Pubmed du 18/03/21

jeudi 18 mars 2021

1. Al Malki JS, Hussien NA, Al Malki F. Maternal toxoplasmosis and the risk of childhood autism : serological and molecular small-scale studies. BMC pediatrics. 2021 ; 21(1) : 133.

BACKGROUND : Toxoplasmosis resulting from infection with the Toxoplasma parasite has become an endemic disease worldwide. Recently, a few studies have reported a high prevalence of Toxoplasmosis infections among Saudi Arabian women. This disease could become life threatening for pregnant women and for immunodeficient people. There is evidence that infections during pregnancy, especially in the early stages, are associated with neurodevelopmental disorders. Autism disorder represents one of the most common neurodevelopmental disorders worldwide ; it is associated with delayed language development, weak communication interaction, and repetitive behavior. The relationship between prenatal toxoplasmosis and autism in childhood remains unclear. The present study aims to report a link between maternal toxoplasmosis and autistic offspring among Saudi Arabian women. METHOD : Blood samples (36 maternal, 36 from their non-autistic children, and 36 from their autistic children) were collected for serological and molecular evaluation. RESULTS : A toxoplasmosis infection was reported for 33.34% of participants using an ELISA assay (5.56% IgG+/IgM+, 11.11% IgG-/IgM+, and 16.67% IgG+/IgM-) ; however, a nested PCR assay targeting B1 toxoplasmosis specific genes recorded positive tests for 80.56% of the samples. In addition, the present study detected several points of mutation of mtDNA including NADH dehydrogenase (ND1, ND4) and Cyt B genes and the nDNA pyruvate kinase (PK) gene for autistic children infected with toxoplasmosis. CONCLUSION : Considering previous assumptions, we suggest that a maternal toxoplasmosis infection could have a role in the development of childhood autism linked to mtDNA and nDNA impairment.

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2. Arutiunian V, Lopukhina A, Minnigulova A, Shlyakhova A, Davydova E, Pereverzeva D, Sorokin A, Tyushkevich S, Mamokhina U, Danilina K, Dragoy O. Language Abilities of Russian Primary-School-Aged Children with Autism Spectrum Disorder : Evidence from Comprehensive Assessment. J Autism Dev Disord. 2021.

The purpose of the present research was to comprehensively assess the language abilities of Russian primary-school-aged children with Autism Spectrum Disorder (ASD), varying in non-verbal IQ, at all linguistic levels (phonology, lexicon, morphosyntax, and discourse) in production and comprehension. Yet, the influence of such non-language factors as children’s age, the severity of autistic traits, and non-verbal IQ on language functioning was studied. Our results indicate a high variability of language skills in children with ASD (from normal to impaired) which is in line with the previous studies. Interestingly, the number of children with normal language abilities was related to the linguistic levels : according to more complex morphosyntax and discourse tests, fewer children with ASD were within the normal range unlike the results in simpler phonological and lexical tests. Importantly, we found that language abilities were best predicted by non-verbal IQ but were independent from age and the severity of autistic traits. The findings support the claim that formal language assessment of children with ASD needs to include all linguistic levels, from phonology to discourse, for helping speech-language therapists to choose an appropriate therapy target.

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3. Bastable K, Klopper S, Samuels A, Dada S. How Are Stakeholders With Autism Spectrum Disorder Included in the Social Validation of Augmentative and Alternative Communication Research ? A Scoping Review. American journal of speech-language pathology. 2021 : 1-16.

