Pubmed du 29/06/17

jeudi 29 juin 2017

1. Barber C. Autism spectrum network. Nurs Stand. 2017 ; 31(44) : 30.

I was unable to attend this year’s RCN congress, but as a nurse with Asperger’s syndrome I followed the congress autism resolution debate with interest (’More research for autism,’ say nurses across disciplines, online news, 16 May).

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2. Besaury L, Amato P, Wirgot N, Sancelme M, Delort AM. Draft Genome Sequence of Pseudomonas graminis PDD-13b-3, a Model Strain Isolated from Cloud Water. Genome Announc. 2017 ; 5(26).

The whole genome of Pseudomonas graminis PDD-13b-3, a strain of bacteria isolated from cloud water, was sequenced. This showed that this microorganism is equipped with genes that could potentially be involved in its survival in the atmosphere and clouds : those for oxidative stress and carbon starvation responses, DNA repair, and iron uptake.

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3. Cheung CC, Politzer-Ahles S, Hwang H, Chui RLY, Leung MT, Tang TPY. Comprehension of presuppositions in school-age Cantonese-speaking children with and without autism spectrum disorders. Clin Linguist Phon. 2017 : 1-16.

While an enormous amount of research has been done on the deficient conversation skills in individuals with autism spectrum disorders (ASD), little is known about their performance on presuppositions, a domain of knowledge that is crucial for successful communication. This study investigated the comprehension of four types of presupposition, namely existential, factive, lexical and structural presuppositions, in school-age Cantonese-speaking children with and without ASD. A group of children with ASD (n = 21), mean age 8.8, was compared with a group of typically developing children (n = 106). Knowledge of presuppositions was evaluated based on children’s ability to judge whether a given utterance was a correct presupposition of a preceding utterance. Children with ASD were found to show a deficit in the comprehension of presuppositions, even after controlling for differences in general language ability and non-verbal intelligence. The relative difficulty of the four types of presupposition did not differ between the two groups of children. The present findings provide new empirical evidence that children with ASD have a deficit in the comprehension of presuppositions. Future research should explore whether the deficit in the comprehension of presuppositions is related to the development of theory of mind skills in children with ASD.

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4. De Santis B, Raggi ME, Moretti G, Facchiano F, Mezzelani A, Villa L, Bonfanti A, Campioni A, Rossi S, Camposeo S, Soricelli S, Moracci G, Debegnach F, Gregori E, Ciceri F, Milanesi L, Marabotti A, Brera C. Study on the Association among Mycotoxins and other Variables in Children with Autism. Toxins (Basel). 2017 ; 9(7).

Environmental factors and genetic susceptibility are implicated in the increased risk of autism spectrum disorder (ASD). Mycotoxins are agricultural contaminants of fungal origin that represent real risk factors for human health and especially for children. Thus, the main hypothesis of this work is that the deterioration of the clinical manifestation of autism in children may result from the exposure to mycotoxins through the consumption of contaminated food. Within a cross-sectional study, a group of autistic children (n = 172) and a group of controls (n = 61) (siblings and non-parental) were recruited in North and South Italy. All children had blood and urine samples taken, for testing some mycotoxins by a LC-MS/MS validated method. Blood samples were also tested for assessing specific IgG against food and fungal antigens and cytokines. The analyses outputs highlighted statistically significant differences comparing mycotoxins levels between (i) children groups both in urine (deoxynivalenol and de-epoxydeoxynivalenol, p = 0.0141 and p = 0.0259, respectively) and serum (aflatoxin M1, ochratoxin A and fumonisin B1, p = 0.0072, p = 0.0141 and p = 0.0061, respectively) ; (ii) a group of selected fungal IgGs, and IgGs against wheat and gluten and (iii) cytokines. These results suggest the need for a deeper examination of the role that mycotoxins may have on the etiology of ASD.

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5. DiLalla LF, McCrary M, Diaz E. A review of endophenotypes in schizophrenia and autism : The next phase for understanding genetic etiologies. Am J Med Genet C Semin Med Genet. 2017.

