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It has recently been shown that a lack of vestibular sensory information decreases spatial memory performance and induces biochemical changes in the hippocampus in rodents. After vestibular neurectomy, patients display spatial memory deficit and hippocampal atrophy. Our objectives were to explore: (a) spatial (Y maze, radial-arm maze), and non-spatial (object recognition) memory performance, (b) modulation of NMDA receptors within the hippocampus using radioligand binding, and (c) hippocampal atrophy, using MRI, in a rat model of bilateral labyrinthectomy realized in two operations. Chemical vestibular lesions (VLs) were induced in 24 animals by transtympanic injections of sodium arsanilate (30 mg/0.1 ml/ear), one side being lesioned 3 weeks after the other. The control group received transtympanic saline solution (0.1 ml/ear) ( n = 24). Spatial memory performance (Y maze and radial maze) decreased after VL. Conversely, non-spatial memory performance (object recognition) was not affected by VL. No hippocampal atrophy was observed with MRI, but density of NMDA receptors were increased in the hippocampus after VL. These findings show that the lack of vestibular information induced specific deficits in spatial memory. Additionally, quantitative autoradiographic data suggest the involvement of the glutamatergic system in spatial memory processes related to vestibular information. When studying spatial memory performances in the presence of vestibular syndrome, two-step labyrinthectomy is a suitable procedure for distinguishing between the roles of the specific components of vestibular input loss and those of impaired locomotor activity. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Destruction of the inner ear in rats for medical research has been performed since 1936. Nevertheless, descriptions of the technique used and clinical analysis are poor and often involve coagulation of the stapedial artery. We suggest a description of a surgical ventrolateral approach to labyrinthectomy in rats, with preservation of the stapedial artery. Methods: Twenty-five Wistar rats were operated on via a right ventrolateral approach to the bulla, followed by labyrinthectomy with preservation of the stapedial artery. Clinical observation and tests were carried out from the time of the surgery until day one. Twenty-four hours after the surgery on the right side, the same surgery was performed on the left side, followed by clinical observation. Twenty-five other rats were used as controls, with sham surgery. Histologic analysis of the vestibular nerve with silver staining was performed in six rats 3 or 7 days after the labyrinthectomy. Results: The ventrolateral approach made it possible to reach the middle- and inner-ear with preservation of nervous and vascular elements such as the facial nerve and stapedial artery. Unilateral labyrinthectomy induced ocular skew deviation, head torsion and limb asymmetry. Dynamic signs were first rolling, then rotation, which increased considerably during tail suspension. Bilateral labyrinthectomy produces instability with major body oscillation. Animals show head and neck dorsiflexion with limb extension, sometimes followed by fast backward walking. Conclusion: The ventrolateral approach is an efficient technique for surgical labyrinthectomy with stapedial artery preservation. Clinical analysis shows a wide range of signs to evaluate the functional destruction of the vestibular organ. [ABSTRACT FROM AUTHOR]

Abstract: Neural control circuits that coordinate the motor activity of the diaphragm (DIA) and the geniohyoid muscle (GH) are potentially involved in pathological conditions such as various forms of sleep apnea. Here we investigated a differential role of the raphe magnus (RMg), pallidus (RPa) and the obscurus (ROb) nuclei in the neural control of DIA and GH muscle activity in rats under volatile anesthesia. In order to characterize a topographical organization of the raphe nuclei we analyzed changes in DIA and GH during high-frequency stimulation (HFS, 10–130Hz, 60μs pulse width, 40–160μA, 30s). HFS of the RMg and the ROb induced apnea, in the latter case apnea was associated with massive tonic discharge in the GH. By contrast, HFS of the RPa induced tachypnea. At caudal stimulation sites the tachypnea was accompanied by tonic DIA activity and cessation of GH. These data suggest a differential distribution of inhibitory and excitatory drives of DIA and GH muscles within distinct raphe nuclei. [Copyright &y& Elsevier]

