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Biomolecules May 2024The primary nucleation process of α-synuclein (AS) that forms toxic oligomeric species is the early stage of the pathological cause of Parkinson's disease. It is...
The primary nucleation process of α-synuclein (AS) that forms toxic oligomeric species is the early stage of the pathological cause of Parkinson's disease. It is well-known that copper influences this primary nucleation process. While significant efforts have been made to solve the structures of polymorphic AS fibrils, the structures of AS oligomers and the copper-bound AS oligomers at the molecular level and the effect of copper concentrations on the primary nucleation are elusive. Here, we propose and demonstrate new molecular mechanism pathways of primary nucleation of AS that are tuned by distinct copper concentrations and by a specific copper-binding site. We present the polymorphic AS dimers bound to different copper-binding sites at the atomic resolution in high- and low-copper concentrations, using extensive molecular dynamics simulations. Our results show the complexity of the primary nucleation pathways that rely on the copper concentrations and the copper binding site. From a broader perspective, our study proposes a new strategy to control the primary nucleation of other toxic amyloid oligomers in other neurodegenerative diseases.
Topics: alpha-Synuclein; Copper; Binding Sites; Molecular Dynamics Simulation; Humans; Protein Multimerization; Protein Binding; Parkinson Disease
PubMed: 38927031
DOI: 10.3390/biom14060627 -
Journal of Neuroengineering and... Jun 2024People with Parkinson's Disease (PD) show abnormal gait patterns compromising their independence and quality of life. Among all gait alterations due to PD, reduced step...
INTRODUCTION
People with Parkinson's Disease (PD) show abnormal gait patterns compromising their independence and quality of life. Among all gait alterations due to PD, reduced step length, increased cadence, and decreased ground-reaction force during the loading response and push-off phases are the most common. Wearable biofeedback technologies offer the possibility to provide correlated single or multi-modal stimuli associated with specific gait events or gait performance, hence promoting subjects' awareness of their gait disturbances. Moreover, the portability and applicability in clinical and home settings for gait rehabilitation increase the efficiency in the management of PD. The Wearable Vibrotactile Bidirectional Interface (BI) is a biofeedback device designed to extract gait features in real-time and deliver a customized vibrotactile stimulus at the waist of PD subjects synchronously with specific gait phases. The aims of this study were to measure the effect of the BI on gait parameters usually compromised by the typical bradykinetic gait and to assess its usability and safety in clinical practice.
METHODS
In this case series, seven subjects (age: 70.4 ± 8.1 years; H&Y: 2.7 ± 0.3) used the BI and performed a test on a 10-meter walkway (10mWT) and a two-minute walk test (2MWT) as pre-training (Pre-trn) and post-training (Post-trn) assessments. Gait tests were executed in random order with (Bf) and without (No-Bf) the activation of the biofeedback stimulus. All subjects performed three training sessions of 40 min to familiarize themselves with the BI during walking activities. A descriptive analysis of gait parameters (i.e., gait speed, step length, cadence, walking distance, double-support phase) was carried out. The 2-sided Wilcoxon sign-test was used to assess differences between Bf and No-Bf assessments (p < 0.05).
RESULTS
After training subjects improved gait speed (Pre-trn_No-Bf: 0.72(0.59,0.72) m/sec; Post-trn_Bf: 0.95(0.69,0.98) m/sec; p = 0.043) and step length (Pre-trn_No-Bf: 0.87(0.81,0.96) meters; Post-trn_Bf: 1.05(0.96,1.14) meters; p = 0.023) using the biofeedback during the 10mWT. Similarly, subjects' walking distance improved (Pre-trn_No-Bf: 97.5 (80.3,110.8) meters; Post-trn_Bf: 118.5(99.3,129.3) meters; p = 0.028) and the duration of the double-support phase decreased (Pre-trn_No-Bf: 29.7(26.8,31.7) %; Post-trn_Bf: 27.2(24.6,28.7) %; p = 0.018) during the 2MWT. An immediate effect of the BI was detected in cadence (Pre-trn_No-Bf: 108(103.8,116.7) step/min; Pre-trn_Bf: 101.4(96.3,111.4) step/min; p = 0.028) at Pre-trn, and in walking distance at Post-trn (Post-trn_No-Bf: 112.5(97.5,124.5) meters; Post-trn_Bf: 118.5(99.3,129.3) meters; p = 0.043). SUS scores were 77.5 in five subjects and 80.3 in two subjects. In terms of safety, all subjects completed the protocol without any adverse events.
CONCLUSION
The BI seems to be usable and safe for PD users. Temporal gait parameters have been measured during clinical walking tests providing detailed outcomes. A short period of training with the BI suggests improvements in the gait patterns of people with PD. This research serves as preliminary support for future integration of the BI as an instrument for clinical assessment and rehabilitation in people with PD, both in hospital and remote environments.
