1,594 research outputs found

    Decreased functional connectivity within a language subnetwork in benign epilepsy with centrotemporal spikes.

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    OBJECTIVE: Benign epilepsy with centrotemporal spikes (BECTS, also known as Rolandic epilepsy) is a common epilepsy syndrome that is associated with literacy and language impairments. The neural mechanisms of the syndrome are not known. The primary objective of this study was to test the hypothesis that functional connectivity within the language network is decreased in children with BECTS. We also tested the hypothesis that siblings of children with BECTS have similar abnormalities. METHODS: Echo planar magnetic resonance (MR) imaging data were acquired from 25 children with BECTS, 12 siblings, and 20 healthy controls, at rest. After preprocessing with particular attention to intrascan motion, the mean signal was extracted from each of 90 regions of interest. Sparse, undirected graphs were constructed from adjacency matrices consisting of Spearman's rank correlation coefficients. Global and nodal graph metrics and subnetwork and pairwise connectivity were compared between groups. RESULTS: There were no significant differences in graph metrics between groups. Children with BECTS had decreased functional connectivity relative to controls within a four-node subnetwork, which consisted of the left inferior frontal gyrus, the left superior frontal gyrus, the left supramarginal gyrus, and the right inferior parietal lobe (p = 0.04). A similar but nonsignificant decrease was also observed for the siblings. The BECTS groups had significant increases in connectivity within a five-node, five-edge frontal subnetwork. SIGNIFICANCE: The results provide further evidence of decreased functional connectivity between key mediators of speech processing, language, and reading in children with BECTS. We hypothesize that these decreases reflect delayed lateralization of the language network and contribute to specific cognitive impairments

    E-cadherin can limit the transforming properties of activating β-catenin mutations

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    Wnt pathway deregulation is a common characteristic of many cancers. But only Colorectal Cancer predominantly harbours mutations in APC, whereas other cancer types (hepatocellular carcinoma, solid pseudopapillary tumours of pancreas) have activating mutations in β-catenin (CTNNB1). We have compared the dynamics and the potency of β-catenin mutations in vivo. Within the murine small intestine (SI), an activating mutation of β-catenin took much longer to achieve a Wnt deregulation and acquire a crypt-progenitor-cell (CPC) phenotype than Apc or Gsk3 loss. Within the colon, a single activating mutation of β-catenin was unable to drive Wnt deregulation or induce the CPC phenotype. This ability of β-catenin mutation to differentially transform the SI versus the colon correlated with significantly higher expression of the β-catenin binding partner E-cadherin. This increased expression is associated with a higher number of E-cadherin:β-catenin complexes at the membrane. Reduction of E-cadherin synergised with an activating mutation of β-catenin so there was now a rapid CPC phenotype within the colon and SI. Thus there is a threshold of β-catenin that is required to drive transformation and E-cadherin can act as a buffer to prevent β-catenin accumulation

    The Union of Hearts Depicted: Gladstone, Home Rule and United Ireland

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    First paragraph: William Ewart Gladstone detested political cartoons. They embodied caricature, the exaggeration of a particular feature into a deformity to excite ridicule or hatred. Cartoons, Gladstone once pointed out, had not existed in ancient Greece. There the ideal of human beauty was so deeply cherished that its distortion was not tolerated. Yet cartoons did the statesman powerful service during his long career. Their very frequency consolidated his image as a popular politician, bringing out qualities such as courage and tenacity that he was happy to have publicised. Nowhere, however, did they advance his cause more than in Ireland after the introduction of Home Rule. The nationalist journal United Ireland, as the illustrations in this paper will show, gave currency to striking depictions of Gladstone; and they vividly portrayed the union of hearts between England and Ireland that he preached so persistently in the late 1880s. The purpose of this article is to examine a sample of the cartoons, but first they need to be placed in their context

    Individual variation in levels of haptoglobin-related protein in children from Gabon

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    Background: Haptoglobin related protein (Hpr) is a key component of trypanosome lytic factors (TLF), a subset of highdensity lipoproteins (HDL) that form the first line of human defence against African trypanosomes. Hpr, like haptoglobin (Hp) can bind to hemoglobin (Hb) and it is the Hpr-Hb complexes which bind to these parasites allowing uptake of TLF. This unique form of innate immunity is primate-specific. To date, there have been no population studies of plasma levels of Hpr, particularly in relation to hemolysis and a high prevalence of ahaptoglobinemia as found in malaria endemic areas. Methods and Principal Findings: We developed a specific enzyme-linked immunosorbent assay to measure levels of plasma Hpr in Gabonese children sampled during a period of seasonal malaria transmission when acute phase responses (APR), malaria infection and associated hemolysis were prevalent. Median Hpr concentration was 0.28 mg/ml (range 0.03-1.1). This was 5-fold higher than that found in Caucasian children (0.049 mg/ml, range 0.002-0.26) with no evidence of an APR. A general linear model was used to investigate associations between Hpr levels, host polymorphisms, parasitological factors and the acute phase proteins, Hp, C-reactive protein (CRP) and albumin. Levels of Hpr were associated with Hp genotype, decreased with age and were higher in females. Hpr concentration was strongly correlated with that of Hp, but not CRP

