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    ABSTRACT: ABSTRACT Background: No validated patient-reported outcome measure (PROM) exists specifically to assess quality of life in mild cognitive impairment (MCI); we report a study conducted to develop such a measure. Methods: Semi-structured in-depth interviews were carried out with 23 people with MCI in order to determine items for a draft questionnaire. These interviews were audio-recorded, transcribed, and content analyzed. The draft questionnaire was refined following feedback from a focus group. 280 questionnaires were posted to subjects recruited from memory clinics and research databases, the response rate was 56% i.e. 146 questionnaires were included in the final analysis. The completed questionnaires were analyzed using factor analytic techniques to produce the final measure; construct validity was assessed by correlation with a generic patient-reported outcome measure, the SF-12v2. Results: Factor analysis produced a 13-item measure tapping two domains of patient-reported quality of life ("Emotional Effects" and "Practical Concerns"). Internal consistency reliability was high for both domains (α was 0.91 and 0.85 respectively). Both dimensions were highly and significantly correlated with the Mental Component Summary score of the SF-12v2 ("emotional effects" ρ = -0.43, p < 0.001 and "practical concerns" ρ = -0.56, p < 0.001). Conclusions: The Mild Cognitive Impairment Questionnaire (MCQ) is a 13-item measure developed specifically to measure patient-reported outcomes in people with MCI. It was created on the basis of patient report and has been shown to have good psychometric properties. It is likely to prove valuable in the evaluation of treatment regimes in this patient group.
    International Psychogeriatrics 12/2013;
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    ABSTRACT: Full-length KIR3DL1*01501 differing from KIR3DL1*0150201 with 10 SNPs and 2 nucleotide deletion in intron 7.
    Tissue Antigens 11/2013;
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    ABSTRACT: KIR3DL1*0150203 allele differs from KIR3DL1*0150201 at 3037G>A, 4115A>G, 6053G>C, 8034A>G, 10723C>A, and 10747C>G.
    Tissue Antigens 11/2013;
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    ABSTRACT: ABSTRACT Background: The aim of this study was to investigate the experiences of people with mild cognitive impairment (MCI; PWMCI) and their "advocates," particularly within healthcare services. Methods: Semi-structured interviews were conducted with 23 PWMCI diagnosed ≤6 months ago and 20 advocates recruited via patients. The resulting data were content-analyzed. Results: PWMCI interviewed rarely reported negative impressions of their general practitioner (GP). Reports regarding memory services were more mixed: positive impressions related to finding the service to be "well run" and the staff "pleasant," negative ones to the assessment process or a perceived lack of feedback. Aside from improved information provision, most PWMCI had no suggestions for improvements to their healthcare. However, these results should be interpreted with caution as many of the PWMCI interviewed displayed evidence of impaired recall and/or insight relating to their condition and healthcare. Advocates generally reported more negative impressions of both contact with the PWMCI's GP (most commonly reporting a "dismissive" attitude) and memory services (with common complaints relating to the assessments used in clinics and lengthy waiting times). This group generally had suggestions for improvements to services - particularly regarding information provision, changes in the assessment process, and improvements in communication by services. Conclusions: To our knowledge, this is the first in-depth study of the difficulties experienced by PWMCI and their advocates which includes the context of healthcare provision. The specific needs of these groups, as described here, as well as those of people with dementia, should be considered when designing memory clinics and other related services.
    International Psychogeriatrics 11/2013;
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    ABSTRACT: The novel KIR3DL1*0150204 has four point mutations: 3037G>A, 4115A>G, 6053G>C, and 8034A>G compared to KIR3DL1*0150201.
    Tissue Antigens 11/2013;
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    ABSTRACT: KIR3DL1*0150205 and KIR3DL1*0150206 alleles have five and six mutations, respectively, compared with KIR3DL1*0150201.
    Tissue Antigens 11/2013;
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    ABSTRACT: Posttranslational modification with ubiquitin (Ub) controls many cellular processes, and aberrant ubiquitination can contribute to cancer, immunopathology, and neurodegeneration. The versatility arises from the ability of Ub to form polymer chains with eight distinct linkages via lysine side chains and the N terminus. In this study, we engineered Di-Ub probes mimicking all eight different poly-Ub linkages and profiled the deubiquitinating enzyme (DUB) selectivity for recognizing Di-Ub moieties in cellular extracts. Mass spectrometric profiling revealed that most DUBs examined have broad selectivity, whereas a subset displays a clear preference for recognizing noncanonical over K48/K63 Ub linkages. Our results expand knowledge of Ub processing enzyme functions in cellular contexts that currently depends largely on using recombinant enzymes and substrates.
    Chemistry & biology 11/2013;
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    ABSTRACT: The lung is the portal of entry for Mycobacterium tuberculosis (Mtb) and animal experimental evidence indicates that local immune defense mechanisms are crucial for protective immunity. Immunization via the lower respiratory tract efficiently induces a dividing, activated, antigen-dependent, lung-resident, memory T-cell population, which is partly recoverable by bronchoalveolar lavage. These cells can inhibit the growth of Mtb in the lungs immediately after infection. Delivery of appropriate signals to the lung innate immune system is critical for induction of effective local immunity. In contrast after parenteral immunization, antigen-specific cells may be found in lung tissue but few are recoverable by lavage and inhibition of mycobacterial growth is delayed. Harnessing both local and systemic immunity can provide highly effective protection in animal models and the evidence suggests that taken in aggregate, multiple animal models may predict the success of novel vaccine strategies in humans.Mucosal Immunology advance online publication, 20 November 2013; doi:10.1038/mi.2013.99.
    Mucosal Immunology 11/2013;
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    ABSTRACT: KIR3DS1*0130104 is identical to KIR3DS1*0130101 except for changes at positions 1768 (C>T) and 12617 (C>A).
    Tissue Antigens 11/2013;
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    ABSTRACT: Proteomic research facilities and laboratories are facing increasing demands for the integration of biological data from multiple "-OMICS" approaches. The aim to fully understand biological processes requires the integrated study of genomes, proteomes and metabolomes. While genomics and proteomic workflows are different, the study of the metabolome overlaps significantly with the latter, both in instrumentation and methodology. However, chemical diversity complicates an easy and direct access to the metabolome by mass spectrometry. The present review provides an introduction into metabolomics workflows from the viewpoint of proteomic researchers. We compare the physicochemical properties of proteins and peptides with metabolites/small molecules to establish principle differences between these analyte classes based on human data. We highlight the implications this may have on sample preparation, separation, ionisation, detection and data analysis. We argue that a typical proteomic workflow (nLC-MS) can be exploited for the detection of a number of aliphatic and aromatic metabolites, including fatty acids, lipids, prostaglandins, di-/tri-peptides, steroids and vitamins, thereby providing a straight-forward entry point for metabolomics-based studies. Limitations and requirements are discussed as well as extensions to the standard workflow to expand the range of detectable molecular classes without investing into dedicated instrumentation such as GC-MS, CE-MS or NMR. This article is protected by copyright. All rights reserved.
    Proteomics 10/2013;
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