Dimerization of the Pragmin Pseudo-Kinase Regulates Protein Tyrosine Phosphorylation.

The pseudo-kinase and signaling protein Pragmin has been linked to cancer by regulating protein tyrosine phosphorylation via unknown mechanisms. Here we present the crystal structure of the Pragmin 906-1,368 amino acid C terminus, which encompasses its kinase domain. We show that Pragmin contains a classical protein-kinase fold devoid of catalytic activity, despite a conserved catalytic lysine (K997).

Neural Decoding of Robot-Assisted Gait During Rehabilitation After Stroke.

Objective: Advancements in robot-assisted gait rehabilitation and brain-machine interfaces may enhance stroke physiotherapy by engaging patients while providing information about robot-induced cortical adaptations. We investigate the feasibility of decoding walking from brain activity in stroke survivors during therapy using a powered exoskeleton integrated with an electroencephalography-based brain-machine interface.

Design: The H2 powered exoskeleton was designed for overground gait training with actuated hip, knee, and ankle joints.

Comparing Recalibration Strategies for Electroencephalography-Based Decoders of Movement Intention in Neurological Patients with Motor Disability.

Motor rehabilitation based on the association of electroencephalographic (EEG) activity and proprioceptive feedback has been demonstrated as a feasible therapy for patients with paralysis. To promote long-lasting motor recovery, these interventions have to be carried out across several weeks or even months. The success of these therapies partly relies on the performance of the system decoding movement intentions, which normally has to be recalibrated to deal with the nonstationarities of the cortical activity.

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 (IC > 10 μM) that contrast with the highly efficient anti-Toxoplasma activity (IC < 1.

Assessing sensorimotor excitability after spinal cord injury: a reflex testing method based on cycling with afferent stimulation.

Unlabelled: Several studies have examined spinal reflex modulation during leg cycling in healthy and spinal cord injury (SCI) subjects. However, the effect of cutaneous plantar afferent input on spinal excitability during leg cycling after SCI has not been characterised. The aim of the study was to test the feasibility of using controlled leg cycling in combination with plantar cutaneous electrical stimulation (ES) cycling to assess lower limb spinal sensorimotor excitability in subjects with motor complete or incomplete SCI.

Volition-adaptive control for gait training using wearable exoskeleton: preliminary tests with incomplete spinal cord injury individuals.

Background: Gait training for individuals with neurological disorders is challenging in providing the suitable assistance and more adaptive behaviour towards user needs. The user specific adaptation can be defined based on the user interaction with the orthosis and by monitoring the user intentions. In this paper, an adaptive control model, commanded by the user intention, is evaluated using a lower limb exoskeleton with incomplete spinal cord injury individuals (SCI).

Metabarcoding for the parallel identification of several hundred predators and their prey: Application to bat species diet analysis.

Assessing diet variability is of main importance to better understand the biology of bats and design conservation strategies. Although the advent of metabarcoding has facilitated such analyses, this approach does not come without challenges. Biases may occur throughout the whole experiment, from fieldwork to biostatistics, resulting in the detection of false negatives, false positives or low taxonomic resolution.

Extracellular ATP Activates the NLRP3 Inflammasome and Is an Early Danger Signal of Skin Allograft Rejection.

Immune cells are equipped with a number of receptors that recognize sterile injury and pathogens. We find that host immune cells release ATP as an inflammatory signal in response to allogeneic transplantation. ATP then acts via a feedback mechanism on the P2X7 channel to activate the NLRP3 inflammasome and subsequently process and release interleukin (IL)-18.

Influence of donor liver CYP3A4*20 loss-of-function genotype on tacrolimus pharmacokinetics in transplanted patients.

Objective: Cytochrome P450 3A4 (CYP3A4) metabolizes about half of all drugs on the market; however, the impact of CYP3A4 loss-of-function variants on drug exposures remains poorly characterized. Here, we report the effect of the CYP3A4*20 frameshift allele in two Spanish liver transplant patients treated with tacrolimus.

Patients And Methods: A series of 90 transplanted patients (with DNA available for 89 of the recipients and 76 of the liver donors) treated with tacrolimus were included in the study.

Productive common light chain libraries yield diverse panels of high affinity bispecific antibodies.

The commercial success of bispecific antibodies generally has been hindered by the complexities associated with generating appropriate molecules for both research scale and large scale manufacturing purposes. Bispecific IgG (BsIgG) based on two antibodies that use an identical common light chain can be combined with a minimal set of Fc mutations to drive heavy chain heterodimerization in order to address these challenges. However, the facile generation of common light chain antibodies with properties similar to traditional monoclonal antibodies has not been demonstrated and they have only been used sparingly.

[Exhaustivity and critical tone of the news in print media reporting medical innovations].

Objective: To quantify how exhaustive and critical were stories reporting medical innovations published in print media and to analyze the characteristics that may be related.

Method: Content analysis of the newspapers stories related to the discovery, introduction or improvement of a medical innovation through a questionnaire with ten criteria that allows calculating an overall score of exhaustiveness. The critical view was also included.

