Movement-Based Control for Upper-Limb Prosthetics: Is the Regression Technique the Key to a Robust and Accurate Control?

Due to the limitations of myoelectric control (such as dependence on muscular fatigue and on electrodes shift, difficulty in decoding complex patterns or in dealing with simultaneous movements), there is a renewal of interest in the movement-based control approaches for prosthetics. The latter use residual limb movements rather than muscular activity as command inputs, in order to develop more natural and intuitive control techniques. Among those, several research works rely on the interjoint coordinations that naturally exist in human upper limb movements. These relationships are modeled to control the distal joints (e.g., elbow) based on the motions of proximal ones (e.g., shoulder). The regression techniques, used to model the coordinations, are various [Artificial Neural Networks, Principal Components Analysis (PCA), etc.] and yet, analysis of their performance and impact on the prosthesis control is missing in the literature. Is there one technique really more efficient than the others to model interjoint coordinations? To answer this question, we conducted an experimental campaign to compare the performance of three common regression techniques in the control of the elbow joint on a transhumeral prosthesis. Ten non-disabled subjects performed a reaching task, while wearing an elbow prosthesis which was driven by several interjoint coordination models obtained through different regression techniques. The models of the shoulder-elbow kinematic relationship were built from the recordings of fifteen different non-disabled subjects that performed a similar reaching task with their healthy arm. Among Radial Basis Function Networks (RBFN), Locally Weighted Regression (LWR), and PCA, RBFN was found to be the most robust, based on the analysis of several criteria including the quality of generated movements but also the compensatory strategies exhibited by users. Yet, RBFN does not significantly outperform LWR and PCA. The regression technique seems not to be the most significant factor for improvement of interjoint coordinations-based control. By characterizing the impact of the modeling techniques through closed-loop experiments with human users instead of purely offline simulations, this work could also help in improving movement-based control approaches and in bringing them closer to a real use by patients

Muscle-to-Brain communication in the context of obesity: impact of physical exercise?

editorial reviewedMuscle-to-Brain communication in the context of obesity: impact of physical exercise? A. Delpierre (1), C. Deroux (2), L. Ris (2), A-E. Declèves (3), A. Legrand (1), A. Villers (2) and A. Tassin (1) (1) Lab. of Respiratory Physiology and Rehabilitation, UMONS (2) Lab. of Neurosciences, UMONS (3) Lab. of Metabolic and Molecular Biochemistry, UMONS Exercise training (ET) has a positive effect on brain health. During ET, skeletal muscle releases specific myokines among them potential regulators of hippocampal function, like Irisin, released by cleavage of FNDC5. Also expressed in the brain, FNDC5 contributes to increase the level of brain-derived neurotrophic factor (BDNF). However, the contribution of muscle-derived Irisin on cognitive function remains controversial, as well as the influence of obesity or ET modalities. The goal of our study is to determine (i) inter-relationships between FNDC5/Irisin pathway and cognition depending on ET modalities and (ii) whether muscle-to-brain crosstalk is altered in the context of obesity. Two ET modalities were compared in Low-Fat (LF) and High-Fat (HF) fed mice: volontary (enriched environment) and forced ET (endurant). Irisin plasmatic level is increased by ET, whatever ET modality or diet. As concern FNDC5, volontary ET is associated to an increased protein level in LF but not in HF mouse muscles while forced ET does not modify FNDC5 protein level in muscular or brain tissues. Enrichment in mice improves spatial learning and memory. However, the BDNF protein level is not modified by volontary ET in the cortex and hippocampus. Forced ET does not modify spatial learning and memory and BDNF protein level in the hippocampus. However, BDNF protein level is increased in the brain cortex by endurance- training and surprisingly, by HF diet. In conclusion, ET increases Irisin plasmatic level and enrichment improves cognitive function in mice. FNDC5 protein level depend on training modalities, is tissue-specific and influenced by diet.Etude translationnelle de la communication muscle-cerveau lors d’un reconditionnement musculaire appliqué dans un contexte d’obésité. - Sources privée

Muscle-to-brain communication in the context of obesity : impact of physical exercise

editorial reviewedExercise training (ET) has a positive effect on brain health. Although molecular mechanisms underlying ET benefits are still poorly understood, a cross-talk between skeletal muscle and brain has been described. During ET, muscle releases specific myokines among which potential regulators of hippocampal function, like Irisin. This exerkine is a PGC1α-dependant myokine released by cleavage of FNDC5. Also expressed in the brain, FNDC5 contributes to increase the level of brain-derived neurotrophic factor. However, the contribution of muscle-derived Irisin on cognitive function remains controversial, as the influence of obesity or ET modalities. The goal of our study is to determine (i) inter-relationships between FNDC5/Irisin pathway and cognition in function of ET modalities and (ii) whether muscle-to-brain crosstalk is altered in the context of obesity. To this aim, two ET modalities were compared in mice: spontaneous ET (environmental enrichment) and endurance ET (training sessions on a treadmill). Mice were fed either with a Low-Fat (LF) or an High-Fat (HF) diet. ET reduces weight gain and fasting glycaemia in obese mice. Environmental enrichment improves spatial learning and memory (Morris Water Maze test), particularly in obese animals. Irisin plasmatic level is enhanced by a HF diet and endurance ET. In muscles, FNDC5 protein level is also modified by ET and diet. In brain, ET improves BDNF protein level. In conclusion, ET modalities and obesity influence FNDC5/Irisin pathway and cognitive functions in mice. Further studies are necessary to understand the contribution of muscle-derived Irisin to ET effects

