Comparative Analysis of the WISC between Two ADHD Subgroups.

OBJECTIVE: The prevalence of attention deficit/hyperactivity disorder (ADHD) in school-age children is 7.2%, and ADHD is divided into clinical subtypes. METHODS: The current study explored whether specific cognitive profiles as assessed using the Wechsler Intelligence Scale for Children (WISC)-IV could be obtained for each clinical ADHD subtype (ADHD-Inattentive type and ADHD-Combined type) and investigated the correlation between WISC scores and parental age at their children's birth or birthweight. The enrolled sample comprised 12 ADHD-I and 15 ADHD-C subjects. RESULTS: An impaired Processing Speed Index was found in ADHD-I. The age of the father at the child's birth and birthweight positively correlated with the full scale intelligence quotient (FSIQ) score in the WISC assessment. CONCLUSION: Inattentiveness within the behaviors of the children with ADHD-I is partly due to the impaired processing speed, therefore effective support for ADHD will be conducted if educator decreases their speaking speed. Since biological basis of ADHD is still largely unknown, future studies using both psychological and biological methods will reveal the etiology of ADHD. These scientific assessments will provide information for more effective approaches in the care of children with ADHD.

Correlation between frontal lobe oxy-hemoglobin and severity of depression assessed using near-infrared spectroscopy.

INTRODUCTION: The search for objective biomarkers of psychiatric disorders has a long history. Despite this, no universally accepted instruments or methods to detect biomarkers have been developed. One potential exception is near-infrared spectroscopy, although interpreting the measures of blood flow recorded with this technique remains controversial. In this study, we aimed to investigate the relationship between recorded blood flow and depression severity assessed using the Hamilton depression scale in patients with various psychiatric disorders. METHODS: Enrolled patients (n=43) had DSM-IV diagnoses of major depressive disorder (n=25), bipolar disorder I (n=5), schizophrenia (n=3), dysthymic disorder (n=3), psychotic disorder (n=3), panic disorder (n=2), and Obsessive Compulsive Disorder (n=2). The verbal fluency task was administered during blood flow recording from the frontal and temporal lobes. RESULTS: We found that severity of depression was negatively correlated with the integral value of blood flow in the frontal lobe, irrespective of psychiatric diagnosis (F=5.94, p=0.02). DISCUSSION: Our results support blood flow in the frontal lobe as a potential biomarker of depression severity across various psychiatric disorders. LIMITATION: Limited sample size, no replication in the second set.

Increases in iPS Transcription Factor (Oct4, Sox2, c-Myc, and Klf4) Gene Expression after Modified Electroconvulsive Therapy.

OBJECTIVE: Electroconvulsive therapy (ECT) is a reasonable option for intractable depression or schizophrenia, but a mechanism of action has not been established. One credible hypothesis is related to neural plasticity. Three genes (Oct4, Sox2, c-Myc) involved in the induction of induced pluripotent stem (iPS) cells are Wnt-target genes, which constitute a key gene group involved in neural plasticity through the TCF family. Klf4 is the other gene among Yamanaka's four transcription factors, and increases in its expression are induced by stimulation of the canonical Wnt pathway. METHODS: We compared the peripheral blood gene expression of the four iPS genes (Oct4, Sox2, c-Myc, and Klf4) before and after modified ECT (specifically ECT with general anesthesia) of patients with intractable depression (n=6) or schizophrenia (n=6). Using Thymatron ten times the total bilateral electrical stimulation was evoked. RESULTS: Both assessments of the symptoms demonstrated significant improvement after mECT stimulation. Expression of all four genes was confirmed to increase after initial stimulation. The gene expression levels after treatment were significantly different from the initial gene expression in all twelve cases at the following treatment stages: at the 3rd mECT for Oct4; at the 6th and 10th mECT for Sox2; and at the 3rd, 6th and 10th mECT for c-Myc. CONCLUSION: These significant differences were not present after correction for multiple testing; however, our data have the potential to explain the molecular mechanisms of mECT from a unique perspective. Further studie should be conducted to clarify the pathophysiological involvement of iPS-inducing genes in ECT.

Biodiesel production process from microalgae oil by waste heat recovery and process integration.

