55 research outputs found

    Anamneses-Based Internet Information Supply: Can a Combination of an Expert System and Meta-Search Engine Help Consumers find the Health Information they Require?

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    An increasing number of people search for health information online. During the last 10 years various researchers have determined the requirements for an ideal consumer health information system. The aim of this study was to figure out, whether medical laymen can find a more accurate diagnosis for a given anamnesis via the developed prototype health information system than via ordinary internet search

    Exposure to ambient particulate matter is associated with accelerated functional decline in idiopathic pulmonary fibrosis

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    BACKGROUND: Idiopathic pulmonary fibrosis (IPF), a progressive disease with an unknown pathogenesis, may be due in part to an abnormal response to injurious stimuli by alveolar epithelial cells. Air pollution and particulate inhalation of matter evoke a wide variety of pulmonary and systemic inflammatory diseases. We therefore hypothesized that increased average ambient particulate matter (PM) concentrations would be associated with an accelerated rate of decline in FVC in IPF. METHODS: We identified a cohort of subjects seen at a single university referral center from 2007 to 2013. Average concentrations of particulate matter < 10 and < 2.5 μg/m3 (PM10 and PM2.5, respectively) were assigned to each patient based on geocoded residential addresses. A linear multivariable mixed-effects model determined the association between the rate of decline in FVC and average PM concentration, controlling for baseline FVC at first measurement and other covariates. RESULTS: One hundred thirty-five subjects were included in the final analysis after exclusion of subjects missing repeated spirometry measurements and those for whom exposure data were not available. There was a significant association between PM10 levels and the rate of decline in FVC during the study period, with each μg/m3 increase in PM10 corresponding with an additional 46 cc/y decline in FVC (P = .008). CONCLUSIONS: Ambient air pollution, as measured by average PM10 concentration, is associated with an increase in the rate of decline of FVC in IPF, suggesting a potential mechanistic role for air pollution in the progression of disease

    Clostridium difficile 027/BI/NAP1 encodes a hypertoxic and antigenically variable form of TcdB.

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    The Clostridium difficile exotoxin, TcdB, which is a major virulence factor, varies between strains of this pathogen. Herein, we show that TcdB from the epidemic BI/NAP1/027 strain of C. difficile is more lethal, causes more extensive brain hemorrhage, and is antigenically variable from TcdB produced by previously studied strains of this pathogen (TcdB003). In mouse intoxication assays, TcdB from a ribotype 027 strain (TcdB027) was at least four fold more lethal than TcdB003. TcdB027 caused a previously undescribed brain hemorrhage in mice and this correlated with a heightened sensitivity of brain microvascular endothelial cells to the toxin. TcdB003 and TcdB027 also differed in their antigenic profiles and did not share cross-neutralizing epitopes in a major immunogenic region of the protein. Solid phase humoral mapping of epitopes in the carboxy-terminal domains (CTD) of TcdB027 and TcdB003 identified 11 reactive epitopes that varied between the two forms of TcdB, and 13 epitopes that were shared or overlapping. Despite the epitope differences and absence of neutralizing epitopes in the CTD of TcdB027, a toxoid form of this toxin primed a strong protective response. These findings indicate TcdB027 is a more potent toxin than TcdB003 as measured by lethality assays and pathology, moreover the sequence differences between the two forms of TcdB alter antigenic epitopes and reduce cross-neutralization by antibodies targeting the CTD

    In vivo pathologies of TcdB<sub>003</sub> and TcdB<sub>027</sub>.

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    <p>(A) Top- Liver pathologies from BALB/c mice injected with (from left to right) 2.5 µg/kg, 50 µg/kg, 25 µg/kg, and 5 µg/kg of TcdB<sub>003</sub>. Bottom- Liver pathologies from BALB/c mice injected with (from left to right) 625 ng/kg, 10 µg/kg, 5 µg/kg, or 2.5 µg/kg of TcdB<sub>027</sub>. All photos are a 20× magnification of H&E stained sections and are listed by survival time. (B) Pathologies of the cerebrum and cerebellum with arrows pointing to areas of hemorrhaging. Representative photos (20×) of H&E stained sections from BALB/c mice injected with 5 µg/kg TcdB<sub>003</sub> (top) or 2.5 µg/kg of TcdB<sub>027</sub> (bottom).</p

    Identification of unique and shared epitopes between TcdB<sub>003</sub> and TcdB<sub>027</sub> using synthetic peptide ELISAs.

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    <p>Solid phase epitope mapping of αCTD<sub>003</sub> (black) and αCTD<sub>027</sub> (red) rabbit sera binding to overlapping decapeptides of the TcdB<sub>003</sub> CTD. (a) Peptides from the CTD<sub>003</sub> were constructed spanning amino acid 1651 through 2366, and the bars indicate the magnitude of reactivity of the sera to overlapping peptide sequences from the CTD of TcdB<sub>003</sub>. Reactivity is shown for αCTD<sub>003</sub> (black) and αCTD<sub>027</sub> (red), and represents an average of sera from 2 rabbits per group. (B) The peaks were numbered and identified as either unique to αCTD<sub>003</sub> (left), unique to αCTD<sub>027</sub> (middle), or overlapping/shared between αCTD<sub>003</sub> and αCTD<sub>027</sub> (right). The amino acid location of each epitope is indicated, as well as the sequence of the peptides in TcdB<sub>003</sub>, with amino acids that vary in TcdB<sub>027</sub> identified in red.</p

    Comparative survival curves of mice injected with TcdB<sub>003</sub> and TcdB<sub>027.</sub>

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    <p>Kaplan-Meier graphs showing the time to death of BALB/c mice that were injected intravenously with TcdB. (A) Survival time of mice (n = 4) injected with 50 ug/kg, 25 ug/kg, 5 ug/kg, and 2.5 ug/kg of TcdB<sub>003</sub>. (B) Survival time of mice (n = 4) injected with 10 ug/kg, 5 ug/kg, 2.5 ug/kg, 1.25 ug/kg, and 625 ng/kg of TcdB<sub>027</sub>. (C) Kaplan-Meier graph comparing the time to death of mice injected with 5 ug/kg of TcdB<sub>003</sub> or TcdB<sub>027</sub>. The difference between the curves is indicated by the p value determined from a log-rank analysis. (D) Kaplan-Meier graph comparing the time to death of mice injected with 2.5 ug/kg of TcdB<sub>003</sub> or TcdB<sub>027</sub>. The difference between the curves is indicated by the p value determined from a log-rank analysis.</p
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