Effect of Helicobacter pylori infection on deep vein thrombosis seen in patients with Behçet's disease

Objective: To investigate the role of homocysteine metabolism due to Helicobacter pylori infection on the development of deep vein thrombosis (DVT) in patients with Behcet's disease (BD). Design: Prospective clinical study. Setting: Teaching hospital. Subject: Fifty-five patients with BD divided into groups, with DVT and without DVT, 19 healthy individuals and 18 patients with coronary artery disease (CAD) were enrolled into the study. Interventions: Plasma homocysteine and Hp seropositivity were determined. Results: There was significant Hp positivity in all groups (p>0.05). Homocysteine levels were not significantly different for each group except patients with CAD (p>0.05). Conclusion: There was no difference for frequency of Hp infection in all groups. We conclude that Hp does not influence DVT seen in BD via homocysteine metabolism, but the methinnin-loading test would be appropriate for enlighting patients whose fasting plasma homocysteine levels are found to be normal. East African Medical Journal Vol. 83(1) 2006: 49-5

Distorted Cognitive Processing in Youth: The Structure of Negative Cognitive Errors and Their Associations with Anxiety

The Children’s Negative Cognitive Error Questionnaire (CNCEQ) is commonly used to measure four errors in young people’s thinking, but research has failed to support the factorial validity of the measure. The primary objective of the present study was to examine the factor structure of a refined and extended version of the CNCEQ. Revision of the CNCEQ involved the exclusion of items rated as contaminated, and the addition of items measuring cognitive errors closely associated with anxiety (‘threat conclusion’ and ‘underestimation of the ability to cope’). A secondary objective was to determine the relation between the negative cognitive errors and anxiety. Principal component analysis of data from 481 children and adolescents indicated five distinct negative cognitive error subscales labeled ‘underestimation of the ability to cope’, ‘personalizing without mind reading’, ‘selective abstraction’, ‘overgeneralizing’, and ‘mind reading’ which contained the new ‘threat conclusion’ items. Confirmatory factor analysis in an independent sample of 295 children and adolescents yielded further support for the five-factor solution. All cognitive errors except ‘selective abstraction’ were correlated with anxiety. Multiple regression analysis indicated that the strongest predictors of anxiety were the two subscales containing new items, namely ‘underestimation of the ability to cope’ and ‘mind reading’. The results are discussed with respect to further development of the instrument so as to advance the assessment of distorted cognitive processing in young people with internalizing symptoms

An ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy

The extracellular matrix comprises a network of macromolecules such as collagens, proteoglycans and glycoproteins. VWA1 (von Willebrand factor A domain containing 1) encodes a component of the extracellular matrix that interacts with perlecan/collagen VI, appears to be involved in stabilizing extracellular matrix structures, and demonstrates high expression levels in tibial nerve. Vwa1-deficient mice manifest with abnormal peripheral nerve structure/function; however, VWA1 variants have not previously been associated with human disease. By interrogating the genome sequences of 74 180 individuals from the 100K Genomes Project in combination with international gene-matching efforts and targeted sequencing, we identified 17 individuals from 15 families with an autosomal-recessive, non-length dependent, hereditary motor neuropathy and rare biallelic variants in VWA1. A single disease-associated allele p.(G25Rfs*74), a 10-bp repeat expansion, was observed in 14/15 families and was homozygous in 10/15. Given an allele frequency in European populations approaching 1/1000, the seven unrelated homozygote individuals ascertained from the 100K Genomes Project represents a substantial enrichment above expected. Haplotype analysis identified a shared 220 kb region suggesting that this founder mutation arose >7000 years ago. A wide age-range of patients (6–83 years) helped delineate the clinical phenotype over time. The commonest disease presentation in the cohort was an early-onset (mean 2.0 ± 1.4 years) non-length-dependent axonal hereditary motor neuropathy, confirmed on electrophysiology, which will have to be differentiated from other predominantly or pure motor neuropathies and neuronopathies. Because of slow disease progression, ambulation was largely preserved. Neurophysiology, muscle histopathology, and muscle MRI findings typically revealed clear neurogenic changes with single isolated cases displaying additional myopathic process. We speculate that a few findings of myopathic changes might be secondary to chronic denervation rather than indicating an additional myopathic disease process. Duplex reverse transcription polymerase chain reaction and immunoblotting using patient fibroblasts revealed that the founder allele results in partial nonsense mediated decay and an absence of detectable protein. CRISPR and morpholino vwa1 modelling in zebrafish demonstrated reductions in motor neuron axonal growth, synaptic formation in the skeletal muscles and locomotive behaviour. In summary, we estimate that biallelic variants in VWA1 may be responsible for up to 1% of unexplained hereditary motor neuropathy cases in Europeans. The detailed clinical characterization provided here will facilitate targeted testing on suitable patient cohorts. This novel disease gene may have previously evaded detection because of high GC content, consequential low coverage and computational difficulties associated with robustly detecting repeat-expansions. Reviewing previously unsolved exomes using lower QC filters may generate further diagnoses

An ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy.

