Search Results (5,169)

Restless legs syndrome (RLS) is one of the most prevalent sleep disorders, yet its diagnosis continues to rely almost entirely on subjective symptom descriptions. This persistent dependence on phenomenology reflects the absence of reliable biological markers to aid in the process of diagnosis or monitoring. However, there is accumulating molecular evidence that suggests that RLS is associated with systemic biological alterations. These extend beyond the traditional paradigm of iron deficiency. The present scoping review synthesizes the current research on circulating serum biomarkers investigated in RLS outside classical iron indices. A comprehensive search of PubMed, Scopus, and Web of Science databases identified 1050 records, of which 50 studies met eligibility criteria and were included. In the processing of data, clusters emerged into several recurring biological domains, including dysregulated iron regulatory signaling (hepcidin), low-grade immune activation, oxidative stress, and neuroaxonal injury markers. High-throughput omics studies reveal molecular network perturbations involving inflammatory pathways, complement activation, metabolic signaling, and cellular stress responses. Biomarker associations appear stronger when linked to objective motor burden. These findings suggest that RLS may involve multifarious molecular changes detectable in the serum. Consequently, this can support the transition from symptom-based diagnosis toward biomarker-informed stratification, which may enable more precise disease characterization and improved diagnostic accuracy. Full article

Schizophrenia spectrum disorders (SSD) are severe psychiatric conditions characterized by disturbances in cognition, emotion, and behavior, with increasing evidence suggesting an involvement of the gut microbiome in their pathophysiology. This PRISMA-informed structured review synthesizes 114 studies using a taxa-centered framework that maps microbial changes across SSD stages and phenotypes and serves as a structural basis for identifying cross-study patterns. Across heterogeneous cohorts, convergent alterations include depletion of short-chain fatty acid (SCFA)-producing taxa (including Faecalibacterium, Roseburia, and Coprococcus) and enrichment of potentially pro-inflammatory and fermentative taxa (such as Proteobacteria, Enterobacteriaceae, Streptococcus, Collinsella, and Desulfovibrio). These taxonomic patterns suggest potential functional alterations, including reduced SCFA availability. Reduced abundance of butyrate-producing taxa has been associated with impaired intestinal barrier function and increased microbial translocation (e.g., lipopolysaccharide), which may contribute to the activation of immune pathways, including Toll-like receptor 4 signaling and elevated inflammatory markers such as IL-6 and TNF-α. Additional alterations reported across studies include changes in lactate metabolism, bile acid profiles, aromatic amino acid metabolism, and the tryptophan-kynurenine pathway. These pathways may interact with neurobiological processes relevant to SSD, including glutamate-GABA balance, NMDA receptor function, microglial activation, and synaptic regulation, although much of the current evidence remains associative. Multi-kingdom studies and fecal microbiota transplantation models provide further support for the functional relevance of these observations, though causal relationships remain to be fully established. Overall, SSD-associated dysbiosis appears to reflect ecosystem-level metabolic alterations rather than isolated taxonomic abnormalities, supporting a Microbiota–Gut–Immune–Glia conceptual framework and highlighting the gut ecosystem as a potential therapeutic target. Full article

Background: Exposure to intimate partner violence (IPV) represents a major risk factor for both maternal psychological well-being and child development. Maternal psychopathology—particularly depression and post-traumatic stress disorder (PTSD)—has been shown to impair parenting functioning and increase children’s vulnerability to emotional and behavioral difficulties. Objectives: This study examined the associations between maternal depression and PTSD symptoms and children’s internalizing and externalizing problems, and explored whether parenting stress and maternal mentalization capacities mediate these relationships. Methods: The sample included 42 mothers (mean age = 43.38, SD = 10.56) and their preschool- and school-aged children (n = 42; mean age = 8.30, SD = 2.53) exposed to IPV. Mothers completed self-report measures assessing depressive and PTSD symptoms, parenting stress, and mentalization (uncertainty and certainty about mental states). Children’s internalizing and externalizing problems were assessed through maternal report. Mediation analyses with bootstrapping procedures were conducted to examine indirect effects. Results: Maternal depressive symptoms emerged as the strongest predictor of children’s internalizing problems. Parenting stress was associated with stronger relationships between maternal symptoms and children’s internalizing problems, while polarized mentalization—particularly uncertainty and, to a lesser extent, excessive certainty about mental states—partially mediated the relationship. Maternal PTSD symptoms predicted both internalizing and externalizing problems. Parenting stress fully mediated the association between PTSD symptoms and children’s externalizing behaviors, whereas excessive certainty and uncertainty about mental states showed partial mediation effects. Conclusions: These findings suggest that maternal psychopathology may influence child adjustment both directly and indirectly through increased parenting stress and dysregulated mentalization. The results highlight the importance of trauma-informed, dyadic interventions targeting maternal mental health, parenting stress, and reflective functioning to prevent the intergenerational transmission of trauma and support resilience in families exposed to IPV. Full article

