Pervasive alterations of intra-axonal volume and network organization in young children with a 16p11.2 deletion.

Reciprocal Copy Number Variants (CNVs) at the 16p11.2 locus confer high risk for autism spectrum disorder (ASD) and other neurodevelopmental disorders (NDDs). Morphometric MRI studies have revealed large and pervasive volumetric alterations in carriers of a 16p11.

Adrenomedullin Secreted by Melanoma Cells Promotes Melanoma Tumor Growth through Angiogenesis and Lymphangiogenesis.

Introduction: Metastatic melanoma is an aggressive tumor and can constitute a real therapeutic challenge despite the significant progress achieved with targeted therapies and immunotherapies, thus highlighting the need for the identification of new therapeutic targets. Adrenomedullin (AM) is a peptide with significant expression in multiple types of tumors and is multifunctional. AM impacts angiogenesis and tumor growth and binds to calcitonin receptor-like receptor/receptor activity-modifying protein 2 or 3 (CLR/RAMP2; CLR/RAMP3).

Intelligent personalized shopping recommendation using clustering and supervised machine learning algorithms.

Next basket recommendation is a critical task in market basket data analysis. It is particularly important in grocery shopping, where grocery lists are an essential part of shopping habits of many customers. In this work, we first present a new grocery Recommender System available on the MyGroceryTour platform.

De novo variants in CACNA1E found in patients with intellectual disability, developmental regression and social cognition deficit but no seizures.

Background: De novo variants in the voltage-gated calcium channel subunit α1 E gene (CACNA1E) have been described as causative of epileptic encephalopathy with contractures, macrocephaly and dyskinesias.

Methods: Following the observation of an index patient with developmental delay and autism spectrum disorder (ASD) without seizures who had a de novo deleterious CACNA1E variant, we screened GeneMatcher for other individuals with CACNA1E variants and neurodevelopmental phenotypes without epilepsy. The spectrum of pathogenic CACNA1E variants was compared to the mutational landscape of variants in the gnomAD control population database.

[Complex situations in adults with severe intellectual disabilities - A new support model].

Challenging behaviors constitute a real pitfall in supporting people with severe intellectual disabilities. Undermining patients and host institutions as well as psychiatric services, these crisis situations are usually underpinned by many factors including somatic, psychiatric, educational and environmental factors. New models, including the one developed by our team in Lausanne, offer a more specific approach for these complex cases, involving individualized, collaborative and multidisciplinary care to resolve the crisis but also for the overall improvement of the person's life course.

Sex differences in sensory processing in children with autism spectrum disorder.

Despite the high prevalence of sensory processing difficulties in children with autism spectrum disorder (ASD), little research has focused on the sex differences in sensory processing. Furthermore, there is a lack of knowledge on the female-specific symptoms of ASD, contributing to later referral, diagnosis and intervention. In this study, we examined the sex differences in sensory processing symptoms in large cohorts of ASD children (N = 168; 26 females, 142 males) and typically developing (TD) children (N = 439; 209 females, 230 males).

Considerations and Perspectives on Interventions to Improve Social Cognition in Adolescents With ASD Without ID: Involving Parents in Social Skills Groups.

Improving social cognition and social skills is a challenge faced by individuals with Autism Spectrum Disorder without Intellectual Disability at any age. This process is particularly critical during late adolescence (15-18 years), a developmental phase generally characterized by rich social experiences that usually foster the development of friendships. Nevertheless, for youth with ASD, lingering difficulties in social cognition often hinder their ability to generate responses considered socially appropriated.

Cancer Care of Children, Adolescents and Adults With Autism Spectrum Disorders: Key Information and Strategies for Oncology Teams.

Delivering optimal cancer care to children, adolescents and adults with ASD has recently become a healthcare priority and represents a major challenge for all providers involved. In this review, and after consideration of the available evidence, we concisely deliver key information on this heterogenous group of neurodevelopmental disorders, as well as recommendations and concrete tools for the enhanced oncological care of this vulnerable population of patients.

Touch and olfaction/taste differentiate children carrying a 16p11.2 deletion from children with ASD.

Background: Sensory processing atypicalities are frequent in Autism Spectrum Disorder (ASD) and neurodevelopmental disorders (NDD). Different domains of sensory processing appear to be differentially altered in these disorders. In this study, we explored the sensory profile of two clinical cohorts, in comparison with a sample of typically developing children.

