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.

[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.

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.

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 .

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.

[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.

Study of the motion artefacts of skin-mounted inertial sensors under different attachment conditions.

A common problem shared by accelerometers, inertial sensors and any motion measurement method based on skin-mounted sensors is the movement of the soft tissues covering the bones. The aim of this work is to propose a method for the validation of the attachment of skin-mounted sensors. A second-order (mass-spring-damper) model was proposed to characterize the behaviour of the soft tissue between the bone and the sensor. Three sets of experiments were performed. In the first one, different procedures to excite the system were evaluated to select an adequate excitation stimulus. In the second one, the selected stimulus was applied under varying attachment conditions while the third experiment was used to test the model. The heel drop was chosen as the excitation method because it showed lower variability and could discriminate between different attachment conditions. There was, in agreement with the model, a trend to increase the natural frequency of the system with decreasing accelerometer mass. An important result is the development of a standard procedure to test the bandwidth of skin-mounted inertial sensors, such as accelerometers mounted on the skin or markers heavier than a few grams.

[Importance of the time for stopping the combined use of aspirin and clopidogrel in patients undergoing coronary artery by-pass graft surgery]. / Importancia del tiempo de suspensión del uso combinado de aspirina y clopidogrel en pacientes sometidos a cirugía de revascularización coronaria.

The combined use of aspirin and clopidogrel is the standard of care for patients with acute coronary syndromes. The risk for perioperative bleeding is considerably increased after coronary artery by-pass graft surgery (CABG). This study was designed to evaluate the effect of antiplatelet therapy on perioperative CABG outcome. We studied 49 consecutive patients undergoing first time CABG, and compared two groups: Group A, patients who stopped antiplatelet treatment at least 6 days before surgery, and group B, those who received antiplatelet therapy within 5 days before surgery or did not suspended therapy. The groups were comparable in their demographic characteristics, manifestations of disease, perioperative medication use and the characteristics of surgery. There was a non significant tendency for more cardiovascular complications (primary cardiovascular endpoint) in the group that stopped antiplatelet therapy 6 or more days before surgery (Group A 12%, group B 8%; p = 0.923). The bleeding endpoint was significantly higher in group B, that remained on antiplatelet therapy within 5 days before surgery (Group A 4%, group B 29%; p = 0.023), as well as the need for transfusion. We concluded that the combined use of aspirin and clopidogrel before CABG increases postoperative bleeding and morbidity; there was no definitive difference in the cardiovascular outcome.

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.

Design and validation of a rehabilitation robotic exoskeleton for tremor assessment and suppression.

Exoskeletons are mechatronic systems worn by a person in such a way that the physical interface permits a direct transfer of mechanical power and exchange of information. Upper limb robotic exoskeletons may be helpful for people with disabilities and/or limb weakness or injury. Tremor is the most common movement disorder in neurological practice. In addition to medication, rehabilitation programs, and deep brain stimulation, biomechanical loading has appeared as a potential tremor suppression alternative. This paper introduces the robotic exoskeleton called WOTAS (wearable orthosis for tremor assessment and suppression) that provides a means of testing and validating nongrounded control strategies for orthotic tremor suppression. This paper describes in detail the general concept for WOTAS, outlining the special features of the design and selection of system components. Two control strategies developed for tremor suppression with exoskeletons are described. These two strategies are based on biomechanical loading and notch filtering the tremor through the application of internal forces. Results from experiments using these two strategies on patients with tremor are summarized. Finally, results from clinical trials are presented, which indicate the feasibility of ambulatory mechanical suppression of tremor.

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.

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.

[Infectious or inflammatory aortitis? One case report]. / Aortite infectieuse ou inflammatoire ? A propos d'un cas.

INTRODUCTION: The infectious or inflammatory nature of an aortitis is difficult to assert because the microbiological results are often negative. The development of an aneurysm under treatment is rare, but requires a change in the therapeutic strategy and the etiologic diagnosis needs to be discussed again. EXEGESIS: We report the case of a 69-year-old woman treated by corticotherapy for an aortitis thought to be inflammatory, who required emergency surgery when a dissected aneurysm appeared. The peroperative samples were positive to Streptococcus pneumoniae using polymerase chain reaction and allowed a change of the diagnosis. The patient evolved favorably under antibiotic therapy. CONCLUSION: The decision to treat an aortitis by corticotherapy must be made with caution even if the microbiological tests are negative.

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.

Multilocus enzyme typing of human and animal strains of Clostridium perfringens.

Multilocus enzyme electrophoresis was developed to evaluate the genetic diversity of 71 human strains and 17 animal strains of Clostridium perfringens. Crude protein extracts, obtained by sonication of washed bacteria, were analyzed by polyacrylamide-agarose gel electrophoresis to characterize electrophoretic mobility variants of seven enzymes (esterase, glutamate dehydrogenase, glutamic-oxaloacetic transaminase, nucleoside phosphorylase, phosphoglucose isomerase, phosphoglucomutase, threonine dehydrogenase). Genetic diversity of the enzyme loci ranged from 0.340 to 0.813. Sixty-nine electrophoretic types were described among the 88 strains tested and the index of discrimination was 0.994. All strains were typable, and epidemiological relationships between isolates could be established. This method showed a fair correlation with esterase electrophoretic typing based on hydrolytic and electrophoretic polymorphism of esterases. This work demonstrates that multilocus enzyme polymorphism is a reliable and discriminant marker of genetic diversity of strains of C. perfringens.

