Search

Background As the global prevalence of diabetes increases, so will the numbers of people with diabetic retinopathy. Our review aimed to provide a comprehensive picture of available studies of diabetic retinopathy and how prevalence varies around the developed and developing world. Methods A detailed literature search using PubMed was undertaken. The following search term was used: 'diabetic retinopathy AND prevalence'. The titles and abstracts of all publications identified by the search were reviewed and 492 studies were retrieved. Inclusion and exclusion criteria were applied. Results A total of 72 articles from 33 countries were included. There were only 26 population-based studies using fundus photography (12 in developing countries), of which only 16 (eight in developing countries) were published since 2000. Prevalence estimates varied from as low as 10% to as high as 61% in persons with known diabetes and from 1.5 to 31% in newly diagnosed diabetes. Across all the studies, the median (interquartile range) prevalence of any diabetic retinopathy in known diabetes was 27.9% (22-37%) and 10.5% (6-16%) in newly diagnosed diabetes. Prevalence of diabetic retinopathy was higher in developing countries. Conclusion Significant gaps exist in that reliable population-based data from developing nations and indigenous populations in particular are lacking. Major differences in study characteristics and methodologies make comparisons very difficult. More research is required and study methodologies must be better standardized. This will provide important information for prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

The objective of this study is to examine the occurrence and characteristic features of obsessive-compulsive behaviours in children and adolescents with Asperger syndrome (AS), with respect to a matched obsessive compulsive disorder group (OCD) and a typically developing control group (CG). For this purpose, 60 subjects (20 OCD; 18 AS; 22 CG), aged 8-15 years, matched for age, gender and IQ were compared. AS and OCD patients were diagnosed according to the DSM-IV-TR criteria. The Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule were used to assist in the AS diagnosis; the WISC-R was administered to assess IQ. Obsessive and compulsive symptoms were evaluated by using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). None of the AS children received a formal diagnosis of OCD. The AS group presented significantly higher frequencies of Hoarding obsessions and Repeating, Ordering and Hoarding compulsions compared to CG. The OCD group, in turn, reported significantly higher frequencies of Contamination and Aggressive obsessions and Checking compulsions compared to both the AS group and CG. As expected, the OCD group displayed a higher severity of symptoms ( Moderate level of severity) than did the AS group ( Mild level of severity). Finally, in our sample, neither the OCD group nor the AS group demonstrated a completely full awareness of the intrusive, unreasonable and distressing nature of symptoms, and the level of insight did not differ between the OCD group and CG, although an absence of insight was observed in the AS group. Children with AS showed higher frequencies of obsessive and compulsive symptoms than did typically developing children, and these features seem to cluster around Hoarding behaviours. Additionally, different patterns of symptoms emerged between the OCD and AS groups. Finally, in our sample, the level of insight was poor in both the OCD and the AS children. Further research should be conducted to better understand the characteristics of repetitive thoughts and behaviours in autism spectrum disorders, and to clarify the underlying neurobiological basis of these symptoms. [ABSTRACT FROM AUTHOR]

Dimethylarginine dimethylaminohydrolase-1 (DDAH-1) accounts for the catabolism of the endogenous inhibitors of nitric oxide (NO) synthases, namely, ADMA ( N ω -dimethyl-l-arginine) and NMMA ( N -monomethyl-l-arginine). Inhibition of DDAH-1 may prove a therapeutic benefit in diseases associated with elevated nitric oxide (NO) levels by providing a tissue-specific increase of ADMA and NMMA. In this work, we have used molecular dynamics to generate a pool of DDAH-1 conformations in the apo and holo forms. Ensemble docking has been instrumental in screening an in-house fragment-based library of 824 compounds. Resulting virtual hits have been validated for their binding activity to recombinant human DDAH-1 using microscale thermophoresis (MST). As a key result, three non-amino acidic ligands of DDAH-1 (VIS212, VIS268, VIS726) are identified with higher binding efficiency index than ADMA. Amid these compounds, purpurogallin (VIS726) proves a potent ligand of DDAH-1, showing a mixed behavior of enzymatic inhibition in a biochemical assay. This finding widens the panel of known molecular targets of purpurogallin and provides clues into the molecular mechanisms of its cellular NO inhibition activity as well as its anti-inflammatory and neuroprotective effects.ω -dimethyl-l-arginine) and NMMA ( N ω -monomethyl-l-arginine). Inhibition of DDAH-1 may prove a therapeutic benefit in diseases associated with elevated nitric oxide (NO) levels by providing a tissue-specific increase of ADMA and NMMA. In this work, we have used molecular dynamics to generate a pool of DDAH-1 conformations in the apo and holo forms. Ensemble docking has been instrumental in screening an in-house fragment-based library of 824 compounds. Resulting virtual hits have been validated for their binding activity to recombinant human DDAH-1 using microscale thermophoresis (MST). As a key result, three non-amino acidic ligands of DDAH-1 (VIS212, VIS268, VIS726) are identified with higher binding efficiency index than ADMA. Amid these compounds, purpurogallin (VIS726) proves a potent ligand of DDAH-1, showing a mixed behavior of enzymatic inhibition in a biochemical assay. This finding widens the panel of known molecular targets of purpurogallin and provides clues into the molecular mechanisms of its cellular NO inhibition activity as well as its anti-inflammatory and neuroprotective effects.

