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The deficit in social interaction skills among individuals with autism spectrum disorder (ASD) is strongly influenced by personal experiences and social environments. Neuroimaging studies have previously highlighted the link between social impairment and brain activity in ASD. This study aims to develop a method for assessing and identifying ASD using a social cognitive game-based paradigm combined with electroencephalo-graphy (EEG) signaling features. Typically developing (TD) participants and autistic preadolescents and teenagers were recruited to participate in a social game while 12-channel EEG signals were recorded. The EEG signals underwent preprocessing to analyze local brain activities, including event-related potentials (ERPs) and time-frequency features. Additionally, the global brain network’s functional connectivity between brain regions was evaluated using phase-lag indices (PLIs). Subsequently, machine learning models were employed to assess the neurophysiological features. Results indicated pronounced ERP components, particularly the late positive potential (LPP), in parietal regions during social training. Autistic preadolescents and teenagers exhibited lower LPP amplitudes and larger P200 amplitudes compared to TD participants. Reduced theta synchronization was also observed in the ASD group. Aberrant functional connectivity within certain time intervals was noted in the ASD group. Machine learning analysis revealed that support-vector machines achieved a sensitivity of 100%, specificity of 91.7%, and accuracy of 95.8% as part of the performance evaluation when utilizing ERP and brain oscillation features for ASD characterization. These findings suggest that social interaction difficulties in autism are linked to specific brain activation patterns. Traditional behavioral assessments face challenges of subjectivity and accuracy, indicating the potential use of social training interfaces and EEG features for cognitive assessment in ASD.

The design goals of recently developed serious games are to improve attention, affective recognition, and social interactions among individuals with autism. However, most previous studies on serious games used behavioral questionnaires to evaluate their effectiveness. The cognitive assessment of individuals with autism after behavioral intervention or drug treatment has become important because it provides promising biomarkers to assess improvement after cognitive intervention. In this study, we developed a game-based social interaction platform incorporating an eye-tracking system for children and preadolescents with autism. Three modules (focusing on gaze following, facial emotion recognition, and social interaction skills) are included in the platform; participants with autism learn these according to their cognitive abilities. The eye-tracking results showed decreased fixation durations when autistic children looked at positive emotional expressions and focused on multiple targets. Prolonged saccade durations and shorter fixation times for social-related facial emotion expressions were also found in preadolescents and teenagers with autism. Our findings suggest that these atypical gaze patterns are reliable biomarkers for evaluating the social and cognitive functions of autistic individuals while playing serious games. The proposed platform’s game-based modules and the findings regarding aberrant gaze patterns in autistic individuals demonstrate the possibility of evaluating cognitive functions and intervention effectiveness by using eye-tracking signals in a serious game or real-life environment.

