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1.
J Neuroeng Rehabil ; 21(1): 90, 2024 05 29.
Artículo en Inglés | MEDLINE | ID: mdl-38812037

RESUMEN

BACKGROUND: Movement smoothness is a potential kinematic biomarker of upper extremity (UE) movement quality and recovery after stroke; however, the measurement properties of available smoothness metrics have been poorly assessed in this group. We aimed to measure the reliability, responsiveness and construct validity of several smoothness metrics. METHODS: This ancillary study of the REM-AVC trial included 31 participants with hemiparesis in the subacute phase of stroke (median time since stroke: 38 days). Assessments performed at inclusion (Day 0, D0) and at the end of a rehabilitation program (Day 30, D30) included the UE Fugl Meyer Assessment (UE-FMA), the Action Research Arm Test (ARAT), and 3D motion analysis of the UE during three reach-to-point movements at a self-selected speed to a target located in front at shoulder height and at 90% of arm length. Four smoothness metrics were computed: a frequency domain smoothness metric, spectral arc length metric (SPARC); and three temporal domain smoothness metrics (TDSM): log dimensionless jerk (LDLJ); number of submovements (nSUB); and normalized average rectified jerk (NARJ). RESULTS: At D30, large clinical and kinematic improvements were observed. Only SPARC and LDLJ had an excellent reliability (intra-class correlation > 0.9) and a low measurement error (coefficient of variation < 10%). SPARC was responsive to changes in movement straightness (rSpearman=0.64) and to a lesser extent to changes in movement duration (rSpearman=0.51) while TDSM were very responsive to changes in movement duration (rSpearman>0.8) and not to changes in movement straightness (non-significant correlations). Most construct validity hypotheses tested were verified except for TDSM with low correlations with clinical metrics at D0 (rSpearman<0.5), ensuing low predictive validity with clinical metrics at D30 (non-significant correlations). CONCLUSIONS: Responsiveness and construct validity of TDSM were hindered by movement duration and/or noise-sensitivity. Based on the present results and concordant literature, we recommend using SPARC rather than TDSM in reaching movements of uncontrolled duration in individuals with spastic paresis after stroke. TRIAL REGISTRATION: NCT01383512, https://clinicaltrials.gov/ , June 27, 2011.


Asunto(s)
Movimiento , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Extremidad Superior , Humanos , Masculino , Femenino , Extremidad Superior/fisiopatología , Persona de Mediana Edad , Movimiento/fisiología , Anciano , Fenómenos Biomecánicos , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/complicaciones , Rehabilitación de Accidente Cerebrovascular/métodos , Reproducibilidad de los Resultados , Paresia/etiología , Paresia/rehabilitación , Paresia/fisiopatología , Adulto , Recuperación de la Función/fisiología
2.
Ann Phys Rehabil Med ; 65(3): 101622, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34929355

RESUMEN

BACKGROUND: Commercial gaming systems are increasingly being used for stroke rehabilitation; however, their effect on upper-limb recovery versus compensation is unknown. OBJECTIVES: We aimed to compare the effect of upper-limb rehabilitation using interactive gaming (Nintendo Wii) with dose-matched conventional therapy on elbow extension (recovery) and forward trunk motion (compensation) in individuals with chronic stroke. Secondary aims were to compare the effect on (1) clinical tests of impairment and activity, pain and effort, and (2) trajectory kinematics. We also explored arm and trunk motion (acceleration) during Wii sessions to understand how participants performed movements during Wii gaming. METHODS: This single-centre, randomized controlled trial compared 12 hourly sessions over 4 weeks of upper-limb Wii therapy to conventional therapy. Outcomes were evaluated at baseline and 4 weeks. The change in elbow extension and trunk motion during a reaching task was evaluated by electromagnetic sensors. Secondary outcomes were change in Fugl-Meyer assessment, Box and Block test, Action Research Arm Test, Motor Activity Log, and Stroke Impact Scale scores. Arm and trunk acceleration during Wii therapy was evaluated by using inertial sensors. A healthy control group was included for reference data. RESULTS: Nineteen participants completed Wii therapy and 21 conventional therapy (mean [SD] time post-stroke 66.4 [57.2] months). The intervention and control groups did not differ in mean change in elbow extension angle (Wii: +4.5°, 95% confidence interval [CI] 0.1; 9.1; conventional therapy: +6.4°, 95%CI 0.6; 12.2) and forward trunk position (Wii: -3.3 cm, 95%CI -6.2;-0.4]; conventional therapy: -4.1 cm, 95%CI -6.6; -1.6) (effect size: elbow, d = 0.16, p = 0.61; trunk, d = 0.13, p = 0.65). Clinical scores improved similarly but to a small extent in both groups. The amount of arm but not trunk acceleration produced during Wii sessions increased with training. CONCLUSIONS: Supervised upper-limb gaming therapy induced similar recovery of elbow extension as conventional therapy and did not enhance the development of compensatory forward trunk movement in individuals with chronic stroke. More sessions may be necessary to induce greater improvements. CLINICALTRIALS: GOV: NCT01806883.