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) protects against cardiovascular disease by metabolising the risk factor asymmetric dimethylarginine (ADMA). However, the question whether the second DDAH isoform, DDAH2, directly metabolises ADMA has remained unanswered. Consequently, it is still unclear if DDAH2 may be a potential target for ADMA-lowering therapies or if drug development efforts should focus on DDAH2's known physiological functions in mitochondrial fission, angiogenesis, vascular remodelling, insulin secretion, and immune responses. Here, an international consortium of research groups set out to address this question using in silico, in vitro, cell culture, and murine models. The findings uniformly demonstrate that DDAH2 is incapable of metabolising ADMA, thus resolving a 20-year controversy and providing a starting point for the investigation of alternative, ADMA-independent functions of DDAH2., (© 2023. The Author(s).)

PD-1/PD-L1 protein complex is attracting a great deal of interest as a drug target for the design of immune therapies able to block its assembly. Although some biologic drugs have entered clinical use, their poor response rate in patients are demanding further efforts to design small molecule inhibitors of PD-1/PD-L1 complex with higher efficacy and optimal physicochemical properties. Dysregulation of pH in the tumor microenvironment is indeed one of the key mechanisms promoting drug resistance and lack of response in cancer therapy. Integrating computational and biophysical approaches, herein we report a screening campaign that has led to identifying VIS310 as a novel ligand of PD-L1, with physicochemical properties enabling a pH-dependent binding potency. Additional optimization efforts by analogue-based screening have been instrumental to disclosing VIS1201, which exhibits improved binding potency against PD-L1 and is able to inhibit PD-1/PD-L1 complex formation in a ligand binding displacement assay. While providing preliminary structure-activity relationships (SARs) of a novel class of PD-L1 ligands, our results lay the foundation for the discovery of immunoregulatory small molecules resilient to tumor microenvironmental conditions for escaping drug-resistance mechanisms.

In the field of autism intervention, a large amount of evidence has demonstrated that parent-mediated interventions are effective in promoting a child's learning and parent caring skills. Furthermore, remote delivery treatments are feasible and can represent a promising opportunity to reach families at distance with positive results. Recently, the sudden outbreak of COVID-19 dramatically disrupted intervention services for autism and forced an immediate reorganization of the territory services toward tele-assisted intervention programs, according to professional and local resources. Our study aimed to conduct a retrospective pilot exploratory investigation on parental compliance, participation, and satisfaction in relation to three different telehealth intervention modalities, such as video feedback, live streaming, and psychoeducation, implemented in the context of a public community setting delivering early autism intervention during the COVID-19 emergency. We found that parents who attended video feedback expressed the highest rate of compliance and participation, while parental psychoeducation showed significantly lower compliance and the highest drop-out rate. Regardless of the tele-assistance modality, all the participants expressed satisfaction with the telehealth experience, finding it useful and effective. Potential benefits and advantages of different remote modalities with reference to parent involvement and effectiveness are important aspects to be taken into account and should be further investigated in future studies.

Autism spectrum disorder is a neurodevelopmental disorder with a rising prevalence disorder. This high-cost/high-burden condition needs evidence-based behavioral treatments that are able to reduce the impact of symptoms on children’s functioning. This retrospective chart review study compared the impact of different types of early interventions on toddlers diagnosed with an autism spectrum disorder developmental profile. Analyses were conducted on 90 subjects (mean = 27.76 months, range 18−44 months; M:F = 4.29:1), of which 36 children underwent the usual treatment, 13 children underwent an intervention based on early intensive behavioral intervention (EIBI) and 41 children received the Early Start Denver Model, for one year, with the same weekly frequency of about 6 h a week. A significant decrease in the severity of autism symptoms was observed for all children when looking at the Ados-2 severity score (average difference = 3.05, SD = 0.71, p = < 0.001) and the Ados-2 social subscale (average difference = 2.87, SD = 0.59, p < 0.001). Otherwise, for most of the Griffiths subscales, we found a significant improvement only for those children who underwent the Early Start Denver Model intervention (General Quotient average difference = 14.47, SD = 3.22, corrected p < 0.001). Analyzing the influence of age on the investigated scores, we found a significant association with the Eye−hand Coordination Quotient (p = 0.003), Performance Quotient (p = 0.042) and General Quotient (p = 0.006). In all these domains, a mild negative correlation with age was observed, as measured by the Pearson’s correlation coefficient (r = −0.32, p = 0.002; r = −0.21, p = 0.044; r = −0.25, p = 0.019, respectively), suggesting less severe developmental skills at the start of treatment for older children. Our results are consistent with the literature that underlines the importance of early intervention, since prompt diagnosis can reduce the severity of autism symptoms; nevertheless, in toddlers, our study demonstrated that an intervention model based on naturalistic developmental behavioral principles such as the Early Start Denver Model is more effective on children’s developmental profile. Further studies are required to assess the extent of effectiveness of different early intervention models in community settings.

Children typically prefer to attend to social stimuli (e.g. faces, smiles) over non-social stimuli (e.g. natural scene, household objects). This preference for social stimuli is believed to be an essential building block for later social skills and healthy social development. Preference for social stimuli are typically measured using either passive viewing or instrumental choice paradigms, but not both. Since these paradigms likely tap into different mechanisms, the current study addresses this gap by administering both of these paradigms on an overlapping sample. In this study, we use a preferential looking task and an instrumental choice task to measure preference for social stimuli in 3-9 year old typically developing children. Children spent longer looking at social stimuli in the preferential looking task but did not show a similar preference for social rewards on the instrumental choice task. Task performance in these two paradigms were not correlated. Social skills were found to be positively related to the preference for social rewards on the choice task. This study points to putatively different mechanisms underlying the preference for social stimuli, and highlights the importance of choice of paradigms in measuring this construct., Competing Interests: The authors declare that they have no conflict of interest.

