99 research outputs found

    A crucial role for the cortico-striato-cortical loop in the pathogenesis of stroke-related neurogenic stuttering

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    Neurogenic stuttering is an acquired speech disorder characterized by the occurrence of stuttering-like dysfluencies following brain damage. Because the onset of stuttering in these patients is associated with brain lesions, this condition provides a unique opportunity to study the neural processes underlying speech dysfluencies. Lesion localizations of 20 stroke subjects with neurogenic stuttering and 17 control subjects were compared using voxel-based lesion symptom mapping. The results showed nine left-hemisphere areas associated with the presen ce of neurogenic stuttering. These areas were largely overlapping with the cortico-basal ganglia-cortical network comprising the inferior frontal cortex, superior temporal cortex, intraparietal cortex, basal ganglia, and their white matter interconnections through the superior longitudinal fasciculus and internal capsule. These results indicated that stroke-induced neurogenic stuttering is not associated with neural dysfunction in one specific brain area but can occur following one or more lesion throughout the cortico-basal ganglia-cortical network. It is suggested that the onset of neurogenic stuttering in stroke subjects results from a disintegration of neural functions necessary for fluent speech. © 2012 Wiley Periodicals, Inc

    Genomic aberrations relate early and advanced stage ovarian cancer

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    Background Because of the distinct clinical presentation of early and advanced stage ovarian cancer, we aim to clarify whether these disease entities are solely separated by time of diagnosis or whether they arise from distinct molecular events. Methods Sixteen early and sixteen advanced stage ovarian carcinomas, matched for histological subtype and differentiation grade, were included. Genomic aberrations were compared for each early and advanced stage ovarian cancer by array comparative genomic hybridization. To study how the aberrations correlate to the clinical characteristics of the tumors we clustered tumors based on the genomic aberrations. Results The genomic aberration patterns in advanced stage cancer equalled those in early stage, but were more frequent in advanced stage (p=0.012). Unsupervised clustering based on genomic aberrations yielded two clusters that significantly discriminated early from advanced stage (p= 0.001), and that did differ significantly in survival (p= 0.002). These clusters however did give a more accurate prognosis than histological subtype or differentiation grade. Conclusion This study indicates that advanced stage ovarian cancer either progresses from early stage or from a common precursor lesion but that they do not arise from distinct carcinogenic molecular events. Furthermore, we show that array comparative genomic hybridization has the potential to identify clinically distinct patients

    Overcoming language barriers with foreign-language speaking patients: a survey to investigate intra-hospital variation in attitudes and practices

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    Background Use of available interpreter services by hospital clincial staff is often suboptimal, despite evidence that trained interpreters contribute to quality of care and patient safety. Examination of intra-hospital variations in attitudes and practices regarding interpreter use can contribute to identifying factors that facilitate good practice. The purpose of this study was to describe attitudes, practices and preferences regarding communication with limited French proficiency (LFP) patients, examine how these vary across professions and departments within the hospital, and identify factors associated with good practices. Methods A self-administered questionnaire was mailed to random samples of 700 doctors, 700 nurses and 93 social workers at the Geneva University Hospitals, Switzerland. Results Seventy percent of respondents encounter LFP patients at least once a month, but this varied by department. 66% of respondents said they preferred working with ad hoc interpreters (patient's family and bilingual staff), mainly because these were easier to access. During the 6 months preceding the study, ad hoc interpreters were used at least once by 71% of respondents, and professional interpreters were used at least once by 51%. Overall, only nine percent of respondents had received any training in how and why to work with a trained interpreter. Only 23.2% of respondents said the clinical service in which they currently worked encouraged them to use professional interpreters. Respondents working in services where use of professional interpreters was encouraged were more likely to be of the opinion that the hospital should systematically provide a professional interpreter to LFP patients (40.3%) as compared with those working in a department that discouraged use of professional interpreters (15.5%) and they used professional interpreters more often during the previous 6 months. Conclusion Attitudes and practices regarding communication with LFP patients vary across professions and hospital departments. In order to foster an institution-wide culture conducive to ensuring adequate communication with LFP patients will require both the development of a hospital-wide policy and service-level activities aimed at reinforcing this policy and putting it into practice

    Ion conducting and paramagnetic d-PCL(530)/siloxane-based biohybrids doped with Mn 2+ ions

