965 research outputs found

    Different secretion patterns of matrix metalloproteinases and IL-8 and effect of corticotropin-releasing hormone in preterm and term cervical fibroblasts

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    The aims of the present study were to compare the levels of mRNA and protein expression of matrix metalloproteinase (MMP)-1, -3, -8 and -9 in human cervical tissue in preterm and term labor as well as not in labor and to determine if corticotropin-releasing hormone (CRH) has an effect on MMP-1, -3 and interleukin (IL)-8 secretion in both preterm and term cervical fibroblasts. Cervical biopsies were taken from 60 women: 18 at preterm labor, 7 at preterm not in labor, 18 at term labor and 17 at term not in labor. ELISA and Immulite were used for protein and real-time RT–PCR for mRNA analysis. Cervical fibroblast cultures were incubated for 18 h with different CRH concentrations (10−13–10−6 M). The mRNA expression of MMP-1, -3 and -9 was higher in laboring groups compared with term not in labor. Protein levels of MMP-8 and -9 were higher in term in labor group compared with non-laboring groups. There were no significant differences in mRNA and protein expression between the preterm and respective term control groups. CRH significantly increased secretion of IL-8 in preterm and term cervical fibroblasts compared with controls. The secretion of IL-8 and MMP-1 was significantly higher and MMP-3 secretion lower in preterm cervical fibroblasts. In conclusion, cervical ripening at preterm seems to be a similar inflammatory process as at term with CRH involved. However, preterm and term cervical fibroblasts might have different phenotypes based on different secretion patterns of IL-8, MMP-1 and MMP-3

    Establishing the entatic state in folding metallated Pseudomonas aeruginosa azurin

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    Understanding how the folding of proteins establishes their functional characteristics at the molecular level challenges both theorists and experimentalists. The simplest test beds for confronting this issue are provided by electron transfer proteins. The environment provided by the folded protein to the cofactor tunes the metal's electron transport capabilities as envisioned in the entatic hypothesis. To see how the entatic state is achieved one must study how the folding landscape affects and in turn is affected by the metal. Here, we develop a coarse-grained functional to explicitly model how the coordination of the metal (which results in a so-called entatic or rack-induced state) modifies the folding of the metallated Pseudomonas aeruginosa azurin. Our free-energy functional-based approach directly yields the proper nonlinear extra-thermodynamic free energy relationships for the kinetics of folding the wild type and several point-mutated variants of the metallated protein. The results agree quite well with corresponding laboratory experiments. Moreover, our modified free-energy functional provides a sufficient level of detail to explicitly model how the geometric entatic state of the metal modifies the dynamic folding nucleus of azurin

    Development of a universal short patient satisfaction questionnaire on the basis of SERVQUAL : Psychometric analyses with data of diabetes and stroke patients from six different European countries

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    Objective A short questionnaire which can be applied for assessing patient satisfaction in different contexts and different countries is to be developed. Methods Six items addressing tangibles, reliability, responsiveness, assurance, empathy, and communication were analysed. The first five items stem from SERVQUAL (SERVice QUALity), the last stems from the discussion about SERVQUAL. The analyses were performed with data from 12 surveys conducted in six different countries (England, Finland, Germany, Greece, the Netherlands, Spain) covering two different conditions (type 2 diabetes, stroke). Sample sizes for included participants are 247 in England, 160 in Finland, 231 in Germany, 152 in Greece, 316 in the Netherlands and 96 in Spain for the diabetes surveys; and 101 in England, 139 in Finland, 107 in Germany, 58 in Greece, 185 in the Netherlands, and 92 in Spain for the stroke surveys. The items were tested by (1) bivariate correlations between the items and an item addressing 'general satisfaction', (2) multivariate regression analyses with 'general satisfaction' as criterion and the items as predictors, and (3) bivariate correlations between sum scores and 'general satisfaction'. Results The correlations with 'general satisfaction' are 0.48 for tangibles, 0.56 for reliability, 0.58 for responsiveness, 0.47 for assurance, 0.53 for empathy, and 0.56 for communication. In the multivariate regression analysis, the regression coefficient for assurance is significantly negative while all other regression coefficients are significantly positive. In a multivariate regression analysis without the item 'assurance' all regression coefficients are positive. The correlation between the sum score and 'general satisfaction' is 0.608 for all six items and 0.618 for the finally remaining five items. The country specific results are similar. Conclusions The five items which remain after removing 'assurance', i.e. the SERVQUAL-MOD-5, constitute a short patient satisfaction index which can usefully be applied for different medical conditions and in different countries.Peer reviewe

    The impact of accessibility and service quality on the frequency of patient visits to the primary diabetes care provider : results from a cross-sectional survey performed in six European countries