Asunto(s)
Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Juegos de Video , Fenómenos Biomecánicos , Daño Encefálico Crónico , Humanos , Accidente Cerebrovascular/complicaciones , Resultado del Tratamiento , Extremidad Superior
3.
JCI Insight ; 4(20)2019 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-31465303

RESUMEN

Chromatin modifiers act to coordinate gene expression changes critical to neuronal differentiation from neural stem/progenitor cells (NSPCs). Lysine-specific methyltransferase 2D (KMT2D) encodes a histone methyltransferase that promotes transcriptional activation and is frequently mutated in cancers and in the majority (>70%) of patients diagnosed with the congenital, multisystem intellectual disability disorder Kabuki syndrome 1 (KS1). Critical roles for KMT2D are established in various non-neural tissues, but the effects of KMT2D loss in brain cell development have not been described. We conducted parallel studies of proliferation, differentiation, transcription, and chromatin profiling in KMT2D-deficient human and mouse models to define KMT2D-regulated functions in neurodevelopmental contexts, including adult-born hippocampal NSPCs in vivo and in vitro. We report cell-autonomous defects in proliferation, cell cycle, and survival, accompanied by early NSPC maturation in several KMT2D-deficient model systems. Transcriptional suppression in KMT2D-deficient cells indicated strong perturbation of hypoxia-responsive metabolism pathways. Functional experiments confirmed abnormalities of cellular hypoxia responses in KMT2D-deficient neural cells and accelerated NSPC maturation in vivo. Together, our findings support a model in which loss of KMT2D function suppresses expression of oxygen-responsive gene programs important to neural progenitor maintenance, resulting in precocious neuronal differentiation in a mouse model of KS1.


Asunto(s)
Anomalías Múltiples/genética , Encéfalo/crecimiento & desarrollo , Diferenciación Celular/genética , Proteínas de Unión al ADN/deficiencia , Cara/anomalías , Enfermedades Hematológicas/genética , N-Metiltransferasa de Histona-Lisina/deficiencia , Proteína de la Leucemia Mieloide-Linfoide/deficiencia , Proteínas de Neoplasias/deficiencia , Células-Madre Neurales/patología , Neuronas/patología , Enfermedades Vestibulares/genética , Anomalías Múltiples/patología , Animales , Encéfalo/citología , Hipoxia de la Célula/genética , Proliferación Celular/genética , Cromatina/metabolismo , Proteínas de Unión al ADN/genética , Modelos Animales de Enfermedad , Cara/patología , Femenino , Fibroblastos , Enfermedades Hematológicas/patología , N-Metiltransferasa de Histona-Lisina/genética , Humanos , Células Madre Pluripotentes Inducidas , Masculino , Ratones , Mutación , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteínas de Neoplasias/genética , Oxígeno/metabolismo , Cultivo Primario de Células , RNA-Seq , Análisis de la Célula Individual , Piel/citología , Piel/patología , Enfermedades Vestibulares/patología
4.
PLoS Negl Trop Dis ; 13(5): e0007354, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-31067234

RESUMEN

BACKGROUND: Toll-like receptors (TLRs) are sentinel receptors of the innate immune system. TLR4 detects bacterial lipopolysaccharide (LPS) and TLR5 detects bacterial flagellin. A common human nonsense polymorphism, TLR5:c.1174C>T, results in a non-functional TLR5 protein. Individuals carrying this variant have decreased mortality from melioidosis, infection caused by the flagellated Gram-negative bacterium Burkholderia pseudomallei. Although impaired flagellin-dependent signaling in carriers of TLR5:c.1174C>T is well established, this study tested the hypothesis that a functional effect of TLR5:c.1174C>T is flagellin-independent and involves LPS-TLR4 pathways. METHODOLOGY/PRINCIPAL FINDINGS: Whole blood from two independent cohorts of individuals genotyped at TLR5:c.1174C>T was stimulated with wild type or aflagellated B. pseudomallei or purified bacterial motifs followed by plasma cytokine measurements. Blood from individuals carrying the TLR5:c.1174C>T variant produced less IL-6 and IL-10 in response to an aflagellated B. pseudomallei mutant and less IL-8 in response to purified B. pseudomallei LPS than blood from individuals without the variant. TLR5 expression in THP1 cells was silenced using siRNA; these cells were stimulated with LPS before cytokine levels in cell supernatants were quantified by ELISA. In these cells following LPS stimulation, silencing of TLR5 with siRNA reduced both TNF-α and IL-8 levels. These effects were not explained by differences in TLR4 mRNA expression or NF-κB or IRF activation. CONCLUSIONS/SIGNIFICANCE: The effects of the common nonsense TLR5:c.1174C>T polymorphism on the host inflammatory response to B. pseudomallei may not be restricted to flagellin-driven pathways. Moreover, TLR5 may modulate TLR4-dependent cytokine production. While these results may have broader implications for the role of TLR5 in the innate immune response in melioidosis and other conditions, further studies of the mechanisms underlying these observations are required.


