Abolishing spontaneous epileptiform activity in human brain tissue through AMPA receptor inhibition

Objective: The amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is increasingly recognized as a therapeutic target in drug-refractory pediatric epilepsy. Perampanel (PER) is a non-competitive AMPAR antagonist, and pre-clinical studies have shown the AMPAR-mediated anticonvulsant effects of decanoic acid (DEC), a major medium-chain fatty acid provided in the medium-chain triglyceride ketogenic diet. Methods: Using brain tissue resected from children with intractable epilepsy, we recorded the effects of PER and DEC in vitro. Results: We found resected pediatric epilepsy tissue exhibits spontaneous epileptic activity in vitro, and showed that DEC and PER inhibit this epileptiform activity in local field potential recordings as well as excitatory synaptic transmission. Interpretation: This study confirms AMPAR antagonists inhibit epileptiform discharges in brain tissue resected in a wide range of pediatric epilepsies

Predicting first-episode psychosis patients who will never relapse over 10 years.

BACKGROUND: Although relapse in psychosis is common, a small proportion of patients will not relapse in the long term. We examined the proportion and predictors of patients who never relapsed in the 10 years following complete resolution of positive symptoms from their first psychotic episode. METHOD: Patients who previously enrolled in a 12-month randomized controlled trial on medication discontinuation and relapse following first-episode psychosis (FEP) were followed up after 10 years. Relapse of positive symptoms was operationalized as a change from a Clinical Global Impression scale positive score of <3 for at least 3 consecutive months to a score of ⩾3 (mild or more severe). Baseline predictors included basic demographics, premorbid functioning, symptoms, functioning, and neurocognitive functioning. RESULTS: Out of 178 first-episode patients, 37 (21%) never relapsed during the 10-year period. Univariate predictors (p ⩽ 0.1) of patients who never relapsed included a duration of untreated psychosis (DUP) ⩽30 days, diagnosed with non-schizophrenia spectrum disorders, having less severe negative symptoms, and performing better in logical memory immediate recall and verbal fluency tests. A multivariate logistic regression analysis further suggested that the absence of any relapsing episodes was significantly related to better short-term verbal memory, shorter DUP, and non-schizophrenia spectrum disorders. CONCLUSIONS: Treatment delay and neurocognitive function are potentially modifiable predictors of good long-term prognosis in FEP. These predictors are informative as they can be incorporated into an optimum risk prediction model in the future, which would help with clinical decision making regarding maintenance treatment in FEP

Investigating the Near-Infrared Properties of Planetary Nebula II. Medium Resolution Spectra

We present medium-resolution (R~700) near-infrared (lambda = 1 - 2.5 micron) spectra of a sample of planetary nebulae (PNe). A narrow slit was used which sampled discrete locations within the nebulae; observations were obtained at one or more positions in the 41 objects included in the survey. The PN spectra fall into one of four general categories: H I emission line-dominated PNe, H I and H_2 emission line PNe, H_2-dominated PNe, and continuum-dominated PNe. These categories correlate with morphological type, with the elliptical PNe falling into the first group, and the bipolar PNe primarily in the H_2 and continuum emission groups. Other spectral features were observed in all categories, such as continuum emission from the central star, C_2, CN, and CO emission, and warm dust continuum emission. Molecular hydrogen was detected for the first time in four PNe. An excitation analysis was performed using the H_2 line ratios for all of the PN spectra in the survey where a sufficient number of lines were observed. One unexpected result from this analysis is that the H_2 is excited by absorption of ultraviolet photons in most of the PNe surveyed, although for several PNe in our survey collisional excitation in moderate velocity shocks plays an important role. The correlation between bipolar morphology and H_2 emission has been strengthened with the new detections of H_2 in this survey.Comment: 13 pages, 8 tables, 33 figure

Characterization of Nipah Virus from Outbreaks in Bangladesh, 2008–2010

New genotyping scheme facilitates classification of virus sequences

Genomic Organization and Evolution of the Vomeronasal Type 2 Receptor-Like (OlfC) Gene Clusters in Atlantic Salmon, Salmo salar

There are three major multigene superfamilies of olfactory receptors (OR, V1R, and V2R) in mammals. The ORs are expressed in the main olfactory organ, whereas the V1Rs and V2Rs are located in the vomeronasal organ. Fish only possess one olfactory organ in each nasal cavity, the olfactory rosette; therefore, it has been proposed that their V2R-like genes be classified as olfactory C family G protein-coupled receptors (OlfC). There are large variations in the sizes of OR gene repertoires. Previous studies have shown that fish have between 12 and 46 functional V2R-like genes, whereas humans have lost all functional V2Rs, and frog sp. have more than 240. Pseudogenization of V2R genes is a prevalent event across species. In the mouse and frog genomes, there are approximately double the number of pseudogenes compared with functional genes. An oligonucleotide probe was designed from a conserved sequence from four Atlantic salmon OlfC genes and used to screen the Atlantic salmon bacterial artificial chromosome (BAC) library. Hybridization-positive BACs were matched to fingerprint contigs, and representative BACs were shotgun cloned and sequenced. We identified 55 OlfC genes. Twenty-nine of the OlfC genes are classified as putatively functional genes and 26 as pseudogenes. The OlfC genes are found in two genomic clusters on chromosomes 9 and 20. Phylogenetic analysis revealed that the OlfC genes could be divided into 10 subfamilies, with nine of these subfamilies corresponding to subfamilies found in other teleosts and one being salmon specific. There is also a large expansion in the number of OlfC genes in one subfamily in Atlantic salmon. Subfamily gene expansions have been identified in other teleosts, and these differences in gene number reflect species-specific evolutionary requirements for olfaction. Total RNA was isolated from the olfactory epithelium and other tissues from a presmolt to examine the expression of the odorant genes. Several of the putative OlfC genes that we identified are expressed only in the olfactory epithelium, consistent with these genes encoding odorant receptors

