Search Results (10,566)

The etiology of neurodevelopmental disorders and epilepsy is very heterogeneous and partly still unknown, and the research of causative genes related to these diseases is still in progress. In 2020, pathogenic variants of the TET3 gene were associated with Beck–Fahrner syndrome, which is characterized by neurodevelopmental delay, intellectual and learning disabilities of variable degree, growth abnormalities, hypotonia and seizures. Variants of TET3 have been described having both an autosomal dominant with a milder phenotype and an autosomal recessive pattern. To date, in the literature, only 28 patients are reported with pathogenic variants of the TET3 gene, and only 9 of them have epilepsy. We describe a 31-year-old woman with macrocephaly, mild neurodevelopmental delay and a long history of epilepsy. Trio-based exome sequencing identified a de novo heterozygous TET3 variant, c.2867G>A p.(Arg956Gln), never described before, absent in the general population and predicted to be potentially pathogenetic by bioinformatics tools. This report aims to describe the clinical history of our patient, the pharmacological treatment and clinical response, as well as the biological characteristics of this new variant. Full article

Helping people with intellectual and visual disabilities engage in activity and mobility is considered crucially important to promote constructive occupation and a basic form of physical exercise (i.e., objectives that are essential for the individuals’ wellbeing and in line with their rights). This study assessed two new programs aimed at helping eight participants with intellectual and visual disabilities (four in each program) to independently move through specific indoor destinations, collect and transport objects, and access stimulation events (e.g., music) with the support of technology systems involving a smartphone linked to mini cameras and speakers. The second program was more advanced than the first and (a) required the participants to discriminate the objects used and transport two (rather than one) of them before any stimulation event, and (b) included telephone calls to and stories from preferred communication partners among the stimulation events. Each program was implemented using a single-case research design (i.e., a non-concurrent multiple baseline design across participants). The results showed that both programs were effective in enabling the participants to collect, transport, and put away objects and access stimulation independently during 20-min sessions. Based on the results, both programs might be considered useful tools to help people with intellectual and visual disabilities manage independent activity and mobility. Full article

Background/Objectives: Cervical facet joint syndrome (CFJS) is a frequent cause of neck pain and motor disability. Among the available therapies for CFJS, ultrasound (US)-guided injections are becoming more and more widespread, but the evidence about their accuracy and effectiveness is still debated in the scientific literature. The aim of this systematic review is to assess efficacy, accuracy and feasibility of US-guided cervical facet injections for the related chronic neck pain treatment. Methods: This review was conducted following the preferred reporting items for systematic reviews and meta-analysis 2020 (PRISMA) statement guidelines. The scientific articles were identified through the PubMed, Google Scholar and Cochrane Library databases. Qualitative assessment of the selected studies was carried out using the modified Oxford quality scoring system. Nine studies with a total of 958 patients were included in this review. The risk of bias was assessed using the Cochrane Collaboration tool. The protocol was registered at PROSPERO 2024 (n°CRD42024512214). Results: The results of this review suggest that the US-guided cervical facet injection for CFJS treatment is an effective technique in terms of accuracy (using the lateral technique it ranges from 92% to 98%), and efficiency (it grants pain relief with a decrease in the procedure time and fewer needle passes in comparison with the X-ray-guided technique, which also involves radiation exposure). Conclusions: US-guided injections are a safe and effective method to treat this musculoskeletal disease, granting a high functional recovery and long-lasting pain relief, net of the used drugs. However, these procedures are strictly operator-dependent and require important training to acquire good expertise. Full article