Asunto(s)
Burkholderia pseudomallei/inmunología , Flagelina/inmunología , Melioidosis/genética , Melioidosis/inmunología , Polimorfismo Genético , Receptor Toll-Like 5/genética , Adolescente , Adulto , Anciano , Burkholderia pseudomallei/genética , Codón sin Sentido , Estudios de Cohortes , Femenino , Flagelina/genética , Humanos , Inmunidad Innata , Interleucina-10/genética , Interleucina-10/inmunología , Masculino , Melioidosis/microbiología , Persona de Mediana Edad , FN-kappa B/genética , FN-kappa B/inmunología , Mutación Puntual , Receptor Toll-Like 5/inmunología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología , Adulto Joven
5.
Cell Rep ; 22(2): 441-455, 2018 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-29320739

RESUMEN

Single-cell RNA sequencing has generated catalogs of transcriptionally defined neuronal subtypes of the brain. However, the cellular processes that contribute to neuronal subtype specification and transcriptional heterogeneity remain unclear. By comparing the gene expression profiles of single layer 6 corticothalamic neurons in somatosensory cortex, we show that transcriptional subtypes primarily reflect axonal projection pattern, laminar position within the cortex, and neuronal activity state. Pseudotemporal ordering of 1,023 cellular responses to sensory manipulation demonstrates that changes in expression of activity-induced genes both reinforced cell-type identity and contributed to increased transcriptional heterogeneity within each cell type. This is due to cell-type biased choices of transcriptional states following manipulation of neuronal activity. These results reveal that axonal projection pattern, laminar position, and activity state define significant axes of variation that contribute both to the transcriptional identity of individual neurons and to the transcriptional heterogeneity within each neuronal subtype.


Asunto(s)
Axones/metabolismo , Neocórtex/crecimiento & desarrollo , Neuronas/metabolismo , Neocórtex/patología
6.
PLoS One ; 12(11): e0187608, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29125855

RESUMEN

This study aimed to identify and qualify grasp-types used by patients with stroke and determine the clinical parameters that could explain the use of each grasp. Thirty-eight patients with chronic stroke-related hemiparesis and a range of motor and functional capacities (17 females and 21 males, aged 25-78), and 10 healthy subjects were included. Four objects were used (tissue packet, teaspoon, bottle and tennis ball). Participants were instructed to "grasp the object as if you are going to use it". Three trials were video-recorded for each object. A total of 456 grasps were analysed and rated using a custom-designed Functional Grasp Scale. Eight grasp-types were identified from the analysis: healthy subjects used Multi-pulpar, Pluri-digital, Lateral-pinch and Palmar grasps (Standard Grasps). Patients used the same grasps with in addition Digito-palmar, Raking, Ulnar and Interdigital grasps (Alternative Grasps). Only patients with a moderate or relatively good functional ability used Standard grasps. The correlation and regression analyses showed this was conditioned by sufficient finger and elbow extensor strength (Pluri-digital grasp); thumb extensor and wrist flexor strength (Lateral pinch) or in forearm supinator strength (Palmar grasp). By contrast, the patients who had severe impairment used Alternative grasps that did not involve the thumb. These strategies likely compensate specific impairments. Regression and correlation analyses suggested that weakness had a greater influence over grasp strategy than spasticity. This would imply that treatment should focus on improving hand strength and control although reducing spasticity may be useful in some cases.


Asunto(s)
Fuerza de la Mano , Hemiplejía/fisiopatología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad
7.
Motor Control ; 21(2): 168-194, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27111914

RESUMEN

This study explored the coordination between the components of the shoulder girdle (clavicle, scapula and humerus), and how they contribute to hand movement in the peri-personal space. Shoulder girdle motion was recorded in 10 healthy subjects during pointing movements to 9 targets in the peri-personal space, using electromagnetic sensors fixed to the trunk, scapula and upper arm. Most of the 9 degrees of freedom (DoF) of the shoulder girdle were finely scaled to target position. Principle component analysis revealed that the 6 DoF of scapula-thoracic motion were coordinated in three elementary patterns (protraction, shrug and lateral rotation). The ratio of gleno-humeral to scapulo-thoracic global motion was close to 2:1. A direct kinematic procedure showed that if no scapular motion occurred, the workspace would be reduced by 15.8 cm laterally, 13.7 cm vertically and 4.8 cm anteriorly. Scapulo-thoracic motion should be taken into account when investigating the physiology of upper-limb movements.


