Behavioural and Developmental Interventions for Autism Spectrum Disorder: A Clinical Systematic Review

Background: Much controversy exists regarding the clinical efficacy of behavioural and developmental interventions for improving the core symptoms of autism spectrum disorders (ASD). We conducted a systematic review to summarize the evidence on the effectiveness of behavioural and developmental interventions for ASD. Methods and Findings: Comprehensive searches were conducted in 22 electronic databases through May 2007. Further information was obtained through hand searching journals, searching reference lists, databases of theses and dissertations, and contacting experts in the field. Experimental and observational analytic studies were included if they were written in English and reported the efficacy of any behavioural or developmental intervention for individuals with ASD. Two independent reviewers made the final study selection, extracted data, and reached consensus on study quality. Results were summarized descriptively and, where possible, meta-analyses of the study results were conducted. One-hundred-and-one studies at predominantly high risk of bias that reported inconsistent results across various interventions were included in the review. Meta-analyses of three controlled clinical trials showed that Lovaas treatment was superior to special education on measures of adaptive behaviour, communication and interaction, comprehensive language, daily living skills, expressive language, overall intellectual functioning and socialization. High-intensity Lovaas was superior to low-intensity Lovaas on measures of intellectual functioning in two retrospective cohort studies. Pooling the results of two randomized controlle

Heterocyclic carbene–metal-catalyzed Csp2–Csp2 and Csp–Csp2 couplings using nonmetallic substrates

The use of carbene ligands for transition-metal complexes has been developed in the last decades, being of special interest those carbenes derived from a nitrogen-containing heterocyclic system. An interesting variety of carbene-metal complexes has been tested in the Mizoroki-Heck reaction. In comparison, few examples can be found for the Matsuda-Heck version of this coupling reaction. Additionally, the Sonogashira coupling has been also catalyzed with different carbene-metal catalysts.Financial support from the Ministerio de Ciencia e Innovación (MICINN) of Spain (Project Nos. CTQ2007-65218, CTQ2011-24165, Consolider Ingenio 2010 CSD2007-00006), and the Generalitat Valencia (PROMETEO/2009/0349 and FEDER), and the University of Alicante is acknowledged

Neurofeedback training produces normalization in behavioural and electrophysiological measures of high-functioning autism

Autism spectrum disorder (ASD) is a neurodevelopmental condition exhibiting impairments in behaviour, social and communication skills. These deficits may arise from aberrant functional connections that impact synchronization and effective neural communication. Neurofeedback training (NFT), based on operant conditioning of the electroencephalogram (EEG), has shown promise in addressing abnormalities in functional and structural connectivity. We tested the efficacy of NFT in reducing symptoms in children with ASD by targeting training to the mirror neuron system (MNS) via modulation of EEG mu rhythms. The human MNS has provided a neurobiological substrate for understanding concepts in social cognition relevant to behavioural and cognitive deficits observed in ASD. Furthermore, mu rhythms resemble MNS phenomenology supporting the argument that they are linked to perception and action. Thirty hours of NFT on ASD and typically developing (TD) children were assessed. Both groups completed an eyes-open/-closed EEG session as well as a mu suppression index assessment before and after training. Parents filled out pre- and post-behavioural questionnaires. The results showed improvements in ASD subjects but not in TDs. This suggests that induction of neuroplastic changes via NFT can normalize dysfunctional mirroring networks in children with autism, but the benefits are different for TD brains

Identification of Potent, Selective, and Orally Bioavailable Small-Molecule GSPT1/2 Degraders from a Focused Library of Cereblon Modulators

International audienceWhereas the PROTAC approach to target protein degradation greatly benefits from rational design, the discovery of small-molecule degraders relies mostly on phenotypic screening and retrospective target identification efforts. Here, we describe the design, synthesis, and screening of a large diverse library of thalidomide analogues against a panel of patient-derived leukemia and medulloblastoma cell lines. These efforts led to the discovery of potent and novel GSPT1/2 degraders displaying selectivity over classical IMiD neosubstrates, such as IKZF1/3, and high oral bioavailability in mice. Taken together, this study offers compound 6 (SJ6986) as a valuable chemical probe for studying the role of GSPT1/2 in vitro and in vivo, and it supports the utility of a diverse library of CRBN binders in the pursuit of targeting undruggable oncoproteins