Quantification of push-off and collision work during step-to-step transition in amputees walking at self-selected speed: Effect of amputation level.

Maintaining forward walking during human locomotion requires mechanical joint work, mainly provided by the ankle-foot in non-amputees. In lower-limb amputees, their metabolic overconsumption is generally attributed to reduced propulsion. However, it remains unclear how altered walking patterns resulting from amputation affect energy exchange.

Predictive factors of return-to-work trajectory after work-related rotator cuff syndrome: A prospective study of 96 workers.

Objective: Sustained return to work after surgery for work-related rotator cuff syndrome (WRRCS) remains quite difficult. The main purpose of the present study was to identify predictive factors of a return-to-work (RTW) trajectory.

Methods: A total of 96 workers with WRRCS were identified by 4 surgeons.

Comparison of compensatory shoulder movements, functionality and satisfaction in transradial amputees fitted with two prosthetic myoelectric hooks.

The functionalities of myoelectric hooks, such as whether they allow wrist movements, as well as the volume and design of the devices, may impact how fitted transradial amputees use their upper limbs. The aim of the current study was to compare two prosthetic myoelectric hooks in terms of compensatory shoulder movements, functionality and user satisfaction. This monocentric, randomized, controlled, cross-over trial evaluated eight transradial amputees fitted with two prosthetic myoelectric hooks, the Greifer and the Axon-Hook, during two consecutive periods.

Effects of a microprocessor-controlled ankle-foot unit on energy expenditure, quality of life, and postural stability in persons with transtibial amputation: An unblinded, randomized, controlled, cross-over study.

Background: Microprocessor-controlled prostheses are designed to improve mobility and quality of life through better balance and energy restoration in persons with transtibial amputation. Quasi-active microprocessor-controlled ankles (MPA) adapt to variable terrain by ankle angle adjustment.

Objectives: To compare energy expenditure, balance, quality of life, and satisfaction of Proprio-foot® (a quasi-active MPA model) with standard prescribed ankle prosthesis (prescribed ankle-foot units [PA]) (standard energy storage and return prosthesis).

Kinematic analysis of impairments and compensatory motor behavior during prosthetic grasping in below-elbow amputees.

After a major upper limb amputation, the use of myoelectric prosthesis as assistive devices is possible. However, these prostheses remain quite difficult to control for grasping and manipulation of daily life objects. The aim of the present observational case study is to document the kinematics of grasping in a group of 10 below-elbow amputated patients fitted with a myoelectric prosthesis in order to describe and better understand their compensatory strategies.

Predictive factors for the duration until return to work after surgery for work-related rotator cuff syndrome: A prospective study of 92 workers.

Background: Return to work (RTW) after surgery for a work-related rotator cuff disorder (WRRCD) is often difficult. The study's purpose was to identify preoperative factors predicting RTW.

Methods: Ninety-two workers with a WRRCD were identified by four surgeons.

Guiding the Training of Users With a Pattern Similarity Biofeedback to Improve the Performance of Myoelectric Pattern Recognition.

Next generation prosthetics will rely massively on myoelectric "Pattern Recognition" (PR) based control approaches, to improve their users' dexterity. One major identified factor of successful functioning of these approaches lies in the training of amputees and in their understanding of how those prosthetics works. We thus propose here an intuitive pattern similarity biofeedback which can be easily used to train amputees and allow them to optimize their muscular contractions to improve their control performance.

Cross-cultural adaptation and measurement properties of the French version of the Trinity Amputation and Prosthesis Experience Scales-Revised (TAPES-R).

Background: The Trinity Amputation and Prosthesis Experience Scales-Revised (TAPES-R) is a self-administered questionnaire to measure multidimensional adjustment to a prosthetic limb. Our aim was to assess the validity and reliability of the French version of the TAPES-R (TAPES-R-F).

Materials And Methods: The cross-cultural adaptation was performed according to the recommendations.

