Examining Practice and Learning Effects With Serial Administration of the Clinical Reaction Time Test in Healthy Young Athletes.

CONTEXT: The clinical reaction time (RTclin) test has been recommended as a valid test for assessing concussion and determining recovery of reaction time function following concussion. However, it is unknown whether repeat assessment, as is used in postconcussion testing, is affected by learning or practice phenomena. OBJECTIVE: To determine if a practice or learning effect is present with serial administration of the RTclin test. DESIGN: Randomized control trial. SETTING: University athletic training clinics. PARTICIPANTS: A total of 112 healthy collegiate athletes (age = 19.46 [1.34] y). INTERVENTIONS: The control group completed the RTclin test on days 1 and 60. The experimental group completed the RTclin test on days 1, 2, 3, 7, and 60. MAIN OUTCOME MEASURE: Reaction time as measured with the RTclin test. RESULTS: The difference in RTclin test performance from day 1 to day 60 was not significant (mean change = -2.77 [14.46] ms, P = .42, 95% confidence intervals, -6.40 to 0.862) between groups. The experimental group experienced significant improvement (λ = 0.784, F4,49 = 3.365, P = .02, η2 = .216, power = 0.81) with acute repeat testing. However, post hoc analysis did not reveal a significant difference between scores during the 5 test periods. CONCLUSIONS: The results suggest serial administration of the RTclin test does not produce a practice or learning effect. Clinicians, however, should be cautious as the results do provide evidence patients may demonstrate improved scores when testing occurs on repetitive days after initial exposure to the test.

A qPCR-based metric of Th2 airway inflammation in asthma.

BACKGROUND: Using microarray profiling of airway epithelial cells, we previously identified a Th2-high molecular phenotype of asthma based on expression of periostin, CLCA1 and serpinB2 and characterized by specific inflammatory, remodeling, and treatment response features. The goal of the current study was to develop a qPCR-based assay of Th2 inflammation to overcome the limitations of microarray-based methods. METHODS: Airway epithelial brushings were obtained by bronchoscopy from two clinical studies comprising 44 healthy controls and 62 subjects with asthma, 39 of whom were studied before and after a standardized 8 week course of inhaled corticosteroids (ICS). The qPCR-based expression of periostin, CLCA1 and serpinB2 were combined into a single metric. RESULTS: In asthma, the three-gene-mean of periostin, CLCA1 and serpinB2 correlated with FeNO (r = 0.75, p = 0.0002), blood eosinophils (r = 0.58, p = 0.003) and PC20 methacholine (r = -0.65, p = 0.0006), but not total serum IgE (r = 0.33, p = 0.1). Higher baseline three-gene-mean correlated with greater improvement in FEV1 with ICS at 2, 4 and 8 weeks (all p < 0.05). By ROC analysis, the area under the curve (AUC) of the three-gene-mean for FEV1 improvement with ICS at 4 and 8 weeks was 0.94 and 0.87, respectively, which are higher than the AUCs of FeNO, blood eosinophils, IgE or PC20. Th2 airway inflammation as measured by this three-gene-mean also had predictive capacity for an improvement in symptoms. CONCLUSIONS: The three-gene-mean of periostin, CLCA1 and serpinB2 in airway epithelial brushings identifies Th2-high and low populations, is correlated with other Th2 biomarkers, and performs well for prediction of FEV1 improvement with ICS. The three-gene-mean provides a measurement of Th2 airway inflammation that is clinically relevant and that can serve as a valuable tool to evaluate non-invasive biomarkers to predict treatment responses to existing and emerging asthma therapies.

TrkB (tropomyosin-related kinase B) controls the assembly and maintenance of GABAergic synapses in the cerebellar cortex.

Inhibitory interneurons play a critical role in coordinating the activity of neural circuits. To explore the mechanisms that direct the organization of inhibitory circuits, we analyzed the involvement of tropomyosin-related kinase B (TrkB) in the assembly and maintenance of GABAergic inhibitory synapses between Golgi and granule cells in the mouse cerebellar cortex. We show that TrkB acts directly within each cell-type to regulate synaptic differentiation. TrkB is required not only for assembly, but also maintenance of these synapses and acts, primarily, by regulating the localization of synaptic constituents. Postsynaptically, TrkB controls the localization of a scaffolding protein, gephyrin, but acts at a step subsequent to the localization of a cell adhesion molecule, Neuroligin-2. Importantly, TrkB is required for the localization of an Ig superfamily cell adhesion molecule, Contactin-1, in Golgi and granule cells and the absence of Contactin-1 also results in deficits in inhibitory synaptic development. Thus, our findings demonstrate that TrkB controls the assembly and maintenance of GABAergic synapses and suggest that TrkB functions, in part, through promoting synaptic adhesion.