Examining How CBT Interventions for Anxious Youth Are Delivered Across Settings.

Most efforts to assess treatment integrity-the degree to which a treatment is delivered as intended-have conflated content (i.e., therapeutic interventions) and delivery (i.e., strategies for conveying the content, such as modeling). However, there may be value in measuring content and delivery separately. This study examined whether the quantity (how much) and quality (how well) of delivery strategies for individual cognitive behavioral therapy (ICBT) for youth anxiety varied when the same evidence-based treatment was implemented in research and community settings. Therapists (N = 29; 69.0% White; 13.8% male) provided ICBT to 68 youths (M age = 10.60 years, SD = 2.03; 82.4% white; 52.9% male) diagnosed with a principal anxiety disorder in research or community settings. Training and supervision protocols for therapists were comparable across settings. Two independent teams of trained coders rated 744 sessions using observational instruments designed to assess the quantity and quality of delivery of interventions found in ICBT approaches. Overall, both the quantity and quality of delivery of interventions found in ICBT approaches were significantly lower in the community settings. The extent to which didactic teaching, collaborative teaching, and rehearsal were used systematically varied over the course of treatment. In general, differences in the quantity and quality of delivery observed between settings held when differences in youth characteristics between settings were included in the model. Our findings suggest the potential relevance of measuring how therapists deliver treatment separate from the content.

Factors associated with perceived containment.

There is growing evidence indicating that a lack of perceived containment, or youth's beliefs about whether adults can control their behavior, is associated with problem behavior. However, little research has examined factors that may contribute to perceived containment, which would be helpful in further tailoring prevention and intervention efforts for problem behavior. The current study evaluated associations between callous-unemotional (C/U) traits, peer delinquency, neighborhood problems, and perceived containment. Associations were examined using a sample of detained youth. Findings indicated that while all three factors were correlated with perceived containment, only C/U traits (particularly the callousness and uncaring subscales) and peer delinquency were uniquely associated with perceived containment. Further, C/U traits did not moderate the links between peer delinquency or neighborhood problems and perceived containment. This study supports the influence of both individual and contextual factors on perceived containment, suggesting multiple factors to target for prevention and intervention.

The Role of Toll-Like Receptor 2 and 4 Innate Immunity Pathways in Intracortical Microelectrode-Induced Neuroinflammation.

We have recently demonstrated that partial inhibition of the cluster of differentiation 14 (CD14) innate immunity co-receptor pathway improves the long-term performance of intracortical microelectrodes better than complete inhibition. We hypothesized that partial activation of the CD14 pathway was critical to a neuroprotective response to the injury associated with initial and sustained device implantation. Therefore, here we investigated the role of two innate immunity receptors that closely interact with CD14 in inflammatory activation. We implanted silicon planar non-recording neural probes into knockout mice lacking Toll-like receptor 2 (Tlr2-/-), knockout mice lacking Toll-like receptor 4 (Tlr4-/-), and wildtype (WT) control mice, and evaluated endpoint histology at 2 and 16 weeks after implantation. Tlr4-/- mice exhibited significantly lower BBB permeability at acute and chronic time points, but also demonstrated significantly lower neuronal survival at the chronic time point. Inhibition of the Toll-like receptor 2 (TLR2) pathway had no significant effect compared to control animals. Additionally, when investigating the maturation of the neuroinflammatory response from 2 to 16 weeks, transgenic knockout mice exhibited similar histological trends to WT controls, except that knockout mice did not exhibit changes in microglia and macrophage activation over time. Together, our results indicate that complete genetic removal of Toll-like receptor 4 (TLR4) was detrimental to the integration of intracortical neural probes, while inhibition of TLR2 had no impact within the tests performed in this study. Therefore, approaches focusing on incomplete or acute inhibition of TLR4 may still improve intracortical microelectrode integration and long term recording performance.

Inhibition of the cluster of differentiation 14 innate immunity pathway with IAXO-101 improves chronic microelectrode performance.

OBJECTIVE: Neuroinflammatory mechanisms are hypothesized to contribute to intracortical microelectrode failures. The cluster of differentiation 14 (CD14) molecule is an innate immunity receptor involved in the recognition of pathogens and tissue damage to promote inflammation. The goal of the study was to investigate the effect of CD14 inhibition on intracortical microelectrode recording performance and tissue integration. APPROACH: Mice implanted with intracortical microelectrodes in the motor cortex underwent electrophysiological characterization for 16 weeks, followed by endpoint histology. Three conditions were examined: (1) wildtype control mice, (2) knockout mice lacking CD14, and (3) wildtype control mice administered a small molecule inhibitor to CD14 called IAXO-101. MAIN RESULTS: The CD14 knockout mice exhibited acute but not chronic improvements in intracortical microelectrode performance without significant differences in endpoint histology. Mice receiving IAXO-101 exhibited significant improvements in recording performance over the entire 16 week duration without significant differences in endpoint histology. SIGNIFICANCE: Full removal of CD14 is beneficial at acute time ranges, but limited CD14 signaling is beneficial at chronic time ranges. Innate immunity receptor inhibition strategies have the potential to improve long-term intracortical microelectrode performance.

High-throughput in vitro assay to evaluate the cytotoxicity of liberated platinum compounds for stimulating neural electrodes.

BACKGROUND: It is currently unclear how the platinum (Pt) species released from platinum-containing stimulating electrodes may affect the health of the surrounding tissue. This study develops an effective system to assess the cytotoxicity of any electrode-liberated Pt over a short duration, to screen systems before future in vivo testing. NEW METHOD: A platinum electrode was stimulated for two hours under physiologically relevant conditions to induce the liberation of Pt species. The total concentration of liberated Pt species was quantified and the concentration found was used to develop a range of Pt species for our model system comprised of microglia and neuron-like cells. RESULTS: Under our stimulation conditions (k=2.3, charge density of 57.7µC/cm2), Pt was liberated to a concentration of 1ppm. Interestingly, after 24h of Pt exposure, the dose-dependent cytotoxicity plots revealed that cell death became statistically significant at 10ppm for microglia and 20ppm for neuronal cells. However, in neuron-like cell cultures, concentrations above 1ppm resulted in significant neurite loss after 24h. COMPARISON WITH EXISTING METHODS: To our knowledge, there does not exist a simple, in vitro assay system for assessing the cytotoxicity of Pt liberated from stimulating neural electrodes. CONCLUSIONS: This work describes a simple model assay that is designed to be applicable to almost any electrode and stimulation system where the electrode is directly juxtaposed to the neural target. Based on the application, the duration of stimulation and Pt exposure may be varied.