-
NPJ Parkinson's Disease Jun 2024Most neurodegenerative diseases lack definitive diagnostic tests, and the identification of easily accessible and reliable biomarkers remains a critical unmet need....
Most neurodegenerative diseases lack definitive diagnostic tests, and the identification of easily accessible and reliable biomarkers remains a critical unmet need. Since tau protein is highly expressed in skin of tauopathies patients, we aimed to exploit the ultrasensitive seeding activity assay (SAA) to assess tau seeding activity in skin of patients with tauopathies. In this multicentric, case-control study, patients with tauopathies and synucleinopathies were consecutively recruited and sex-matched to healthy controls (HC). Subjects underwent a double 3 mm skin biopsy in cervical area and ankle. Skin tau-SAA, using TauK18 and TauK19 as reaction substrates for 4R and 3R isoforms, seeding score, clinical scales, biochemical and morphological characterization of SAA end-products were evaluated. We analyzed 58 subjects: 24 tauopathies (18 progressive supranuclear palsy, PSP, and 6 corticobasal degeneration, CBD), 20 synucleinopathies (14 Parkinson's disease, PD, and 6 multiple system atrophy, MSA), and 14 HC. PSP and CBD showed higher tau seeding activity at both anatomical sites. A greater sensitivity of 4R-SAA than 3R-SAA was observed. 4R tau-SAA identified tauopathies with 71% sensitivity and 93% specificity. Accuracy was higher for PSP than CBD: PSP vs HC / PD (AUC 0.825), while CBD vs HC / PD (AUC 0.797), and PSP vs MSA (AU 0.778). SAA end-products showed differences in biochemical and morphological characterization according to the anatomical site. Skin tau-SAA identifies tauopathies with good accuracy and can be used to implement the in-vivo clinical diagnosis of patients with neurodegenerative diseases. Further characterization of peripheral tau seed in skin may elucidate the structure of tau deposits in brain.
PubMed: 38879633
DOI: 10.1038/s41531-024-00728-9 -
Journal of Neurodevelopmental Disorders Jun 2024Angelman syndrome (AS) is a neurodevelopmental disorder associated with severe global developmental delay. However, the ages at which different developmental skills are...
BACKGROUND
Angelman syndrome (AS) is a neurodevelopmental disorder associated with severe global developmental delay. However, the ages at which different developmental skills are achieved in these individuals remain unclear. We seek to determine the probability and the age of acquisition of specific developmental milestones and daily living skills in individuals with AS across the different molecular subtypes, viz. class I deletion, class II deletion, uniparental disomy, imprinting defect, and UBE3A variants.
METHODS
Caregivers participating in a longitudinal multicenter Angelman Syndrome Natural History Study completed a questionnaire regarding the age at which their children achieved specific developmental milestones and daily living skills. The Cox Proportional Hazard model was applied to analyze differences in the probability of achievement of skills at various ages among five molecular subtypes of AS.
RESULTS
Almost all individuals, regardless of molecular subtype, were able to walk with support by five years of age. By age 15, those with a deletion had at least a 50% probability of acquiring 17 out of 30 skills compared to 25 out of 30 skills among those without a deletion. Overall, fine and gross motor skills such as holding and reaching for small objects, sitting, and walking with support were achieved within a fairly narrow range of ages, while toileting, feeding, and hygiene skills tend to have greater variability in the ages at which these skills were achieved. Those without a deletion had a higher probability (25-92%) of achieving daily living skills such as independently toileting and dressing compared to those with a deletion (0-13%). Across all molecular subtypes, there was a low probability of achieving independence in bathing and brushing teeth.
CONCLUSION
Individuals with AS without a deletion are more likely to achieve developmental milestones and daily living skills at an earlier age than those with a deletion. Many individuals with AS are unable to achieve daily living skills necessary for independent self-care.
Topics: Humans; Angelman Syndrome; Activities of Daily Living; Female; Child, Preschool; Male; Child; Adolescent; Infant; Child Development; Longitudinal Studies; Motor Skills; Developmental Disabilities; Adult; Young Adult
PubMed: 38879552
DOI: 10.1186/s11689-024-09548-7 -
Nature Communications Jun 2024Lewy body (LB) diseases, characterized by the aggregation of misfolded α-synuclein proteins, exhibit notable clinical heterogeneity. This may be due to variations in...
