4,163 research outputs found

    Proteomic Analysis of a Noninvasive Human Model of Acute Inflammation and Its Resolution: The Twenty-one Day Gingivitis Model

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    The 21-day experimental gingivitis model, an established noninvasive model of inflammation in response to increasing bacterial accumulation in humans, is designed to enable the study of both the induction and resolution of inflammation. Here, we have analyzed gingival crevicular fluid, an oral fluid comprising a serum transudate and tissue exudates, by LC−MS/MS using Fourier transform ion cyclotron resonance mass spectrometry and iTRAQ isobaric mass tags, to establish meta-proteomic profiles of inflammation-induced changes in proteins in healthy young volunteers. Across the course of experimentally induced gingivitis, we identified 16 bacterial and 186 human proteins. Although abundances of the bacterial proteins identified did not vary temporally, Fusobacterium outer membrane proteins were detected. Fusobacterium species have previously been associated with periodontal health or disease. The human proteins identified spanned a wide range of compartments (both extracellular and intracellular) and functions, including serum proteins, proteins displaying antibacterial properties, and proteins with functions associated with cellular transcription, DNA binding, the cytoskeleton, cell adhesion, and cilia. PolySNAP3 clustering software was used in a multilayered analytical approach. Clusters of proteins that associated with changes to the clinical parameters included neuronal and synapse associated proteins

    Cost-effectiveness of alternative methods of surgical repair of inguinal hernia

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    Objectives: To assess the relative cost-effectiveness of laparoscopic methods of inguinal hernia repair compared with open flat mesh and open non-mesh repair. Methods: Data on the effectiveness of these alternatives came from three systematic reviews comparing: (i) laparoscopic methods with open flat mesh or non-mesh methods; (ii) open flat mesh with open non-mesh repair; and (iii) methods that used synthetic mesh to repair the hernia defect with those that did not. Data on costs were obtained from the authors of economic evaluations previously conducted alongside trials included in the reviews. A Markov model was used to model cost-effectiveness for a five-year period after the initial operation. The outcomes of the model were presented using a balance sheet approach and as cost per hernia recurrence avoided and cost per extra day at usual activities. Results: Open flat mesh was the most cost-effective method of preventing recurrences. Laparoscopic repair provided a shorter period of convalescence and less long-term pain compared with open flat mesh but was more costly. The mean incremental cost per additional day back at usual activities compared with open flat mesh was €38 and €80 for totally extraperitoneal and transabdominal preperitoneal repair, respectively. Conclusions: Laparoscopic repair is not cost-effective compared with open flat mesh repair in terms of cost per recurrence avoided. Decisions about the use of laparoscopic repair depend on whether the benefits (reduced pain and earlier return to usual activities) outweigh the extra costs and intraoperative risks. On the evidence presented here, these extra costs are unlikely to be offset by the short-term benefits of laparoscopic repair.Luke Vale, Adrian Grant, Kirsty McCormack, Neil W. Scott and the EU Hernia Trialists Collaboratio

    The Basics of Training for Muscle Size and Strength: A Brief Review on the Theory

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    The periodization of resistance exercise is often touted as the most effective strategy for optimizing muscle size and strength adaptations. This narrative persists despite a lack of experimental evidence to demonstrate its superiority. In addition, the general adaptation syndrome, which provides the theoretical framework underlying periodization, does not appear to provide a strong physiological rationale that periodization is necessary. Hans Selye conducted a series of rodent studies which used toxic stressors to facilitate the development of the general adaptation syndrome. To our knowledge, normal exercise in humans has never been shown to produce a general adaptation syndrome. We question whether there is any physiological rationale that a periodized training approach would facilitate greater adaptations compared with nonperiodized approaches employing progressive overload. The purpose of this article is to briefly review currently debated topics within strength and conditioning and provide some practical insight regarding the implications these reevaluations of the literature may have for resistance exercise and periodization. In addition, we provide some suggestions for the continued advancement within the field of strength and conditioning

    Limb Occlusion Pressure: A Method to Assess Changes in Systolic Blood Pressure

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    Although often used as a surrogate, comparisons between traditional blood pressure measurements and limb occlusion assessed via hand-held Doppler have yet to be completed. Using limb occlusion pressure as a method of assessing systolic pressure is of interest to those studying the acute effects of blood flow restriction, where the removal of the cuff may alter the physiological response. Purpose: We sought to determine how changes in limb occlusion pressure track with changes in traditional assessments of blood pressure. Basic Procedures: Limb occlusion pressure measured by hand-held Doppler and blood pressure measured by an automatic blood pressure cuff were assessed at rest and following isometric knee extension (post and 5 minutes post). Main Findings: Each individual had a similar dispersion from the mean value for both the limb occlusion pressure measurement and traditional systolic blood pressure measurement [BF10: 0.33; median (95% credible interval): 0.02 (−6.0, 5.9) %]. In response to lower body isometric exercise, blood pressure changed across time. The difference between measurements was small at immediately post and 5 minutes post. The Bayes factors were in the direction of the null but did not exceed the threshold needed to accept the null hypothesis. However, at 5 minutes post, the differences were within the range of practical equivalence (within ± 4.6%). Principal Conclusions: Our findings suggest that changes in limb occlusion pressure measured by hand-held Doppler track similarly to traditional measurements of brachial systolic blood pressure following isometric knee extension exercise

    Helicobacter pylori-Induced Histone Modification, Associated Gene Expression in Gastric Epithelial Cells, and Its Implication in Pathogenesis

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    Histone modifications are critical in regulating gene expression, cell cycle, cell proliferation, and development. Relatively few studies have investigated whether Helicobacter pylori, the major cause of human gastric diseases, affects histone modification. We therefore investigated the effects of H. pylori infection on histone modifications in a global and promoter-specific manner in gastric epithelial cells. Infection of gastric epithelial cells by wild-type H. pylori induced time- and dose-dependent dephosphorylation of histone H3 at serine 10 (H3 Ser10) and decreased acetylation of H3 lysine 23, but had no effects on seven other specific modifications. Different cag pathogenicity island (PAI)-containing-clinical isolates showed similar abilities to induce H3 Ser10 dephosphorylation. Mutation of cagA, vacA, nonphosphorylateable CagA mutant cagAEPISA, or disruption of the flagella showed no effects, while deletion of the entire cagPAI restored the H3 Ser10 phosphorylation to control levels. Analysis of 27 cagPAI mutants indicated that the genes that caused H3 Ser10 dephosphorylation were similar to those that were previously found to induce interleukin-8, irrespective of CagA translocation. This effect was independent of ERK or p38 pathways and type I interferon signaling. Additionally, c-Jun and hsp70 gene expression was associated with this histone modification. These results demonstrate that H. pylori alters histone modification and host response via a cagA-, vacA-independent, but cagPAI-dependent mechanisms, which contribute to its persistent infection and pathogenesis
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