Over the last two decades, indoleamine 2,3-dioxygenase 1 (IDO1) has attracted wide interest as a key player in immune regulation, fostering the design and development of small molecule inhibitors to restore immune response in tumor immunity. In this framework, biochemical, structural, and pharmacological studies have unveiled peculiar structural plasticity of IDO1, with different conformations and functional states that are coupled to fine regulation of its catalytic activity and non-enzymic functions. The large plasticity of IDO1 may affect its ligand recognition process, generating bias in structure-based drug design campaigns. In this work, we report a screening campaign of a fragment library of compounds, grounding on the use of three distinct conformations of IDO1 that recapitulate its structural plasticity to some extent. Results are instrumental to discuss tips and pitfalls that, due to the large plasticity of the enzyme, may influence the identification of novel and differentiated chemical scaffolds of IDO1 ligands in structure-based screening campaigns.

COVID-19 has impacted negatively on the mental health of children with autism spectrum disorder (ASD), as well as on their parents. Remote health services are a sustainable approach to behavior management interventions and to giving caregivers emotional support in several clinical domains. During the COVID-19 pandemic, we investigated the feasibility of a web-based behavioral skills training (BST) program for 16 parents and their children with ASD at home. The BST parent training package was tailored to each different specific behavioral disorder that characterizes children with ASD. After training, we found a significant reduction in the frequency of all the targeted behavioral disorders, as well as an improvement in psychological distress and the perception of the severity of ASD-related symptoms in parents. Our data confirm the efficacy of remote health care systems in the management of behavioral disorders of children with ASD, as well as of their parents during the COVID-19 pandemic.

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorders (ASD) are two of the most represented neurodevelopmental conditions in childhood. The diagnostic shift introduced by the DSM-5, allowing a combined diagnosis of ADHD and ASD, poses different clinical challenges related to diagnostic overshadowing, accuracy of clinical judgment and potential delay in an ASD diagnosis in children presenting with ADHD. Here we tried to disentangle the clinical phenotype and specificity of the two co-occurring conditions in relation to autism traits and empathy, by comparing children with ASD with and without comorbid ADHD with children presenting ADHD only and children with typical development. The child versions of the Autism Quotient (C-AQ) and Empathy Quotient (C-EQ) were administered to a total sample of 198 male children between 6 and 14 years old with age appropriate language skills and normal intelligence. Univariate analysis demonstrated no significant differences in the C-AQ total and subscale scores as well as the C-EQ between children with ASD and children with ASD + ADHD, while children with ADHD alone presented an intermediate phenotype between ASD and TD. Furthermore, a receiver operating characteristic (ROC) analysis was applied to discriminate among the different phenotypes. We found that the C-AQ and C-EQ were accurate at distinguishing with satisfactory reliability between: (a) ASD vs. non- ASD (N-ASD) groups comprising both ADHD and TD children (Area Under the Curve AUC 88% for C-AQ and 81% for C-EQ); (b) ASD and TD (AUC 92% for C-AQ and 95% for C-EQ); (c) ASD and ADHD (AUC 80% for C-AQ and 68% for C-EQ). Our data confirm the reliability of the C-AQ and C-EQ as behavioral markers to differentiate ASD (regardless of comorbid ADHD) from an ADHD condition and TD. Interestingly, in our sample an ADHD condition does not increase the severity of the clinical phenotype in terms of autism traits distribution and empathy, suggesting that the psychological measures detected by the two quantitative instruments are independent of ADHD traits. This evidence will contribute to the translational efforts in developing better tailored treatments and preventive strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Aiello, Vagni, Cerasa, Leonardi, Carrozza, Famà, Campisi, Marino, Siracusano, Alquino, Mainiero, Germano, Tartarisco, Pioggia, Gagliano and Ruta.)

We provide a conceptual model on the complex interaction between stress, psychological predisposition, and personality traits, accounting for gender, in parents of children with and without autism. We performed a path analysis using a structural equation modeling approach in a sample of parents including 60 ASD and 53 TD couples. In parents of typically developing children (TD), depression level and age are the main direct predictors of stress through the mediating effect of anxiety. Otherwise, in the ASD parent group, the personality trait 'openness' directly predicts the defensive response and stress levels without the mediating effect of anxiety. Our data suggest a route of action in promoting new behavioral strategies to prevent parenting stress, making families run smoothly.

A plethora of neuroimaging studies have focused on the discovery of potential neuroendophenotypes useful to understand the etiopathogenesis of autism and predict treatment response. Social robotics has recently been proposed as an effective tool to strengthen the current treatments in children with autism. However, the high clinical heterogeneity characterizing this disorder might interfere with behavioral effects. Neuroimaging is set to overcome these limitations by capturing the level of heterogeneity. Here, we provide a preliminary evaluation of the neural basis of social robotics and how extracting neural hallmarks useful to design more effective behavioral applications. Despite the endophenotype-oriented neuroimaging research approach is in its relative infancy, this preliminary evidence encourages innovation to address its current limitations.

Background: Acceptance and Commitment Therapy (ACT) has been demonstrated as effective in improving psychological well-being in several clinical domains, but there is no evidence regarding the parents of children with Autism Spectrum Disorder (ASD)., Methods: In this randomized controlled trial, we evaluated the efficacy of the ACT matrix behavioral protocol in comparison to the Parent Training (PT) program, measuring several primary and secondary outcomes prior to and following treatments. Twelve parents were randomly and equally assigned to two demographically matched groups wherein individuals underwent 24 weekly meetings of ACT protocol (experimental group) or conventional PT (control group)., Results: Parents enrolled in the ACT protocol demonstrated significant improvement in psychological flexibility, awareness states, personal values in everyday life, and parental stress, whereas reduced scores were elicited in parents' perceptions of their child's disruptive behaviors., Conclusions: The results of this randomized controlled trial, if repeated with a large number of subjects, could open the way to include ACT protocols in daily practice to support the development of new parenting skills.

