Increased sodium channel immunofluorescence at myelinated and demyelinated sites following an inflammatory and partial axotomy lesion of the rat infraorbital nerve

The localization of sodium channels (NaChs) change following nerve lesions and this change may contribute to the development of increased pain states. Here we examine the change in distribution of NaChs within the rat infraorbital nerve (ION) two weeks after a combined inflammatory/partial axotomy lesion that results in behavior showing increased sensitivity to mechanical stimuli. Sections from experimental and normal control IONs were double-stained for indirect immunofluorescence using an antibody that identifies all NaCh isoforms and caspr-antibody to identify nodes of Ranvier, and a confocal microscope z-series of optically sectioned images were then obtained. ImageJ (NIH) software was used to quantify the area of pixels showing maximum NaCh intensity within both caspr and non-caspr associated accumulations. Analysis showed that the lesioned IONs had many more split nodes, heminodes and caspr-negative "naked" accumulations, a significantly increased area of NaCh staining within typical nodes and "naked" accumulations, as well as an increased density and size of significant accumulations when compared to normal IONs. This study demonstrates a dramatic redistribution and increased immunofluorescence of NaChs especially at myelinated and demyelinated sites in fibers located just proximal to the lesion. The remodeling of NaChs seen in this study may represent an important event associated with the development of increased nerve excitability after lesions.     

Adolescent Girls in Out-of-Home Care: Associations Between Substance Use and Sexual Risk Behavior

ABSTRACT

Substance use and sexual risk behaviors continue to be major concerns for today's youths, and are particularly problematic for those who have been placed in out-of-home care settings. The purpose of this study was to explore these associations in a sample of 120 girls placed in a residential treatment setting and attending an on-site school in a major metropolitan area in the Midwest. A modified Youth Risk Behavior Survey (YRBS) was administered including questions relating to the youths' foster care or adjudicated status. The substance use variables targeted were alcohol and drug use. The sexual risk behavior variables were age of onset of first sexual intercourse, virginity status, contraceptive use, age of first sexual partner, and experience with ever having been forced to have sex. Results indicate that earlier onset and greater frequency of substance use were both correlated with number of sexual partners. Frequency of substance use was a significant and consistent contributor. Age of sexual partner was an inconsistent contributor, and history of forced sexual activity was not a contributor. Implications for policy and practice are offered to enhance the health and well-being of this unique population.     

High detection rate of clinically relevant genomic abnormalities in plasma cells enriched from patients with multiple myeloma

Multiple myeloma is a heterogeneous disease, which is characterized by the occurrence of specific genomic abnormalities that are both of diagnostic and prognostic relevance. Since the detection of these abnormalities through molecular‐genetic techniques is hampered by the overall low percentage of plasma cells present in primary bone marrow aspirates, we assessed the efficacy of these techniques in enriched plasma cell fractions from 61 multiple myeloma patients. Using interphase FISH, genomic abnormalities could be detected in 96% of the enriched samples as compared to 61% in the cultured whole bone marrow samples. We also found that microarray‐based genomic profiling of enriched plasma samples facilitates the detection of additional, possibly clinically relevant, genomic abnormalities. We conclude that the genomic delineation of enriched plasma cells from multiple myeloma patients results in a significantly increased detection rate of clinically relevant genomic abnormalities. In order to facilitate molecular‐genetic data interpretation, we recommend morphological assessment of plasma cell purity after enrichment. © 2012 Wiley Periodicals, Inc.     

The Interplay Between Attentional Strategies and Language Processing in High-functioning Adults with Autism Spectrum Disorder

This study examined the hypothesis of an atypical interaction between attention and language in ASD. A dual-task experiment with three conditions was designed, in which sentences were presented that contained errors requiring attentional focus either at (a) low level, or (b) high level, or (c) both levels of language. Speed and accuracy for error detection were measured from 16 high-functioning adults with ASD, and 16 matched controls. For controls, there was an attentional cost of dual level processing for low level performance but not for high level performance. For participants with ASD, there was an attentional cost both for low level and for high level performance. These results suggest a compensatory strategic use of attention during language processing in ASD.     

Agrin-signaling is necessary for the integration of newly generated neurons in the adult olfactory bulb

In the adult forebrain, new interneurons are continuously generated and integrated into the existing circuitry of the olfactory bulb (OB). In an attempt to identify signals that regulate this synaptic integration process, we found strong expression of agrin in adult generated neuronal precursors that arrive in the olfactory bulb after their generation in the subventricular zone. While the agrin receptor components MuSK and Lrp4 were below detection level in neuron populations that represent synaptic targets for the new interneurons, the alternative receptor α3-Na(+)K(+)-ATPase was strongly expressed in mitral cells. Using a transplantation approach, we demonstrate that agrin-deficient interneuron precursors migrate correctly into the OB. However, in contrast to wild-type neurons, which form synapses and survive for prolonged periods, mutant neurons do not mature and are rapidly eliminated. Using in vivo brain electroporation of the olfactory system, we show that the transmembrane form of agrin alone is sufficient to mediate integration and demonstrate that excess transmembrane agrin increases the number of dendritic spines. Last, we provide in vivo evidence that an interaction between agrin and α3-Na(+)K(+)-ATPase is of functional importance in this system.