In this work, the optimization of microalgae oil (MO) based biodiesel production process is carried out by waste heat recovery and process integration. The exergy analysis of each heat exchanger presented an efficient heat coupling between hot and cold streams, thus minimizing the total exergy destruction. Simulation results showed that the unit production cost of optimized process is 0.592$/L biodiesel, and approximately 0.172$/L biodiesel can be avoided by heat integration. Although the capital cost of the optimized biodiesel production process increased 32.5% and 23.5% compared to the reference cases, the operational cost can be reduced by approximately 22.5% and 41.6%.

Microarray Analysis of Human Blood During Electroconvulsive Therapy.

INTRODUCTION: Electroconvulsive therapy (ECT) is currently regarded as a significant treatment option for intractable psychiatric disorders, such as catatonic schizophrenia or treatment-resistant depression; however, the underlying molecular mechanism for its therapeutic effect remains obscure. METHODS: Employing microarray analysis (Human Genome U133 Plus 2.0 Array; Affymetrix, United States) of cDNA derived from the peripheral blood of patients with catatonic schizophrenia (n = 5), we detected a significant change in 145 genes (0.68%) before and after modified ECT (mECT). Moreover, we performed quantitative polymerase chain reaction validation of genes that had previously been suggested to be functionally related to schizophrenia. RESULTS: Of 4 genes examined (AKT3, TCF7, PPP3R1, and GADD45B), only TCF7 was increased during the mECT procedure (P = 0.0025). DISCUSSION: This study describes the first attempt to uncover the molecular mechanism of mECT using a microarray assay of mRNA derived from peripheral blood, and our results suggest that the TCF family may play a role in the functional mechanism of mECT.

Micro-tubular solid oxide fuel cell based on a porous yttria-stabilized zirconia support.

Solid oxide fuel cells (SOFCs) are promising electrochemical energy conversion devices owing to their high power generation efficiency and environmentally benign operation. Micro-tubular SOFCs, which have diameters ranging from a few millimeters to the sub-millimeter scale, offer several advantages over competing SOFCs such as high volumetric power density, good endurance against thermal cycling, and flexible sealing between fuel and oxidant streams. Herein, we successfully realized a novel micro-tubular SOFC design based on a porous yttria-stabilized zirconia (YSZ) support using multi-step dip coating and co-sintering methods. The micro-tubular SOFC consisted of Ni-YSZ, YSZ, and strontium-doped lanthanum manganite (LSM)-YSZ as the anode, electrolyte, and cathode, respectively. In addition, to facilitate current collection from the anode and cathode, Ni and LSM were applied as an anode current collector and cathode current collector, respectively. Micro-crystalline cellulose was selected as a pore former to achieve better shrinkage behavior of the YSZ support so that the electrolyte layer could be densified at a co-sintering temperature of 1300 °C. The developed micro-tubular design showed a promising electrochemical performance with maximum power densities of 525, 442, and 354 mW cm(-2) at 850, 800, and 750 °C, respectively.

Genome-wide association study of atypical psychosis.

Atypical psychosis with a periodic course of exacerbation and features of major psychiatric disorders [schizophrenia (SZ) and bipolar disorder (BD)] has a long history in clinical psychiatry in Japan. Based upon the new criteria of atypical psychosis, a Genome-Wide Association Study (GWAS) was conducted to identify the risk gene or variants. The relationships between atypical psychosis, SZ and BD were then assessed using independent GWAS data. Forty-seven patients with solid criteria of atypical psychosis and 882 normal controls (NCs) were scanned using an Affymetrics 6.0 chip. GWAS SZ data (560 SZ cases and 548 NCs) and GWAS BD (107 cases with BD type 1 and 107 NCs) were compared using gene-based analysis. The most significant SNPs were detected around the CHN2/CPVL genes (rs245914, P = 1.6 × 10(-7)) , COL21A1 gene (rs12196860, P = 2.45 × 10(-7) ), and PYGL/TRIM9 genes (rs1959536, P = 7.73 × 10(-7) ), although none of the single-nucleotide polymorphisms exhibited genome-wide significance (P = 5 × 10(-8) ). One of the highest peaks was detected on the major histocompatibility complex region, where large SZ GWASs have previously disclosed an association. The gene-based analysis suggested significant enrichment between SZ and atypical psychosis (P = 0.01), but not BD. This study provides clues about the types of patient whose diagnosis lies between SZ and BD. Studies with larger samples are required to determine the causal variant.

Structure and orientation of bovine lactoferrampin in the mimetic bacterial membrane as revealed by solid-state NMR and molecular dynamics simulation.