Tenofovir lamivudine plus adefovir in chronic hepatitis B: TENOSIMP-B study.

Aim: To demonstrate the non-inferiority (15% non-inferiority limit) of monotherapy with tenofovir disoproxil fumarate (TDF) the combination of lamivudine (LAM) plus adefovir dipivoxil (ADV) in the maintenance of virologic response in patients with chronic hepatitis B (CHB) and prior failure with LAM.

Methods: This study was a Phase IV prospective, randomized, open, controlled study with 2 parallel groups (TDF and LAM+ADV) of adult patients with hepatitis B e antigen (HBeAg)-negative CHB, prior failure with LAM, on treatment with LAM+ADV for at least 6 mo, without prior resistance to ADV and with an undetectable viral load at the start of the study, in 14 Spanish hospitals. The follow-up time for each patient was 48 wk after randomization, with quarterly visits in which the viral load, biochemical and serological parameters, adverse effects, adherence to treatment and consumption of hospital resources were analysed.

The effects of single- and multiple-dose administration of bococizumab (RN316/PF-04950615), a humanized IgG2Δa monoclonal antibody binding proprotein convertase subtilisin/kexin type 9, in hypercholesterolemic subjects treated with and without atorvastatin: Results from four phase I studies.

Aims: Three single-dose and one multiple-dose phase I studies were conducted in subjects with primary hypercholesterolemia to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of bococizumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor.

Methods: The dosing schedules for hypercholesterolemic subjects randomized in the four phase I studies were (1) ascending, single, intravenous (IV) bococizumab (0.3, 1, 3, 6, 12, or 18 mg/kg), or placebo (N = 48; baseline low-density lipoprotein cholesterol [LDL-C] ≥130 mg/dL); (2) single, IV bococizumab (0.

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.

Double Catalytic Kinetic Resolution (DoCKR) of Acyclic anti-1,3-Diols: The Additive Horeau Amplification.

The concept of a synergistic double catalytic kinetic resolution (DoCKR) as described in this article was successfully applied to racemic acyclic anti-1,3-diols, a common motif in natural products. This process takes advantage of an additive Horeau amplification involving two successive enantioselective organocatalytic acylation reactions, and leads to diesters and recovered diols with high enantiopurities. It was first developed with C -symmetrical diols and then further extended to non-C -symmetrical anti diols to prepare useful chiral building blocks.

Surveillance study on the tolerability and safety of Flebogamma DIF (10% and 5% intravenous immunoglobulin) in adult and pediatric patients.

Direct comparisons of tolerability and safety of concentrated intravenous immunoglobulin (IVIG) versus less concentrated products are scarce. In this postauthorization, prospective, observational, multicenter study, a systematic comparison of 10% and 5% concentrations of Flebogamma® DIF IVIG was performed in both adult and pediatric patients treated with the studied IVIG products according to the approved indications under routine conditions. Dose of product administered, adverse events (AEs), physical assessments, laboratory tests, and concomitant therapy were analyzed.

A modified multilocus sequence typing protocol to genotype Kingella kingae from oropharyngeal swabs without bacterial isolation.

Background: Outbreaks of Kingella kingae infection are an emerging public health concern among daycare attendees carrying epidemic clones in the oropharynx. However, genotyping of such epidemic clones from affected cases is limited by the low performance of current methods to detect K. kingae from blood samples and lack of specimens available from infected sites.

Bank vole immunoheterogeneity may limit Nephropatia Epidemica emergence in a French non-endemic region.

Ecoevolutionary processes affecting hosts, vectors and pathogens are important drivers of zoonotic disease emergence. In this study, we focused on nephropathia epidemica (NE), which is caused by Puumala hantavirus (PUUV) whose natural reservoir is the bank vole, Myodes glareolus. We questioned the possibility of NE emergence in a French region that is considered to be NE-free but that is adjacent to a NE-endemic region.

Tapping the woodpecker tree for evolutionary insight.

Molecular phylogenetic studies of woodpeckers (Picidae) have generally focused on relationships within specific clades or have sampled sparsely across the family. We compared DNA sequences of six loci from 203 of the 217 recognized species of woodpeckers to construct a comprehensive tree of intrafamilial relationships. We recovered many known, but also numerous unknown, relationships among clades and species.

Combining muscle synergies and biomechanical analysis to assess gait in stroke patients.

The understanding of biomechanical deficits and impaired neural control of gait after stroke is crucial to prescribe effective customized treatments aimed at improving walking function. Instrumented gait analysis has been increasingly integrated into the clinical practice to enhance precision and inter-rater reliability for the assessment of pathological gait. On the other hand, the analysis of muscle synergies has gained relevance as a novel tool to describe the neural control of walking.

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.

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.

Joint stiffness modulation of compliant actuators for lower limb exoskeletons.

Lower limb exoskeletons are being used to assist people with movement disorders during activities of daily living or rehabilitation. However, providing a natural interface that automatically adapts to the patient's movement limitations remains an open challenge. In this paper, we present a control implementation that combines a compliant actuator technology with the concept of tacit learning to improve the synchronisation between the exoskeleton and the user during locomotion.