Search Results (22,767)

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

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

Tuberculosis (TB) remains a major public health challenge in Peru, where interindividual variability in treatment response and drug-induced hepatotoxicity may be influenced by host genetic background. This study aimed to characterize clinically relevant polymorphisms in NAT2, CYP2E1, and SLCO1B1 in a cohort of TB patients from Southern Peru, a genetically underrepresented Andean population. Thirty-five adults receiving first-line therapy (isoniazid and rifampicin) underwent targeted Sanger sequencing of key functional variants among these three genes. NAT2 acetylator phenotypes were predominantly intermediate (68.6%), followed by rapid (20%) and slow (11.4%) profiles, with high minor allele frequencies for rs1041983 and rs1801280. CYP2E1 functional promoter variants were infrequent, whereas SLCO1B1 exhibited notable allelic heterogeneity, suggesting potential variability in rifampicin transport. Comparative analysis with previously reported Peruvian data revealed regional differences in acetylator distribution, supporting population-specific pharmacogenomic stratification. Although clinical toxicity outcomes were not evaluated, the high prevalence of reduced acetylation genotypes suggests a substantial proportion of patients may benefit from genotype-informed isoniazid dosing strategies. These findings provide foundational data for implementing precision medicine approaches using affordable and targeted technologies in TB management within Andean populations and support the integration of pharmacogenomics into national TB control programs. Full article

Background: The first 1000 days of life represent a critical window for developmental programming, during which specific nutritional exposures, such as vitamin D levels, may influence long-term health trajectories. Vitamin D plays a central role in skeletal development, but increasing evidence also supports its possible involvement in immune, metabolic, and neurodevelopmental processes during early life. In this narrative review, we summarize current evidence on the biological functions of vitamin D across the first 1000 days, focusing on its roles in skeletal, immune, metabolic, and neurodevelopmental processes, and its potential role as a programming factor. Methods: We conducted our research using the PubMed, Scopus, and Cochrane databases. We included systematic reviews, randomized controlled trials, and high-quality observational studies published from 2015 onward, focusing on pregnancy, neonatal life, and early childhood. Results: Vitamin D acts through placental, epigenetic, skeletal, immune, metabolic, and neurodevelopmental pathways that are particularly active during early development. Low maternal or early-life vitamin D status has been associated with adverse birth outcomes and impaired bone health. It has also been linked to increased susceptibility to infections and allergic diseases, altered metabolic trajectories, and mild neurodevelopmental differences. Evidence from supplementation trials remains heterogeneous, with benefits appearing more consistent in populations with baseline deficiency. Conclusions: Vitamin D fulfills several biological plausibility criteria for a potential early-life programming factor, although current human evidence remains heterogeneous. Full article

Background/Objectives: Anterior cruciate ligament reconstruction (ACLR) is a common orthopedic procedure; however, successful return to sport (RTS) remains a major challenge influenced by both physical and psychological factors. Kinesiophobia and psychological readiness are crucial yet inadequately studied components of rehabilitation that may change across distinct phases. This study aimed to examine longitudinal, phase-specific changes in kinesiophobia, psychological readiness, and patient-reported knee function across standardized ACLR rehabilitation phases. Methods: A retrospective longitudinal cohort design was employed. Data were extracted from 45 patients who completed ACLR rehabilitation at a specialized musculoskeletal center in Riyadh, Saudi Arabia. Participants were assessed across four rehabilitation phases: Phase One (0–1 month), Phase Two (>1–3 months), Phase Three (>3–6 months), and Phase Four (>6 months post-ACLR). Outcomes included the Tampa Scale of Kinesiophobia (TSK-17), the ACL–Return to Sport after Injury scale (ACL-RSI), and the International Knee Documentation Committee subjective knee form (IKDC), administered using validated Arabic versions. Linear mixed-effects models with Bonferroni-adjusted pairwise comparisons were used to evaluate phase-related changes. Results: Significant fixed effects of rehabilitation phase were observed for all outcomes (p < 0.001). Kinesiophobia declined substantially from Phase One (mean 51.5) to Phase Three (34.7), with the greatest reduction between Phases Two and Three, followed by stabilization in Phase Four. Psychological readiness increased progressively across all phases (ACL-RSI: 37.1 to 61.8). Knee function demonstrated the greatest improvement during late rehabilitation (IKDC: 37.6 to 75.8). Conclusions: Psychological and functional recovery following ACLR follow distinct temporal trajectories rather than improving synchronously. Kinesiophobia declines most markedly during mid-rehabilitation, while functional gains peak in late rehabilitation. These findings support integrating structured psychological screening into phase-specific ACLR rehabilitation protocols. Full article

