French Institute of Health and Medical Research

About: French Institute of Health and Medical Research is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Receptor. The organization has 109367 authors who have published 174236 publications receiving 8365503 citations.

CARD15 mutations in Blau syndrome.

Abstract: We have identified three missense mutations in the nucleotide-binding domain (NBD) of CARD15/NOD2 in four French and German families with Blau syndrome. Our findings indicate that, in addition to Crohn disease, CARD15 is involved in the susceptibility to a second granulomatous disorder.

ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology

Abstract: The International League Against Epilepsy (ILAE) classification of the epilepsies has been updated to reflect the gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for the clinical diagnosis of patients but it is also critical for epilepsy research, development of antiepileptic treatment and communication around the world. The new classification is based on a draft document submitted for public comments in 2013, which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It consists of three levels starting with seizure type, where it is assumed that the epileptic seizures of the patient are defined by the new 2017 ILAE seizure classification. After diagnosis of the seizure type, the next step is the diagnosis of the epilepsy type, which includes focal epilepsy, generalized epilepsy, combined generalized and focal epilepsy and also an unclassified epilepsy group. At the third level the disease is assigned to a specific epilepsy syndrome. The new classification incorporates etiology at each stage, emphasizing the need to consider etiology at each step of the diagnosis, as it often carries significant treatment implications. The various etiologies can be assigned to six subgroups, defined with respect to the potential therapeutic consequences. New terminology is introduced, such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self-limiting and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the twenty-first century.

Plasticity of reward neurocircuitry and the 'dark side' of drug addiction.

Abstract: Drug seeking is associated with activation of reward neural circuitry. Here we argue that drug addiction also involves a ‘dark side’—a decrease in the function of normal reward-related neurocircuitry and persistent recruitment of anti-reward systems. Understanding the neuroplasticity of the dark side of this circuitry is the key to understanding vulnerability to addiction. Drug addiction has been conceptualized as a progression from impulsive to compulsive behavior, ending in chronic, relapsing drug taking. Patients with impulse control disorders experience an increasing sense of tension or arousal before committing an impulsive act; pleasure, gratification or relief at the time of committing the act; and then regret, selfreproach or guilt after the act 1 . In contrast, patients with compulsive disorders experience anxiety and stress before committing a compulsive repetitive behavior, then relief from the stress by performing the behavior 1 . In addiction, drug-taking behavior progresses from impulsivity to compulsivity in a three-stage cycle: binge/intoxication, withdrawal/negative affect and preoccupation/anticipation 2 . In the impulsive stage, the drive for the drug-taking behavior is positive reinforcement, in which stimuli increase the probability of the response. As individuals move to the compulsive stage, the drive transitions to negative reinforcement, in which removal of the aversive state increases the probability of the response. Different theoretical perspectives from experimental psychology (positive and negative reinforcement framework), social psychology (self-regulation failure framework) and neurobiology (counteradaptive and sensitization framework) can be superimposed on the stages of the addiction cycle 2 . These stages are thought to feed into each other, becoming more intense and ultimately leading to the pathological state known as addiction. Our thesis is that addiction involves a longterm, persistent plasticity in the activity of neural circuits mediating two different motivational systems: decreased function of brain reward systems driven by natural rewards, and recruitment of anti-reward systems that drive aversive states. The concept of anti-reward is based on the hypothesis that there are brain systems in place to limit reward (see footnote in ref. 2), an ‘opponent process’ concept that is a general feature of biological systems 3 . From a neurobiological perspective, progression through the three stages of the addiction cycle induces plasticity in neural circuitry that drives compulsive drug taking, narrowing the behavioral repertoire to drug seeking. Animal models have been developed that have face validity (resembles the human condition) and some construct validity (possesses explanatory power) for all three stages of the addiction cycle and the transition to drug addiction. Acute selfadministration of drugs (intravenous and oral) has construct validity for drug intoxication and elements of drug binges in humans. Self-stimulation and place conditioning (learning to avoid a location previously paired with an aversive stimulus or state) are sensitive measures of ‘motivational’ withdrawal. Cue-induced or

The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial: First Randomized Placebo-Controlled Study of Myoblast Transplantation

Abstract: Background— Phase I clinical studies have demonstrated the feasibility of implanting autologous skeletal myoblasts in postinfarction scars. However, they have failed to determine whether this procedure was functionally effective and arrhythmogenic. Methods and Results— This multicenter, randomized, placebo-controlled, double-blind study included patients with left ventricular (LV) dysfunction (ejection fraction ≤35%), myocardial infarction, and indication for coronary surgery. Each patient received either cells grown from a skeletal muscle biopsy or a placebo solution injected in and around the scar. All patients received an implantable cardioverter-defibrillator. The primary efficacy end points were the 6-month changes in global and regional LV function assessed by echocardiography. The safety end points comprised a composite index of major cardiac adverse events and ventricular arrhythmias. Ninety-seven patients received myoblasts (400 or 800 million; n=33 and n=34, respectively) or the placebo (n=30). ...

Parkinson's disease: from monogenic forms to genetic susceptibility factors

Abstract: Research in Parkinson's disease (PD) genetics has been extremely prolific over the past decade. More than 13 loci and 9 genes have been identified, but their implication in PD is not always certain. Point mutations, duplications and triplications in the alpha-synuclein (SNCA) gene cause a rare dominant form of PD in familial and sporadic cases. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are a more frequent cause of autosomal dominant PD, particularly in certain ethnic groups. Loss-of-function mutations in Parkin, PINK1, DJ-1 and ATP13A2 cause autosomal recessive parkinsonism with early-onset. Identification of other Mendelian forms of PD will be a main challenge for the next decade. In addition, susceptibility variants that contribute to PD have been identified in several populations, such as polymorphisms in the SNCA, LRRK2 genes and heterozygous mutations in the beta-glucocerebrosidase (GBA) gene. Genome-wide associations and re-sequencing projects, together with gene-environment interaction studies, are expected to further define the causal role of genetic determinants in the pathogenesis of PD, and improve prevention and treatment.