Bovine lactoferrampin (LFampinB) is a newly discovered antimicrobial peptide found in the N1-domain of bovine lactoferrin (268-284), and consists of 17 amino-acid residues. It is important to determine the orientation and structure of LFampinB in bacterial membranes to reveal the antimicrobial mechanism. We therefore performed (13)C and (31)P NMR, (13)C-(31)P rotational echo double resonance (REDOR), potassium ion-selective electrode, and quartz-crystal microbalance measurements for LFampinB with mimetic bacterial membrane and molecular-dynamics simulation in acidic membrane. (31)P NMR results indicated that LFampinB caused a defect in mimetic bacterial membranes. Ion-selective electrode measurements showed that ion leakage occurred for the mimetic bacterial membrane containing cardiolipin. Quartz-crystal microbalance measurements revealed that LFampinB had greater affinity to acidic phospholipids than that to neutral phospholipids. (13)C DD-MAS and static NMR spectra showed that LFampinB formed an α-helix in the N-terminus region and tilted 45° to the bilayer normal. REDOR dephasing patterns between carbonyl carbon nucleus in LFampinB and phosphorus nuclei in lipid phosphate groups were measured by (13)C-(31)P REDOR and the results revealed that LFampinB is located in the interfacial region of the membrane. Molecular-dynamics simulation showed the tilt angle to be 42° and the rotation angle to be 92.5° for Leu(3), which are in excellent agreement with the experimental values.

The genetic validation of heterogeneity in schizophrenia.

INTRODUCTION: Schizophrenia is a heritable disorder, however clear genetic architecture has not been detected. To overcome this state of uncertainty, the SZGene database has been established by including all published case-control genetic association studies appearing in peer-reviewed journals. In the current study, we aimed to determine if genetic variants strongly suggested by SZGene are associated with risk of schizophrenia in our case-control samples of Japanese ancestry. In addition, by employing the additive model for aggregating the effect of seven variants, we aimed to verify the genetic heterogeneity of schizophrenia diagnosed by an operative diagnostic manual, the DSM-IV. METHODS: Each positively suggested genetic polymorphism was ranked according to its p-value, then the seven top-ranked variants (p < 0.0005) were selected from DRD2, DRD4, GRIN2B, TPH1, MTHFR, and DTNBP1 (February, 2007). 407 Schizophrenia cases and 384 controls participated in this study. To aggregate the vulnerability of the disorder based on the participants' genetic information, we calculated the "risk-index" by adding the number of genetic risk factors. RESULTS: No statistically significant deviation between cases and controls was observed in the genetic risk-index derived from all seven variants on the top-ranked polymorphisms. In fact, the average risk-index score in the schizophrenia group (6.5+/-1.57) was slightly lower than among controls (6.6+/-1.39). CONCLUSION: The current work illustrates the difficulty in identifying universal and definitive risk-conferring polymorphisms for schizophrenia. Our employed number of samples was small, so we can not preclude the possibility that some or all of these variants are minor risk factors for schizophrenia in the Japanese population. It is also important to aggregate the updated positive variants in the SZGene database when the replication work is conducted.

Chronic treatment with NGF induces spontaneous fluctuations of intracellular Ca(2+) in icilin-sensitive dorsal root ganglion neurons of the rat.

Adult rat dorsal root ganglion (DRG) neurons cultured in the presence of 100 ng/ml NGF show spontaneous action potentials and fluctuations in their cytosolic Ca(2+) concentrations ([Ca(2+)](i)). In the present study, the Ca(2+) sources of the [Ca(2+)](i) fluctuations and the types of neurons whose excitability was affected by NGF were examined. In the subpopulation of NGF-treated neurons, obvious fluctuations of [Ca(2+)](i) were observed. The [Ca(2+)](i) fluctuations were inhibited by Ca(2+) removal or inhibitors of voltage-gated Ca(2+) channels. Regardless of the treatment with NGF, about half of the neurons responded to capsaicin and 10% of the neurons responded to icilin, and almost all icilin-responding neurons also responded to capsaicin. Fluctuations of [Ca(2+)](i) with large amplitudes were observed in 12 out of 131 NGF-treated neurons. Among these 12 neurons, 10 neurons responded to both capsaicin and icilin. The degree of the [Ca(2+)](i) fluctuations in the NGF-treated neurons responding to both capsaicin and icilin was significantly larger than in other neurons. These results suggest that neurons expressing both capsaicin- and icilin-sensitive TRP channels are susceptible to NGF and become hyperexcitable and that Ca(2+) influx through voltage-gated Ca(2+) channels is the major source contributing to the [Ca(2+)](i) fluctuations. Since such DRG neurons could play a physiological role as nociceptors, the NGF-induced spontaneous activity of DRG neurons may be the underlying mechanism of neuropathic pain.

