagnostic pathways and the development of pediatric-specific reference standards are key priorities for future research and clinical practice. Full article

Excess post-exercise oxygen consumption (EPOC) reflects cardiorespiratory fitness, energy metabolism and the residual physiological effects of preceding exercise. We aimed to compare EPOC profiles of master swimmers across different age groups and performance levels. Fourteen male master swimmers performed a 200 m all-out front crawl and breath-by-breath gas exchange and their heart rates were recorded during exercise and for 5 min post-exercise. A single exponential regression model was fitted to the post-exercise oxygen uptake kinetics to determine the EPOC amplitude, time constant and time delay. The EPOC magnitude was calculated as the area under the oxygen uptake–time curve. Swimmers were grouped into younger vs. older and faster vs. slower clusters using the 50th percentile, and the associations between age, performance and physiological variables were examined. Older swimmers were slower and showed a lower peak oxygen uptake than their younger counterparts (213.9 ± 27.9 vs. 165.7 ± 24.9 s and 39.1 ± 4.8 vs. 50.2 ± 8.1 mL∙kg⁻¹∙min⁻¹; p < 0.05). Slower swimmers were older and displayed a lower EPOC amplitude than faster performers (69.8 ± 7.3 vs. 45.7 ± 1.7 years and 23.2 ± 4.0 vs. 36.8 ± 10.2 mL∙kg⁻¹∙min⁻¹; p < 0.05). Although many of the variables did not differ between groups, effect sizes were moderate to very large (except for time constant and time delay). The swimmers’ age related directly to their performance and inversely to their peak oxygen uptake, peak heart rate and EPOC amplitude, while performance presented inverse associations with peak oxygen uptake, peak heart rate, EPOC amplitude and EPOC magnitude (p < 0.05). Master swimmers of different ages and performance levels exhibited distinct EPOC characteristics, which may provide relevant information regarding the individualisation of training and recovery strategies in this population. Full article

The management of hazardous municipal solid waste incineration (MSWI) residues represents a critical challenge for sustainable development due to their increasing generation and environmental risk. At the same time, the cement industry faces urgent pressure to reduce CO₂ emissions associated with clinker production, creating a demand for alternative supplementary cementitious materials. The aim of this study was to evaluate the feasibility of valorising hazardous municipal solid waste incineration (MSWI) air pollution control fly ash (EWC 19 01 07*) as a constituent of Portland composite cement, in line with circular economy principles and the need to reduce CO₂ emissions associated with clinker production. The investigated fly ash, originating from flue gas cleaning processes, is characterised by high alkalinity and elevated concentrations of heavy metals, which currently necessitate controlled landfilling. To enable its safe reuse, the ash was subjected to high-temperature thermal treatment following granulation and subsequently incorporated into cement formulations under semi-industrial conditions. Two Portland composite cements were produced with different ash contents, corresponding to CEM II/A-07 and CEM II/B-07, while a Portland cement manufactured from the same clinker was used as a reference material. The chemical and phase composition of the ash before and after thermal treatment was analysed using XRF and XRD, supported by SEM/EDS observations. The results demonstrate that thermal treatment at 1150 °C induces partial phase stabilisation of APC fly ash without full vitrification, allowing its integration into cement systems under semi-industrial conditions. The incorporation of ash significantly alters hydration behaviour through increased water demand governed by particle porosity, CaO-rich phase composition, and early ionic interactions in the pore solution, leading to reduced workability and mechanical performance. While immobilisation efficiencies exceeding 99.5% were achieved for most heavy metals due to precipitation and incorporation into hydration products, barium exhibited persistent leaching controlled by its solubility under highly alkaline conditions and limited incorporation into C–S–H phases. These findings define both the technological feasibility and the key environmental constraints of APC fly ash utilisation in Portland composite cement. From a sustainability perspective, the proposed approach contributes to the reduction in hazardous waste landfilling and supports clinker substitution in cement production. The results demonstrate the potential of integrating waste management and low-carbon material design within a circular economy framework while highlighting current environmental limitations related to barium leaching. Full article

