Pubmed du 09/09/17

samedi 9 septembre 2017

1. Budimirovic DB. Can a Neurosteroid Ameliorate Fragile X-Associated Tremor/Ataxia Syndrome ?. Neurotherapeutics ;2017 (Sep 07)

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2. Chyung E, LeBlanc HF, Fallon JR, Akins MR. Fragile X granules are a family of axonal ribonucleoprotein particles with circuit-dependent protein composition and mRNA cargos. J Comp Neurol ;2017 (Sep 07)

Local axonal protein synthesis plays a crucial role in the formation and function of neuronal circuits. Understanding the role of this mechanism in specific circuits requires identifying the protein composition and mRNA cargos of the ribonucleoprotein particles (RNPs) that form the substrate for axonal translation. FXGs (Fragile X granules) are axonal RNPs present in a stereotyped subset of mature axons in the intact brain that contain one or more of the Fragile X related (FXR) proteins (FMRP, FXR2P, and FXR1P) along with mRNA and ribosomes. Here we performed a systematic survey of the FXR protein composition and mRNA association of FXGs in the brain. We have identified four FXG types that can be categorized based on their FXR protein complement. All FXGs contain FXR2P, with FMRP and/or FXR1P present in circuit-selective subsets. Individual neuronal cell types predominantly express a single FXG type, with FMRP-containing FXGs the most prevalent in forebrain neurons. All FXG types associate with ribosomes and mRNA, but the specific mRNA cargos are a function of FXG type, brain region and neuron class. Transcripts for beta-catenin and its regulator APC associate with a subset of forebrain FXGs. Moreover, both these transcripts can colocalize within individual FXGs, suggesting that the axonal translation of functionally related proteins may be coordinately regulated with high spatiotemporal resolution. Cell type-dependent expression of specific RNP types with distinct mRNA cargos, such as FXGs, presents a potential mechanism for regulating local translation and its output in a circuit-dependent manner. This article is protected by copyright. All rights reserved.

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3. Duan F, Watanabe K, Yoshimura Y, Kikuchi M, Minabe Y, Aihara K. Detection of atypical network development patterns in children with autism spectrum disorder using magnetoencephalography. PLoS One ;2017 ;12(9):e0184422.

Autism spectrum disorder (ASD) is a developmental disorder that involves developmental delays. It has been hypothesized that aberrant neural connectivity in ASD may cause atypical brain network development. Brain graphs not only describe the differences in brain networks between clinical and control groups, but also provide information about network development within each group. In the present study, graph indices of brain networks were estimated in children with ASD and in typically developing (TD) children using magnetoencephalography performed while the children viewed a cartoon video. We examined brain graphs from a developmental point of view, and compared the networks between children with ASD and TD children. Network development patterns (NDPs) were assessed by examining the association between the graph indices and the raw scores on the achievement scale or the age of the children. The ASD and TD groups exhibited different NDPs at both network and nodal levels. In the left frontal areas, the nodal degree and efficiency of the ASD group were negatively correlated with the achievement scores. Reduced network connections were observed in the temporal and posterior areas of TD children. These results suggested that the atypical network developmental trajectory in children with ASD is associated with the development score rather than age.

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4. Dudas RB, Lovejoy C, Cassidy S, Allison C, Smith P, Baron-Cohen S. The overlap between autistic spectrum conditions and borderline personality disorder. PLoS One ;2017 ;12(9):e0184447.

BACKGROUND : Both people with autism spectrum conditions (ASC) and borderline personality disorder (BPD) are significantly challenged in terms of understanding and responding to emotions and in interpersonal functioning. AIMS : To compare ASC, BPD, and comorbid patients in terms of autistic traits, empathy, and systemizing. METHODS : 624 ASC, 23 BPD, and 16 comorbid (ASC+BPD) patients, and 2,081 neurotypical controls (NC) filled in the Autism Spectrum Quotient (AQ), the Empathy Quotient (EQ) and the Systemizing Quotient-Revised (SQ-R). RESULTS : On the AQ, the ASC group scored higher than the BPD group, who in turn scored higher than the comorbid group, who scored higher than controls. On the EQ, we found the comorbid and ASC groups scored lower than the BPD group, who were not different from controls. Finally, on the SQ-R, we found the ASC and BPD group both scored higher than controls. CONCLUSIONS : Similar to ASC, BPD patients have elevated autistic traits and a strong drive to systemize, suggesting an overlap between BPD and ASC.

