Pubmed du 19/06/19

mercredi 19 juin 2019

1. Abdelli LS, Samsam A, Naser SA. Propionic Acid Induces Gliosis and Neuro-inflammation through Modulation of PTEN/AKT Pathway in Autism Spectrum Disorder. Sci Rep ;2019 (Jun 19) ;9(1):8824.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by glia over-proliferation, neuro-inflammation, perturbed neural circuitry, and gastrointestinal symptoms. The role of gut dys-biosis in ASD is intriguing and should be elucidated. We investigated the effect of Propionic acid (PPA), a short-chain fatty acid (SCFA) and a product of dys-biotic ASD gut, on human neural stem cells (hNSCs) proliferation, differentiation and inflammation. hNSCs proliferated to 66 neuropsheres when exposed to PPA versus 45 in control. The neurosphere diameter also increased at day 10 post PPA treatment to (Mean : 193.47 um +/- SEM : 6.673 um) versus (154.16 um +/- 9.95 um) in control, p < 0.001. Pre-treatment with beta-HB, SCFA receptor inhibitor, hindered neurosphere expansion (p < 0.001). While hNSCs spontaneously differentiated to (48.38% +/- 6.08%) neurons (Tubulin-IIIbeta positive) and (46.63% +/- 2.5%) glia (GFAP positive), PPA treatment drastically shifted differentiation to 80% GFAP cells (p < 0.05). Following 2 mM PPA exposure, TNF-alpha transcription increased 4.98 fold and the cytokine increased 3.29 fold compared to control (P < 0.001). Likewise, GPR41 (PPA receptor) and pro-survival p-Akt protein were elevated (p < 0.001). PTEN (Akt inhibitor) level decreased to (0.42 ug/ul +/- 0.04 ug/ul) at 2 mM PPA compared to (0.83 ug/ul +/- 0.09 ug/ul) in control (p < 0.001). PPA at 2 mM decreased neurite outgrowth to (80.70 um +/- 5.5 um) compared to (194.93 um +/- 19.7 um) in control. Clearly, the data supports a significant role for PPA in modulating hNSC patterning leading to gliosis, disturbed neuro-circuitry, and inflammatory response as seen in ASD.

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2. Alawami AH, Perrin EC, Sakai C. Implementation of M-CHAT Screening for Autism in Primary Care in Saudi Arabia. Glob Pediatr Health ;2019 ;6:2333794x19852021.

Background. Integration of autism screening into primary care practice in Saudi Arabia is not well established. Objectives. To evaluate the feasibility and effectiveness of implementing the Arabic Modified Checklist for Autism in Toddlers (M-CHAT) in a primary care practice at John Hopkins Aramco Healthcare Center in Saudi Arabia. Method. The Arabic version of M-CHAT was distributed to caregivers of 1207 toddlers (16-32 months) from January to December 2014. Feasibility was assessed by measuring the proportion of visits with M-CHAT completed, and reports of workflow challenges and provider satisfaction. The effectiveness of screening was evaluated based on the number of referrals for autism evaluation and autism identification rates. Results. Total M-CHAT completion rate was 89% (1078 out of 1207 child-specific visits). Those identified as low risk (n = 951 ; 88%) were reassured and followed routinely. Those screening positive (n = 127 ; 12%) were referred for diagnostic assessment. Twelve (1% of toddlers screened) were diagnosed with autism at a mean age of 24 months. In addition, positive M-CHAT detected speech delay and social anxiety. Providers acknowledged their satisfaction with the M-CHAT implementation process ; the main challenge was communicating to families the importance of screening. Referrals for diagnostic evaluations increased from 23 to 43 cases in the first year, and 35 in the second year. Conclusion. Implementation of the autism screening using the Arabic M-CHAT is feasible and effective in a primary care setting in Saudi Arabia. Sustaining the implementation of developmental screening in practice requires staff engagement and systematic monitoring of the impact of change.

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3. Alvares GA, Bebbington K, Cleary D, Evans K, Glasson EJ, Maybery MT, Pillar S, Uljarevic M, Varcin K, Wray J, Whitehouse AJ. The misnomer of ’high functioning autism’ : Intelligence is an imprecise predictor of functional abilities at diagnosis. Autism ;2019 (Jun 19):1362361319852831.

’High functioning autism’ is a term often used for individuals with autism spectrum disorder without an intellectual disability. Over time, this term has become synonymous with expectations of greater functional skills and better long-term outcomes, despite contradictory clinical observations. This study investigated the relationship between adaptive behaviour, cognitive estimates (intelligence quotient) and age at diagnosis in autism spectrum disorder. Participants (n = 2225, 1-18 years of age) were notified at diagnosis to a prospective register and grouped by presence (n = 1041) or absence (n = 1184) of intellectual disability. Functional abilities were reported using the Vineland Adaptive Behaviour Scales. Regression models suggested that intelligence quotient was a weak predictor of Vineland Adaptive Behaviour Scales after controlling for sex. Whereas the intellectual disability group’s adaptive behaviour estimates were close to reported intelligence quotients, Vineland Adaptive Behaviour Scales scores fell significantly below intelligence quotients for children without intellectual disability. The gap between intelligence quotient and Vineland Adaptive Behaviour Scales scores remained large with increasing age at diagnosis for all children. These data indicate that estimates from intelligence quotient alone are an imprecise proxy for functional abilities when diagnosing autism spectrum disorder, particularly for those without intellectual disability. We argue that ’high functioning autism’ is an inaccurate clinical descriptor when based solely on intelligence quotient demarcations and this term should be abandoned in research and clinical practice.