The present paper exposes algorithmic results providing a vision about sleep functions which complements biological theory and experiments. Derived from the algorithmic theory of information, the theory of adaptation aims at quantifying how an inherited or acquired piece of knowledge helps individuals to survive. It gives a scale of complexity for survival problems and proves that some of them can only be solved by a dynamical management of memory associating continuous learning and forgetting methods. In this paper we explain how a virtual robot “Picota” has been designed to simulate the behavior of a living hen. In order to survive in its synthetical environnement, our robot must recognize good seeds from bad ones, and should take rest during night periods. Within this frame, and facing the rapid evolution of to-be-recognized forms, the best way to equilibrate the energetic needs of the robot and ensure survival is to use the nightly rest to reorganize the pieces of data acquired during the daily learning, and to trash the less useful ones. Thanks to this time sharing, the same circuits can be used for both daily learning and nightly forgetting and thus costs are lower ; however, this also forces the system to “paralyse” the virtual robot, and therefore the night algorithm is reminiscent of paradoxical (REM) sleep. The algorithm of the robot takes advantage of the alternation between wakefulness or activity and the rest period. This diagram quite accurately recalls the REM period. In the future, the convergence between the neurophysiology of sleep and the theory of complexity may give us a new line of research in order to elucidate sleep functions. [Copyright &y& Elsevier]

Presents a method for the autonomous calibration of six degrees-of-freedom parallel robots. The calibration makes use of the motorized prismatic joint positions corresponding to some sets of configurations where in each set either a passive universal joint or a passive spherical joint is fixed using a lock mechanism. Simulations give us an idea about the number of sets that must be used, the number of configurations by set and the effect of noise on the calibration accuracy. The main advantage of this method is that it can be executed rapidly without need to external sensors to measure the position or the orientation of the mobile platform. [ABSTRACT FROM PUBLISHER]

Background Serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE) are used for diagnosis and follow-up of patients with intact immunoglobulin multiple myeloma. However, the numerous limitations of these methods led to the development of a nephelometric immunoassay (Hevylite™) for the specific measurement of serum IgGκ, IgGλ, IgAκ and IgAλ concentrations. Methods In this study, we evaluated the correlation between this assay and SPE and IFE in 114 sera of 15 patients (12 IgG and 3 IgA patients) and its impact on the clinical care of patients, especially for diagnosis, for the evaluation of residual disease and for early detection of relapse. Results At inclusion and during follow-up, we found a good correlation between monoclonal immunoglobulin concentrations and SPE (R 2 = 0.902 for IgA and R 2 = 0.915 for IgG) and nephelometric quantification (R 2 = 0.948 for IgA and R 2 = 0.920 for IgG) for the evaluation of monoclonal and polyclonal immunoglobulins. Our results illustrate that the Hevylite™ test is less sensitive than the IFE for detection of residual disease: 5 patients who obtained very good partial response or complete response had normalization of the Hevylite™ ratio while IFE was still positive. A relapse had been detectable with the Hevylite™ ratio 1 to 2 months earlier than with SPE and IFE in 3 patients out of 15, but no recommendations for treating patients with only slight biological relapse are available. Conclusion Our results demonstrate that heavy/light chain specific immunoglobulin ratios provides no additional information than serum proteins electrophoresis and immunofixation for the diagnosis and the follow-up of intact immunoglobulin multiple myeloma patients. We also studied the correlation between the concentration of total immunoglobulin measured by Hevylite™ (sum of Ig’κ + Ig’λ) and nephelometric measurement of total IgG or IgA. For this correlation analysis, all 114 sera were analyzed. The correlation coefficient was R 2 = 0.948 for IgA and R 2 = 0.920 for IgG. [ABSTRACT FROM AUTHOR]

Background Flow cytometry allows single-cell analysis of peripheral biological samples and is useful in many fields of research and clinical applications, mainly in hematology, immunology, and oncology. In the neurosciences, the flow cytometry separation method was first applied to stem cell extraction from healthy or cerebral tumour tissue and was more recently tested in order to phenotype brain cells, hippocampal neurogenesis, and to detect prion proteins. However, it remains sparsely applied in quantifying membrane receptors in relation to synaptic plasticity. New method We aimed to optimize a flow cytometric procedure for receptor quantification in neurons and non-neurons. A neural dissociation process, myelin separation, fixation, and membrane permeability procedures were optimized to maximize cell survival and analysis in hippocampal tissue obtained from adult rodents. We then aimed to quantify membrane muscarinic acetylcholine receptors (mAChRs) in rats with and without bilateral vestibular loss (BVL). Results mAChR’s were quantified for neuronal and non-neuronal cells in the hippocampus and striatum following BVL. At day 30 but not at day 7 following BVL, there was a significant increase (P ≤ 0.05) in the percentage of neurons expressing M 2/4 mAChRs in both the hippocampus and the striatum. Conclusion Here, we showed that flow cytometry appears to be a reliable method of membrane receptor quantification in ex-vivo brain tissue. [ABSTRACT FROM AUTHOR]