Lewy body (LB) diseases, characterized by the aggregation of misfolded α-synuclein proteins, exhibit notable clinical heterogeneity. This may be due to variations in accumulation patterns of LB neuropathology. Here we apply a data-driven disease progression model to regional neuropathological LB density scores from 814 brain donors with Lewy pathology. We describe three inferred trajectories of LB pathology that are characterized by differing clinicopathological presentation and longitudinal antemortem clinical progression. Most donors (81.9%) show earliest pathology in the olfactory bulb, followed by accumulation in either limbic (60.8%) or brainstem (21.1%) regions. The remaining donors (18.1%) initially exhibit abnormalities in brainstem regions. Early limbic pathology is associated with Alzheimer's disease-associated characteristics while early brainstem pathology is associated with progressive motor impairment and substantial LB pathology outside of the brain. Our data provides evidence for heterogeneity in the temporal spread of LB pathology, possibly explaining some of the clinical disparities observed in Lewy body disease.
Topics: Humans; alpha-Synuclein; Disease Progression; Lewy Body Disease; Aged; Male; Female; Lewy Bodies; Aged, 80 and over; Alzheimer Disease; Brain; Brain Stem; Olfactory Bulb; Middle Aged
PubMed: 38879548
DOI: 10.1038/s41467-024-49402-x -
Acta Neuropathologica Communications Jun 2024Wasteosomes (or corpora amylacea) are polyglucosan bodies that appear in the human brain with aging and in some neurodegenerative diseases, and have been suggested to...
Wasteosomes (or corpora amylacea) are polyglucosan bodies that appear in the human brain with aging and in some neurodegenerative diseases, and have been suggested to have a potential role in a nervous system cleaning mechanism. Despite previous studies in several neurodegenerative disorders, their status in frontotemporal lobar degeneration (FTLD) remains unexplored. Our study aims to characterize wasteosomes in the three primary FTLD proteinopathies, assessing frequency, distribution, protein detection, and association with aging or disease duration. Wasteosome scores were obtained in various brain regions from 124 post-mortem diagnosed sporadic FTLD patients, including 75 participants with tau (FTLD-tau), 42 with TAR DNA-binding protein 43 (FTLD-TDP), and 7 with Fused in Sarcoma (FTLD-FUS) proteinopathies, along with 29 control subjects. The wasteosome amount in each brain region for the different FLTD patients was assessed with a permutation test with age at death and sex as covariables, and multiple regressions explored associations with age at death and disease duration. Double immunofluorescence studies examined altered proteins linked to FTLD in wasteosomes. FTLD patients showed a higher accumulation of wasteosomes than control subjects, especially those with FTLD-FUS. Unlike FTLD-TDP and control subjects, wasteosome accumulation did not increase with age in FTLD-tau and FTLD-FUS. Cases with shorter disease duration in FTLD-tau and FTLD-FUS seemed to exhibit higher wasteosome quantities, whereas FTLD-TDP appeared to show an increase with disease progression. Immunofluorescence studies revealed the presence of tau and phosphorylated-TDP-43 in the periphery of isolated wasteosomes in some patients with FTLD-tau and FTLD-TDP, respectively. Central inclusions of FUS were observed in a higher number of wasteosomes in FTLD-FUS patients. These findings suggest a role of wasteosomes in FTLD, especially in the more aggressive forms of FLTD-FUS. Detecting these proteins, particularly FUS, in wasteosomes from cerebrospinal fluid could be a potential biomarker for FTLD.
Topics: Humans; Frontotemporal Lobar Degeneration; Female; Male; RNA-Binding Protein FUS; Aged; tau Proteins; Middle Aged; Aged, 80 and over; DNA-Binding Proteins; Brain
PubMed: 38879502
DOI: 10.1186/s40478-024-01812-0 -
Scientific Reports Jun 2024Parkinson's Disease (PD) is a prevalent neurological condition characterized by motor and cognitive impairments, typically manifesting around the age of 50 and...