Are wearable insoles a validated tool for quantifying transfemoral amputee gait asymmetry?

Background: Amputee gait is known to be asymmetrical, especially during loading of the lower limb. Monitoring asymmetry could be useful in quantifying patient performance during rehabilitation. Wearable insoles can provide normal ground reaction force asymmetry in real-life conditions.

Phantom-Mobility-Based Prosthesis Control in Transhumeral Amputees Without Surgical Reinnervation: A Preliminary Study.

Transhumeral amputees face substantial difficulties in efficiently controlling their prosthetic limb, leading to a high rate of rejection of these devices. Actual myoelectric control approaches make their use slow, sequential and unnatural, especially for these patients with a high level of amputation who need a prosthesis with numerous active degrees of freedom (powered elbow, wrist, and hand). While surgical muscle-reinnervation is becoming a generic solution for amputees to increase their control capabilities over a prosthesis, research is still being conducted on the possibility of using the surface myoelectric patterns specifically associated to voluntary Phantom Limb Mobilization (PLM), appearing naturally in most upper-limb amputees without requiring specific surgery.

Characteristics of phantom upper limb mobility encourage phantom-mobility-based prosthesis control.

There is an increasing need to extend the control possibilities of upper limb amputees over their prosthetics, especially given the development of devices with numerous active joints. One way of feeding pattern recognition myoelectric control is to rely on the myoelectric activities of the residual limb associated with phantom limb movements (PLM). This study aimed to describe the types, characteristics, potential influencing factors and trainability of upper limb PLM.

Cross-cultural adaptation and validation of the ABIS questionnaire for French speaking amputees.

: The Amputee Body Image Scale (ABIS) and its shortened version (ABIS-R) are self-administered questionnaires to measure body image perception of amputee. Our aim was to assess the validity and reliability of the French ABIS (ABIS-F and ABIS-R-F). Ninety-nine patients were included.

Imidazo[2,1-]benzothiazol Derivatives as Potential Allosteric Inhibitors of the Glucocorticoid Receptor.

Glucocorticoid receptor (GCR) transactivation reporter gene assays were used as an initial high-throughput screening on a diversified library of 1200 compounds for their evaluation as GCR antagonists. A class of imidazo[2,1-]benzothiazole and imidazo[2,1-]benzoimidazole derivatives were identified for their ability to modulate GCR transactivation and anti-inflammatory transrepression effects utilizing GCR and NF-κB specific reporter gene assays. Modeling studies on the crystallographic structure of the GCR ligand binding domain provided three new analogues bearing the tetrahydroimidazo[2,1-]benzothiazole scaffold able to antagonize the GCR in the presence of dexamethasone (DEX) and also defined their putative binding into the GCR structure.

Can We Achieve Intuitive Prosthetic Elbow Control Based on Healthy Upper Limb Motor Strategies?

Most transhumeral amputees report that their prosthetic device lacks functionality, citing the control strategy as a major limitation. Indeed, they are required to control several degrees of freedom with muscle groups primarily used for elbow actuation. As a result, most of them choose to have a one-degree-of-freedom myoelectric hand for grasping objects, a myoelectric wrist for pronation/supination, and a body-powered elbow.

A High-throughput Screening of a Chemical Compound Library in Ovarian Cancer Stem Cells.

Background: Epithelial ovarian cancer has a poor prognosis, mostly due to its late diagnosis and the development of drug resistance after a first platinum-based regimen. The presence of a specific population of "cancer stem cells" could be responsible of the relapse of the tumor and the development of resistance to therapy. For this reason, it would be important to specifically target this subpopulation of tumor cells in order to increase the response to therapy.

Voluntary phantom hand and finger movements in transhumerai amputees could be used to naturally control polydigital prostheses.

An arm amputation is extremely invalidating since many of our daily tasks require bi-manual and precise control of hand movements. Perfect hand prostheses should therefore offer a natural, intuitive and cognitively simple control over their numerous biomimetic active degrees of freedom. While efficient polydigital prostheses are commercially available, their control remains complex to master and offers limited possibilities, especially for high amputation levels.