Introduction: Adolescent suicide behavior is a global concern and a leading cause of morbidity and mortality in this age group. Pharmaceutical ingestion is a frequent method of suicide attempts, requiring toxicology and psychiatric interventions. This study analyzed data from a pediatric tertiary hospital to elucidate the trends, demographics, and methods used. Methods: This retrospective study was conducted at a single tertiary pediatric hospital in Romania and included adolescents aged 10–18 years admitted for suicide attempts between 2014 and 2024. Data extracted from electronic medical records included age, sex, residence, suicide method, psychiatric history, and clinical outcomes. Temporal trends were analyzed using regression-based methods, and group comparisons were performed using chi-square tests, with statistical significance set at p < 0.05. Results: The study included 1840 adolescents, with a significant increasing trend over time (p < 0.0001), but with a transient decline in 2020. The female-to-male ratio was 5.4:1 (p < 0.0001). The median age of the patients was 15.2 years. The suicide attempt methods were pharmaceutical poisoning (95%), chemical ingestion (4%), and violent methods (1%). Females were more prone to pharmaceutical poisoning, while males were associated with chemical ingestion and violent methods (p < 0.0001). Previously documented psychiatric disorders were present in 32.8% of patients, while 9.6% had a history of prior suicide attempts. Two fatalities (0.1%) were recorded, both involving defenestration. Conclusions: Hospital-treated suicide attempts among Romanian adolescents increased over time, mainly affecting females through pharmaceutical poisoning. Adolescents without prior psychiatric diagnoses reveal gaps in early identification and prevention. These findings highlight important patterns among hospital-treated adolescents and may inform targeted prevention efforts. Full article

Background: Intimate partner violence (IPV) is a pervasive medical concern affecting millions of people worldwide, with the majority being women. IPV is linked to a number of long-term physical and mental health consequences, including brain injuries and associated persistent post-concussion symptoms (PPCS) and post-traumatic stress disorder (PTSD). Despite the high prevalence of these conditions, there is sparse literature assessing accessible and effective therapeutic avenues specific to IPV victim-survivors. Methods: This narrative review had two aims: to identify therapeutic studies addressing PTSD and PPCS in women IPV survivors, and to provide a narrative overview of potential therapeutic categories, including psychotherapy, mindfulness and meditation, exercise, and pharmacotherapy. A comprehensive literature search was conducted using PubMed and Google Scholar. Inclusion criteria required full-text, peer-reviewed articles published in English, conducted in women with a history of IPV, reporting treatment outcomes related to PTSD or PPCS. Where no IPV-specific evidence was identified, findings from closely related populations including military veterans, athletes, and general TBI samples were narratively reviewed to inform potential therapeutic implications. Results: Nineteen studies addressing PTSD in women IPV survivors were identified, predominantly utilizing psychotherapeutic or mindfulness and meditation-based interventions. No intervention studies targeting PPCS specifically in IPV survivors were identified. Consequently, results for PPCS are largely extrapolated from adjacent populations. Although potential therapeutic avenues were narratively identified across psychotherapy, mindfulness and meditation, exercise, and pharmacotherapy, IPV-specific evidence remains limited, and validation for PTSD and PPCS in this population is needed before clinical recommendations can be made. Conclusions: While 19 studies identified promising therapeutic options for IPV-related PTSD, no IPV-specific PPCS interventions were identified, and implications for PPCS management remain largely inferential. Validation and integrated trauma-informed approaches addressing the intersection of PTSD and PPCS are needed for this understudied population. Full article

