The Rat Genome Database (RGD) facilitates genomic and phenotypic data integration across multiple species for biomedical research.

Model organism research is essential for discovering the mechanisms of human diseases by defining biologically meaningful gene to disease relationships. The Rat Genome Database (RGD, ( https://rgd.mcw.edu )) is a cross-species knowledgebase and the premier online resource for rat genetic and physiologic data. This rich resource is enhanced by the inclusion and integration of comparative data for human and mouse, as well as other human disease models including chinchilla, dog, bonobo, pig, 13-lined ground squirrel, green monkey, and naked mole-rat. Functional information has been added to records via the assignment of annotations based on sequence similarity to human, rat, and mouse genes. RGD has also imported well-supported cross-species data from external resources. To enable use of these data, RGD has developed a robust infrastructure of standardized ontologies, data formats, and disease- and species-centric portals, complemented with a suite of innovative tools for discovery and analysis. Using examples of single-gene and polygenic human diseases, we illustrate how data from multiple species can help to identify or confirm a gene as involved in a disease and to identify model organisms that can be studied to understand the pathophysiology of a gene or pathway. The ultimate aim of this report is to demonstrate the utility of RGD not only as the core resource for the rat research community but also as a source of bioinformatic tools to support a wider audience, empowering the search for appropriate models for human afflictions.

[Robot therapy with the H2 exoskeleton for gait rehabilitation in patients with incomplete spinal cord injry. A clinical experience]. / Terapia robótica con el exoesqueleto H2 en la rehabilitación de la marcha en pacientes con lesión medular incompleta. Una experiencia clínica.

BACKGROUND AND OBJECTIVE: Robotic exoskeletons have emerged as a promising tool in gait rehabilitation in patients with a spinal cord injury. The aim of this study was to assess the clinical applicability of a new robotic exoskeleton model (Exo H2) in the rehabilitation of people with incomplete spinal cord injury. MATERIAL AND METHODS: Exo H2 exoskeleton training was performed for 15 sessions in patients with incomplete subacute spinal cord injury. We analysed the appearance of undesirable events and the patient's perception of pain, fatigue and comfort. In addition, a pilot test was carried out on the possible effectiveness of the device by analysing gait characteristics before and after treatment measured by the 10mWT, the 6mWT, the TUG, the WISCI-II, and the impact on the SCIM III scale. RESULTS: Of a group of 8 patients recruited, we were able to analyse data from 4. No undesirable effects were reported. The VAS value was 2.28±1.55 for pain, 3.75±1.55 for fatigue and 4.17±1.68 for comfort. All values improved on the WISCI-I and the TUG and almost all in the 10MWT and in the 6MWT. CONCLUSIONS: The performance of the Exo H2 exoskeleton was robust during a clinical protocol for gait rehabilitation. The treatment was safe, without undesirable effects and with good patient tolerance. These results might justify the performance of clinical trials with an adequate sample size.

[Subcontracting a steam sterilization activity: Impact on surgical instruments]. / Externalisation de l'activité de stérilisation : impact sur l'état des instruments chirurgicaux.

Subcontracting our institution's sterilization activity induced the implementation of an automated cleaning facility. Following this development, some of the resterilizable stainless steel needle holders started to show abnormal corrosion. Our study goal was to investigate the causes of this corrosion in order to optimize the sterilization circuit. A full sterilization process mapping and Ishikawa diagram enabled us to identify potential causes of corrosion. The needle holders' intrinsic characteristics, like steel quality and manufacturing, were analyzed as well as extrinsic factors such as the influence of preprocessing soaking conditions, steel passivation, water quality and the impact of corrosion inhibitors. Each potential factor of corrosion was tested in real conditions on needle holders' kits. The needle holders steel grade complies with medical standards and the tests showed that passivation and pre-processing conditions were not involved in the occurrence of corrosion, contrary to soaking length and use of softened rinsing water, containing more chloride than reverse osmosis water, and, thus conducive to rust formation. Moreover, corrosion inhibitors were deemed ineffective or incompatible. Due to this analysis, the incidence of corrosion was reduced by switching softened water to osmosis water and by introducing dynamic drying in the automated cleaning process. In addition, this work stresses the importance of minimizing waiting times and auditing the sterilization circuit before any subcontracting. Management Guidelines related to sterilization's outsourcing would probably have helped to limit this episode.

Synthesis of aminophenylhydroxamate and aminobenzylhydroxamate derivatives and in vitro screening for antiparasitic and histone deacetylase inhibitory activity.

