GOLIAH (Gaming Open Library for Intervention in Autism at Home): a 6-month single blind matched controlled exploratory study

BackgroundTo meet the required hours of intensive intervention for treating children with autism spectrum disorder (ASD), we developed an automated serious gaming platform (11 games) to deliver intervention at home (GOLIAH) by mapping the imitation and joint attention (JA) subset of age-adapted stimuli from the Early Start Denver Model (ESDM) intervention. Here, we report the results of a 6-month matched controlled exploratory study.MethodsFrom two specialized clinics, we included 14 children (age range 5–8 years) with ASD and 10 controls matched for gender, age, sites, and treatment as usual (TAU). Participants from the experimental group received in addition to TAU four 30-min sessions with GOLIAH per week at home and one at hospital for 6 months. Statistics were performed using Linear Mixed Models.ResultsChildren and parents participated in 40% of the planned sessions. They were able to use the 11 games, and participants trained with GOLIAH improved time to perform the task in most JA games and imitation scores in most imitation games. GOLIAH intervention did not affect Parental Stress Index scores. At end-point, we found in both groups a significant improvement for Autism Diagnostic Observation Schedule scores, Vineland socialization score, Parental Stress Index total score, and Child Behavior Checklist internalizing, externalizing and total problems. However, we found no significant change for by time × group interaction.ConclusionsDespite the lack of superiority of TAU + GOLIAH versus TAU, the results are interesting both in terms of changes by using the gaming platform and lack of parental stress increase. A large randomized controlled trial with younger participants (who are the core target of ESDM model) is now discussed. This should be facilitated by computing GOLIAH for a web platform.Trial registration Clinicaltrials.gov NCT0256041

Effects of Reducing Norepinephrine Levels via DSP4 Treatment on Amyloid-β Pathology in Female Rhesus Macaques (Macaca Mulatta)

The degeneration in the locus coeruleus associated with Alzheimer's disease suggests an involvement of the noradrenergic system in the disease pathogenesis. The role of depleted norepinephrine was tested in adult and aged rhesus macaques to develop a potential model for testing Alzheimer's disease interventions. Monkeys were injected with the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) or vehicle at 0, 3, and 6 months; brains were harvested at 9 months. Reduced norepinephrine in the locus coeruleus was accompanied by decreased dopamine β-hydroxylase staining and increased amyloid-β load in the aged group, and the proportion of potentially toxic amyloid-β42 peptide was increased. Immunohistochemistry revealed no effects on microglia or astrocytes. DSP4 treatment altered amyloid processing, but these changes were not associated with the induction of chronic neuroinflammation. These findings suggest norepinephrine deregulation is an essential component of a nonhuman primate model of Alzheimer's disease, but further refinement is necessary

Supplementary Data 1 from ETV4-Dependent Transcriptional Plasticity Maintains <i>MYC</i> Expression and Results in IMiD Resistance in Multiple Myeloma

Lenalidomide differentially expressed genes and GSEA for MM1S and OPM2 cells treated with 10 µM lenalidomide for 12 and 24 hours, respectively.</p

Supplementary Table S1 from ETV4-Dependent Transcriptional Plasticity Maintains <i>MYC</i> Expression and Results in IMiD Resistance in Multiple Myeloma

Univariate and multi-variate analysis of ETV4 expression in the CoMMpass NDMM patients treated with IMiD as part of front-line therapy (N=567).</p

Supplementary Table S2 from ETV4-Dependent Transcriptional Plasticity Maintains <i>MYC</i> Expression and Results in IMiD Resistance in Multiple Myeloma

List of antibodies used in this study.</p

Supplementary Figures S1-S11 from ETV4-Dependent Transcriptional Plasticity Maintains <i>MYC</i> Expression and Results in IMiD Resistance in Multiple Myeloma

Supplementary Figures S1-S11, which provide supporting data for the main figures.</p

Supplementary Data 4 from ETV4-Dependent Transcriptional Plasticity Maintains <i>MYC</i> Expression and Results in IMiD Resistance in Multiple Myeloma

JASPAR transcription factor binding motifs enriched in IKZF1-bound regions in RPMI8226 cells where the cognate transcription factor was expressed at greater than 1 FPKM and the FDR enrichment significance P ≤ 10e-10.</p