Industrial processing of apple to obtain products like juice or cider generates a significant amount of pomace, which represents 25–30% of the fresh fruit mass. Different technologies are needed to valorize apple pomace (AP), considering its significant amount of high-value compounds, such as fiber, vitamins, and polyphenols. Hot-air convection (CA) and infrared (IR) drying are widely used methods for preserving polyphenols from by-products, such as apple pomace (AP), while also extending their shelf life. This study aimed to evaluate the influence of CA and IR drying on drying kinetics, color parameters, and the preservation of polyphenolic compounds, as well as to identify a sustainable extraction approach. Both drying methods significantly affected the color characteristics and content of polyphenols with high antioxidant activity. A significant impact was noticed at higher temperatures, which may be associated with the partial inactivation of browning enzymes. IR drying resulted in a shorter drying time and lower specific energy consumption compared to CA. Furthermore, the assessment of solvent efficiency in ultrasound-assisted extraction (UAE) indicated that the natural deep eutectic solvent (NaDES) composed of choline chloride and glycerol (1:1 molar ratio) provided superior recovery of phenolic compounds with high antioxidant activity compared to conventional solvents and the other NaDES analyzed. Optimization of UAE conditions using this polyol-based NaDES allowed for achieving an extract characterized by a polyphenolic profile dominated by flavan-3-ols (catechin and epigallocatechin), followed by phenolic acids, mainly chlorogenic acid. These results confirm the potential of AP as a valuable source of bioactive compounds and of polyol-based NaDESs as a sustainable and efficient alternative for their recovery. Full article

Research based on the similarities between canine and human mammary tumors should extend beyond clinical, pathophysiological, epidemiological, and histopathological characteristics to include applicable molecular markers with prognostic significance. However, despite shared similarities, important differences must also be considered in comparative and translational studies. The nuclear erythroid 2-related factor (NRF2), a nuclear transcription factor that regulates the expression of antioxidant proteins, is pathologically activated during carcinogenesis. The role of NRF2 in human breast cancer is well established, making it a potential prognostic marker. Objectives: This study aimed to evaluate NRF2 tissue expression in mammary neoplasms of female dogs and its association with tumor progression, other prognostic factors, and survival. Methods: A group of 57 female dogs was studied. Tissue samples of mammary glands from 10 healthy dogs and 47 dogs with mammary neoplasms (39 malignant tumors and 8 benign tumors) were examined for NRF2 immunoexpression. Clinicopathological data and immunohistochemical expression, assessed by histochemical score (H-score), were correlated. Results: NRF2 tissue expression showed a predominantly cytoplasmic distribution and a lower H-score in tumors with higher malignancy grading. Dogs with higher NRF2 H-scores had improved survival rates (p = 0.0036). Univariate analysis revealed significant associations between H-scores < 135 and behavior (p = 0.007), tumor size (p = 0.001), and Ki-67 index (p = 0.018). Conclusions: These results suggest that NRF2 also holds prognostic value in the evaluation of canine mammary tumors. Full article

Concerns about weight gain are commonly cited with combined oral contraceptive pill (COCP) use, yet it remains unclear whether perceived weight gain as a reason for discontinuation differs by body mass index (BMI). We analyzed data from the 2017–2019 National Survey of Family Growth (NSFG), including 3709 non-pregnant women aged 20–49 years who had ever used COCPs and had BMI calculated from self-reported height and weight. Trained NSFG staff interviewed participants on reasons for discontinuation and coded them into predefined categories, including weight gain. Discontinuation was examined by BMI category (underweight, normal weight, overweight, obesity) using survey-weighted logistic regression adjusted for demographic and socioeconomic covariates. Overall, 35.2% (95% CI 32.3–38.1%) of women reported discontinuing COCPs due to dissatisfaction, with 20.2% (95% CI 18.1–22.3%) citing side effects. Weight gain was reported by 7.0% (95% CI 5.6–8.4%) of ever-users, with higher prevalence among women with overweight (8.4%) and obesity (7.7%) compared with normal-weight women (5.5%). In adjusted analyses, women with overweight (aOR 1.76, p = 0.048) and obesity (aOR 1.68, p = 0.033) had higher odds of COCP discontinuation due to self-reported weight gain. These findings highlight the importance of addressing weight-related concerns during contraceptive counseling, particularly for women with higher BMI. Full article