Many psychiatric disorders are caused by multiple genes and multiple environmental factors, making the identification of specific genetic risk factors for these disorders difficult. Endophenotypes are behaviors or characteristics that are intermediate between the genotype and a phenotype of interest. Because they are more directly related to the gene action than is the endpoint disorder, they may be useful in the identification of specific genes related to psychiatric disorders and the classification of disorders or traits that share an underlying genetic etiology. We discuss genetic and endophenotype research on schizophrenia and autism spectrum disorder (ASD) in this review. Some of the psychophysiological endophenotypes that have been studied for schizophrenia include prepulse inhibition of the startle response, the antisaccadic task assessing frontal lobe function, inhibition of the P50 event-related potential (ERP), and other auditory ERP measures. Potential ASD endophenotypes include theory of mind, language skills (specifically, age at first spoken word and first spoken phrase), social skills, and certain brain functions, such as asynchronization of neural activity and brain responses to emotional faces. Because the link between genes and specific psychiatric disorders is difficult to determine, identification of endophenotypes is useful for beginning the search to identify specific genes that affect these disorders.

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6. Hudry K, Dimov S. Spoken language shows some improvement following intervention for children with autism : but for which children and why ?. Evid Based Ment Health. 2017.

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7. Jeffrey Farrar M, Seung HK, Lee H. Language and False-Belief Task Performance in Children With Autism Spectrum Disorder. J Speech Lang Hear Res. 2017 : 1-15.

Purpose : Language is related to false-belief (FB) understanding in both typically developing children and children with autism spectrum disorder (ASD). The current study examined the role of complementation and general language in FB understanding. Of interest was whether language plays similar or different roles in the groups’ FB performance. Method : Participants were 16 typically developing children (mean age = 5.0 years ; mental age = 6.7) and 18 with ASD (mean age = 7.3 years ; mental age = 8.3). Children were administered FB and language tasks (say- and think-complements), receptive and expressive vocabulary tests, and relative clauses. Results : When mental age and receptive and expressive vocabulary were used as separate covariates, the typical control group outperformed the children with ASD in FB task performance. Chi-square analyses indicated that passing both complementation tasks was linked to the FB understanding of children with ASD. Children with ASD who passed FB tasks all passed say- and think-complement tasks. However, some children in the control group were able to pass the FB tasks, even if they failed the say- and think-complement tasks. Conclusion : The results indicate that children with ASD relied more on complement understanding to pass FB than typically developing children. Results are discussed regarding the developmental pathways for FB understanding.

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8. Kaiser E, Jaganathan SK, Supriyanto E, Ayyar M. Fabrication and characterization of chitosan nanoparticles and collagen-loaded polyurethane nanocomposite membrane coated with heparin for atrial septal defect (ASD) closure. 3 Biotech. 2017 ; 7(3) : 174.

Atrial septal defect (ASD) constitutes 30-40% of all congenital heart diseases in adults. The most common complications in the treatment of ASD are embolization of the device and thrombosis formation. In this research, an occluding patch was developed for ASD treatment using a well-known textile technology called electrospinning. For the first time, a cardiovascular occluding patch was fabricated using medical grade polyurethane (PU) loaded with bioactive agents namely chitosan nanoparticles (Cn) and collagen (Co) which is then coated with heparin (Hp). Fourier transform infrared spectrum showed characteristic vibrations of several active constituents and changes in the absorbance due to the inclusion of active ingredients in the patch. The contact angle analysis demonstrated no significant decrease in contact angle compared to the control and the composite patches. The structure of the electrospun nanocomposite (PUCnCoHp) was examined through scanning electron microscopy. A decrease in nanofiber diameter between control PU and PUCnCoHp nanocomposite was observed. Water uptake was found to be decreased for the PUCnCoHp nanocomposite against the control. The hemocompatibility properties of the PUCnCoHp ASD occluding patch was inferred through in vitro hemocompatibility tests like activated partial thromboplastin time (APTT), prothrombin time (PT) and hemolysis assay. It was found that the PT and APTT time was significantly prolonged for the fabricated PUCnCoHp ASD occluding patch compared to the control. Likewise, the hemolysis percentage was also decreased for the PUCnCoHp ASD patch against the control. In conclusion, the developed PUCnCoHp patch demonstrates potential properties to be used for ASD occlusion.

