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Various accelerometry protocols have been used to quantify upper extremity (UE) activity, encompassing diverse epoch lengths and thresholding methods. However, there is no consensus on the most effective approach. The aim of this study was to delineate the optimal parameters for analyzing accelerometry data to quantify UE use in individuals with unilateral cerebral palsy (CP). METHODS: A group of adults with CP (n = 15) participated in six activities of daily living, while a group of children with CP (n = 14) underwent the Assisting Hand Assessment. Both groups performed the activities while wearing ActiGraph GT9X-BT devices on each wrist, with concurrent video recording. Use ratio (UR) derived from accelerometry and video analysis and accelerometer data were compared for different epoch lengths (1, 1.5, and 2 s) and activity count (AC) thresholds (between 2 and 150). RESULTS: In adults, results are comparable across epoch lengths, with the best AC thresholds being ≥ 100. In children, results are similar across epoch lengths of 1 and 1.5 (optimal AC threshold = 50), while the optimal threshold is higher with an epoch length of 2 (AC = 75). CONCLUSIONS: The combination of epoch length and AC thresholds should be chosen carefully as both influence the validity of the quantification of UE use.
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Paralisia Cerebral , Criança , Adulto , Humanos , Atividades Cotidianas , Extremidade Superior , Acelerometria/métodos , PunhoRESUMO
Adults living with cerebral palsy (CP) report bimanual and unimanual difficulties that interfere with their participation in activities of daily living (ADL). There is a lack of quantitative methods to assess the impact of these motor dysfunctions on the relative use of each arm. The objective of this study was to evaluate the concurrent and discriminative validity of accelerometry-based metrics when used to assess bimanual and unimanual functions. METHODS: A group of control subjects and hemiplegic adults living with CP performed six ADL tasks, during which they were wearing an Actigraph GT9X on each wrist and being filmed. Four bimanual and unimanual metrics were calculated from both accelerometry-based and video-based data; these metrics were then compared to one other with an intraclass correlation coefficient (ICC). Some of these metrics were previously validated in other clinical population, while others were novel. The discriminative validity was assessed through comparisons between groups and between tasks. RESULTS: The concurrent validity was considered as good to excellent (ICC = 0.61-0.97) depending on the experience of the raters. The tasks made it possible to discriminate between groups. CONCLUSION: The proposed accelerometry-based metrics are a promising tool to evaluate bimanual and unimanual functions in adults living with CP.
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Paralisia Cerebral , Acelerometria , Atividades Cotidianas , Adulto , Braço , Benchmarking , Paralisia Cerebral/diagnóstico , Humanos , Extremidade SuperiorRESUMO
BACKGROUND: A popular outcome in rehabilitation studies is the activity intensity count, which is typically measured from commercially available accelerometers. However, the algorithms are not openly available, which impairs long-term follow-ups and restricts the potential to adapt the algorithms for pathological populations. The objectives of this research are to design and validate open-source algorithms for activity intensity quantification and classification. METHODS: Two versions of a quantification algorithm are proposed (fixed [FB] and modifiable bandwidth [MB]) along with two versions of a classification algorithm (discrete [DM] vs. continuous methods [CM]). The results of these algorithms were compared to those of a commercial activity intensity count solution (ActiLife) with datasets from four activities (n = 24 participants). RESULTS: The FB and MB algorithms gave similar results as ActiLife (r > 0.96). The DM algorithm is similar to a ActiLife (r ≥ 0.99). The CM algorithm differs (r ≥ 0.89) but is more precise. CONCLUSION: The combination of the FB algorithm with the DM results is a solution close to that of ActiLife. However, the MB version remains valid while being more adaptable, and the CM is more precise. This paper proposes an open-source alternative for rehabilitation that is compatible with several wearable devices and not dependent on manufacturer commercial decisions.