Parkinson's Disease (PD) is a prevalent neurological condition characterized by motor and cognitive impairments, typically manifesting around the age of 50 and presenting symptoms such as gait difficulties and speech impairments. Although a cure remains elusive, symptom management through medication is possible. Timely detection is pivotal for effective disease management. In this study, we leverage Machine Learning (ML) and Deep Learning (DL) techniques, specifically K-Nearest Neighbor (KNN) and Feed-forward Neural Network (FNN) models, to differentiate between individuals with PD and healthy individuals based on voice signal characteristics. Our dataset, sourced from the University of California at Irvine (UCI), comprises 195 voice recordings collected from 31 patients. To optimize model performance, we employ various strategies including Synthetic Minority Over-sampling Technique (SMOTE) for addressing class imbalance, Feature Selection to identify the most relevant features, and hyperparameter tuning using RandomizedSearchCV. Our experimentation reveals that the FNN and KSVM models, trained on an 80-20 split of the dataset for training and testing respectively, yield the most promising results. The FNN model achieves an impressive overall accuracy of 99.11%, with 98.78% recall, 99.96% precision, and a 99.23% f1-score. Similarly, the KSVM model demonstrates strong performance with an overall accuracy of 95.89%, recall of 96.88%, precision of 98.71%, and an f1-score of 97.62%. Overall, our study showcases the efficacy of ML and DL techniques in accurately identifying PD from voice signals, underscoring the potential for these approaches to contribute significantly to early diagnosis and intervention strategies for Parkinson's Disease.
Topics: Parkinson Disease; Humans; Machine Learning; Male; Female; Middle Aged; Aged; Neural Networks, Computer; Voice; Deep Learning
PubMed: 38877028
DOI: 10.1038/s41598-024-64004-9 -
Applied Ergonomics Jun 2024Many physically straining occupations involve lifting movements over the full-vertical range of motion, which over time may lead to the development of musculoskeletal...
Many physically straining occupations involve lifting movements over the full-vertical range of motion, which over time may lead to the development of musculoskeletal injuries. To address this, occupational exoskeletons can be designed to provide meaningful support to the back and shoulders during lifting movements. This paper introduces the main functional design features of the OmniSuit, a novel passive occupational exoskeleton. We present the technical and biomechanical considerations for the expected support level, as well as an evaluation of the physiological benefit and usability of the exoskeleton in a sample of 31 healthy volunteers performing physically demanding tasks in a laboratory setting. The OmniSuit exoskeleton significantly reduced Deltoid, Trapezius and Erector Spinae muscle activity between 4.1%MVC and 15.7%MVC when lifting a 2.5kg weight above shoulder level (p<0.001), corresponding to a reduction of up to 49.1% compared to without exoskeleton. A position-dependent reduction of Erector Spinae muscle activity was observed (p<0.001), with reductions ranging between 4.6%MVC and 14.0%MVC during leaning and squatting, corresponding to a reduction up to 41.5% compared to without exoskeleton. The measured muscular support and the predicted support torque based on the biomechanical model were found to show a similar profile for those phases of the movement which are most straining to the shoulder and back muscles. Participants reported experiencing good device usability and minimal discomfort (<1/10) in the shoulder and back during task execution with exoskeleton support. These first results validate that the considered biomechanical model helped design an ergonomic and efficient exoskeleton, and confirm the potential of such wearable assistive devices to provide support over multiple joints during physically demanding tasks.
PubMed: 38876001
DOI: 10.1016/j.apergo.2024.104332 -
Medicine Jun 2024Botulinum toxin (BoNT) injection serves as the primary modality for addressing hemifacial spasm (HFS) and blepharospasm (BFS), which are prevalent movement disorders... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Botulinum toxin (BoNT) injection serves as the primary modality for addressing hemifacial spasm (HFS) and blepharospasm (BFS), which are prevalent movement disorders affecting the craniofacial region. However, even though the short-term effectiveness of the botulinum injection may reach over 80%, the long-term effectiveness is still a debatable point Herein, we aim to investigate whether facial self-exercise following the BoNT injection can extend the time period of effectiveness.