Résumé Introduction Les myopathies nécrosantes auto-immunes à anticorps anti-3-hydroxy-3-méthylglutaryl-coenzyme A réductase sont de découverte récente (2011). Elles sont à différencier des myopathies nécrosantes toxiques liées à la prise de statines. L’objectif de notre étude est d’illustrer les caractéristiques cliniques et paracliniques de ces myopathies et de montrer les difficultés de prise en charge thérapeutique. Observations Nous décrivons les observations de 4 patients suivis en Bretagne. Les dossiers ont été analysés rétrospectivement. L’âge moyen de nos patients était de 59,5 ans et le sex-ratio était de 1. Leur présentation clinique était homogène avec une faiblesse proximale douloureuse symétrique d’installation subaiguë sans atteinte extra-musculaire. D’autres présentations sont possibles (notamment pseudo-dystrophiques). Une prise de statines antérieure était retrouvée chez tous nos patients (durée moyenne d’utilisation de 3,75 ans) mais n’est pas obligatoire. Les créatines kinases étaient très élevées et l’électromyogramme était anormal pour tous. La biopsie musculaire retrouvait une myopathie nécrosante sans infiltrat inflammatoire significatif. Le bilan cardio-respiratoire et le bilan à la recherche d’une néoplasie étaient négatifs. La prise en charge thérapeutique montrait une corticodépendance marquée non améliorée par les traitements immunosuppresseurs (azathioprine ou méthotrexate). Le bénéfice des immunoglobulines intraveineuses était net avec des réponses parfois prolongées. Conclusion Un diagnostic précoce de ces myopathies est nécessaire afin d’instaurer un traitement immunosuppresseur ainsi qu’un suivi rapproché. La stratégie thérapeutique (au sein de laquelle la place immunoglobulines semble croissante) doit être précisée par des études prospectives avec de longues périodes de suivi. Introduction Anti-3-hydroxy-3-méthylglutaryl-coenzyme A reductase antibody-associated necrotizing autoimmune myopathy has been recently described (2011). This myopathy is distinct from statin toxic myopathy. Our objective is to report on the clinical and para-clinical characteristics of this myopathy and to show the difficulties of therapeutic care. Case reports We describe 4 cases of patients followed-up in Brittany, France. All data have been analyzed retrospectively. The mean age of our patients was 59.5 years, with a sex ratio of 1. The clinical presentation was homogeneous, with a subacute painful proximal and symmetrical weakness, without extra-muscular involvement. Other presentations have been described (including pseudo-dystrophic presentation). All patients had a previous statin medication (mean duration of 3.75 years) although this criteria is not a requisite. All patients had high levels of creatine kinase and abnormal electromyographic examination. The pathological pattern on muscular biopsy was a necrotizing myopathy without significant inflammatory cells infiltration. Cardio-respiratory function was normal and no associated neoplasia was found. Over the follow-up, we observed a marked corticosteroid-dependence, not improved by immunosuppressive drugs (azathioprine and methotrexate). The benefit of intravenous immunoglobulin was clear with, sometimes, prolonged responses. Conclusion An early diagnosis of this myopathy is necessary in order to introduce an immunotherapy associated with a close monitoring. The therapeutic strategy (within which the stead of intravenous immunoglobulin seems increased) remains to be defined and long-term prospective studies are thus needed. [ABSTRACT FROM AUTHOR]

