Spatial compartmentalization of AMPA glutamate receptor subunits at the calyx of Held synapse

The mature calyx of Held ending on principal neurons of the medial nucleus of the trapezoid body (MNTB) has very specialized morphological and molecular features that make it possible to transmit auditory signals with high fidelity. In a previous work we described an increased localization of the ionotropic α‐amino‐3‐hydroxy‐5‐methyl‐4 isoxazolepropionic acid (AMPA) glutamate receptor (GluA) subunits at postsynaptic sites of the calyx of Held‐principal cell body synapses from postnatal development to adult. The aim of the present study was to investigate whether the pattern of the synaptic distribution of GluA2/3/4c and ‐4 in adult MNTB principal cell bodies correlated with preferential subcellular domains (stalks and swellings) of the calyx. We used a postembedding immunocytochemical method combined with specific antibodies to GluA2/3/4c and GluA4 subunits. We found that the density of GluA2/3/4c in calyceal swellings (19 ± 1.54 particles/μm) was higher than in stalks (10.93 ± 1.37 particles/μm); however, the differences for GluA4 were not statistically significant (swellings: 13.84 ± 1.39 particles/μm; stalks: 10.42 ± 1.24 particles/μm). Furthermore, GluA2/3/4c and GluA4 labeling co‐localized to some extent in calyceal stalks and swellings. Taking these data together, the distribution pattern of GluA subunits in postsynaptic specializations are indicative of a spatial compartmentalization of AMPA subunits in mature calyx‐principal neuron synapses that may support the temporally precise transmission required for sound localization in the auditory brainstem. J. Comp. Neurol. 518:163–174, 2010. © 2009 Wiley‐Liss, Inc.     

Bioequivalence of Long Half-Life Drugs—Informative Sampling Determination—Using Truncated Area in Parallel-Designed Studies for Slow Sustained-Release Formulations

A simulation study was done to determine if 72 h is the most informative sampling duration for bioequivalence (BE) determination in paralleldesigned BE studies with drugs that have half-lives of at least 30 h. The impact of absorption and elimination half-lives on informative sampling was evaluated. Two-treatment parallel-designed BE studies using a one-compartment oral absorption model with half-lives of 30 and 350 h was simulated. Area under the curve (AUC) values were truncated at 12–360 h. Experimental BE data [median time to reach the maximum concentration (T_max) = 20 h and low clearance = 0.192 L/h) indicated a decrease and then an increase in the intrasubject variability [root mean square error (RMSE)] for truncated AUC as a function of time. Simulations supported these findings with the highest probability of passing the BE confidence interval criteria being between 60 and 96 h, depending on half-life and percent coefficient of variation. The 30-h simulation exhibited a minimum in RMSE at 24-h truncation that continued to increase up to 360 h, whereas the 350-h simulation exhibited a minimum at 60 h, which increased after 96 h. Power curves at the 350-h half-life showed higher probabilities of rejection of BE for true test/reference ratios greater than 0.9. For parallel-designed BE studies, sampling beyond 120 h will not affect the BE decision and therefore is unnecessary. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:4337–4346, 2012     

The impact of violence exposure on aggressive behavior through social information processing in adolescents

The purpose of this study was to determine whether exposure to violence (EV) in several contexts predicts aggressive behavior through social information processing (SIP) in adolescents. Six hundred and fifty adolescents between the ages of 12 and 17 participated in a 3-wave longitudinal study. The participants completed measures of proactive and reactive aggression at all waves, SIP measures at Time 1 and Time 2, and violence exposure at Time 1. It was expected that SIP would mediate the predictive relationship between EV and aggressive behavior. We found that total Time 1 EV predicted Time 3 reactive aggression. The influence of EV on proactive aggression was direct. Slight differences emerged, however, for victimization and witnessing violence. Witnessing was associated with reactive aggression via both hostile attribution and response selection, whereas victimization predicted reactive aggression via hostile attribution only. Results also suggested that the types of exposure that are most relevant for the development of aggressive behavior are community and school violence. Finally, male adolescents experienced more EV than female adolescents in all contexts except in the home. The findings indicate that intervention in social-cognitive mechanisms is important to reduce aggressive behavior in adolescents who have been exposed to violence.     

The use of a vodcast to support eating and reduce anxiety in people with eating disorder: A case series

Individuals with eating disorders have difficulty controlling obsessive intrusions and ritualistic behaviours relating to food and exercise. An imagery‐based intervention using a vodcast (small video file played on a mobile phone or portable media device), with visual and aural components, was designed to target eating related psychopathology in a consecutive series of four patients. The vodcast was used to support consumption of a smoothie, both as a behavioural experiment and at home, in naturalistic circumstances. More of the smoothie was drunk in a shorter time when the smoothie was offered with the vodcast (mean of 218 g, SD = 64) than in the comparison condition (mean of 160 g, SD = 71). The vodcast condition was associated with reduced anxiety in three out of four patients. Three out of four patients used the vodcasts at home and found they provided them with support and motivation. All patients' weight increased after 3 months. Using a vodcast to support patients during meal times may be a useful addition to treatment for anorexia nervosa. Copyright © 2010 John Wiley & Sons, Ltd and Eating Disorders Association.