Developmental cascades of peer rejection, social information processing biases, and aggression during middle childhood.

This study tested a developmental cascade model of peer rejection, social information processing (SIP), and aggression using data from 585 children assessed at 12 time points from kindergarten through Grade 3. Peer rejection had direct effects on subsequent SIP problems and aggression. SIP had direct effects on subsequent peer rejection and aggression. Aggression had direct effects on subsequent peer rejection. Each construct also had indirect effects on each of the other constructs. These findings advance the literature beyond a simple mediation approach by demonstrating how each construct effects changes in the others in a snowballing cycle over time. The progressions of SIP problems and aggression cascaded through lower liking, and both better SIP skills and lower aggression facilitated the progress of social preference. Findings are discussed in terms of the dynamic, developmental relations among social environments, cognitions, and behavioral adjustment.

Evaluating intra-articular drug delivery for the treatment of osteoarthritis in a rat model.

Osteoarthritis (OA) is a degenerative joint disease that can result in joint pain, loss of joint function, and deleterious effects on activity levels and lifestyle habits. Current therapies for OA are largely aimed at symptomatic relief and may have limited effects on the underlying cascade of joint degradation. Local drug delivery strategies may provide for the development of more successful OA treatment outcomes that have potential to reduce local joint inflammation, reduce joint destruction, offer pain relief, and restore patient activity levels and joint function. As increasing interest turns toward intra-articular drug delivery routes, parallel interest has emerged in evaluating drug biodistribution, safety, and efficacy in preclinical models. Rodent models provide major advantages for the development of drug delivery strategies, chiefly because of lower cost, successful replication of human OA-like characteristics, rapid disease development, and small joint volumes that enable use of lower total drug amounts during protocol development. These models, however, also offer the potential to investigate the therapeutic effects of local drug therapy on animal behavior, including pain sensitivity thresholds and locomotion characteristics. Herein, we describe a translational paradigm for the evaluation of an intra-articular drug delivery strategy in a rat OA model. This model, a rat interleukin-1beta overexpression model, offers the ability to evaluate anti-interleukin-1 therapeutics for drug biodistribution, activity, and safety as well as the therapeutic relief of disease symptoms. Once the action against interleukin-1 is confirmed in vivo, the newly developed anti-inflammatory drug can be evaluated for evidence of disease-modifying effects in more complex preclinical models.