Search Results (4,566)

Background/Objectives: Huntington’s disease (HD) is an autosomal dominant, neurodegenerative disorder that, because of the availability of presymptomatic genetic testing, places at-risk individuals in an anticipatory situation of great emotional, ethical, and social complexity. This review synthesizes the subjective experiences and coping strategies of individuals aware of their genetic risk before clinical diagnosis, emphasizing the importance of patient and family narratives as critical sources of evidence for enhancing care protocols. Methods: This work is a narrative review supported by a systematic literature search. Of the 75 studies analyzed, 22 met the inclusion criteria—i.e., qualitative research, reviews, and case studies addressing emotional, cognitive, behavioral, and ethical coping mechanisms. The information was structured within a thematic matrix, and inductive coding was applied to identify recurring patterns, unresolved tensions, and gaps in the literature. Results: Presymptomatic genetic diagnosis may trigger processes of anticipatory grief, disrupt individual and familial identity, and lead to constant somatic self-monitoring. Coping strategies vary from proactive approaches—e.g., seeking information and building support networks—to narrative reframing that emphasizes acceptance and the resignification of risk. Analyzing these narratives allowed us to identify silenced ethical dilemmas and family rituals that help alleviate uncertainty—dimensions often overlooked by traditional quantitative methods. Moreover, risk awareness also impacts reproductive and care planning decisions, underscoring the importance of ongoing, context-sensitive support. Conclusions: Coping with genetic risk in Huntington’s disease extends beyond the biomedical aspects to encompass relational, ethical, and narrative dimensions. Incorporating narrative-based medicine into genetic and psychosocial counseling is crucial for identifying implicit needs and providing more empathetic, individualized care. Full article

Students with autism spectrum disorder (ASD) often face difficulties in solving arithmetic word problems, particularly in transitioning from informal counting strategies to more efficient methods based on number facts and formal operations. This study examined the development of problem-solving strategies in a single student with ASD and intellectual disability across two sequential single-case experiments using multiple baseline designs. Study 1 (age 13 years 9 months; 17 sessions) employed Modified Schema-Based Instruction (MSBI) to teach addition and subtraction change problems, while Study 2 (age 14 years 10 months; 18 sessions) utilized the Conceptual Model-based Problem Solving (COMPS) approach for multiplication and division equal-group problems. Success was defined as both correctness of the response and correctly identifying the required operation. Results indicated that the student’s performance improved in all problem types in both studies, with maintenance observed 8 weeks after Study 1 and 5 weeks after Study 2. Instruction effects generalized to two-step addition and subtraction problems in Study 1, and to two-step addition and multiplication problems in Study 2. The findings indicate that both MSBI and COMPS facilitated the student’s shift from informal strategies to efficient operation-based problem solving. Implications for practice include the need for individualized reinforcements, careful adaptation of instruction, and providing teachers with a variety of problems and knowledge of these teaching methods to support students with ASD in developing advanced problem-solving skills. Full article

The global rise in the elderly population inherently escalates the demand for health and social care. Ensuring cognitive performance for healthy brain aging presents significant challenges for researchers and health professionals promoting self-care behaviors. This article aims to provide a comprehensive and critical analysis of the latest research on healthy brain aging by employing a biopsychosocial framework. It integrates biological, psychological, and social dimensions to elucidate their collective influence on cognitive health in older adults. Methodologically, this article provides a narrative review of the existing literature. A diverse array of bibliographic resources was obtained from prominent electronic databases, including MEDLINE, PubMed, Scopus and Web of Science, to ensure broad coverage of the topic. The search was designed to capture relevant studies published between 2010 and 2025, using key terms such as ‘aging’, ‘biomarker’, ‘neurodegeneration’, and ‘cognitive performance’. Following a rigorous selection process, two field specialists evaluated a total of 106 full-text articles to identify those that met the eligibility criteria, ultimately yielding 70 relevant studies. The findings reveal important connections between psychosocial and biological biomarkers and brain morphology, highlighting lifestyle factors—such as diet, exercise, and social engagement—as crucial for cognitive health. The article also underscores specific biomarkers relevant for assessing brain age and their relationship to neurodegenerative disorders. Notably, while biological markers like Aβ, tau, and α-synuclein (proteins that define the core molecular pathology of common neurodegenerative diseases) are present, they do not guarantee the onset of neurodegenerative diseases; psychosocial factors play an essential role in determining disease manifestation. In conclusion, these results support a holistic approach to healthy aging, which integrates psychosocial environments and lifestyle choices that enhance cognitive resilience. We propose further cross-sectional descriptive studies to better identify the biopsychosocial variables influencing cognitive performance and healthy brain aging, aiming to improve clinical practices and inform public health strategies. Full article