TRIAL REGISTRATION
The study protocol was registered (DGDMF.VI/P/I.5.i.m.2/2019/1297) and approved by the General Directorate of Medical Devices and Pharmaceutical Service of the Italian Ministry of Health and by the ethics committee of the Lombardy region (Milan, Italy).
Topics: Humans; Parkinson Disease; Aged; Male; Wearable Electronic Devices; Biofeedback, Psychology; Female; Gait Disorders, Neurologic; Middle Aged; Gait
PubMed: 38926876
DOI: 10.1186/s12984-024-01403-z -
BMC Surgery Jun 2024Lumbar degenerative conditions are a major cause of back pain and disability in individuals aged 45 and above. Gait analysis utilizes sensor technology to collect...
BACKGROUND
Lumbar degenerative conditions are a major cause of back pain and disability in individuals aged 45 and above. Gait analysis utilizes sensor technology to collect movement data, aiding in the evaluation of various gait aspects like spatiotemporal parameters, joint angles, neuromuscular activity, and joint forces. It is widely used in conditions such as cerebral palsy and knee osteoarthritis. This research aims to assess the effectiveness of 3D gait analysis in evaluating surgical outcomes and postoperative rehabilitation for lumbar degenerative disorders.
METHODS
A prospective self-controlled before-after study (n = 85) carried out at our Hospital (Sep 2018 - Dec 2021) utilized a 3D motion analysis system to analyze gait in patients with lumbar degenerative diseases. The study focused on the multifidus muscle, a crucial spinal muscle, during a minimally invasive lumbar interbody fusion surgery conducted by Shandong Weigao Pharmaceutical Co., Ltd. Pre- and postoperative assessments included time-distance parameters (gait speed, stride frequency, stride length, stance phase), hip flexion angle, and stride angle. Changes in 3D gait parameters post-surgery and during rehabilitation were examined. Pearson correlation coefficient was employed to assess relationships with the visual analog pain scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopedic Association (JOA) scores. Patient sagittal alignment was evaluated using "Surgimap" software from two types of lateral radiographs to obtain parameters like pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), intervertebral space height (DH), posterior height of the intervertebral space (PDH) at the operative segment, and anterior height of the intervertebral space (ADH).
RESULTS
By the 6th week post-operation, significant improvements were observed in the VAS score, JOA score, and ODI score of the patients compared to preoperative values (P < 0.05), along with notable enhancements in 3D gait quantification parameters (P < 0.05). Pearson correlation analysis revealed a significant positive correlation between improvements in 3D gait quantification parameters and VAS score, JOA score, and ODI value (all P < 0.001).
CONCLUSION
3D gait analysis is a valuable tool for evaluating the efficacy of surgery and rehabilitation training in patients.
Topics: Humans; Male; Gait Analysis; Female; Middle Aged; Prospective Studies; Lumbar Vertebrae; Spinal Fusion; Aged; Treatment Outcome; Imaging, Three-Dimensional; Intervertebral Disc Degeneration; Pain Measurement; Disability Evaluation
PubMed: 38926745
DOI: 10.1186/s12893-024-02486-0 -
Scientific Reports Jun 2024Visual hallucinations in Lewy body disease (LBD) can be differentiated based on phenomenology into minor phenomena (MVH) and complex hallucinations (CVH). MVH include a...
Visual hallucinations in Lewy body disease (LBD) can be differentiated based on phenomenology into minor phenomena (MVH) and complex hallucinations (CVH). MVH include a variety of phenomena, such as illusions, presence and passage hallucinations occurring at early stages of LBD. The neural mechanisms of visual hallucinations are largely unknown. The hodotopic model posits that the hallucination state is due to abnormal activity in specialized visual areas, that occurs in the context of wider network connectivity alterations and that phenomenology of VH, including content and temporal characteristics, may help identify brain regions underpinning these phenomena. Here we investigated both the topological and hodological neural basis of visual hallucinations integrating grey and white matter imaging analyses. We studied LBD patients with VH and age matched healthy controls (HC). VH were assessed using a North-East-Visual-Hallucinations-Interview that captures phenomenological detail. Then we applied voxel-based morphometry and tract based spatial statistics approaches to identify grey and white matter changes. First, we compared LBD patients and HC. We found a reduced grey matter volume and a widespread damage of white tracts in LBD compared to HC. Then we tested the association between CVH and MVH and grey and white matter indices. We found that CVH duration was associated with decreased grey matter volume in the fusiform gyrus suggesting that LBD neurodegeneration-related abnormal activity in this area is responsible for CVH. An unexpected finding was that MVH severity was associated with a greater integrity of white matter tracts, specifically those connecting dorsal, ventral attention networks and visual areas. Our results suggest that networks underlying MVH need to be partly intact and functional for MVH experiences to occur, while CVH occur when cortical areas are damaged. The findings support the hodotopic view and the hypothesis that MVH and CVH relate to different neural mechanisms, with wider implications for the treatment of these symptoms in a clinical context.