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4. Aspromonte MC, Bellini M, Gasparini A, Carraro M, Bettella E, Polli R, Cesca F, Bigoni S, Boni S, Carlet O, Negrin S, Mammi I, Milani D, Peron A, Sartori S, Toldo I, Soli F, Turolla L, Stanzial F, Benedicenti F, Marino-Buslje C, Tosatto SCE, Murgia A, Leonardi E. Characterization of Intellectual disability and Autism comorbidity through gene panel sequencing. Hum Mutat ;2019 (Jun 17)

Intellectual disability (ID) and autism spectrum disorder (ASD) are clinically and genetically heterogeneous diseases. Recent whole exome sequencing studies indicated that genes associated with different neurological diseases are shared across disorders and converge on common functional pathways. Using the Ion Torrent platform, we developed a low-cost next generation sequencing (NGS) gene panel that has been transferred into clinical practice, replacing single disease gene analyses for the early diagnosis of individuals with ID/ASD. The gene panel was designed using an innovative in silico approach based on disease networks and mining data from public resources to score disease-gene associations. We analyzed 150 unrelated individuals with ID and/or ASD and a confident diagnosis has been reached in 26 cases (17%). Likely pathogenic mutations have been identified in another 15 patients, reaching a total diagnostic yield of 27%. Our data also support the pathogenic role of genes recently proposed to be involved in ASD. Although many of the identified variants need further investigation to be considered disease-causing, our results indicate the efficiency of the targeted gene panel on the identification of novel and rare variants in patients with ID and ASD. This article is protected by copyright. All rights reserved.

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5. Baghdadli A, Miot S, Rattaz C, Akbaraly T, Geoffray MM, Michelon C, Loubersac J, Traver S, Mortamais M, Sonie S, Pottelette J, Robel L, Speranza M, Vesperini S, Maffre T, Falissard B, Picot MC. Investigating the natural history and prognostic factors of ASD in children : the multicEntric Longitudinal study of childrEN with ASD - the ELENA study protocol. BMJ Open ;2019 (Jun 19) ;9(6):e026286.

INTRODUCTION : There is global concern about the increasing prevalence of autism spectrum disorders (ASDs), which are early-onset and long-lasting disorders. Although ASDs are considered to comprise a unique syndrome, their clinical presentation and outcome vary widely. Large-scale and long-term cohort studies of well-phenotyped samples are needed to better understand the course of ASDs and their determinants. The primary objective of the multicEntric Longitudinal study of childrEN with ASD (ELENA) study is to understand the natural history of ASD in children and identify the risk and prognostic factors that affect their health and development. METHODS AND ANALYSIS : This is a multicentric, longitudinal, prospective, observational cohort in which 1000 children with ASD diagnosed between 2 and 16 years of age will be recruited by 2020 and followed over 6 years. The baseline follow-up starts with the clinical examination to establish the ASD diagnosis. A battery of clinical tools consisting of the Autism Diagnostic Observation Schedule, the revised version of the Autism Diagnostic Interview, measures of intellectual functioning, as well as large-scale behavioural and developmental measurements will allow us to study the heterogeneity of the clinical presentation of ASD subtypes. Subsequent follow-up at 18 months and at 3, 4.5 and 6 years after the baseline examination will allow us to explore the developmental trajectories and variables associated with the severity of ASD. In addition to the children’s clinical and developmental examinations, parents are invited to complete self-reported questionnaires concerning perinatal and early postnatal history, congenital anomalies, genetic factors, lifestyle factors, medical and psychiatric comorbidities, and the socioeconomic environment. As of 1 November 2018, a total of 766 participants have been included. ETHICS AND DISSEMINATION : Ethical approval was obtained through the Marseille Mediterranean Ethics Committee (ID RCB : 2014-A01423-44), France. We aim to disseminate the findings through national and international conferences, international peer-reviewed journals, and social media. TRIAL REGISTRATION NUMBER : NCT02625116 ; Pre-results.

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6. Black MH, Chen NT, Lipp OV, Bolte S, Girdler S. Complex facial emotion recognition and atypical gaze patterns in autistic adults. Autism ;2019 (Jun 19):1362361319856969.

