36 research outputs found

    Comparison of 20nm silver nanoparticles synthesized with and without a gold core: Structure, dissolution in cell culture media, and biological impact on macrophages

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    Widespread use of silver nanoparticles raises questions of environmental and biological impact. Many synthesis approaches are used to produce pure silver and silver-shell gold-core particles optimized for specific applications. Since both nanoparticles and silver dissolved from the particles may impact the biological response, it is important to understand the physicochemical characteristics along with the biological impact of nanoparticles produced by different processes. The authors have examined the structure, dissolution, and impact of particle exposure to macrophage cells of two 20 nm silver particles synthesized in different ways, which have different internal structures. The structures were examined by electron microscopy and dissolution measured in Rosewell Park Memorial Institute media with 10% fetal bovine serum. Cytotoxicity and oxidative stress were used to measure biological impact on RAW 264.7 macrophage cells. The particles were polycrystalline, but 20 nm particles grown on gold seed particles had smaller crystallite size with many high-energy grain boundaries and defects, and an apparent higher solubility than 20 nm pure silver particles. Greater oxidative stress and cytotoxicity were observed for 20 nm particles containing the Au core than for 20 nm pure silver particles. A simple dissolution model described the time variation of particle size and dissolved silver for particle loadings larger than 9 μg/ml for the 24-h period characteristic of many in-vitro studies

    Development of a questionnaire to measure health-related quality of life (HRQoL) in patients with atrial fibrillation (AF-QoL)

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    <p>Abstract</p> <p>Background</p> <p>The Health-Related Quality of Life (HRQoL) assessment in atrial fibrillation (AF) patients has traditionally been carried out in a poorly standardised fashion, or via the use of non disease-specific HRQoL questionnaires. The development of a HRQoL questionnaire with a good measuring performance will allow for a standardised assessment of the impact of this disease on the patient's daily living.</p> <p>Methods</p> <p>A bibliography review was conducted to identify the most relevant domains of daily living in AF patients. Subsequently, a focus group was created with the aid of cardiologists, and 17 patients were interviewed to identify the most-affected HRQoL domains. A qualitative analysis of the interview answers was performed, which was used to develop a pilot questionnaire administered to a 112-patient sample. Based on patient responses, an analysis was carried out following the statistical procedures defined by the Classical Test Theory (CTT) and the Item Response Theory (IRT). Reliablility was assessed via Cronbach's coefficient alpha and item-total score correlations. A factorial analysis was performed to determine the number of domains. For each domain, a Rasch analysis was carried out, in order to reduce and stand hierarchically the questionnaire items.</p> <p>Results</p> <p>By way of the bibliography review and the expert focus group, 10 domains were identified. The patient interviews allowed for the identification of 286 items that later were downsized to 40 items. The resultant preliminary questionnaire was administered to a 112-patient sample (pilot study). The Rasch analysis led to the definition of two domains, comprising 7 and 11 items respectively, which corresponded to the psychological and physical domains (18 items total), thereby giving rise to the initial AF-QoL-18 questionnaire. Cronbach's coefficient alpha was acceptable (0.91).</p> <p>Conclusion</p> <p>An initial HRQoL questionnaire, AFQoL-18, has been developed to assess HRQoL in AF patients.</p

    Soluble TNF Mediates the Transition from Pulmonary Inflammation to Fibrosis

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    BACKGROUND: Fibrosis, the replacement of functional tissue with excessive fibrous tissue, can occur in all the main tissues and organ systems, resulting in various pathological disorders. Idiopathic Pulmonary Fibrosis is a prototype fibrotic disease involving abnormal wound healing in response to multiple sites of ongoing alveolar epithelial injury. METHODOLOGY/PRINCIPAL FINDINGS: To decipher the role of TNF and TNF-mediated inflammation in the development of fibrosis, we have utilized the bleomycin-induced animal model of Pulmonary Fibrosis and a series of genetically modified mice lacking components of TNF signaling. Transmembrane TNF expression is shown to be sufficient to elicit an inflammatory response, but inadequate for the transition to the fibrotic phase of the disease. Soluble TNF expression is shown to be crucial for lymphocyte recruitment, a prerequisite for TGF-b1 expression and the development of fibrotic lesions. Moreover, through a series of bone marrow transfers, the necessary TNF expression is shown to originate from the non-hematopoietic compartment further localized in apoptosing epithelial cells. CONCLUSIONS: These results suggest a primary detrimental role of soluble TNF in the pathologic cascade, separating it from the beneficial role of transmembrane TNF, and indicate the importance of assessing the efficacy of soluble TNF antagonists in the treatment of Idiopathic Pulmonary Fibrosis

