17 research outputs found

    Downbeat nystagmus: aetiology and comorbidity in 117 patients

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    Objectives: Downbeat nystagmus (DBN) is the most common form of acquired involuntary ocular oscillation overriding fixation. According to previous studies, the cause of DBN is unsolved in up to 44% of cases. We reviewed 117 patients to establish whether analysis of a large collective and improved diagnostic means would reduce the number of cases with ``idiopathic DBN'' and thus change the aetiological spectrum.Methods: The medical records of all patients diagnosed with DBN in our Neurological Dizziness Unit between 1992 and 2006 were reviewed. In the final analysis, only those with documented cranial MRI were included. Their workup comprised a detailed history, standardised neurological, neuro-otological and neuro-ophthalmological examination, and further laboratory tests.Results: In 62% (n = 72) of patients the aetiology was identified (``secondary DBN''), the most frequent causes being cerebellar degeneration (n = 23) and cerebellar ischaemia (n = 10). In 38% (n = 45), no cause was found (``idiopathic DBN''). A major finding was the high comorbidity of both idiopathic and secondary DBN with bilateral vestibulopathy (36%) and the association with polyneuropathy and cerebellar ataxia even without cerebellar pathology on MRI.Conclusions: Idiopathic DBN remains common despite improved diagnostic techniques. Our findings allow the classification of ``idiopathic DBN'' into three subgroups: ``pure'' DBN (n = 17); ``cerebellar'' DBN (ie, DBN plus further cerebellar signs in the absence of cerebellar pathology on MRI; n = 6); and a ``syndromatic'' form of DBN associated with at least two of the following: bilateral vestibulopathy, cerebellar signs and peripheral neuropathy (n = 16). The latter may be caused by multisystem neurodegeneration

    Cellular analysis of the action of epigenetics drugs and probes

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    Small molecule drugs and probes are important tools in drug discovery, pharmacology, and cell biology. This is of course also true for epigenetic inhibitors. Important examples for the use of established epigenetic inhibitors are the study of the mechanistic role of a certain target in a cellular setting or the modulation of a certain phenotype in an approach that aims towards therapeutic application. Alternatively, cellular testing may aim at the validation of a new epigenetic inhibitor in drug discovery approaches. Cellular and eventually animal models provide powerful tools for these different approaches but certain caveats have to be recognized and taken into account. This involves both the selectivity of the pharmacological tool as well as the specificity and the robustness of the cellular system. In this article, we present an overview of different methods that are used to profile and screen for epigenetic agents and comment on their limitations. We describe not only diverse successful case studies of screening approaches using different assay formats, but also some problematic cases, critically discussing selected applications of these systems

    Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline

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    Streptococcus agalactiae (Group B Streptococcus, GBS) is a commensal of the digestive and genitourinary tracts of humans that emerged as the leading cause of bacterial neonatal infections in Europe and North America during the 1960s. Due to the lack of epidemiological and genomic data, the reasons for this emergence are unknown. Here we show by comparative genome analysis and phylogenetic reconstruction of 229 isolates that the rise of human GBS infections corresponds to the selection and worldwide dissemination of only a few clones. The parallel expansion of the clones is preceded by the insertion of integrative and conjugative elements conferring tetracycline resistance (TcR). Thus, we propose that the use of tetracycline from 1948 onwards led in humans to the complete replacement of a diverse GBS population by only few TcR clones particularly well adapted to their host, causing the observed emergence of GBS diseases in neonates. \ua9 2014 Macmillan Publishers Limited. All rights reserved

    Facilitator guide for rapid food system appraisal in RAISE-FS : manual on rapid food system appraisal

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    The Rapid Food System Appraisal is a methodological approach developed within the context of the RAISE-FS programme. This document provides an overview of the Rapid Food System Appraisal and detailed methodological guidance for facilitators implementing this approach

    The Impact of Hispanic and White Group Cues on Attitudes Towards the Violation of Generic Norms

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    While much work in political science has examined the impact of racial cues on individual perceptions, we know little about how individuals evaluate members of minority outgroups on issues that are not linked to stereotypes. We measure the impacts of Hispanic and White cues on individual assessments related to a stereotype-independent norm violation: alcoholism. We test three competing theories – cognition, intergroup emotions, and social identity – using a population-based vignette experiment included in the General Social Survey. Our results contradict much of the literature, but keep with social identity theory's predictions. Hispanic alcoholics, when Hispanics constitute the outgroup, are assessed less negatively than White alcoholics in the ingroup, the latter experiencing what is called the black sheep effect. The black sheep effect occurs when ingroup members are more punitive towards members of the ingroup than the outgroup. However, the black sheep effect does not extend to measures that are more consistent with outgroup stereotypes, such as violence or money mismanagement; Hispanic alcoholics are evaluated more negatively than Whites on these measures. The implication is that the effect of racial cues depends strongly on issue linkages to group stereotypes
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