The management of testicular rupture in children with a large tunical defect is challenging. We describe a technique suitable when primary closure cannot be achieved. A 16-year-old boy presented with right testicular rupture. Owing to the large tunical separation and excessive edema, primary closure could not be achieved. A tunica vaginalis flap was then fashioned with a broad-based pedicle to complete closure. The patient had an uneventful recovery. At 4 months postoperatively, the testis was of normal size and position, and the ultrasound findings were normal. The vascularized tunica vaginalis flap provides an excellent alternative method for closure of pediatric testicular rupture.

Rett syndrome and MECP2 duplication syndrome are neurodevelopmental disorders that arise from loss-of-function and gain-of-function alterations in methyl-CpG binding protein 2 (MeCP2) expression, respectively. Although there have been studies examining MeCP2 loss of function in animal models, there is limited information on MeCP2 overexpression in animal models. Here, we characterize a mouse line with MeCP2 overexpression restricted to neurons (Tau-Mecp2). This MeCP2 overexpression line shows motor coordination deficits, heightened anxiety, and impairments in learning and memory that are accompanied by deficits in long-term potentiation and short-term synaptic plasticity. Whole-cell voltage-clamp recordings of cultured hippocampal neurons from Tau-Mecp2 mice reveal augmented frequency of miniature EPSCs with no change in miniature IPSCs, indicating that overexpression of MeCP2 selectively impacts excitatory synapse function. Moreover, we show that alterations in transcriptional repression mechanisms underlie the synaptic phenotypes in hippocampal neurons from the Tau-Mecp2 mice. These results demonstrate that the Tau-Mecp2 mouse line recapitulates many key phenotypes of MECP2 duplication syndrome and support the use of these mice to further study this devastating disorder.

PURPOSE: Recent comparisons of the impact of the surgical approach on pediatric pyeloplasty outcomes have generally incorporated a form of internal ureteral drainage. We hypothesized that the surgical approach does not affect outcomes in children who undergo unstented pyeloplasty and stenting offers no long-term benefit in those with pediatric pyeloplasty. MATERIALS AND METHODS: After receiving institutional review board approval we examined the records of all children who underwent initial pyeloplasty from December 2001 to December 2009. We compared unstented and stented pyeloplasties, and each surgical approach in the unstented group. RESULTS: During the study period 367 pyeloplasties were performed, including 231 unstented and 136 stented procedures. When comparing unstented to stented pyeloplasties, there was no difference in the complication or failure rate. Of unstented pyeloplasties 71, 67 and 93 were done using a transperitoneal laparoscopic approach, a flank approach and dorsal lumbotomy, respectively. There were 5 failures, of which 2 were laparoscopic, 2 used a flank approach and 1 used dorsal lumbotomy (p = 0.51). A total of 31 patients, including 10 treated with a laparoscopic approach, 3 with a flank approach and 18 with dorsal lumbotomy (p = 0.02), required second procedures, of which 24 were temporary drainage for a urine leak. Univariate analysis of factors associated with secondary procedures in the unstented pyeloplasty group showed that only surgical approach was significant (p = 0.05). CONCLUSIONS: In pediatric pyeloplasty there is no significant difference in outcome between stented and unstented repairs. In unstented repairs complications may vary by surgical approach. Regardless of the approach unstented pyeloplasty is safe and effective in the pediatric population.

An imbalance between the strengths of excitatory and inhibitory synaptic inputs has been proposed as the cellular basis of autism and related neurodevelopmental disorders. Previous studies examining spontaneous levels of excitatory and inhibitory neurotransmission in the forebrain regions of methyl-CpG-binding protein 2 (Mecp2) mutant mice, models of the autism spectrum disorder Rett syndrome, have identified a decrease in excitatory drive, in some cases coupled with an increase in inhibitory synaptic strength, as a major source of this imbalance. Here, we reevaluated this question by examining the short-term dynamics of evoked neurotransmission between hippocampal neurons cultured from MeCP2 knockout mice and found a marked increase in evoked excitatory neurotransmission that is consistent with an increase in presynaptic release probability. This increase in evoked excitatory drive was not matched with alterations in evoked inhibitory neurotransmission. Moreover, we observed similar excitatory drive specific changes after the loss of key histone deacetylases (histone deacetylase 1 and 2) that form a complex with MeCP2 and mediate transcriptional regulation. These findings suggest a distinct role for MeCP2 and its cofactors in the regulation of evoked excitatory neurotransmission compared with their essential role in basal synaptic activity.