Comparison of MRC-5 and continuous cell lines for detection of cytomegalovirus in centrifugation cultures.

Continuous cell lines were assessed for use for rapid human cytomegalovirus (HCMV) detection procedures combining tissue culture, centrifugation, and immediate early antigen (IEA) immunostaining. Human cells (MRC-5 embryonic fibroblasts, U-373MG astrocytoma cells, differentiated teratocarcinoma (Tera-2) cells), murine cells (BALB/c-3T3 and Y-1 cells), BHK21 hamster cells, and mink lung (ML) cells were first inoculated with HCMV laboratory strain. IEA synthesizing cells were detected by immunoperoxidase assay using a monoclonal antibody. ML cells and differentiated Tera-2 cells exhibited more positive cells than MRC-5 cells. BHK21, and MRC-5 cells were equivalent in sensitivity whereas U-373MG, BALB/c-3T3, and Y-1 cells had only reduced IEA positive cells. When 63 urine specimens were inoculated onto MRC-5, ML and differentiated Tera-2 cells, 20 (31.7%) were positive in MRC-5 cells versus 18 (28.5%) in ML or Tera-2 cells. Moreover, greater numbers of infected cells were detected in MRC-5 cells than in these two cell lines. MRC-5 cells were superior for detection of HCMV in clinical samples by centrifugation cultures.

Genetic relationships within the genus Prevotella analyzed by multilocus enzyme electrophoresis and DNA-DNA hybridization.

The genetic diversity and relationships within the genus Prevotella were studied by analyzing twenty-five strains by multilocus enzyme electrophoresis (MLEE) at nine metabolic enzyme loci and DNA-DNA hybridization. MLEE revealed a high genetic diversity with 25 electrophoretic types (ETs) for the 25 strains studied, a mean number of alleles per enzyme locus of 6.8 and a mean genetic diversity per locus of 0.786. The index of association described by Maynard Smith et al. (1993) revealed a clonal structure within the genus Prevotella. A dendrogram generated by cluster analysis of a matrix of ETs showed that species like P. bivia, P. buccae, P. oris, P. oralis, P. nigrescens, and P. denticola form clusters that are consistent with DNA homologies. However, strains identified as P. melaninogenica or P. loescheii by DNA-DNA hybridization did not constitute distinct subpopulations in MLEE. MLEE analysis demonstrated its high power in differentiating closely related strains. It provides an alternative to 16S rRNA analysis for the study of phylogenetic relationships within the genus Prevotella, especially for differentiating strains with high DNA homology or high rRNA homology.

[A campaign for detection of beta-thalassemia minor and prevention of beta-thalassemia major in the island of Minorca. 2 years' experience]. / Campaña para la detección de la betatalasemia minor y prevención de la major en la isla de Menorca. Experiencia de dos años.

The high prevalence of beta-thalassemia minor and the occurrence of thalassemia major in Minorca prompted us to develop a prevention campaign. The selected population consisted of primary school students. The campaign was operative during the terms 1986-87 and 1987-88 and had three stages: 1.) informative; 2.) analytical study and diagnosis of carriers; 3.) report of the results and genetic counselling. We studied overall 1862 schoolchildren. The prevalence of beta-thalassemia minor was 3.38%. We discuss the methodology, the results and the effectiveness of the campaign.

High torque ultrasonic motors for hand prosthetics: current status and trends.

This paper presents the work carried out at the Instituto de Automática Industrial, in the framework of the EU MANUS project and with the co-operation of the Katholieke Universiteit of Leuven, to develop a specifically designed TWUM for driving our prototype of hand prosthesis. The application of TWUM to prosthetic devices has clear advanteges, namely, noiseless operation, self-braking drive, high torque and low speed characteristics. Here we analyse main actuation advantages, point out main drawbacks of this technology and describe our research in the area of specific design of TWUM for high torque actuation, improved control characteristics and enhanced overall performance. We intend to provide a concurrent approach to the overall actuator design involving electronics, mechanical design as well as improved control strategies having in mind the prosthetic application.

[Clostridium difficile, nosocomial enteropathogen: phylogeny and virulence]. / Clostridium difficile, entéropathogène nosocomial: phylogénie et virulence.

Clostridium difficile is recognized as a potentially nosocomial enteric pathogen. It induces diarrhea or pseudomembranous colitis in patients whose digestive flora has been altered by antibiotic treatment and thus allows the colonization with a strain producing toxin A (enterotoxin) and toxin B (cytotoxin) (A+B+, sometimes A-B+ strains). We studied the phylogeny of C. difficile by developing MultiLocus Sequence Typing (MLST) analysis, which reports allelic polymorphism of housekeeping genes through DNA sequencing. C. difficile exhibits genomic stability, with mutational clonal evolution and individualization of phylogenetic lineages. These lineages are not correlated with human or animal hosts. Strains involved in pseudomembranous colitis or in diarrhea do not define distinct lineages, and bi-toxinogenic strains do not segregate from non toxinogenic strains. Conversely, A-B+ strains define a unique clone, highly divergent from the population studied. Allelic sequence data may be available from an centralized internet site, allowing phylogenetic and macro-epidemiologic analyses.