Background: Recently, there has been an increased interest in the efficacy of mindfulness-based interventions (MBI) for people with cardiovascular diseases (CVD), although the exact beneficial effects remain unclear., Methods: This review aims to establish the role of MBI in the management of wellbeing for patients with CVD. Seventeen articles have been included in this systematic synthesis of the literature and eleven in the meta-analysis., Results: Considering physical (i.e., heart rate, blood pressure) and psychological outcomes (i.e., depression, anxiety, stress, styles of coping), the vast majority of studies confirmed that MBI has a positive influence on coping with psychological risk factors, also improving physiological fitness. Random-effects meta-analysis models suggested a moderate-to-large effect size in reducing anxiety, depression, stress, and systolic blood pressure., Conclusions: Although a high heterogeneity was observed in the methodological approaches, scientific literature confirmed that MBI can now be translated into a first-line intervention tool for improving physical and psychological wellbeing in CVD patients., Competing Interests: The authors declare no conflict of interest.

Objective: This is a prospective population screening study for autism in toddlers aged 18-30 months old using the Quantitative Checklist for Autism in Toddlers (Q-CHAT), with follow-up at age 4., Design: Observational study., Setting: Luton, Bedfordshire and Cambridgeshire in the UK., Participants: 13 070 toddlers registered on the Child Health Surveillance Database between March 2008 and April 2009, with follow-up at age 4; 3770 (29%) were screened for autism at 18-30 months using the Q-CHAT and the Childhood Autism Spectrum Test (CAST) at follow-up at age 4., Interventions: A stratified sample across the Q-CHAT score distribution was invited for diagnostic assessment (phase 1). The 4-year follow-up included the CAST and the Checklist for Referral (CFR). All with CAST ≥15, phase 1 diagnostic assessment or with developmental concerns on the CFR were invited for diagnostic assessment (phase 2). Standardised diagnostic assessment at both time-points was conducted to establish the test accuracy of the Q-CHAT., Main Outcome Measures: Consensus diagnostic outcome at phase 1 and phase 2., Results: At phase 1, 3770 Q-CHATs were returned (29% response) and 121 undertook diagnostic assessment, of whom 11 met the criteria for autism. All 11 screened positive on the Q-CHAT. The positive predictive value (PPV) at a cut-point of 39 was 17% (95% CI 8% to 31%). At phase 2, 2005 of 3472 CASTs and CFRs were returned (58% response). 159 underwent diagnostic assessment, including 82 assessed in phase 1. All children meeting the criteria for autism identified via the Q-CHAT at phase 1 also met the criteria at phase 2. The PPV was 28% (95% CI 15% to 46%) after phase 1 and phase 2., Conclusions: The Q-CHAT can be used at 18-30 months to identify autism and enable accelerated referral for diagnostic assessment. The low PPV suggests that for every true positive there would, however, be ~4-5 false positives. At follow-up, new cases were identified, illustrating the need for continued surveillance and rescreening at multiple time-points using developmentally sensitive instruments. Not all children who later receive a diagnosis of autism are detectable during the toddler period., Competing Interests: Competing interests: TC has received research grant support from the Medical Research Council (UK), the National Institute for Health Research, Horizon 2020 and the Innovative Medicines Initiative (European Commission), MQ, Autistica, FP7 (European Commission), the Charles Hawkins Fund and the Waterloo Foundation. He has served as a consultant to F Hoffmann-La Roche. He has received royalties from Sage Publications and Guilford Publications. All other authors report no biomedical financial interests or potential conflicts of interest., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

In the past two decades, several screening instruments were developed to detect toddlers who may be autistic both in clinical and unselected samples. Among others, the Quantitative CHecklist for Autism in Toddlers (Q-CHAT) is a quantitative and normally distributed measure of autistic traits that demonstrates good psychometric properties in different settings and cultures. Recently, machine learning (ML) has been applied to behavioral science to improve the classification performance of autism screening and diagnostic tools, but mainly in children, adolescents, and adults. In this study, we used ML to investigate the accuracy and reliability of the Q-CHAT in discriminating young autistic children from those without. Five different ML algorithms (random forest (RF), naïve Bayes (NB), support vector machine (SVM), logistic regression (LR), and K-nearest neighbors (KNN)) were applied to investigate the complete set of Q-CHAT items. Our results showed that ML achieved an overall accuracy of 90%, and the SVM was the most effective, being able to classify autism with 95% accuracy. Furthermore, using the SVM-recursive feature elimination (RFE) approach, we selected a subset of 14 items ensuring 91% accuracy, while 83% accuracy was obtained from the 3 best discriminating items in common to ours and the previously reported Q-CHAT-10. This evidence confirms the high performance and cross-cultural validity of the Q-CHAT, and supports the application of ML to create shorter and faster versions of the instrument, maintaining high classification accuracy, to be used as a quick, easy, and high-performance tool in primary-care settings.

Background: Telehealth is useful for both autism spectrum disorder (ASD) diagnosis and treatment, but studies with a direct comparison between teletherapy and traditional in-person therapy are limited., Methods: This randomized control trial-ISRCTN (International Standard Randomised Controlled Trial Number) primary clinical trial registry ID ISRCTN15312724-was aimed at comparing the effect of a tele-assisted and in-person intervention based on a behavioral intervention protocol for families with children affected by ASDs. Forty-two parents with children with autism (30 months to 10 years old) were randomly assigned to 12 sessions of an applied behavioral analysis (ABA) intervention implemented in an individual and group setting, either with or without the inclusion of tele-assistance. Pre- and postintervention assessments were conducted using the Home Situation Questionnaire (HSQ-ASD) and the Parental Stress Index (PSI/SF)., Results: Substantial improvements in the perception and management of children's behavior by parents, as well as in the influence of a reduction in parent stress levels on said children's behavior through the use of a tele-assisted intervention, were obtained., Conclusions: This randomized controlled trial demonstrates the evidence-based potential for telehealth to improve treatment of ASDs.