Disabled people are uniquely positioned in relation to the digital turn. Academic ableism, the inaccessibility of digital space, and gaps in digital literacy present barriers, while, at the same time, disabled, Deaf, and neurodivergent people’s access knowledge is at the forefront of innovations in culture and crip technoscience. This article explores disability, technology, and access through the concept of crip digital intimacy, a term that describes the relational and affective advances that disabled people make within digital space and through digital technology toward accessing the arts. We consider how moments of crip digital intimacy emerged through Accessing the Arts: Centring Disability Perspectives in Access Initiatives—a research project that explored how to make the arts more accessible through engaging disabled artist-participants in virtual storytelling, knowledge sharing, and art-making activities. Our analysis tracks how crip digital intimacies emerged through the ways participants collectively organized and facilitated access for themselves and each other. Guided by affordance theory and in line with the political thrust of crip technoscience, crip legibility, and access intimacy, we argue that crip digital intimacy emphasizes the interdependent and relational nature of access, recognizes the creativity and vitality of nonnormative bodyminds, and understands disability as a political—and frequently transgressive—way of being in the world. Full article

Background: Mental and behavioral disorders significantly impair psychophysical functioning, leading to challenges in daily activities. The increasing recognition of the importance of mental health in global development goals has resulted in its inclusion in the United Nations’ Sustainable Development Goals. The burden of mental disorders has grown worldwide due to demographic changes, with substantial economic and social impacts. Objective: This study aimed to examine the indirect costs of mental disorders in Poland by analyzing the expenditures by the Social Insurance Institution (ZUS) on work incapacity benefits and disability pensions from 2012 to 2023. The goal was to identify trends, dependencies, and the economic impact of policy changes. Material and Methods: Data were collected from ZUS reports on annual expenditures for work incapacity benefits and disability pensions. Advanced statistical methods, including linear regression and Pearson correlation, were employed to analyze trends and relationships. Student’s t-tests assessed the statistical significance of the observed trends. Results: The expenditures on benefits for work incapacity due to mental disorders increased significantly over the past decade, particularly from 2020 to 2023, partly due to the COVID-19 pandemic. Short-term absenteeism due to mental disorders accounted for 10.5% of the total sick leave days. A strong positive correlation was found between years and benefit expenditures. Conversely, the disability pension expenditures exhibited a downward trend, potentially reflecting improvements in public health or policy changes. Conclusions: The significant increase in expenditures on benefits related to mental disorders may reflect greater awareness, improved diagnostics, and the impact of the COVID-19 pandemic. In contrast, the decline in disability pension expenditures could suggest improved mental health or effective policy measures. However, it is important to emphasize that the presented data are not the only factor influencing this situation. Multiple variables, including societal, economic, and healthcare system changes, contribute to these trends. Therefore, further research is necessary to fully understand the underlying causes and to guide effective policy development. Regular monitoring and continued investment in mental health are essential to managing indirect costs such as absenteeism and presenteeism efficiently. Full article

Experiences of occupational participation of adults with Intellectual Disabilities (IDs) were explored through the lens of the Model of Occupational Justice (MOJ) and Critical Theory in order to shape and develop an occupation-centered model of quality of life (QoL). This qualitative study involved thirteen adults with IDs (N = 13). A semi-structured interview, constructed based on MOJ and Critical Theory principles, was administered to explore perspectives on QoL, as well as injustices regarding occupational participation. The interviews were analyzed using QSR NVivo8 and followed a content analysis methodology. A preliminary model of Occupational Quality of Life (O-QoL), with an everyday occupations core component, has been formed. The model includes three core O-QoL domains: (i) social well-being, (ii) emotional–physical well-being, and (iii) material adequacy. Key indicators of O-QoL were identified as leisure and social activities, while socioenvironmental factors such as occupational deprivation were noted as aggravating. Specific occupations, including leisure activities, physical exercise/sports, art, video games, and vocational training, were found to be beneficial for O-QoL. Moreover, the importance of promoting and supporting the rights of people with IDs for employment, independent living, and sexual expression was highlighted. The model of O-QoL (version 1) could be a valuable alternative conceptual framework of QoL in the field of IDs; however, further research is needed to validate and refine the model. Full article