Using Medline and Scopus as search engines, we identified reports of 10 clinical studies (published up to 1 September 2025) on botulinum neurotoxin therapy for hereditary spastic paraplegia (HSP). Nine studies were conducted in adults and one in children. Only one of the ten studies was double-blind and placebo-controlled. The search strategy included only articles published in English and articles providing basic information such as the type of the study, type and dose of the toxin and results of the treatment. Articles not in English, case reports and review articles were excluded. A total of 258 patients were included across all studies. The injected toxin in the open-label studies was botulinumtoxin-A (Botox or Dysport or Xeomin), whereas in the blinded study, the investigators used Prosigne. All open-label studies, which used FDA approved botulinumtoxin-A neurotoxins, demonstrated a degree of motor and non-motor improvement, whereas treatment with Prosigne did not improve patients’ function. The possible reasons for this discrepancy between the blinded study and the open-label studies are discussed. We found no studies on the effect of BoNTs on bladder dysfunction in HSP. There is a need for double-blind, placebo-controlled studies assessing the efficacy of FDA-approved botulinum neurotoxins in children and adults affected by hereditary spastic paraparesis. Such studies should also investigate the effect(s) of early botulinum neurotoxin therapy in this disorder. The novelty of this review is that it represents a comprehensive and critical literature review on this subject, with no other studies of this kind published previously. It also includes data not present in previous reviews of this subject. Full article

Background/Objectives: Limited access to mental health services contributes to poorer outcomes among individuals with mental health conditions, including major depressive disorder (MDD). Nurse-led interventions serve as a strategic model of care to improve mental health service delivery and enhance patient outcomes. This project aims to co-design a nurse-led telehealth family psychoeducation (FPE) for MDD and primarily assess its feasibility by evaluating the recruitment and retention rates. Methods: A multi-methods study encompassing a co-design phase (Study Phase 1) and a feasibility study (Study Phase 2). Study Phase 1 will involve semi-structured interviews with individuals with MDD and their families or significant others, as well as surveys and focus groups with mental health professionals to develop telehealth FPE for MDD. Study Phase 2 will evaluate the feasibility and acceptability of the intervention, which comprises three biweekly FPE sessions and a six-week follow-up with patient–family dyads using a single-group pre-post design. The primary outcomes comprise the feasibility and acceptability of intervention. Exploratory secondary outcomes include personal recovery, medication necessity beliefs and concerns, antidepressant adherence, and depression severity, measured at baseline, immediately post-intervention, and at 6-week follow-up using validated measures. Data analysis will primarily involve descriptive statistics and thematic analysis. The TIDieR checklist will be followed in reporting the intervention development. Conclusions: Findings from the proposed study will inform the design and protocol for a future randomised trial of telehealth FPE for improving clinical and non-clinical outcomes in MDD. The feasibility study was prospectively registered with the ClinicalTrial.gov on 8 June 2025 (NCT07014241). Full article

Psychiatric disorders affect nearly one billion people worldwide and remain a major therapeutic challenge due to frequent treatment resistance. Pharmacogenetics provides a precision-informed approach by accounting for interindividual variability in drug metabolism and response, and population-specific data offer valuable information for therapeutic considerations. This study analyzed 3011 Greek individuals to assess 24 pharmacogenetic variants across 13 genes. Genotyping was performed using TaqMan OpenArray^® assays, and metabolic phenotypes were predicted based on established genotype-to-phenotype translation guidelines. Allele frequencies were compared with those in European, African, and East Asian populations. Population structure and genetic differentiation were evaluated using Principal Component Analysis (PCA), K-means clustering, fixation index (F_ST), and STRUCTURE analysis. Results indicated that most allele frequencies in Greeks aligned with those in European populations, while several CYP2D6 and CYP2C19 variants differed significantly from those in African and East Asian cohorts. PCA and clustering confirmed strong European affinity, supported by low F_ST values, whereas STRUCTURE revealed minimal non-European admixture. Predicted metabolic phenotypes showed that 36%, 57.7%, and 41.6% of individuals exhibited altered CYP2D6, CYP2C19, and CYP2C9 activity, respectively. These findings highlight clinically actionable variation in the Greek population and emphasize the use of population-specific pharmacogenetic data to inform optimized strategies in precision psychiatry. Full article