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Algoritmos , Dispositivos Eletrônicos Vestíveis , Aceleração , HumanosRESUMO
Background: Workplace adaptation is the preferred method of intervention to diminish risk factors associated with the development of work-related shoulder disorders. However, the majority of the workplace assessments performed are subjective (e.g., questionnaires). Quantitative assessments are required to support workplace adaptations. The aims of this study are to assess the concurrent validity of inertial measurement units (IMUs; MVN, Xsens) in comparison to a motion capture system (Vicon) during lifting tasks, and establish the discriminative validity of a wireless electromyography (EMG) system for the evaluation of muscle activity. Methods: Sixteen participants performed 12 simple tasks (shoulder flexion, abduction, scaption) and 16 complex lifting tasks (lifting crates of different weights at different heights). A Delsys Trigno EMG system was used to record anterior and middle deltoids' EMG activity, while the Xsens and Vicon simultaneously recorded shoulder kinematics. Results: For IMUs, correlation coefficients were high (simple task: >0.968; complex task: >0.84) and RMSEs were low (simple task: <6.72°; complex task: <11.5°). For EMG, a significant effect of weight, height and a weight x height interaction (anterior: p < 0.001; middle: p < 0.03) were observed for RMS EMG activity. Conclusions: These results suggest that wireless EMG and IMUs are valid units that can be used to measure physical demand in workplace assessments.
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Técnicas Biossensoriais , Amplitude de Movimento Articular/fisiologia , Articulação do Ombro/fisiologia , Dispositivos Eletrônicos Vestíveis , Adulto , Fenômenos Biomecânicos , Eletromiografia , Feminino , Humanos , Masculino , Músculo Esquelético/fisiologia , Tecnologia sem Fio/tendências , Local de TrabalhoRESUMO
Motion capture systems are recognized as the gold standard for joint angle calculation. However, studies using these systems are restricted to laboratory settings for technical reasons, which may lead to findings that are not representative of real-life context. Recently developed commercial and home-made inertial measurement sensors (M/IMU) are potentially good alternatives to the laboratory-based systems, and recent technology improvements required a synthesis of the current evidence. The aim of this systematic review was to determine the criterion validity and reliability of M/IMU for each body joint and for tasks of different levels of complexity. Five different databases were screened (Pubmed, Cinhal, Embase, Ergonomic abstract, and Compendex). Two evaluators performed independent selection, quality assessment (consensus-based standards for the selection of health measurement instruments [COSMIN] and quality appraisal tools), and data extraction. Forty-two studies were included. Reported validity varied according to task complexity (higher validity for simple tasks) and the joint evaluated (better validity for lower limb joints). More studies on reliability are needed to make stronger conclusions, as the number of studies addressing this psychometric property was limited. M/IMU should be considered as a valid tool to assess whole body range of motion, but further studies are needed to standardize technical procedures to obtain more accurate data.
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Articulações/fisiologia , Dispositivos Eletrônicos Vestíveis , Acelerometria , Bases de Dados Factuais , Humanos , Movimento , Amplitude de Movimento Articular , Reprodutibilidade dos TestesRESUMO
Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by polyglutamine expansions in the amino-terminal region of the huntingtin (Htt) protein. At the cellular level, neuronal death is accompanied by the proteolytic cleavage, misfolding and aggregation of huntingtin. Abnormal hyperphosphorylation of tau protein is a characteristic feature of a class of neurodegenerative diseases called tauopathies. As a number of studies have reported tau pathology in HD patients, we investigated whether HD pathology may promote tau hyperphosphorylation and if so tackle some of its underlying mechanisms. For that purpose, we used the R6/2 mouse, a well-characterized model of HD, and analyzed tau phosphorylation before and after the onset of HD-like symptoms. We found a significant increase in tau hyperphosphorylation at the PHF-1 epitope in pre-symptomatic R6/2 mice, whereas symptomatic mice displayed tau hyperphosphorylation at multiple tau phosphoepitopes (AT8, CP13, PT205 and PHF-1). There was no activation of major tau kinases that could explain this observation. However, when we examined tau phosphatases, we found that calcineurin/PP2B was downregulated by 30% in pre-symptomatic and 50% in symptomatic R6/2 mice, respectively. We observed similar changes in tau phosphorylation and calcineurin expression in Q175 mice, another HD model. Calcineurin was also reduced in Q111 compared with Q7 cells. Finally, pharmacological or genetic inhibition of endogenous calcineurin was sufficient to promote tau hyperphosphorylation in neuronal cells. Taken together, our data suggest that mutant huntingtin can induce abnormal tau hyperphosphorylation in vivo, via the deregulation of calcineurin.
