The Efficacy of a Novel Video Game Intervention (MindLight) in Reducing Children's Anxiety

Anxiety disorders are the most prevalent form of psychopathology among children and adolescents. Because demand for treatment far exceeds availability, there is a need for alternative approaches that are engaging, accessible, cost-effective, and incorporate practice to reach as many youth as possible. One novel approach is a video game intervention called MindLight that uses two evidence-based strategies to target childhood anxiety problems. Using neurofeedback mechanics to train players to: (1) attend to positive rather than threatening stimuli and (2) down-regulate arousal during stressful situations, MindLight teaches children how to practice overcoming anxious thoughts and arousal in a fun and engaging context. The present study examined the effectiveness of MindLight versus online cognitive-behavioural therapy (CBT) based psychoeducation sessions as a comparison in reducing anxiety in a sample of 144 anxious children, which was measured in three ways: (1) anxiety symptoms, (2) state anxiety in response to stress, and (3) psychophysiological arousal in response to stress. Children between the ages of 8.05–17.78 years (M=13.61, SD=1.79) were randomly assigned to play MindLight or complete psychoeducation for five hours over three weeks. State anxiety and psychophysiological arousal were assessed in response to two stress tasks before and after exposure to MindLight or psychoeducation. Anxiety symptoms were also measured via a questionnaire. Overall, participants showed significant reductions in anxiety symptoms and state anxiety in response to stress, but not psychophysiological arousal in response to stress. Moreover, the magnitude of reductions in anxiety did not differ between interventions but by age and sex. Specifically, older participants showed a greater decrease in severity of state anxiety in response to a social stressor than younger participants and girls showed a greater decrease in severity of state anxiety in response to a cognitive stressor than boys. The present study suggests that playing MindLight results in similar reductions in anxiety as one of the more common means of delivering CBT principles to youth.

Enhancement of a novel gene therapy approach for Sandhoff disease through complimentary drug therapy

GM2 gangliosidoses is a family of severe, neurodegenerative disorders resulting from a deficiency in the β-hexosaminidase A (Hex A) enzyme. This disorder is typically caused by a mutation to either the HEXA gene, causing Tay Sachs disease, or a mutation to the HEXB gene, causing Sandhoff disease. The HEXA and HEXB genes are required to produce the α and β subunits of the Hex A enzyme respectively. Using a Sandhoff disease (SD) mouse model (Hexb-/-) we tested the potential of a low dose of systemically delivered single stranded adeno-associated virus 9 (ssAAV9) expressing human HEXB and human HEXA cDNA under the control of a single promoter through the use of a bicistronic vector design with a P2A linker to correct the neurological phenotype. Neonatal mice were injected with either this ssAAV9-HexB-P2A-HexA vector (HexB-HexA) or a vehicle solution via the superficial temporal vein. HexB-HexA treatment alone conferred an increase in survival of 56% compared to vehicle-injected controls and biochemical analysis of the brain tissue and serum revealed an increase in HexA activity and a decrease in brain GM2 ganglioside buildup. Additionally, treatments with the non-steroidal anti-inflammatory drug indomethacin (Indo), the histone deactylase inhibitor ITF2357 (ITF) and the pharmacological chaperone pyrimethamine (Pyr) were tested. The anti-inflammatory treatments of Indo and ITF conferred an increase in survival of 12% and 8% respectively while causing no alteration in the HexA activity or GM2 ganglioside buildup. Pyr had no observable effect on disease progression. Lastly HexB-HexA treatment was tested in conjunction with Indo, ITF and Pyr individually. Additive increases in survival and behavioural testing results were observed with Indo and ITF treatments while no additional benefit to HexA activity or GM2 ganglioside levels in the brain tissue was observed. This indicates the two treatments slowed the progression of the disease through a different mechanism than the reduction of the GM2 ganglioside substrate. Pyr treatment was shown to have no effect when combined with HexB-HexA treatment. This study demonstrates the potential amelioration of SD with a novel AAV9 gene therapy approach as well as helped to identify the additive potential of anti-inflammatory treatments in gene therapy of GM2 gangliosidoses.

Preparation of Polymer Nanoparticles by Ring Opening Metathesis Polymerization in Aqueous Dispersed Systems with Water-Soluble Ruthenium-based Catalyst

Ring opening metathesis polymerization (ROMP) is a variant of olefin metathesis used to polymerize strained cyclic olefins. Ruthenium-based Grubbs’ catalysts are widely used in ROMP to produce industrially important products. While highly efficient in organic solvents such as dichloromethane and toluene, these hydrophobic catalysts are not typically applied in aqueous systems. With the advancements in emulsion and miniemulsion polymerization, it is promising to conduct ROMP in an aqueous dispersed phase to generate well-defined latex nanoparticles while improving heat transfer and reducing the use of volatile organic solvents (VOCs). Herein I report the efforts made using a PEGylated ruthenium alkylidene as the catalyst to initiate ROMP in an oil-in-water miniemulsion. 1H NMR revealed that the synthesized PEGylated catalyst was stable and reactive in water. Using 1,5-cyclooctadiene (COD) as monomer, we showed the highly efficient catalyst yielded colloidally stable polymer latexes with ~ 100% conversion at room temperature. Kinetic studies demonstrated first-order kinetics with good livingness as confirmed by the shift of gel permeation chromatography (GPC) traces. Depending on the surfactants used, the particle sizes ranged from 100 to 300 nm with monomodal distributions. The more strained cyclic olefin norbornene (NB) could also be efficiently polymerized with a PEGylated ruthenium alkylidene in miniemulsion to full conversion and with minimal coagulum formation.