Potential identification of vitamin B6 responsiveness in autism spectrum disorder utilizing phenotype variables and machine learning methods.

We investigated whether machine learning methods could potentially identify a subgroup of persons with autism spectrum disorder (ASD) who show vitamin B6 responsiveness by selected phenotype variables. We analyzed the existing data from our intervention study with 17 persons. First, we focused on signs and biomarkers that have been identified as candidates for vitamin B6 responsiveness indicators. Second, we conducted hypothesis testing among these selected variables and their combinations. Finally, we further investigated the results by conducting cluster analyses with two different algorithms, affinity propagation and k-medoids. Statistically significant variables for vitamin B6 responsiveness, including combination of hypersensitivity to sound and clumsiness, and plasma glutamine level, were included. As an a priori variable, the Pervasive Developmental Disorders Autism Society Japan Rating Scale (PARS) scores was also included. The affinity propagation analysis showed good classification of three potential vitamin B6-responsive persons with ASD. The k-medoids analysis also showed good classification. To our knowledge, this is the first study to attempt to identify subgroup of persons with ASD who show specific treatment responsiveness using selected phenotype variables. We applied machine learning methods to further investigate these variables' ability to identify this subgroup of ASD, even when only a small sample size was available.

Preliminary ecological risk assessment of butylparaben and benzylparaben -1. Removal efficiency in wastewater treatment, acute/chronic toxicity for aquatic organisms, and effects on medaka gene expression.

Butylparaben and benzylparaben, used as preservatives mainly in cosmetic products, have recently been found to be weakly estrogenic. Batch activated-sludge treatment and batch chlorination were carried out to roughly determine the removal efficiency of a wastewater treatment plant. Combining the removal efficiency with the estimated annual consumption and the unaltered excretion ratio, the maximum predicted environmental concentration (PEC) was estimated. Conventional acute/chronic toxicity tests were conducted using Japanese medaka (Oryzias latipes), daphnia (Daphnia magna), and green algae (Pseudokirchneriella subcapitata) for n-butylparaben, i-butylparaben, and benzylparaben. Medaka vitellogenin assays were also conducted for the three compounds and DNA microarray analysis was carried out to examine the effects of benzylparaben on gene expression. The plasma vitellogenin concentration of male medaka increased for concentrations of 200, 100, and 100 microg L(-1) n-butylparaben, i-butylparaben, and benzylparaben for 14 days, respectively, while the expression levels of genes encoding proteins such as p53, cytochrome P450 3A40, and choriogenin-L increased for concentrations higher than 4 microg L(-1) of benzylparaben. Furthermore, the predicted no-effect concentration (PNEC) was calculated using the lethal or effect concentration 50 (LC50 or EC50) values and no-effect concentrations (NOECs) obtained in the toxicity tests for these compounds. The maximum concentrations found in the aquatic environment or sewage effluent (MEC eff) were used to carry out preliminary environmental risk assessment. The calculated MEC/PNEC ratio suggests the necessity of further study such as a more detailed large-scale monitoring and chronic toxicity tests including reproduction inhibition and endocrine disruption.

Preliminary ecological risk assessment of butylparaben and benzylparaben -2. Fate and partitioning in aquatic environments.

Butylparaben and benzylparaben, used as preservatives mainly in cosmetic products, have recently been shown to be weakly estrogenic. Batch sunlight photolysis and river water biodegradation experiments were conducted to determine the persistence of these compounds in aquatic environments. As a result, benzylparaben was found to be moderately photodegradable whereas both n-butylparaben and i-butylparaben were highly stable against sunlight. Both benzylparaben and butylparabens were relatively biodegradable in the river water but the degradability was dependent on the sampling site and time. Batch sorption experiments were also conducted to determine the coefficients of sorption into river sediments and a model soil sample. The determined coefficients were slightly higher for benzylparaben than the two butylparabens and comparable to that of the natural estrogen 17beta-estradiol. The coefficients were also higher for sediment/soil with a higher organic content and the organic-carbon-based sorption coefficient (log K oc) shows a moderate linear correlation with the octanol-water partition coefficient (log K ow). These results suggest that hydrophobic interaction plays a predominant role in sorption at neutral pH.

[A clinical study of pyridoxine treatment for pervasive developmental disorders with hypersensitivity to sound].

In our earlier study we conducted a randomized, placebo-controlled, triple blind trial, and showed that pyridoxine treatment of pervasive developmental disorders with expressive verbal disorders and hypersensitivity to sound as significantly effective in improving VIQ scores. This study analyzed the long-term changes of the subjects. We confirmed that their VIQ scores improved over time. An analysis of the reports of their daily life provided by their parents and teachers showed that the children's hypersensitivity to sound was also improved. They became able to adjust to their daily life at home and school without any panic. Our results indicate there are PDD subgroups whose expressive language capabilities and hypersensitivity to sound can be improved by pyridoxine treatment.

Cytokine and cellular inflammatory sequence in enteroviral meningitis.

OBJECTIVE: To clarify the sequence of cytokines and inflammatory cells in enteroviral meningitis. METHODS: Cerebrospinal fluid (CSF) was collected from 86 patients who received a diagnosis of enteroviral meningitis after detection of the enteroviral genome in the CSF using polymerase chain reaction. Twenty-one of 86 patients had repeated lumbar punctures. Cytokine concentrations were measured acutely and in 32 samples collected during recovery. RESULTS: The proinflammatory cytokines (interleukin [IL]-6, IL-8, and interferon-gamma) were detected at significantly higher concentrations during the acute phase when enteroviral genomes were present. Proinflammatory cytokines decreased to normal levels in the recovery phase when enteroviral genomes disappeared. Anti-inflammatory concentrations (IL-10 and transforming growth factor-beta1) were significantly higher in the recovery phase than in the acute phase. Of the 86 CSF samples collected in the acute phase, 11 had no pleocytosis (<10 white blood cells/mm(3)). In 7 of those 11 CSF samples, IL-6 and IL-8 levels were as high as those in the 75 samples with pleocytosis (>or=10 white blood cells/mm(3)). Seven patients were considered to be in the initial stage of their illness when production of proinflammatory cytokines were high but leukocytes had not yet infiltrated the cerebrospinal cavity. CONCLUSIONS: The inflammatory process observed in human enteroviral meningitis is comparable with that observed in animal models: 1) infection induces proinflammatory cytokine production, followed by infiltration of white blood cells into the infected area, and 2) inflammation is terminated by the anti-inflammatory cytokines that are produced when pathogens are eliminated.