Background/purpose: Youths with autism spectrum disorder (ASD) are at a high risk of involvement in school bully. The study investigated whether comorbid psychopathologies mediated the link between ASD and bullying involvement. Methods: We assessed 353 youths (mean age, 11.8 ± 3.1 years), including 121 youths with ASD and 232 typically developing (TD) controls, using semi-structured diagnostic interviews on ASD and other psychiatric conditions. Follow-up assessments took place 2–5 years (37.6 ± 15 months) later. Meanwhile, their parents reported on the Social Adjustment Inventory for Children and Adolescents about bullying involvement statuses. We identified significant mediators by simple mediation models, followed by multiple mediation models to scrutinize the mediation effects of selected mediators. Results: The results showed a sevenfold increased risk of bullying involvement among youths with ASD compared with TD controls at follow-up. In general, psychopathologies mediated the link between ASD and bullying involvement, even independent of age and sex. Specifically, we found mediating effects of social problems on victimization-only and aggressive behaviors on victimization-perpetration. Conclusion: Our findings strongly suggest the link between ASD and later bullying involvement is mediated by pre-existing comorbid psychiatric conditions, besides the direct effect of ASD on bullying victimization. Hence, early identification and intervention of these psychopathologies are highly suggested.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder globally, and is often caused by abnormal fatty acid metabolism. Plant-based fatty acid may lower the risk of NAFLD, but evidence shows that plant-based fatty acid can still induce fatty liver. Lignosus rhinoceros is a mushroom that is widely used as folk medicine in Southeast Asia. Studies indicate that L. rhinoceros can act as an antioxidant and immune modulator, might be a potent modulator for NAFLD. In this study, a plant-based high-fat diet (HFD) was used to induce fatty liver in hamsters. Hot water extract of L. rhinoceros was applied during the induction period. The antioxidant capacity of L. rhinoceros was evaluated. Results: Data reveal that L. rhinoceros extract had promising DPPH scavenging and ferrous ion chelating compacities. The total phenolic and flavonoid contents were 366.23 ± 5.06 mg gallic acid and 28.67 ± 2.5 mg rutin equivalents per gram of raw L. rhinocerus powder, respectively. Lignosus rhinoceros extract lowered body weight, and reduced liver damage which was induced by HFD in hamster, possibly by reducing mononuclear cell infiltration in the liver. Lignosus rhinoceros treatment also lowered the cholesterol content and improved the HDL-c/LDL-c level in hamster serum. Finally, L. rhinoceros reduced the reactive oxygen species content in the liver which was caused by HFD. Conclusions: This investigation provides evidence that a plant-based HFD may be a risk factor in fatty liver. It also proves that L. rhinoceros promotes liver health, and so can be used in functional food.How to cite: Tsai W-C, Hoe T-L, Lu S-C, et al. Lignosus rhinocerus attenuates non-alcoholic fatty liver induced by plant-based high-fat diet in hamster. Electron J Biotechnol 2022;58. https://doi.org/10.1016/j.ejbt.2022.05.004.

The World Health Organization (WHO) developed the Caregiver Skills Training for Families of Children with Developmental Delays and Disabilities (CST) with support from Autism Speaks to address the resource gaps and worldwide needs for interventions for children with developmental disorders or delays, especially those with autism spectrum disorder (ASD), and their families. Evidence has indicated that parent-mediated interventions benefit both caregivers and children by strengthening caregivers' knowledge and confidence and children's social communication skills and behavioral regulation. The CST-Taiwan team began the prepilot field trial in 2017 and developed the project to serve families in various locations. This study (1) delineated the adaptations and promotion of CST-Taiwan; (2) determined the program's effectiveness in the promotional stage, in terms of caregiver and child outcomes, and (3) examined the maintenance of its effects. The materials, delivery, and facilitator training procedure of the original CST were adapted to Taiwan. The quantitative data indicated that CST-Taiwan is a promising program, it positively affected caregiver knowledge and confidence and reduced the severity of the children's autistic symptoms. The 3-month follow-up results suggested that the effects persisted. Thus, CST-Taiwan, and its promotional strategies are feasible and effective.

Background: Koelreuteria henryi Dummer is an indigenous plant in Taiwan. The species has been used in traditional folk medicine for the promotion of liver functions and for treating malaria and urethritis. The present study investigated the antioxidant activity of the flower extract of Koelreuteria henryi Dummer. The extraction conditions were optimized by the contents of total phenolic acids and total flavonoids, and antioxidant activity assays. Moreover, an in vitro study for investigating antioxidant activity of K. henryi flower extract was demonstrated by hydrogen peroxide (H2O2)-induced apoptosis. Results: K. henryi flower extracted for 150 min showed high contents of total phenolic acids and total flavonoids. In an in vitro model, L929 cells were pretreated with K. henryi flower extract, and then treated with H2O2 to induce oxidative damage. Results demonstrated that H2O2-induced apoptosis was inhibited by the treatment of 200 μg/ml K. henryi flower extract through the mitochondria-mediated pathway and mitogen-activated protein kinase (MAPK) pathway. The caspase 8/9 activity and expression of p-p38 and pERK were repressed by K. henryi flower extract. In addition, the prevention of H2O2-induced apoptosis by K. henryi flower extract activated the nuclear factor-erythroid 2-related factor (Nrf2) stress response pathway to transcript heme oxygenase 1 (HO-1). Also, K. henryi flower extract prevented H2O2-induced apoptosis through HO-1 production, as evident by the use of HO-1 inhibitor. Conclusions: The present study demonstrated that K. henryi flower extract could inhibit the H2O2-induced apoptosis in L929 cells through the activation of the Nrf2/HO-1 pathway.How to cite: Tsai WC, Chang HC, Yin HY, et al. The protective ability and cellular mechanism of Koelreuteria henryi Dummer flower extract against hydrogen peroxide-induced cellular oxidative damage. Electron J Biotechnol 2020;47. https://doi.org/10.1016/j.ejbt.2020.07.006.