Background: The interrelationship between craniofacial morphology and respiratory function is a central focus of orthodontic and dentofacial orthopedic research. This study aimed to evaluate the volumetric changes in the sinonasal complex (combined nasal cavity and paranasal sinuses) following Right Angle Maxillary Protraction Appliance (RAMPA) therapy using cone-beam computed tomography (CBCT) and to compare these outcomes with established longitudinal growth benchmarks. Methods: A retrospective cohort analysis was conducted on 60 pediatric patients (24 males, 36 females; mean age: 86.60 ± 24.22 months) with radiologically clear paranasal sinuses at baseline (T1). Participants underwent RAMPA therapy for an average of 8.38 months. Volumetric quantification of the entire sinonasal complex—including the nasal cavity and all four paranasal sinuses (maxillary, ethmoid, sphenoid, and frontal)—was performed to ensure methodological alignment with existing normative growth data. Results: Total sinonasal volume increased significantly from 27,741.63 ± 10,675.85 mm³ at T1 to 32,248.00 ± 10,084.07 mm³ at T2 (p < 0.001), representing a mean gain of 4506.37 mm³ (16.24%). Notably, the annualized growth velocity under RAMPA therapy (6453 mm³/year) exceeded the physiological increment of age-matched normative data (~5418 mm³/year) by approximately 1.2 times. Despite a constricted baseline at T1 compared to normative values, the treatment group demonstrated a rapid “catch-up” growth trajectory. Conclusions: RAMPA therapy induces rapid and significant volumetric expansion of the sinonasal complex in pediatric patients, demonstrating a potent “acceleration effect” that surpasses natural physiological maturation. These findings suggest that orthopedic midfacial remodeling can effectively restructure the upper respiratory environment, bridging the gap between pathological constriction and normative developmental benchmarks in patients with maxillary hypoplasia. Full article

Background/Objectives: Demand for functional foods is growing due to the desire to prevent cardiometabolic disorders. Pseudocereals, particularly quinoa, buckwheat, and amaranth, stand out for their functional properties related to cardiometabolic health. The dietary fiber, plant proteins, vitamins, minerals, and phytochemicals in pseudocereals primarily help to regulate glycemic response and lipid profile, as well as blood pressure. The aim of this review is to briefly explain the role of pseudocereals in biological mechanisms underlying cardiometabolic effects and evaluate the findings of human studies. Methods: The biological mechanisms that emphasize potential cardiometabolic effects of pseudocereals were summarized based on preclinical studies. Human studies were searched on Web of Science, PubMed, and ScienceDirect between June and December 2025. Findings of human studies on potential cardiometabolic health benefits of pseudocereals, including their anti-hyperlipidemic, anti-hyperglycemic, anti-obesity, and anti-hypertensive effects, are discussed. Results: The revealed mechanisms in preclinical studies and current outcomes of thirty-three human studies included in this review indicated that pseudocereals, especially quinoa and buckwheat, might be a part of healthy nutrition to assist the prevention and management of cardiometabolic disorders. In human studies, the most notable improvements were reported in plasma triglyceride and total cholesterol levels. Nevertheless, the number of human studies is limited, and existing studies have methodological variations to state cumulative and evidence-based consumption recommendations. Conclusions: Despite the potential protective effects of pseudocereals on cardiometabolic health, well-designed, controlled human studies are needed to elucidate the outcomes and provide clear evidence of the role of pseudocereals in relation to cardiometabolic effects. Full article