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9. Mahic M, Che X, Susser E, Levin B, Reichborn-Kjennerud T, Magnus P, Stoltenberg C, Chauhan L, Briese T, Bresnahan M, Suren P, Hornig M, Mjaaland S, Lipkin WI. Epidemiological and Serological Investigation into the Role of Gestational Maternal Influenza Virus Infection and Autism Spectrum Disorders. mSphere. 2017 ; 2(3).

The literature concerning gestational maternal influenza virus infection and risk of autism spectrum disorders (ASD) is inconclusive. To address this uncertainty, we obtained information from questionnaires and samples from the Autism Birth Cohort, a prospective birth cohort comprising mothers, fathers, and offspring recruited in Norway in 1999 to 2008. Through questionnaires, referrals, and linkages to the Norwegian National Patient Registry, we identified 338 mothers of children with ASD and 348 frequency-matched controls for whom plasma samples that had been collected midpregnancy and after delivery were available for influenza virus serology via luciferase immunoprecipitation and hemagglutinin inhibition assays for influenza virus strains circulating during the study period. Assay data were combined to define serological status and integrated with self-reports of influenza-like illness to estimate ASD risk. Neither influenza A nor influenza B virus infection was associated with increased ASD risk. Integration of reports of symptoms of influenza-like illness with serology revealed an increase in risk for seropositive women with symptoms, but this increase did not achieve statistical significance (a level of P < 0.05) in the comparison with seronegative women without symptoms (adjusted odds ratio, 1.93 ; 95% confidence interval, 0.95 to 3.89 ; P = 0.068). Although chance may explain our findings, the magnitude of the potential association may be of biological importance, and dismissing our findings could result in failure to detect a bona fide association (type II error). If the association is true, we posit that the risk is due to activation of the maternal immune system following infection rather than direct fetal infection. Data on levels of cytokines or other mediators of inflammation would allow us to test the validity of this hypothesis. IMPORTANCE The causes of most cases of autism spectrum disorders (ASD) are unknown. Some epidemiological studies suggest that maternal gestational influenza virus infection may increase the risk of ASD in offspring. Here, we describe an analysis of a large birth cohort with results based on questionnaires that prospectively addressed subjective reports of influenza-like illness and serological assays for objective determination of influenza virus infection. Although serologic evidence of gestational influenza virus infection alone was not associated with risk, positive serology and symptoms of influenza-like illness cannot yet be definitely ruled out as a risk factor.

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10. Metcalfe SA, Martyn M, Ames A, Anderson V, Archibald AD, Couns GDG, Carter R, Cohen J, Cotter M, GenCouns M, Dang W, Delatycki MB, Donath S, Edwards S, Educ PD, Forbes R, Gavrila M, MedSci M, Halliday J, Hickerton C, Hill M, Jacobs L, Ultrasound PD, Petrou V, Plunkett L, Sheffield L, Racp F, Thornton A, Younie S, Econ PDH, Emery JD. Informed decision making and psychosocial outcomes in pregnant and nonpregnant women offered population fragile X carrier screening. Genet Med. 2017.

