Effects of Sensitive Electrical Stimulation-Based Somatosensory Cueing in Parkinson's Disease Gait and Freezing of Gait Assessment

International audienceThis study aims to investigate the effect of a somatosensory cueing on gait disorders in subjects with Parkinson's disease (PD). After having performed stepping in place and timed up and go assessing tasks, 13 participants with PD were equipped with an electrical stimulator and an inertial measurement unit (IMU) located under the lateral malleolus on the sagittal plane. Electrodes were positioned under the arch of the foot and electrical stimulation (ES) parameters (five 500 ms/phase charge-balanced biphasic pulses delivered at 200 Hz, repeated four times at 10 Hz) adjusted to deliver a sensitive signal. Online IMU signal was processed in order to trigger ES at heel off detection. Starting from a quiet standing posture, subjects were asked to walk at their preferred speed on a path including 5 m straight line, u-turn, and walk around tasks. Three situations were considered: no stimulation baseline precondition (C0), ES condition (C1), and no stimulation baseline post-condition (C0bis), for eliminating a learning effect possibility. In ES condition (C1) the time to execute the different tasks was globally decreased in all the subjects (n 5 13). Participants' results were then grouped regarding whether they experienced freezing of gait (FOG) or not during C0 no stimulation baseline precondition. In " freezer " subjects (n 5 9), the time to complete the entire path was reduced by 19%. FOG episodes occurrence was decreased by 12% compared to baseline conditions. This preliminary work showed a positive global effect on gait and FOG in PD by a somatosensory cueing based on sensitive electrical stimulation

Troïka. Parcours antiques. Volume I

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Troïka. Parcours antiques. Volume II

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Traduire les scholies de Pindare... II : Interprétation, histoire, spectacle

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: De la traduction au commentaire : problèmes de méthode

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Effects of sensitive electrical stimulation based cueing in Parkinson's disease: a preliminary study

This study aims to investigate the effect of a sensitive cueing on Freezing of Gait (FOG) and gait disorders in subjects suffering from Parkinson’s disease (PD). 13 participants with Parkinson’s disease were equipped with an electrical stimulator and a foot mounted inertial measurement unit (IMU). An IMU based algorithm triggered in real time an electrical stimulus applied on the arch of foot at heel off detection. Starting from standing, subjects were asked to walk at their preferred speed on a path comprising 5m straight, u-turn and walk around tasks. Cueing globally decreased the time to achieve the different tasks in all the subjects. In “freezer” subjects, the time to complete the entire path was reduced by 19%. FOG events occurrence was lowered by 12% compared to baseline before and after cueing. This preliminary work showed a positive global effect of an electrical stimulation based cueing on gait and FOG in PD

Differential innervation of superficial versus deep laminae of the dorsal horn by bulbo-spinal serotonergic pathways in the rat

International audienceConvergent data showed that bulbo-spinal serotonergic projections exert complex modulatory influences on nociceptive signaling within the dorsal horn. These neurons are located in the B3 area which comprises the median raphe magnus (RMg) and the lateral paragigantocellular reticular (LPGi) nuclei. Because LPGi 5-HT neurons differ from RMg 5-HT neurons regarding both their respective electro-physiological properties and responses to noxious stimuli, we used anatomical approaches for further characterization of the respective spinal projections of LPGi versus RMg 5-HT neuron subgroups. Adult Sprague-Dawley rats were stereotaxically injected into the RMg or the LPGi with the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). The precise location of injection sites and RMg vs LPGi spinal projections into the different dorsal horn laminae were visualized by PHA-L immunolabeling. Double immunofluorescent labeling of PHA-L and the serotonin transporter (5-HTT) allowed detection of serotonergic fibers among bulbo-spinal projections. Anterograde tracing showed that RMg neurons project preferentially into the deep laminae V-VI whereas LPGi neuron projections are confined to the superficial laminae I-II of the ipsilateral dorsal horn. All along the spinal cord, double-labeled PHA-L/5-HTT immunoreactive fibers, which represent only 5 e15% of all PHA-L-immunoreactive projections, exhibit the same differential locations depending on their origin in the RMg versus the LPGi. The clear-cut distinction between dorsal horn laminae receiving bulbo-spinal serotonergic projections from the RMg versus the LPGi provides further anatomical support to the idea that the descending serotonergic pathways issued from these two bulbar nuclei might exert different modulatory influences on the spinal relay of pain signaling neuronal pathways

PLA2G1B is involved in CD4 anergy and CD4 lymphopenia in HIV-infected patients.