Introduction Social validation or the inclusion of stakeholders in the research process is beneficial, as it may decrease bias, increases efficacy, and prevents harm. For direct stakeholders such as individuals with autism spectrum disorder (ASD), social validation has mostly included participants who do not experience significant speech, language, and communication limitations while frequently omitting individuals with ASD who have complex communication needs (CCN). The presence of CCN indicates that augmentative and alternative communication (AAC) strategies are needed for individuals to express themselves. Social validation should not be limited to being participants in an intervention but should include involvement in the research process. This requires an understanding of the current trends, levels, and mechanisms of involvement in AAC research. Purpose This review aimed to identify and describe the inclusion of direct stakeholders with ASD in the social validation of AAC research. Method A scoping review was conducted following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews) methodology to identify AAC research that included stakeholders with ASD (direct and indirect) for social validation and to evaluate their level of involvement using the Typology of Youth Participation and Empowerment pyramid framework. Results Twenty-four studies were identified. Studies primarily included indirect stakeholders (e.g., caregivers) giving in-depth perspectives, while direct stakeholders were limited to being intervention participants. Conclusions Voices of direct stakeholders with ASD and CCN remain limited or excluded in research. Reasons for the exclusion of individuals with ASD and CCN from research and strategies for future inclusion are raised and discussed.

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4. Brice S, Rodgers J, Ingham B, Mason D, Wilson C, Freeston M, Le Couteur A, Parr JR. The importance and availability of adjustments to improve access for autistic adults who need mental and physical healthcare : findings from UK surveys. BMJ Open. 2021 ; 11(3) : e043336.

OBJECTIVES : To investigate autistic people’s views on the importance and availability of adjustments to mental and physical healthcare provision. To explore whether specific categories of adjustments can be identified and to identify any differences in their importance and availability between mental and physical healthcare. DESIGN : Data from two studies, both employing a cross-sectional survey design. SETTING : UK-based autistic adults registered with the Adult Autism Spectrum Cohort-UK were contacted by post or online. In both studies, recruitment was staged over a 12-month period. Non-responders were sent a single reminder letter 2 weeks after initial contact. PARTICIPANTS : 537 autistic adults completed a survey about mental health services (51% response rate), 407 completed the physical health survey (49% response rate). Within these samples, 221 participants completed both surveys. PRIMARY OUTCOME MEASURES : Each study developed a bespoke survey to explore participants’ views on mental and physical health services, respectively. Both included an identical list of adjustments that participants rated based on importance and availability. RESULTS : Three factors of important adjustments were identified : sensory environment, clinical and service context, and clinician knowledge and communication. Adjustments across healthcare settings were widely rated as being important yet rarely available. One significant difference between the importance of adjustments available through mental and physical health services was identified. Participants reported that having access to a clinician who is willing to adapt their approach to suit the person’s preferences was significantly more important for participants attending mental health settings (p=0.001). CONCLUSIONS : Autistic people reported the limited availability of important adjustments in current healthcare provision. To address unmet need and tackle the health inequalities faced by autistic people attending physical and mental healthcare settings, healthcare providers should offer adjustments relating to the three identified factors. Future research should focus on identifying and addressing service provider barriers to implementation.

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5. Christiansen A, Minich NM, Clark M. Pilot Survey : Police Understanding of Autism Spectrum Disorder. J Autism Dev Disord. 2021.

This piliot study assessed the experiences of police officers related to persons with Autism Spectrum Disorder (ASD) via a survey assessing prior experience, comfort, knowledge, and ability to identify autistic persons. Fifty-one officers completed the survey : 52.9% reported previous ASD training, 34.8% reported personal experience with ASD, and 56.9% endorsed low overall knowledge of ASD. Officers reported neutral comfort (mean 3.24) and moderate practical knowledge (mean 3.74) [Likert scale 1-5 ; 5 = highest]. Those with previous training or with personal experience reported higher comfort and knowledge. Those with personal experience were more likely to recognize features of ASD in clinical vignettes. Further study is necessary to understand what additional training about ASD may be helpful to police officers.

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6. Dahiya AV, Openden D, Ostmeyer KF, Anderson RM, Scarpa A. Pivotal response treatment for autism : A brief report on training for rural communities. Journal of community psychology. 2021.