A series of aminophenylhydroxamates and aminobenzylhydroxamates were synthesized and screened for their antiparasitic activity against Leishmania, Trypanosoma, and Toxoplasma. Their anti-histone deacetylase (HDAC) potency was determined. Moderate to no antileishmanial or antitrypanosomal activity was found (IC50 > 10 µM) that contrast with the highly efficient anti-Toxoplasma activity (IC50 < 1.0 µM) of these compounds. The antiparasitic activity of the synthetized compounds correlates well with their HDAC inhibitory activity. The best-performing compound (named 363) express a high anti-HDAC6 inhibitory activity (IC50 of 0.045 ±â€¯0.015 µM) a moderate cytotoxicity and a high anti-Toxoplasma activity in the range of known anti-Toxoplasma compounds (IC50 of 0.35-2.25 µM). The calculated selectivity index (10-300 using different human cell lines) of the compound 363 makes it a lead compound for the future development of anti-Toxoplasma molecules.

Adaptive hybrid robotic system for rehabilitation of reaching movement after a brain injury: a usability study.

BACKGROUND: Brain injury survivors often present upper-limb motor impairment affecting the execution of functional activities such as reaching. A currently active research line seeking to maximize upper-limb motor recovery after a brain injury, deals with the combined use of functional electrical stimulation (FES) and mechanical supporting devices, in what has been previously termed hybrid robotic systems. This study evaluates from the technical and clinical perspectives the usability of an integrated hybrid robotic system for the rehabilitation of upper-limb reaching movements after a brain lesion affecting the motor function. METHODS: The presented system is comprised of four main components. The hybrid assistance is given by a passive exoskeleton to support the arm weight against gravity and a functional electrical stimulation device to assist the execution of the reaching task. The feedback error learning (FEL) controller was implemented to adjust the intensity of the electrical stimuli delivered on target muscles according to the performance of the users. This control strategy is based on a proportional-integral-derivative feedback controller and an artificial neural network as the feedforward controller. Two experiments were carried out in this evaluation. First, the technical viability and the performance of the implemented FEL controller was evaluated in healthy subjects (N = 12). Second, a small cohort of patients with a brain injury (N = 4) participated in two experimental session to evaluate the system performance. Also, the overall satisfaction and emotional response of the users after they used the system was assessed. RESULTS: In the experiment with healthy subjects, a significant reduction of the tracking error was found during the execution of reaching movements. In the experiment with patients, a decreasing trend of the error trajectory was found together with an increasing trend in the task performance as the movement was repeated. Brain injury patients expressed a great acceptance in using the system as a rehabilitation tool. CONCLUSIONS: The study demonstrates the technical feasibility of using the hybrid robotic system for reaching rehabilitation. Patients' reports on the received intervention reveal a great satisfaction and acceptance of the hybrid robotic system. TRIAL REGISTRATION: Retrospective trial registration in ISRCTN Register with study ID ISRCTN12843006 .

Simultaneous estimation of human and exoskeleton motion: A simplified protocol.

Adequate benchmarking procedures in the area of wearable robots is gaining importance in order to compare different devices on a quantitative basis, improve them and support the standardization and regulation procedures. Performance assessment usually focuses on the execution of locomotion tasks, and is mostly based on kinematic-related measures. Typical drawbacks of marker-based motion capture systems, gold standard for measure of human limb motion, become challenging when measuring limb kinematics, due to the concomitant presence of the robot. This work answers the question of how to reliably assess the subject's body motion by placing markers over the exoskeleton. Focusing on the ankle joint, the proposed methodology showed that it is possible to reconstruct the trajectory of the subject's joint by placing markers on the exoskeleton, although foot flexibility during walking can impact the reconstruction accuracy. More experiments are needed to confirm this hypothesis, and more subjects and walking conditions are needed to better characterize the errors of the proposed methodology, although our results are promising, indicating small errors.

Towards an ankle neuroprosthesis for hybrid robotics: Concepts and current sources for functional electrical stimulation.

Hybrid rehabilitation robotics combine neuro-prosthetic devices (close-loop functional electrical stimulation systems) and traditional robotic structures and actuators to explore better therapies and promote a more efficient motor function recovery or compensation. Although hybrid robotics and ankle neuroprostheses (NPs) have been widely developed over the last years, there are just few studies on the use of NPs to electrically control both ankle flexion and extension to promote ankle recovery and improved gait patterns in paretic limbs. The aim of this work is to develop an ankle NP specifically designed to work in the field of hybrid robotics. This article presents early steps towards this goal and makes a brief review about motor NPs and Functional Electrical Stimulation (FES) principles and most common devices used to aid the ankle functioning during the gait cycle. It also shows a current sources analysis done in this framework, in order to choose the best one for this intended application.