    Motor Competence between Children with and without Additional Learning Needs: A Cross-Sectional Population-Level Study

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    The aim of this study was to examine associations in motor competence between children with additional learning needs (ALN) and typically developing children. This cross-sectional study involved a nationally representative cohort of 4555 children (48.98% boys; 11.35 ± 0.65 years) from sixty-five schools across Wales (UK). Demographic data were collected from schools, and children were assessed using the Dragon Challenge assessment of motor competence, which consists of nine tasks completed in a timed circuit. A multi-nominal multi-level model with random intercept was fitted to explore the proficiency between children with ALN and those without. In all nine motor competence tasks, typically developing children demonstrated higher levels of proficiency than their peers with ALN, with these associations evident after accounting for age, sex, ethnicity, and socioeconomic status. This study highlights motor competence inequalities at a population level and emphasises the need for policymakers, practitioners, and researchers to prioritise motor competence development, particularly for children with ALN.</jats:p

    Decreased functional connectivity within a language subnetwork in benign epilepsy with centrotemporal spikes

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    Objective: Benign epilepsy with centrotemporal spikes (BECTS, also known as Rolandic epilepsy) is a common epilepsy syndrome that is associated with literacy and language impairments. The neural mechanisms of the syndrome are not known. The primary objective of this study was to test the hypothesis that functional connectivity within the language network is decreased in children with BECTS. We also tested the hypothesis that siblings of children with BECTS have similar abnormalities. Methods: Echo planar magnetic resonance (MR) imaging data were acquired from 25 children with BECTS, 12 siblings, and 20 healthy controls, at rest. After preprocessing with particular attention to intrascan motion, the mean signal was extracted from each of 90 regions of interest. Sparse, undirected graphs were constructed from adjacency matrices consisting of Spearman's rank correlation coefficients. Global and nodal graph metrics and subnetwork and pairwise connectivity were compared between groups. Results: There were no significant differences in graph metrics between groups. Children with BECTS had decreased functional connectivity relative to controls within a four‐node subnetwork, which consisted of the left inferior frontal gyrus, the left superior frontal gyrus, the left supramarginal gyrus, and the right inferior parietal lobe (p = 0.04). A similar but nonsignificant decrease was also observed for the siblings. The BECTS groups had significant increases in connectivity within a five‐node, five‐edge frontal subnetwork. Significance: The results provide further evidence of decreased functional connectivity between key mediators of speech processing, language, and reading in children with BECTS. We hypothesize that these decreases reflect delayed lateralization of the language network and contribute to specific cognitive impairments

    Prevalence of bullying and aggressive behavior and their relationship to mental health problems among 12- to 15-year-old Norwegian adolescents

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    The aim of this study was to examine the relationships between being bullied and aggressive behavior and self-reported mental health problems among young adolescents. A representative population sample of 2,464 young Norwegian adolescents (50.8% girls) aged 12–15 years was assessed. Being bullied was measured using three items concerning teasing, exclusion, and physical assault. Self-esteem was assessed by Harter’s self-perception profile for adolescents. Emotional and behavioral problems were measured by the Moods and Feelings Questionnaire (MFQ) and the youth self-report (YSR). Aggressive behavior was measured by four items from the YSR. One-tenth of the adolescents reported being bullied, and 5% reported having been aggressive toward others during the past 6 months. More of the students being bullied and students being aggressive toward others reported parental divorce, and they showed higher scores on all YSR subscales and on the MFQ questions, and lower scores on the global self-worth subscale (Harter) than students not being bullied or aggressive. A few differences emerged between the two groups being bullied or being aggressive toward others: those who were aggressive showed higher total YSR scores, higher aggression and delinquency scores, and lower social problems scores, and reported higher scores on the social acceptance subscale (Harter) than bullied students. However, because social problems were demonstrated in both the involved groups, interventions designed to improve social competence and interaction skills should be integrated in antibullying programs
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