In our study, we explored the construct of alexithymia in parents of children with and without ASD using a multi-method approach based on self-rated and external rater assessment. We also assessed the level of self-report measures of negative affect states such as trait anxiety and depression, and investigated the correlation between the alexithymia construct, trait anxiety, and depression within the broader autism phenotype (BAP). A total sample of 100 parents (25 mothers and 25 fathers in each group) were administered the TAS-20 and the TSIA to measure self-reported and observer-rated alexithymia traits, as well as self-report measures of anxiety and depression. Study results showed that the TSIA but not the TAS-20 was able to detect significant group differences in alexithymia traits among parents of children with and without ASD, with parents of ASD children displaying significantly higher levels of alexithymia. Furthermore, differently from the TAS-20, no significant correlations between the TSIA and measures of anxiety and depression were detected. Taken together, our results suggest the importance of using multi-method approaches to control for potential measurement bias and to detect psychological constructs such as alexithymia in subclinical samples such as parents of children with ASD.

This study is a randomized control trial aimed at testing the role of a human-assisted social robot as an intervention mediator in a socio-emotional understanding protocol for children with autism spectrum disorders (ASD). Fourteen children (4-8 years old) were randomly assigned to 10 sessions of a cognitive behavioural therapy (CBT) intervention implemented in a group setting either with or without the assistance of a social robot. The CBT protocol was based on Rational Emotive Behaviour Therapy (REBT) principles. Pre- and post-intervention assessments were conducted using the Test of Emotional Comprehension (TEC) and the Emotional Lexicon Test (ELT). Substantial improvements in contextualized emotion recognition, comprehension and emotional perspective-taking through the use of human-assisted social robots were attained.

Background: Deficits in working memory tasks have been widely documented in Attention Deficit Hyperactivity Disorder (ADHD) studies. The aim of this study is to evaluate the effects of working memory load in impulsivity during decision-making processes. A delayed discounting (DD) paradigm was used, comparing children with ADHD and age-matched controls., Method: Thirty-two children equally divided between typically developing and ADHD, from 8 to 10 years of age were assigned to sessions of a dual-task paradigm. In the primary task the child has to choose between two different amounts of money at different time delays, while in the secondary task the child has to repeat a random series of digits with different lengths. The experiment was conducted in a school setting., Results: Compared to peers with typical development, delayed discounting was significantly stronger in children with ADHD and discounting rates increased in both groups for heavier memory loads. Furthermore, the memory load impact on frequency of immediate rewards was stronger in children with ADHD compared to typically developing children., Discussion: Results are discussed in terms of the relation between working memory load and decision-making processes, their impact on impulsive behaviour in ADHD and the need for future research to understand possible neurocognitive correlates and use that information to develop better inclusive policies.

Adolescence is a stage in life when dramatic physical, cognitive and socio-emotional changes occur. When adolescents grow-up in deprived social environments, the chance of psychophysical well-being severely decreases and problems such as delinquency, substance abuse and mental health issues are much more likely to ensue. Third wave cognitive-behavioral interventions are increasingly becoming the chosen instruments to support psychological intervention for young people and adolescents. In this study, we aim to test the feasibility and the adequacy of the outcome measures of an intervention for adolescents at high psychosocial risk, using a modified Discoverer, Noticer, Advisor and Values (DNA-V) protocol aimed at increasing flexible and positive values. The project was conducted in a school located in a low Socio-Economic Status (SES) and severely deprived district of a metropolitan area in Messina, Italy, with 3 classes from 6th to 8th grade. All parents and teachers allowed participants to take part in the pilot study. However, the participants' willingness to engage in the study was low (1 out of 3 classes). Overall, 13 adolescents (72% of the enrolled class) participated in the pilot and only 2 out of 7 teachers and no parents were available for interviews. In its current form, a full RCT is not considered feasible due to general low motivation showed by the participants. Although the sample size was small, the intervention program showed a statistically significant main effect for students' self-report questionnaire, suggesting that those measures were appropriate. Modifications and additional measures are suggested to increase participants' engagement and to overcome the need for parents and teachers' interviews., (Copyright © 2019 Marino, Crimi, Carrozza, Failla, Sfrazzetto, Chilà, Bianco, Arnao, Tartarisco, Cavallaro, Ruta, Vagni and Pioggia.)

Background: The Quantitative Checklist for Autism in Toddlers (Q-CHAT) is parent-report screening questionnaire for detecting threshold and sub-threshold autistic features in toddlers. The Q-CHAT is a dimensional measure normally distributed in the general population sample and is able to differentiate between a group of children with a diagnosis of autism and unselected toddlers. Objectives: We aim to investigate the psychometric properties, score distribution, and external validity of the Q-CHAT in an Italian clinical sample of young children with autism versus children with developmental delay and typically developing children. Method: N = 126 typically developing children (TD), n = 139 children with autism, and n = 50 children presenting developmental delay (DD) were administered the Q-CHAT. Standardized measures of cognitive functions, language, and behaviors were also obtained. Results: The Q-CHAT scores were normally distributed and demonstrated adequate internal consistency and good item to total score correlations. The mean Q-CHAT score in the autism group was significantly higher than those found in the DD sample and TD children. No difference on the mean Q-CHAT score between DD and TD children was found. The accuracy of the Q-CHAT to discriminate between autism and TD was very good. Two different cut-points (27 and 31, respectively) maximized sensitivity and specificity for autism versus TD and DD, respectively. Finally, higher Q-CHAT scores were correlated with lower language and social communication skills. Conclusions: In clinical settings, the Q-CHAT demonstrated good psychometric properties and external validity to discriminate autism children not just from children with typical development but also from children with developmental delay.

