Robotic Rehabilitation and Multimodal Instrumented Assessment of Post-stroke Elbow Motor Functions—A Randomized Controlled Trial Protocol

Background: The reliable assessment, attribution, and alleviation of upper-limb joint stiffness are essential clinical objectives in the early rehabilitation from stroke and other neurological disorders, to prevent the progression of neuromuscular pathology and enable proactive physiotherapy toward functional recovery. However, the current clinical evaluation and treatment of this stiffness (and underlying muscle spasticity) are severely limited by their dependence on subjective evaluation and manual limb mobilization, thus rendering the evaluation imprecise and the treatment insufficiently tailored to the specific pathologies and residual capabilities of individual patients. Methods: To address these needs, the proposed clinical trial will employ the NEUROExos Elbow Module (NEEM), an active robotic exoskeleton, for the passive mobilization and active training of elbow flexion and extension in 60 sub-acute and chronic stroke patients with motor impairments (hemiparesis and/or spasticity) of the right arm. The study protocol is a randomized controlled trial consisting of a 4-week functional rehabilitation program, with both clinical and robotically instrumented assessments to be conducted at baseline and post-treatment. The primary outcome measures will be a set of standard clinical scales for upper limb spasticity and motor function assessment, including the Modified Ashworth Scale and Fugl-Meyer Index, to confirm the safety and evaluate the efficacy of robotic rehabilitation in reducing elbow stiffness and improving function. Secondary outcomes will include biomechanical, muscular activity, and motor performance parameters extracted from instrumented assessments using the NEEM along with synchronous EMG recordings. The study protocol has been registered on clinicaltrials.gov with registration trial number NCT04484571. Conclusions: This randomized controlled trial aims to validate an innovative instrumented methodology for clinical spasticity assessment and functional rehabilitation, relying on the precision and accuracy of an elbow exoskeleton combined with EMG recordings and the expertise of a physiotherapist, thus complementing and maximizing the benefits of both practices

Synthesis and Biological Evaluation of a-Tubulin-Binding Pironetin Analogues with Enhanced Lipophilicity

The preparation of four new lipophilic analogues of the natural pyrone pironetin is described. The nine-carbon side chain of the latter has been replaced in one analogue by a 4-phenylbutyl chain and in the other three analogues by long aliphatic chains of thirteen and sixteen carbons, all of them bearing two stereogenic centers. Their cytotoxic activity and their interactions with tubulin have been investigated. It has been found that all four are cytotoxic towards two either sensitive or resistant tumoral cell lines with similar IC50 values in each case, thus indicating that, like the parent natural compound, they also display a covalent mechanism of action. However, one of them operates in all likelihood through a mechanism very similar to pironetin whereas the other three seem to be cytotoxic via a different mechanism

Mecanismo de accion de los macrolidos citotoxicos amphinolidas X y J

Trabajo presentado en el XI Congreso de la Sociedad de Biofísica de España: "XXV años y más allá", celebrado en Murcia (España) , del 1 al 4 de junio de 201

Self-Aligning Finger Exoskeleton for the Mobilization of the Metacarpophalangeal Joint

In the context of hand and finger rehabilitation, kinematic compatibility is key for the acceptability and clinical exploitation of robotic devices. Different kinematic chain solutions have been proposed in the state of the art, with different trade-offs between characteristics of kinematic compatibility, adaptability to different anthropometries, and the ability to compute relevant clinical information. This study presents the design of a novel kinematic chain for the mobilization of the metacarpophalangeal (MCP) joint of the long fingers and a mathematical model for the real-time computation of the joint angle and transferred torque. The proposed mechanism can self-align with the human joint without hindering force transfer or inducing parasitic torque. The chain has been designed for integration into an exoskeletal device aimed at rehabilitating traumatic-hand patients. The exoskeleton actuation the unit has a series-elastic architecture for compliant human-robot interaction and has been assembled and preliminarily tested in experiments with eight human subjects. Performance has been investigated in terms of (i) the accuracy of the MCP joint angle estimation through comparison with a video-based motion tracking system, (ii) residual MCP torque when the exoskeleton is controlled to provide null output impedance and (iii) torque-tracking performance. Results showed a root-mean-square error (RMSE) below 5 degrees in the estimated MCP angle. The estimated residual MCP torque resulted below 7 mNm. Torque tracking performance shows an RMSE lower than 8 mNm in following sinusoidal reference profiles. The results encourage further investigations of the device in a clinical scenario

Synthesis and Biological Evaluation As Microtubule-Active Agents of Several Tetrahydrofuran and Spiroacetal Derivatives

The stereoselective preparation of several molecules containing structural fragments of the tetrahydrofuran and spiroacetal type is described. Their degree of cytotoxicity and their interactions with tubulin have been investigated. It has been confirmed that the tetrahydrofuran derivatives are cytotoxic but, in contrast to previous reports, it has been found that the cytoxicity is not due to interactions with the microtubule network. Furthermore, and also in contrast to a previous report on closely related compounds, the spiroacetal derivatives do show interactions with tubulin, even though the precise mechanism and the binding site still remain to be established