Many providers from rural communities feel ill-prepared to treat children with autism spectrum disorder (ASD). Cost-effective training in Pivotal Response Treatment (PRT), an evidence-based ASD treatment, can address unmet needs for rural communities. The current study examined a 1-day general PRT workshop for parents and professionals followed by a 3-day small, intensive training for professionals. Fifty-two parents and providers completed surveys before and after Day 1, indicating improvements in perceived stress and confidence. Three providers were trained during Days 2-4, and submitted four 10-min videos (i.e., baseline, 1-week, 1-month, and 2-months post-training) working with a target child discussed in the training and another child. Videos were coded for correct PRT implementation and analyzed using a single-subject A-B design with generalization and maintenance probes. All providers learned to apply PRT techniques with the target child and generalized skills to another child within 1-week post-training, with partial maintenance. Implications for rural mental health training in evidence-based practices are discussed.

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7. Dawson G. Assessment of outcomes in autism clinical trials over the course of development. Eur Neuropsychopharmacol. 2021.

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8. Dell’Aringa AR, Juanico JF, Harrison KL. Using Transfer Trials to Teach Tacting to Children With Autism Spectrum Disorder. Behavior analysis in practice. 2021 ; 14(1) : 120-30.

Transfer trials are a component of discrete-trial training in which the therapist re-presents the initial instruction following a prompted trial to provide an opportunity for the learner to answer independently. Transfer trials may expedite the transfer of stimulus control, are commonly used by practitioners and researchers, and are often recommended as best practice by applied behavior analysis organizations. However, there is little research comparing the efficiency and efficacy of transfer trials to more traditional teaching procedures. The current study evaluated and compared transfer trials to a nontransfer trial procedure for two-component tacting with three children diagnosed with an autism spectrum disorder. Results indicated both procedures were both effective and efficient for teaching two-component tacts for all learners, supporting the inclusion of transfer trials in discrete-trial training.

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9. Demartini B, Nisticò V, Bertino V, Tedesco R, Faggioli R, Priori A, Gambini O. Eating disturbances in adults with autism spectrum disorder without intellectual disabilities. Autism Res. 2021.

There is a growing interest in the relationship between autism spectrum disorders (ASDs) and eating disorders (EDs), two relatively common conditions lying on a spectrum from mild to severe clinical features. However, only limited data are available about pathological eating behaviors throughout adults on the autistic spectrum. The aim of the present study is to assess dysfunctional eating behaviors, including EDs manifestations and ASDs-related eating disturbances, in a population of adults with ASDs without intellectual disabilities. We recruited 106 adults on the autistic spectrum, without intellectual disability and 103 neurotypical adults (NAs). Participants completed the "Eating Attitude Test" (EAT-26), to measure symptoms and concerns characteristic of EDs, and the "Swedish Eating Assessment for Autism Spectrum Disorders" (SWEAA), to assess eating behaviors frequently observed within the autistic spectrum. Participants with ASDs scored significantly higher than NA at the EAT-26 and at the SWEAA. Moreover, participants with ASDs scored higher than NA at the EAT-26 subscales Dieting and Bulimia. The difference between groups remained significant after controlling for the effect of age, biological sex, and BMI. These results suggest that adults with ASDs without intellectual disability presented not only a higher prevalence of eating disturbances typical of the autistic spectrum, but also other symptoms of EDs in comparison to NA. LAY SUMMARY : For both scales assessing eating disturbances (EAT-26 and SWEAA), participants with ASDs scored higher than NA, presenting a higher prevalence both of eating disturbances typical of ASDs and of ED symptoms (distorted body image, tendency toward bulimic behaviors, and self-control of eating).

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10. Di Renzo M, di Castelbianco FB, Alberto V, Antonio DV, Giovanni C, Vanadia E, Petrillo M, Davide T, Racinaro L, Rea M. Prognostic factors and predictors of outcome in children with autism spectrum disorder : the role of the paediatrician. Italian journal of pediatrics. 2021 ; 47(1) : 67.