Human induced pluripotent stem cell (iPSC)-derived brain organoids have emerged as powerful three-dimensional (3D) platforms for modeling human neurodevelopment and neurological disorders. However, the absence of a functional vascular network remains a critical limitation, restricting oxygen and nutrient delivery, impairing metabolic stability, and constraining long-term maturation. Conventional extracellular matrix (ECM) mimetics, such as Matrigel and other static synthetic hydrogels, provide biochemical support but fail to recapitulate the dynamic remodeling that characterizes the developing neurovascular niche. Recent advances in stimuli-responsive hydrogels offer spatiotemporal control over matrix stiffness, degradability, viscoelasticity, and biochemical cue presentation. In this review, we discuss dynamic hydrogel systems within a structure–property–function framework, highlighting how network chemistry and architecture may regulate endothelial sprouting, lumen formation, vascular stabilization, and neurovascular unit maturation in vascularized brain organoid models, based on evidence from both organoid studies and related biomaterial or vascular systems. Photoresponsive, enzyme-cleavable, thermo-responsive, supramolecular, bio-orthogonal click-based, and bioprinted platforms are discussed with emphasis on mechanotransduction, angiocrine signaling, and barrier specialization. Functional outcomes, including trans-endothelial electrical resistance, selective permeability, transporter expression, electrophysiological integration, and sustained perfusion, are discussed alongside translational challenges such as cytocompatibility, oxidative stress, scalability, and regulatory feasibility. Collectively, dynamic hydrogels provide a versatile biomaterial strategy for improving vascularization and aspects of functional maturation in brain organoid models with enhanced physiological relevance. Ultimately, stimuli-responsive hydrogel systems may serve as enabling platforms for engineering vascularized brain organoids and advancing human-relevant neurovascular disease modeling. Full article

Background: Ketogenic dietary therapies (KDTs), characterized by substantial carbohydrate restriction and increased dietary fat intake, were originally developed for the treatment of drug-resistant epilepsy but have recently attracted broader scientific interest. In the context of population aging and the increasing prevalence of cognitive impairment and dementia, their potential relevance for brain health has received growing attention. Experimental and emerging clinical evidence suggests that ketogenic metabolism may influence biological processes involved in brain aging, including cerebrovascular regulation, neuroinflammatory signaling, and cerebral energy metabolism. Objective: This narrative review aims to synthesize current evidence on the relationship between ketogenic dietary therapies and brain health, with particular emphasis on cerebrovascular mechanisms, neuroinflammatory pathways, and neuroprotective processes relevant to aging. The review also briefly introduces the Semmelweis Study as an example of a translational research framework for evaluating nutrition-related interventions in real-world preventive settings. Methods: A narrative literature review was conducted using structured searches of major scientific databases to identify experimental and human studies investigating ketogenic dietary interventions, cerebrovascular mechanisms, and neuroprotective outcomes. Publications related to the Semmelweis Study were included solely to illustrate implementation-oriented research approaches and not as evidence supporting dietary efficacy. Results: Available evidence indicates that ketogenic dietary interventions may modulate several biological pathways relevant to brain health, including cerebral energy metabolism, mitochondrial function, oxidative stress regulation, and inflammatory signaling. However, the current evidence base is dominated by preclinical studies and short-term human investigations, and direct evidence linking ketogenic dietary therapies to long-term cerebrovascular or cognitive outcomes remains limited. Conclusions: Ketogenic dietary therapies represent metabolically distinct dietary strategies with potential relevance for cerebrovascular and neuroprotective mechanisms. Nevertheless, human evidence remains heterogeneous and insufficient to support broad clinical recommendations. Future research should prioritize well-designed long-term human studies with clearly defined metabolic, cerebrovascular, and cognitive endpoints. Translational research frameworks may facilitate the evaluation of feasibility, safety, and implementation of ketogenic interventions in aging populations. Full article

Plant growth-promoting microorganisms (PGPMs) and microbial biocontrol agents have emerged as key tools for improving crop productivity while maintaining environmental sustainability. However, central questions remain regarding which factors determine their consistent field performance and how these factors interact under real agronomic conditions. Previous research has demonstrated that PGPMs enhance nutrient acquisition, regulate phytohormone balance, improve stress tolerance, and suppress plant pathogens through diverse biochemical and ecological mechanisms. Advances in omics technologies, genome mining, and synthetic microbial communities have further expanded understanding of their functional potential. Nevertheless, many studies rely on laboratory-scale experiments or short-term trials, with limited multi-season and cross-regional validation. This gap contributes to inconsistent field outcomes and restricts large-scale agricultural adoption. Long-term multi-season validation and reproducibility assessment remain essential priorities for improving reliability of microbial agricultural products. This review synthesizes recent advances in PGPM-based biofertilizers and microbial biocontrol technologies, critically examining their mechanisms of action, scalability constraints, formulation challenges, and regulatory limitations. It identifies major translational barriers, including context dependency, mechanistic uncertainties, reproducibility gaps, and insufficient systems-level integration. Full article

