Inner retinal layer thinning in radiologically isolated syndrome predicts conversion to multiple sclerosis.

BACKGROUND AND PURPOSE: Individuals with radiologically isolated syndrome (RIS) are at increased risk of converting to multiple sclerosis (MS). Early identification of later converters is crucial for optimal treatment decisions. The purpose of this study was to assess the predictive potential of optical coherence tomography (OCT) measures in individuals with RIS regarding conversion to MS. METHODS: This prospective observational cohort study included 36 individuals with RIS and 36 healthy controls recruited from two German MS centers. All individuals received baseline OCT and clinical examination and were longitudinally followed over up to 6 years. The primary outcome measure was the conversion to MS. RESULTS: During clinical follow-up of 46 (26-58) months (median, 25%-75% interquartile range), eight individuals with RIS converted to MS. Individuals converting to MS showed a thinning of the peripapillary retinal nerve fiber layer (pRNFL) and the common ganglion cell and inner plexiform layer (GCIP) at baseline and during follow-up. Individuals with a pRNFL of 99 µm or lower or a GCIP of 1.99 mm3 or lower were at a 7.5- and 8.0-fold risk for MS conversion, respectively, compared to individuals with higher measures. After correction for other known risk factors, Cox proportional hazards regression revealed a hazard ratio of 1.08 for conversion to MS for each 1 µm decline in pRNFL. CONCLUSIONS: Reduction of the pRNFL might be a novel and independent risk factor for conversion to MS in individuals with RIS. OCT might be useful for risk stratification and therapeutic decision-making in individuals with RIS.

RNA editing adds flavor to complexity.

A-to-I RNA editing results in the conversion of single adenosines into inosines, which alters coding and non-coding sequences in RNA molecules, increasing the complexity of the transcriptome. This modification is vital in a number of brain-specific coding transcripts, where the introduced alternative amino acids impact protein function substantially. Indeed, deviations from normal editing levels have been detected in tissues from individuals affected by neurological diseases and cancer, underscoring the importance of correct and regulated editing. Since the discovery of A-to-I RNA editing, considerable effort has been made to uncover additional editing targets and analyze the subsequent functional consequences for the recoded substrates. The effects of editing on non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) or long ncRNAs are less well explored. ncRNAs act as regulators of gene expression through chromatin modification, imprinting, alternative splicing, and mRNA translation and stability. Editing has the potential to dynamically alter and diversify ncRNAs, thereby redirecting their functions. How editing intersects, interferes with, and modulates the roles of ncRNAs, possibly in response to external stimuli, therefore warrants a deeper look. This review discusses recent advances and new insights in the field.

Genome-wide evaluation and discovery of vertebrate A-to-I RNA editing sites.

RNA editing by adenosine deamination, catalyzed by adenosine deaminases acting on RNA (ADAR), is a post-transcriptional modification that contributes to transcriptome and proteome diversity and is widespread in mammals. Here we administer a bioinformatics search strategy to the human and mouse genomes to explore the landscape of A-to-I RNA editing. In both organisms we find evidence for high excess of A/G-type discrepancies (inosine appears as a guanosine in cloned cDNA) at non-polymorphic, non-synonymous codon sites over other types of discrepancies, suggesting the existence of several thousand recoding editing sites in the human and mouse genomes. We experimentally validate recoding-type A-to-I RNA editing in a number of human genes with high scoring positions including the coatomer protein complex subunit alpha (COPA) as well as cyclin dependent kinase CDK13.

A semiquantitative food frequency questionnaire for use in epidemiologic research among the elderly: validation by comparison with dietary history.

A self-administered semiquantitative food frequency questionnaire including 75 food items and providing information on the habitual intake of 31 nutritional parameters, based on the intake of protein, fat, carbohydrate, fiber and 11 vitamins and minerals, was developed for use in epidemiologic research on chronic disease among the elderly, such as diabetes and cardiovascular disease. By means of detailed frequency and quantity questions, specifications of types of food, preparation methods and seasonal variation, the questionnaire was expected to be an improvement on existing instruments. The relative validity of the questionnaire was examined in 74 men and women, aged 50-75, by comparison with a modified dietary history. Systematic differences were absent or negligible for all nutrients, except vitamin C. Bias depending on the level of intake could be ruled out for all but seven nutrients. Pearson correlation coefficients for estimates from the questionnaire and dietary history were on average 0.71 (range: 0.65-0.78) and 0.66 (range: 0.36-0.81) for macronutrients, and vitamins and minerals, respectively. Classifying individual intake estimates into tertiles of the distribution for both methods, on average 62.4 and 54.7% of the intakes were categorized into the same tertile and 3.9 and 5.9% into the opposite tertile for macronutrients, vitamins and minerals, respectively. These results demonstrate an acceptable relative validity for this newly developed questionnaire, as compared to the dietary history method.