Asunto(s)
Rango del Movimiento Articular/fisiología , Articulación del Hombro/fisiopatología , Adulto , Femenino , Humanos , Masculino , Movimiento (Física)
8.
Neurorehabil Neural Repair ; 30(3): 209-20, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26089311

RESUMEN

BACKGROUND: The velocity of reaching movements is often reduced in patients with stroke-related hemiparesis; however, they are able to voluntarily increase paretic hand velocity. Previous studies have proposed that faster speed improves movement quality. OBJECTIVE: To investigate the combined effects of reaching distance and speed instruction on trunk and paretic upper-limb coordination. The hypothesis was that increased speed would reduce elbow extension and increase compensatory trunk movement. METHODS: A single session study in which reaching kinematics were recorded in a group of 14 patients with spastic hemiparesis. A 3-dimensional motion analysis system was used to track the trajectories of 5 reflective markers fixed on the finger, wrist, elbow, acromion, and sternum. The reaching movements were performed to 2 targets at 60% and 90% arm length, respectively, at preferred and maximum velocity. The experiment was repeated with the trunk restrained by a strap. RESULTS: All the patients were able to voluntarily increase reaching velocity. In the trunk free, faster speed condition, elbow extension velocity increased but elbow extension amplitude decreased and trunk movement increased. In the trunk restraint condition, elbow extension amplitude did not decrease with faster speed. Seven patients scaled elbow extension and elbow extension velocity as a function of reach distance, the other 7 mainly increased trunk compensation with increased task constraints. There were no clear clinical characteristics that could explain this difference. CONCLUSIONS: Faster speed may encourage some patients to use compensation. Individual indications for therapy could be based on a quantitative analysis of reaching coordination.


Asunto(s)
Brazo/fisiopatología , Destreza Motora/fisiología , Espasticidad Muscular/fisiopatología , Accidente Cerebrovascular/fisiopatología , Torso/fisiopatología , Adulto , Anciano , Fenómenos Biomecánicos , Enfermedad Crónica , Femenino , Humanos , Imagenología Tridimensional , Masculino , Persona de Mediana Edad
9.
Front Hum Neurosci ; 8: 947, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25520638

RESUMEN

Upper-limb impairment after stroke is caused by weakness, loss of individual joint control, spasticity, and abnormal synergies. Upper-limb movement frequently involves abnormal, stereotyped, and fixed synergies, likely related to the increased use of sub-cortical networks following the stroke. The flexible coordination of the shoulder and elbow joints is also disrupted. New methods for motor learning, based on the stimulation of activity-dependent neural plasticity have been developed. These include robots that can adaptively assist active movements and generate many movement repetitions. However, most of these robots only control the movement of the hand in space. The aim of the present text is to analyze the potential of robotic exoskeletons to specifically rehabilitate joint motion and particularly inter-joint coordination. First, a review of studies on upper-limb coordination in stroke patients is presented and the potential for recovery of coordination is examined. Second, issues relating to the mechanical design of exoskeletons and the transmission of constraints between the robotic and human limbs are discussed. The third section considers the development of different methods to control exoskeletons: existing rehabilitation devices and approaches to the control and rehabilitation of joint coordinations are then reviewed, along with preliminary clinical results available. Finally, perspectives and future strategies for the design of control mechanisms for rehabilitation exoskeletons are discussed.

10.
Top Stroke Rehabil ; 21(6): 477-83, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25467395

RESUMEN

BACKGROUND: Timed Up and Go (TUG) performance is reduced following stroke. Gait training improves gait-related activities in hemiparetic patients. However, no study has compared the impact of a single overground training session with a treadmill training session on gait-related activities (assessed by TUG). OBJECTIVE: To compare the immediate effect of a single overground training session versus a single treadmill training session on TUG performance in hemiparetic patients. METHODS: In this randomized controlled clinical trial, 56 hemiparetic patients were randomized to 1 or 2 distinct groups: a single gait training session overground (O group) or on a treadmill (T group). Time taken to perform the TUG (in seconds) was assessed before and immediately after the completion of each session. RESULTS: Time taken to perform the TUG decreased significantly, and to a similar extent, in both groups following the training session (O group, 5.9%; T group, 5.2%). CONCLUSIONS: An overground training session and a treadmill training session were equally effective in improving TUG performance in hemiparetic patients. Hemiparetic patients should be encouraged to walk regularly overground including turns for 20 minutes without stopping. This is an easy and inexpensive self-rehabilitation method to improve functional gait-related activities involved in the TUG test.