Background: Taraxacum species (commonly known as dandelion) used as herbal medicine have been reported to exhibit an antiproliferative effect on hepatoma cells and antitumor activity in non-small-cell lung cancer cells. Although several investigations have demonstrated the safety of Taraxacum officinale, the safety of tissue-cultured plants of T. formosanum has not been assessed so far. Therefore, the present study examines the safety of the water extract of the entire plant of tissue cultured T. formosanum based on acute and subacute toxicity tests in rats, as well as the Ames tests. Results: No death or toxicity symptoms were observed in the acute and subacute tests. The results of the acute test revealed that the LD50 (50% of lethal dose) value of the T. formosanum water extract for rats exceeded 5 g/kg bw. No abnormal changes in the body weight, weekly food consumption, organ weight, or hematological, biochemical, and morphological parameters were observed in the subacute toxicity test. Thus, the no observed adverse effect level (NOAEL) of T. formosanum water extract was estimated to be higher than 2.0 g/kg. Finally, the results of the Ames test revealed that T. formosanum water extract was not genotoxic at any tested concentration to any of five Salmonella strains. Conclusions: The water extract of tissue-cultured T. formosanum was non-toxic to rats in acute and subacute tests and exhibited no genotoxicity to five Salmonella strains.How to cite: Tsai WC, Chang HC, Tseng YH, et al. Toxicity evaluation of water extract of tissue-cultured Taraxacum formosanum by acute, subacute administration, and Ames test. Electron J Biotechnol 2020;45. https://doi.org/10.1016/j.ejbt.2020.04.001

This pilot study investigates the feasibility and assesses the impact of "Lactobacillus plantarum" PS128 probiotics on the neurological function in Rett syndrome. We conducted a randomized, double-blind, and placebo-controlled trial on Rett syndrome with MECP2 mutation aged between 1 and 50 years in Taiwan. In this pilot study, twice-daily "L. plantarum" PS128 or placebo was administered for 16 weeks. In addition to feasibility, we also assessed the changes utilizing the Mullen Scales of Early Learning. In total, 36 participants were finally randomized into "L. plantarum" PS128 (n = 18) or placebo (n = 18) groups. At the end of intervention, the retention rates were 100% for "L. plantarum" PS128 and 94.44% for placebo, with withdrawal rates of 5.56% for the placebo group. Both groups tolerated well, except for one "L. plantarum" PS128 participant who reported loose stool. The probiotic group showed a change of 2.19 ± 3.76, while the placebo group had -0.85 ± 5.09 (p = 0.051) in the total age-equivalent scores of Mullen Scales of Early Learning. There was a significant difference in the change of the total score on the Burke-Fahn-Marsden Movement Scale between probiotic group and placebo group (-12.19 ± 12.12 vs -4.59 ± 4.20, p = 0.020). In leg dystonia, the probiotic group exhibited a change of -4.11 ± 5.11 compared with -0.38 ± 1.50 in the placebo group (p = 0.008). Our findings affirm the feasibility of "L. plantarum" PS128 in Rett syndrome. Future clinical trials are mandatory to further explore its long-term impact on Rett syndrome.