[Autism spectrum disorder : a diagnosis for a better support].

Autism spectrum disorders (ASD) are neurodevelopmental disorders at the origin of severe handicap. The clinical expression of these disorders is strongly variable according to the presence of an intellectual deficiency or an associated organic and\or psychiatric disorder. Getting a correct diagnosis of ASD as a child or an adult can help a person and the professionals understand past difficulties, identify his or her strengths, and adapt the right kind of help.

On the nature of the speech perception deficits in children with autism spectrum disorders.

Previous studies have claimed to show deficits in the perception of speech sounds in autism spectrum disorders (ASD). The aim of the current study was to clarify the nature of such deficits. Children with ASD might only exhibit a lesser amount of precision in the perception of phoneme categories (CPR deficit).

Atypical coordination of cortical oscillations in response to speech in autism.

Subjects with autism often show language difficulties, but it is unclear how they relate to neurophysiological anomalies of cortical speech processing. We used combined EEG and fMRI in 13 subjects with autism and 13 control participants and show that in autism, gamma and theta cortical activity do not engage synergistically in response to speech. Theta activity in left auditory cortex fails to track speech modulations, and to down-regulate gamma oscillations in the group with autism.

The French version of the autism-spectrum quotient in adolescents: a cross-cultural validation study.

We assessed the accuracy of the French version of the Autism Spectrum Quotient (AQ) in adolescents with Asperger syndrome (AS) and high-functioning autism (HFA) compared to healthy controls and adolescents with psychiatric disorders (PDs). Three groups of adolescents, aged 11-18, were assessed: 116 with AS/HFA (93 with IQ ≥ 85 and 20 with 70 ≤ IQ < 85), 39 with other PDs, and 199 healthy controls. The AS/HFA group scored significantly higher than the healthy control and PD groups.

Social cognition and the superior temporal sulcus: implications in autism.

The most common clinical sign of autism spectrum disorders (ASD) is social interaction impairment, which is associated with communication deficits and stereotyped behaviors. Based on brain-imaging results, our hypothesis is that abnormalities in the superior temporal sulcus (STS) are highly implicated in ASD. These abnormalities are characterized by decreased grey matter concentration, rest hypoperfusion and abnormal activation during social tasks.

[Brain imaging of infantile autism].

Understanding of brain structural anomalies seen in children with autism has considerably progressed since the apparition of MRI and functional imaging. All the results are converging toward the description of anatomical and functional anomalies in the regions of the so-called "social brain". Statistical analyses show diminution of gray matter in the region of the superior temporal sulcus (STS).

Feature selection and classification of imbalanced datasets: application to PET images of children with autistic spectrum disorders.

Learning with discriminative methods is generally based on minimizing the misclassification of training samples, which may be unsuitable for imbalanced datasets where the recognition might be biased in favor of the most numerous class. This problem can be addressed with a generative approach, which typically requires more parameters to be determined leading to reduced performances in high dimension. In such situations, dimension reduction becomes a crucial issue.

Valproic acid suppresses interleukin-1ß-induced microsomal prostaglandin E2 synthase-1 expression in chondrocytes through upregulation of NAB1.

Objective: Microsomal prostaglandin E(2) synthase-1 (mPGES-1) catalyzes the terminal step in the biosynthesis of PGE(2). Early growth response factor-1 (Egr-1) is a key transcription factor in the regulation of mPGES-1, and its activity is negatively regulated by the corepressor NGF1-A-binding protein-1 (NAB1). We examined the effects of valproic acid (VA), a histone deacetylase inhibitor, on interleukin 1ß (IL-1ß)-induced mPGES-1 expression in human chondrocytes, and evaluated the roles of Egr-1 and NAB1 in these effects.

Contribution of H3K4 methylation by SET-1A to interleukin-1-induced cyclooxygenase 2 and inducible nitric oxide synthase expression in human osteoarthritis chondrocytes.

Objective: To investigate the role of histone H3 lysine 4 (H3K4) methylation in interleukin-1β (IL-1β)-induced cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in human osteoarthritic (OA) chondrocytes.

Methods: Chondrocytes were stimulated with IL-1, and the expression of iNOS and COX-2 messenger RNA and proteins was evaluated by real-time reverse transcriptase-polymerase chain reaction analysis and Western blotting, respectively. H3K4 methylation and the recruitment of the histone methyltransferases SET-1A and MLL-1 to the iNOS and COX-2 promoters were evaluated using chromatin immunoprecipitation assays.