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Encéfalo/citologia , Calcineurina/metabolismo , Doença de Huntington/metabolismo , Neurônios/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Proteínas tau/metabolismo , Animais , Encéfalo/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Doença de Huntington/genética , Camundongos , Camundongos Transgênicos , FosforilaçãoRESUMO
Introduction: Children with cerebral palsy (CP) exhibit a variety of sensory impairments that can interfere with motor performance, but how these impairments persist into adulthood needs further investigation. The objective of this study was to describe the sensory impairments in adults having CP and how they relate to motor impairments. Methods: Nineteen adults having CP performed a set of robotic and clinical assessments. These assessments were targeting different sensory functions and motor functions (bilateral and unilateral tasks). Frequency of each type of impairments was determined by comparing individual results to normative data. Association between the sensory and motor impairments was assessed with Spearman correlation coefficient. Results: Impairment in stereognosis was the most frequent, affecting 57.9% of participants. Although less frequently impaired (26.3%), tactile discrimination was associated with all the motor tasks (unilateral and bilateral, either robotic or clinical). Performance in robotic motor assessments was more frequently associated with sensory impairments than with clinical assessments. Finally, sensory impairments were not more closely associated with bilateral tasks than with unilateral tasks. Discussion: Somatosensory and visuo-perceptual impairments are frequent among adults with CP, with 84.2% showing impairments in at least one sensory function. These sensory impairments show a moderate association with motor impairments.
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PURPOSE: Most activities of daily living (ADLs) require the use of both upper extremities. However, few assessments exist to assess bimanual performance, especially among adults living with cerebral palsy (CP). The aim of this preliminary study is to assess the interrater reliability and convergent validity of the Assisting Hand Assessment (AHA) scoring grid applied to unstandardized ADLs. MATERIALS AND METHODS: For this validation study, nineteen adults living with spastic unilateral CP were videotaped performing seven bimanual ADLs. Three raters assessed the videos independently using the 20-item grid of the AHA. Gwet's AC2 was used to assess interrater reliability. Kendall's Tau-b correlation was used between the observation-based scoring grid and Jebsen-Taylor Hand Function Test (JTHFT) scores to assess convergent validity. RESULTS: Interrater reliability was good (0.84, SD = 0.02). The correlation with the JTHFT was high (τb = -0.74; p < 0.001). CONCLUSION: The results show the potential of using an observation-based scoring grid with unstandardized ADLs to assess bimanual performance in adults living with CP, but further research on psychometric properties is needed. This method allows for an assessment that is occupation-oriented, ecological, and meaningful.
An observation-based scoring grid (Assisting Hand Assessment) can be applied in unstandardized activities of daily living to assess bimanual performance in adults with cerebral palsy.This method allows an occupation-oriented, ecological, and client-meaningful assessment.Although this approach is a pilot measure, it can be used by clinicians and researchers until further psychometric analyses are undertaken.
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People living with cerebral palsy (CP) exhibit motor and sensory impairments that affect unimanual and bimanual functions. The importance of sensory functions for motor control is well known, but the association between motor and sensory functions remains unclear in people living with CP. The objective of this systematic review was to characterize the relationship between sensory deficits and upper limb motor function in individuals living with CP. METHODS: Five databases were screened. The inclusion criteria were: (1) including people living with CP, (2) reporting measurements of upper limb motor and sensory functions. A qualitative analysis of the studies' level of evidence was done. RESULTS: Thirty-three articles were included. Twenty-five articles evaluated tactile functions, 10 proprioceptive functions and 7 visual functions; 31 of the articles reported on unimanual functions and 17 of them reported on bimanual functions. Tactile functions showed a moderate to high association; it was not possible to reach definitive conclusions for proprioceptive and visual functions. CONCLUSIONS: The heterogeneity of the results limits the ability to draw definitive conclusions. Further studies should aim to perform more comprehensive assessments of motor and sensory functions, to determine the relative contribution of various sensory modalities to simple and more complex motor functions.
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Preclinical studies have shown that anesthesia might accelerate the clinical progression of Alzheimer's disease (AD) and can have an impact on tau pathology, a hallmark of AD. Although benzodiazepines have been suggested to increase the risk of incident dementia, their impact on tau pathology in vivo is unknown. We thus examined the impact of midazolam, a benzodiazepine that is often administered perioperatively as an anxiolytic, on tau hyperphosphorylation in nontransgenic and in hTau mice, the latter a model of AD-like tau pathology. The acute administration of midazolam in C57BL/6 mice was associated with downregulation of protein phosphatase-1 and a significant and persistent increase in brain tau phosphorylation. In hTau mice, tau hyperphosphorylation was also observed; however, midazolam was neither associated with proaggregant changes nor spatial reference memory impairment. In C57BL/6 mice, chronic midazolam administration immediately increased hippocampal tau phosphorylation, and this effect was more pronounced in older mice. Interestingly, in young C57BL/6 mice, chronic midazolam administration induced hippocampal tau hyperphosphorylation, which persisted for 1 week. In hTau mice, chronic midazolam administration increased hippocampal tau phosphorylation and, although this was not associated with proaggregant changes, this correlated with a decreased capacity of tau to bind to preassembled microtubules. These findings suggest that midazolam can induce significant tau hyperphosphorylation in vivo, which persists well beyond recovery from its sedative effects. Moreover, it can disrupt one of tau's critical functions. Hence, future studies should focus on the impact of more prolonged or repeated benzodiazepine exposure on tau pathology and cognitive decline.