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    BackgroundVisits to the primary diabetes care provider play a central role in diabetes care. Therefore, patients should attend their primary diabetes care providers whenever a visit is necessary. Parameters that might affect whether this condition is fulfilled include accessibility (in terms of travel distance and travel time to the practice), as well as aspects of service quality (for example in-practice waiting time and quality of the provider's communication with the patient). The relationships of these variables with the frequency of visits to the primary diabetes care provider are investigated.MethodsThe investigation is performed with questionnaire data of 1086 type 2 diabetes patients from study regions in England (213), Finland (135), Germany (218), Greece (153), the Netherlands (296) and Spain (71). Data were collected between October 2011 and March 2012. Data were analysed using log-linear Poisson regression models with self-reported numbers of visits in a year to the primary diabetes care provider as the criterion variable. Predictor variables of the core model were: country; gender; age; education; stage of diabetes; heart problems; previous stroke; problems with lower extremities; problems with sight; kidney problems; travel distance and travel time; in-practice waiting time; and quality of communication. To test region-specific characteristics, the interaction between the latter four predictor variables and study region was also investigated.ResultsWhen study regions are merged, travel distance and in-practice waiting time have a negative effect, travel time no effect and quality of communication a positive effect on visit frequency (with the latter effect being by far largest). When region specific effects are considered, there are strong interaction effects shown for travel distance, in-practice waiting time and quality of communication. For travel distance, as well as for in-practice waiting time, there are region-specific effects in opposite directions. For quality of communication, there are only differences in the strength with which visit frequency increases with this variable.ConclusionsThe impact of quality of communication on visit frequency is the largest and is stable across all study regions. Hence, increasing quality of communication seems to be the best approach for increasing visit frequency.Peer reviewe

    Leukotriene antagonists as first-line or add-on asthma controller therapy

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    Most randomized trials of treatment for asthma study highly selected patients under idealized conditions. METHODS: We conducted two parallel, multicenter, pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist (LTRA) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist (LABA) as add-on therapy in patients already receiving inhaled glucocorticoid therapy. Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life (Mini Asthma Quality of Life Questionnaire [MiniAQLQ] score =6) or inadequate asthma control (Asthma Control Questionnaire [ACQ] score =1). We randomly assigned patients to 2 years of open-label therapy, under the care of their usual physician, with LTRA (148 patients) or an inhaled glucocorticoid (158 patients) in the first-line controller therapy trial and LTRA (170 patients) or LABA (182 patients) added to an inhaled glucocorticoid in the add-on therapy trial. RESULTS: Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials. At 2 months, differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence (95% confidence interval [CI] for an adjusted mean difference, -0.3 to 0.3). At 2 years, mean MiniAQLQ scores approached equivalence, with an adjusted mean difference between treatment groups of -0.11 (95% CI, -0.35 to 0.13) in the first-line controller therapy trial and of -0.11 (95% CI, -0.32 to 0.11) in the add-on therapy trial. Exacerbation rates and ACQ scores did not differ significantly between the two groups. CONCLUSIONS: Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients. Equivalence was not proved at 2 years. The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group

    Critical specific heats of the N-vector spin models on the sc and the bcc lattices

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    We have computed through order β21\beta^{21} the high-temperature expansions for the nearest-neighbor spin correlation function G(N,β)G(N,\beta) of the classical N-vector model, with general N, on the simple-cubic and on the body-centered-cubic lattices. For this model, also known in quantum field theory as the lattice O(N) nonlinear sigma model, we have presented in previous papers extended expansions of the susceptibility, of its second field derivative and of the second moment of the correlation function. Here we study the internal specific energy and the specific heat C(N,β)C(N,\beta), obtaining new estimates of the critical parameters and therefore a more accurate direct test of the hyperscaling relation dν(N)=2α(N)d \nu(N)=2 - \alpha(N) on a range of values of the spin dimensionality N, including N=0 [the self-avoiding walk model], N=1 [the Ising spin 1/2 model], N=2 [the XY model], N=3 [the classical Heisenberg model]. By the newly extended series, we also compute the universal combination of critical amplitudes usually denoted by Rξ+(N)R^+_{\xi}(N), in fair agreement with renormalization group estimates.Comment: 15 pages, latex, no figure

    PhosphoPep—a phosphoproteome resource for systems biology research in Drosophila Kc167 cells

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    The ability to analyze and understand the mechanisms by which cells process information is a key question of systems biology research. Such mechanisms critically depend on reversible phosphorylation of cellular proteins, a process that is catalyzed by protein kinases and phosphatases. Here, we present PhosphoPep, a database containing more than 10 000 unique high-confidence phosphorylation sites mapping to nearly 3500 gene models and 4600 distinct phosphoproteins of the Drosophila melanogaster Kc167 cell line. This constitutes the most comprehensive phosphorylation map of any single source to date. To enhance the utility of PhosphoPep, we also provide an array of software tools that allow users to browse through phosphorylation sites on single proteins or pathways, to easily integrate the data with other, external data types such as protein–protein interactions and to search the database via spectral matching. Finally, all data can be readily exported, for example, for targeted proteomics approaches and the data thus generated can be again validated using PhosphoPep, supporting iterative cycles of experimentation and analysis that are typical for systems biology research
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