Reachability and the sense of embodiment in amputees using prostheses.

Amputated patients are hardly satisfied with upper limb prostheses, and tend to favour the use of their contralateral arm to partially compensate their disability. This may seem surprising in light of recent evidences that external objects (rubber hand or tool) can easily be embodied, namely incorporated in the body representation. We investigated both implicit body representations (by evaluating the peripersonal space using a reachability judgement task) and the quality of bodily integration of the patient's prosthesis (assessed via questionnaires).

Synthesis of a selective HDAC6 inhibitor active in neuroblasts.

In recent years, the role of HDAC6 in neurodegeneration has been partially elucidated, which led some authors to propose HDAC6 inhibitors as a therapeutic strategy to treat neurodegenerative diseases. In an effort to develop a selective HDAC6 inhibitor which can cross the blood brain barrier (BBB), a modified hydroxamate derivative (compound 3) was designed and synthetized. This compound was predicted to have potential for BBB penetration based on in silico and in vitro evaluation of passive permeability.

Discovery and Pharmacokinetic and Pharmacological Properties of the Potent and Selective MET Kinase Inhibitor 1-{6-[6-(4-Fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl]benzothiazol-2-yl}-3-(2-morpholin-4-ylethyl)urea (SAR125844).

The HGF/MET pathway is frequently activated in a variety of cancer types. Several selective small molecule inhibitors of the MET kinase are currently in clinical evaluation, in particular for NSCLC, liver, and gastric cancer patients. We report herein the discovery of a series of triazolopyridazines that are selective inhibitors of wild-type (WT) MET kinase and several clinically relevant mutants.

Classification of Phantom Finger, Hand, Wrist, and Elbow Voluntary Gestures in Transhumeral Amputees With sEMG.

Decoding finger and hand movements from sEMG electrodes placed on the forearm of transradial amputees has been commonly studied by many research groups. A few recent studies have shown an interesting phenomenon: simple correlations between distal phantom finger, hand and wrist voluntary movements and muscle activity in the residual upper arm in transhumeral amputees, i.e.

Tandem virtual screening targeting the SRA domain of UHRF1 identifies a novel chemical tool modulating DNA methylation.

Ubiquitin-like protein UHRF1 that contains PHD and RING finger domain 1 is a key epigenetic protein enabling maintenance of the DNA methylation status through replication. A tandem virtual screening approach was implemented for identifying small molecules able to bind the 5-methylcytosine pocket of UHRF1 and inhibit its functionality. The NCI/DTP small molecules Repository was screened in silico by a combined protocol implementing structure-based and ligand-based methodologies.

Cross metathesis with hydroxamate and benzamide BOC-protected alkenes to access HDAC inhibitors and their biological evaluation highlighted intrinsic activity of BOC-protected dihydroxamates.

Conditions for the metathesis of alkenes in the convergent synthesis of HDAC inhibitors have been improved by continuous catalyst flow injection in the reaction media. Intermediate and target compounds obtained were tested for their ability to induce HDAC inhibition and tubulin acetylation, revealing the key role of the tert-butyloxycarbonyl (BOC) group for more HDAC6 selectivity. Molecular modelling added rationale for this BOC effect.

Phantom hand and wrist movements in upper limb amputees are slow but naturally controlled movements.

After limb amputation, patients often wake up with a vivid perception of the presence of the missing limb, called "phantom limb". Phantom limbs have mostly been studied with respect to pain sensation. But patients can experience many other phantom sensations, including voluntary movements.

Natural Products and Cancer Stem Cells.

The development of modern technologies casts a new light on the natural products as an invaluable source of lead compounds that could guide drug discovery. Cancer stem cells are a subpopulation of cancer cells with a high clonogenic capacity and the ability to reform the parental tumours upon transplantation. They have been proposed to drive tumorigenesis and metastases.