Interferons (IFNs) are key cytokines at the intersection of innate and adaptive immunity. While their antiviral and antitumor roles are well recognized, emerging evidence implicates IFNs—particularly types I, II, and III—in the initiation and progression of autoimmune diseases (ADs). This review synthesizes current data on IFN biology, their immunoregulatory and pathogenic mechanisms, and their contributions to distinct AD phenotypes. We conducted a comprehensive review of peer-reviewed literature on IFNs and autoimmune diseases, focusing on publications indexed in PubMed and Scopus. Studies on molecular pathways, immune cell interactions, disease-specific IFN signatures, and clinical correlations were included. Data were extracted and thematically organized by IFN type, signaling pathway, and disease context, with emphasis on rheumatic and systemic autoimmune disorders. Across systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, systemic sclerosis, idiopathic inflammatory myopathies, multiple sclerosis, type 1 diabetes, psoriasis, and inflammatory bowel diseases, IFNs were consistently associated with aberrant activation of pattern recognition receptors, sustained expression of interferon-stimulated genes (ISGs), and dysregulated T cell and B cell responses. Type I IFNs often preceded clinical onset, suggesting a triggering role, whereas type II and III IFNs modulated disease course and severity. Notably, IFNs exhibited dual immunostimulatory and immunosuppressive effects, contingent on tissue context, cytokine milieu, and disease stage. IFNs are central mediators in autoimmune pathogenesis, functioning as both initiators and amplifiers of chronic inflammation. Deciphering the context-dependent effects of IFN signaling may inform targeted therapeutic strategies and advance precision immunomodulation in autoimmune diseases. Full article

Objectives: To evaluate dental students’ and recent graduates’ perceptions of the integration, effectiveness, quality, and clinical relevance of orofacial pain (OFP) and temporomandibular disorders (TMDs) education in the Oral Medicine (OM) course at Umm Al-Qura University’s Faculty of Dental Medicine (UQUDENT), and to identify educational gaps and opportunities for curriculum improvement. Methods: This cross-sectional study was conducted using a self-administered online questionnaire distributed via Google Forms to 117 participants, including fourth- to sixth-year students, interns, and recent (2022–2024) graduates. Respondents provided demographic information and assessed the effectiveness (10 items), quality (4 items), and value/relevance (4 items) of the OM course using a 5-point Likert scale. Results: Respondents provided moderate ratings for course effectiveness (mean = 35.2/50) and quality (mean = 13.5/20), and rated OFP/TMD content as having high clinical value (mean = 16.1/20). They had limited confidence in OFP/TMD diagnosis (mean = 3.09/5) and management (mean = 3.19/5). More than 80% believed the curriculum should include more OFP/TMD content. No significant differences were observed by gender, sector, study/work area, clinical exposure (all p > 0.05). Conclusions: Students recognize the importance of OFP/TMD education, but the current curriculum may be insufficiently structured to build competence. Improvement of curricular depth, teaching methods, and clinical exposure is recommended. Full article

Objectives: Chronic pain corresponds to hypersensitivity to painful stimuli; however, its relation to acute pain sensitivity in children is poorly understood. We explored this relationship by comparing acute and chronic pain measures, along with related factors, in children with chronic pain syndromes versus controls, before and after therapeutic intervention. Methods: This prospective controlled cohort study involved 57 children with chronic pain undergoing intensive interdisciplinary pain treatment in a hospital-based pain rehabilitation program and 50 controls. Participants, aged 7–18, were tested using a cold pressor task (CPT) at admission, discharge, and first follow-up visit. Data on sleep, anxiety, psychological distress, functional impairment, and pain were collected. Results: Significant differences were found between control and treatment groups in average pain threshold (p < 0.001), pain tolerance (p = 0.035), sleep visual analog scale (VAS) (p < 0.001), functional disability inventory (p < 0.001), patient reported outcomes information system anxiety assessment tool (p < 0.001), general anxiety disorder 7-item scale (p < 0.001), pain VAS (p < 0.001) and total brief symptom inventory (BSI) (p < 0.001) scores at admission with children with chronic pain scoring worse on all measures save the pain VAS during the CPT. After treatment and at follow-up, function and mental health measures improved but not acute pain threshold. Conclusions: At treatment completion, function and mental health significantly improved but acute pain threshold and sleep quality were unchanged. These findings suggest that while chronic pain treatment improves overall function and mental health, acute pain thresholds may not be a suitable indicator for evaluating the efficacy of interventions. Full article