Neurological injuries and disorders affecting hand motor control can severely impair the ability to perform activities of daily living and substantially reduce quality of life. Technologies such as virtual reality (VR) are increasingly used to address fundamental challenges in therapy, including motivation and engagement; further, programmable features of digital interfaces offer additional opportunities to personalize and optimize motor training. In this proof-of-concept study, we developed and evaluated a novel VR-based training framework to support improved dexterity and hand function using physiological (sensory-driven) and cognitive (memory) cues designed to promote greater task-relevant neural engagement. The proposed approach leverages the integration of augmented sensory feedback (ASF) with memory-anchored cues for motor learning of target hand gestures. Using a within-subjects design, thirteen neurotypical adults completed four training conditions: (1) control (baseline gesture-matching in VR), (2) visual ASF (enhanced visualization and feedback of gesture accuracy), (3) memory-anchored cues (associating gestures with semantically meaningful entities, loosely analogous to American Sign Language), and (4) hybrid multimodal (visual ASF + memory-anchored cues). Training with the hybrid condition produced the fastest skill acquisition (9.3 trials to reach an 80% accuracy threshold) and the steepest initial learning slope (1.86 ± 0.12%/trial), with all conditions differing significantly in initial slope (all p < 0.002). Post-training assessment showed that the hybrid condition achieved the highest gesture accuracy (95.2%), greatest normalized post-training accuracy gain (14.3% above baseline), fastest execution time to target gesture (1.14 s), and lowest variability in gestural kinematics (SD = 3.9%). Both ASF and memory-anchored cue conditions each also independently outperformed the control condition on gesture accuracy (both p ≤ 0.002), with omnibus ANOVAs indicating significant condition effects across metrics. Together, these findings suggest that pairing ASF cues with memory-based cognitive scaffolding can yield additive benefits for motor skill acquisition and stability. Pending validation in clinical populations, such approaches may inform the design of VR-based motor training frameworks for rehabilitation. Full article

Background and Objectives: Rates of obesity have been consistently increasing in recent years across all age groups, with a notable rise among young people. Obesity represents a persistent inflammatory condition and a key contributor to various chronic health problems, such as cardiovascular disorders, metabolic abnormalities, cancer, and psychological conditions. The move from high school to university is a transitional phase accompanied by specific pressures that can affect both body weight control and mental health in students. This cross-sectional investigation aimed to investigate potential associations between excess weight and the presence of depressive and anxiety symptoms in university populations. Methods: This cross-sectional analysis included 5298 students enrolled at universities across ten geographic areas of Greece. Participants filled out questionnaires concerning demographic information and lifestyle behaviors. Levels of depression and anxiety were measured using the Beck Depression Inventory (BDI-II) and the short form of the State Anxiety Inventory (STAI-6), respectively. Measurements of height and body weight were obtained to compute Body Mass Index (BMI). Results: The presence of overweight or obesity among students was significantly and independently related to female sex, urban residence, living independently, tobacco use, and lower academic performance (p = 0.0103, p = 0.0102, p = 0.0203, p = 0.0075, and p = 0.0168, respectively). Individuals reporting insufficient physical activity had 85% higher odds of being overweight or obese (p = 0.0068). Similarly, participants experiencing depressive or anxious symptomatology had more than double odds of excess body weight compared with those without such symptoms (p = 0.0015 and p = 0.0012, respectively). Furthermore, poor Mediterranean diet adherence was linked to more than a twofold increase in the odds of overweight or obesity (p = 0.0005). Conclusions: These findings offer considerable evidence that symptoms of depression and anxiety may serve as significant contributors to the development of overweight and obesity among university students. Additional longitudinal studies are strongly encouraged to substantiate these observations. Full article

Substance use disorder (SUD) undermines social connection, identity, and well-being. While art therapy is formally incorporated into clinical treatment, far less is known about how informal, group-based creative activities contribute to recovery. This qualitative study examines whether and how participation in a creative arts group fosters social support and human flourishing among individuals with SUD. We conducted semi-structured, individual interviews of eight adults enrolled in SUD outpatient treatment at the Johns Hopkins Broadway Center for Addiction who voluntarily participated in a creative arts class. Recordings were transcribed and analyzed using an iterative, thematic approach. Analysis revealed four themes: (1) Social connectedness and support—artmaking fostered camaraderie, accountability, and peer encouragement; (2) Holistic and supportive environment—the group offered a safe, nonjudgmental space that affirmed participants beyond their addiction; (3) Emotional renewal through art—creative engagement reduced anxiety, promoted joy, and provided a constructive outlet for emotions; and (4) Reclaiming agency through artistic expression—participants experienced autonomy, skill development, and identity building, which fostered hope and personal growth. Overall, participants viewed artmaking as a catalyst for relational and personal transformation. These exploratory findings generate hypotheses for future research on the role of informal creative arts groups within recovery-oriented care settings. Full article

