White matter abnormalities and neurocognitive correlates in children and adolescents with myotonic dystrophy type 1: a diffusion tensor imaging study

Diffusion tensor imaging was used to evaluate cerebral white matter in eight patients (ages 10-17), with myotonic dystrophy type 1 (3 congenital-onset, 5 juvenile-onset) compared to eight controls matched for age and sex. Four regions of interest were examined: inferior frontal, superior frontal, supracallosal, and occipital. The myotonic dystrophy group showed white matter abnormalities compared to controls in all regions. All indices of white matter integrity were abnormal: fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. With no evidence of regional variation, correlations between whole cerebrum white matter fractional anisotropy and neurocognitive functioning were examined in the patients. Strong correlations were observed between whole cerebrum fractional anisotropy and full-scale intelligence and a measure of executive functioning. Results indicate that significant white matter abnormality is characteristic of young patients with myotonic dystrophy type 1 and that the white matter abnormality seen with neuroimaging has implications for cognitive functioning.     

High throughput multiplex assay for species identification of Papua New Guinea malaria vectors: members of the Anopheles punctulatus (Diptera: Culicidae) species group

Malaria and filariasis are transmitted in the Southwest Pacific region by Anopheles punctulatus sibling species including An. punctulatus, An. koliensis, the An. farauti complex 1-8 (includes An. hinesorum [An. farauti 2], An. torresiensis [An. farauti 3]). Distinguishing these species from each other requires molecular diagnostic methods. We developed a multiplex polymerase chain reaction (PCR)-based assay specific for known species-specific nucleotide differences in the internal transcribed spacer 2 region and identified the five species most frequently implicated in transmitting disease (An. punctulatus, An. koliensis, An. farauti 1, An. hinesorum, and An. farauti 4). A set of 340 individual mosquitoes obtained from seven Papua New Guinea provinces representing a variety of habitats were analyzed by using this multiplex assay. Concordance between molecular and morphological diagnosis was 56.4% for An. punctulatus, 85.3% for An. koliensis, and 88.9% for An. farauti. Among 158 mosquitoes morphologically designated as An. farauti, 33 were re-classified by PCR as An. punctulatus, 4 as An. koliensis, 26 as An. farauti 1, 49 as An. hinesorum, and 46 as An. farauti 4. Misclassification results from variable coloration of the proboscis and overlap of An. punctulatus, An. koliensis, the An. farauti 4. This multiplex technology enables further mosquito strain identification and simultaneous detection of microbial pathogens.     

Inhibition of 3,4-methylenedioxymethamphetamine metabolism leads to marked decrease in 3,4-dihydroxymethamphetamine formation but no change in serotonin neurotoxicity: implications for mechanisms of neurotoxicity

3,4-Methylenedioxymethamphetamine (MDMA)'s O-demethylenated metabolite, 3,4-dihydroxymethamphetamine (HHMA), has been hypothesized to serve as a precursor for the formation of toxic catechol-thioether metabolites (e.g., 5-N-acetylcystein-S-yl-HHMA) that mediate MDMA neurotoxicity. To further test this hypothesis, HHMA formation was blocked with dextromethorphan (DXM), which competitively inhibits cytochrome P450 enzyme-mediated O-demethylenation of MDMA to HHMA. In particular, rats were randomly assigned to one of four treatment groups (n = 9-12 per group): (1) Saline/MDMA; (2) DXM/MDMA; (3) DXM/Saline; (4) Saline/Saline. During drug exposure, time-concentration profiles of MDMA and its metabolites were determined, along with body temperature. One week later, brain serotonin (5-HT) neuronal markers were measured in the same animals. DXM did not significantly alter core temperature in MDMA-treated animals. A large (greater than 70%) decrease in HHMA formation had no effect on the magnitude of MDMA neurotoxicity. These results cast doubt on the role of HHMA-derived catechol-thioether metabolites in the mechanism of MDMA neurotoxicity.