Central nervous system (CNS) patterning genes are recognized as candidate genes for autism spectrum disorders (ASDs) based on neuroimaging and neuropathological evidence. Several genes that regulate CNS development are shown to be associated with ASD. Our previous family-based association study also revealed that a specific haplotype of WNT2 (wingless-type MMTV integration site family member 2) gene was overtransmitted to probands with ASD. Whether the CNS patterning genes moderate the clinical phenotype of ASD is unclear. This study investigated the genetic associations of WNT2, engrailed 2 (EN2), and forkhead box P2 (FOXP2) with the clinical symptom severity. Methods: The sample included 391 patients (males, 88.3%; mean age±standard deviation, 9.5±4.4 years) diagnosed with ASDs. Tag single nucleotide polymorphisms (SNPs) of EN2, WNT2, and FOXP2 were genotyped. The single-locus and multilocus markers were tested for association. Results: We found that multilocus markers of WNT2 were associated with stereotyped behaviors whereas the markers of FOXP2 tended to be associated with social deficits. Moreover, an SNP of WNT2 showed a trend to be associated with less inattentive symptoms. Conclusion: Our findings that WNT2 and FOXP2 may moderate the clinical phenotypes of ASD provide evidence to support the possible universal effect of WNT2 and FOXP2 on neurodevelopmental symptom dimensions. Such findings warrant further validation in other independent samples. Trial registration: Clinical trial registration identifier: NCT00494754

Abstract Background The presence of attention-deficit/hyperactive disorder (ADHD) symptoms and impaired attention performance are commonly noted in individuals with autism spectrum disorder (ASD). However, little is known about attention performance in their unaffected siblings. This study aimed to investigate the ADHD-related traits and attention performance in unaffected siblings of probands with autism and Asperger syndrome (AS), as well as the clinical correlates of ADHD-related traits. Methods We assessed the intention, hyperactivity-impulsivity, and oppositional symptoms, and attention profiles of 199 probands with a diagnosis of ASD (122 autism, 77 AS), their unaffected siblings, and 196 typically developing controls (TD) by their parents’ reports on the ADHD-related symptoms and the Connors' Continuous Performance Test (CCPT), respectively. Results Compared to TD, unaffected siblings of ASD probands were more hyperactive/impulsive and oppositional, particularly unaffected siblings of AS probands. In CCPT, unaffected siblings of AS have intermediate levels of performance between probands with AS and TD on focused attention and sustained attention but were not statistically different from AS probands or TD in these attention profiles. In contrast, unaffected siblings of autism probands have significantly better CCPT performance when compared to autism probands but not to TD. In addition, stereotyped behaviors predicted ADHD-related traits in both sibling groups, but distinctive patterns of other correlates for ADHD-related traits were found between the two sibling groups. Conclusions This work suggested that unaffected siblings of AS, but not autism, have more hyperactive/impulsive traits and a trend of pervasive attention deficits assessed by CCPT which might serve as potential endophenotypes for genetic studies in AS. Trial registration ClinicalTrials.gov, NCT01582256

FOXG1-related syndrome is a rare neurodevelopmental encephalopathy characterized by early onset hyperkinetic movement disorders, absent language, autistic features, epilepsy, and severe cognitive impairment. However, detailed evaluation of cognition and evolution of movement disorders over time have not been clearly described before. In this study, we performed whole-exome sequencing in a cohort with unknown severe encephalopathy and movement disorders, with/without autistic behaviors. We identified FOXG1 mutations in three patients. One of them had a novel mutation that has not been described before. The neuropsychological test by Mullen Scales of Early Learning (MSEL) showed severe psychomotor impairments in all patients. There were uneven cognitive abilities in terms of verbal and non-verbal cognitive domains in all of them, with approximately 2 months differences. Gross motor skills and expressive language were more severely affected than the other domains in all the patients. All individuals had early onset hyperkinetic movement disorders. The movement disorders in one of our patients changed from predominantly hyperkinetic in early childhood to more hypokinetic in adolescence with the development of dystonia. To the best of our knowledge, this evolution had never been described before. In conclusion, individuals with FOXG1-related syndrome may show clinical progression from hyperkinetic to hypokinetic features over time. There were also uneven cognitive abilities in verbal and non-verbal cognitive domains. The FOXG1 mutation should be considered in individuals with a history of hyperkinetic movements, microcephaly, and uneven cognitive abilities with characteristic brain images.