Increasing leaf vein density by mutagenesis: laying the foundations for C4 rice

A high leaf vein density is both an essential feature of C4 photosynthesis and a foundation trait to C4 evolution, ensuring the optimal proportion and proximity of mesophyll and bundle sheath cells for permitting the rapid exchange of photosynthates. Two rice mutant populations, a deletion mutant library with a cv. IR64 background (12,470 lines) and a T-DNA insertion mutant library with a cv. Tainung 67 background (10,830 lines), were screened for increases in vein density. A high throughput method with handheld microscopes was developed and its accuracy was supported by more rigorous microscopy analysis. Eight lines with significantly increased leaf vein densities were identified to be used as genetic stock for the global C4 Rice Consortium. The candidate population was shown to include both shared and independent mutations and so more than one gene controlled the high vein density phenotype. The high vein density trait was found to be linked to a narrow leaf width trait but the linkage was incomplete. The more genetically robust narrow leaf width trait was proposed to be used as a reliable phenotypic marker for finding high vein density variants in rice in future screens

Noninvasive Prenatal Diagnosis of Fetal Trisomy 18 and Trisomy 13 by Maternal Plasma DNA Sequencing

Massively parallel sequencing of DNA molecules in the plasma of pregnant women has been shown to allow accurate and noninvasive prenatal detection of fetal trisomy 21. However, whether the sequencing approach is as accurate for the noninvasive prenatal diagnosis of trisomy 13 and 18 is unclear due to the lack of data from a large sample set. We studied 392 pregnancies, among which 25 involved a trisomy 13 fetus and 37 involved a trisomy 18 fetus, by massively parallel sequencing. By using our previously reported standard z-score approach, we demonstrated that this approach could identify 36.0% and 73.0% of trisomy 13 and 18 at specificities of 92.4% and 97.2%, respectively. We aimed to improve the detection of trisomy 13 and 18 by using a non-repeat-masked reference human genome instead of a repeat-masked one to increase the number of aligned sequence reads for each sample. We then applied a bioinformatics approach to correct GC content bias in the sequencing data. With these measures, we detected all (25 out of 25) trisomy 13 fetuses at a specificity of 98.9% (261 out of 264 non-trisomy 13 cases), and 91.9% (34 out of 37) of the trisomy 18 fetuses at 98.0% specificity (247 out of 252 non-trisomy 18 cases). These data indicate that with appropriate bioinformatics analysis, noninvasive prenatal diagnosis of trisomy 13 and trisomy 18 by maternal plasma DNA sequencing is achievable

Comparison of primary care experiences among adults in general outpatient clinics and private general practice clinics in Hong Kong

Abstract. Background. The main goal of Hong Kong's publicly-funded general outpatient clinics (GOPCs) is to provide primary medical services for the financially vulnerable. The objective of the current study was to compare the primary care experiences of GOPC users and the users of care provided by private general practitioners (GPs) in Hong Kong via a territory-wide telephone survey. Methods. One thousand adults in Hong Kong aged 18 and above were interviewed by a telephone survey. The modified Chinese translated Primary Care Assessment Tool was used to collect data on respondents' primary care experience. Results. Our results indicated that services provided by GOPC were more often used by female, older, poorer, chronically-ill and less educated population. GOPC participants were also more likely to have visited a specialist or used specialist services (69.7% vs. 52.0%; p < 0.001), although this difference in utilization of specialist services disappeared after adjusting for age (55.7% vs. 52.0%, p = 0.198). Analyses were also performed to asses the relationship between healthcare settings (GOPCs versus private GPs) and primary care quality. Private GP patients achieved higher overall PCAT scores largely due to better accessibility (Mean: 6.88 vs. 8.41, p < 0.001) and person-focused care (Mean: 8.37 vs. 11.69, p < 0.001). Conclusions. Our results showed that patients primarily receiving care from private GPs in Hong Kong reported better primary care experiences than those primarily receiving care from GOPCs. This was largely due to the greater accessibility and better interpersonal relationships offered by the private GPs. As most patients use both GOPCs and private GPs, their overall primary care experiences may not be as different as the findings of this study imply. © 2010 Wong et al; licensee BioMed Central Ltd.link_to_subscribed_fulltex