For several decades, the dopamine hypothesis contributed to the discovery of numerous typical and atypical antipsychotics and was the sole hypothesis for the pathophysiology of schizophrenia. However, neither typical nor atypical antipsychotics, other than clozapine, have been effective in addressing negative symptoms and cognitive impairments, which are indices for the prognostic and disability outcomes of schizophrenia. Following the development of atypical antipsychotics, the therapeutic targets for antipsychotics expanded beyond the blockade of dopamine D2 and serotonin 5-HT2A receptors to explore the partial agonism of the D2 receptor and the modulation of new targets, such as D3, 5-HT1A, 5-HT7, and metabotropic glutamate receptors. Despite these efforts, to date, psychiatry has not successfully developed antipsychotics with antipsychotic properties proven to be superior to those of clozapine. The glutamate hypothesis, another hypothesis regarding the pathophysiology/pathomechanism of schizophrenia, was proposed based on clinical findings that N-methyl-D-aspartate glutamate receptor (NMDAR) antagonists, such as phencyclidine and ketamine, induce schizophrenia-like psychotic episodes. Large-scale genome-wide association studies (GWASs) revealed that approximately 30% of the risk genes for schizophrenia (the total number was over one hundred) encode proteins associated with glutamatergic transmission. These findings supported the validation of the glutamate hypothesis, which was inspired by the clinical findings regarding NMDAR antagonists. Additionally, these clinical and genetic findings suggest that schizophrenia is possibly a syndrome with complicated pathomechanisms that are affected by multiple biological and genetic vulnerabilities. The glutamate hypothesis has been the most extensively investigated pathophysiology/pathomechanism hypothesis, other than the dopamine hypothesis. Studies have revealed the possibility that functional abnormalities of the NMDAR play important roles in the pathophysiology/pathomechanism of schizophrenia. However, no antipsychotics derived from the glutamatergic hypothesis have yet been approved for the treatment of schizophrenia or treatment-resistant schizophrenia. Considering the increasing evidence supporting the potential pro-cognitive effects of glutamatergic agents and the lack of sufficient medications to treat the cognitive impairments associated with schizophrenia, these previous setbacks cannot preclude research into potential novel glutamate modulators. Given this background, to emphasize the importance of the dysfunction of the NMDAR in the pathomechanism and/or pathophysiology of schizophrenia, this review introduces the increasing findings on the functional abnormalities in glutamatergic transmission associated with the NMDAR. Full article

Background: The increasing prevalence of child and adolescent overweight and obesity (CAOAO) in Beijing poses significant health and economic challenges. This study assesses the potential health and economic outcomes of implementing specific interventions to address CAOAO in Beijing. Methods: A deterministic Markov cohort model was used to estimate the impact of five interventions from 2025 to 2115: restrictions on unhealthy food marketing to children, mandatory front of package labeling (FOPL), family-based nutrition and exercise education, school-based nutritional health education, and nutritional counseling in primary healthcare. The model evaluated societal costs, healthcare savings, wages, and economic productivity in adulthood, calculating the return on investment (ROI) for each intervention and their combined effect. Result: Without intervention, Beijing is projected to experience a loss of 13.4 million disability-adjusted life years (DALYs) due to CAOAO. The health and economic impact of childhood obesity in Beijing is projected to be CNY 14.6 trillion (USD 2.1 trillion), or a lifetime loss of CNY 6.8 million (USD 0.96 million) per affected child, exceeding the sum of Beijing’s GDP from 2021 to 2023. Restrictions on unhealthy food marketing to children and nutrition counseling in primary healthcare are projected to yield the highest returns, with benefits accruing within one year of implementation. Owing to the substantial upfront costs, including personnel, materials, and training, school-based and family-based interventions require a longer time horizon to realize significant health and economic benefits. Conclusions: Effective management of CAOAO in Beijing demands a multifaceted approach. The combination of restrictions on unhealthy food marketing to children, mandatory front of package labeling, nutrition counseling in primary healthcare, school-based intervention, and family-based intervention presents the most substantial health and economic returns. This comprehensive strategy aligns with global best practices and addresses the unique challenges faced by Beijing in combating childhood obesity. Full article

Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation, demyelination, and neurodegeneration, resulting in significant disability and reduced quality of life. Current therapeutic strategies primarily target immune dysregulation, but limitations in efficacy and tolerability highlight the need for alternative treatments. Plant-derived compounds, including alkaloids, phenylpropanoids, and terpenoids, have demonstrated anti-inflammatory effects in both preclinical and clinical studies. By modulating immune responses and promoting neuroregeneration, these compounds offer potential as novel adjunctive therapies for MS. This review provides insights into the molecular and cellular basis of MS pathogenesis, emphasizing the role of inflammation in disease progression. It critically evaluates emerging evidence supporting the use of plant-derived compounds to attenuate inflammation and MS symptomology. In addition, we provide a comprehensive source of information detailing the known mechanisms of action and assessing the clinical potential of plant-derived compounds in the context of MS pathogenesis, with a focus on their anti-inflammatory and neuroprotective properties. Full article

SIRTs were demonstrated to play an important role in inflammatory, degenerative, and metabolic alterations, constituting the background of the central nervous system. Thus, they seem to be an appropriate object of investigation (as potential biomarkers of disease activity and/or novel therapeutic targets) in multiple sclerosis (MS), which has a complex etiology that comprises a cross-talk between all these processes. The aim of this study was to evaluate the levels of SIRT1 and SIRT2 in the serum of patients with the relapsing–remitting type of MS (RRMS), as well as their relationships with various aspects of MS-related disability. Methods: A total of 115 patients with RRMS (78 women, 37 men, mean age 43 ± 9.9) and 39 healthy controls were included in the study. SIRT1 and SIRT2 were detected in the serum using the enzyme-linked immunoassay (ELISA) method. In the RRMS group, relationships were investigated between the SIRT 1 and 2 levels and the demographic data, MS-related clinical variables, and the results of tests evaluating fatigue, sleep problems, cognitive performance, autonomic dysfunction, and depression. Results: The levels of SIRT1 and SIRT2 in RRMS patients were significantly lower than in the controls (11.14 vs. 14. 23, p = 0.04; 8.62 vs. 14.2, p < 0.01). In the RRMS group, the level of both SIRTs was higher in men than in women (15.7 vs. 9.0; 11.3 vs. 7.3, p = 0.002) and showed a significant correlation with the degree of disability (R = −0.25, p = 0.018). No other relationships were found between SIRT levels and the analyzed data. Conclusions: The serum levels of SIRT1 and 2 were decreased in the RRMS patients (especially in the female ones) and correlated with the degree of neurological deficit. The role of SIRTs as biomarkers of disease activity or mediators relevant for “invisible disability” in MS warrants further investigation. Full article

Background: Epidemiological data indicate that low back pain (LBP) affected 619 million people globally in 2020, representing a significant health and economic burden. Additionally, chronic LBP (cLBP) strongly impairs quality of life and leads to disability and premature retirement, thus emphasizing the need for providing deeper insight into the factors that affect treatment outcomes and for offering thorough guidance for the assessment and management of this condition. Taking into consideration the rising prevalence of cLBP and the knowledge gap referring to the overall health benefits of balneotherapy (BT), the aim of this study was to assess the effects of BT on functional status, quality of life, and psychological symptoms in patients with cLBP. Methods: Among 220 patients from the database, two groups were retrospectively identified: patients receiving conventional pharmacological therapy (CT) and patients receiving BT. The effectiveness of the treatment was assessed through a visual analog scale for pain intensity, EuroQol (EQ-5D), and the Work Ability Index Questionnaire. In order to provide deeper insight into the quality of life and also factors associated with functional status and mental health affected by BT, we also used the Short Form Health Survey Questionnaire and the Center of Epidemiologic Studies Depression Scale. Results: Both age and treatment protocol were found to have a significant impact on all observed parameters, i.e., older patients and those receiving CT tended to report lower overall health and physical functioning. On the other hand, BT was associated with better functionality and disability perception status. Conclusions: Understanding the association between individual perceptions of functionality and its emotional and social elements provides a basis for providing comprehensive guidelines and recommendations for cLBP management. Full article