PurposePopulation-based carrier screening for fragile X syndrome (FXS) is still not universally endorsed by professional organizations due to concerns around genetic counseling for complex information and potential for psychosocial harms.MethodsWe determined uptake levels, decision making, and psychosocial impact in a prospective study of pregnant and nonpregnant Australian women offered FXS carrier screening in clinical settings. Women received pretest genetic counseling, and completed questionnaires when deciding and one month later.ResultsOf 1,156 women recruited, 83.1% returned the first questionnaire with 70.6% nonpregnant and 58.8% pregnant women choosing testing (chi2=16.98, P<0.001). Overall, informed choice was high in both nonpregnant (77.4%) and pregnant (72.9%) women (chi2=0.21, P=0.644), and more tested (76.0%) than not-tested (66.7%) women (chi2=6.35, P=0.012) made an informed choice. Measures of depression, stress, and anxiety were similar to population norms for 85% of women. Decisional conflict and regret were generally low ; however, decisional uncertainty and regret were greater in pregnant than nonpregnant women, and not-tested than tested women (uncertainty : chi2=18.51, P<0.001 and chi2=43.11, P<0.001, respectively ; regret : chi2=6.61, P<0.037 and chi2=35.54, P<0.001, respectively).ConclusionWe provide evidence to inform guidelines that population FXS carrier screening can be implemented with minimal psychosocial harms following appropriate information and prescreening genetic counseling.Genetics in Medicine advance online publication, 29 June 2017 ; doi:10.1038/gim.2017.67.

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11. Pellerin D, Lortie A, Corbin F. Platelets as a surrogate disease model of neurodevelopmental disorders : Insights from Fragile X Syndrome. Platelets. 2017 : 1-12.

Fragile X Syndrome (FXS) is the most common inherited form of intellectual disability and the leading monogenic cause of autism spectrum disorders (ASD). Despite a large number of therapeutics developed in past years, there is currently no targeted treatment approved for FXS. In fact, translation of the positive and very promising preclinical findings from animal models to human subjects has so far fallen short owing in part to the low predictive validity of the Fmr1 ko mouse, an overly simplistic model of the complex human disease. This issue stresses the critical need to identify new surrogate human peripheral cell models of FXS, which may in fact allow for the identification of novel and more efficient therapies. Of all described models, blood platelets appear to be one of the most promising and appropriate disease models of FXS, in part owing to their close biochemical similarities with neurons. Noteworthy, they also recapitulate some of FXS neuron’s core molecular dysregulations, such as hyperactivity of the MAPK/ERK and PI3K/Akt/mTOR pathways, elevated enzymatic activity of MMP9 and decreased production of cAMP. Platelets might therefore help furthering our understanding of FXS pathophysiology and might also lead to the identification of disease-specific biomarkers, as was shown in several psychiatric disorders such as schizophrenia and Alzheimer’s disease. Moreover, there is additional evidence suggesting that platelet signaling may assist with prediction of cognitive phenotype and could represent a potent readout of drug efficacy in clinical trials. Globally, given the neurobiological overlap between different forms of intellectual disability, platelets may be a valuable window to access the molecular underpinnings of ASD and other neurodevelopmental disorders (NDD) sharing similar synaptic plasticity defects with FXS. Platelets are indeed an attractive model for unraveling pathophysiological mechanisms involved in NDD as well as to search for diagnostic and therapeutic biomarkers.

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12. Saghazadeh A, Ahangari N, Hendi K, Saleh F, Rezaei N. Status of essential elements in autism spectrum disorder : systematic review and meta-analysis. Rev Neurosci. 2017.

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder that imposes heavy financial burden on governments and families of affected children. It is considered a multifactorial condition, where trace elements are among environmental factors that may contribute to ASD. Meanwhile, the between-study variance is high. The present systematic review was designed to investigate the difference in trace element measures between patients with ASD and control subjects. Meta-analyses showed that the hair concentrations of chromium (p=0.024), cobalt (p=0.012), iodine (p=0.000), iron (p=0.017), and magnesium (p=0.007) in ASD patients were significantly lower than those of control subjects, while there were higher magnesium levels in the hair of ASD patients compared to that of controls (p=0.010). Patients with ASD had higher blood levels of copper (p=0.000) and lower levels of zinc compared to controls (p=0.021). Further urinary iodine levels in patients with ASD were decreased in comparison with controls (p=0.026). Sensitivity analyses showed that ASD patients in non-Asian but not in Asian countries had lower hair concentrations of chromium compared to controls. Also, such analyses indicated that ASD patients in Asian countries had lower hair zinc concentrations, whereas ASD patients in non-Asian countries had higher hair zinc concentrations in comparison with control subjects. This study found significant differences in the content of trace elements between patients with ASD compared to controls. The findings help highlighting the role of trace elements as environmental factors in the etiology of ASD.