Modular control of gait after incomplete spinal cord injury: differences between sides.

STUDY DESIGN: This is an analytical descriptive study. OBJECTIVES: The main goal of this study was to compare the modular organization of bilateral lower limb control in incomplete spinal cord injury (iSCI) patients during overground walking, using muscle synergies analysis. The secondary goal was to determine whether the similarity between the patients and control group correlate with clinical indicators of walking performance. SETTING: This study was conducted in National Hospital for Spinal Cord Injury (Toledo, Spain). METHODS: Eight iSCI patients and eight healthy subjects completed 10 walking trials at matched speed. For each trial, three-dimensional motion analysis and surface electromyography (sEMG) analysis of seven leg muscles from both limbs were performed. Muscle synergies were extracted from sEMG signals using a non-negative matrix factorization algorithm. The optimal number of synergies has been defined as the minimum number needed to obtain variability accounted for (VAF) ⩾90%. RESULTS: When compared with healthy references, iSCI patients showed fewer muscle synergies in the most affected side and, in both sides, significant differences in the composition of synergy 2. The degree of similarity of these variables with the healthy reference, together with the composition of synergy 3 of the most affected side, presented significant correlations (P<0.05) with walking performance. CONCLUSION: The analysis of muscle synergies shows potential to detect differences between the two sides in patients with iSCI. Specifically, the VAF may constitute a new neurophysiological metric to assess and monitor patients' condition throughout the gait recovery process.

Usefulness of daily surveillance blood cultures in allogeneic hematopoietic stem cell transplant recipients on steroids: a 1-year prospective study.

BACKGROUND: Bloodstream infections (BSI) are frequent and potentially severe complications in allogeneic hematopoietic stem cell transplant (AHSCT) recipients. In patients on steroids, surveillance blood cultures (SBCs) are routinely performed to detect asymptomatic BSI but their usefulness remains controversial. METHODS: We performed a 1-year, observational, prospective, single-center study to assess the utility of daily SBCs in AHSCT recipients on steroids and a case-control study to identify risk factors associated with positive SBCs. All blood cultures (BCs) obtained from adults hospitalized in the HSCT unit were prospectively studied throughout 1 year. Characteristics, treatments, and outcome of patients were retrieved from medical charts. RESULTS: A total of 3594 BCs were obtained in 177 patients, including 1450 SBCs in 82 AHSCT recipients on steroids. In 33 patients, 103 SBCs (7%) were positive. Low-virulence bacteria were identified in 74% of episodes. When analyzing first episode of positive SBCs (28 patients), 6 (21%) true BSI were identified. CONCLUSIONS: Patients with positive SBCs were receiving antibiotic treatment less frequently at the time of SBCs (P < 0.001) and had more frequently BCs obtained through central venous access (P < 0.04) when compared to patients with negative SBCs. Daily SBCs in AHSCT recipients on steroids only rarely identify BSI and clear benefit for patients could not be demonstrated.

Predictive classification of self-paced upper-limb analytical movements with EEG.

The extent to which the electroencephalographic activity allows the characterization of movements with the upper limb is an open question. This paper describes the design and validation of a classifier of upper-limb analytical movements based on electroencephalographic activity extracted from intervals preceding self-initiated movement tasks. Features selected for the classification are subject specific and associated with the movement tasks. Further tests are performed to reject the hypothesis that other information different from the task-related cortical activity is being used by the classifiers. Six healthy subjects were measured performing self-initiated upper-limb analytical movements. A Bayesian classifier was used to classify among seven different kinds of movements. Features considered covered the alpha and beta bands. A genetic algorithm was used to optimally select a subset of features for the classification. An average accuracy of 62.9 ± 7.5% was reached, which was above the baseline level observed with the proposed methodology (30.2 ± 4.3%). The study shows how the electroencephalography carries information about the type of analytical movement performed with the upper limb and how it can be decoded before the movement begins. In neurorehabilitation environments, this information could be used for monitoring and assisting purposes.

Detection of the onset of upper-limb movements based on the combined analysis of changes in the sensorimotor rhythms and slow cortical potentials.

