Staged Bilateral MRI-Guided Focused Ultrasound Subthalamotomy for Parkinson Disease.

Importance: Unilateral magnetic resonance imaging (MRI)-guided focused ultrasound subthalamotomy (FUS-STN) improves cardinal motor features among patients with asymmetrical Parkinson disease (PD). The feasibility of bilateral FUS-STN is as yet unexplored. Objective: To assess the safety and effectiveness of staged bilateral FUS-STN to treat PD. Design, Setting, and Participants: This prospective, open-label, case series study was conducted between June 18, 2019, and November 7, 2023, at HM-CINAC, Puerta del Sur University Hospital, Madrid, Spain, and included 6 patients with PD who had been treated with unilateral FUS-STN contralateral to their most affected body side and whose parkinsonism on the untreated side had progressed and was not optimally controlled with medication. Intervention: Staged bilateral FUS-STN. Main Outcomes and Measures: Primary outcomes were assessed 6 months after the second treatment and included safety (incidence and severity of adverse events after second treatment) and effectiveness in terms of motor change (measured with the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III [MDS-UPDRS III]) in the off-medication state (ie, after at least 12 hours of antiparkinsonian drug withdrawal) compared with baseline (ie, prior to the first side ablation). Secondary outcomes included motor change in patients in the on-medication state (ie, after usual antiparkinsonian medication intake), motor complications (measured with the MDS-UPDRS IV), daily living activities (measured with the MDS-UPDRS I-II), quality of life (measured with the 39-item Parkinson's Disease Questionnaire), change in dopaminergic treatment, patient's global impression of change (measured with the Global Impression of Change [PGI-C] scale), and long-term (24-month) follow-up. Results: Of 45 patients previously treated with unilateral FUS-STN, 7 were lost to follow-up, and 4 were excluded due to adverse events. Of the remaining 34 patients, 6 (median age at first FUS-STN, 52.6 years [IQR, 49.0-57.3 years]; 3 women [50%]) experienced progression of parkinsonism on the untreated body side and were included. At the time of the first FUS-STN, patients' median duration of disease was 5.7 years (IQR, 4.7-7.3 years). The median time between procedures was 3.2 years (IQR, 1.9-3.5 years). After the second FUS-STN, 4 patients presented with contralateral choreic dyskinesia, which resolved by 3 months. Four patients developed speech disturbances, which gradually improved but remained in a mild form for 2 patients at 6 months; 1 patient experienced mild imbalance and dysphagia during the first week after treatment, which subsided by 3 months. No behavioral or cognitive disturbances were found on neuropsychological testing. For patients in the off-medication state, MDS-UPDRS III scores improved by 52.6% between baseline and 6 months after the second FUS-STN (from 37.5 [IQR, 34.2-40.0] to 20.5 [IQR, 8.7-24.0]; median difference, 23.0 [95% CI, 7.0-33.7]; P = .03). The second treated side improved by 64.3% (MDS-UPDRS III score, 17.0 [IQR, 16.0-19.5] prior to the second treatment vs 5.5 [IQR, 3.0-10.2]; median difference, 9.5 [95% CI, 3.2-17.7]; P = .02). After the second procedure, all self-reported PGI-C scores were positive. Conclusions: Findings of this pilot study suggest that staged bilateral FUS-STN was safe and effective for the treatment of PD, although mild but persistent speech-related adverse events were observed among a small number of patients.

Unilateral focused ultrasound subthalamotomy in early Parkinson's disease: a pilot study.

BACKGROUND: Unilateral focused ultrasound subthalamotomy (FUS-STN) improves motor features of Parkinson's disease (PD) in moderately advanced patients. The less invasive nature of FUS makes its early application in PD feasible. We aim to assess the safety and efficacy of unilateral FUS-STN in patients with PD of less than 5 years from diagnosis (early PD). METHODS: Prospective, open-label study. Eligible patients with early PD had highly asymmetrical cardinal features. The primary outcome was safety, defined as treatment-related adverse events at 6 months. Secondary outcomes included efficacy, assessed as motor improvement in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), motor fluctuations, non-motor symptoms, daily living activities, quality of life, medication and patients' impression of change. RESULTS: Twelve patients with PD (median age 52.0 (IQR 49.8-55.3) years, median time from diagnosis 3.0 (2.1-3.9) years) underwent unilateral FUS-STN. Within 2 weeks after treatment, five patients developed dyskinesia on the treated side, all resolved after levodopa dose adjustment. One patient developed mild contralateral motor weakness which fully resolved in 4 weeks. One patient developed dystonic foot and another hand and foot dystonia. The latter impaired gait and became functionally disabling initially. Both cases were well controlled with botulinum toxin injections. The off-medication motor MDS-UPDRS score for the treated side improved at 12 months by 68.7% (from 14.5 to 4.0, p=0.002), and the total motor MDS-UPDRS improved by 49.0% (from 26.5 to 13.0, p=0.002). Eleven patients (92%) reported global improvement 12 months after treatment. CONCLUSION: Unilateral FUS-STN may be safe and effective to treat motor manifestations in patients with early PD. A larger confirmatory trial is warranted. TRIAL REGISTRATION NUMBER: NCT04692116.