Fetal MRI has been increasingly used in diagnosis and assessment of congenital anomalies and conditions by providing detailed structural information. However, such information is only part of the whole landscape of these genetic disorders. Given that genetic disorders are associated with significant morbidity and mortality in infants, multidisciplinary team management is essential for perinatal management and parental counseling. In the past two decades, there are advances in both fetal MRI and genetic testing for prenatal diagnosis of genetic disorders. This narrative review consolidates the current literature and aims to provide a systematic overview of fetal MRI applications in genetic disorders affecting the central nervous system, craniofacial structures, skeletal system, lungs, and urinary system. Understanding embryological and genetic basis as well as imaging phenotypes of genetic disorders are important in improving perinatal diagnosis and management. Full article

Different methodologies have been developed for the analysis and study of dynamical systems, including both theoretical models and natural systems. Examples span a wide range of applications, such as astronomy, financial and economic time series, biophysical systems, physiological phenomena, and Earth sciences, including seismicity and climatic processes. The study of these complex systems is commonly based on the analysis of the signals they generate, using mathematical tools to extract relevant information. A broad spectrum of mathematical disciplines converges in this context, including stochastic, probability and statistical theory, entropic and informational measures, fractal and multifractal analysis, natural time analysis, modeling of non-linearity and recurrence methods, generalized entropies, non-extensive systems, machine learning, and high-dimensional and multivariate complexity. Research in this area is largely focused on the characterization of complex systems, providing indicators of determinism or stochasticity, distinguishing between regularity, chaos, and noise, and identifying topological as well as disorder-regularity features. In addition, short- and long-term forecasting, together with the identification of short- and long-range correlations, play a central role in such characterization. To address these objectives, numerous mathematical tools have been developed for the analysis of time series and point processes, each designed to capture specific signal properties. In this work, many of the most important tools used in time series analysis are compiled and reviewed, highlighting their main characteristics and the different types of complex systems to which they have been applied. Full article

Background/Objectives: Joubert syndrome (JS) is a rare neurodevelopmental disorder characterized by cerebellar and brainstem malformations, resulting in a complex and heterogeneous motor phenotype. Despite increasing clinical recognition, functional assessment and physiotherapy strategies in this population remain insufficiently characterized. This study aimed to synthesize current rehabilitation evidence and to propose a conceptual framework for functional motor assessment in children with JS. Methods: A structured narrative review was conducted across PubMed, Scopus, Web of Science, EBSCOhost, the Cochrane Library, and PEDro databases, including studies published between 2000 and 2026. Eligible studies involved pediatric patients (0–18 years) with JS and reported physiotherapy or motor-related outcomes. Data were synthesized descriptively, and recurring functional domains were identified to inform the development of a conceptual framework. Results: Ten studies (eight case reports and two case series) were included. Rehabilitation approaches were heterogeneous and predominantly multidisciplinary, focusing on postural control, trunk stability, and motor milestone acquisition. Functional improvements were reported across studies; however, outcome measures were primarily based on generic pediatric tools such as GMFM-88 and WeeFIM. These tools did not fully capture the multidimensional nature of motor impairment, particularly in relation to regulatory and sensorimotor domains. Evidence also suggested that postural control and gross motor performance may not fully correspond, highlighting additional functional components such as axial control and thoracoabdominal organization. Given the absence of formal risk-of-bias assessment and the low methodological quality of included studies, all findings should be interpreted as exploratory. Conclusions: Current functional assessment in JS may not adequately reflect the interaction between regulatory processes, sensorimotor integration, and motor control. The proposed conceptual framework provides a multidimensional, hypothesis-generating perspective that may support clinical reasoning and physiotherapy planning. Further research is required to validate this framework and to develop more sensitive, syndrome-specific assessment tools. Full article

The temporomandibular joint (TMJ) relies on specialized progenitor cells for tissue maintenance and repair. We characterized TMJ-derived progenitor cells in mice and investigated the role of Evc2-mediated Hedgehog signaling. Progenitor cells from the anterior TMJ exhibited greater colony-forming capacity and an elongated morphology, while posterior cells were cuboidal, highlighting regional heterogeneity. TMJ-derived progenitors demonstrated multipotency, differentiating into osteogenic and chondrogenic lineages. Gli1-expressing, slow-cycling cells localized to the ligament attachment regions, initially accumulating there and not overlapping with specialized cells (Col1⁺ cells). Conditional Evc2 disruption in Gli1-expressing cells paradoxically augmented expression of Gli1 and mechanosensors (Yap, Wwtr1, Piezo1), and produced more confluent, rapidly expanding colonies. We hypothesize that these colonies are primarily composed of transit amplifying cells (TACs), which may proliferate robustly but face challenges in terminal differentiation. These results reveal critical roles for EVC2 and regional progenitor cell diversity in TMJ regenerative biology and suggest that targeting cell signaling and mechanical factors may inform novel strategies for TMJ disorder therapies. Full article