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13. Simpson K, Keen D, Adams D, Alston-Knox C, Roberts J. Participation of children on the autism spectrum in home, school, and community. Child Care Health Dev. 2017.

BACKGROUND : Children on the autism spectrum participate less frequently, and in a narrower range of activities, than their nonautistic peers, but little is known about exact participation patterns across contexts or how this is perceived by caregivers. This study aimed to document patterns of participation and caregiver views with regard to frequency and intensity of activities. METHOD : Caregivers of children on the spectrum aged 5 (n = 90) and 9-10 years (n = 128) completed the Participation and Environment Measure for Children and Youth for home, school, and community. Caregivers reported on frequency of child’s participation, level of involvement, and caregivers’ desire for change in participation patterns. RESULTS : Item-level analyses revealed similar patterns of participation across home, school, and community for both cohorts with some small age-appropriate differences. Caregivers generally desired increased diversity, frequency, and involvement in activities but a decreased use of electronics (computers, games, TV, and DVDs). CONCLUSION : The possibility of autism-specific participation patterns could inform future interventions aimed at enhancing social inclusion. This warrants further investigation through multiinformant designs that seek the perspectives of the child and caregivers.

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14. Skalny AV, Simashkova NV, Skalnaya AA, Klyushnik TP, Bjorklund G, Skalnaya MG, Tinkov AA. Assessment of gender and age effects on serum and hair trace element levels in children with autism spectrum disorder. Metab Brain Dis. 2017.

The primary objective of the present study was to investigate the levels of essential trace elements in hair and serum in children with autism spectrum disorder (ASD) and investigate the age and gender effects. Children with ASD were characterized by significantly higher levels of copper (Cu) (+8%), iron (Fe) (+5%), and selenium (Se) (+13%) levels in hair and only 8% higher serum Cu levels. After stratification for gender, ASD boys were characterized by significantly increased hair Cu (+ 25%), Fe (+ 25%), and Se (+ 9%) levels, whereas in girls only Se content was elevated (+ 15%). Boys and girls suffering from ASD were characterized by significantly higher serum manganese (Mn) (+20%) and Cu (+18%) as compared to the control values, respectively. In the group of younger children (2-5 years), no significant group difference in hair trace element levels was detected, whereas serum Cu levels were significantly higher (+7%). In turn, the serum concentration of Se in ASD children was 11% lower than that in neurotypical children. In the group of older children with ASD (6-10 years), hair Fe and Se levels were 21% and 16% higher, whereas in serum only Cu levels were increased (+12%) as compared to the controls. Correlation analysis also revealed a different relationship between serum and hair trace element levels with respect to gender and age. Therefore, it is highly recommended to assess several bioindicative matrices for critical evaluation of trace element status in patients with ASD in order to develop adequate personalized nutritional correction.

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15. Subbaraju V, Sundaram S, Narasimhan S. Identification of lateralized compensatory neural activities within the social brain due to autism spectrum disorder in adolescent males. Eur J Neurosci. 2017.

Socio-behavioral impairments are important characteristics of Autism Spectrum Disorders (ASD) and MRI based studies are pursued to identify a neurobiological basis behind these conditions. This paper presents an MRI based study undertaken to (i) identify the differences in brain activities due to ASD, (ii) verify whether such differences exist within the "social brain" circuit which is hypothesized to be responsible for social functions and (iii) uncover potential compensatory mechanisms within the identified differences in brain activities. In this study, a whole brain voxel wise analysis is performed using resting state fMRI data from 598 adolescent males, that is openly available from the ABIDE consortium. A new method is developed, that can (i) extract the discriminative brain activities, that provide high separability between the blood oxygenation time-series signals from ASD and neurotypical populations, (ii) select the activities that are relevant to ASD by evaluating the correlation between the separability and traditional severity scores and (iii) map the spatial pattern of regions responsible for generating the discriminative activities. The results show that the most discriminative brain activities occur within a subset of the social brain that is involved with affective aspects of social processing, thereby supporting the idea of the social brain and also its fractionalization in ASD. Further, it has also been found that the diminished activities in the posterior cingulate area is potentially compensated by enhanced activities in the ventromedial prefrontal and anterior temporal areas within the social brain. Hemispherical lateralization is also observed on such compensatory activities. This article is protected by copyright. All rights reserved.