Topics: Humans; Hallucinations; Lewy Body Disease; Gray Matter; Female; White Matter; Male; Aged; Magnetic Resonance Imaging; Aged, 80 and over; Case-Control Studies; Middle Aged
PubMed: 38926597
DOI: 10.1038/s41598-024-65536-w -
Pediatric Research Jun 2024Cerebral palsy (CP) is the core neurodevelopmental disorder affecting movement. Several distinct movement disorders can occur in people with cerebral palsy. Dystonia is...
Cerebral palsy (CP) is the core neurodevelopmental disorder affecting movement. Several distinct movement disorders can occur in people with cerebral palsy. Dystonia is a movement disorder that causes non-velocity-dependent hypertonia and/or abnormal, often repetitive, twisting movements, and/or postures. Dystonia occurs more frequently in patients with CP than has been recognized previously, and is treated differently than other aspects of CP. Dystonia is an important cause of chronic pain, hospitalization, and musculoskeletal complications. We describe recent advances in dystonia diagnosis in patients with cerebral palsy and highlight focus areas for ongoing research and clinical care. IMPACT: Dystonia is a movement disorder that is more common in people with cerebral palsy (CP) than previously thought. Dystonia contributes to hospitalization, chronic pain, and complications in CP patients. People with dystonic CP require different tools to diagnose and treat their condition. We summarize current state of the art in dystonia in CP and identify areas of focus for future work.
PubMed: 38926549
DOI: 10.1038/s41390-024-03327-9 -
Journal of Neurology, Neurosurgery, and... Jun 2024While isolated rapid eye movement sleep behaviour disorder (iRBD) is known as a prodrome of α-synucleinopathies, the prediction for its future phenoconversion to...
OBJECTIVE
While isolated rapid eye movement sleep behaviour disorder (iRBD) is known as a prodrome of α-synucleinopathies, the prediction for its future phenoconversion to parkinsonism-first or dementia-first subtype remains a challenge. This study aimed to investigate whether visuospatial dysfunction predicts dementia-first phenoconversion in iRBD.
METHODS
Patients with iRBD and control subjects were enrolled in this prospective cohort study. Baseline neuropsychological assessment included the Unified Parkinson's Disease Rating Scale part III, Montreal Cognitive Assessment (MoCA), Rey-Osterrieth complex figure (ROCF), Colour Trails test (CTT), Farnsworth-Munsell 100-hue test and Digit Span test. The anterior and posterior subscores of MoCA as well as their modified versions were explored. A composite score derived from ROCF and CTT was also explored. Regular follow-up was conducted to determine the phenoconversion status of iRBD patients.
RESULTS
The study included 175 iRBD patients and 98 controls. During a mean follow-up of 5.1 years, 25.7% of patients experienced phenoconversion. Most of the neuropsychological tests could differentiate dementia-first but not parkinsonism-first convertors from non-convertors. The modified posterior subscore of MoCA, by integrating the Alternating Trail Making and Clock Drawing components into original the posterior subscore, which mainly reflects visuospatial function, was the strongest predictor for dementia-first phenoconversion (adjusted HR 5.48, 95% CI 1.67 to 17.98).
CONCLUSION
Visuospatial dysfunction, as reflected mainly by the modified posterior subscore of MoCA, is a predictive factor for dementia-first phenoconversion in iRBD, suggesting its potential for being a biomarker for clinical prognostic prediction and potential neuroprotective trials aiming to delay or prevent dementia.
PubMed: 38925912
DOI: 10.1136/jnnp-2024-333865 -
Journal of Biomedical Informatics Jun 2024Parkinson's Disease (PD), a neurodegenerative disorder, significantly impacts the quality of life for millions of people worldwide. PD primarily impacts dopaminergic...