BACKGROUND : Autism spectrum disorder is a complex condition with wide variation in type and severity that involves persistent challenges in social interaction, speech and nonverbal communication, restricted/repetitive behaviours and adaptive behaviours. In recent years, research has deepened the study of the predictive factors of optimal outcome, intended as indicators of positive trajectory in children with a previous diagnosis of autism who, after a therapeutic path, show a significant reduction in the "core" symptoms of autism and a positive evolution in social, adaptive, affective, and relational skills. METHODS : The study included 40 children aged 21 to 66 months, enrolled between 2015 and 2016 for an autism spectrum disorder clinical suspicious. Children were re-evaluated after at least 2 years of therapy and they were divided into two groups : the ASD-ASD group included children with a confirmed diagnosis of ASD, and the ASD-OO comparison group included children who no longer met the criteria for an autism classification. The aim of this retrospective study was to investigate the presence of cognitive, emotional and relational predictors capable of predicting the presence of optimal outcome in with a diagnosis of autism ; the predictors taken into consideration were the intelligence quotient, the play, the emotional contagion and the understanding of other’s intentions. In this way, it is possible to support clinicians in defining a more complete diagnostic framework of autism, using assessment tools that can be administered quickly and therefore suitable for short observation sessions in paediatric patients. RESULTS : The findings showed that 15 out of 40 children, after at least for 2 years, no longer fell into the diagnostic ASD category based on the ADOS-2, DSM-5 and clinical criteria. The children in the ASD-OO group initially had a higher IQ than those in the ASD-ASD group, lower severity of autistic symptoms, greater understanding of intentions, more emotional contagion, and better quality of play. The results suggest that the initial coexistence of skills in these areas at the time of the first diagnostic assessment may allow us to predict the possibility of achieving optimal outcome after 2 years of therapy. CONCLUSIONS : The data of this study highlight the importance of considering, during assessment, intelligence quotient, play, emotional contagion, and understanding of the intentions of others as potential prognostic predictors that can become useful tools for clinicians and paediatricians. This allows us to focus attention, in both the diagnostic and prognostic phases, on emotional-relational variables that can support the clinician in defining a more complete diagnostic framework and in planning a more personalized therapeutic path.

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11. Ebadi M, Samadi SA, Mardani-Hamooleh M, Seyedfatemi N. Living under psychosocial pressure : Perception of mothers of children with autism spectrum disorders. Journal of child and adolescent psychiatric nursing : official publication of the Association of Child and Adolescent Psychiatric Nurses, Inc. 2021.

PROBLEM : Mothers of children with autism spectrum disorders (ASD) experience higher levels of stress compared to mothers of typically developing children. This study identified mothers’ perceptions of the stress caused by lifelong caregiving to a child with ASD. METHODS : The current study was conducted in Iran using qualitative methods. In-depth, semi-structured interviews were conducted with twenty-seven mothers. Content analysis was used to analyze and categorize the data. FINDINGS : The main categories included (1) psychological concerns and suffering and (2) sociocultural challenges. The first category consisted of two subcategories, including disruption in mother-child relationships and fears and worries. Also, the second category included subcategories of cultural constraints and lack of social support. CONCLUSIONS : In this study, the mothers of autistic children experienced psychosocial pain. Identifying the stressors for these mothers could lead to appropriate planning to provide psychological, social, and cultural support for them in Iranian society.

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12. Lin KZ, Liu H, Roeder K. Covariance-based sample selection for heterogeneous data : Applications to gene expression and autism risk gene detection. Journal of the American Statistical Association. 2021 ; 116(533) : 54-67.

Risk for autism can be influenced by genetic mutations in hundreds of genes. Based on findings showing that genes with highly correlated gene expressions are functionally interrelated, "guilt by association" methods such as DAWN have been developed to identify these autism risk genes. Previous research analyze the BrainSpan dataset, which contains gene expression of brain tissues from varying regions and developmental periods. Since the spatiotemporal properties of brain tissue is known to affect the gene expression’s covariance, previous research have focused only on a specific subset of samples to avoid the issue of heterogeneity. This analysis leads to a potential loss of power when detecting risk genes. In this article, we develop a new method called COBS (COvariance-Based sample Selection) to find a larger and more homogeneous subset of samples that share the same population covariance matrix for the downstream DAWN analysis. To demonstrate COBS’s effectiveness, we use genetic risk scores from two sequential data freezes obtained in 2014 and 2020. We show COBS improves DAWN’s ability to predict risk genes detected in the newer data freeze when using the risk scores of the older data freeze as input.