The mediators of real-world executive functions in autism during the transition into adulthood are mainly unknown. This study aimed to identify the mediators for the behavioral and cognitive domains of real-world executive functions in late adolescent and young adult autistic populations. We followed up 289 autistic children (aged 11.6 ± 3.8, male 82.2%) and 203 non-autistic controls (10.7 ± 2.9, 66.5%) to their ages of 16.9 ± 4.7 and 15.8 ± 3.9, respectively. The Behavior Rating Inventory of Executive Function, comprising two global scales (Behavioral Regulation Index and the Metacognitive Index), was used to assess real-world executive functions at Time 2. Mediators of behavior regulation and metacognition were explored among a wide range of clinical correlates and parental bonding. We found that the autistic group had lower executive functions than the non-autistic group with lower behavior regulation and metacognition subscores. Several childhood factors were significant mediators. Multiple mediation analyses revealed that childhood inattention remained a significant mediator for both behavior regulation and metacognition in late adolescence, and peer problems were the specific mediators of metacognition. Our findings suggest several childhood factors may mediate real-world executive functions during late adolescence. Treating common mediators such as inattention may improve real-world executive functions in autistic individuals during adulthood.

OBJECTIVE:PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) regulates components of the cell cycle, including cell growth, immune responses, DNA damage repair, apoptosis, and inflammation. PBK/TOPK may also accelerate tumorigenesis in colorectal cancer. METHODS:We investigated the impact of PBK/TOPK on the clinical outcome of colorectal cancer patients to further identify its role in colorectal cancer. PBK/TOPK immunoreactivity was analyzed by immunohistochemistry in 162 cancer specimens from primary colorectal cancer patients. RESULTS:The mean follow-up time after surgery was 5.4 years (medium: 3.9 years; range 0.01 to 13.1 years). The prognostic value of PBK/TOPK on overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. PBK/TOPK was expressed in both the cytoplasm and nucleus. High PBK/TOPK expression in tumor cells was significantly associated with advanced T value. The 5-year survival rate was greater for patients with high total PBK/TOPK expression than with low PBK/TOPK expression (58.3% vs 34.4%, P = 0.005). Multivariate analyses showed that low-scoring cytoplasmic PBK/TOPK, negative nuclear PBK/TOPK, low total PBK/TOPK, and advanced tumor stage were correlated with poor overall patient survival. CONCLUSIONS:We suggest that PBK/TOPK expression, detected by IHC staining, could be used as an independent prognostic marker for colorectal cancer patients.

BACKGROUND:Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic components. Several recent genome-wide association (GWA) studies in Caucasian samples have reported a number of gene regions and loci correlated with the risk of ASD--albeit with very little consensus across studies. METHODS:A two-stage GWA study was employed to identify common genetic variants for ASD in the Taiwanese Han population. The discovery stage included 315 patients with ASD and 1,115 healthy controls, using the Affymetrix SNP array 6.0 platform for genotyping. Several gene regions were then selected for fine-mapping and top markers were examined in extended samples. Single marker, haplotype, gene-based, and pathway analyses were conducted for associations. RESULTS:Seven SNPs had p-values ranging from 3.4~9.9*10-6, but none reached the genome-wide significant level. Five of them were mapped to three known genes (OR2M4, STYK1, and MNT) with significant empirical gene-based p-values in OR2M4 (p = 3.4*10(-5)) and MNT (p = 0.0008). Results of the fine-mapping study showed single-marker associations in the GLIS1 (rs12082358 and rs12080993) and NAALADL2 (rs3914502 and rs2222447) genes, and gene-based associations for the OR2M3-OR2T5 (olfactory receptor genes, p = 0.02), and GLIPR1/KRR1 gene regions (p = 0.015). Pathway analyses revealed important pathways for ASD, such as olfactory and G protein-coupled receptors signaling pathways. CONCLUSIONS:We reported Taiwanese Han specific susceptibility genes and variants for ASD. However, further replication in other Asian populations is warranted to validate our findings. Investigation in the biological functions of our reported genetic variants might also allow for better understanding on the underlying pathogenesis of autism.