Electronic Eye Based on RGB Analysis for the Identification of Tequilas.

The present work reports the development of a biologically inspired analytical system known as Electronic Eye (EE), capable of qualitatively discriminating different tequila categories. The reported system is a low-cost and portable instrumentation based on a Raspberry Pi single-board computer and an 8 Megapixel CMOS image sensor, which allow the collection of images of Silver, Aged, and Extra-aged tequila samples. Image processing is performed mimicking the trichromatic theory of color vision using an analysis of Red, Green, and Blue components (RGB) for each image's pixel. Consequently, RGB absorbances of images were evaluated and preprocessed, employing Principal Component Analysis (PCA) to visualize data clustering. The resulting PCA scores were modeled with a Linear Discriminant Analysis (LDA) that accomplished the qualitative classification of tequilas. A Leave-One-Out Cross-Validation (LOOCV) procedure was performed to evaluate classifiers' performance. The proposed system allowed the identification of real tequila samples achieving an overall classification rate of 90.02%, average sensitivity, and specificity of 0.90 and 0.96, respectively, while Cohen's kappa coefficient was 0.87. In this case, the EE has demonstrated a favorable capability to correctly discriminated and classified the different tequila samples according to their categories.

Bimanual wheelchair propulsion by people with severe hemiparesis after stroke.

PURPOSE: Individuals who require manual wheelchairs after stroke are typically taught to ambulate with compensatory propulsion (i.e., using their non-paretic arm and foot), risking disuse of the paretic arm. We investigated whether stroke survivors can instead ambulate in a bimanual, lever-driven wheelchair that requires the paretic arm to contribute half the propulsive input. MATERIALS AND METHODS: Seventeen individuals with chronic stroke and severe hemiparesis (upper extremity Fugl-Meyer scores between 10 and 24) participated across two experiments. In the first experiment, participants (n = 12) ambulated in straight paths. In the second experiment, participants (n = 12) also performed turns, using an improved version of the wheelchair that incorporated handbrakes. Twelve unimpaired controls also completed the second experiment. Motion capture and EMG were used to compare biomechanics between groups. RESULTS: Altogether, 15 of 17 participants with stroke could ambulate 30 m in straight paths, and 9 of 12 could turn 1800° entirely under the power of their paretic arm. Participants with stroke exhibited largely healthy biomechanics, with minimal shoulder hiking/leaning or trunk inclination. Their arm muscle EMG patterns were similar to those used by unimpaired participants, excepting delayed elbow extensor activation. CONCLUSIONS: Individuals with severe arm impairment in the chronic stage of stroke retain sufficient strength and coordination with their paretic arm to manoeuvre bimanual, lever-driven wheelchairs. We suggest bimanual, lever-driven propulsion should be explored in stroke rehabilitation practice as an alternative to compensatory wheelchair propulsion, as it has the potential to exercise healthy movement synergies, which may in turn help drive use-dependent motor recovery. Implications for rehabilitation Severe arm impairment arising after stroke does not generally eliminate the motor dexterity needed to bimanually propel a manual wheelchair, provided that the wheelchair is modified to remove the requirement to grasp and release the push rim. Such exercise appears a good candidate to facilitate rehabilitation outcomes because it depends on alternating muscle activity and improving elbow extension. Such wheelchair propulsion involves largely normal biomechanics; shoulder hiking and leaning are absent and trunk inclination is rare.

Neuromusculoskeletal model self-calibration for on-line sequential bayesian moment estimation.