Introduction: Mastocytosis is a clonal haematological disease characterized by uncontrolled proliferation and the activation of mast cells. The value of FDG-PET/CT (FDG-PET) in mastocytosis has yet to be determined. Methods: We retrospectively identified patients with an established diagnosis of systemic mastocytosis (SM), according to the WHO criteria, who underwent PET using the French Reference Centre for Mastocytosis database. Semi-quantitative and visual analysis of FDG-PET was performed and compared to the clinico-biological data. Results: Our cohort included 19 adult patients, median age 65 years [range 58-74], including three with smouldering SM (SSM), three with aggressive SM (ASM), 10 with an associated clonal haematological non-mast-cell lineage disease (SM-AHNMD), and three with mast cell sarcoma (MCS). FDG-PET was performed at the time of the SM diagnosis (15/19), to evaluate lymph node (LN) activity (3/19) or the efficacy of therapy (1/19). FDG uptake was observed in the bone marrow (BM) (9/19, 47 %), LN (6/19, 32 %), spleen (12/19, 63 %), or liver (1/19, 5 %). No significant FDG uptake was observed in the SSM and ASM patients. A pathological FDG uptake was observed in the BM of 6/10 patients with SM-AHNMD, appearing as diffuse and homogeneous, and in the LN of 5/10 patients. All 3 MCS patients showed intense and multifocal BM pathological uptake, mimicking metastasis. No correlation was found between the FDG-PET findings and serum tryptase levels, BM mast cell infiltration percentage, and CD30 and CD2 expression by mast cells. Conclusions: FDG uptake does not appear to be a sensitive marker of mast cell activation or proliferation because no significant FDG uptake was observed in most common forms of mastocytosis (notably purely aggressive SM). However, pathological FDG uptake was observed in the SM-AHNMD and in MCS cases, suggesting a role of FDG-PET in their early identification and as a tool of therapeutic assessment in this subgroup of patients. [ABSTRACT FROM AUTHOR]

The French National Cancer Institute (INCa) and Société française de sénologie et pathologie mammaire (SFSPM), in collaboration with a multidisciplinary experts group, have published the French national clinical practice guidelines on a selection of 11 currently debated questions regarding the management of non metastatic invasive breast cancer. Those guidelines are based on a comprehensive analysis of the current published evidence dealing with those issues, secondly reviewed by 100 French reviewers. [ABSTRACT FROM AUTHOR]

It is now well established that vestibular information plays an important role in spatial memory processes. Although vestibular lesions induce anxiety in humans, this finding remains controversial in rodents. However, it is possible that anxiety-related behavior is associated with spatial memory impairments after vestibular lesions. We aimed to evaluate anxiety-like behavior and the effect of an anxiolytic treatment during a complex spatial memory task in a rat model of compensated bilateral vestibular lesions. Adult rats were divided into four groups, with or without vestibular lesions and, treated or untreated by diazepam. The vestibular lesion was performed by transtympanic injection of arsanilate and compared to transtympanic saline injection. Diazepam or saline was administered 1 h before each test or learning session. Vestibular-lesioned rats exhibited anxiety-like behavior which was decreased with diazepam. Spatial memory performance was similar in control-treated and untreated groups, suggesting no effect on memory at the dose of diazepam used. Spatial memory performances were not modified by anxiolytic drug treatment in vestibular-lesioned rats compared to vestibular-lesioned rats without drug treatment. We conclude that bilateral vestibular lesions in rats induced anxiety-like behavior which was unrelated to spatial memory impairment and was probably specifically related to the loss of vestibular information. [ABSTRACT FROM AUTHOR]

Abstract: Vestibular deafferentation induces strong spatial memory impairments in rodents and dorsal hippocampal atrophy in humans, suggesting that vestibular information plays an important role in spatial-memory processes. However, previous studies have not discriminated between the role of the semi-circular canals, gravisensors and cochlear sense organ in such impairments due to complete damage of the vestibular and cochlear organs in their models of lesions. This is the first time that mutant mice (het/het) devoid of otoconia (lack of vestibular gravisensors) have been evaluated in behavioral tests. Results show different levels of achievement in the tests. The rotarod and elevated plus-maze were not executable, the rotarod being a safer test for differentiating the het/het mouse phenotype compared to the more anxiogenic swimming pool. Y-maze and place recognition tests were achieved, but chance values were not reached in the het/het group. Additionally, het/het mice presented uncommon behavior when faced with objects during the object recognition test. Impairments in het/het mice in the Y-maze test suggest a crucial role of the vestibular gravisensors in spatial-memory processes. [Copyright &y& Elsevier]