This study develops a rapid lateral flow assay (LFA) that uses immunomagnetic nanoparticles (IMNPs) to detect mango major allergen (Man i1) in food products. Monoclonal antibodies (2F1 and 21A5) were prepared; mAb-2F1 was modified on the surface of IMNPs and mAb-21A5 was immobilized on the test line of the LFA strips. Following optimization, the limit of detection (LOD) of this developed LFA was 6.2 ng/mL for rMan i1 with a linear range of 5-100 ng/mL. The assay also had high specificity in the analysis of nine vegetables and fruits. Furthermore, 22 food products were analyzed by this assay and mango allergens were detected in 13 food products that contained mango. In conclusion, a rapid LFA that uses IMNPs was developed herein for the detection of the major mango allergen Man i1 in processed foods. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests that cortical anatomy may be aytpical in autism spectrum disorder. The wingless-type MMTV integration site family, member 2 (WNT2), a candidate gene for autism spectrum disorder, may regulate cortical development. However, it is unclear whether WNT2 variants are associated with altered cortical thickness in autism spectrum disorder. Methods: In a sample of 118 people with autism spectrum disorder and 122 typically developing controls, we investigated cortical thickness using FreeSurfer software. We then examined the main effects of the WNT2 variants and the interactions of group × SNP and age × SNP for each hemisphere and brain region that was altered in people with autism spectrum disorder. Results: Compared to neurotypical controls, people with autism spectrum disorder showed reduced mean cortical thickness in both hemispheres and 9 cortical regions after false discovery rate correction, including the right cingulate gyrus, the orbital gyrus, the insula, the inferior frontal gyrus (orbital part and triangular part), the lateral occipitotemporal gyrus, the posterior transverse collateral sulcus, the lateral sulcus and the superior temporal sulcus. In the full sample, 2 SNPs of WNT2 (rs6950765 and rs2896218) showed age × SNP interactions for the mean cortical thickness of both hemispheres, the middle-posterior cingulate cortex and the superior temporal cortex. Limitations: We examined the genetic effect for each hemisphere and the 9 regions that were altered in autism spectrum disorder. The age effect we found in this cross-sectional study needs to be examined in longitudinal studies. Conclusion: Based on neuroimaging and genetic data, our findings suggest that WNT2 variants might be associated with altered cortical thickness in autism spectrum disorder. Whether and how these WNT2 variants might involve cortical thinning requires further investigation. [ABSTRACT FROM AUTHOR]

A conventional growth mode as well as flow-rate modulation epitaxy at various growth temperatures were used to study the InN nanodots grown on GaN by metal organic chemical vapor deposition. The results showed that the surface morphology of InN nanodots and their photoluminescence (PL) properties is greatly influenced by the different precursor injection schemes and the growth temperatures.

Background: Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder with complex genetic underpinning in its etiology. Copy number variations (CNVs) as one of the genetic factors associated with ASD have been addressed in recent genome-wide association studies (GWAS). However, the significance of CNV has not been well investigated in non-Caucasian ASD population. Methods: To identify the pathogenic CNVs responsible for ASD in Han Chinese, we performed a segment-based GWAS of CNV in 335 ASD cases and 1093 healthy controls using Affymetrix single nucleotide polymorphism (SNP) array by focusing on case-specific CNVs. PARK2 was one of the important genes with several case-specific regions overlapped on it. The findings were validated in the initial screen sample set and replicated in another sample set by real-time quantitative PCR (qPCR). Results: A total of six CNVs at 6q26 that spanned different exons of PARK2 were identified. The PARK2 expression level was down-regulated at exon-dependent manner in cases with either deletion or duplication. The result revealed that the gene function might be disrupted by exonic deletion and duplication. We also observed that the ASD case with exonic duplication demonstrated a more severe interference of PARK2 expression and the clinical feature than the ones with deletion at the exons 2-4 of the PARK2 gene. Conclusions: Our finding provides evidence to support that CNVs affecting PARK2 function might contribute to genetic etiology of a proportion of cases with ASD. The intriguing results of this work warrant further study on characterizing the functional impact of various exonic CNVs on the PARK2 gene. [ABSTRACT FROM AUTHOR]