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13. Lovell B, Elder GJ, Wetherell MA. Sleep disturbances and physical health problems in caregivers of children with ASD. Res Dev Disabil. 2021 ; 113 : 103932.

OBJECTIVES : Caregivers of children with autism spectrum disorder self-report more physical health problems than controls. Sleep disturbances are also more prevalent in caregivers, and are positively associated with physical health problems. The negative impact of caring for a child with ASD on physical health therefore, might occur indirectly via poorer sleep. METHODS : Participants, of which n = 43 were caregivers and n = 17 were controls, completed self-report measures of physical health problems and, to capture objective measures of sleep, wore an actigraphy device. RESULTS : Physical health problems were greater in caregivers, as were subjective reports of disturbed sleep. Objectively, waking after sleep onset (WASO) and average number of awakenings were higher, as was sleep latency, and sleep efficiency was poorer, in caregivers. Total sleep time however, was greater in caregivers, as was time in bed. Physical health problems, while unrelated to actigraphy measures, were positively associated with self-reported sleep disturbances. Caregivers’ increased risk for physical health problems occurred indirectly via greater self-reports of disturbed sleep. CONCLUSIONS : Interventions that help alleviate caregivers’ sleep disturbances might be effective, by reducing physical health problems, for improving quality of provided care, and this might be explored in future research.

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14. Lu M, Chen J, He W, Pang F, Zou Y. Association between perceived social support of parents and emotional/behavioral problems in children with ASD : A chain mediation model. Res Dev Disabil. 2021 ; 113 : 103933.

BACKGROUND : Parental psychosocial factors are associated with emotional/behavioral problems in children with Autism Spectrum Disorder (ASD), but studies investigating their relationships are limited. AIMS : To explore the relationships between parents’ perceived social support, parental resilience, parenting self-efficacy, and emotional/behavioral problems in children with ASD, and the mechanism underlying these relationships. METHOD : The participants were 289 parents of children with ASD (including fathers and mothers) in China. A survey comprising the Multidimensional Scale of Perceived Social Support, Resilience Scale, Parenting Sense of Competence Scale, and Strengths and Difficulties Questionnaire was administered. RESULTS : (1) Parents’ perceived social support, parental resilience, and parenting self-efficacy were significantly associated with emotional/behavioral problems in children with ASD ; (2) parental resilience and parenting self-efficacy were found to play a chain-mediating role in the association between perceived social support of parents and emotional/behavioral problems in children with ASD. CONCLUSION : It is crucial to improve parents’ perceived social support, parental resilience, and parenting self-efficacy to reduce emotional/behavioral problems in children with ASD.

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15. Lyall K, Ames JL, Pearl M, Traglia M, Weiss LA, Windham GC, Kharrazi M, Yoshida CK, Yolken R, Volk HE, Ashwood P, Van de Water J, Croen LA. A profile and review of findings from the Early Markers for Autism study : unique contributions from a population-based case-control study in California. Mol Autism. 2021 ; 12(1) : 24.