Background: Neuropathic pain remains a major unmet clinical challenge. Growing evidence identifies sigma receptors (σRs) as pivotal intracellular modulators of maladaptive stress signaling, positioning them as promising non-opioid targets for chronic pain management. Notably, despite the pleiotropic nature of σRs in regulating diverse cellular pathways—which might theoretically suggest a high risk of off-target effects—current selective antagonists have demonstrated remarkable safety and tolerability profiles. Sigma-1 and sigma-2 receptors (σ1R and σ2R) are molecularly and functionally distinct proteins that regulate neuronal excitability, proteostasis, and neuroimmune communication, all mechanisms that characterize neuronal excitability and cellular stress adaptation. σ1R acts as a ligand-operated molecular chaperone at the mitochondria-associated endoplasmic reticulum membrane. Extensive preclinical data demonstrate that σ1R antagonism attenuates peripheral and central sensitization, suppresses neuroinflammation, and restores opioid analgesic efficacy. These findings are supported by the advanced clinical candidate E-52862, which has shown efficacy and a favorable safety profile in neuropathic pain conditions. σ2R, identified as transmembrane protein 97 (σ2R/TMEM97), functions as a regulator of cholesterol trafficking, lysosomal integrity, and integrated stress response (ISR). σ2R modulation alleviates neuropathic pain by restoring proteostatic balance and reducing ISR-driven neuronal vulnerability rather than directly suppressing excitability. Emerging σ2R ligands such as FEM-1689, UKH-1114, and CM-398 provide compelling proof-of-concept for durable, disease-modifying analgesia. Methods: A structured literature search was conducted using PubMed, Scopus, and Web of Science to identify studies published within the last decade describing σ1R and σ2R/TMEM97 biology, ligand development, and their preclinical or clinical evaluation in neuropathic pain. Reference lists were manually screened to ensure comprehensive coverage. Conclusions: This review synthesizes pharmacology, ligand development, and translational evidence supporting σRs as next-generation targets for neuropathic pain therapy, highlighting convergent roles of σ1R and σ2R in pain chronification and outlining future directions for structure-guided therapeutic strategies. Full article

Italy and the surrounding seas are recognised as one of the European hotspots for tornadoes and waterspouts. In recent years, the town of Rosignano Solvay (on the Northern Tyrrhenian coast) experienced repeated waterspouts affecting the same areas, raising local concern about the possible influence of heated wastewater discharged into the sea by a nearby industrial site. We reconstruct the mesoscale meteorological conditions of four intense waterspouts near Rosignano Solvay using a limited-area weather model at a high-to-very-high resolution (inner domain grid spacing of 500 m; sensitivity tests at 100 m). At the reported event times, the intensity of key mesoscale precursors (low-level wind shear, 1 km storm-relative helicity, maximum updraft intensity, and lifting condensation level) is consistent with the values typically associated with EF1 (or stronger) tornadoes and waterspouts. The model systematically predicts the peak of instability indices 2–3 h earlier than the reported event times. For one case study, we conduct two sea surface temperature sensitivity experiments to assess the potential atmospheric impact of heated wastewater discharge (temperature increases of +1.5 K and +5 K over a 10 km² area). The resulting changes in instability indices are marginal, with differences of at most 3% relative to the control run. A simple mass-balance estimate for the modified sea patch suggests that, given the reported discharge rates, a plausible impact of the warm water released from the industrial site could lead to an increase in the local sea surface temperature of approximately +0.7 °C over two months. We conclude that synoptic and mesoscale conditions primarily govern waterspout initiation in this region, while the direct effect of the small warm coastal plume from the industrial discharge appears to be minor. Full article

Virtual reality (VR) sickness induced by wearing a head-mounted display and viewing 360° videos has primarily been studied using subjective questionnaires administered before and after content viewing. However, this approach is limited to identifying the onset of sickness during content viewing. This study quantitatively addresses the association between objective measures (gaze direction, head pose, electrocardiogram, and optical flow) and VR sickness, adopting an exploratory approach. Real-time sickness during 360° video viewing was measured using the fast motion sickness scale, and overall sickness susceptibility was evaluated using the simulator sickness questionnaire. The results indicated that a higher VR sickness severity was associated with reduced gaze entropy and an increase in the magnitude and entropy of optical flow, suggesting its potential as an objective measure for real-time VR sickness assessment. Furthermore, in the comparison between susceptibility groups, the high-susceptibility group had a nominally significantly lower heart rate variability than the low-susceptibility group, indicating that physiological signals may serve as auxiliary tools for sensing the baseline of VR sickness. The optical flow reflects the visual stimuli of VR content independent of personal susceptibility, suggesting its potential as a content-driven indicator of VR sickness. Full article