METHODS
In this study, 51 volunteers who received Onabotilinumtoxin A (BoNTA) treatment for the diagnosis of HFS or BFS, were randomized into 2 groups. A detailed instruction about the self-exercise was given by an experienced physician to the subjects in Group 1. Volunteers were asked to repeat the exercise program afterward and continue to each movement for 5 seconds, to repeat each movement 10 times with a 10-second break, every day, 3 times a week for 1 week. hemifacial spasm grating scale (HSGS) and Jankovic scales were used to assess the efficacy of the treatment.
RESULTS
Both groups are similar to each other based on demographic features and the severity of the diseases. According to HSGS and Jankovic scales, at the end of the first month, there was no significant difference between the groups. At the end of the third month, the improvement achieved in the first month remained the same in each parameter in Group 1. On the other hand, in Group 2, most of the values returned to the baseline.
CONCLUSION
Facial self-exercise following the botulinum toxin application may extend the period of effectiveness of botulinum toxin treatment the subjects with HFS and BFS.
Topics: Humans; Female; Male; Middle Aged; Hemifacial Spasm; Botulinum Toxins, Type A; Blepharospasm; Neuromuscular Agents; Treatment Outcome; Exercise Therapy; Aged; Adult
PubMed: 38875371
DOI: 10.1097/MD.0000000000038215 -
PloS One 2024To describe changes in balance, walking speed, functional mobility, and eye movements following an activity-oriented physiotherapy (AOPT) or its combination with eye... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of activity-oriented physiotherapy with and without eye movement training on dynamic balance, functional mobility, and eye movements in patients with Parkinson's disease: An assessor-blinded randomised controlled pilot trial.
OBJECTIVES
To describe changes in balance, walking speed, functional mobility, and eye movements following an activity-oriented physiotherapy (AOPT) or its combination with eye movement training (AOPT-E) in patients with Parkinson's disease (PD). To explore the feasibility of a full-scale randomised controlled trial (RCT).
METHODS
Using an assessor-blinded pilot RCT, 25 patients with PD were allocated to either AOPT or AOPT-E. Supervised interventions were performed 30 minutes, 4x/weekly, for 4 weeks, alongside inpatient rehabilitation. Outcomes were assessed at baseline and post-intervention, including dynamic balance, walking speed, functional and dual-task mobility, ability to safely balance, health-related quality of life (HRQoL), depression, and eye movements (number/duration of fixations) using a mobile eye tracker. Freezing of gait (FOG), and falls-related self-efficacy were assessed at baseline, post-intervention, and 4-week follow-up. Effect sizes of 0.10 were considered weak, 0.30 moderate, and ≥0.50 strong. Feasibility was assessed using predefined criteria: recruitment, retention and adherence rates, adverse events, falls, and post-intervention acceptability using qualitative interviews.
RESULTS
Improvements were observed in dynamic balance (effect size r = 0.216-0.427), walking speed (r = 0.165), functional and dual-task mobility (r = 0.306-0.413), ability to safely balance (r = 0.247), HRQoL (r = 0.024-0.650), and depression (r = 0.403). Falls-related self-efficacy (r = 0.621) and FOG (r = 0.248) showed varied improvements, partly sustained at follow-up. Eye movement improvements were observed after AOPT-E only. Feasibility analysis revealed that recruitment was below target, with less than two patients recruited per month due to COVID-19 restrictions. Feasibility targets were met, with a retention rate of 96% (95% confidence interval [CI]: 77.68-99.79) and a 98.18% (95% CI: 96.12-99.20) adherence rate, exceeding the targets of 80% and 75%, respectively. One adverse event unrelated to the study intervention confirmed intervention safety, and interview data indicated high intervention acceptability.
CONCLUSIONS
AOPT-E and AOPT appeared to be effective in patients with PD. Feasibility of a larger RCT was confirmed and is needed to validate results.
Topics: Humans; Parkinson Disease; Male; Female; Aged; Postural Balance; Pilot Projects; Middle Aged; Physical Therapy Modalities; Quality of Life; Eye Movements; Accidental Falls; Treatment Outcome
PubMed: 38875243
DOI: 10.1371/journal.pone.0304788 -
Biology Open Jun 2024The neural crest (NC) is an embryonic multipotent and transitory population of cells that appears during late gastrulation/early neurulation in the developing embryos of...