Over the past several years there has been intense effort to delineate the role of epigenetic factors, including methyl-CpG-binding protein 2, histone deacetylases, and DNA methyltransferases, in synaptic function. Studies from our group as well as others have shown that these key epigenetic mechanisms are critical regulators of synapse formation, maturation, as well as function. Although most studies have identified selective deficits in excitatory neurotransmission, the latest work has also uncovered deficits in inhibitory neurotransmission as well. Despite the rapid pace of advances, the exact synaptic mechanisms and gene targets that mediate these effects on neurotransmission remain unclear. Nevertheless, these findings not only open new avenues for understanding neuronal circuit abnormalities associated with neurodevelopmental disorders but also elucidate potential targets for addressing the pathophysiology of several intractable neuropsychiatric disorders.

The role of epigenetic mechanisms in control of gene expression during mammalian development is well established. Associations between specific DNA or histone modifications and numerous neurodevelopmental and neurodegenerative disorders implies significant consequences of epigenetic dysregulation in both the developing and mature brain, the latter of which is the general focus of this review. Accumulating evidence suggests that epigenetic changes are involved in normal cognitive processes in addition to neurological and psychiatric disorders. Recent investigations into the regulation of epigenetic modifications in the adult brain have revealed novel and surprisingly dynamic mechanisms for controlling learning and memory-related behaviors as well as long-term synaptic plasticity. DNA methylation and histone acetylation have also been implicated in the modulation of basal synaptic transmission and the balance between excitation and inhibition in various brain regions. Studies have begun to uncover some of the alterations in gene expression that appear to mediate many of these effects, but an understanding of the precise mechanisms involved is still lacking. Nevertheless, the fundamental importance of epigenetic processes in influencing neuronal activity is becoming increasingly evident.

The utility of temperature/humidity data loggers are evaluated as a low-cost approach to enrich practical understanding of the actual time dependent humidity that a pharmaceutical product is exposed to. While this approach is found to have significant utility in general, small systematic biases in the measurements due to the presence of the data logger are observed. Taking these biases into account enables more productive extrapolation of measured time/humidity profiles.

The structural assembly of synapses can be accomplished in a rapid time frame, although most nascent synapses formed during early development are not fully functional and respond poorly to presynaptic action potentials. The mechanisms that are responsible for this delay in synapse maturation are unknown. Histone deacetylases (HDACs) regulate the activity state of chromatin and repress gene expression through the removal of acetyl groups from histones. Class I HDACs, which include HDAC1 and HDAC2, are expressed in the CNS, although their specific role in neuronal function has not been studied. To delineate the contribution of HDAC1 and HDAC2 in the brain, we have used pharmacological inhibitors of HDACs and mice with conditional alleles to HDAC1 and HDAC2. We found that a decrease in the activities of both HDAC1 and HDAC2 during early synaptic development causes a robust facilitation of excitatory synapse maturation and a modest increase in synapse numbers. In contrast, in mature neurons a decrease in HDAC2 levels alone was sufficient to attenuate basal excitatory neurotransmission without a significant change in the numbers of detectable nerve terminals. Therefore, we propose that HDAC1 and HDAC2 form a developmental switch that controls synapse maturation and function acting in a manner dependent on the maturational states of neuronal networks.

Solvent effects on the AIBN and ACVA forced degradation of cumene are explored. The degradant formation rates of the three cumene oxidative degradants, cumene hydroperoxide, acetophenone, and 2-phenyl-2-propanol are reported. The relative abundance and ratios of these three degradants provide insight into the fate of the peroxy radical oxidants generated by the forced stress system, and suggest that alkoxy radicals are actually a significant source of the observed reactivity. The presence of even 1% methanol in the forced stress solvent significantly quenches this alkoxy radical reactivity, dramatically reducing the overall degradation rate and leaving cumene hydroperoxide as the major product of the oxidation reaction. The origin of this significant solvent effect on the oxidation product distribution is shown to be related to the preferential H-atom abstraction from methanol and its trace impurities by any alkoxy radicals present in the reaction solution. The implications for these observations are explored with the intent of producing more predictive oxidative forced stress experiments.(c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci.

Learning and memory depend on the activity-dependent structural plasticity of synapses and changes in neuronal gene expression. We show that deletion of the MEF2C transcription factor in the CNS of mice impairs hippocampal-dependent learning and memory. Unexpectedly, these behavioral changes were accompanied by a marked increase in the number of excitatory synapses and potentiation of basal and evoked synaptic transmission. Conversely, neuronal expression of a superactivating form of MEF2C results in a reduction of excitatory postsynaptic sites without affecting learning and memory performance. We conclude that MEF2C limits excessive synapse formation during activity-dependent refinement of synaptic connectivity and thus facilitates hippocampal-dependent learning and memory.