Asunto(s)
Terapia por Ejercicio/instrumentación , Terapia por Ejercicio/métodos , Paresia/rehabilitación , Modalidades de Fisioterapia/instrumentación , Rehabilitación de Accidente Cerebrovascular , Adulto , Anciano , Enfermedad Crónica , Femenino , Marcha/fisiología , Humanos , Masculino , Persona de Mediana Edad , Paresia/fisiopatología , Accidente Cerebrovascular/fisiopatología , Resultado del Tratamiento , Caminata/fisiología
11.
J Rehabil Res Dev ; 51(3): 467-79, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25019668

RESUMEN

Information technology plays a very important role in society. People with disabilities are often limited by slow text input speed despite the use of assistive devices. This study aimed to evaluate the effect of a dynamic on-screen keyboard (Custom Virtual Keyboard) and a word-prediction system (Sibylle) on text input speed in participants with functional tetraplegia. Ten participants tested four modes at home (static on-screen keyboard with and without word prediction and dynamic on-screen keyboard with and without word prediction) for 1 mo before choosing one mode and then using it for another month. Initial mean text input speed was around 23 characters per minute with the static keyboard and 12 characters per minute with the dynamic keyboard. The results showed that the dynamic keyboard reduced text input speed by 37% compared with the standard keyboard and that the addition of word prediction had no effect on text input speed. We suggest that current forms of dynamic keyboards and word prediction may not be suitable for increasing text input speed, particularly for subjects who use pointing devices. Future studies should evaluate the optimal ergonomic design of dynamic keyboards and the number and position of words that should be predicted.


Asunto(s)
Equipos de Comunicación para Personas con Discapacidad , Cuadriplejía/rehabilitación , Interfaz Usuario-Computador , Adulto , Vértebras Cervicales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Musculares/complicaciones , Satisfacción del Paciente , Cuadriplejía/complicaciones , Cuadriplejía/etiología , Traumatismos de la Médula Espinal/complicaciones , Factores de Tiempo , Estudios de Tiempo y Movimiento , Adulto Joven
12.
J Electromyogr Kinesiol ; 24(2): 292-9, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24491960

RESUMEN

INTRODUCTION: The aim of this study was to assess the effects of neuromuscular fatigue on stretch reflex-related torque and electromyographic activity of spastic knee extensor muscles in hemiplegic patients. The second aim was to characterize the time course of quadriceps muscle fatigue during repetitive concentric contractions. METHODS: Eighteen patients performed passive, isometric and concentric isokinetic evaluations before and after a fatigue protocol using an isokinetic dynamometer. Voluntary strength and spasticity were evaluated following the simultaneous recording of torque and electromyographic activity of rectus femoris (RF), vastus lateralis (VL) and biceps femoris (BF). RESULTS: Isometric knee extension torque and the root mean square (RMS) value of VL decreased in the fatigued state. During the fatigue protocol, the normalized peak torque decreased whereas the RMS of RF and BF increased between the first five and last five contractions. There was a linear decrease in the neuromuscular efficiency-repetitions relationships for RF and VL. The peak resistive torque and the normalized RMS of RF and VL during passive stretching movements were not modified by the fatigue protocol for any stretch velocity. DISCUSSION: This study showed that localized quadriceps muscle fatigue caused a decrease in voluntary strength which did not modify spasticity intensity. Changes in the distribution of muscle fiber type, with a greater number of slow fibers on the paretic side, may explain why the stretch reflex was not affected by fatigue.


Asunto(s)
Electromiografía/métodos , Hemiplejía/fisiopatología , Fatiga Muscular/fisiología , Espasticidad Muscular/fisiopatología , Músculo Cuádriceps/fisiología , Adulto , Anciano , Femenino , Humanos , Contracción Isométrica/fisiología , Rodilla/fisiología , Articulación de la Rodilla/fisiología , Pierna , Masculino , Persona de Mediana Edad , Movimiento/fisiología , Contracción Muscular/fisiología , Fuerza Muscular , Proyectos Piloto , Reflejo de Estiramiento , Torque
13.
Infect Immun ; 82(4): 1445-52, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24452686