The neural crest (NC) is an embryonic multipotent and transitory population of cells that appears during late gastrulation/early neurulation in the developing embryos of vertebrate organisms. Often called "the fourth germ layer", the NC is characterised by incredible mobility, which allows the NC cells to migrate throughout the whole embryo, giving rise to an astonishing number of different derivatives in the adult organism, such as craniofacial skeleton, adrenal gland, enteric nervous system and melanocytes. Because of these properties, neurocristopathies (NCPs), which is the term used to classify genetic diseases associated with NC developmental defects, are often syndromic and, taken all together, are the most common type of genetic disease. The NEUcrest consortium is an EU funded innovative training network (ITN) that aims to study the NC and NCPs. In March 2024, the early stage researchers (ESRs) in the NEUcrest consortium organised an in-person conference for well-established and early career researchers to discuss new advances in the NC and NCPs field, starting from the induction of the NC, and then moving on to migration and differentiation processes they undergo. The conference focused heavily on NCPs associated with each of these steps. The conference also included events, such as a round table to discuss the future of the NC research, plus a talk by a person living with an NCP. This 3-day conference aimed to bring together the past, present and future of this field to try and unravel the mysteries of this unique cell population.
Topics: Neural Crest; Humans; Animals; Cell Differentiation; Cell Movement
PubMed: 38874999
DOI: 10.1242/bio.060530 -
Frontiers in Public Health 2024The Syrian conflict has been ongoing since 2011. Practical and scalable solutions are urgently needed to meet an increase in need for specialised psychological support...
BACKGROUND
The Syrian conflict has been ongoing since 2011. Practical and scalable solutions are urgently needed to meet an increase in need for specialised psychological support for post-traumatic stress disorder given limited availability of clinicians. Training forcibly displaced Syrians with a mental health background to remotely deliver specialised interventions increases the availability of evidence based psychological support. Little is known about the effectiveness of online therapy for forcibly displaced Syrian women provided by forcibly displaced Syrian women therapists.
PURPOSE
To pilot an evidence-based trauma therapy, Eye Movement Desensitisation and Reprocessing (EMDR), carried out online by trained forcibly displaced Syrian women therapists for forcibly displaced Syrian women who require treatment for post-traumatic stress disorder (PTSD).
METHODS
83 forcibly displaced Syrian women, living in Türkiye or inside Syria, with diagnosable PTSD, were offered up to 12 sessions of online EMDR over a period of 3 months. This was delivered by forcibly displaced Syrian women therapists who were trained in EMDR. Data were gathered, using Arabic versions, on PTSD symptoms using the Impact of Events Scale Revised, depression symptoms using the Patient Health Questionnaire-9 and anxiety symptoms using the Generalised Anxiety Disorder Assessment-7 at baseline, mid-point, and end of therapy.
RESULTS
PTSD scores, depression scores and anxiety scores all significantly reduced over the course of treatment, with lower scores at midpoint than baseline and lower scores at end of treatment than at midpoint. Only one participant (1%) exceeded the cutoff point for PTSD, and 13 (16%) exceeded the cutoff points for anxiety and depression at the end of treatment.
CONCLUSION
In this pilot study up to 12 sessions of online EMDR were associated with reductions in PTSD, anxiety and depression symptoms in Syrian women affected by the Syrian conflict. The training of forcibly displaced Syrian mental health professionals to deliver online therapy is a relatively low cost, scalable, sustainable solution to ensure that those who are affected by the conflict can access specialised support. Further research is needed using a control group to confirm that the observed effects are due to EMDR treatment, as is research with post-treatment follow-up to ascertain that benefits are maintained.
Topics: Humans; Female; Syria; Stress Disorders, Post-Traumatic; Eye Movement Desensitization Reprocessing; Pilot Projects; Adult; Refugees; Middle Aged; Mental Health; Depression; Surveys and Questionnaires; Anxiety
PubMed: 38873297
DOI: 10.3389/fpubh.2024.1295033