Water pollution is one of the most critical societal and environmental challenges and remains a persisting problem worldwide. The origin of this pollution is diverse, while organic matter occupies a significant portion, originating from different sources. This creates major environmental and health risks, requiring reliable and sensitive analytical tools for effective monitoring. The permanganate index stands as a conventional assessment method for organic pollution, but it demonstrates compound non-specificity toward compounds and limited sensitivity to various contaminant structures. This research introduces cyclic voltammetry as a standalone electrochemical method that provides sensitive detection and characterization of organic oxidizing compounds. Six organic compounds, including gallic acid, phenol, oxalic acid, ascorbic acid, salicylic acid and p-benzoquinone, were used as model compounds and studied in aqueous media. These compounds were analyzed individually, in single-compound mode, to characterize their redox behavior and to identify the voltammetric peaks. Subsequently, a multi-compound analysis was studied to check for the validity of the concept in a more complex matrix. Notably, a strong linear correlation was observed between the measured charge and the theoretical permanganate index, highlighting the quantitative reliability of the electrochemical method. Comparing the obtained results with the permanganate index method confirmed the superiority of cyclic voltammetry in terms of response time and detection capability. The outcomes demonstrate that cyclic voltammetry functions as a robust alternative to the classical chemical oxidation method for environmental water assessment. Full article

Esophageal cancer is a highly aggressive malignancy with a poor prognosis. More precise prognostic biomarkers are therefore needed. Disulfidptosis is a recently identified form of regulated cell death driven by disulfide stress. It has been implicated in tumor progression. However, its prognostic role in esophageal cancer remains largely unexplored. This study aimed to develop a disulfidptosis-related gene signature for risk stratification and outcome prediction in esophageal cancer patients. Based on 23 disulfidptosis-related genes, consensus clustering was performed to identify molecular subtypes. Differentially expressed genes (DEGs) between subtypes were subjected to functional enrichment, immune microenvironment, and drug sensitivity analyses. Univariate and multivariate Cox regression were used to construct a prognostic risk model, which was evaluated using time-dependent receiver operating characteristic (ROC) curve and Kaplan–Meier analysis. A clinical nomogram integrating the risk score and clinicopathological factors was developed and validated. Two distinct disulfidptosis-related subtypes were identified, showing significant differences in gene expression, immune infiltration, and stromal scores. A total of 1080 DEGs were enriched in pathways related to epidermal differentiation, NRF2 signaling, and glucocorticoid receptor activity. A five-gene prognostic signature was established and effectively stratified patients into high- and low-risk groups. The risk model exhibited strong discrimination for 1-, 3-, and 5-year overall survival outcomes. The predictive accuracy was further maximized through an integrated clinical nomogram, which achieved an outstanding area under the curve (AUC) of 0.94 for 5-year survival predictions. Drug sensitivity analysis revealed subtype-specific therapeutic vulnerabilities, supporting potential precision treatment strategies. This study proposes a novel disulfidptosis-related five-gene signature and nomogram that robustly predict prognosis in esophageal cancer. The findings highlight the clinical relevance of disulfidptosis in tumor biology and offer a potential tool for risk stratification and personalized therapeutic decision-making. Full article

