Mapping corpus callosum deficits in autism: an index of aberrant cortical connectivity.

BACKGROUND: Volumetric studies have reported reductions in the size of the corpus callosum (CC) in autism, but the callosal regions contributing to this deficit have differed among studies. In this study, a computational method was used to detect and map the spatial pattern of CC abnormalities in male patients with autism. METHODS: Twenty-four boys with autism (aged 10.0 +/- 3.3 years) and 26 control boys (aged 11.0 +/- 2.5 years) underwent a magnetic resonance imaging (MRI) scan at 3 Tesla. Total and regional areas of the CC were determined using traditional morphometric methods. Three-dimensional (3D) surface models of the CC were also created from the MRI scans. Statistical maps were created to visualize morphologic variability of the CC and to localize regions of callosal thinning in autism. RESULTS: Traditional morphometric methods detected a significant reduction in the total callosal area and in the anterior third of the CC in patients with autism; however, 3D maps revealed significant reductions in both the splenium and genu of the CC in patients. CONCLUSIONS: Statistical maps of the CC revealed callosal deficits in autism with greater precision than traditional morphometric methods. These abnormalities suggest aberrant connections between cortical regions, which is consistent with the hypothesis of abnormal cortical connectivity in autism.     

Spatiotemporal pattern of striatal ERK1/2 phosphorylation in a rat model of L-DOPA-induced dyskinesia and the role of dopamine D1 receptors.

BACKGROUND: We examined the activation pattern of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and its dependence on D1 versus D2 dopamine receptors in hemiparkinsonian rats treated with 3,4-dihydroxyphenyl-L-alanine (L-DOPA). METHODS: 6-Hydroxydopamine-lesioned rats were treated acutely or chronically with L-DOPA in combination with antagonists for D1 or D2 receptors. Development of dyskinesia was monitored in animals receiving chronic drug treatment. Phosphorylation of ERK1/2, mitogen- and stress-activated protein kinase-1 (MSK-1), and the levels of FosB/DeltaFosB expression were examined immunohistochemically. RESULTS: L-DOPA treatment caused phosphorylation of ERK1/2 in the dopamine-denervated striatum after acute and chronic administration. Similar levels were observed in matrix and striosomes, and in enkephalin-positive and dynorphin-positive neurons. The severity of dyskinesia was positively correlated with phospho-ERK1/2 levels. Phosphorylation of ERK1/2 and MSK-1 was dose-dependently blocked by SCH23390, but not by raclopride. SCH23390 also inhibited the development of dyskinesia and the induction of FosB/DeltaFosB. CONCLUSIONS: L-DOPA produces pronounced activation of ERK1/2 signaling in the dopamine-denervated striatum through a D1-receptor-dependent mechanism. This effect is associated with the development of dyskinesia. Phosphorylated ERK1/2 is localized to both dynorphinergic and enkephalinergic striatal neurons, suggesting a general role of ERK1/2 as a plasticity molecule during L-DOPA treatment.     

A performance curve for assessing change in Percentage of Consonants Correct Revised (PCC-R).

PURPOSE: Interpreting the rapidly changing speech skills of young children recovering from neurological injury is difficult because developmental expectations are generally available only at relatively lengthy intervals (e.g., 6 or 12 months). In this research note, the authors describe the process of generating a Percentage of Consonants Correct-Revised (PCC-R; L. D. Shriberg, D. Austin, B. A. Lewis, J. L. McSweeny, & D. L. Wilson, 1997a) performance curve and illustrate some of its applications for assessing change in performance over time. METHOD: The authors compiled mean PCC-R scores from 16 samples of typically developing children (18-172 months) and used curve fitting to test more than 11,000 statistical models of monthly growth in PCC-R. They selected a parsimonious and developmentally plausible model with R(2) = .9839 (p < .0005) and used it to generate the PCC-R, standard deviation, and standard error expected at each monthly age. RESULTS: The PCC-R performance curve distinguished among 65 children (37-57 months of age) diagnosed independently with normal or disordered speech with a high degree of success. More important, the PCC-R performance curve can be used to identify the points at which children (18-172 months) recovering from neurological injury achieve normal-range consonant production. CONCLUSION: The curve-fitting approach holds promise as a means of interpreting temporal variations in speech production at a finer grain than existing normative data currently allow.     