While altered gaze behaviour during facial emotion recognition has been observed in autistic individuals, there remains marked inconsistency in findings, with the majority of previous research focused towards the processing of basic emotional expressions. There is a need to examine whether atypical gaze during facial emotion recognition extends to more complex emotional expressions, which are experienced as part of everyday social functioning. The eye gaze of 20 autistic and 20 IQ-matched neurotypical adults was examined during a facial emotion recognition task of complex, dynamic emotion displays. Autistic adults fixated longer on the mouth region when viewing complex emotions compared to neurotypical adults, indicating that altered prioritization of visual information may contribute to facial emotion recognition impairment. Results confirm the need for more ecologically valid stimuli for the elucidation of the mechanisms underlying facial emotion recognition difficulty in autistic individuals.

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7. Blair LM, Ford JL. Neighborhood Context and the Risk for Developmental Disabilities in Early Childhood. Matern Child Health J ;2019 (Jun 17)

The effects of place on human health and development have been extensively studied in recent years in the adult and adolescent populations, but minimal research has addressed neighborhood effects in early childhood. This analysis of the National Survey of Children’s Health 2011/2012 cross-sectional survey examined relationships between risk for developmental disability in early childhood and neighborhood characteristics in a nationally-representative sample of children ages 0-5 years. Parents reported on their child’s development using a well-validated parent report screening tool for developmental problems (the Parent’s Evaluation of Developmental Status tool), and neighborhood and family characteristics. Multinomial logistic regression analyses were conducted for each of three neighborhood variables : physical disorder, safety, and isolation. After controlling for parental and child characteristics, the three neighborhood variables were each significantly associated with moderate (but not severe) risk versus low to no risk for developmental disabilities. When all neighborhood characteristics were included simultaneously in the same model, only physical disorder remained statistically significant [OR 1.44 (95% CI 1.09-1.91)], though modestly attenuated. These results suggest that neighborhoods may have effects on early childhood development, after controlling for individual child, parental, and family characteristics.

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8. Campbell-Scherer D. Evidence from large Danish cohort does not support an association between the MMR vaccine and autism : facts in a post-truth world. BMJ Evid Based Med ;2019 (Jun 19)

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9. Capriola-Hall NN, Wieckowski AT, Swain D, Tech V, Aly S, Youssef A, Abbott AL, White SW. Group Differences in Facial Emotion Expression in Autism : Evidence for the Utility of Machine Classification. Behav Ther ;2019 (Jul) ;50(4):828-838.

Effective social communication relies, in part, on accurate nonverbal expression of emotion. To evaluate the nature of facial emotion expression (FEE) deficits in children with autism spectrum disorder (ASD), we compared 20 youths with ASD to a sample of typically developing (TD) youth (n = 20) using a machine-based classifier of FEE. Results indicate group differences in FEE for overall accuracy across emotions. In particular, a significant group difference in accuracy of FEE was observed when participants were prompted by a video of a human expressing an emotion, F(2, 36) = 4.99, p = .032, eta(2) = .12. Specifically, youth with ASD made significantly more errors in FEE relative to TD youth. Findings support continued refinement of machine-based approaches to assess and potentially remediate FEE impairment in youth with ASD.

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10. Corbett BA, Blain SD, Kale Edmiston E. The Role of Context in Psychosocial Stress among Adolescents with Autism Spectrum Disorder : Piloting a Semi-structured, Videogame-based Paradigm. J Intellect Dev Disabil ;2018 ;43(1):20-28.

Background : Autism Spectrum Disorder (ASD) is characterised by altered social patterns, often associated with increased stress. While puberty is associated with increased stress, there is limited research on stress response to social interaction in adolescents with ASD. The study investigated stress response to semi-structured, videogame-based interaction in adolescents with and without ASD, and the impact of puberty. Method : Twelve adolescents with ASD and 12 typically developing (TD) peers participated in a semi-structured, videogame-based social interaction. Stress was measured via salivary cortisol. Results : There were no significant between-group differences in cortisol. Pubertal development was correlated with cortisol in ASD (r = -0.901, p < 0.0001), but not TD (r = 0.022, p = 0.949). Conclusions : Findings contribute to a fuller picture of the developmental trajectories of physiological stress in ASD, including the importance of context, structure, and puberty. The current investigation underscores the necessity of incorporating varied social contexts when assessing stress and social interaction.

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11. Crandall MC, McDaniel J, Watson LR, Yoder PJ. The Relation Between Early Parent Verb Input and Later Expressive Verb Vocabulary in Children With Autism Spectrum Disorder. J Speech Lang Hear Res ;2019 (Jun 19) ;62(6):1787-1797.

Purpose The purpose of this study was to evaluate if higher quantity, diversity, and grammatical informativeness of verb phrases in parent follow-in utterances (i.e., utterances that mapped onto child attentional leads) were significantly related to later expressive verb vocabulary in children with autism spectrum disorder (ASD). Method We examined these associations in a sample of 31 toddlers with ASD and their parents in a longitudinal correlational study. Key aspects of parents’ verb input were measured in 2 video-recorded 15-min parent-child free-play sessions. Child expressive verb vocabulary was measured using parent report. Results An aggregate variable composed of the quantity, diversity, and grammatical informativeness of parent verb input in follow-in utterances across the 2 parent-child sessions strongly and positively predicted later child expressive verb vocabulary, total R (2) = .25, even when early child expressive verb vocabulary was controlled, R (2) change = .17. Parent follow-in utterances without verbs were not significantly related to later child expressive verb vocabulary, R (2) = .001. Conclusions These correlational findings are initial steps toward developing a knowledge base for how strong verb vocabulary skills might be facilitated in children with ASD.