Abstract:: This study consists of a first assessment of a new technological solution (e-Celsius™ prototype) designed to perform intra peritoneal (IP) temperature measurements in animals. The tested prototype temperature sensor is composed of a miniaturized electronic sensor (capsule), which uses wireless technology to transmit temperature data to a dedicated monitor. The performance assessment was based on the comparison with commercially available analog tools (VitalSense, Jonah™ ingestible core temperature capsules) considered as gold standards. The variability (mean absolute deviation) of the calculated difference score around its mean value was taken as a reliability index. Thus, 6 pairs of capsules (1 Jonah™+1 e-Celsius™ prototype temperature sensor) were constituted. All the electronic capsules were first tested in a water bath heated to 37°C and then implanted intra-abdominally in 6 male Sprague Dawley rats. The capsules'' performances were assessed while rats were in free living conditions (24h alone in cage) and then again during the cooling process (anesthesia+ice). In a second step, a test was designed to assess the maximum distance of communication between sensors and the monitor. The mean absolute deviation of the difference scores was greater in the 24h free living conditions (±0.17°C) compared to the water bath conditions (±0.04°C). No difference was observed when compared to the cooling stage (±0.1°C). Considering that 50% of the data collected as a satisfactory performance criterion, the Jonah™ device could not be used at a distance exceeding 0.5m while the maximum distance recorded for the e-Celsius™ was 3m. The minimum life span for the tested e-Celsius™ and Jonah™ capsules was 14 days. The development of a precise calibration method is needed to finalize its validation. [Copyright &y& Elsevier]

Abstract: Several animal models of vestibular deficits that mimic the human pathology phenotype have previously been developed to correlate the degree of vestibular injury to cognate vestibular deficits in a time-dependent manner. Sodium arsanilate is one of the most commonly used substances for chemical vestibular lesioning, but it is not well described in the literature. In the present study, we used histological and functional approaches to conduct a detailed exploration of the model of vestibular lesions induced by transtympanic injection of sodium arsanilate in rats. The arsanilate-induced damage was restricted to the vestibular sensory organs without affecting the external ear, the oropharynx, or Scarpa''s ganglion. This finding strongly supports the absence of diffusion of arsanilate into the external ear or Eustachian tubes, or through the eighth cranial nerve sheath leading to the brainstem. One of the striking observations of the present study is the complete restructuring of the sensory epithelia into a non sensory epithelial monolayer observed at 3months after arsanilate application. This atrophy resembles the monolayer epithelia observed postmortem in the vestibular epithelia of patients with a history of lesioned vestibular deficits such as labyrinthectomy, antibiotic treatment, vestibular neuritis, or Ménière''s disease. In cases of Ménière''s disease, aminoglycosides, and platinum-based chemotherapy, vestibular hair cells are destroyed, regardless of the physiopathological process, as reproduced with the arsanilate model of vestibular lesion. These observations, together with those presented in this study of arsanilate vestibular toxicity, suggest that this atrophy process relies on a common mechanism of degeneration of the sensory epithelia. [Copyright &y& Elsevier]

• Vestibular nuclei were optogenetically stimulated, to asses for glutamate and GABA neurons functions in posturo-locomotor behaviors. • Brief optogenetic activation of VNVGluT2+, but not VNGAD2+, induced immediate and strong postural deficit. • Stimulation of VNVGluT2+ neurons provoked an imbalance with continuous effect on locomotion for a short period of time after stimulation. • Stimulation are comparable to classical vestibular deafferentation models at their peak, setting it as a new model to study vestibular deficits. Glutamatergic and GABAergic neurons represent the neural components of the medial vestibular nuclei. We assessed the functional role of glutamatergic and GABAergic neuronal pathways arising from the vestibular nuclei (VN) in the maintenance of gait and balance by optogenetically stimulating the VN in VGluT2-cre and GAD2-cre mice. We demonstrate that glutamatergic, but not GABAergic VN neuronal subpopulation is responsible for immediate and strong posturo-locomotor deficits, comparable to unilateral vestibular deafferentation models. During optogenetic stimulation, the support surface dramatically increased in VNVGluT2+ mice, and rapidly fell back to baseline after stimulation, whilst it remained unchanged during similar stimulation of VNGAD2+ mice. This effect persisted when vestibular tactilo kinesthesic plantar inputs were removed. Posturo-locomotor alterations evoked in VNVGluT2+ animals were still present immediately after stimulation, while they disappeared 1 h later. Overall, these results indicate a fundamental role for VNVGluT2+ neurons in balance and posturo-locomotor functions, but not for VNGAD2+ neurons, in this specific context. This new optogenetic approach will be useful to characterize the role of the different VN neuronal populations involved in vestibular physiology and pathophysiology. [ABSTRACT FROM AUTHOR]