OBJECTIVE: Neuromusculoskeletal models involve many subject-specific physiological parameters that need to be adjusted to adequately represent muscle properties. Traditionally, neuromusculoskeletal models have been calibrated with a forward-inverse dynamic optimization which is time-consuming and unfeasible for rehabilitation therapy. Non self-calibration algorithms have been applied to these models. To the best of our knowledge, the algorithm proposed in this work is the first on-line calibration algorithm for muscle models that allows a generic model to be adjusted to different subjects in a few steps. APPROACH: In this paper we propose a reformulation of the traditional muscle models that is able to sequentially estimate the kinetics (net joint moments), and also its full self-calibration (subject-specific internal parameters of the muscle from a set of arbitrary uncalibrated data), based on the unscented Kalman filter. The nonlinearity of the model as well as its calibration problem have obliged us to adopt the sum of Gaussians filter suitable for nonlinear systems. MAIN RESULTS: This sequential Bayesian self-calibration algorithm achieves a complete muscle model calibration using as input only a dataset of uncalibrated sEMG and kinematics data. The approach is validated experimentally using data from the upper limbs of 21 subjects. SIGNIFICANCE: The results show the feasibility of neuromusculoskeletal model self-calibration. This study will contribute to a better understanding of the generalization of muscle models for subject-specific rehabilitation therapies. Moreover, this work is very promising for rehabilitation devices such as electromyography-driven exoskeletons or prostheses.

Colorimetric Analysis of Ochratoxin A in Beverage Samples.

This manuscript describes the use of a portable and low cost fluorescence setup to quantify the concentration of ochratoxin A (OTA) in beverage samples using an in-house developed system and different color models. It is reported that OTA is naturally fluorescent, for that reason an ultraviolet light at 365 nm was used to excite the samples and a Complementary Metal Oxide Semiconductor (CMOS) sensor was used to get a photograph of the OTA under excitation conditions, which is controlled by an executable interface designed in MATLAB. For each concentration of OTA, the coordinates with respect to each model color were obtained and plotted to quantify the mycotoxin present in the sample. It was possible to observe that despite the fact no extraction column was employed, the Red, Green, Blue (RGB) model shows a proportional relation to the evaluated concentrations. Despite the fact more analysis and other methods are required to quantify the OTA concentration, the brightness and a,b for the color-opponent dimensions (L*a*b) and Hue, Saturation, Value (HSV) tests provide results whereby it is possible to identify the concentration of OTA in beverage samples such as beer and wine.

Portable and low cost fluorescence set-up for in-situ screening of Ochratoxin A.

The present article describes a portable and low cost fluorescence set-up designed and characterized for in-situ screening of Ochratoxin A (OTA) in cocoa samples at field settings. The sensing module (the set up) consists of a LED with the wavelength of 370-380nm and a color complementary metal oxide semiconductor (CMOS) micro-camera inbuilt at upright position of a black box to obtain an image of the sensing molecule. It allows the user to get an image of the sensing analytes under excitation conditions and process the image in order to predict the toxicity of the samples. The image capturing and processing of the system was based on the OTA concentration in the sample and analyzed data can be presented as RGB values. For each concentration of the OTA, the R, G, B co-ordinates were obtained and plotted to quantify actual OTA presents in the sample. Moreover, the system was tested for real sample analysis using cocoa contaminated with OTA. The system could detect OTA as low as 1.25ng/ml with the maximum recovery of 87.5% in cocoa samples. The OTA was extracted in 1% NaHCO3 and cleaned up using molecular imprinted polymer column (MIP). The method demonstrated a good linear range between 1.25 and 10ng/ml. The obtained results were cross validated using chromatographic method HPLC and also compared with commercially available fluorescence instrument. The developed fluorescence setup is simple, economical, and portable with added advantages of digital image processing. The system could be deployable to cocoa fields for monitoring of OTA in quick successions. It is noteworthy to mention that this is the first report of such portable fluorescence setup where, OTA sensing was explored.

Ligand Assisted Stabilization of Fluorescence Nanoparticles; an Insight on the Fluorescence Characteristics, Dispersion Stability and DNA Loading Efficiency of Nanoparticles.