Habituation in prepulse inhibition is affected by a polymorphism on the NMDA receptor 2B subunit gene (GRIN2B).

OBJECTIVES: To identify the reliable connectivity between causal genes or variants with an abnormality expressed in a certain endophenotype has been viewed as a crucial step in unraveling the etiology of schizophrenia because of the considerable heterogeneity in this disorder. METHODS: According to this practical and scientific demand, we aimed to investigate the relationship between seven top-ranked variants in the SZgene database [120-bpTR in DRD4, rs1801028 and rs6277 in DRD2, rs1019385 (T200G) in GRIN2B, rs1800532 in TPH1, rs1801133 (C677T) in MTHFR, rs2619528 (P1765) in DTNBP1] and prepulse inhibition (PPI) and habituation after acoustic stimulus (HAB). RESULTS: Both PPI and HAB were decreased significantly in patients with schizophrenia. In addition, we observed a significant effect of GRIN2B (human NMDA receptor 2B subunit gene, NR2B) genotype on HAB (P<0.05, not corrected). CONCLUSION: Although these findings need to be replicated in other samples, an underlying mechanism of impaired biological reaction may be influenced by NMDA hypofunctioning in schizophrenia.

Partial analysis of hepatitis B virus DNA from hepatocellular carcinoma showing negative hepatitis B virus surface antigen: an analysis of two Japanese cases.

It has been reported that hepatitis B virus (HBV) DNA is detected in serum and/or liver in patients with hepatocellular carcinoma (HCC) without HBsAg. To adress this issue, we analyzed HBV genome in 2 HCC cases without HBsAg. The DNA from serum from patients with HCC was amplified with a nested PCR, and 'a' determinant of S region, core promoter region and precore region were sequenced. The first case, a 50 years-old male, was negative for HBsAg and HBeAg, and positive for anti-HBs, anti-HBe and anti-HBc. Viral load of HBV in serum was 4.0 log genome equivalent/ml by TMA assay, and was 1.1 X 105 copy/ml by real-time PCR system. A nucleotide analysis of the common 'a' determinant of S gene showed that the 5 first amino acids of 'a' determinant, CTIPA, were changed to CKTCTTPA. The second case, a 76 years-old male, was positive for anti-HBe, but negative for HBsAg, anti-HBs, HBeAg and anti-HBc. No missense or nonsense mutations were seen in 'a' determinant of S region. Viral load of serum HBV was < 3.7 log genome equivalent/ml by TMA assay, but was 2.4X103 copy/ml by real-time PCR system. The results of the present study suggest that the mechanisms of HBsAg loss are diverse among HCC patients without HBsAg, and that an analysis of HBV genome is a useful tool to dissolve molecular mechanisms losing HBs antigenicity.

Electrochemical properties of polyaniline/carboxydextran (PANI/carDEX) composite films for biofuel cells in neutral aqueous solutions.

Electrochemical properties of composite films consisting of polyaniline/carboxydextran (PANI/carDEX) as a biofuel cell electrode platform were investigated. These composite films were formed on a planar gold surface through electropolymerization after a simple chemical modification of dextran with carboxyl groups. Cyclic voltammetry indicated that the composite films retained a redox activity in neutral pH environment. The PANI/carDEX composite films showed an electrocatalytic activity for the oxidation of ascorbic acid. The PANI/carDEX composite films also demonstrated an excellent electron-transfer mediating capability for the bioelectrocatalytic activation of glucose oxidase (GOx) toward the oxidation of glucose.

Genetic polymorphisms in dopamine- and serotonin-related genes and treatment responses to risperidone and perospirone.