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12. Doan RN, Lim ET, De Rubeis S, Betancur C, Cutler DJ, Chiocchetti AG, Overman LM, Soucy A, Goetze S, Freitag CM, Daly MJ, Walsh CA, Buxbaum JD, Yu TW. Recessive gene disruptions in autism spectrum disorder. Nat Genet ;2019 (Jun 17)

Autism spectrum disorder (ASD) affects up to 1 in 59 individuals(1). Genome-wide association and large-scale sequencing studies strongly implicate both common variants(2-4) and rare de novo variants(5-10) in ASD. Recessive mutations have also been implicated(11-14) but their contribution remains less well defined. Here we demonstrate an excess of biallelic loss-of-function and damaging missense mutations in a large ASD cohort, corresponding to approximately 5% of total cases, including 10% of females, consistent with a female protective effect. We document biallelic disruption of known or emerging recessive neurodevelopmental genes (CA2, DDHD1, NSUN2, PAH, RARB, ROGDI, SLC1A1, USH2A) as well as other genes not previously implicated in ASD including FEV (FEV transcription factor, ETS family member), which encodes a key regulator of the serotonergic circuitry. Our data refine estimates of the contribution of recessive mutation to ASD and suggest new paths for illuminating previously unknown biological pathways responsible for this condition.

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13. El Fotoh W, El Naby SAA, Abd El Hady NMS. Autism Spectrum Disorders : The Association with Inherited Metabolic Disorders and Some Trace Elements. A Retrospective Study. CNS Neurol Disord Drug Targets ;2019 (Apr 30)

BACKGROUND : Autism spectrum disorders (ASD) as a considerable health obstacle in kids characterized by compromised social collaboration, and stereotyped behavior. Autism is triggered by an interaction of environmental and genetic influences. It is assumed that some inborn errors of metabolism are implicated in a sector of developmental disabilities. Also, a number of trace elements may have an important role in human behavior and neurological development. This study was designed to verify the frequency of inherited metabolic disorders and /or trace element abnormalities in children with ASD. METHODS : In a retrospective analytical study, 320 children diagnosed with ASD according to the DSM-V criteria and Childhood Autism Rating Scale criteria were enrolled in this study. Serum ammonia, blood lactate, and arterial blood gases, plasma amino acid profile by tandem mass spectrophotometry, and a urinary organic acid assay was performed in all patients. Likewise, the estimation of a number of trace elements in the form of serum lead, mercury, copper, and plasma zinc was done in all patients. RESULTS : A total of 320 children with ASD, inherited metabolic disorders were identified in eight (2.5%) patients as follows : seven (2.19) patients with phenylketonuria, and only one (0.31%) patient with glutaric aciduria type 1. As regards the trace element deficiency, sixteen (5%) patients had low plasma zinc level, five (1.56%) children had a high serum copper level, two (0.62%) children had a high serum lead level and only one (0.31%) autistic child had high serum mercury level. EEG abnormalities were reported in 13.12% and MRI abnormalities in 8.43% of cases. CONCLUSION : Screening for metabolic diseases and trace elements is required in any child with ASD even no apparent clinical attributes of metabolic complaints and trace elements discrepancies.

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14. Ess KC, Franz DN. Everolimus for cognition/autism in children with tuberous sclerosis complex : Definitive outcomes deferred. Neurology ;2019 (Jun 19)

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15. Ferguson RH, Falcomata TS, Ramirez-Cristoforo A, Vargas Londono F. An Evaluation of the Effects of Varying Magnitudes of Reinforcement on Variable Responding Exhibited by Individuals With Autism. Behav Modif ;2019 (Jun 19):145445519855615.

Interventions aimed at increasing communicative response variability hold particular importance for individuals with autism spectrum disorders (ASD). Several procedures have been demonstrated in the applied and translational literature to increase response variability. However, little is known about the relationship between reinforcer magnitude and response variability. In the basic literature, Doughty, Giorno, and Miller evaluated the effects of reinforcer magnitude on behavioral variability by manipulating reinforcer magnitude across alternating relative frequency threshold contingencies, with results suggesting that larger reinforcers induced repetitive responding. The purpose of this study was to translate Doughty et al.’s findings to evaluate the relative effects of different magnitudes of reinforcement on communicative response variability in children with ASD. A Lag 1 schedule of reinforcement was in place during each condition within an alternating treatments design. Magnitudes of reinforcement contingent on variable communicative responding were manipulated across the two conditions. Inconsistent with basic findings, the results showed higher levels of variable communicative responding associated with the larger magnitude of reinforcement. These outcomes may have potential implications for interventions aimed at increasing response variability in individuals with ASD, as well as future research in this area.