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Benzodiazepinas/farmacologia , Encéfalo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas tau/metabolismo , Doença de Alzheimer/patologia , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Transtornos da Memória/patologia , Camundongos Endogâmicos C57BL , Memória Espacial/efeitos dos fármacos , Memória Espacial/fisiologia , Proteínas tau/efeitos dos fármacosRESUMO
Parkinson's disease (PD) is characterized by motor deficits, although cognitive disturbances are frequent and have been noted early in the disease. The main pathological characteristics of PD are the loss of dopaminergic neurons and the presence of aggregated α-synuclein in Lewy bodies of surviving cells. Studies have also documented the presence of other proteins within Lewy bodies, particularly tau, a microtubule-associated protein implicated in a wide range of neurodegenerative diseases, including Alzheimer's disease (AD). In AD, tau pathology correlates with cognitive dysfunction, and tau mutations have been reported to lead to dementia associated with parkinsonism. However, the role of tau in PD pathogenesis remains unclear. To address this question, we induced parkinsonism by injecting the toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in hTau mice, a mouse model of tauopathy expressing human tau, and a mouse model knock-out for tau (TKO). We found that although MPTP impaired locomotion (gait analysis) and cognition (Barnes maze), there were no discernable differences between hTau and TKO mice. MPTP also induced a slight but significant increase in tau phosphorylation (Thr205) in the hippocampus of hTau mice, as well as a significant decrease in the soluble and insoluble tau fractions that correlated with the loss of dopaminergic neurons in the brainstem. Overall, our findings suggest that, although MPTP can induce an increase in tau phosphorylation at specific epitopes, tau does not seem to causally contribute to cognitive and locomotor deficits induced by this toxin.
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1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/metabolismo , Tauopatias/metabolismo , Proteínas tau/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Encéfalo/metabolismo , Cognição/fisiologia , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Feminino , Hipocampo/metabolismo , Humanos , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Fosforilação , Tauopatias/fisiopatologia , alfa-Sinucleína/metabolismoRESUMO
There is a large body of evidence showing substantial sensorimotor reorganizations after an amputation. These reorganizations are believed to contribute to the development of phantom limb pain, but alternatively, pain might influence the plasticity triggered by the deafferentation. The aim of this study was to test whether pain impacts on deafferentation-induced plasticity in the somatosensory pathways. Fifteen healthy subjects participated in 2 experimental sessions (Pain, No Pain) in which somatosensory evoked potentials (SSEPs) associated with electrical stimulation of the ulnar nerve were assessed before and after temporary ischemic deafferentation induced by inflation of a cuff around the wrist. In the Pain session capsaicin cream was applied on the dorsum of the hand 30 minutes prior to cuff inflation. Results show that pain decreased the amplitude of the N20 (main effect of condition, p = 0.033), with a similar trend for the P25. Temporary ischemic deafferentation had a significant effect on SSEPs (main effect of time), with an increase in the P25 (p = 0.013) and the P45 amplitude (p = 0.005), together with a reduction of the P90 amplitude (p = 0.002). Finally, a significant time x condition interaction, reflecting state-dependent plasticity, was found for the P90 only, the presence of pain decreasing the reduction of amplitude observed in response to deafferentation. In conclusion, these results show that nociceptive input can influence the plasticity induced by a deafferentation, which could be a contributing factor in the cortical somatosensory reorganization observed in chronic pain populations.