Autism in three patients with cystic or hyperechogenic kidneys and chromosome 17q12 deletion.

Background: We report autism in 3 out of 53 children with cystic or hyperechogenic kidneys and heterozygous 17q12 region deletion encompassing hepatocyte nuclear factor-1beta (HNF1B).

Results: They presented mental retardation, social interaction impairments, verbal and non-verbal communication deficits and stereotyped behaviours. Deletion size and location of breakpoints were similar to those reported in patients with renal disease/diabetes only.

Human articular chondrocytes express 15-lipoxygenase-1 and -2: potential role in osteoarthritis.

Introduction: 15-Lipoxygenases and their metabolites have been shown to exhibit anti-inflammatory and immunomodulatory properties, but little is known regarding their expression and function in chondrocytes. The objective of this study was to evaluate the expression of 15-lipoxygenase-1 and -2 in human articular chondrocytes, and to investigate the effects of their metabolites 13(S)-hydroxy octadecadienoic and 15(S)-hydroxyeicosatetraenoic acids on IL-1beta-induced matrix metalloproteinase (MMP)-1 and MMP-13 expression.

Methods: The expression levels of 15-lipoxygenase-1 and -2 were analyzed by reverse transcription PCR and Western blotting in chondrocytes, and by immunohistochemistry in cartilage.

MRI findings in 77 children with non-syndromic autistic disorder.

Background: The clinical relevance of MR scanning in children with autism is still an open question and must be considered in light of the evolution of this technology. MRI was judged to be of insufficient value to be included in the standard clinical evaluation of autism according to the guidelines of the American Academy of Neurology and Child Neurology Society in 2000. However, this statement was based on results obtained from small samples of patients and, more importantly, included mostly insufficient MRI sequences.

HDAC4 contributes to IL-1-induced mPGES-1 expression in human synovial fibroblasts through up-regulation of Egr-1 transcriptional activity.

Microsomal prostaglandin E synthase-1 (mPGES-1) catalyzes the terminal step in the biosynthesis of PGE(2), which contributes to many physiopathological processes. We show here that inhibitors of histone deacetylase (HDAC) activity, trichostatin A (TSA), butyric acid (BA), and valproic acid (BA) prevented IL-1-induced mPGES-1 protein expression in human synovial fibroblasts. TSA also inhibited IL-1-induced mPGES-1 mRNA expression and promoter activation.

Increased expression of lipocalin-type prostaglandin D2 synthase in osteoarthritic cartilage.

Introduction: Prostaglandin D synthase (PGDS) is responsible for the biosynthesis of PGD and J series, which have been shown to exhibit anti-inflammatory and anticatabolic effects. Two isoforms have been identified: hematopoietic- and lipocalin-type PGDS (H-PGDS and L-PGDS, respectively). The aims of this study were to investigate the expressions of H-PGDS and L-PGDS in cartilage from healthy donors and from patients with osteoarthritis (OA) and to characterize their regulation by interleukin-1-beta (IL-1beta) in cultured OA chondrocytes.

Inhibition of interleukin-1beta-induced matrix metalloproteinases 1 and 13 production in human osteoarthritic chondrocytes by prostaglandin D2.

Objective: To investigate the effects of prostaglandin D2 (PGD2) on interleukin-1beta (IL-1beta)-induced matrix metalloproteinase 1 (MMP-1) and MMP-13 expression in human chondrocytes and the signaling pathways involved in these effects.

Methods: Chondrocytes were stimulated with IL-1 in the presence or absence of PGD2, and expression of MMP-1 and MMP-13 proteins was evaluated by enzyme-linked immunosorbent assay. Messenger RNA (mRNA) expression and promoter activity were analyzed by real-time reverse transcription-polymerase chain reaction and transient transfections, respectively.

Four-factor structure of obsessive-compulsive disorder symptoms in children, adolescents, and adults.

Objective: To determine whether the four-factor category-based obsessive-compulsive disorder (OCD) symptom structure from a previous confirmatory factor analysis (CFA) may be appropriately used in child, adolescent, and adult groups. Symptom dimensions are increasingly used as quantitative traits in genetic, neuroimaging, and treatment studies of OCD across all ages. Identification of a category-based OCD symptom dimension structure that is validated for use across child, adolescent, and adult age groups is necessary to guide ongoing translational research.