Psychosocial factors at work and perceived health among agricultural meat industry workers in France

Objective  The objective of this study was to describe the perceived health status of the meat industry employees—i.e., working in the slaughtering, cutting, and boning of large animals and poultry—and its relation to their organisational and psychosocial constraints at work. Methods  This postal survey included all 3,000 employees of the meat industry (beef, pork and poultry) in four districts in Brittany, France, whose companies were affiliated with the agricultural branch of the national health insurance fund. The questionnaire asked for social and demographic data and information describing their job and the organisation of their work. The psychosocial factors at work were described according to Karasek’s questionnaire (demand, latitude and social support at work). Perceived health was measured with the Nottingham Health Profile perceived health indicator. Results  This study shows the high prevalence of poor health reported by the workers in this industry. This poor perceived health was worse in women and increased regularly with age. Among the psychosocial factors studied, high quantitative and qualitative demand at work, inadequate resources for good work and to a lesser extent, inadequate prospects for promotion appear especially associated with poor perceived health. Other factors often associated with poor perceived health included young age at the first job and work hours that disrupt sleep rhythms (especially for women). Conclusion  Our results show that this population of workers is especially vulnerable from the point of view of perceived physical and psychological health and is exposed to strong physical, organisational and psychosocial constraints at work. They also demonstrate that poor perceived health is associated with some psychosocial (such as high psychological demand and insufficient resources) and organisational factors at work. These results, in conjunction with those from other disciplines involved in studying this industry, may help the companies to develop preventive activities.     

Construction and validation of a Parkinson's disease mutation genotyping array for the Parkin gene.

Parkin mutations account for the majority of familial and sporadic early onset Parkinson's disease (EOPD) cases with a known genetic association. More than 100 mutations have been described in the Parkin gene that includes homozygous, compound heterozygous, and single heterozygous mutations. We have designed a Parkin mutation genotyping array (gene chip) that includes published Parkin sequence variants and allows their simultaneous detection. The chip was validated by screening 85 PD cases and 47 controls previously tested for Parkin mutations. Similar genotyping microarrays have been developed for other genetically heterogeneous diseases including age-related macular degeneration. Here, we show the utility of a genotyping array for Parkinson's disease by analysis of 60 subjects from the Genetic Epidemiology of Parkinson Disease (GEPD) study that includes 15 early-onset PD case probands and 45 relatives.     

Rat Cytomegalovirus-Accelerated Transplant Vascular Sclerosis Is Reduced with Mutation of the Chemokine-Receptor R33

Cytomegalovirus (CMV) infection accelerates transplant vascular sclerosis (TVS) and chronic rejection (CR) in both human and animal solid organ transplantation models. The host/viral mechanisms involved in this process are unclear. We examine the role of the rat CMV (RCMV)-encoded chemokine-receptor R33 in the development of TVS using a rat heart transplantation/CR model. F344 heart grafts were transplanted heterotopically into Lewis recipients. The ability of RCMV lacking the R33 gene (RCMV-Deltar33) to accelerate CR/TVS (neointimal index, NI) was compared to wild-type (WT) RCMV. Allograft recipients were infected with 1 x 10(5) pfu RCMV or RCMV-Deltar33 on postoperative day (POD) 1. Grafts from RCMV-Deltar33-infected recipients demonstrated an accelerated time to allograft CR compared to grafts from uninfected recipients (POD = 56 vs. 90), this was slower than that seen in grafts from WT-RCMV-infected recipients (POD = 45). Similarly, the degree of graft TVS formation at terminal rejection in RMCV-Deltar33 infected recipients was more severe than uninfected recipients (NI = 63 vs. 45), yet not as severe as in WT-RCMV infected recipients (NI = 83). In parallel, RCMV-Deltar33 failed to induce vascular smooth muscle cell (SMC) migration in vitro, whereas WT-RCMV induced substantial migration. The RCMV-encoded chemokine-receptor r33 is critical for RCMV-accelerated TVS/CR and vascular SMC migration.     

Reconstruction of lateral skull base defects after tumor ablation.

Neoplasms located in the lateral skull base region present a challenge for evaluation and management due to their difficult anatomic location and the complex reconstruction that is required following extensive tumor resection. Repair following tumor ablation requires a watertight dural seal, obliteration of the dead space, and coverage with vascularized soft tissue. Advances in radiologic imaging, diagnostic pathology, and surgical techniques and a multidisciplinary team for tumor ablation and reconstruction have significantly improved the treatment of these patients, minimized the occurrence of postoperative complications, and maximized patient outcome and quality of life. In this article, we present our experience in the reconstruction of extensive lateral skull base defects after tumor ablation.