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16. Yamaguchi H, Hara Y, Ago Y, Takano E, Hasebe S, Nakazawa T, Hashimoto H, Matsuda T, Takuma K. Environmental enrichment attenuates behavioral abnormalities in valproic acid-exposed autism model mice. Behav Brain Res. 2017.

We recently demonstrated that prenatal exposure to valproic acid (VPA) at embryonic day 12.5 causes autism spectrum disorder (ASD)-like phenotypes such as hypolocomotion, anxiety-like behavior, social deficits and cognitive impairment in mice and that it decreases dendritic spine density in the hippocampal CA1 region. Previous studies show that some abnormal behaviors are improved by environmental enrichment in ASD rodent models, but it is not known whether environmental enrichment improve cognitive impairment. In the present study, we examined the effects of early environmental enrichment on behavioral abnormalities and neuromorphological changes in prenatal VPA-treated mice. We also examined the role of dendritic spine formation and synaptic protein expression in the hippocampus. Mice were housed for 4 weeks from 4 weeks of age under either a standard or enriched environment. Enriched housing was found to increase hippocampal brain-derived neurotrophic factor mRNA levels in both control and VPA-exposed mice. Furthermore, in VPA-treated mice, the environmental enrichment improved anxiety-like behavior, social deficits and cognitive impairment, but not hypolocomotion. Prenatal VPA treatment caused loss of dendritic spines in the hippocampal CA1 region and decreases in mRNA levels of postsynaptic density protein-95 and SH3 and multiple ankyrin repeat domains 2 in the hippocampus. These hippocampal changes were improved by the enriched housing. These findings suggest that the environmental enrichment improved most ASD-like behaviors including cognitive impairment in the VPA-treated mice by enhancing dendritic spine function.

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17. Yang PY, Menga YJ, Li T, Huang Y. Associations of endocrine stress-related gene polymorphisms with risk of autism spectrum disorders : Evidence from an integrated meta-analysis. Autism Res. 2017.

Autism spectrum disorders (ASD) are related to serotonin transporter (5-HTT) and catechol-O-methyl transferase (COMT) as two most monoaminergic polymorphic variations. However, multiple studies assessing rs4680 and 5-HTTLPR variants in ASD have reported inconsistent results. Therefore, we conducted an integrated meta-analysis to combine case-control and transmission/disequilibrium test (TDT) studies to determine whether COMT and 5-HTT are associated with ASD. We searched multiple electronic databases (PubMed, EmBase and Web of Science) to identify studies assessing the rs4680 and 5-HTTLPR variants in ASD from Jan 1997 to Dec 2016. Then allelic data from case-control and TDT studies were analyzed by the Catmap package in the R software. A total of 5 studies were eligible for the meta-analysis of rs4680, including 3 case-control, 1 TDT and 1 TDT & case-control studies. Meanwhile, 22 studies of 5-HTTLPR were available, including 16 TDT, 4 case-control and 2 TDT & case-control studies. The current meta-analysis included 814 ASD cases, 741 controls and 311 families related to rs4680 ; 749 ASD cases, 1,118 controls and 1,861 families relevant to 5-HTTLPR were also evaluated. For rs4680, the pooled OR was 1.18 (95% CI = 0.87-1.59, P = 0.29, Pheterogeneity < 0.00001). There was no significant association of rs4680 with risk of ASD between the two subgroups. For 5-HTTLPR, the pooled OR was 1.05 (95% CI = 0.92-1.20, P = 0.4652, Pheterogeneity < 0.00001). Meanwhile, we found no significant risk in individual case-control or TDT studies. The above findings indicated that neither COMT rs4680 nor 5-HTT 5-HTTLPR polymorphism significantly affects ASD risk. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.

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