RESUMEN

The type VI secretion system (T6SS) has emerged as a critical virulence factor for the group of closely related Burkholderia spp. that includes Burkholderia pseudomallei, B. mallei, and B. thailandensis. While the genomes of these bacteria, referred to as the Bptm group, appear to encode several T6SSs, we and others have shown that one of these, type VI secretion system 5 (T6SS-5), is required for virulence in mammalian infection models. Despite its pivotal role in the pathogenesis of the Bptm group, the effector repertoire of T6SS-5 has remained elusive. Here we used quantitative mass spectrometry to compare the secretome of wild-type B. thailandensis to that of a mutant harboring a nonfunctional T6SS-5. This analysis identified VgrG-5 as a novel secreted protein whose export depends on T6SS-5 function. Bioinformatics analysis revealed that VgrG-5 is a specialized VgrG protein that harbors a C-terminal domain (CTD) conserved among Bptm group species. We found that a vgrG-5 ΔCTD mutant is avirulent in mice and is unable to stimulate the fusion of host cells, a hallmark of the Bptm group previously shown to require T6SS-5 function. The singularity of VgrG-5 as a detected T6SS-5 substrate, taken together with the essentiality of its CTD for virulence, suggests that the protein is critical for the effector activity of T6SS-5. Intriguingly, we show that unlike the bacterial-cell-targeting T6SSs characterized so far, T6SS-5 localizes to the bacterial cell pole. We propose a model whereby the CTD of VgrG-5-, propelled by T6SS-5-, plays a key role in inducing membrane fusion, either by the recruitment of other factors or by direct participation.


Asunto(s)
Sistemas de Secreción Bacterianos/fisiología , Burkholderia/patogenicidad , Células Gigantes/fisiología , Animales , Western Blotting , Burkholderia/metabolismo , Células Cultivadas , Células Gigantes/metabolismo , Interacciones Huésped-Parásitos/fisiología , Macrófagos/metabolismo , Espectrometría de Masas , Fusión de Membrana/fisiología , Ratones , Microscopía Fluorescente , Virulencia/genética , Virulencia/fisiología , Factores de Virulencia/metabolismo
14.
J Immunol ; 192(1): 300-7, 2014 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-24298015

RESUMEN

Nucleotide-binding oligomerization domain 2 (NOD2) is a cytosolic pathogen recognition receptor that regulates susceptibility to a variety of infections and chronic diseases. Burkholderia pseudomallei, a facultative intracellular bacterium, causes the tropical infection melioidosis. We hypothesized that NOD2 may participate in host defense in melioidosis. We performed a series of in vitro assays and in vivo experiments and analyzed the association of human genetic variation with infection to delineate the contribution of NOD2 to the host response to B. pseudomallei. We found that transfection with NOD2 mediated NF-κB activation induced by B. pseudomallei stimulation of HEK293 cells. After low-dose inoculation with aerosolized B. pseudomallei, Nod2-deficient mice showed impaired clinical responses and permitted greater bacterial replication in the lung and dissemination to the spleen compared with wild-type mice. IL-6 and KC levels were higher in the lungs of Nod2-deficient mice. In a cohort of 1562 Thai subjects, a common genetic polymorphism in the NOD2 region, rs7194886, was associated with melioidosis, and this effect was most pronounced in women. rs7194886 was not associated with differences in cytokine production induced by whole-blood stimulation with the NOD2 ligand, muramyl dipeptide, or B. pseudomallei. To our knowledge, these findings are the first to characterize the role of NOD2 in host defense in mammalian melioidosis.


Asunto(s)
Burkholderia pseudomallei/inmunología , Melioidosis/genética , Melioidosis/inmunología , Proteína Adaptadora de Señalización NOD2/genética , Animales , Línea Celular Tumoral , Citocinas/sangre , Citocinas/metabolismo , Modelos Animales de Enfermedad , Células HEK293 , Humanos , Inmunidad Innata/genética , Interleucina-6/sangre , Interleucina-6/metabolismo , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/microbiología , Melioidosis/metabolismo , Melioidosis/mortalidad , Ratones , Ratones Noqueados , Proteína Adaptadora de Señalización NOD2/deficiencia , Proteína Adaptadora de Señalización NOD2/metabolismo , Polimorfismo de Nucleótido Simple
15.
Gait Posture ; 39(1): 235-40, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23948331

RESUMEN

Gait patterns in adults with cerebral palsy have, to our knowledge, never been assessed. This contrasts with the large number of studies which have attempted to categorize gait patterns in children with cerebral palsy. Several methodological approaches have been developed to objectively classify gait patterns in patients with central nervous system lesions. These methods enable the identification of groups of patients with common underlying clinical problems. One method is cluster analysis, a multivariate statistical method which is used to classify an entire data set into homogeneous groups or "clusters". The aim of this study was to determine, using cluster analysis, the principal gait patterns which can be found in adults with cerebral palsy. Data from 3D motion analyses of 44 adults with cerebral palsy were included. A hierarchical cluster analysis was used to subgroup the different gait patterns based on spatiotemporal and kinematic parameters in the sagittal and frontal planes. Five clusters were identified (C1-C5) among which, 3 subgroups were determined, based on spontaneous gait speed (C1/C2: slow, C3/C4: moderate and C5: almost normal). The different clusters were related to specific kinematic parameters that can be assessed in routine clinical practice. These 5 classifications can be used to follow changes in gait patterns throughout growth and aging as well to assess the effects of different treatments (physiotherapy, surgery, botulinum toxin, etc.) on gait patterns in adults with cerebral palsy.


