Development of an Fe sensing system based on the inner filter effect between upconverting nanoparticles and ferrozine.

The ferrozine (FZ) assay is a vital oxidation state-specific colorimetric assay for the quantification of Fe ions in environmental samples due to its sharp increase in absorbance at 562 nm upon addition of Fe. However, it has yet to be applied to corresponding fluoresence assays which typically offer higher sensitivites and lower detection limits. In this article we present for the first time its pairing with upconverting luminescent nanomaterials to enable detection of Fe the inner filter effect using a low-power continuous wave diode laser (45 mW).

Three Brothers With Autism Carry a Stop-Gain Mutation in the HPA-Axis Gene NR3C2.

Whole exome sequencing and copy-number variant analysis was performed on a family with three brothers diagnosed with autism. Each of the siblings shares an alteration in the nuclear receptor subfamily 3 group C member 2 (NR3C2) gene that is predicted to result in a stop-gain mutation (p.Q919X) in the mineralocorticoid receptor (MR) protein.

Pharmacotherapy of Autism Spectrum Disorder: Results from the Randomized BAART Clinical Trial.

The objective of this trial, Biomarkers in Autism of Aripiprazole and Risperidone Treatment (BAART), was to provide support and guidance for an evidence-based approach for the selection and monitoring of initial pharmacotherapy in patients with autism by assessing predictors of efficacy, tolerability, and safety. This randomized double-blind parallel-group study was conducted in three academic medical centers and a single private pediatric practice. Eighty children or adolescents (aged 6-17 yrs) with autistic disorder were enrolled, and 61 patients were randomized to the study drug.

Genetic polymorphisms associated with the risk of concussion in 1056 college athletes: a multicentre prospective cohort study.

Background/aim: To evaluate the association of genetic polymorphisms APOE, G-219T promoter, microtubule associated protein(MAPT)/ exon 6 SerPro, MAPT/ HistTyr, 572 G/C and 358 with the risk of concussion in college athletes.

Methods: A 23-centre prospective cohort study of 1056 college athletes with genotyping was completed between August 2003 and December 2012. All athletes completed baseline medical and concussion questionnaires, and post-concussion data were collected for athletes with a documented concussion.

Comparison of serum carnitine levels and clinical correlates between outpatients and acutely hospitalised individuals with bipolar disorder and schizophrenia: A cross-sectional study.

Objectives: We sought to compare serum carnitine levels and clinical correlates between stable outpatients and acutely hospitalised individuals with diagnoses of bipolar disorder and schizophrenia.

Methods: We obtained clinical information as well as serum levels for total and free carnitine, high-density lipoprotein (HDL) and triglycerides in 60 consenting individuals.

Results: We found higher total serum carnitine levels in our outpatient group in comparison to acutely hospitalised psychiatric patients, with a statistically significant P value of 0.

Candidate glutamatergic and dopaminergic pathway gene variants do not influence Huntington's disease motor onset.

Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and behavioral disturbances. It is caused by the expansion of the HTT CAG repeat, which is the major determinant of age at onset (AO) of motor symptoms. Aberrant function of N-methyl-D-aspartate receptors and/or overexposure to dopamine has been suggested to cause significant neurotoxicity, contributing to HD pathogenesis.

Evaluating mitochondrial DNA variation in autism spectrum disorders.

Despite the increasing speculation that oxidative stress and abnormal energy metabolism may play a role in Autism Spectrum Disorders (ASD), and the observation that patients with mitochondrial defects have symptoms consistent with ASD, there are no comprehensive published studies examining the role of mitochondrial variation in autism. Therefore, we have sought to comprehensively examine the role of mitochondrial DNA (mtDNA) variation with regard to ASD risk, employing a multi-phase approach. In phase 1 of our experiment, we examined 132 mtDNA single-nucleotide polymorphisms (SNPs) genotyped as part of our genome-wide association studies of ASD.

The expanding role of MBD genes in autism: identification of a MECP2 duplication and novel alterations in MBD5, MBD6, and SETDB1.

The methyl-CpG-binding domain (MBD) gene family was first linked to autism over a decade ago when Rett syndrome, which falls under the umbrella of autism spectrum disorders (ASDs), was revealed to be predominantly caused by MECP2 mutations. Since that time, MECP2 alterations have been recognized in idiopathic ASD patients by us and others. Individuals with deletions across the MBD5 gene also present with ASDs, impaired speech, intellectual difficulties, repetitive behaviors, and epilepsy.