OBJECTIVE: Characterizing the intention to move by means of electroencephalographic activity can be used in rehabilitation protocols with patients' cortical activity taking an active role during the intervention. In such applications, the reliability of the intention estimation is critical both in terms of specificity 'number of misclassifications' and temporal accuracy. Here, a detector of the onset of voluntary upper-limb reaching movements based on the cortical rhythms and the slow cortical potentials is proposed. The improvement in detections due to the combination of these two cortical patterns is also studied. APPROACH: Upper-limb movements and cortical activity were recorded in healthy subjects and stroke patients performing self-paced reaching movements. A logistic regression combined the output of two classifiers: (i) a naïve Bayes classifier trained to detect the event-related desynchronization preceding the movement onset and (ii) a matched filter detecting the bereitschaftspotential. The proposed detector was compared with the detectors by using each one of these cortical patterns separately. In addition, differences between the patients and healthy subjects were analysed. MAIN RESULTS: On average, 74.5 ± 13.8% and 82.2 ± 10.4% of the movements were detected with 1.32 ± 0.87 and 1.50 ± 1.09 false detections generated per minute in the healthy subjects and the patients, respectively. A significantly better performance was achieved by the combined detector (as compared to the detectors of the two cortical patterns separately) in terms of true detections (p = 0.099) and false positives (p = 0.0083). SIGNIFICANCE: A rationale is provided for combining information from cortical rhythms and slow cortical potentials to detect the onsets of voluntary upper-limb movements. It is demonstrated that the two cortical processes supply complementary information that can be summed up to boost the performance of the detector. Successful results have been also obtained with stroke patients, which supports the use of the proposed system in brain-computer interface applications with this group of patients.

A tool for balance control training using muscle synergies and multimodal interfaces.

Balance control plays a key role in neuromotor rehabilitation after stroke or spinal cord injuries. Computerized dynamic posturography (CDP) is a classic technological tool to assess the status of balance control and to identify potential disorders. Despite the more accurate diagnosis generated by these tools, the current strategies to promote rehabilitation are still limited and do not take full advantage of the technologies available. This paper presents a novel balance training platform which combines a CDP device made from low-cost interfaces, such as the Nintendo Wii Balance Board and the Microsoft Kinect. In addition, it integrates a custom electrical stimulator that uses the concept of muscle synergies to promote natural interaction. The aim of the platform is to support the exploration of innovative multimodal therapies. Results include the technical validation of the platform using mediolateral and anteroposterior sways as basic balance training therapies.

Task independent identification of sensor location on upper limb from orientation data.

In this paper we describe a novel method for sensor placement identification, and demonstrate the effectiveness of this method on an upper limb neuroprothesis for tremor suppression under a variety of tasks. Our objective is to facilitate long-term tremor monitoring; tremor is the most prevalent movement disorder. Two assumptions are made: 1) movement and tremor demonstrate an additive effect further down the kinematic chain; 2) most applications have chained or fixed sensor locations. These assumptions justify obtaining absolute location through identifying relative location and thus to allow us to simplify the classification algorithm. Seventeen tasks were performed by patients suffering from essential tremor or Parkinson's disease. Ten features were found that resulted in 98.30% average accuracy (min: 92.31%; max: 100%) for the best configuration, irrespective of the task being performed. The method presented here is an important step towards more user-friendly and context-aware neuroprostheses for tremor suppression and monitoring, and facilitates the use of wearable sensors by non-trained personnel.

Upper-limb muscular electrical stimulation driven by EEG-based detections of the intentions to move: a proposed intervention for patients with stroke.

This study proposes an intervention for stroke patients in which electrical stimulation of muscles in the affected arm is supplied when movement intention is detected from the electroencephalographic signal. The detection relies on the combined analysis of two movement related cortical patterns: the event-related desynchronization and the bereitschaftspotential. Results with two healthy subjects and three chronic stroke patients show that reliable EEG-based estimations of the movement onsets can be generated (on average, 66.9 ± 26.4 % of the movements are detected with 0.42 ± 0.17 false activations per minute) which in turn give rise to electrical stimuli providing sensory feedback tightly associated to the movement planning (average detection latency of the onsets of the movements was 54.4 ± 287.9 ms).

Principles of human locomotion: a review.

In this article the principles of human locomotion are revisited and reviewed. This has been done in the framework of two European projects, where the elicitation of these mechanisms inform, on the one hand, the design of artificial bipedal walkers (H2R), and on the other hand the design of lower limb exoskeletons (BETTER) for rehabilitation of gait in post-stroke patients. Passive dynamics emerging from the morphology of the human musculoskeletal system, reflexes as stabilization mechanisms, modular control of movement as well as supra-spinal control of gait are reviewed to get insight on how these mechanisms can be used to explain human locomotion.

Design and validation of a neuroprosthesis for the treatment of upper limb tremor.

Pathological tremor is the most prevalent movement disorder. In spite of the existence of various treatments for it, tremor poses a functional problem to a large proportion of patients. This paper presents the design and implementation of a novel neuroprosthesis for tremor management. The paper starts by reviewing a series of design criteria that were established after analyzing users needs and the expected functionality of the system. Then, it summarizes the design of the neuroprosthesis, which was built to meet the criteria defined previously. Experimental results with a representative group of 12 patients show that the neuroprosthesis provided significant (p < 0.001) and systematic tremor attenuation (in average 52.33 ± 25.48 %), and encourage its functional evaluation as a potential new treatment for tremor in a large cohort of patients.