Parkinson's Disease (PD), a neurodegenerative disorder, significantly impacts the quality of life for millions of people worldwide. PD primarily impacts dopaminergic neurons in the brain's substantia nigra, resulting in dopamine deficiency and gait impairments such as bradykinesia and rigidity. Currently, several well-established tools, such as the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Hoehn and Yahr (H&Y) Scale, are used for evaluating gait dysfunction in PD. While insightful, these methods are subjective, time-consuming, and often ineffective in early-stage diagnosis. Other methods using specialized sensors and equipment to measure movement disorders are cumbersome and expensive, limiting their accessibility. This study introduces a hierarchical approach to evaluating gait dysfunction in PD through videos. The novel 2-Stream Spatial-Temporal Neural Network (2S-STNN) leverages the spatial-temporal features from the skeleton and silhouette streams for PD classification. This approach achieves an accuracy rate of 89% and outperforms other state-of-the-art models. The study also employs saliency values to highlight critical body regions that significantly influence model decisions and are severely affected by the disease. For a more detailed analysis, the study investigates 21 specific gait attributes for a more nuanced quantification of gait disorders. Parameters such as walking pace, step length, and neck forward angle are found to be strongly correlated with PD gait severity categories. This approach offers a comprehensive and convenient solution for PD management in clinical settings, enabling patients to receive a more precise evaluation and monitoring of their gait impairments.
PubMed: 38925280
DOI: 10.1016/j.jbi.2024.104679 -
Sleep Medicine Jun 2024Poor sleep is frequently reported in children with neuromuscular diseases (NMD) and cerebral palsy (CP) however breathing disorders during sleep are often the clinical...
OBJECTIVES
Poor sleep is frequently reported in children with neuromuscular diseases (NMD) and cerebral palsy (CP) however breathing disorders during sleep are often the clinical focus. Periodic limb movements (PLMs) have an increased prevalence in adults with NMD and may contribute to sleep disturbance in this population. We assessed the prevalence of PLMs in children with NMD or CP.
METHODS
Retrospective review of polysomnography (PSG) with leg electromyography in children age 1-18 years with NMD (including Duchenne muscular dystrophy, myotonic dystrophy, spinal muscular atrophy) or CP performed at a paediatric sleep centre 2004-2022.
RESULTS
Leg electromyography was available in at least 1 PSG in 239 children (125 NMD, 114 CP), and in 2 PSGs in 105 children (73 NMD, 32 CP). At initial PSG, 72 (30 %) were female with a median age 9y and respiratory disturbance index 3.5/h (interquartile range 1.3-9.9/h). Elevated PLM index (PLMI; >5/h) occurred in 9.6 % of each of the CP and NMD groups, quantified by initial PSG. Overall, PLMI increased from baseline (median 0, maximum 33/h) to follow-up (median 0, maximum 55.8/h; p < 0.05). In those with an elevated PLMI, arousal percentage attributable to PLMs was up to 25 % (median 7.5 %).
CONCLUSIONS
Elevated PLMI occurred at a higher prevalence in children with NMD and CP than reported in other clinic-referred paediatric populations. It is important that PLMs are not overlooked as identification and treatment may help improve sleep outcomes. Further research is required to understand the pathophysiology and consequences of PLMs specifically in this population.
PubMed: 38924830
DOI: 10.1016/j.sleep.2024.06.017 -
Clinical and Translational Medicine Jul 2024
Topics: Huntington Disease; Humans; Cholesterol; Brain
PubMed: 38924677
DOI: 10.1002/ctm2.1746 -
Journal of Child and Adolescent... Aug 2024Depression, anxiety, and eating disorders are all common during adolescence. This study aims to investigate the potential relationship between eating at night, physical...
OBJECTIVE
Depression, anxiety, and eating disorders are all common during adolescence. This study aims to investigate the potential relationship between eating at night, physical activity, and depression/suicide risk in adolescents.
METHODS
This study followed a cross-sectional descriptive design and involved collecting data from adolescents aged 13-18 years who attend four different high schools. The data collection was done through an online survey using Google Forms. Sociodemographic form, eating at night questionnaire, International Physical Activity Questionnaire (Short Form), Reynolds Adolescent Depression Scale, and Suicide Probability Scale were used for data collection. The data collected were analyzed electronically using descriptive statistics and correlation tests to examine relationships between different parameters.
RESULTS
The study revealed significant associations between academic achievement, daily sleep duration, and daily walking distance with depression and suicide probability (p < 0.05) among the participants. Adolescents who consumed food after 10 pm exhibited higher depression and suicide probability scores than their counterparts (p < 0.05). Additionally, an analysis of physical activity levels demonstrated that highly active adolescents had lower depression and suicide probability scores.
CONCLUSIONS
In conclusion, this study suggests that there is a significant relationship between eating at night, physical activity, and depression/suicide risk in adolescents. Specifically, academic success, daily sleep duration, daily walking distance, and eating habits were found to be associated with depression and suicide probability. Encouraging physical activity and healthy eating habits, particularly avoiding eating late at night, may be beneficial in reducing the risk of depression and suicide among adolescents.
Topics: Humans; Adolescent; Male; Female; Turkey; Cross-Sectional Studies; Depression; Exercise; Suicide; Sedentary Behavior; Adolescent Behavior; Feeding Behavior
PubMed: 38924640
DOI: 10.1111/jcap.12474