TAA repeat variation in the GRIK2 gene does not influence age at onset in Huntington's disease.

Huntington's disease is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat whose length is the major determinant of age at onset but remaining variation appears to be due in part to the effect of genetic modifiers. GRIK2, which encodes GluR6, a mediator of excitatory neurotransmission in the brain, has been suggested in several studies to be a modifier gene based upon a 3' untranslated region TAA trinucleotide repeat polymorphism. Prior to investing in detailed studies of the functional impact of this polymorphism, we sought to confirm its effect on age at onset in a much larger dataset than in previous investigations.

Evaluation of copy number variations reveals novel candidate genes in autism spectrum disorder-associated pathways.

Autism spectrum disorders (ASDs) are highly heritable, yet relatively few associated genetic loci have been replicated. Copy number variations (CNVs) have been implicated in autism; however, the majority of loci contribute to <1% of the disease population. Therefore, independent studies are important to refine associated CNV regions and discover novel susceptibility genes.

Common SNP-based haplotype analysis of the 4p16.3 Huntington disease gene region.

Age at the onset of motor symptoms in Huntington disease (HD) is determined largely by the length of a CAG repeat expansion in HTT but is also influenced by other genetic factors. We tested whether common genetic variation near the mutation site is associated with differences in the distribution of expanded CAG alleles or age at the onset of motor symptoms. To define disease-associated single-nucleotide polymorphisms (SNPs), we compared 4p16.

Serum carnitine levels and levocarnitine supplementation in institutionalized Huntington's disease patients.

Along with antioxidant properties, carnitine is an important regulator of lipid metabolism in humans. While beneficial effects of carnitine have been demonstrated in animal models of Huntington's disease (HD), metabolism of carnitine has not been studied in humans with this illness. In this retrospective database review from 23 patients admitted to a HD-specialized nursing home unit, we found a relatively high prevalence of hypocarnitinemia (6 cases, 26%).

Exploring the relationship between autism spectrum disorder and epilepsy using latent class cluster analysis.

Epilepsy co-occurs frequently in autism spectrum disorders (ASD). Understanding this co-occurrence requires a better understanding of the ASD-epilepsy phenotype (or phenotypes). To address this, we conducted latent class cluster analysis (LCCA) on an ASD dataset (N = 577) which included 64 individuals with epilepsy.

An X chromosome-wide association study in autism families identifies TBL1X as a novel autism spectrum disorder candidate gene in males.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic component. The skewed prevalence toward males and evidence suggestive of linkage to the X chromosome in some studies suggest the presence of X-linked susceptibility genes in people with ASD.

Methods: We analyzed genome-wide association study (GWAS) data on the X chromosome in three independent autism GWAS data sets: two family data sets and one case-control data set.

Copy number variants in extended autism spectrum disorder families reveal candidates potentially involved in autism risk.

Copy number variations (CNVs) are a major cause of genetic disruption in the human genome with far more nucleotides being altered by duplications and deletions than by single nucleotide polymorphisms (SNPs). In the multifaceted etiology of autism spectrum disorders (ASDs), CNVs appear to contribute significantly to our understanding of the pathogenesis of this complex disease. A unique resource of 42 extended ASD families was genotyped for over 1 million SNPs to detect CNVs that may contribute to ASD susceptibility.

Microduplications in an autism multiplex family narrow the region of susceptibility for developmental disorders on 15q24 and implicate 7p21.

Copy number variations (CNVs) play a crucial role in the intricate genetics of autism spectrum disorders. A region on chromosome 15q24 vulnerable to both deletions and duplications has been previously implicated in a range of phenotypes including autism, Asperger's syndrome, delayed development, and mild to severe mental retardation. Prior studies have delineated a minimal critical region of approximately 1.

A de novo 1.5 Mb microdeletion on chromosome 14q23.2-23.3 in a patient with autism and spherocytosis.