The precise mechanism leading to profound immunodeficiency of HIV-infected patients is still only partially understood. Here, we show that more than 80% of CD4+ T cells from HIV-infected patients have morphological abnormalities. Their membranes exhibited numerous large abnormal membrane microdomains (aMMDs), which trap and inactivate physiological receptors, such as that for IL-7. In patient plasma, we identified phospholipase A2 group IB (PLA2G1B) as the key molecule responsible for the formation of aMMDs. At physiological concentrations, PLA2G1B synergized with the HIV gp41 envelope protein, which appears to be a driver that targets PLA2G1B to the CD4+ T cell surface. The PLA2G1B/gp41 pair induced CD4+ T cell unresponsiveness (anergy). At high concentrations in vitro, PLA2G1B acted alone, independently of gp41, and inhibited the IL-2, IL-4, and IL-7 responses, as well as TCR-mediated activation and proliferation, of CD4+ T cells. PLA2G1B also decreased CD4+ T cell survival in vitro, likely playing a role in CD4 lymphopenia in conjunction with its induced IL-7 receptor defects. The effects on CD4+ T cell anergy could be blocked by a PLA2G1B-specific neutralizing mAb in vitro and in vivo. The PLA2G1B/gp41 pair constitutes what we believe is a new mechanism of immune dysfunction and a compelling target for boosting immune responses in HIV-infected patients.This work was part of the ANRS programs EP20, EP33, and EP36 (J.F. Delfraissy, O. Lambotte). It was initially supported by the Institut Pasteur (PTR 424) and the Pasteur-Weizmann Foundation. We are grateful to P. Pouletty for continuous interest and support. We wish to thank U. Schwarz (Leica Microsystems, Mannheim), E. Perret, P. Roux, A. Salles, and S. Shorte (Imagopole, Institut Pasteur) for their microscopy expertise, as well as A.H. Pillet for her expertise in biochemistry and P. Bochet for data processing and Benoit Colsch (Laboratoire d’Etude du Métabolisme des Médicaments (LEMM), CEA, INRA, Université Paris Saclay, MetaboHUB) for lipidomics analysis by mass spectrometry of CD4+ and CD8+ T cells. We thank Yoann Madec and Fredj Tekaia for their help and expertise in statistics. We acknowledge SOLEIL for the provision of synchrotron radiation facilities and thank the staff of the PROXIMA-1 beamline for their assistance. We benefited greatly from help and numerous discussions with C. Abrial, L. Touqui, B. Colsch, D. Troisvallet, M.L. Gougeon, P. Bruhns, and J. Tiollier. We also gratefully acknowledge J.P. Routy and B. Malissen for their critical review of the manuscript.S

Regulation of the apical extension morphogenesis tunes the mechanosensory response of microvilliated neurons.

Multiple types of microvilliated sensory cells exhibit an apical extension thought to be instrumental in the detection of sensory cues. The investigation of the mechanisms underlying morphogenesis of sensory apparatus is critical to understand the biology of sensation. Most of what we currently know comes from the study of the hair bundle of the inner ear sensory cells, but morphogenesis and function of other sensory microvilliated apical extensions remain poorly understood. We focused on spinal sensory neurons that contact the cerebrospinal fluid (CSF) through the projection of a microvilliated apical process in the central canal, referred to as cerebrospinal fluid-contacting neurons (CSF-cNs). CSF-cNs respond to pH and osmolarity changes as well as mechanical stimuli associated with changes of flow and tail bending. In vivo time-lapse imaging in zebrafish embryos revealed that CSF-cNs are atypical neurons that do not lose their apical attachment and form a ring of actin at the apical junctional complexes (AJCs) that they retain during differentiation. We show that the actin-based protrusions constituting the microvilliated apical extension arise and elongate from this ring of actin, and we identify candidate molecular factors underlying every step of CSF-cN morphogenesis. We demonstrate that Crumbs 1 (Crb1), Myosin 3b (Myo3b), and Espin orchestrate the morphogenesis of CSF-cN apical extension. Using calcium imaging in crb1 and espin mutants, we further show that the size of the apical extension modulates the amplitude of CSF-cN sensory response to bending of the spinal cord. Based on our results, we propose that the apical actin ring could be a common site of initiation of actin-based protrusions in microvilliated sensory cells. Furthermore, our work provides a set of actors underlying actin-based protrusion elongation shared by different sensory cell types and highlights the critical role of the apical extension shape in sensory detection

Xanthine-based gold(I) N-heterocyclic carbene complexes: synthesis and anticancer evaluation

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