Identifying effective, community-based specialized interventions for young children with autism spectrum disorder is an international clinical and research priority. We evaluated the effectiveness of the Early Start Denver Model intervention in a group of young children with autism spectrum disorder living in an Italian community compared to a group of Italian children who received treatment as usual. A total of 22 young children diagnosed with autism spectrum disorder received the Early Start Denver Model in a center-based context for 6 h per week over 6 months. The Early Start Denver Model group was compared to a group of 70 young children diagnosed with autism spectrum disorder who received treatment as usual for an average of 5.2 h over 6 months. Children in both groups improved in cognitive, adaptive, and social skills after 3 months and 6 months of treatment. Children in the Early Start Denver Model group made larger gains in cognitive and social skills after 3 and 6 months of treatment. The Early Start Denver Model group made larger gains in adaptive skills after 3 months of treatment. Our results are discussed in terms of implications for intervention research and clinical practice. Our study supports the positive impact of the Early Start Denver Model in a non-English-speaking community.

Introduction: Autism Spectrum Disorder represents a burdensome condition in early childhood, with a number of risk factors proposed to explain its pathogenesis, most of which without a reliable scientific basis. Allergic asthma is likely to be one of the possible comorbilities of autism., Evidence Acquisition: In this paper, the relationship between autism and allergic asthma was analyzed through a systematic literature review, conducted according to the PRISMA Guidelines. The review was performed on PubMed and Science Direct database and covered the period January 1, 2004-July 9, 2016. The search was limited to articles published in peer-reviewed journals. The obtained results were sorted by relevance and the most significant case-control, epidemiological and nationwide-based works associating autism and allergic asthma in humans were selected., Evidence Synthesis: A slight correlation between these conditions has been found in more than a half studies selected, suggesting a possible association between the two diseases. Small sample sizes of some works and some methodological limitations rise uncertainty about this link., Conclusions: Autism Spectrum Disorder and asthma could be associated conditions, as evidenced by the higher prevalence of asthma in autistic children with respect to typically developed controls, with also a verisimilar biological basis. Despite that, future studies are required to provide more reliable data, also by employing animal models, to better clarify this, still unsure, relationship. Methods for study selection and inclusion criteria were specified in advance and documented in PROSPERO protocol #CRD42014012851.

Atypical responsivity to social rewards has been observed in young children with or at risk of Autism Spectrum Disorders (ASD). These observations contributed to the hypothesis of reduced social motivation in ASD. In the current study we develop a novel task to test social reward preference using a tablet computer (iPad), where two differently coloured buttons were associated with a social and a nonsocial rewarding image respectively. 63 young children, aged 14-68 months, with and without a diagnosis of ASD took part in the study. The experimental sessions were also recorded on video, using an in-built webcam on the tablet as well as an external camera. Children with ASD were found to show a reduced relative preference for social rewards, indexed by a lower proportion of touches for the button associated with the social reward image. Greater social preference as measured using the tablet-based task was associated with increased use of social communicative behaviour such as eye contact with the experimenter and social smile in response to the social reward image. These results are consistent with earlier findings from eye-tracking studies, and provide novel empirical insights into atypical social reward responsivity in ASD.

Olfactory function is a well-known early biomarker for neurodegeneration and neural functioning in the adult population, being supported by a number of brain structures that could be dysfunctioning in neurodegenerative processes. Evidence has suggested that atypical sensory and, particularly, olfactory processing is present in several neurodevelopmental conditions, including autism spectrum disorders (ASDs). In this paper, we present data obtained by a systematic literature review, conducted according to PRISMA guidelines, regarding the possible association between olfaction and ASDs, and analyze them critically in order to evaluate the occurrence of olfactory impairment in ASDs, as well as the possible usefulness of olfactory evaluation in such conditions. The results obtained in this analysis suggested a possible involvement of olfactory impairment in ASDs, underlining the importance of olfactory evaluation in the clinical assessment of ASDs. This assessment could be potentially included as a complementary evaluation in the diagnostic protocol of the condition. Methods for study selection and inclusion criteria were specified in advance and documented in PROSPERO protocol #CRD42014013939.

Social robotics could be a promising method for Autism Spectrum Disorders (ASD) treatment. The aim of this article is to carry out a systematic literature review of the studies on this topic that were published in the last 10 years. We tried to address the following questions: can social robots be a useful tool in autism therapy? We followed the PRISMA guidelines, and the protocol was registered within PROSPERO database (CRD42015016158). We found many positive implications in the use of social robots in therapy as for example: ASD subjects often performed better with a robot partner rather than a human partner; sometimes, ASD patients had, toward robots, behaviors that TD patients had toward human agents; ASDs had a lot of social behaviors toward robots; during robotic sessions, ASDs showed reduced repetitive and stereotyped behaviors and, social robots manage to improve spontaneous language during therapy sessions. Therefore, robots provide therapists and researchers a means to connect with autistic subjects in an easier way, but studies in this area are still insufficient. It is necessary to clarify whether sex, intelligence quotient, and age of participants affect the outcome of therapy and whether any beneficial effects only occur during the robotic session or if they are still observable outside the clinical/experimental context., (© 2015 International Society for Autism Research, Wiley Periodicals, Inc.)