Cardiomyopathies comprise a heterogeneous group of myocardial disorders characterized by structural and/or functional abnormalities in the absence of secondary causes of myocardial dysfunction. Although genetic determinants play a central role in many forms of the disease, incomplete penetrance and the frequent absence of identifiable pathogenic variants suggest that additional mechanisms contribute to disease onset and progression. Growing evidence supports the pathogenic role of autoimmune processes in several cardiomyopathy phenotypes. A spectrum of autoantibodies targeting cardiac self-antigens, including structural proteins, intercalated disc components, intracellular proteins such as calreticulin, and G protein-coupled receptors, has been identified in affected patients. Experimental and clinical data suggest that these autoantibodies may exert functional effects on cardiomyocyte signaling pathways and intercellular coupling, thereby promoting maladaptive remodeling, progressive ventricular dysfunction, and an increased risk of arrhythmias. Accordingly, autoantibody profiling may facilitate the identification of biologically distinct cardiomyopathy subsets with potential diagnostic and prognostic implications. From a therapeutic perspective, pathogenic autoantibodies can be removed from patient serum through plasmapheresis or immunoadsorption strategies, and these approaches have been associated with improvements in hemodynamic parameters and clinical outcomes in selected patients. Full article

Background: Serum neurofilament light chain (sNfL) is an established biomarker of neuroaxonal damage in multiple sclerosis (MS). Despite its prognostic utility, patient awareness of its clinical application remains poorly characterized. The objective of this study was to assess the acceptance of sNfL monitoring among patients with early-stage relapsing–remitting MS (RRMS) and identify factors predicting their willingness to adopt this tool. Methods: This non-interventional, cross-sectional study was conducted across 16 neuroimmunology clinics. We included RRMS patients with a disease duration of ≤3 years receiving disease-modifying therapy. Acceptance was assessed following a standardized educational tutorial. Multivariable logistic regression was employed to identify predictors of patient acceptance. Results: The study included 144 patients (mean age 37.6 [SD 10.3] years, 69.4% female). Only 19.4% (n = 28) had prior awareness of sNfL. However, after the tutorial, 84.0% (n = 121) expressed willingness to adopt sNfL testing. Furthermore, 62.5% (n = 90) indicated that normal sNfL levels would provide emotional reassurance between clinical visits. Patients willing to undergo testing showed higher disease knowledge, less treatment regret, and better physical quality of life and cognitive performance. In the multivariable analysis, higher disease knowledge (OR = 1.52, 95%CI 1.16–1.99; p = 0.002) and lower symptom burden (OR = 0.96, 95%CI 0.93–0.99; p = 0.038) were associated with greater acceptance. Conclusions: Patients demonstrate high receptivity to sNfL monitoring when provided with adequate clinical context. Because disease knowledge is a primary driver of acceptance, personalized educational initiatives may be a complementary strategy to facilitate the integration of precision biomarkers into MS management. Full article

Conventional concrete masonry construction consists of an assemblage of concrete blocks, mortar, grout, and steel reinforcement. While effective, this constructive method is constrained by its low productivity. In recent decades, advances in construction and manufacturing technologies now allow for the production of larger and more complex block typologies, enabling designers to reassess conventional designs to optimize structural performance and construction efficiency. As such, this study introduces the “mega-interlocking block”, a novel block that integrates the benefits of mega blocks (i.e., blocks with larger sizes) with a newly designed interlocking mechanism to enhance structural performance and expedite the construction of masonry walls in work sites where forklifts, scissor lifts and other smaller crane equipment are available. A numerical study was conducted to evaluate the in-plane (IP) and out-of-plane (OOP) behaviors of masonry walls constructed with mega-interlocking blocks, including both unreinforced masonry (URM) and reinforced masonry (RM) configurations, compared to standard block walls. A simplified micro-modeling approach was utilized to account for various possible failure modes associated with masonry structures. Results indicate that mega-interlocking blocks significantly improve wall stiffness and load-bearing capacity under IP loading, both with and without mortar, outperforming standard block walls. Under OOP loading, interlocking blocks provide moderate performance gains when mortar is present, though their effectiveness diminishes in mortarless configurations. For URM walls under IP loading, the implementation of mega-interlocking blocks yielded substantial improvements in stiffness and capacity, with the most notable benefits observed in walls with larger aspect ratios. Although the relative advantages in RM walls were less pronounced due to the homogenizing effects of grout and reinforcement, mega-interlocking blocks still demonstrated robust structural performance, making them a promising alternative to standard masonry units. Full article