We investigated the possible association between genetic polymorphisms in the dopamine receptor and serotonin transporter genes and the responses of schizophrenic patients treated with either risperidone or perospirone. The subjects comprised 27 patients with schizophrenia who were clinically evaluated both before and after treatment. The genotyping of the polymorphisms of the dopamine D2 receptor gene (DRD2) (rs1801028 and rs6277), the dopamine D4 receptor gene (DRD4) (120-bp tandem repeats and rs1800955), and serotonin transporter gene (5HTT)(variable number of tandem repeats; VNTR) were performed using the real-time polymerase chain reaction and sequencing. In DRD2 and 5HTT-VNTR, there were no significant correlations between clinical response and polymorphism in the case of risperidone, and for perospirone treatment it was impossible to analyze the clinical evaluation due to the absence of genotype information. On the other hand, in DRD4 there were significant correlations in the two-factor interaction effect on the Positive and Negative Syndrome Scale (PANSS) between the two drugs [120-bp tandem repeat, p=0.003; rs1800955, p=0.043]. Although the small sample represents a serious limitation, these results suggest that variants in DRD4 are a predictor of whether treatment will be more effective with risperidone or with perospirone in individual patients.

NGF-induced hyperexcitability causes spontaneous fluctuations of intracellular Ca2+ in rat nociceptive dorsal root ganglion neurons.

NGF is a candidate for a pathogenic mediator of neuropathic pain after nerve injury and inflammation. It has been reported that adult rat dorsal root ganglion (DRG) neurons cultured in the presence of NGF at 100 ng/ml generate spontaneous action potentials. However, it is unclear what types of subpopulation of DRG neurons are affected by NGF and how the intracellular Ca(2+) concentration ([Ca(2+)](i)) changes in such neurons. To elucidate these points, we measured [Ca(2+)](i) in adult rat DRG neurons cultured with or without NGF. [Ca(2+)](i) fluctuated spontaneously in the absence of any stimuli in subpopulations of NGF-treated neurons, but such fluctuations were not observed in all NGF-untreated neurons. NGF-induced [Ca(2+)](i) fluctuations were inhibited by decreases in extracellular Na(+) concentration, TTX and Lidocaine, suggesting that spontaneous action potentials provoked the [Ca(2+)](i) fluctuation. NGF-induced [Ca(2+)](i) fluctuation was observed in small and medium sized neurons and in Capsaicin-sensitive neurons more frequently than in Capsaicin-non-responsive neurons. These results suggest that NGF acted on the nociceptive neurons and made them hyperexcitable to generate spontaneous action potentials and spontaneous [Ca(2+)](i) fluctuations. The [Ca(2+)](i) fluctuation induced by NGF may play some role in the regulation of membrane excitability of nociceptive sensory neurons and neuropathic pain.

An association study of the signal transducer and activator of transcription 6 gene with periodic psychosis.

OBJECTIVE: Recent molecular and genetic investigations have suggested that the current nosology for major psychiatric disorders, based on the "two-entities-principal" is not accurate with respect to clinical observations; patient groups that do not fit to the current operative diagnostic boundaries are readily identified. We aimed to perform an investigation of the signal transducer and activator of transcription 6 (STAT6) gene (located on 12q13), which has an important role in the apoptotic cascade, with patients suffering from periodic psychosis. METHODS: Genetic association study has been employed for the current work. Investigated six tag-SNPs were chosen from Hapmap database. RESULTS: Among six tag-SNPs, one marker (rs10783813), located in the STAT6 gene, showed modest association (p<0.05), although no marker or haplotype block showed association after Bonferroni's correction. CONCLUSION: Future studies will reveal the etiological role of STAT6, and of other genes of the apoptotic cascade, in major psychiatric disorders.

Schizophrenia is not associated with the functional candidate gene ERBB3: results from a case-control study.

Increasing evidence has supported the hypothesis of a neurodevelopmental component in the etiology of schizophrenia. Recently, several independent microarray gene expression studies have revealed downregulated expression of myelin-related genes in the postmortem brains of schizophrenia patients. Complete myelination of the cortex has been observed to occur in late adolescence and early adulthood, which is typically the age of onset of schizophrenia. ERBB3 is a gene which has not only been found to be downregulated in schizophrenia simultaneously in three microarray studies, but also is a strong candidate because of its potential role in neurodevelopment as a receptor of NRG1. Therefore, we performed association analysis of seven nonsynonymous SNPs in this gene. Two SNPs in ERBB3 (rs773123 and rs2271188) were polymorphic in our samples, neither of which showed significant evidence of association with the illness (P = 0.639 and 0.561, respectively). Because replication across such studies is notoriously difficult, the microarray evidence implicating ERBB3 still strongly supports some role of this gene in schizophrenia. However, our failure to find genetic association suggests that the differential expression of ERBB3 in schizophrenia may be environmentally driven, or involve cis- or trans-acting genetic factors beyond the boundaries of the gene itself.