Physiological Responses During Hybrid BNCI Control of an Upper-Limb Exoskeleton

When combined with assistive robotic devices, such as wearable robotics, brain/neural-computer interfaces (BNCI) have the potential to restore the capabilities of handicapped people to carry out activities of daily living. To improve applicability of such systems, workload and stress should be reduced to a minimal level. Here, we investigated the user’s physiological reactions during the exhaustive use of the interfaces of a hybrid control interface. Eleven BNCI-naive healthy volunteers participated in the experiments. All participants sat in a comfortable chair in front of a desk and wore a whole-arm exoskeleton as well as wearable devices for monitoring physiological, electroencephalographic (EEG) and electrooculographic (EoG) signals. The experimental protocol consisted of three phases: (i) Set-up, calibration and BNCI training; (ii) Familiarization phase ; and (iii) Experimental phase during which each subject had to perform EEG and EoG tasks. After completing each task, the NASA-TLX questionnaire and self-assessment manikin (SAM) were completed by the user. We found significant differences (p-value < 0.05) in heart rate variability (HRV) and skin conductance level (SCL) between participants during the use of the two different biosignal modalities (EEG, EoG) of the BNCI. This indicates that EEG control is associated with a higher level of stress (associated with a decrease in HRV) and mental work load (associated with a higher level of SCL) when compared to EoG control. In addition, HRV and SCL modulations correlated with the subject’s workload perception and emotional responses assessed through NASA-TLX questionnaires and SAM

Hybrid brain/neural interface and autonomous vision-guided whole-arm exoskeleton control to perform activities of daily living (ADLs)

[EN] Background The aging of the population and the progressive increase of life expectancy in developed countries is leading to a high incidence of age-related cerebrovascular diseases, which affect people's motor and cognitive capabilities and might result in the loss of arm and hand functions. Such conditions have a detrimental impact on people's quality of life. Assistive robots have been developed to help people with motor or cognitive disabilities to perform activities of daily living (ADLs) independently. Most of the robotic systems for assisting on ADLs proposed in the state of the art are mainly external manipulators and exoskeletal devices. The main objective of this study is to compare the performance of an hybrid EEG/EOG interface to perform ADLs when the user is controlling an exoskeleton rather than using an external manipulator. Methods Ten impaired participants (5 males and 5 females, mean age 52 +/- 16 years) were instructed to use both systems to perform a drinking task and a pouring task comprising multiple subtasks. For each device, two modes of operation were studied: synchronous mode (the user received a visual cue indicating the sub-tasks to be performed at each time) and asynchronous mode (the user started and finished each of the sub-tasks independently). Fluent control was assumed when the time for successful initializations ranged below 3 s and a reliable control in case it remained below 5 s. NASA-TLX questionnaire was used to evaluate the task workload. For the trials involving the use of the exoskeleton, a custom Likert-Scale questionnaire was used to evaluate the user's experience in terms of perceived comfort, safety, and reliability. Results All participants were able to control both systems fluently and reliably. However, results suggest better performances of the exoskeleton over the external manipulator (75% successful initializations remain below 3 s in case of the exoskeleton and bellow 5s in case of the external manipulator). Conclusions Although the results of our study in terms of fluency and reliability of EEG control suggest better performances of the exoskeleton over the external manipulator, such results cannot be considered conclusive, due to the heterogeneity of the population under test and the relatively limited number of participants.This study was funded by the European Commission under the project AIDE (G.A. no: 645322), Spanish Ministry of Science and Innovation, through the projects PID2019-108310RB-I00 and PLEC2022-009424 and by the Ministry of Universities and European Union, "fnanced by European Union-Next Generation EU" through Margarita Salas grant for the training of young doctors.Catalán, JM.; Trigili, E.; Nann, M.; Blanco-Ivorra, A.; Lauretti, C.; Cordella, F.; Ivorra, E.... (2023). Hybrid brain/neural interface and autonomous vision-guided whole-arm exoskeleton control to perform activities of daily living (ADLs). Journal of NeuroEngineering and Rehabilitation. 20(1):1-16. https://doi.org/10.1186/s12984-023-01185-w11620

Probing the Pore Drug Binding Site of Microtubules with Fluorescent Taxanes: Evidence of Two Binding Poses

The pore site in microtubules has been studied with the use of Hexaflutax, a fluorescent probe derived from paclitaxel. The compound is active in cells with similar effects to paclitaxel, indicating that the pore may be a target to microtubule stabilizing agents. While other taxanes bind microtubules in a monophasic way, thus indicating a single type of sites, Hexaflutax association is biphasic. Analysis of the phases indicates that two different binding sites are detected, reflecting two different modes of binding, which could arise from different arrangements of the taxane or fluorescein moieties in the pore. Association of the 4-4-20 antifluorescein monoclonal antibody-Hexaflutax complex to microtubules remains biphasic, thus indicating that the two phases observed arise from two different poses of the taxane moiety.This work was supported in part by grant BIO2007-61336 from the Ministry of Science and Innovation to J.F.D., BIPPED-CM from Comunidad de Madrid to J.F.D. and J.M.A., and grant MOST No. 2006DFA31490 to W.S.F

Synthesis and biological evaluation as microtubule-active agents of several tetrahydrofuran and spiroacetal derivatives

The stereoselective preparation of several molecules containing structural fragments of the tetrahydrofuran and spiroacetal type is described. Their degree of cytotoxicity and their interactions with tubulin have been investigated. It has been confirmed that the tetrahydrofuran derivatives are cytotoxic but, in contrast to previous reports, it has been found that the cytoxicity is not due to interactions with the microtubule network. Furthermore, and also in contrast to a previous report on closely related compounds, the spiroacetal derivatives do show interactions with tubulin, even though the precise mechanism and the binding site still remain to be established.Financial support has been granted by the Spanish Ministry of Education and Science (CTQ2008-02800), by the Consellería d´Empresa, Universitat i Ciencia de la Generalitat Valenciana (ACOMP09/113) and by the BANCAJA-UJI Foundation (P1-1B2002-06 and P1-1B-2008-14). The biological work has been supported in part by grants from the Spanish Ministry of Education and Science (BIO2007- 61336) and from the Comunidad de Madrid (grants S2010/ BMD-2457 and BIPEDD2-CM) (both to J.F.D.). We further thank the Matadero Municipal Vicente de Lucas in Segovia for providing the calf brains which were the source of tubuli