Gait analysis study comparing unicompartmental vs. total knee arthroplasty, differences in knee kinematics: a retrospective cohort study. Background and Objectives: Total knee arthroplasty (TKA) is an effective treatment for advanced knee osteoarthritis, although functional outcomes may remain suboptimal in many patients. Unicompartmental knee arthroplasty (UKA) often provides better functional recovery but shows lower long-term implant survival. Recently, personalized TKA approaches have been developed to improve kinematic restoration and patient satisfaction. This study aimed to compare knee kinematics among patients who underwent personalized TKA, medial UKA, and healthy controls. Materials and Methods: This retrospective cohort study included 9 patients treated with robotic-assisted personalized TKA, 9 patients treated with medial UKA, and 9 healthy controls matched for age, sex, and BMI. Inclusion criteria were age 60–80 years, Kellgren–Lawrence grade III–IV, a minimum follow-up of 12 months, deviation from neutral HKA < 15°, healthy contralateral knee, and high postoperative functional scores. Exclusion criteria included valgus knees (HKA > 180°), postoperative complications, and neuromotor disorders. In the TKA group, a Medial Congruent implant was implanted with ROSA robotic assistance using a restricted kinematic alignment (±5° HKA) and asymmetric intercompartmental balancing. In the UKA group, a fixed-bearing medial implant (Physica ZUK) was used. Gait analysis was performed on a markerless instrumented treadmill (WalkerView™; Dalmine, Italy). Differences between groups were analyzed using one-way ANOVA and Tukey’s post-hoc test (p < 0.05). Results: UKA patients walked with a stiffer knee during stance. Knee range of motion during stance increased from UKA (6.3° ± 7.2°) to TKA (13.6° ± 8.8°, p = 0.045) and to controls (16.6° ± 4.5°, p = 0.02). During loading response, UKA patients showed lower flexion (10.2° ± 6.1°) than TKA (19.4° ± 7.9°, p = 0.049) and controls (19.6° ± 2.8°, p = 0.004). Knee flexion during swing was comparable between UKA and TKA. Conclusions: UKA patients demonstrated reduced knee flexion during early stance compared with robotic-assisted TKA and healthy controls. The observed differences may reflect multiple factors, including surgical technique, implant design, and patient-related characteristics. Because preoperative functional data were not available, potential selection bias cannot be excluded. These findings should be interpreted cautiously and warrant confirmation in larger prospective studies. Full article

Background: There is limited contemporary evidence on predictors of adverse outcomes in ST-elevation myocardial infarction (STEMI) involving the right coronary artery (RCA). We examined this in a single-centre retrospective cohort study, focusing on 30-day outcomes. Methods: Consecutive patients presenting to an Australian tertiary hospital between May 2022 and April 2024 with acute STEMI who underwent primary percutaneous coronary intervention (PCI) or rescue PCI were eligible. Patients were divided into STEMI due to RCA and non-RCA culprit lesions, and their characteristics were compared. The primary outcome was a composite of 30-day all-cause mortality and cardiogenic shock. Results: Among 320 included patients, the primary composite outcome was similar between the RCA and non-RCA groups (12% vs. 15%, p = 0.44), although 30-day mortality was lower in the RCA-STEMI group (2% vs. 8%, p = 0.01). In the RCA-STEMI cohort, right ventricular (RV) longitudinal dysfunction on echocardiogram, defined as a tricuspid annular plane systolic excursion (TAPSE) < 17 mm or RV tissue doppler lateral annular systolic velocity (RV S′) < 10 cm/s (p = 0.04), and Thrombolysis in Myocardial Infarction (TIMI) flow < 3 in the RV marginal branch post-PCI (p = 0.04) were independently associated with the primary outcome. The latter was also associated with a higher risk of intensive care unit admission for cardiogenic shock (p < 0.01) and heart failure requiring inpatient diuresis (p = 0.02). Conclusions: In patients with RCA-STEMI, compromised RV marginal branch flow post-PCI and impaired RV function were independently associated with the composite primary outcome of 30-day all-cause mortality and cardiogenic shock. These characteristics may assist early identification of at-risk individuals who could benefit from pro-active monitoring and early implementation of therapies for cardiogenic shock. Full article

Postural balance is a foundational component of human motor behavior, yet it remains conceptually ambiguous and methodologically heterogeneous across the clinical, educational, and sport sciences. This narrative review aims to provide an integrative framework that clarifies key concepts (postural control vs. postural balance), synthesizes the main sensorimotor and biomechanical mechanisms underpinning balance, and organizes current assessment approaches and functional implications across populations. Narrative literature synthesis was conducted to integrate evidence covering multisensory integration and sensory reweighting, central neural control (spinal, brainstem, cerebellar, and cortical contributions), neuromuscular and biomechanical strategies (e.g., ankle/hip/stepping), and cognitive influences (e.g., dual-task effects). We further summarize commonly used instrumental outcomes derived from force-platform center-of-pressure metrics and widely adopted clinical and functional balance tests, highlighting their typical applications and limitations across the lifespan including pediatric, general adults, older adults, and athletic populations. This review proposes a closed-loop, systems-based model in which postural balance is conceptualized as an emergent functional outcome arising from distributed postural control processes shaped by task, environmental, and individual constraints. In conclusion, integrating mechanistic understanding with population-specific assessment enhances interpretability and supports more precise, context-sensitive balance evaluation and intervention in both health and performance settings. Full article