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5. Elder JH, Kreider CM, Brasher SN, Ansell M. Clinical impact of early diagnosis of autism on the prognosis and parent-child relationships. Psychol Res Behav Manag ;2017 ;10:283-292.

Autism spectrum disorder (ASD) refers to a lifelong condition that usually appears in late infancy or early childhood, and is characterized by social and communication deficits that impede optimal functioning. Despite widespread research and greater public awareness, ASD has an unclear etiology and no known cure, making it difficult to acquire accurate and timely diagnoses. In addition, once an ASD diagnosis is made, parents find it challenging to navigate the healthcare system and determine which interventions are most effective and appropriate for their child. A growing body of evidence supports the value of early diagnosis and treatment with evidence-based interventions, which can significantly improve the quality of life of individuals with ASD as well as of their carers and families. Particularly noteworthy are early interventions that occur in natural surroundings and can be modified to address age-related goals throughout the lifespan. Therefore, the purpose of this review is to : 1) provide readers with a brief background related to ASD ; 2) describe commonly used screening instruments and tools for early diagnosis ; 3) describe early interventions that have empirical support ; and 4) discuss how the parent-child and family relationships can be affected through this process. This information can provide professionals with information they can use to assist families who make critical and potentially life-changing decisions for children with ASD.

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6. Fluegge Ba K. Zinc and Copper Metabolism and Risk of Autism : a reply to Sayehmiri et al. Iran J Child Neurol ;2017 (Summer) ;11(3):66-69.

OBJECTIVE : Sayehmiri et al. recently conducted a meta-analysis to explore the relationship between zinc and copper metabolism and autism spectrum disorders (ASD). Recent reports have elucidated a full behavioral profile of mice exposed to prenatal zinc deficiency and documented a phenotype similar to that found in autism spectrum disorders (ASD). These studies suggest that significant alterations in Zn metabolism may be an important nutritional component in the development of ASD. MATERIALS & METHODS : The idea that prenatal zinc deficiency may be to blame is cursorily challenged. Epidemiological studies show that high-income countries with a low estimated prevalence of inadequate zinc intake report the highest prevalence of ASD. Consistent with other reports indicating a link between air pollution and ASD, it has recently been proposed that use of the herbicide, glyphosate, in agriculture may serve as an instrumental variable in predicting later neurodevelopmental impairment via emissions of the agricultural air pollutant, nitrous oxide (N2O). RESULTS : Work in anesthesiology has demonstrated the neurological effects from subanesthetic doses of N2O, including its inhibition of the alpha 7 nicotinic acetylcholine receptor (alpha7), a receptor coupled to both central nitric oxide (NO) metabolism and peripheral anti-inflammation. CONCLUSION : This correspondence explores how the aforementioned nutritional phenotypes found by Sayehmiri et al. in their systematic review may be a compensatory mechanism to counter the effects (namely, alpha7 inhibition) of air pollutant exposures occurring during the most critical stages of fetal development.

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7. Fujita R, Zismanov V, Jacob JM, Jamet S, Asiev K, Crist C. Fragile X mental retardation protein regulates skeletal muscle stem cell activity by regulating the stability of Myf5 mRNA. Skelet Muscle ;2017 (Sep 07) ;7(1):18.