Study Design: Retrospective Case–Control. Objectives: Sleep disturbances negatively impact quality of life and increase illness susceptibility. Chronic pain is a risk factor for sleep disruption, particularly in patients with degenerative spinal conditions. Existing studies suggest that degenerative cervical myelopathy (DCM) patients often experience sleep disturbances, possibly due to spinal cord compression and pain. However, most research is limited to small, single-center studies, creating a need for broader analyses. Methods: We utilized the Merative Explorys Dataset, focusing on electronic health record data of patients diagnosed with DCM and sleep disorders identified via ICD codes. Comorbidities analyzed included depression/bipolar disorder, chronic pulmonary disease, migraine, osteoarthritis, hypertension, malignancy, diabetes, and cerebrovascular disease. Patient demographic information (age, race, sex, and body mass index (BMI)) was included as covariates. Logistic regression analyses were performed to evaluate the association between each comorbidity and the risk of sleep disturbance. Results: Among 40,551 DCM patients, significant predictors of sleep disturbance included higher BMI (OR: 1.05, 95% CI: 1.05–1.06), depression/bipolar disorder (OR: 1.65, 95% CI: 1.56–1.74), chronic pulmonary disease (OR: 1.26, 95% CI: 1.20–1.33), migraine (OR: 1.32, 95% CI: 1.22–1.43), and hypertension (OR: 1.16, 95% CI: 1.10–1.23). Conclusions: This large-scale analysis demonstrates the multifactorial nature of sleep disturbances in DCM, highlighting strong associations with BMI and respiratory conditions, suggesting a contributory role of sleep-disordered breathing. The identification of migraines as a risk factor highlights the need for multidisciplinary management. Addressing modifiable risk factors such as BMI and mental health may improve sleep quality in DCM patients. Full article

Retinoic acid (RA) binds RA (RAR) and Retinoid X (RXR) receptors to elicit biological effects by regulating transcription. RA is also known to have non-canonical activities mediated, primarily, by cellular retinoic acid-binding protein 1 (CRABP1) which forms protein complexes named “CRABP1 signalosomes” to regulate cytosolic signaling independent of RARs/RXRs. This review focuses on therapeutic applications in neurodegeneration by targeting CRABP1 signalosomes including CRABP1–MAPK, CRABP1–CaMKII, CRABP1–eIF2α, and others recently identified from our proteomic studies. The mouse Crabp1 gene is regulated by various epigenetic factors and is important for the health of multiple cell types including motor neurons (MNs). In humans, CRABP1 gene expression is reduced in ALS- and SMA-patient MNs. RA is a therapeutic agent for leukemias and dermatological disorders and is being investigated for managing neurodegenerative diseases, but its therapeutic effects are accompanied by RAR-mediated toxic effects. We have uncovered a novel class of synthetic retinoids that bind CRABP1 without acting on RARs, circumventing RAR-mediated toxic effects. These first-generation CRABP1-selective compounds C3, C4, and C32 target CRABP1–MAPK and/or CRABP1–CaMKII signalosomes. This knowledge, together with emerging structural information, sheds lights on the strategies in designing next-generation CRABP1-signalosome-selective retinoids for the management of neurodegenerative diseases. Full article

People with Autism Spectrum Disorder (ASD) face significant barriers to accessing and maintaining employment, many of which stem from work environments that fail to accommodate their neurological diversity. This article aims to analyze the occupational risks faced by autistic individuals in the workplace. A total of 39 scientific studies were reviewed, and the results identified nine predominant thematic categories of occupational risks. Particularly prominent were deficient communication, lack of structured support, cognitive overload, and difficulties coping with change. The reported situations were examined in detail, with attention paid to their specific contexts. A clear predominance of psychosocial risks over ergonomic ones was observed. The review also highlights several underexplored yet equally relevant risk factors, such as discontinuity in supported employment programs, difficulties in requesting reasonable accommodations, discrimination, a lack of professional recognition, and the negative effects of digital or remote environments, such as isolation. This study underscores the importance of recognizing unsafe conditions arising from the lack of neurodiversity-informed adjustments as a necessary step toward implementing organizational and social adaptations in the workplace. Full article

