Robotic exoskeletons: A perspective for the rehabilitation of arm coordination in stroke patients

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

Design and acceptability assessment of a new reversible orthosis

International audience— We present a new device aimed at being used for upper limb rehabilitation. Our main focus was to design a robot capable of working in both the passive mode (i.e. the robot shall be strong enough to generate human-like movements while guiding the weak arm of a patient) and the active mode (i.e. the robot shall be able of following the arm without disturbing human natural motion). This greatly challenges the design, since the system shall be reversible and lightweight while providing human compatible strength, workspace and speed. The solution takes the form of an orthotic structure, which allows control of human arm redundancy contrarily to clinically available upper limb rehabilitation robots. It is equipped with an innovative transmission technology, which provides both high gear ratio and fine reversibility. In order to evaluate the device and its therapeutic efficacy, we compared several series of pointing movements in healthy subjects wearing and not wearing the orthotic device. In this way, we could assess any disturbing effect on normal movements. Results show that the main movement characteristics (direction, duration, bell shape profile) are preserved

Posture of the arm when grasping spheres to place them elsewhere

Despite the infinitely many ways to grasp a spherical object, regularities have been observed in the posture of the arm and the grasp orientation. In the present study, we set out to determine the factors that predict the grasp orientation and the final joint angles of reach-tograsp movements. Subjects made reach-to-grasp movements toward a sphere to pick it up and place it at an indicated location. We varied the position of the sphere and the starting and placing positions. Multiple regression analysis showed that the sphere's azimuth from the subject was the best predictor of grasp orientation, although there were also smaller but reliable contributions of distance, starting position, and perhaps even placing position. The sphere's initial distance from the subject was the best predictor of the final elbow angle and shoulder elevation. A combination of the sphere's azimuth and distance from the subject was required to predict shoulder angle, trunkhead rotation, and lateral head position. The starting position best predicted the final wrist angle and sagittal head position. We conclude that the final posture of the arm when grasping a sphere to place it elsewhere is determined to a larger extend by the initial position of the object than by effects of starting and placing position. © 2010 Springer-Verlag

Design and acceptability assessment of a new reversible orthosis

We present a new device aimed at being used for upper limb rehabilitation. Our main focus was to design a robot capable of working in both the passive mode (i.e. the robot shall be strong enough to generate human-like movements while guiding the weak arm of a patient) and the active mode (i.e. the robot shall be able of following the arm without disturbing human natural motion). This greatly challenges the design, since the system shall be reversible and lightweight while providing human compatible strength, workspace and speed. The solution takes the form of an orthotic structure, which allows control of human arm redundancy contrarily to clinically available upper limb rehabilitation robots. It is equipped with an innovative transmission technology, which provides both high gear ratio and fine reversibility. In order to evaluate the device and its therapeutic efficacy, we compared several series of pointing movements in healthy subjects wearing and not wearing the orthotic device . In this way, we could assess any disturbing effect on normal movements. Results show that the main movement characteristics (direction, duration, bell shape profile) are preserved. ©2008 IEEE

Increased immunogenicity of surviving tumor cells enables cooperation between liposomal doxorubicin and IL-18

<p>Abstract</p> <p>Background</p> <p>Liposomal doxorubicin (Doxil) is a cytotoxic chemotherapy drug with a favorable hematologic toxicity profile. Its active drug, doxorubicin, has interesting immunomodulatory properties. Here, the effects of Doxil on surviving tumor cell immunophenotype were investigated.</p> <p>Methods</p> <p>Using ID8 murine ovarian cancer cells, the immunomodulatory effects of Doxil were studied by measuring its impact on ovarian cancer cell expression of MHC class-I and Fas, and susceptibility to immune attack <it>in vitro</it>. To evaluate the ability of Doxil to cooperate with cancer immunotherapy, the interaction between Doxil and Interleukin 18 (IL-18), a pleiotropic immunostimulatory cytokine, was investigated <it>in vivo </it>in mice bearing ID8-Vegf tumors.</p> <p>Results</p> <p>While Doxil killed ID8 tumor cells in a dose-dependent manner, tumor cells escaping Doxil-induced apoptosis upregulated surface expression of MHC-I and Fas, and were sensitized to CTL killing and Fas-mediated death <it>in vitro</it>. We therefore tested the hypothesis that the combination of immunotherapy with Doxil provides positive interactions. Combination IL-18 and Doxil significantly suppressed tumor growth compared with either monotherapy <it>in vivo </it>and uniquely resulted in complete tumor regression and long term antitumor protection in a significant proportion of mice.</p> <p>Conclusion</p> <p>These data demonstrate that Doxil favorably changes the immunophenotype of a large fraction of the tumor that escapes direct killing thus creating an opportunity to expand tumor killing by immunotherapy, which can be capitalized through addition of IL-18 <it>in vivo</it>.</p

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Natural Variation in Partial Resistance to Pseudomonas syringae Is Controlled by Two Major QTLs in Arabidopsis thaliana

BACKGROUND: Low-level, partial resistance is pre-eminent in natural populations, however, the mechanisms underlying this form of resistance are still poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we used the model pathosystem Pseudomonas syringae pv. tomato DC3000 (Pst) - Arabidopsis thaliana to study the genetic basis of this form of resistance. Phenotypic analysis of a set of Arabidopsis accessions, based on evaluation of in planta pathogen growth revealed extensive quantitative variation for partial resistance to Pst. It allowed choosing a recombinant inbred line (RIL) population derived from a cross between the accessions Bayreuth and Shahdara for quantitative genetic analysis. Experiments performed under two different environmental conditions led to the detection of two major and two minor quantitative trait loci (QTLs) governing partial resistance to Pst and called PRP-Ps1 to PRP-Ps4. The two major QTLs, PRP-Ps1 and PRP-Ps2, were confirmed in near isogenic lines (NILs), following the heterogeneous inbred families (HIFs) strategy. Analysis of marker gene expression using these HIFs indicated a negative correlation between the induced amount of transcripts of SA-dependent genes PR1, ICS and PR5, and the in planta bacterial growth in the HIF segregating at PRP-Ps2 locus, suggesting an implication of PRP-Ps2 in the activation of SA dependent responses. CONCLUSIONS/SIGNIFICANCE: These results show that variation in partial resistance to Pst in Arabidopsis is governed by relatively few loci, and the validation of two major loci opens the way for their fine mapping and their cloning, which will improve our understanding of the molecular mechanisms underlying partial resistance