BACKGROUND : Regeneration of adult tissues relies on adult stem cells that are primed to enter a differentiation program, while typically remaining quiescent. In mouse skeletal muscle, these features are reconciled by multiple translational control mechanisms that ensure primed muscle stem cells (MuSCs) are not activated. In quiescent MuSCs, this concept is illustrated by reversible microRNA silencing of Myf5 translation, mediated by microRNA-31 and fragile X mental retardation protein (FMRP). METHODS : In this work, we take advantage of FMRP knockout (Fmr1 -/- ) mice to support the role for FMRP in maintaining stem cell properties of the MuSC. We compare the activity of MuSCs in vivo after acute injury and engraftment, as well as ex vivo during culture. We use RNA immunoprecipitation and 3’UTR poly-adenine (poly(A)) length assays to assess the impact of FMRP on the stability of transcripts for myogenic regulatory factors. RESULTS : We show that RNA-binding FMRP is required to maintain the MuSC pool. More specifically, FMRP is required for stem cell properties of muscle stem cells, which include MuSC capacity to prime the myogenic program, their self-renewal, and their capacity to efficiently regenerate muscle. We provide evidence that FMRP regulation of MuSC activity occurs in part by the capacity of FMRP to directly bind Myf5 transcripts and impact rates of Myf5 deadenylation. CONCLUSIONS : Our results provide further evidence supporting a role for post-transcriptional silencing platforms by RNA-binding proteins in maintaining stemness properties of adult stem cells. In addition, deregulated MuSC activity in the absence of Fmr1 may have implications for fragile X syndrome, which is associated with muscle hypotonia during infancy.

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8. Helland WA, Helland T. Emotional and behavioural needs in children with specific language impairment and in children with autism spectrum disorder : The importance of pragmatic language impairment. Res Dev Disabil ;2017 (Sep 04) ;70:33-39.

BACKGROUND : Language problems may negatively affect children’s behaviour and have detrimental effects on the development of peer-relations. AIMS : We investigated and compared emotional and behavioural profiles in children with SLI and in children with ASD aged 6-15 years and explored to what extent pragmatic language problems contributed to the emotional and behavioural needs (EBN) in these clinical groups. METHODS AND PROCEDURES : The ASD group consisted of 23 children (19 boys ; 4 girls) and the SLI group consisted of 20 children (18 boys ; 2 girls). In order to assess EBN and language abilities, the Strength and Difficulties Questionnaire (SDQ) and the Children’s Communication Checklist -2 (CCC-2) were filled out by parents. OUTCOMES AND RESULTS : Our main findings were that although EBN was common in both groups ; the children in the ASD group were significantly impaired relative to the children in the SLI group. However, in both groups pragmatic language problems were found to be significantly associated with EBN. IMPLICATIONS : A comprehensive assessment of EBN as well as pragmatic language abilities should be an integral part of the assessment procedure. Considering the substantial influence of pragmatic language abilities on social function and in resolving interpersonal conflicts with peers further development of therapy plans and interventions targeting pragmatics is strongly needed.

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9. Holyfield C, Drager KDR, Kremkow JMD, Light J. Systematic review of AAC intervention research for adolescents and adults with autism spectrum disorder. Augment Altern Commun ;2017 (Sep 08):1-12.

Much of augmentative and alternative communication (AAC) research for individuals with autism spectrum disorder has focused on young children. Given that the lives, communication, strengths, and needs of adolescents and adults with autism spectrum disorder are quite different from those of young children, the purpose of the current study was to consolidate current AAC intervention research findings specific to these individuals. A systematic review was conducted to identify and evaluate relevant research. Results indicate that AAC intervention benefits adolescents and adults with autism spectrum disorder. However, more research is urgently needed. Future research focused on supporting communicative functions other than requesting (e.g., social closeness, information transfer) while participating in contexts important to the lives of adolescents and adults may be particularly valuable.

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10. Li YJ, Li YM, Xiang DX. Supplement intervention associated with nutritional deficiencies in autism spectrum disorders : a systematic review. Eur J Nutr ;2017 (Sep 07)

PURPOSE : Nutritional supplements have been used for correction of deficiencies that may occur in patient with autism spectrum disorder (ASD) and to improve core symptoms. We aim to provide current best evidence about supplements for nutritional deficiencies and core symptoms in children with ASD and to evaluate the effectiveness and safety. METHODS : A systematic literature search of scientific databases was performed to retrieve relevant randomized controlled trials. Risk of bias was assessed for each study. RESULTS : 18 randomized controlled trials of five supplements were included. B6/Mg was not helpful for improving ASD symptoms (seven RCTs). Two RCTs of methyl B12 reported some improvement in ASD severity but the effects on the correction of deficiencies were inconclusive. Two RCTs of vitamin D3 both reported increased levels of mean 25(OH)D in serum but inconsistent results in behavioral outcomes. Omega-3 fatty acid supplementation did not affect ASD behaviors but may correct deficiencies (six RCTs). One RCT of folinic acid reported positive results in improving ASD symptoms measured by various behavioral scales. CONCLUSIONS : Current evidence for the use of supplements for correcting nutritional deficiencies in children with ASD and to improve the symptoms is little. More studies are needed.