Asunto(s)
Parálisis Cerebral/fisiopatología , Trastornos Neurológicos de la Marcha/clasificación , Marcha/fisiología , Adolescente , Adulto , Fenómenos Biomecánicos , Parálisis Cerebral/complicaciones , Parálisis Cerebral/rehabilitación , Análisis por Conglomerados , Femenino , Estudios de Seguimiento , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/fisiopatología , Humanos , Masculino , Modalidades de Fisioterapia , Estudios Retrospectivos , Adulto Joven
16.
J Rehabil Med ; 46(2): 132-8, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24162795

RESUMEN

OBJECTIVE: To evaluate the effects of a 20-min gait training session using the Lokomat® combined with a negative kinematic constraint on the non-paretic limb and a positive kinematic constraint on the paretic limb, on peak knee flexion and other biomechanical parameters in chronic hemiparetic subjects. DESIGN: Preliminary study, before-after design. SUBJECTS: Fifteen hemiparetic subjects. METHODS: Subjects were evaluated using 3-dimensional gait analysis before, immediately after the end of the training, and after a 20-min rest period. The positive constraint increased the range of motion of the paretic limb (hip and knee), while the negative constraint reduced the range of motion of the non-paretic limb (hip and knee). RESULTS: Peak knee flexion and other, kinematic, kinetic and spatiotemporal, parameters were significantly improved following the training session. These positive effects occurred predominantly in the paretic limb. Moreover, there was no worsening of biomechanical parameters of the non-paretic limb despite the use of negative constraint on this limb. These effects persisted for at least 20 min following the end of the gait training session. CONCLUSION: This type of training may be effective to improve gait in hemiparetic patients. A larger investigation of the training programme is justified.


Asunto(s)
Trastornos Neurológicos de la Marcha/rehabilitación , Paresia/rehabilitación , Robótica , Rehabilitación de Accidente Cerebrovascular , Adulto , Anciano , Fenómenos Biomecánicos , Femenino , Marcha , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/fisiopatología , Articulación de la Cadera , Humanos , Articulación de la Rodilla , Masculino , Persona de Mediana Edad , Paresia/etiología , Paresia/fisiopatología , Rango del Movimiento Articular , Accidente Cerebrovascular/complicaciones , Resultado del Tratamiento
17.
Man Ther ; 18(6): 473-80, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23726286

RESUMEN

Electromagnetic devices allow the non invasive and accurate measurement of 3D scapula kinematics. The acromial method allows continuous dynamic measurement using a skin surface sensor fixed to the acromion. Inter-session intra and inter-observer repeatability of 3D scapular kinematics have only been partially assessed for analytical movements and never for functional tasks. Inter-session intra and inter-observer repeatability of 3D scapular kinematics were assessed for arm elevation in the sagittal and frontal planes and for two activities of daily living (ADL), hair combing and back washing, in both shoulders of 15 healthy subjects, using the intraclass correlation coefficient (ICC), the standard error of measurement (SEM), the small real difference (SRD) and the Bland and Altman's graphical method. Intra-observer repeatability was good to excellent for every scapular rotation for both arm elevation in isolated planes and ADL (ICC ranged from 0.64 to 0.95). Inter-observer repeatability of scapular rotations was fair to excellent for arm elevation in isolated planes (ICC ranged from 0.49 to 0.92) and poor to excellent for ADL (ICC ranged from 0.35 to 0.89). Inter-observer repeatability of scapular protraction/retraction had the lowest ICC. For both inter-session intra and inter-observer reliability, the SEM and SRD remained low and Bland and Altman's graphical method showed a good repeatability of the measurement method. Longitudinal monitoring of a subject's scapular kinematics by a trained observer is reliable. The inter-observer repeatability of scapular protraction/retraction must be improved.


Asunto(s)
Actividades Cotidianas , Brazo/fisiología , Fenómenos Biomecánicos , Movimiento/fisiología , Escápula/fisiología , Adulto , Fenómenos Electromagnéticos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados
18.
IEEE Trans Neural Syst Rehabil Eng ; 20(3): 247-57, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22481836

RESUMEN

The aim of this paper was to explore how an upper limb exoskeleton can be programmed to impose specific joint coordination patterns during rehabilitation. Based on rationale which emphasizes the importance of the quality of movement coordination in the motor relearning process, a robot controller was developed with the aim of reproducing the individual corrections imposed by a physical therapist on a hemiparetic patient during pointing movements. The approach exploits a description of the joint synergies using principal component analysis (PCA) on joint velocities. This mathematical tool is used both to characterize the patient's movements, with or without the assistance of a physical therapist, and to program the exoskeleton during active-assisted exercises. An original feature of this controller is that the hand trajectory is not imposed on the patient: only the coordination law is modified. Experiments with hemiparetic patients using this new active-assisted mode were conducted. Obtained results demonstrate that the desired inter-joint coordination was successfully enforced, without significantly modifying the trajectory of the end point.