Autism is a neuro-developmental disorder characterized by deficits in social interaction and communication as well as restricted interests or repetitive behaviors. Cytogenetic studies have implicated large chromosomal aberrations in the etiology of approximately 5-7% of autism patients, and the recent advent of array-based techniques allows the exploration of submicroscopic copy number variations (CNVs). We genotyped a 14-year-old boy with autism, spherocytosis and other physical dysmorphia, his parents, and two non-autistic siblings with the Illumina Human 1M Beadchip as part of a study of the molecular genetics of autism and determined copy number variants using the PennCNV algorithm.

Carnitine and metabolic correlates in hospitalized psychiatric patients: a follow-through report.

Background: Carnitine deficiency may be encountered in the context of chronic psychiatric illness, particularly with the chronic use of valproic acid. Despite the importance of carnitine in lipid metabolism and mitochondrial function, its metabolic effects have not been studied in a psychiatric population.

Objective: To raise awareness regarding the possible metabolic implications of carnitine homeostasis in psychiatric patients.

Clinical correlates of low serum carnitine levels in hospitalized psychiatric patients.

Objective: We sought to evaluate clinical correlates of low serum carnitine levels in hospitalized psychiatric patients.

Methods: We retrospectively reviewed the charts of 40 psychiatric inpatients identified to have low serum carnitine levels.

Results: Cognitive impairment was present in 38 (95%) cases, frequently accompanied by imbalance, agitation and extrapyramidal symptoms.

Clinical outcomes and low-dose levocarnitine supplementation in psychiatric inpatients with documented hypocarnitinemia: a retrospective chart review.

Background: Metabolic encephalopathy is one of the crucial manifestations of carnitine deficiency. In psychiatric patients, low serum carnitine levels may result from chronic valproate therapy. Despite the widespread use of valproate in psychiatry, neither carnitine deficiency nor supplementation has been studied in a psychiatric population.

Novel variants identified in methyl-CpG-binding domain genes in autistic individuals.

Misregulation of the methyl-CpG-binding protein 2 (MECP2) gene has been found to cause a myriad of neurological disorders including autism, mental retardation, seizures, learning disabilities, and Rett syndrome. We hypothesized that mutations in other members of the methyl-CpG-binding domain (MBD) family may also cause autistic features in individuals. We evaluated 226 autistic individuals for alterations in the four genes most homologous to MECP2: MBD1, MBD2, MBD3, and MBD4.

Genomic and epigenetic evidence for oxytocin receptor deficiency in autism.

Background: Autism comprises a spectrum of behavioral and cognitive disturbances of childhood development and is known to be highly heritable. Although numerous approaches have been used to identify genes implicated in the development of autism, less than 10% of autism cases have been attributed to single gene disorders.

Methods: We describe the use of high-resolution genome-wide tilepath microarrays and comparative genomic hybridization to identify copy number variants within 119 probands from multiplex autism families.

Sleep patterns in patients with Huntington's disease and their unaffected first-degree relatives: a brief report.

Polysomnographic sleep patterns in Huntington's disease (HD) have been studied sporadically in small groups of patients, providing variable results. In this study, by comparing the polysomnographic sleep patterns of HD patients and their unaffected relatives, identifying sleep traits more specifically related to the HD gene was attempted. The results corroborated previously reported findings of prolonged sleep latency and the virtual absence of nocturnal respiratory disturbances in early HD.

Brief report: perception and lateralization of spoken emotion by youths with high-functioning forms of autism.

The perception and the cerebral lateralization of spoken emotions were investigated in children and adolescents with high-functioning forms of autism (HFFA), and age-matched typically developing controls (TDC). A dichotic listening task using nonsense passages was used to investigate the recognition of four emotions: happiness, sadness, anger, and neutrality. The participants with HFFA did not differ significantly in overall performance from the TDC, suggesting that the pervasive difficulty in processing emotions is not uniformly present in emotions expressed verbally.

A genome-wide association study of autism reveals a common novel risk locus at 5p14.1.

Although autism is one of the most heritable neuropsychiatric disorders, its underlying genetic architecture has largely eluded description. To comprehensively examine the hypothesis that common variation is important in autism, we performed a genome-wide association study (GWAS) using a discovery dataset of 438 autistic Caucasian families and the Illumina Human 1M beadchip. 96 single nucleotide polymorphisms (SNPs) demonstrated strong association with autism risk (p-value < 0.