A novel FES control paradigm based on muscle synergies for postural rehabilitation therapy with hybrid exoskeletons.

Hybrid exoskeletons combine robotic orthoses and motor neuroprosthetic devices to compensate for motor disabilities and assist rehabilitation. The basic idea is to take benefits from the strength of each technology, primarily the power of robotic actuators and the clinical advantages of using patient's muscles, while compensating for the respective weaknesses: weight and autonomy for the former, fatigue and stability for the latter. While a wide repertory of solutions have been proposed in literature for the control of robotic orthoses and simple motor neuroprosthesis, the same problem on a complex hybrid architecture, involving a wide number of muscles distributed on multiple articulations, still waits for a practical solution. In this article we present a general algorithm for the control of the neuroprosthesis in the execution of functional coordinated movements. The method extracts muscle synergies as a mean to diagnose residual neuromotor capabilities, and adapts the rehabilitation exercise to patient requirements in a dynamic way. Fatigue effects and unexpected perturbations are compensated by monitoring functional state variables estimated from sensors in the robot. The proposed concept is applied to a case-study scenario, in which a postural balance rehabilitation therapy is presented.

Modular control of mediolateral postural sway.

Is voluntary motor control of mediolateral rhythmic sway ruled by modular organization? Answering this question has potential implications in diagnosis and rehabilitation of neurologically impairments. Superficial EMG and computerized dynamic posturography has been used in this study to investigate modular control of six healthy subjects. Postural movements have been performed at three different frequencies to also test the influence of speed on the composition of synergies and activations. Results showed that two synergies account for more than 75% of EMG variance and are shared by all subjects across all frequency conditions. These evidences, together with a functional interpretation of computed muscle synergies, support the existence of consistent modular control across healthy subjects during mediolateral voluntary movements.

Analysis of biomechanical data to determine the degree of users participation during robotic-assisted gait rehabilitation.

Recent studies have shown evidence indicating that effective robotic rehabilitation is only possible when the user actively participates during training. Providing a complete effective biofeedback to the patient representing his compliance to the therapy and his performance is thought that his active participation will be enhanced significantly, thus, improving his rehabilitation. We have performed a study with the driven gait orthosis (DGO) Lokomat (Hocoma AG, Volketswil, Switzerland). The objective of the present study is the analysis of the effect of different types of participation (attention to the functional task) from subjects receiving robotic assisted gait training on the kinematic and kinetic patterns. The obtained results provide useful evidence of specific biomechanical features that can be used to design more useful, robust, focused and intuitive biomechanical biofeedback during robotic assisted gait rehabilitation in stroke survivors.

[Does pulmonary contusion expose to the risk of Streptococcus pneumoniae infections? Results of an experimental study]. / La contusion pulmonaire expose-t-elle au risque de prolifération bactérienne à pneumocoque ? Résultats d'une étude expérimentale.

OBJECTIVE: To create a reliable and reproducible model of pulmonary contusion (PC) in rats in order to evaluate the influence of PC on bacterial lung proliferation. STUDY DESIGN: Experimental. ANIMALS: Male albino CD rats. METHODS: Animals were anesthetized and a PC was performed using a spring-loaded metal bar. The existence of an isolated right PC was confirmed by macroscopic, histological and radiological analysis. This model was used to compare four randomized groups of animals. These were either injured or only anesthetized and inoculated with a pneumococcal solution concentrated in 2 or 4 log(CFU/mL). The animals' lungs were collected for microbiological culture at 24 hours. The bacterial count evolution per gram of lung was the primary endpoint. RESULTS: Twelve rats were needed to validate the model, 84 to determine the morbidity and mortality and its reproducibility and 66 to assess the intra-pulmonary bacterial proliferation. The PC obtained was unilateral and isolated in 95% of cases. Mortality rate was 43%. For a low initial inoculum concentration (2 log [CFU/mL]), there is bacterial overgrowth in the PC group versus the no-PC group (P=0.0017). This difference was not found when the inoculum was more concentrated. CONCLUSION: This experimental model is reliable and reproducible. The initially high mortality seems to decrease with the experience of operators. The CP significantly increases intra-pulmonary bacterial proliferation when the inoculation is low. A high inoculum neutralizes the effect of CP. These results suggest that enhanced prevention of micro-inhalation could be beneficial in cases of CP.