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16. Hattori A, Kamagata K, Kirino E, Andica C, Tanaka S, Hagiwara A, Fujita S, Maekawa T, Irie R, Kumamaru KK, Suzuki M, Wada A, Hori M, Aoki S. White matter alterations in adult with autism spectrum disorder evaluated using diffusion kurtosis imaging. Neuroradiology ;2019 (Jun 18)

PURPOSE : Autism spectrum disorder (ASD) is related to impairment in various white matter (WM) pathways. Utility of the recently developed two-compartment model of diffusion kurtosis imaging (DKI) to analyse axial diffusivity of WM is restricted by several limitations. The present study aims to validate the utility of model-free DKI in the evaluation of WM alterations in ASD and analyse the potential relationship between DKI-evident WM alterations and personality scales. METHODS : Overall, 15 participants with ASD and 15 neurotypical (NT) controls were scanned on a 3 T magnetic resonance (MR) scanner, and scores for autism quotient (AQ), systemising quotient (SQ) and empathising quotient (EQ) were obtained for both groups. Multishell diffusion-weighted MR data were acquired using two b-values (1000 and 2000 s/mm(2)). Differences in mean kurtosis (MK), radial kurtosis (RK) and axial kurtosis (AK) between the groups were evaluated using tract-based spatial statistics (TBSS). Finally, the relationships between the kurtosis indices and personality quotients were examined. RESULTS : The ASD group demonstrated significantly lower AK in the body and splenium of corpus callosum than the NT group ; however, no other significant differences were identified. Negative correlations were found between AK and AQ or SQ, predominantly in WM areas related to social-emotional processing such as uncinate fasciculus, inferior fronto-occipital fasciculus, and inferior and superior longitudinal fasciculi. CONCLUSIONS : Model-free DKI and its indices may represent a novel, objective method for detecting the disease severity and WM alterations in patients with ASD.

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17. Hens K. The many meanings of autism : conceptual and ethical reflections. Dev Med Child Neurol ;2019 (Jun 17)

Autism is a polysemous concept. It is defined as a neurodevelopmental disorder that is diagnosed based on an assessment of behaviour and dysfunction. Autism also refers to a specific way of information or sensorial processing. For those diagnosed with autism, it is a real and shared experience. In this paper, I sketch the moral work that biological conceptions of autism perform. They help to conceptualize the diagnosis and associated challenges as real and they remove some of the blame from the diagnosed person and/or their parents. But such approaches also risk neglecting the role of behaviour as a meaningful reaction to experiences. In thinking about the ethics of autism research, diagnosis of autism, and autism care, the recent findings of epigenetics and systems biology may help us overcome the dichotomy between biology and psyche, and point the way to a more nuanced and ethical view. WHAT THIS PAPER ADDS : The meaning of ’autism’ has different layers and as such autism is a polysemous concept. The lived experience of autistic people matters in research.

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18. Herrera-Moncada M, Campos-Lara P, Hernandez-Cabanillas JC, Bermeo-Escalona JR, Pozos-Guillen A, Pozos-Guillen F, Garrocho-Rangel JA. Autism and Paediatric Dentistry : A Scoping Review. Oral Health Prev Dent ;2019 ;17(3):203-210.

PURPOSE : The objectives of this scoping review were : first, to pose a research question ; second, to identify relevant studies to answer the research question ; third, to select and retrieve the studies ; fourth, to chart the critical data ; and finally, to collate, summarise, and report the results from selected articles on the dental management of children affected with autism. MATERIALS AND METHODS : Relevant articles (randomised controlled trials, reviews, observational studies, and clinical case reports) published over an 11-year period were identified and retrieved from five internet databases : PubMed, Embase/Ovid, Cochrane Library, Google Scholar, and EBSCO. RESULTS : By title and abstract screening and after removing duplicates, 25 articles were finally included in the present scoping review. According to the extracted data, the following four clinical issues were found to be most important : patient behavioural control, prevalence/incidence of dental caries, adverse effects and interactions with medications, and orthodontic management. Additionally, several useful clinical recommendations are provided. CONCLUSIONS : Paediatric dentists should bear in mind that early diagnosis and treatment, effective communication skills, and a long-term follow-up of children with autism continue to be the best approaches for achieving enhanced patient psychological well-being and consequently a better quality of life.

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19. Honma M, Itoi C, Midorikawa A, Terao Y, Masaoka Y, Kuroda T, Futamura A, Shiromaru A, Ohta H, Kato N, Kawamura M, Ono K. Contraction of distance and duration production in autism spectrum disorder. Sci Rep ;2019 (Jun 19) ;9(1):8806.

Autism spectrum disorder (ASD) presents certain hallmark features associated with cognitive and social functions, however, the ability to estimate self-generated distance and duration in individuals with ASD are unclear. We compared the performance of 20 ASD individuals with 20 typical developments (TDs) with respect to two tasks : (1) the drawing of a line of a specified distance (10 or 20 cm) and (2) waiting for a specified time (10 or 20 s). We observed that both the line distances and waiting times were substantially shorter in the ASD group than in the TD group. Furthermore, a trait of "attention to detail," as measured by the Autism-Spectrum Quotient, correlated with some distance and duration productions observed in individuals with ASD. We suggest that attentional functions are related to the contraction of distance and duration in ASD.

