Community Introduction of Practice Parameters for Autistic Spectrum Disorders: Advancing Early Recognition

Objectives: Within a strong interdisciplinary framework, improvement in the quality of care for children with autistic spectrum disorders through a 2year implementation program of Practice Parameters, aimed principally at improving early detection and intervention. Method: We developed Practice Parameters (PPs) for Pervasive Developmental Disorders and circulated the PPs to all child and adolescent psychiatrists practicing in the region. Results: PP development and parallel information strategies resulted in a significant decrease of 1.5years in the mean-age-at-diagnosis. However, further analysis indicated that improvement was only transient. Conclusion: Despite the encouraging improvement in mean-age-at-diagnosis 2years after PP implementation, other indicators showed a failure to maintain the improvements. A systematic screening program would be the most reliable method to reinforce the PP

New complete genome sequences of human rhinoviruses shed light on their phylogeny and genomic features

<p>Abstract</p> <p>Background</p> <p>Human rhinoviruses (HRV), the most frequent cause of respiratory infections, include 99 different serotypes segregating into two species, A and B. Rhinoviruses share extensive genomic sequence similarity with enteroviruses and both are part of the picornavirus family. Nevertheless they differ significantly at the phenotypic level. The lack of HRV full-length genome sequences and the absence of analysis comparing picornaviruses at the whole genome level limit our knowledge of the genomic features supporting these differences.</p> <p>Results</p> <p>Here we report complete genome sequences of 12 HRV-A and HRV-B serotypes, more than doubling the current number of available HRV sequences. The whole-genome maximum-likelihood phylogenetic analysis suggests that HRV-B and human enteroviruses (HEV) diverged from the last common ancestor after their separation from HRV-A. On the other hand, compared to HEV, HRV-B are more related to HRV-A in the capsid and 3B-C regions. We also identified the presence of a 2C <it>cis</it>-acting replication element (<it>cre</it>) in HRV-B that is not present in HRV-A, and that had been previously characterized only in HEV. In contrast to HEV viruses, HRV-A and HRV-B share also markedly lower GC content along the whole genome length.</p> <p>Conclusion</p> <p>Our findings provide basis to speculate about both the biological similarities and the differences (e.g. tissue tropism, temperature adaptation or acid lability) of these three groups of viruses.</p

The HIF1α/JMY pathway promotes glioblastoma stem-like cell invasiveness after irradiation

Human glioblastoma (GBM) is the most common primary malignant brain tumor. A minor subpopulation of cancer cells, known as glioma stem-like cells (GSCs), are thought to play a major role in tumor relapse due to their stem cell-like properties, their high resistance to conventional treatments and their high invasion capacity. We show that ionizing radiation specifically enhances the motility and invasiveness of human GSCs through the stabilization and nuclear accumulation of the hypoxia-inducible factor 1α (HIF1α), which in turn transcriptionally activates the Junction-mediating and regulatory protein (JMY). Finally, JMY accumulates in the cytoplasm where it stimulates GSC migration via its actin nucleation-promoting activity. Targeting JMY could thus open the way to the development of new therapeutic strategies to improve the efficacy of radiotherapy and prevent glioma recurrence.The authors thank members of the LRP for helpful discussions and are indebted to V. Barroca and the staff of the animal facilities and to N. Deschamps and J. Baijer for cell sorting. We also thanks I. Naguibneva for the gift of the pTRIP shHIF1α plasmid. MS is the recipient of a doctoral fellowship from the Ministère de la Recherche. This work was supported by grants from CEA (Segment Radiobiologie), La Ligue contre le Cancer (Comité d’Ile de France), Electricité de France (EDF), Fondation de France (N° Engt: 2013-00042632) and Ramón y Cajal program (RYC-2013-13450)

Rhinovirus Genome Variation during Chronic Upper and Lower Respiratory Tract Infections

Routine screening of lung transplant recipients and hospital patients for respiratory virus infections allowed to identify human rhinovirus (HRV) in the upper and lower respiratory tracts, including immunocompromised hosts chronically infected with the same strain over weeks or months. Phylogenetic analysis of 144 HRV-positive samples showed no apparent correlation between a given viral genotype or species and their ability to invade the lower respiratory tract or lead to protracted infection. By contrast, protracted infections were found almost exclusively in immunocompromised patients, thus suggesting that host factors rather than the virus genotype modulate disease outcome, in particular the immune response. Complete genome sequencing of five chronic cases to study rhinovirus genome adaptation showed that the calculated mutation frequency was in the range observed during acute human infections. Analysis of mutation hot spot regions between specimens collected at different times or in different body sites revealed that non-synonymous changes were mostly concentrated in the viral capsid genes VP1, VP2 and VP3, independent of the HRV type. In an immunosuppressed lung transplant recipient infected with the same HRV strain for more than two years, both classical and ultra-deep sequencing of samples collected at different time points in the upper and lower respiratory tracts showed that these virus populations were phylogenetically indistinguishable over the course of infection, except for the last month. Specific signatures were found in the last two lower respiratory tract populations, including changes in the 5′UTR polypyrimidine tract and the VP2 immunogenic site 2. These results highlight for the first time the ability of a given rhinovirus to evolve in the course of a natural infection in immunocompromised patients and complement data obtained from previous experimental inoculation studies in immunocompetent volunteers