This work reports on the ligand assisted stabilization of Fluospheres® carboxylate modified nanoparticles (FCMNPs), and subsequently investigation on the DNA loading capacity and fluorescence response of the modified particles. The designed fluorescence bioconjugate was characterized with enhanced fluorescence characteristics, good stability and large surface area with high DNA loading efficiency. For comparison purpose, bovine serum albumin (BSA) and polyethylene glycol (PEG) with three different length strands were used as cross linkers to modify the particles, and their DNA loading capacity and fluorescence characteristics were investigated. By comparing the performance of the particles, we found that the most improved fluorescence characteristics, enhanced DNA loading and high dispersion stability were obtained, when employing PEG of long spacer arm length. The designed fluorescence bioconjugate was observed to maintain all its characteristics under varying pH over an extended period of time. These types of bioconjugates are in great demand for fluorescence imaging and in vivo fluorescence biomedical application, especially when most of the as synthesized fluorescence particles cannot withstand to varying in vivo physiological conditions with decreases in fluorescence response and DNA loading efficiency.

Effect of muscular fatigue on fractal upper limb coordination dynamics and muscle synergies.

Rehabilitation exercises cause fatigue because tasks are repetitive. Therefore, inevitable human motion performance changes occur during the therapy. Although traditionally fatigue is considered an event that occurs in the musculoskeletal level, this paper studies whether fatigue can be regarded as context that influences lower-dimensional motor control organization and coordination at neural level. Non Negative Factorization Matrix (NNFM) and Detrended Fluctuations Analysis (DFA) are the tools used to analyze the changes in the coordination of motor function when someone is affected by fatigue. The study establishes that synergies remain fairly stable with the onset of fatigue, but the fatigue affects the dynamical coordination understood as a cognitive process. These results have been validated with 9 healthy subjects for three representative exercises for upper limb: biceps, triceps and deltoid.

Muscular fatigue detection using sEMG in dynamic contractions.

In this work we have studied different indicators of muscle fatigue from the electrical signal produced by the muscles when contract (sEMG or EMG: surface electromyography): Mean Frequency of the power spectrum (MNF), Median Frequency (Fmed), Dimitrov Spectral Index (FInsm5), Root Mean Square (RMS), and Zerocrossing (ZC). The most reliable features are selected to develop a detection algorithm that estimates muscle fatigue. The approach used in the algorithm is probabilistic and is based on the technique of Gaussian Mixture Model (GMM). The system is divided into two stages: training and validation. During training, the algorithm learns the distribution of data regarding fatigue evolution; after that, the algorithm is validated with data that have not been used to train. Therefore, two experimental sessions have been performed with 6 healthy subjects for biceps.

Multijoint upper limb torque estimation from sEMG measurements.

Estimation of joint torques through musculoskeletal models and measurements of muscle activations can be used for real-time control of robotic devices for rehabilitation. Many works developed models for analytic one joint motion, but less are found that develop models for functional multijoint movements. In this work we develop a methodology for tuning and optimizing Hill-based EMG-driven models oriented to the force control of robotic exoskeletons for the upper limb, selecting the more suitable parameters to be optimized. The model is tuned from experimental data obtained from healthy people. The torques estimated by that model will serve as reference for force-based control of an exoskeleton for rehabilitation.

An optimized model for estimation of muscle contribution and human joint torques from sEMG information.

This paper develops a Hill model based technique to estimate human elbow torque from sEMG measurements. Some new parameters are included in the optimization process in order to improve the resulting estimated torque. These parameters correspond to activation levels of muscles involved in motion generation. They have not previously been used in other works dealing with this kind of model. Results from experiments with several subjects in different movement conditions and using the new optimized parameters lead to some conclusions about the generality of the optimized models and the influence of the new parameters on the improvement of the estimation.

El método de ADL y la metapsicoetología humana: análisis de un acto del habla / Adlmethodology and human metapsychoethology: Speech acts analysis

Por metapsicoetología humana se entiende el campo de investigación psicoanalítica acerca de los vínculos humanos con los animales domésticos. La etología humana se incorpora a la metapsicología freudiana como la disciplina que se ocupa del comportamiento del animal doméstico en relación con el humano. El nexo entre los campos mencionados se promueve por la aplicación del método algorítmico David Liberman o ALD, diseñado y desarrollado por David Maldavsky para la investigación sistemática del lenguaje de las erogeneidades y las defensas como manifestaciones centrales de la subjetividad y de la intersubjetividad. El método ADL estudia el discurso en tres niveles: palabra, relato y acto del habla. En esta oportunidad, la autora analiza un acto del habla proferido por Eduardo, un ciruja que vive con tres perros, en ocasión de acercarse a él para concretar una entrevista. Se trata de una frase en acto que permite detectar las escenas que se despliegan en los intercambios entre los actores. El acto del habla es analizado en sus componentes: verbal, paraverbal, táctil, motriz y de los intercambios intersubjetivos.