BACKGROUND : The Early Markers for Autism (EMA) study is a population-based case-control study designed to learn more about early biologic processes involved in ASD. METHODS : Participants were drawn from Southern California births from 2000 to 2003 with archived prenatal and neonatal screening specimens. Across two phases, children with ASD (n = 629) and intellectual disability without ASD (ID, n = 230) were ascertained from the California Department of Developmental Services (DDS), with diagnoses confirmed according to DSM-IV-TR criteria based on expert clinical review of abstracted records. General population controls (GP, n = 599) were randomly sampled from birth certificate files and matched to ASD cases by sex, birth month and year after excluding individuals with DDS records. EMA has published over 20 papers examining immune markers, endogenous hormones, environmental chemicals, and genetic factors in association with ASD and ID. This review summarizes the results across these studies, as well as the EMA study design and future directions. RESULTS : EMA enabled several key contributions to the literature, including the examination of biomarker levels in biospecimens prospectively collected during critical windows of neurodevelopment. Key findings from EMA include demonstration of elevated cytokine and chemokine levels in maternal mid-pregnancy serum samples in association with ASD, as well as aberrations in other immune marker levels ; suggestions of increased odds of ASD with prenatal exposure to certain endocrine disrupting chemicals, though not in mixture analyses ; and demonstration of maternal and fetal genetic influence on prenatal chemical, and maternal and neonatal immune marker and vitamin D levels. We also observed an overall lack of association with ASD and measured maternal and neonatal vitamin D, mercury, and brain-derived neurotrophic factor (BDNF) levels. LIMITATIONS : Covariate and outcome data were limited to information in Vital Statistics and DDS records. As a study based in Southern California, generalizability for certain environmental exposures may be reduced. CONCLUSIONS : Results across EMA studies support the importance of the prenatal and neonatal periods in ASD etiology, and provide evidence for the role of the maternal immune response during pregnancy. Future directions for EMA, and the field of ASD in general, include interrogation of mechanistic pathways and examination of combined effects of exposures.

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16. Robinson-Agramonte MLA, Michalski B, Fernández LG, Vidal-Martinez B, Cuesta HV, Rizo CM, Fahnestock M. Effect of non-invasive brain stimulation on behavior and serum brain-derived neurotrophic factor and insulin-like growth factor-1 levels in autistic patients. Drug development research. 2021.

Aberrant neural connectivity and intra-cortical inhibitory dysfunction are key features of autism. Non-invasive brain stimulation (NIBS) protocols have been proposed that modulate this aberrant plasticity. However, additional investigations are needed to evaluate the impact of this intervention on biological biomarkers of the disease. We recently demonstrated alterations in serum insulin-like growth factor-1 (IGF-1) and brain-derived neurotrophic factor (BDNF) immunoreactivity in subjects with autism compared to controls. The aim of this pilot study was to explore the change in serum levels of the neurotrophic factors BDNF and IGF-1 in patients undergoing NIBS therapy. Sixteen subjects with autism spectrum disorder (ASD) were tested 1 week before and 1 week after NIBS to determine the short-term outcome on behavior using the total score on the autism behavior checklist, autism treatment evaluation checklist, clinical global impression severity and the autism diagnostic interview. ASD subjects younger than 11 years old (n = 11) were treated with transcranial direct current stimulation (tDCS), and those 11 years and older (n = 5) were treated with repetitive transcranial magnetic stimulation (rTMS). Serum levels of BDNF and IGF-1 were evaluated by Enzyme-Linked Immuno-Sorbent Assay before and after the intervention with NIBS. A significant reduction in scores on the clinical behavioral scales was observed in patients treated with NIBS (ABC-T p = .002, CGI-S p = .008, ADI-T and ATEC-T p < .0001). There was a trend towards reduced serum BDNF levels after NIBS (p = .061), while there was no change in IGF-1 levels. These data support further studies on the potential of BDNF as a biomarker to measure the effectiveness of NIBS in autism.

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17. Singer-Dudek J, Sterkin V, Linden LG. Audience Control and the Emission of Stereotypy and Social Verbal Exchanges in Children With Autism and Developmental Disabilities. Behavior analysis in practice. 2021 ; 14(1) : 75-85.

In 2 experiments, using a within-subjects alternating-conditions design, we measured our participants’ stereotypic and verbal behavior under 2 audience conditions. Our participants were 8 children, ages 10 and 11 years, diagnosed with autism and related developmental disabilities. We measured the percentage of intervals with occurrences of stereotypy (Experiment 1) and the number of verbal operants emitted per minute (Experiment 2) in the presence of 2 types of audiences : members of the participants’ own special education class and typically developing peers from general education classes. Results from both experiments demonstrated that participants emitted a lower percentage of intervals with stereotypy and higher rates of social verbal operants in the presence of their typically developing peers than in their self-contained special education classrooms.