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Causalgia/fisiopatologia , Potenciais Somatossensoriais Evocados , Córtex Somatossensorial/fisiologia , Adulto , Capsaicina/administração & dosagem , Capsaicina/farmacologia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Plasticidade Neuronal , Córtex Somatossensorial/fisiopatologia , Nervo Ulnar/fisiologia , Nervo Ulnar/fisiopatologia , Adulto JovemRESUMO
Alzheimer's disease is characterized by the deposition of intracellular aggregates of hyperphosphorylated tau protein. Tau hyperphosphorylation has been attributed in part to the deregulation of kinases and phosphatases activities. Extracellular signal regulated-kinases 1/2 (ERK1/2) were reported to be activated in the first stages of Alzheimer's disease and were proposed as a potential therapeutic target. However, although the phosphorylation of tau by ERK1/2 has been demonstrated in cell-free system, it remains controversial in vivo. Here, we showed that pharmacologic inhibition of ERK1/2 in mice and SH-SY5Y cells did not reduce basal levels of phospho-tau or hypothermia-induced tau hyperphosphorylation. We also found that activating ERK1/2 by hyperthermia did not correlate with increased tau phosphorylation. Finally, ERK1/2 was inhibited, but tau phosphorylation was not altered in Mek1-/- mice. In conclusion, these results do not support the involvement of ERK1/2 in tau phosphorylation under physiological conditions.
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Doença de Alzheimer/etiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Quinases de Proteína Quinase Ativadas por Mitógeno/fisiologia , Proteínas tau/metabolismo , Doença de Alzheimer/terapia , Animais , Células Cultivadas , Humanos , Hipertermia Induzida , Hipotermia Induzida , Técnicas In Vitro , Camundongos Endogâmicos C57BL , Camundongos Knockout , Terapia de Alvo Molecular , FosforilaçãoRESUMO
There is developing interest in the potential association between anesthesia and the onset and progression of Alzheimer's disease. Several anesthetics have, thus, been demonstrated to induce tau hyperphosphorylation, an effect mostly mediated by anesthesia-induced hypothermia. Here, we tested the hypothesis that acute normothermic administration of dexmedetomidine (Dex), an intravenous sedative used in intensive care units, would result in tau hyperphosphorylation in vivo and in vitro. When administered to nontransgenic mice, Dex-induced tau hyperphosphorylation persisting up to 6 hours in the hippocampus for the AT8 epitope. Pretreatment with atipamezole, a highly specific α2-adrenergic receptor antagonist, blocked Dex-induced tau hyperphosphorylation. Furthermore, Dex dose-dependently increased tau phosphorylation at AT8 in SH-SY5Y cells, impaired mice spatial memory in the Barnes maze and promoted tau hyperphosphorylation and aggregation in transgenic hTau mice. These findings suggest that Dex: (1) increases tau phosphorylation, in vivo and in vitro, in the absence of anesthetic-induced hypothermia and through α2-adrenergic receptor activation, (2) promotes tau aggregation in a mouse model of tauopathy, and (3) impacts spatial reference memory.
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Dexmedetomidina/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Proteínas tau/metabolismo , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Animais , Células Cultivadas , Dexmedetomidina/administração & dosagem , Dexmedetomidina/antagonistas & inibidores , Relação Dose-Resposta a Droga , Hipocampo/metabolismo , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipotermia Induzida , Técnicas In Vitro , Infusões Intravenosas , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Agregação Patológica de Proteínas/induzido quimicamente , Memória Espacial/efeitos dos fármacosRESUMO
Tau hyperphosphorylation is one hallmark of Alzheimer's disease (AD) pathology. Pharmaceutical companies have thus developed kinase inhibitors aiming to reduce tau hyperphosphorylation. One obstacle in screening for tau kinase inhibitors is the low phosphorylation levels of AD-related phospho-epitopes in normal adult mice and cultured cells. We have shown that hypothermia induces tau hyperphosphorylation in vitro and in vivo. Here, we hypothesized that hypothermia could be used to assess tau kinase inhibitors efficacy. Hypothermia applied to models of biological gradual complexity such as neuronal-like cells, ex vivo brain slices and adult non-transgenic mice leads to tau hyperphosphorylation at multiple AD-related phospho-epitopes. We show that Glycogen Synthase Kinase-3 inhibitors LiCl and AR-A014418, as well as roscovitine, a cyclin-dependent kinase 5 inhibitor, decrease hypothermia-induced tau hyperphosphorylation, leading to different tau phosphorylation profiles. Therefore, we propose hypothermia-induced hyperphosphorylation as a reliable, fast, convenient and inexpensive tool to screen for tau kinase inhibitors.