Inter-communication muscle - cerveau dans un contexte d'obésité : Impact de l'exercice

L'entrainement en endurance se présente comme bénéfique dans la lutte contre l'obésité et ses troubles associés. En effet, au niveau cérébral, une augmentation de la plasticité, de la différenciation et de la survie neuronale ont été décrites dans la littérature. Ces observations peuvent être causées par une série de facteurs neurotrophiques eux-même stimulé par FNDC5, précurseur d'une exerkine nommée Irisine. La voie entrainement-muscle-Irisine/FNDC5-Cerveau pourrait être la clé dans l'approche de nouvelle stratégies thérapeutiques au niveau cérébral. Cependant les mécanismes par lesquels l'Irisine est modulée et stimule les facteurs neurotrophiques sont peu connus et cela particulièrement dans un contexte d'obésité

Développement d'une trousse de dosage d'organokines par spectrométrie de masse

Lors d'une prise en charge thérapeutique, l'identification de marqueurs biologiques permettant un meilleur diagnostic ainsi qu'une caractérisation évolutive du patient est essentielle. A cet égard, les organokines occupent une place importante car elles sont considérées comme des médiateurs moléculaires de la communication (cross-talk) inter-organes. Nous développons actuellement une méthode de quantification multiplexe de ces organokines. Cette recherche s'inscrit dans une des thématiques phares de l'Institut de Recherche Santé de l'UMONS et résulte d'une collaboration entre 6 services de l'Institut dans le domaine de la biomédecine intégrative. L'identification d'altérations du cross-talk inter-organes vise au développement futur de nouvelles stratégies thérapeutiques dans différents contextes pathologiques. Les organokines sont produites à partir de divers organes tels le tissu adipeux (adipokines), les muscles striés squelettiques (myokines), le foie (hépatokines), ou encore le cerveau (neurokines). Chacune de ces molécules est relarguée dans la circulation sanguine et agit ensuite à distance au niveau d'autres tissus et organes, jouant un rôle essentiel dans la coordination et le maintien de l'homéostasie, notamment métabolique. Il est aujourd'hui reconnu qu'une production ainsi qu'une libération excessive et inappropriée de ces organokines participe au développement et à la progression de pathologies comme l'obésité, le diabète de type 2 et les maladies cardiovasculaires. Actuellement, les organokines sont dosées individuellement par l'utilisation de tests ELISA ou RIA. Ces approches, non seulement coûteuses, n'existent pas pour toutes les organokines d'intérêt. Dans ce contexte, la spectrométrie de masse, approche très sensible, permet la quantification simultanée de nombreuses protéines dans différentes matrices biologiques dont le sérum ou le plasma. Ce projet implique une approche translationnelle directement en lien avec la clinique. Cette approche permettra d'acquérir une vision globale et intégrée des mécanismes de communication inter-organes impliqués dans les pathologies étudiées et de développer ainsi des stratégies thérapeutiques innovantes

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers

The risk of germline copy number variants (CNVs) in BRCA1 and BRCA2 pathogenic variant carriers in breast cancer is assessed, with CNVs overlapping SULT1A1 decreasing breast cancer risk in BRCA1 carriers.The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.Peer reviewe

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

The predictive ability of the 313 variant–based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant

Abstract: Purpose: To evaluate the association between a previously published 313 variant–based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. Methods: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk. Results: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06–1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07–1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS313 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. Conclusion: The PRS313 can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS313 needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making

Photo-acoustic terahertz phonon detection and generation within a semiconductor superlattice

International audienceCurrently, the development of compact opto-acoustic transducers able to generate and detect acoustic wave in the terahertz wavelength is an active research subject. Superlattice made with a periodic stacking of AlAs/GaAs layers has shown the ability to be used as high frequency acoustic generators and detectors. The excitation by a femtosecond laser leads to a temporally short strain in the pattern which produces quasi-monochromatic coherent phonons up to a frequency of 1 THz related to the multilayer period (excitation near $q=0$). This superlattice is an effective phonon detector since strain causes a change of reflectivity measured with a probe light. Unfortunately, generation and detection have differents spectrals responses: generation is more efficient around $q=0$, while detection works with $q=2k$ ($k$ is the light vector). Therefore a single superlattice cannot be used to detect and generate the same wave vector. However, theory predicts a rise of $q=0$ detection in case of strong reflection at the interface between superlattice and substrate. To check this possibility we design a sample made of a 17 nm period superlattice embedded in an optical micro-cavity. We will present experiments performed at low temperatures on a sample designed to generate and detect 300 GHz acoustic waves