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20. Liu J, Wan GB, Huang MS, Agyapong G, Zou TL, Zhang XY, Liu YW, Song YQ, Tsai YC, Kong XJ. Erratum to : Probiotic Therapy for Treating Behavioral and Gastrointestinal Symptoms in Autism Spectrum Disorder : A Systematic Review of Clinical Trials. Curr Med Sci ;2019 (Jun) ;39(3):512.

The original version of this article unfortunately contained two mistakes. The name and the work address of one author are wrong. The corrected name and work address are given below.Guo-bin WAN(2dagger) (2) Shenzhen Maternity & Child Healthcare Hospital, Shenzhen 518048, China.

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21. Mandell DS, Candon MK, Xie M, Marcus SC, Kennedy-Hendricks A, Epstein AJ, Barry CL. Effect of Outpatient Service Utilization on Hospitalizations and Emergency Visits Among Youths With Autism Spectrum Disorder. Psychiatr Serv ;2019 (Jun 19):appips201800290.

OBJECTIVE : Psychiatric hospitalizations and emergency department (ED) visits occur more frequently for youths with autism spectrum disorder (ASD). One mechanism that may reduce the likelihood of these events is utilization of home and community-based care. Using commercial claims data and a rigorous analytical framework, this retrospective study examined whether spending on outpatient services for ASD, including occupational, physical, and speech therapies and other behavioral interventions, reduced the likelihood of psychiatric hospitalizations and ED visits. METHODS : The study sample was composed of >100,000 children and young adults with ASD and commercial insurance from every state between 2008 and 2012. The authors estimated maximum-likelihood complementary log-log link survival models with robust standard errors. The outcomes of interest were a hospitalization or an ED visit with an associated psychiatric diagnosis code (ICD-9-CM 290 through 319) in a given week. RESULTS : An increase of $125 in weekly spending on ASD-specific outpatient services in the 7 to 14 weeks prior to a given week reduced the likelihood of a psychiatric hospitalization in that week by 2%. ASD-specific outpatient spending during the 6 weeks prior to a psychiatric hospitalization did not decrease risk of hospitalization. Spending on ASD-specific outpatient services did not reduce the likelihood of a psychiatric ED visit. CONCLUSIONS : The financial burden associated with ASD is extensive, and psychiatric hospitalizations remain the most expensive type of care, costing more than $4,000 per week on average. Identifying the mechanisms by which psychiatric hospitalizations occur may reduce the likelihood of these events.

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22. Nogay NH, Nahikian-Nelms M. Can we reduce autism-related gastrointestinal and behavior problems by gut microbiota based dietary modulation ? A review. Nutr Neurosci ;2019 (Jun 19):1-12.

Introduction : Autism is a neurodevelopmental disorder that negatively affects a child’s interaction and communication with the environment. The signals between intestine, brain, and microbiota change in autism. Altering the composition of microbiota may contribute to the development of clinical symptoms. Diet is one of the most important factors influencing intestinal microbiota. Aim : This study aimed to investigate the role of intestinal microbiota in gastrointestinal (GI) and behavioral problems seen in children with autism and discuss the potential effect of diet on intestinal microbiota in reducing these problems. Methods : The database Web of Science was searched for relevant studies. The combinations of the following terms were used for the search : ’autism’ or ’autistic’ and ’microbiome’ or ’microbiota’ or ’gut bacteria’ or ’gut microbiota’ or ’gut microbiome.’ The analysis included human studies evaluating the relationship between GI problems and/or behavioral problems and intestinal microbiota in autism in the English language with no time limitation. Results : The initial search resulted in 691 studies, with 14 studies fully meeting the inclusion criteria. In these studies, high growth rates of Clostridium histolyticum, C. perfringens, and Sutterella ; high ratio of Escherichia/Shigella ; and low ratio of Bacteroidetes/Firmicutes were generally related to GI problems, while relative abundance of Desulfovibrio, Clostridium spp., and Bacteroides vulgatus were associated with behavior disorders. Conclusions : Published studies on the relationship of gastrointestinal and behavioral problems with gut microbiota in autism are very limited and contradictory. The fact that the results of the studies are not consistent with each other may be explained by the differences in the age of participants, geographical region, sample size, presence of GI problems in the selected control group, and feces or biopsy samples taken from different regions of GI system. With the available information, it is not yet possible to develop a gut microbiota-based nutritional intervention to treat GI symptoms for people with autism.