Asunto(s)
Paresia/rehabilitación , Robótica/métodos , Extremidad Superior/fisiología , Adulto , Anciano , Algoritmos , Fenómenos Biomecánicos , Daño Encefálico Crónico/rehabilitación , Isquemia Encefálica/complicaciones , Isquemia Encefálica/rehabilitación , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/rehabilitación , Interpretación Estadística de Datos , Femenino , Mano/fisiología , Humanos , Articulaciones/fisiología , Aprendizaje/fisiología , Masculino , Persona de Mediana Edad , Destreza Motora/fisiología , Plasticidad Neuronal/fisiología , Paresia/etiología , Análisis de Componente Principal , Desempeño Psicomotor/fisiología , Accidente Cerebrovascular/etiología , Rehabilitación de Accidente Cerebrovascular , Torque
19.
Brain Res ; 1452: 96-107, 2012 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-22464180

RESUMEN

Adequate grip force modulation is critical to manual dexterity and often impaired in hemiparetic stroke patients. Previous studies in hemiparetic patients suggest that aspects of grip force control may be differently affected by the lesion. We developed a visuomotor power grip force-tracking task allowing quantification of tracking error, force variability and release duration. We investigated force control in 24 chronic stroke patients with varying severity of hemiparesis and in healthy control subjects. Force tracking was performed at 10, 20, and 30% maximal voluntary contraction (MVC). Control subjects were also tested at absolute force levels similar to those of the patients. Patients tracking with their paretic hand at similar relative (%MVC) grip force levels showed increased error, force variability and release duration, but surprisingly, there was no difference in tracking error or variability between patients and control subjects performing at similar absolute force levels. Furthermore, patients improved their tracking performance across repeated blocks similar to control subjects. Release duration, however, was increased (also in the non-paretic hand), was force-independent and did not correlate with MVC strength. Of the three performance measures, only release duration explained some of the variance in arm and hand function (Frenchay Arm Test score), independent of MVC strength. The findings show (i) that hemiparetic stroke patients preserve the ability to modulate (generate and maintain) power grip force within their limited force range and (ii) that MVC grip strength and duration of grip release are differently affected and are two complementary predictors of arm function after stroke.


Asunto(s)
Fuerza de la Mano/fisiología , Paresia/fisiopatología , Accidente Cerebrovascular/fisiopatología , Adulto , Anciano , Brazo/fisiopatología , Femenino , Mano/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Paresia/etiología , Accidente Cerebrovascular/complicaciones
20.
Exp Brain Res ; 218(1): 141-55, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22331168

RESUMEN

Following stroke, control of both the contralesional (paretic) and ipsilesional (less affected) arms is altered. The purpose of this study was to analyse the consequences of stroke on joint rotations of both shoulder girdles, that is, glenohumeral (GH) and scapula motion. Because of hemispheric specialization, we hypothesized that changes would relate to the side of hemisphere damage. Nine stroke patients with left, and 9 with right hemisphere damage (LHD and RHD) and 9 healthy subjects were included. Reaching movements to targets positioned close, far and high in three directions were recorded using an electromagnetic system. Initial and final postures of the scapula, GH and elbow joint were evaluated. Inter-joint rotations throughout the movements were analysed using principal component analysis (PCA). The main finding was that initial and final postures of the contralesional and ipsilesional shoulders differed depending on the side of brain lesion. On the contralesional side, there was less scapula protraction and GH lateral rotation for both groups. Scapula tilt was less anterior in LHD patients, and GH elevation was greater in RHD patients. On the ipsilesional side, GH lateral rotation was reduced in both groups, and scapula protraction was reduced only for LHD patients. PCA confirmed that postures of both shoulders of the LHD group were substantially different to the healthy subjects, while only the contralesional arm of the RHD subjects differed. These results add to existing knowledge of hemispheric specialization, suggesting that the left hemisphere plays a greater role in bilateral joint postures than the right hemisphere.


Asunto(s)
Infarto Encefálico/fisiopatología , Lateralidad Funcional/fisiología , Paresia/fisiopatología , Escápula/fisiología , Accidente Cerebrovascular/fisiopatología , Adulto , Anciano , Brazo/inervación , Brazo/fisiopatología , Daño Encefálico Crónico/fisiopatología , Dominancia Cerebral/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paresia/diagnóstico , Postura/fisiología , Desempeño Psicomotor/fisiología , Escápula/inervación
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