The legalization of cannabis in multiple U.S. states and several other countries, along with its increasing social acceptance across diverse demographic and socioeconomic groups, has led to a growing number of patients presenting for interventional procedures with a history of cannabis use. Although anesthetic and sedation-related implications may be less pronounced than in major surgery, they remain clinically relevant and warrant careful consideration. Key factors include acute intoxication, chronic use, and cannabis use disorder. Cannabis users often require higher—and sometimes unpredictable—doses of propofol and other sedatives. Inhalational use is associated with airway hyperreactivity, increasing the risk of bronchospasm and, in severe cases, life-threatening laryngospasm. Acute intoxication may also impair the patient’s ability to provide informed consent. Cardiovascular manifestations, including tachycardia, hypertension, and an elevated risk of myocardial infarction, may occur depending on the timing and extent of recent cannabis exposure. Although these effects are unlikely to cause major complications during routine screening colonoscopy or diagnostic esophagogastroduodenoscopy, advanced therapeutic procedures may pose significant challenges for sedation providers. This narrative review summarizes the chemistry, pharmacology, and sedation-related implications of cannabis use in patients undergoing sedation requiring interventional procedures, with a specific focus on GI endoscopy. Full article

Background/Objectives: The spinal cord is a critical component of the central nervous system that transmits neural signals between the brain and the body’s peripheral regions through its nerve roots. Despite being partially protected by the vertebral column, the spinal cord remains highly vulnerable to trauma, tumors, infections, and degenerative or inflammatory disorders. These conditions can disrupt neural conduction, resulting in severe functional impairments, such as paralysis, motor deficits, and sensory loss. Therefore, accurate and comprehensive spinal cord segmentation is essential for characterizing its structural features and evaluating neural integrity. Methods: In this study, we propose a fully automated method for segmentation of the cervical spinal cord in sagittal magnetic resonance (MR) images. This method facilitates rapid clinical evaluation and supports early diagnosis. Our approach uses a Swin-Unet architecture, which integrates vision transformer blocks into the U-Net framework. This enables the model to capture both local anatomical details and global contextual information. This design improves the delineation of the thin, curved, low-contrast cervical cord, resulting in more precise and robust segmentation. Results: In experimental studies, the proposed Swin-Unet model (SWU1), which uses transformer blocks in the encoder layer, achieved Dice Similarity Coefficient (DSC) and Hausdorff Distance 95 (HD95) scores of 0.9526 and 1.0707 mm, respectively, for cervical spinal cord segmentation. These results confirm that the model can consistently deliver precise, pixel-level delineations that are structurally accurate, which supports its reliability for clinical assessment. Conclusions: The attention-enhanced Swin-Unet architecture demonstrated high accuracy in segmenting thin and complex anatomical structures, such as the cervical spinal cord. Its ability to generalize with limited data highlights its potential for integration into clinical workflows to support diagnosis, monitoring, and treatment planning. Full article

Background/Objective: Childhood obesity and mental health disorders in preschool-aged children represent critical public health challenges with a rising global prevalence, closely linked to lifestyle behaviors and the family environment. This cross-sectional study aims to investigate the combined influence of maternal sociodemographic, socioeconomic, anthropometric characteristics, and lifestyle factors on the physical and mental health status of preschool-aged children. Methods: Validated questionnaires were administered to assess dietary habits, psychosocial parameters (depression, anxiety, stress), and sociodemographic, socioeconomic, and anthropometric variables among 200 preschool-aged children and their mothers, who served as the primary informants. Results: Maternal obesity was associated with a higher prevalence of childhood overweight/obesity (36.7% vs. 18.5% in children of non-obese mothers, p = 0.009). Maternal psychological factors, specifically depressive symptoms (B = 0.998, OR = 2.712, 95% CI: 1.222–6.020, p = 0.014) and anxiety (B = 1.676, OR = 5.346, 95% CI: 2.471–11.565, p < 0.001), were independently associated with an increased likelihood of child anxiety. Anthropometric measures, including waist circumference (p = 0.032) and hip circumference (p = 0.031), primarily influenced children’s physical health, whereas maternal psychological factors predominantly affected their emotional well-being. Conclusions: The findings underscore the necessity for targeted interventions focusing on enhancing maternal nutrition and mental health literacy, aiming to promote healthy dietary patterns, physical activity, and lifestyle behaviors. Such interventions are pivotal for preventing childhood obesity and fostering overall well-being at the population level. Full article