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23. Overwater IE, Rietman AB, Mous SE, Bindels-de Heus K, Rizopoulos D, Ten Hoopen LW, van der Vaart T, Jansen FE, Elgersma Y, Moll HA, de Wit MY. A randomized controlled trial with everolimus for IQ and autism in tuberous sclerosis complex. Neurology ;2019 (Jun 19)

OBJECTIVE : To investigate whether mammalian target of rapamycin inhibitor everolimus can improve intellectual disability, autism, and other neuropsychological deficits in children with tuberous sclerosis complex (TSC). METHODS : In this 12-month, randomized, double-blind, placebo-controlled trial, we attempted to enroll 60 children with TSC and IQ <80, learning disability, special schooling, or autism, aged 4-17 years, without intractable seizures to be assigned to receive everolimus or placebo. Everolimus was titrated to blood trough levels of 5-10 ng/mL. Primary outcome was full-scale IQ ; secondary outcomes included autism, neuropsychological functioning, and behavioral problems. RESULTS : Thirty-two children with TSC were randomized. Intention-to-treat analysis showed no benefit of everolimus on full-scale IQ (treatment effect -5.6 IQ points, 95% confidence interval -12.3 to 1.0). No effect was found on secondary outcomes, including autism and neuropsychological functioning, and questionnaires examining behavioral problems, social functioning, communication skills, executive functioning, sleep, quality of life, and sensory processing. All patients had adverse events. Two patients on everolimus and 2 patients on placebo discontinued treatment due to adverse events. CONCLUSIONS : Everolimus did not improve cognitive functioning, autism, or neuropsychological deficits in children with TSC. The use of everolimus in children with TSC with the aim of improving cognitive function and behavior should not be encouraged in this age group. CLINICALTRIALSGOV IDENTIFIER : NCT01730209. CLASSIFICATION OF EVIDENCE : This study provides Class I evidence that for children with TSC, everolimus does not improve intellectual disability, autism, behavioral problems, or other neuropsychological deficits.

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24. Schelly D, Gonzalez PJ, Solis PJ. Barriers to an Information Effect on Diagnostic Disparities of Autism Spectrum Disorder in Young Children. Health Serv Res Manag Epidemiol ;2019 (Jan-Dec) ;6:2333392819853058.

Objectives : Autism spectrum disorder (ASD) is underdiagnosed in children from minority and low socioeconomic status families, and reports indicate that parental "lack of awareness" of symptoms is a factor, which implicates the adoption of the category globally. However, parental knowledge of ASD has failed to explain emerging clusters of cases. The objective of the present research was to identify and describe barriers to an "information effect" in diagnosis. Methods : Interviews were conducted with the parents of 54 children with ASD in Costa Rica, many living within clusters that appeared after a genetic study conducted an information campaign for recruitment. The interviews explored factors influencing symptom recognition and help-seeking behaviors. Several barriers were identified that prevent information about ASD or exposure to diagnosed cases from influencing parents’ help-seeking behaviors. Results : Early symptoms in most children gave parents no reason to suspect ASD. Later, parents’ understanding of ASD depended on caricatures of the disorder. Parents often received unsolicited advice from strangers, although rarely from family, and it was always seen as critical of their parenting ; furthermore, the advice was too late to influence the referral process, which was well underway by the time classical symptoms of ASD appeared, if they did at all. Postdiagnosis, the interviewees occasionally gave advice to other parents, mostly strangers, but none had apparently been diagnosed. Conclusions : The results implicate efforts to educate parents about symptoms of ASD, where a focus on generic developmental delays and neurodevelopmental disorders in general may be more effective than ASD-specific information.

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25. Sheikh R, Patino V, Cengher M, Fiani T, Jones EA. Augmenting Sibling Support with Parent-Sibling Training in Families of Children with Autism. Dev Neurorehabil ;2019 (Jun 19):1-11.

Background : Typically developing (TD) siblings are an important part of the family system, but may show strained relationships in families of children with ASD. Objective : We augmented a sibling support group with parent-sibling training in which parents learned (through instructions, modeling, rehearsal, and feedback) how to prompt and reinforce prosocial behaviors in their TD children. Method : We examined the effects of parent-sibling training on parent and TD sibling behaviors in a multiple baseline across families design. Results : Parent prompting and reinforcement of TD sibling prosocial behaviors increase. TD sibling prosocial behaviors such as sharing with and talking to their sibling with ASD also increased. Broader measures of the sibling relationship showed some improvements. Conclusion : Findings suggest ways to support families of children with ASD with future investigations of parent-sibling training examining longer intervention, all family members’ adjustment and relationships, and sibling characteristics that influence response to parent-sibling training.

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26. Spratt E, Norton J, Papa C, Newton J, McDonald C, Mercer MA, Serpe A, Blackmon L, Felty K, Carpenter L. "The PIT Experience" : A Young Adult with Autism Spectrum Disorder’s Opinion of how a Wellness Program Changed her Life. J Autism Dev Disord ;2019 (Jun 17)

Piece it Together (PIT) is a comprehensive wellness program designed for transitional age youth with Autism Spectrum Disorder and mild neurodevelopmental disabilities that focuses on exercise, nutrition, socialization, and stress-reduction. The PIT Summer Program is a 6-week program, consisting of 90-min classes, twice a week. Each class incorporates 45-min of exercise and health and wellness lessons in goal setting, nutrition, bones and muscle anatomy, and stress management. The PIT program has successfully brought together a unique group to build friendships and make healthier lifestyle choices. One female participant has felt positively impacted and many of her in-class achievements have translated to greater success in work and school environments. She describes the impacts of the PIT program in this letter.