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    Amorphous α,ω-hidroxylpoly(ε-caprolactone) (PCL(530))/siloxane ormolytes doped with manganese perchlorate (Mn(ClO4)2) (d-PCL(530)/siloxanenMn(ClO4)2) with n = 20, 50, and 100), thermally stable up to at least 200 ºC, were synthesized by the sol-gel method. Ionic conductivity values up to 4.8×10−8 and 2.0×10−6 S cm−1 at about 25 and 100 ºC, respectively, where obtained for n = 20. FT-IR data demonstrated that the hydrogen bonding interactions present in the non-doped d-PCL(530)/siloxane host hybrid matrix were significantly influenced by the inclusion of Mn(ClO4)2 which promoted the formation of more oxyethylene/urethane and urethane/urethane aggregates. In addition, the Mn2+ ions bonded to all the “free” C=O groups of the urethane cross-links and to some of the “free” ester groups of the amorphous PCL(530) chains. In the electrolytes, the ClO4 − ions were found “free” and bonded to the Mn2+ ions along a bidentate configuration. The magnitude of the electron paramagnetic resonance (EPR) hyperfine constant of the analyzed samples (A ≈ 90×10-4 cm−1 ) suggested that the bonding between Mn2+ ions and the surrounding ligands is moderately ionic. The synthetized d-PCL(530)/siloxanenMn(ClO4)2 biohybrids have potential application in paramagnetic, photoelectrochemical and electrochromic devices.This work was supported by Fundacao para a Ciencia e a Tecnologia (FCT) and Feder (contracts PTDC/CTM-BPC/112774/2009, PEst-OE/QUI/UI0616/2014 and PEst-C/QUI/UI0686/2013) and COST Action MP1202 "Rational design of hybrid organic-inorganic interfaces". R.F.P.P. acknowledges FCT for a grant (SFRH/BPD/87759/2012). M.M.S. acknowledges CNPq (PVE grant 406617/2013-9), for a mobility grant. The financial support of the Brazilian agencies Capes and CNPq are gratefully acknowledged. Research was partially financed by the CeRTEV, Center for Research, Technology and Education in Vitreous Materials, FAPESP 2013/07793-6.info:eu-repo/semantics/publishedVersio

    Integrated analysis of DNA copy number and gene expression microarray data using gene sets

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    Background: Genes that play an important role in tumorigenesis are expected to show association between DNA copy number and RNA expression. Optimal power to find such associations can only be achieved if analysing copy number and gene expression jointly. Furthermore, some copy number changes extend over larger chromosomal regions affecting the expression levels of multiple resident genes.

    Breast tumors from CHEK2 1100delC-mutation carriers: genomic landscape and clinical implications

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    Introduction: Checkpoint kinase 2 (CHEK2) is a moderate penetrance breast cancer risk gene, whose truncating mutation 1100delC increases the risk about twofold. We investigated gene copy-number aberrations and gene-expression profiles that are typical for breast tumors of CHEK2 1100delC-mutation carriers. Methods: In total, 126 breast tumor tissue specimens including 32 samples from patients carrying CHEK2 1100delC were studied in array-comparative genomic hybridization (aCGH) and gene-expression (GEX) experiments. After dimensionality reduction with CGHregions R package, CHEK2 1100delC-associated regions in the aCGH data were detected by the Wilcoxon rank-sum test. The linear model was fitted to GEX data with R package limma. Genes whose expression levels were associated with CHEK2 1100delC mutation were detected by the bayesian method. Results: We discovered four lost and three gained CHEK2 1100delC-related loci. These include losses of 1p13.3-31.3, 8p21.1-2, 8p23.1-2, and 17p12-13.1 as well as gains of 12q13.11-3, 16p13.3, and 19p13.3. Twenty-eight genes located on these regions showed differential expression between CHEK2 1100delC and other tumors, nominating them as candidates for CHEK2 1100delC-associated tumor-progression drivers. These included CLCA1 on 1p22 as well as CALCOCO1, SBEM, and LRP1 on 12q13. Altogether, 188 genes were differentially expressed between CHEK2 1100delC and other tumors. Of these, 144 had elevated and 44, reduced expression levels. Our results suggest the WNT pathway as a driver of tumorigenesis in breast tumors of CHEK2 1100delC-mutation carriers and a role for the olfactory receptor protein family in cancer progression. Differences in the expression of the 188 CHEK2 1100delC-associated genes divided breast tumor samples from three independent datasets into two groups that differed in their relapse-free survival time. Conclusions: We have shown that copy-number aberrations of certain genomic regions are associated with CHEK2 mutation 1100delC. On these regions, we identified potential drivers of CHEK2 1100delC-associated tumorigenesis, whose role in cancer progression is worth investigating. Furthermore, poorer survival related to the CHEK2 1100delC gene-expression signature highlights pathways that are likely to have a role in the development of metastatic disease in carriers of the CHEK2 1100delC mutation

    Integrating genetics and epigenetics in breast cancer: biological insights, experimental, computational methods and therapeutic potential

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