Background: Atopic dermatitis (AD) is an allergic disorder caused by both immunological dysregulation and epidermal barrier defect. Several studies have investigated the association between AD and mental health disorders. Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental conditions characterized by impairments in social communication and restricted, stereotyped interests and behaviors. The concurrent increased prevalence of AD and ASD in the last decades has led many scientists to investigate the relationship between the two diseases., Objective: The aim of this systematic review was to examine the association between AD and ASD., Methods: A systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed and ScienceDirect were searched up to March 2015 for all reports examining the association between ASD and AD. Descriptive statistics of the studies are reported., Results: The review included 18 studies assessing the association between ASD and AD. Of these studies, two focused on ASD in relation to AD alone, 14 discussed ASD in relation to both AD and other atopic disorders, and two evaluated AD in parents of children with ASD. Most of these studies found a positive association between the two disorders, although there were some studies going in the opposite direction. The entity of the association is somewhat inconsistent among the different studies given that the frequencies of AD in ASD compared with a control group ranged from 7 to 64.2%. In addition, odds ratios (ORs) or hazard ratios (HRs) gave different results as three studies found a weak association with an OR below 2 and a nonsignificant p value, and three other studies found a moderate or strong association with an OR ranging from 1.52 to 7.17 and a significant p value. When all atopic disorders were considered when evaluating the risk of ASD, the association was strong with an HR of 3.4 or an OR of 1.24 and p < 0.001., Conclusions: Overall, the results of this systematic review seem to reveal an association between ASD and AD, suggesting that subjects with ASD have an increased risk of presenting with AD compared with typically developing controls, and vice versa. This association is supported by clinical/epidemiological aspects, shared genetic background and common immunological and autoimmune processes. However, the variability in study population and design, and the presence of other risk factors acting as confounding factors, sometimes contribute to inconsistent results. Further studies are needed to clarify the underlying pathophysiologic mechanism explaining the association between ASD and AD and to explore the causal association between the two conditions.

Background: The higher prevalence of Asperger Syndrome (AS) and other autism spectrum conditions in males has been known for many years. However, recent multiplex immunoassay profiling studies have shown that males and females with AS have distinct proteomic changes in serum., Methods: Here, we analysed sera from adults diagnosed with AS (males = 14, females = 16) and controls (males = 13, females = 16) not on medication at the time of sample collection, using a combination of multiplex immunoassay and shotgun label-free liquid chromatography mass spectrometry (LC-MSE). The main objective was to identify sex-specific serum protein changes associated with AS., Results: Multiplex immunoassay profiling led to identification of 16 proteins that were significantly altered in AS individuals in a sex-specific manner. Three of these proteins were altered in females (ADIPO, IgA, APOA1), seven were changed in males (BMP6, CTGF, ICAM1, IL-12p70, IL-16, TF, TNF-alpha) and six were changed in both sexes but in opposite directions (CHGA, EPO, IL-3, TENA, PAP, SHBG). Shotgun LC-MSE profiling led to identification of 13 serum proteins which had significant sex-specific changes in the AS group and, of these, 12 were altered in females (APOC2, APOE, ARMC3, CLC4K, FETUB, GLCE, MRRP1, PTPA, RN149, TLE1, TRIPB, ZC3HE) and one protein was altered in males (RGPD4). The free androgen index in females with AS showed an increased ratio of 1.63 compared to controls., Conclusion: Taken together, the serum multiplex immunoassay and shotgun LC-MSE profiling results indicate that adult females with AS had alterations in proteins involved mostly in lipid transport and metabolism pathways, while adult males with AS showed changes predominantly in inflammation signalling. These results provide further evidence that the search for biomarkers or novel drug targets in AS may require stratification into male and female subgroups, and could lead to the development of novel targeted treatment approaches.

Brachidactyly-Mental Retardation (BDMR) Syndrome (MIM 600430) is associated with terminal deletions at chromosome 2q37 and a limited number of studies also reported an association between 2q37 → qter deletion and autism. Herein we describe two cases of autism in unrelated children with BDMR Syndrome, showing physical, cognitive, behavioral, and disease natural history homologies, with a very prominent social impairment in the first 4 years of life. At follow-up evaluations, spanning a 5-years period, both children experienced a progressive reduction of the autistic symptoms, besides retaining compromised cognitive ability. This report supports the hypothesis that genes in the 2q37 region may contribute to the etiology of autism, leading, however, to a peculiar evolution of the disease, with symptoms severity decreasing over time.

Several psychiatric conditions, both internalizing and externalizing, have been documented in comorbidity with Asperger Syndrome (AS) and High Functioning Autism (HFA). In this review we examine the interplay between psychiatric comorbidities and AS/HFA. In particular, we will focus our attention on three main issues. First, we examine which psychiatric disorders are more frequently associated with AS/HFA. Second, we review which diagnostic tools are currently available for clinicians to investigate and diagnose the associated psychiatric disorders in individuals with AS/HFA. Third, we discuss the challenges that clinicians and researchers face in trying to determine whether the psychiatric symptoms are phenotypic manifestations of AS/HFA or rather they are the expression of a distinct, though comorbid, disorder. We will also consider the role played by the environment in the manifestation and interpretation of these symptoms. Finally, we will propose some strategies to try to address these issues, and we will discuss therapeutic implications.

The Autism Spectrum Quotient (AQ) has been used to define the 'broader' (BAP), 'medium' (MAP) and 'narrow' autism phenotypes (NAP). We used a new Italian version of the AQ to test if difference on AQ scores and the distribution of BAP, MAP and NAP in autism parents (n = 245) versus control parents (n = 300) were replicated in a Sicilian sample. Parents of children with autism spectrum conditions scored higher than the control parents on total AQ, social skills and communication subscales, and exhibited higher rates of BAP, MAP and NAP. We conclude that the Italian AQ is a cross-culturally reliable measure of these different phenotypes, and can be used to identify a phenotypic gradient of severity of autistic traits in families. To understand the molecular basis of these phenotypes will require its use in genetic association studies.