• 3D immersive technology may outperform paper-pen tests in order to explore higher cognitive functions. • Current software remains homemade, not standardized and not directly customizable by researchers or usable by practitioners. • VRmaze software evaluates cognitive functions in humans combining 2 and 3D virtual environments and neuropsychological tests. • Users build or choose calibrated 3D virtual environments, protocols and trials with automatic tracking and analysis modules. • VRmaze offers a translational approach from animal models to patient neuropsychological evaluations. Compared to previous neuropsychological investigations with standard paper-pen tests limited to test complex spatial learning and memory processes, 3-D virtual immersive technology might offer new tools for research purposes and for diagnosis in patients suffering from mild cognitive impairment or dementia. Current software proposes a customizable VR environment combined with an analyser module based on regions of interest and some parameters of analysis or pre-calibrated VR mazes with raw data. We attempted to create the VRmaze software offering either turnkey mazes with automatic tracking and analysis, or more complex and specific virtual mazes for human brain-behavioural research adaptable to all desired settings and parameters of analysis. The software combines 3D pre-calibrated VR tests or free customizable VR tests with digitized neuropsychological 2D standard and validated tests or tasks. We have tested an ERAM, a MWM and a reverse T-maze on 44 healthy subjects, showing gender differences in terms of navigation strategy. We have observed that the choice of benchmarks, instructions, and experimental parameters influence the performances. VRmaze software offers a translational approach for research units that wish to combine animal models and patient evaluations as well as complex 3D tasks and standardized neuropsychological tests combined with an automatic analysis opening a large perspective in the neurosciences to investigate cognitive functions. A clinical module with preconfigured 2- and 3-D tasks should offer clinicians an easy way to evaluate their patients routinely. [ABSTRACT FROM AUTHOR]

Introduction Le syndrome d’Ehlers-Danlos (SED) est l’expression clinique d’atteintes du tissu conjonctif. Sa forme hypermobile (SEDh) s’exprime principalement à travers l’hyperlaxité articulaire, source de troubles proprioceptifs. Cette étude visait à évaluer : – les conséquences de ces troubles sur l’intégration sensori-motrice dans le contrôle postural ; – les effets du port d’orthèses (vêtements compressifs et semelles) à visée proprioceptive sur l’instabilité posturale. Matériel et méthode Six patientes SEDh ont effectué un test de la verticale subjective et une évaluation du contrôle postural (système de posturographie SYNAPSYS) statique ou dynamique (translations sinusoïdales), les yeux ouverts ou fermés, en simple ou double tâche (tâche 2-back concomitante), sans ou avec le port des orthèses. La performance posturale a été évaluée par la mesure des déplacements du centre des pressions. Les paramètres retenus sont : le statokinésigramme (SKG), les écart-types dans les plans antéro-postérieur (AP) et médio-latéral (ML) et le quotient de Romberg. La performance cognitive a été mesurée à partir du temps de réponse et du nombre de réponses correctes. Résultats Chez les patients avec SEDh, le jugement de la verticalité révèle un déficit d’intégration des afférences somesthésiques. Ce déficit est compensé par une plus grande visuodépendance (augmentation du SKG les yeux fermés, notamment dans le plan ML) et un coût attentionnel du contrôle postural accru ; ces derniers se trouvant réduits par le port d’orthèses. Discussion–conclusion Les orthèses permettent une ré-automatisation du contrôle postural dans le SEDh. [ABSTRACT FROM AUTHOR]