Background GABRB3 is a position candidate gene at chromosome 15q12 that has been implicated in the neurobiology of autism spectrum disorders (ASD). The aim of this study was to examine the genetic association of GABRB3 with ASD. Methods The sample consisted of 356 patients with clinical diagnosis of ASD according to the DSMIV diagnostic criteria and confirmed by the Autism Diagnostic Interview-Revised and 386 unrelated controls. We searched for mutations at all the exonic regions and 1.6 Kb of the 5' region of GABRB3 in the genomic DNA of all the participants using the Sanger sequencing. We implemented a case-control association analysis of variants detected in this sample, and conducted a reporter gene assay to assess the functional impact of variants at the 5' regulatory region. Results We detected six known common SNPs; however, they were not associated with ASD. Besides, a total of 22 rare variants (12 at 5' regulatory, 4 at intronic, and 6 at exonic regions) were detected in 18 patients and 6 controls. The frequency of rare variants was significantly higher in the patient group than in the control group (18/356 versus 6/386, odds ratio = 3.37, P = 0.007). All the 12 rare variants at the 5' regulatory region were only detected in 7 patients, but not in any of the controls (7/356 versus 0/386, Fisher's exact test, P = 0.006). Two patients carried multiple rare variants. Family studies showed that most of these rare variants were transmitted from their parents. Reporter gene assays revealed that four rare variants at the 5' regulatory region and 1 at exon 1a untranslated region had elevated reporter gene activities compared to two wild type alleles. Conclusions Our data suggest rare variants of GABRB3 might be associated with ASD, and increased GABRB3 expression may contribute to the pathogenesis of ASD in some patients. Trial registration Clinical trial registration: Identifier: NCT00494754 [ABSTRACT FROM AUTHOR]

The optical properties of single InGaN/GaN heterostructure nanowires (NWs) with a mean diameter down to 18 nm are investigated. Sharp emission lines originating from the recombination of localized excitons in the InGaN disk layer can be resolved. Excitation-dependent energy shifts, together with spectral diffusions of these emission lines, indicate the presence of a weak quantum confined Stark effect (QCSE) caused by nearby charge fluctuations, rather than the screening of piezoelectric polarizations at the InGaN/GaN interface. The absence of a piezoelectric polarization field is further confirmed by time-resolved photoluminescence measurements. Numerical simulations reveal that the elastic strain relaxation via the NW geometry is marginal and occurs only near the NW sidewalls. Carrier localization preferentially near the periphery of the InGaN disk and alloy intermixing are suggested as possible reasons for the absence of a polarization-induced QCSE in thin InGaN/GaN heterostructure NWs. [ABSTRACT FROM AUTHOR]

Background: We recently reported a terminal deletion of approximately 2.4 Mb at chromosome 8p23.2-pter in a boy with autism. The deleted region contained the DLGAP2 gene that encodes the neuronal post-synaptic density protein, discs, large (Drosophila) homolog-associated protein 2. The study aimed to investigate whether DLGAP2 is genetically associated with autism spectrum disorders (ASD) in general. Methods: We re-sequenced all the exons of DLGPA2 in 515 patients with ASD and 596 control subjects from Taiwan. We also conducted bioinformatic analysis and family study of variants identified in this study. Results: We detected nine common single nucleotide polymorphisms (SNPs) and sixteen novel missense rare variants in this sample. We found that AA homozygotes of rs2906569 (minor allele G, alternate allele A) at intron 1 (P = 0.003) and CC homozygotes of rs2301963 (minor allele A, alternate allele C) at exon 3 (P = 0.0003) were significantly over-represented in the patient group compared to the controls. We also found no differences in the combined frequency of rare missense variants between the two groups. Some of these rare variants were predicted to have an impact on the function of DLGAP2 using informatics analysis, and the family study revealed most of the rare missense mutations in patients were inherited from their unaffected parents. Conclusions: We detected some common and rare genetic variants of DLGAP2 that might have implication in the pathogenesis of ASD, but they alone may not be sufficient to lead to clinical phenotypes. We suggest that further genetic or environmental factors in affected patients may be present and determine the clinical manifestations. [ABSTRACT FROM AUTHOR]