Osteoarthritis (OA) is an age-related disease characterized by inflammation, pain, articular cartilage damage, synovitis, and irreversible disability. Gynostemma pentaphyllum (Thunb.) Makino (GP), a herbal medicine traditionally used in East Asia for its anti-inflammatory properties, was investigated for its potential to modulate OA pathology and symptoms. This study evaluated GP’s efficacy in inhibiting pain, functional decline, and cartilage destruction in monosodium iodoacetate-induced OA and acetic acid-induced writhing models. Additionally, the effects of GP on OA-related inflammatory targets were assessed via mRNA and protein expression in rat knee cartilage and lipopolysaccharide-induced RAW 264.7 cells. The GP group demonstrated significant pain relief, functional improvement, and cartilage protection. Notably, GP inhibited key inflammatory mediators, including interleukin (IL)-1β, IL-6, matrix metalloproteinases (MMP)-3 and MMP-13, cyclooxygenase-2, and prostaglandin E receptor 2, surpassing the effects of active controls. These findings suggest that GP is a promising candidate for disease-modifying OA drugs and warrants further comprehensive studies. Full article

Effective communication is crucial in daily life, and for people with hearing disabilities, sign language is no exception, serving as their primary means of interaction. Various technologies, such as cochlear implants and mobile sign language translation applications, have been explored to enhance communication and improve the quality of life of the deaf community. This article presents a new, innovative method that uses real-time machine learning (ML) to accurately identify Mexican sign language (MSL) and is adaptable to any sign language. Our method is based on analyzing six features that represent the angles between the distal phalanges and the palm, thus eliminating the need for complex image processing. Our ML approach achieves accurate sign language identification in real-time, with an accuracy and F1 score of 99%. These results demonstrate that a simple approach can effectively identify sign language. This advance is significant, as it offers an effective and accessible solution to improve communication for people with hearing impairments. Furthermore, the proposed method has the potential to be implemented in mobile applications and other devices to provide practical support to the deaf community. Full article

Chronic threatening limb ischemia of the inferior limbs (CLTI) is the final stage of peripheral arterial disease (PAD) and is one of the most feared atherosclerotic manifestations because if left untreated, in time, it can lead to amputation. Although there are currently numerous treatment techniques, both open and endovascular, it is a pathology that has no underlying treatment. Therefore, current studies are very much focused on new therapeutic possibilities that can be applied in the early stages of the atherosclerotic process. In numerous studies in the literature, miRNAs have been identified as important markers of atherosclerosis. The present study aims to identify the expression of three miRNAs—miR-199a, miR-20a, and miR-30c—in patients with chronic limb-threatening ischemia in the pre- and post-revascularization periods. The aim of the study is to identify whether these three markers play a role in critical ischemia and whether they have the potential for future use in new treatments of this pathology. Full article

Traditional myoelectric controls of trans-humeral prostheses fail to provide intuitive coordination of the necessary degrees of freedom. We previously showed that by using artificial neural network predictions to reconstruct distal joints, based on the shoulder posture and movement goals (i.e., position and orientation of the targeted object), participants were able to position and orient an avatar hand to grasp objects with natural arm performances. However, this control involved rapid and unintended prosthesis movements at each modification of the movement goal, impractical for real-life scenarios. Here, we eliminate this abrupt change using novel methods based on an angular trajectory, determined from the speed of stump movement and the gap between the current and the ‘goal’ distal configurations. These new controls are tested offline and online (i.e., involving participants-in-the-loop) and compared to performances obtained with a natural control. Despite a slight increase in movement time, the new controls allowed twelve valid participants and six participants with trans-humeral limb loss to reach objects at various positions and orientations without prior training. Furthermore, no usability or workload degradation was perceived by participants with upper limb disabilities. The good performances achieved highlight the potential acceptability and effectiveness of those controls for our target population. Full article