    Increased Serum and Musculotendinous Fibrogenic Proteins following Persistent Low-Grade Inflammation in a Rat Model of Long-Term Upper Extremity Overuse.

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    We examined the relationship between grip strength declines and muscle-tendon responses induced by long-term performance of a high-repetition, low-force (HRLF) reaching task in rats. We hypothesized that grip strength declines would correlate with inflammation, fibrosis and degradation in flexor digitorum muscles and tendons. Grip strength declined after training, and further in weeks 18 and 24, in reach limbs of HRLF rats. Flexor digitorum tissues of reach limbs showed low-grade increases in inflammatory cytokines: IL-1β after training and in week 18, IL-1α in week 18, TNF-α and IL-6 after training and in week 24, and IL-10 in week 24, with greater increases in tendons than muscles. Similar cytokine increases were detected in serum with HRLF: IL-1α and IL-10 in week 18, and TNF-α and IL-6 in week 24. Grip strength correlated inversely with IL-6 in muscles, tendons and serum, and TNF-α in muscles and serum. Four fibrogenic proteins, TGFB1, CTGF, PDGFab and PDGFbb, and hydroxyproline, a marker of collagen synthesis, increased in serum in HRLF weeks 18 or 24, concomitant with epitendon thickening, increased muscle and tendon TGFB1 and CTGF. A collagenolytic gelatinase, MMP2, increased by week 18 in serum, tendons and muscles of HRLF rats. Grip strength correlated inversely with TGFB1 in muscles, tendons and serum; with CTGF-immunoreactive fibroblasts in tendons; and with MMP2 in tendons and serum. Thus, motor declines correlated with low-grade systemic and musculotendinous inflammation throughout task performance, and increased fibrogenic and degradative proteins with prolonged task performance. Serum TNF-α, IL-6, TGFB1, CTGF and MMP2 may serve as serum biomarkers of work-related musculoskeletal disorders, although further studies in humans are needed

    The effectiveness of celebrities in conservation marketing

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    Celebrities are frequently used in conservation marketing as a tool to raise awareness, generate funding and effect behaviour change. The importance of evaluating effectiveness is widely recognised in both marketing and conservation but, to date, little research into the effectiveness of celebrity endorsement as a tool for conservation marketing has been published. Using a combination of interviews and an online choice survey instrument, we investigated the extent to which a sample of UK-based conservation organisations, and other charities, evaluate their own usage of celebrity endorsement, and then carried out an experimental evaluation of a hypothetical marketing campaign. This experiment compared participants' willingness-to-engage (WTE) with, and recall of, a conservation message presented in versions of an advert featuring one of three prominent UK celebrities (David Beckham, Chris Packham or HRH Prince William) or a non-celebrity control treatment (featuring Crawford Allan, a director of TRAFFIC USA). We find that the organisations we interviewed did not routinely evaluate their marketing campaigns featuring celebrities. Furthermore, our experiment provides evidence that celebrity endorsement can produce both positive and negative effects. Participants were more willing to engage when presented with an advert featuring one of the three celebrities than the non-celebrity control, and WTE varied according to the characteristics of the celebrity and the respondent. However, celebrities were less effective at generating campaign message recall than non-celebrities. These findings suggest that celebrity endorsement should be used carefully. Further work is required to fully understand the role celebrity endorsers can play in conservation but, drawing on best practice from the field of marketing, this study introduces an approach to evaluation which could be applied more widely to improve the effectiveness of conservation marketing
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