Polycystic ovary syndrome (PCOS) is associated with reproductive, metabolic, and inflammatory disturbances. Alterations in T-cell subpopulations—particularly increased T helper 17 cells (Th17) and decreased regulatory T cells (Treg)—have been reported in PCOS; however, data on normoandrogenic phenotype D remain limited. Hypoxia-inducible factor 1α (HIF-1α), a key regulator of hypoxic response, also influences immune and metabolic processes and may affect the Treg/Th17 balance. To assess Treg and Th17 abundance, HIF-1α expression within these cells, and their ratios in women with phenotype D PCOS compared with healthy controls. The study included 49 women with phenotype D PCOS and 40 controls comparable in terms of age and BMI. Anthropometric, hormonal, metabolic, and inflammatory parameters were evaluated. Peripheral T-cell subsets and intracellular HIF-1α expression were analyzed by multiparameter flow cytometry. Absolute numbers of Treg and Th17 cells did not differ between groups. However, PCOS patients showed significantly higher Treg/Th17 and HIF-1α-positive Treg/HIF-1α-positive Th17 ratios. HIF-1α-positive Treg cells correlated positively with adiposity and insulin resistance markers; however, after False Discovery Rate (FDR) correction, correlations no longer remained statistically significant. Despite normoandrogenemia, PCOS patients exhibited higher hs-CRP levels. Phenotype D PCOS is characterized by altered immune cell ratios rather than absolute T-cell differences, suggesting distinct immunological features and persistent low-grade inflammation. Full article

Background: Uropathogenic Escherichia coli (UPEC) is the primary etiological agent of urinary tract infections (UTIs) worldwide. The emergence of strains combining high virulence with multidrug resistance (MDR) poses a significant challenge to public health. This study aimed to characterize the phylogenetic distribution, virulence profiles, and antimicrobial susceptibility of UPEC isolates recovered from patients in the metropolitan area of Buenos Aires (AMBA), Argentina. Methodology: Phylogenetic groups, the ST131 lineage, and virulence-associated genes were identified using PCR-based assays. Antimicrobial susceptibility testing (AST) was performed using automated methods and extended-spectrum beta-lactamase (ESBL) production was confirmed using the double-disk synergy test. Colistin (COL) resistance was evaluated by Colistin Drop Test and PCR screening for the mcr-1 (mobile colistin resistance gene 1). Biofilm formation was detected by the Tissue Culture Plate (TCP) method, whereas phenotypic virulence factors (VF) were assessed with Congo Red agar, hemagglutination, and hemolysis assays. Results: Phylogenetic groups B2 (43.8%) and D (26.7%), typically associated with extraintestinal infections, were the most frequent. The high-risk clone B2-ST131 was detected in 6.7% of isolates. Biofilm production was observed in 92.4% of the isolates, with curli fimbriae (87.6%) being the most frequently expressed VF. The highest resistance rates were observed for ampicillin (62.1%), ampicillin-sulbactam (39.8%), and trimethoprim-sulfamethoxazole (25.2%). Interestingly, 3.8% of isolates exhibited colistin resistance, despite the absence of the mcr-1 gene. Conclusions: This study highlights the detection of MDR-UPEC isolates that showed strong resistance to fluoroquinolones and were ESBL producers with high virulence in Argentina, justifying future research encompassing genomic and epidemiological monitoring of local UPEC, which is essential for managing infections and developing new therapeutic and preventive measures. Full article