Vitellogenin Underwent Subfunctionalization to Acquire Caste and Behavioral Specific Expression in the Harvester Ant Pogonomyrmex barbatus

PMCID: PMC3744404This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

New Respiratory Enterovirus and Recombinant Rhinoviruses among Circulating Picornaviruses

Increased genomic diversity of these viruses is demonstrated

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Troubles hyperactifs avec déficit de l'attention chez les enfants et les adolescents : situation actuelle et perspectives de traitements médicamenteux

Since Bradley's report in 1937 that described the efficacy of racemic amphetamine sulfate in the treatment of children with disruptive behaviours, numerous studies have documented the safety, efficacy and tolerability of psychostimulant treatment for children and adolescents with attention-deficit/ hyperactivity disorder (ADHD). Stimulants should generally be considered first when initiating pharmacotherapy for most patients with ADHD, but as a part of a multimodal approach of ADHD. The most commonly prescribed and studied psychostimulants include methylphenidate (RitalineReg.), dextroamphetamine (DexaminReg.), recently methylphenidate OROS (ConcertaReg.) and mixed amphetamine salts (AdderallReg.). The lack of pharmacologic coverage throughout the school day may account for the apparent failure of stimulants to affect some key domains of functioning in children with ADHD. Recently sustained-release preparation of psychostimulants have been developed (Ritaline SRReg., Ritaline LAReg., ConcertaReg., Adderall XRReg., [methylphenidate HCI] Metadate CDReg., [dextroamphetamine] SpansulesReg.). Since January 2003, the atomoxetine (Strattera Reg.) with the pharmacological profile approaching an antidepressant is approved by the FDA in United States for children and adults with ADHD. Preliminary data suggests comparable efficacy to stimulant across the ADHD symptoms spectrum without predictors available for who responds better to stimulants versus atomoxetine. The efficacy of other non-stimulants is until now not enough documented (for instance, alpha 2 agonists as clonidine, tricyclic antidepressants as desipramine and nortriptyline, SSRI as fluoxetine, bupropion or modafinil).The medications are second choice alternatives for problematic cases. The prescriptions for ADHD symptoms are under the responsibility of clinicians (usage "label off"). The purpose of this paper is to briefly review the available data about the pharmacotherapy of children and adolescents with ADHD in order to provide the clinician with rational, empirically based strategies. This paper especially describes the medications available in Switzerland, as the short- and long-acting RitalineReg., DexaminReg. and ConcertaReg.. The effects of slow-release preparations of methylphenidate are reported. A persistent question attached to ADHD is the allegation that stimulant therapy can lead to substance abuse or drug addiction in either adolescence or adulthood. This paper briefly reviews the available data about this topic. Scientific data have shown that there is no evidence at this time that long-term treatment with stimulants or other psychoactive drugs prescribed for the treatment of children or adolescents with ADHD is associated with high rates of substance abuse later in life. During the past decade epidemiologic studies have documented high rates of psychiatric comorbidity among children with ADHD, as conduct disorders, oppositional defiant disorders, anxiety disorders, mood disorders and learning disabilities. If not recognised and not treated, the combination of comorbid symptoms and ADHD may lead to high morbidity and disability with poor long-term prognosis. The choice of the currently available drugs in Switzerland is still limited, and the clinician is in an unpleasant situation when the effectiveness of the methylphenidate is insufficient or patients develop problematic side effects. The clinicians in Switzerland await with interest the introduction of new preparations of psychostimulants, as the methylphenidate OROS (ConcertaReg.) or Ritaline LAReg. wich have an action of long duration, or the atomoxetine (StratteraReg.) with the pharmacological profile approaching an antidepressant. The introduction of other preparations already marketed in the United States could widen the pallet of drugs indicated in the treatment of the ADHD in the child and the teenager. (PsycINFO Database Record (c) 2005 APA, all rights reserved