Sestrins are an evolutionarily conserved family of stress-responsive proteins that regulate cellular metabolism, redox balance, and survival. Their expression is induced by diverse cellular stresses through activation of transcription factors such as p53, NRF2, and FOXO. Through antioxidant activity and modulation of mTORC1 and mTORC2 signalling, Sestrins limit the accumulation of reactive oxygen species, regulate metabolic pathways, and promote autophagy. In this review, we analyse published studies reporting SESN1, SESN2, and SESN3 expression in human tissues, circulation, and experimental disease models. The available evidence indicates that Sestrin levels are dynamically regulated across multiple pathologies, including metabolic, ageing, cardiovascular, inflammatory, neurodegenerative, and degenerative disorders. Notably, changes in tissue Sestrin expression are often mirrored in circulation. These observations suggest that Sestrins may serve as informative biomarkers of cellular stress and disease states, and that monitoring their expression in tissues or blood could provide insight into disease progression and therapeutic response. Full article

Speech sound disorder (SSD) is common in childhood and can persist, adversely affecting language, literacy, and social functioning. Yet consonant error patterns in school-age children, particularly in non-English-speaking populations, remain insufficiently characterized. Short-term memory (STM) supports phonological processing and speech learning, but its relationship with SSD severity in school-age children is not well established. This study profiles consonant errors and short-term memory in school-age Chinese children with SSD and examines short-term memory correlates and predictors of disorder severity to inform targeted interventions. A total of 142 Mandarin-speaking school-age children with SSD were recruited. For the short-term memory analyses, we randomly selected 70 children with SSD and recruited 70 typically developing controls. Speech was assessed using a word-level picture-naming task to derive consonant accuracy and characterize error types/patterns, and short-term memory was measured with the WISC-IV Digit Span (forward and backward). Substitutions predominated for most consonants, and individual phonemes often exhibited co-occurring error patterns. In addition, school-age children with SSD showed significantly poorer short-term memory than typically developing peers across multiple indices. Notably, backward digit span was positively associated with consonant accuracy and remained an independent predictor of consonant accuracy. These results advance our understanding of the mechanisms underlying SSD and provide an evidence-based rationale for future interventions that combine speech-focused therapy with cognitive training to enhance clinical outcomes. Full article

Background/Objectives: While intravitreal administration allows for increased ocular exposure to anti-TNF-α monoclonal antibodies, there is still a need for developing delivery systems able to prolong ocular drug exposure and alleviate patient compliance and safety concerns because of repeated injections. Therefore, the objective of this work was to guide the design of sustained-release formulations of anti-TNF-α monoclonal antibodies for intravitreal administration through a model-based strategy in non-infectious uveitis in the preclinical setting. Methods: Using an in-house-developed anterior uveitis disease model in rats, an intravenous reference dose reducing free TNF-α by 90% at the biophase was established. Intravitreal administrations of sustained-release formulations every 24 weeks were then simulated for adalimumab, golimumab and infliximab to evaluate TNF-α kinetics in the anterior chamber of the eye at different release rates. The selected sustained-release formulation was further evaluated for possible formulation issues causing device emptying before the next administration. Results: Intravitreal administration of sustained-release formulations releasing adalimumab, golimumab or infliximab at 1.802, 0.979 and 1.442 μg/week, respectively, met the predefined criteria of ≥90% reduction in free TNF-α at the biophase. TNF-α levels in aqueous humour were anticipated to be the most sensitive to detect possible formulation issues. Formulation emptying 10, 4 or 8 weeks for adalimumab, golimumab and infliximab, respectively, before next administration triggered TNF-α reaching pathological levels at week 24 post-dose. Conclusions: This work underscores the potential of new approach methodologies in the preclinical drug development of sustained-release formulations for intravitreal administration in ocular inflammatory disorders with less animal testing and without compromising the accuracy of model-informed predictions for human translation. Full article