The extracellular matrix comprises a network of macromolecules such as collagens, proteoglycans and glycoproteins. VWA1 (von Willebrand factor A domain containing 1) encodes a component of the extracellular matrix that interacts with perlecan/collagen VI, appears to be involved in stabilizing extracellular matrix structures, and demonstrates high expression levels in tibial nerve. Vwa1-deficient mice manifest with abnormal peripheral nerve structure/function; however, VWA1 variants have not previously been associated with human disease. By interrogating the genome sequences of 74 180 individuals from the 100K Genomes Project in combination with international gene-matching efforts and targeted sequencing, we identified 17 individuals from 15 families with an autosomal-recessive, non-length dependent, hereditary motor neuropathy and rare biallelic variants in VWA1. A single disease-associated allele p.(G25Rfs*74), a 10-bp repeat expansion, was observed in 14/15 families and was homozygous in 10/15. Given an allele frequency in European populations approaching 1/1000, the seven unrelated homozygote individuals ascertained from the 100K Genomes Project represents a substantial enrichment above expected. Haplotype analysis identified a shared 220 kb region suggesting that this founder mutation arose >7000 years ago. A wide age-range of patients (6-83 years) helped delineate the clinical phenotype over time. The commonest disease presentation in the cohort was an early-onset (mean 2.0 ± 1.4 years) non-length-dependent axonal hereditary motor neuropathy, confirmed on electrophysiology, which will have to be differentiated from other predominantly or pure motor neuropathies and neuronopathies. Because of slow disease progression, ambulation was largely preserved. Neurophysiology, muscle histopathology, and muscle MRI findings typically revealed clear neurogenic changes with single isolated cases displaying additional myopathic process. We speculate that a few findings of myopathic changes might be secondary to chronic denervation rather than indicating an additional myopathic disease process. Duplex reverse transcription polymerase chain reaction and immunoblotting using patient fibroblasts revealed that the founder allele results in partial nonsense mediated decay and an absence of detectable protein. CRISPR and morpholino vwa1 modelling in zebrafish demonstrated reductions in motor neuron axonal growth, synaptic formation in the skeletal muscles and locomotive behaviour. In summary, we estimate that biallelic variants in VWA1 may be responsible for up to 1% of unexplained hereditary motor neuropathy cases in Europeans. The detailed clinical characterization provided here will facilitate targeted testing on suitable patient cohorts. This novel disease gene may have previously evaded detection because of high GC content, consequential low coverage and computational difficulties associated with robustly detecting repeat-expansions. Reviewing previously unsolved exomes using lower QC filters may generate further diagnoses

Genetic Basis of Myocarditis: Myth or Reality?

n/

Comparison of the classification ratios of four depression rating scales commonly used in Turkey

Objective: According to literature more than 20 depression scales are in use in Turkey. Considering that depression is a popular area of study, it may not seem abnormally unusual that there are so many measuring scales available. However, so many measuring instruments may lead to a problem of different sensitivity levels and raise the question of whether or not all the instruments have the same sensitivity in measuring the particular entity. The purpose of this study is to compare the four commonly used self-report scales adapted into Turkish, namely CES-Depression Scale, Beck Depression Inventory, the Zung Self-Rating Depression Scale, and the Hospital Anxiety and Depression Scale (depression subscale) by cross-validation. Method: These depression scales had been applied to three hundred and forty-one subjects and total scores of the subjects for each scale have been obtained. Next, the sample group was divided into two according to group averages of total scale scores. Normative scores and cut-off scores have not been considered because the study objective was to compare these scales on a theoretical basis. The groups below and above average for each of the four scales have been compared by the ROC curve analyzes. Results: The results showed that the total score of Beck Depression Inventory had been grouped correctly by the Zung Self-Rating Depression Scale at a ratio of 0.871, the Hospital Anxiety and Depression Scale (depression subscale) at a ratio of 0.885, and by CES-Depression Scale at a ratio of 0.874. The total score of CES-Depression Scale had been correctly grouped by Beck Depression Inventory at a ratio of 0.871, the Zung Self-Rating Depression Scale at a ratio of 0.869, and by the Hospital Anxiety and Depression Scale (depression subscale) at a ratio of 0.862. The total score of the Zung Self-Rating Depression Scale has been correctly grouped by the Hospital Anxiety and Depression Scale depression subscale at a ratio of 0.848, Beck Depression Inventory at a ratio of 0.872, and by CES-Depression Scale at a ratio of 0.878. The total score of the Hospital Anxiety and Depression Scale (depression subscale) has been correctly grouped by the Zung Self-Rating Depression Scale at a ratio of 0.848, Beck Depression Inventory at a ratio of 0.889, and by CES-Depression Scale at a ratio of 0.887. Conclusion: The overall results showed that the scales cross-validated with ratios ranging from 0.85 to 0.89. The classifying ratios obtained by ROC analysis were similar across four depression scales