Background: Comparative gene expression profiling analysis is useful in discovering differentially expressed genes associated with various diseases, including mental disorders. Autism spectrum disorders (ASD) are a group of complex childhood-onset neurodevelopmental and genetic disorders characterized by deficits in language development and verbal communication, impaired reciprocal social interaction, and the presence of repetitive behaviors or restricted interests. The study aimed to identify novel genes associated with the pathogenesis of ASD. Methods: We conducted comparative total gene expression profiling analysis of lymphoblastoid cell lines (LCL) between 16 male patients with ASD and 16 male control subjects to screen differentially expressed genes associated with ASD. We verified one of the differentially expressed genes, FOXP1, using real-time quantitative PCR (RT-qPCR) in a sample of 83 male patients and 83 male controls that included the initial 16 male patients and male controls, respectively. Results: A total of 252 differentially expressed probe sets representing 202 genes were detected between the two groups, including 89 up- and 113 downregulated genes in the ASD group. RT-qPCR verified significant elevation of the FOXP1 gene transcript of LCL in a sample of 83 male patients (10.46 ± 11.34) compared with 83 male controls (5.17 ± 8.20, P = 0.001). Conclusions: Comparative gene expression profiling analysis of LCL is useful in discovering novel genetic markers associated with ASD. Elevated gene expression of FOXP1 might contribute to the pathogenesis of ASD. [ABSTRACT FROM AUTHOR]

Parental explanatory models about autism influence the type of therapy a child receives, the child's well-being, and the parents' own psychological adaptation. This qualitative study explored explanatory models used by parents of children with autism. In-depth interviews were conducted with 13 parents of children with autism from a medical center in Taiwan. Despite high educational background, most of these parents attributed their child's autism to both biomedical and supernatural etiologies without apparent conflicts. These parents chose a wide variety of treatment strategies, including biomedical and alternative treatments, which often created time/energy pressures and financial burden, and were influenced by parents' cause attribution. Parents' illness explanations influence their treatment selections and need to be understood and accepted by health care providers. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to examine changes of attention-deficit–hyperactivity disorder (ADHD) symptoms and psychiatric comorbidities at adolescence, and mother-child agreement on reports of ADHD symptoms among children with ADHD as compared to unaffected controls. Methods: The participants included 93 patients (male, 82.8%) aged 11–16, who were clinically diagnosed with ADHD at the mean age of 7.3 ± 2.8 years, and 93 age-, sex-, and parental education-matched school controls. The participants and their mothers were frist interviewed separately for baseline psychopathology at childhood, followed by current psychopathology using the Chinese Kiddie Epidemiologic version of the Schedule for Affective Disorders and Schizophrenia. Results: At adolescence, 46 patients (49.5%) met full DSM-IV ADHD criteria, 31 (33.3%) had subthreshold ADHD, and 16 (17.2%) had recovered from ADHD. We found a significant progressive decline in the three ADHD core symptoms for the ADHD group: hyperactivity had the greatest effect size, followed by inattention, and then impulsivity. Children with ADHD tended to report less severe ADHD symptoms at childhood and adolescence than their mothers. They were more likely than the controls to have oppositional defiant disorder (odds ratio (OR)=18.0; 95% confidence interval (CI)=8.3–38.9), conduct disorder (OR=23.1, 95%CI =5.3–100.2), mood disorders (OR=3.8, 95%CI = 1.5–9.4), bipolar disorders (Fisher's exact p < 0.001), and sleep disorders (OR=3.1, 95%CI = 1.6–6.0) at adolescence. Conclusions: The present findings are similar to those of Western studies, regarding the patterns of comorbidity, stability of core symptoms, and mother–child differences on symptom reports. [ABSTRACT FROM AUTHOR]

We report Raman measurements on InN islands grown on GaN by metalorganic chemical vapor deposition. The Raman frequency of the InN E2 mode is found to decrease exponentially with the island’s aspect ratio, indicating a size dependent strain relaxation during the island formation. Our results suggest that most of the strain at the InN–GaN interface have been released plastically during the initial stage of island formations. After that, the residual strain of only -3.5×10-3 is further relaxed elastically via surface islanding. The experimental data are in agreement with the strain relaxation predicted from a simplified model analysis as well as three-dimensional finite-element simulations. [ABSTRACT FROM AUTHOR]