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27. Tang JSY, Chen NTM, Falkmer M, Blte S, Girdler S. Atypical Visual Processing but Comparable Levels of Emotion Recognition in Adults with Autism During the Processing of Social Scenes. J Autism Dev Disord ;2019 (Jun 15)

Understanding the underlying visual scanning patterns of individuals with autism spectrum disorder (ASD) during the processing of complex emotional scenes remains limited. This study compared the complex emotion recognition performance of adults with ASD (n = 23) and matched neurotypical participants (n = 25) using the Reading the Mind in Films Task. Behaviourally, both groups exhibited similar emotion recognition accuracy. Visual fixation time towards key social regions of each stimuli was examined via eye tracking. Individuals with ASD demonstrated significantly longer fixation time towards the non-social areas. No group differences were evident for the facial and body regions of all characters in the social scenes. The findings provide evidence of the heterogeneity associated with complex emotion processing in individuals with ASD.

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28. White T, Calhoun VD. Dissecting Static and Dynamic Functional Connectivity : Example From the Autism Spectrum. J Exp Neurosci ;2019 ;13:1179069519851809.

The ability to measure the intrinsic functional architecture of the brain has grown exponentially over the last 2 decades. Measures of intrinsic connectivity within the brain, typically measured using resting-state functional magnetic resonance imaging (MRI), have evolved from primarily "static" approaches, to include dynamic measures of functional connectivity. Measures of dynamic functional connectivity expand the assumptions to allow brain regions to have temporally different patterns of communication between different regions. That is, connections within the brain can differentially fire between different regions at different times, and these differences can be quantified. Applying approaches that measure the dynamic characteristics of functional brain connectivity have been fruitful in identifying differences during brain development and psychopathology. We provide a brief overview of static and dynamic measures of functional connectivity and illustrate the synergy in applying these approaches to identify both age-related differences in children and differences between typically developing children and children with autistic symptoms.

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29. Wilson KP, Steinbrenner JR, Kalandadze T, Handler L. Interventions Targeting Expressive Communication in Adults With Autism Spectrum Disorders : A Systematic Review. J Speech Lang Hear Res ;2019 (Jun 19) ;62(6):1959-1978.

Purpose The aims of this systematic review are to (a) synthesize the literature on interventions targeting expressive communication in adults with autism spectrum disorder and (b) evaluate the effectiveness of the interventions. Method The literature search resulted in 7,196 articles. The research team used 2 reviewers and consensus for title/abstract review, full-text review, and quality review. To be included, studies had to (a) include at least 1 adult (18 years of age and above) with an autism spectrum disorder ; (b) examine an intervention, treatment, or model of care ; (c) provide outcome data related to expressive communication modalities/domains ; (d) be experimental or quasi-experimental ; and (e) be published in English. Twenty-two studies (14 single-case design and 8 group design), with a total of 256 participants and varied interventions and outcome variables, met criteria for inclusion. Effect sizes are presented for group design studies, and visual analysis results are outlined for single-case design studies. Results Examination of treatment effects in the included studies showed positive effects, overall ; however, there was great variability between studies. Single-case design studies showed evidence of functional relations in all but 1 study, with most showing medium to large effects, as well as maintenance and generalization of gains. Group design studies showed a wide range of effects from near-zero to large effects. Differences in intervention strategies and durations, as well as in participant characteristics and outcome measures, presented barriers to aggregation. Conclusions This review highlights the need for increased high-quality research examining interventions targeting expressive communication in adults with autism spectrum disorder and also pinpoints interventions with potential for future study and use in this population.

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30. Zukerman G, Yahav G, Ben-Itzchak E. Increased psychiatric symptoms in university students with autism spectrum disorder are associated with reduced adaptive behavior. Psychiatry Res ;2019 (Mar) ;273:732-738.

High variability in adaptive behavior in cognitively-able adults with autism spectrum disorder has been previously reported, and may be caused by the high prevalence of psychiatric comorbidity in this population. This study’s goals were to examine self-reported psychiatric symptoms in students with ASD, and to identify their relative contribution to the variance in adaptive behaviors. The study population included 95 students : 55 diagnosed with ASD (4 females ; age range 18-34) who participated in a university integration program (ASD group), and 40 regularly matriculated students (non-ASD group, 7 females ; age range 20-36). The ASD group showed a lower adaptive skill level than the non-ASD group as measured by the Adaptive Behavior Assessment System (GAC-ABAS). Significantly higher scores for the ASD group were found for social anxiety, trait anxiety, obsessive-compulsive symptoms, and depression symptoms. The level of adaptive skills correlated negatively and significantly with the severity of social anxiety symptoms in both groups and with severity of obsessive-compulsive symptoms only in the ASD group. Additionally, in a regression model, significant contributions of having an ASD diagnosis and severity of social anxiety explained 41.7% of the variance in adaptive skills. Adequate evaluation and treatment, if needed, are recommended in this population.

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