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23-4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD., Competing Interests: The authors have declared that no competing interests exist.

Background: Sex is an important factor in the prevalence, incidence, progression, and response to treatment of many medical conditions, including autoimmune and cardiovascular diseases and psychiatric conditions. Identification of molecular differences between typical males and females can provide a valuable basis for exploring conditions differentially affected by sex., Methodology/principal Findings: Using multiplexed immunoassays, we analyzed 174 serum molecules in 9 independent cohorts of typical individuals, comprising 196 males and 196 females. Sex differences in analyte levels were quantified using a meta-analysis approach and put into biological context using k-means to generate clusters of analytes with distinct biological functions. Natural sex differences were established in these analyte groups and these were applied to illustrate sexually dimorphic analyte expression in a cohort of 22 males and 22 females with Asperger syndrome. Reproducible sex differences were found in the levels of 77 analytes in serum of typical controls, and these comprised clusters of molecules enriched with distinct biological functions. Analytes involved in fatty acid oxidation/hormone regulation, immune cell growth and activation, and cell death were found at higher levels in females, and analytes involved in immune cell chemotaxis and other indistinct functions were higher in males. Comparison of these naturally occurring sex differences against a cohort of people with Asperger syndrome indicated that a cluster of analytes that had functions related to fatty acid oxidation/hormone regulation was associated with sex and the occurrence of this condition., Conclusions/significance: Sex-specific molecular differences were detected in serum of typical controls and these were reproducible across independent cohorts. This study extends current knowledge of sex differences in biological functions involved in metabolism and immune function. Deviations from typical sex differences were found in a cluster of molecules in Asperger syndrome. These findings illustrate the importance of investigating the influence of sex on medical conditions.

Molecular and behavioural evidence points to an association between sex-steroid hormones and autism spectrum conditions (ASC) and/or autistic traits. Prenatal androgen levels are associated with autistic traits, and several genes involved in steroidogenesis are associated with autism, Asperger Syndrome and/or autistic traits. Furthermore, higher rates of androgen-related conditions (such as Polycystic Ovary Syndrome, hirsutism, acne and hormone-related cancers) are reported in women with autism spectrum conditions. A key question therefore is if serum levels of gonadal and adrenal sex-steroids (particularly testosterone, estradiol, dehydroepiandrosterone sulfate and androstenedione) are elevated in individuals with ASC. This was tested in a total sample of n=166 participants. The final eligible sample for hormone analysis comprised n=128 participants, n=58 of whom had a diagnosis of Asperger Syndrome or high functioning autism (33 males and 25 females) and n=70 of whom were age- and IQ-matched typical controls (39 males and 31 females). ASC diagnosis (without any interaction with sex) strongly predicted androstenedione levels (p<0.01), and serum androstenedione levels were significantly elevated in the ASC group (Mann-Whitney W=2677, p=0.002), a result confirmed by permutation testing in females (permutation-corrected p=0.02). This result is discussed in terms of androstenedione being the immediate precursor of, and being converted into, testosterone, dihydrotestosterone, or estrogens in hormone-sensitive tissues and organs., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Migraine in childhood and adolescence has been associated with the presence of behavioural and emotional difficulties, but only few data are available with respect to unusual types of headache syndromes such as Benign Paroxysmal Vertigo of Childhood (BPVC). Aim of the present study was to evaluate the behavioural and emotional profiles of clinically referred children and adolescents suffering from BPVC and migraine, as compared to normal controls. According to the revised International Classification of Headache Disorders (ICHD-2) the BPVC belongs to the category of "primary headache", as a migraine equivalent, in a subset that is called "periodic syndromes of childhood". A total of 60 clinically referred children and adolescents (4-15 years) 21 suffering from BPVC and 20 from migraine, according to the diagnostic criteria of the ICHD-2, and 19 normal control (NC) were recruited in this study. Psychological assessment were performed using the Child Behaviour Checklist (CBCL), the Children's Depression Inventory (CDI) and the Multidimensional Anxiety Scale for Children (MASC). Although most of the patients suffering from headache had scores within the normative non-pathological range, both BPVC and migraine patients had significantly higher CBCL total, internalizing, and externalizing scores, as compared to NC. Furthermore, both BPVC and migraine groups displayed significantly higher CDI and MASC scores than NC group. No differences were found between the two types of headache. In conclusion, clinically referred children and adolescents with BPVC and migraine showed higher indices of behavioural and emotional symptoms, both internalizing and externalizing, as compared to normal peers., (Copyright © 2010 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

One key step of the bioremediation processes designed to clean up heavy metal contaminated environments is growing resistant cells that accumulate the heavy metals to ensure better removal through a combination of biosorption and continuous metabolic uptake after physical adsorption. Saccharomyces cerevisiae cells can easily act as cation biosorbents, but isolation of mutants that are both hyperaccumulating and tolerant to heavy metals proved extremely difficult. Instead, mutants that are hypersensitive to heavy metals due to increased and continuous uptake from the environment were considered, aiming to use such mutants to reduce the heavy metal content of contaminated waters. In this study, the heavy metal hypersensitive yeast strain pmr1Delta was investigated for the ability to remove Mn2+, Cu2+, Co2+, or Cd2+ from synthetic effluents. Due to increased metal accumulation, the mutant strain was more efficient than the wild-type in removing Mn2+, Cu2+, or Co2+ from synthetic effluents containing 1-2 mM cations, with a selectivity and also in removing Mn2+ and Cd2+ from synthetic effluents containing 20-50 microM cations, with a selectivity Mn2+ > Cd2+.