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18. Vladescu JC, Gureghian D, Goodwyn L, Campanaro AM. Comparing Skill Acquisition Under Different Stimulus Set Sizes With Adolescents With Autism Spectrum Disorder : A Replication. Behavior analysis in practice. 2021 ; 14(1) : 193-7.

A number of variables may influence the effectiveness and efficiency of skill acquisition. One variable that may be important is set size. The current study replicated and extended Kodak et al. (2020, "A Comparison of Stimulus Set Size on Tact Training for Children With Autism Spectrum Disorder," Journal of Applied Behavior Analysis, 53(1), 265-283) by evaluating the stimulus set size that led to the most efficient skill acquisition for 2 adolescents with autism spectrum disorder. More specifically, we evaluated tact acquisition in stimulus set sizes of 3, 6, and 12. The set sizes of 3 and 6 stimuli were associated with the most efficient acquisition, whereas the set size of 12 stimuli was not.

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19. White SW, Stoppelbein L, Scott H, Spain D. It took a pandemic : Perspectives on impact, stress, and telehealth from caregivers of people with autism. Res Dev Disabil. 2021 ; 113 : 103938.

Shelter in place mandates due to the COVID-19 pandemic left caregivers to determine how to best meet the therapeutic requirements of their children with autism spectrum disorder (ASD). Understanding the challenges faced by families, and their experiences using telehealth for the first time, may help make services sustainable in future public health emergencies. A sample of 70 caregivers of people with ASD from across the US completed an anonymous online survey. Results indicate that impaired emotion regulation was a primary contributor of parent-reported stress for persons with ASD during the pandemic, while loss of established structure and routine contributed to parental stress. Nearly half the sample reported using telehealth for the first time. Many caregivers were appreciative that telehealth permitted continuation of services, but expressed concerns about limited effectiveness due in part to their children’s social communication problems.

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20. Zolkipli-Cunningham Z, Naviaux JC, Nakayama T, Hirsch CM, Monk JM, Li K, Wang L, Le TP, Meinardi S, Blake DR, Naviaux RK. Metabolic and behavioral features of acute hyperpurinergia and the maternal immune activation mouse model of autism spectrum disorder. PLoS One. 2021 ; 16(3) : e0248771.

Since 2012, studies in mice, rats, and humans have suggested that abnormalities in purinergic signaling may be a final common pathway for many genetic and environmental causes of autism spectrum disorder (ASD). The current study in mice was conducted to characterize the bioenergetic, metabolomic, breathomic, and behavioral features of acute hyperpurinergia triggered by systemic injection of the purinergic agonist and danger signal, extracellular ATP (eATP). Responses were studied in C57BL/6J mice in the maternal immune activation (MIA) model and controls. Basal metabolic rates and locomotor activity were measured in CLAMS cages. Plasma metabolomics measured 401 metabolites. Breathomics measured 98 volatile organic compounds. Intraperitoneal eATP dropped basal metabolic rate measured by whole body oxygen consumption by 74% ± 6% (mean ± SEM) and rectal temperature by 6.2˚ ± 0.3˚C in 30 minutes. Over 200 metabolites from 37 different biochemical pathways where changed. Breathomics showed an increase in exhaled carbon monoxide, dimethylsulfide, and isoprene. Metabolomics revealed an acute increase in lactate, citrate, purines, urea, dopamine, eicosanoids, microbiome metabolites, oxidized glutathione, thiamine, niacinamide, and pyridoxic acid, and decreased folate-methylation-1-carbon intermediates, amino acids, short and medium chain acyl-carnitines, phospholipids, ceramides, sphingomyelins, cholesterol, bile acids, and vitamin D similar to some children with ASD. MIA animals were hypersensitive to postnatal exposure to eATP or poly(IC), which produced a rebound increase in body temperature that lasted several weeks before returning to baseline. Acute hyperpurinergia produced metabolic and behavioral changes in mice. The behaviors and metabolic changes produced by ATP injection were associated with mitochondrial functional changes that were profound but reversible.

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