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11. Lodhia V, Hautus MJ, Johnson BW, Brock J. Atypical brain responses to auditory spatial cues in adults with autism spectrum disorder. Eur J Neurosci ;2017 (Sep 09)

The auditory processing atypicalities experienced by many individuals on the autism spectrum disorder might be understood in terms of difficulties parsing the sound energy arriving at the ears into discrete auditory "objects." Here we asked whether autistic adults are able to make use of two important spatial cues to auditory object formation - the relative timing and amplitude of sound energy at the left and right ears. Using electroencephalography, we measured the brain responses of 15 autistic adults and 15 age-and verbal-IQ-matched control participants as they listened to dichotic pitch stimuli - white noise stimuli in which interaural timing or amplitude differences applied to a narrow frequency band of noise typically lead to the perception of a pitch sound that is spatially segregated from the noise. Responses were contrasted with those to stimuli in which timing and amplitude cues were removed. Consistent with our previous studies, autistic adults failed to show a significant Object Related Negativity (ORN) for timing-based pitch, although their ORN was not significantly smaller than that of the control group. Autistic participants did show an ORN to amplitude cues, indicating that they do not experience a general impairment in auditory object formation. However, their P400 response - thought to indicate the later attention-dependent aspects of auditory object formation - was missing. These findings provide further evidence of atypical auditory object processing in autism with potential implications for understanding the perceptual and communication difficulties associated with the condition. This article is protected by copyright. All rights reserved.

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12. Naveed M, Wenhua L, Gang W, Mohammad IS, Abbas M, Liao X, Yang M, Zhang L, Liu X, Qi X, Chen Y, Jiadi L, Ye L, Zhijie W, Ding CD, Feng Y, Xiaohui Z. A novel ventricular restraint device (ASD) repetitively deliver Salvia miltiorrhiza to epicardium have good curative effects in heart failure management. Biomed Pharmacother ;2017 (Sep 05) ;95:701-710.

A novel ventricular restraint is the non-transplant surgical option for the management of an end-stage dilated heart failure (HF). To expand the therapeutic techniques we design a novel ventricular restraint device (ASD) which has the ability to deliver a therapeutic drug directly to the heart. We deliver a Traditional Chinese Medicine (TCM) Salvia miltiorrhiza (Danshen Zhusheye) through active hydraulic ventricular support drug delivery system (ASD) and we hypothesize that it will show better results in HF management than the restraint device and drug alone. SD rats were selected and divided into five groups (n=6), Normal, HF, HF+SM (IV), HF+ASD, HF+ASD+SM groups respectively. Post myocardial infarction (MI), electrocardiography (ECG) showed abnormal heart function in all groups and HF+ASD+SM group showed a significant therapeutic improvement with respect to other treatment HF, HF+ASD, and HF+SM (IV) groups on day 30. The mechanical functions of the heart such as heart rate, LVEDP, and LVSP were brought to normal when treated with ASD+SM and show significant (P value<0.01) compared to other groups. BNP significantly declines in HF+ASD+SM group animals compared with other treatment groups. Masson’s Trichrome staining was used to study histopathology of cardiac myocytes and quantification of fibrosis was assessed. The large blue fibrotic area was observed in HF, HF+ASD, and HF+SM (IV) groups while HF+ASD+SM showed negligible fibrotic myocyte at the end of study period (30days). This study proves that novel ASD device augments the therapeutic effect of the drug and delivers Salvia miltiorrhiza to the cardiomyocytes significantly as well as provides additional support to the dilated ventricle by the heart failure.

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