Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis

© 2010 Cascão et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset and perpetuation of this disease. The main goal of this work was to determine whether cytokines driving neutrophil and Th17 activation are dysregulated in very early rheumatoid arthritis patients with less than 6 weeks of disease duration and before treatment (VERA). Methods: Cytokines related to neutrophil and Th17 activation were quantified in the serum of VERA and established RA patients and compared with other very early arthritis (VEA) and healthy controls. Synovial fluid (SF) from RA and osteoarthritis (OA) patients was also analyzed. Results: VERA patients had increased serum levels of cytokines promoting Th17 polarization (IL-1b and IL-6), as well as IL-8 and Th17-derived cytokines (IL-17A and IL-22) known to induce neutrophil-mediated inflammation. In established RA this pattern is more evident within the SF. Early treatment with methotrexate or corticosteroids led to clinical improvement but without an impact on the cytokine pattern. Conclusions: VERA patients already display increased levels of cytokines related with Th17 polarization and neutrophil recruitment and activation, a dysregulation also found in SF of established RA. 0 Thus, our data suggest that a cytokine-milieu favoring Th17 and neutrophil activity is an early event in RA pathogenesis.This work was supported by a grant from Sociedade Portuguesa de Reumatologia/Schering-Plough 2005. RAM and RC were funded by Fundação para a Ciência e a Tecnologia (FCT) SFRH/BD/30247/2006 and SFRH/BD/40513/2007, respectively. MMS-C was funded by Marie Curie Intra-European Fellowship PERG-2008-239422 and a EULAR Young Investigator Award

A Biometric Model for Mineralization of Type-I Collagen Fibrils

The bone and dentin mainly consist of type-I collagen fibrils mineralized by hydroxyapatite (HAP) nanocrystals. In vitro biomimetic models based on self-assembled collagen fibrils have been widely used in studying the mineralization mechanism of type-I collagen. In this chapter, the protocol we used to build a biomimetic model for the mechanistic study of type-I collagen mineralization is described. Type-I collagen extracted from rat tail tendon or horse tendon is self-assembled into fibrils and mineralized by HAP in vitro. The mineralization process is monitored by cryoTEM in combination with two-dimensional (2D) and three-dimensional (3D) stochastic optical reconstruction microscopy (STORM), which enables in situ and high-resolution visualization of the process

How does our motor system determine its learning rate?

Motor learning is driven by movement errors. The speed of learning can be quantified by the learning rate, which is the proportion of an error that is corrected for in the planning of the next movement. Previous studies have shown that the learning rate depends on the reliability of the error signal and on the uncertainty of the motor system’s own state. These dependences are in agreement with the predictions of the Kalman filter, which is a state estimator that can be used to determine the optimal learning rate for each movement such that the expected movement error is minimized. Here we test whether not only the average behaviour is optimal, as the previous studies showed, but if the learning rate is chosen optimally in every individual movement. Subjects made repeated movements to visual targets with their unseen hand. They received visual feedback about their endpoint error immediately after each movement. The reliability of these error-signals was varied across three conditions. The results are inconsistent with the predictions of the Kalman filter because correction for large errors in the beginning of a series of movements to a fixed target was not as fast as predicted and the learning rates for the extent and the direction of the movements did not differ in the way predicted by the Kalman filter. Instead, a simpler model that uses the same learning rate for all movements with the same error-signal reliability can explain the data. We conclude that our brain does not apply state estimation to determine the optimal planning correction for every individual movement, but it employs a simpler strategy of using a fixed learning rate for all movements with the same level of error-signal reliability

How Psychological Stress Affects Emotional Prosody

We explored how experimentally induced psychological stress affects the production and recognition of vocal emotions. In Study 1a, we demonstrate that sentences spoken by stressed speakers are judged by naive listeners as sounding more stressed than sentences uttered by non-stressed speakers. In Study 1b, negative emotions produced by stressed speakers are generally less well recognized than the same emotions produced by non-stressed speakers. Multiple mediation analyses suggest this poorer recognition of negative stimuli was due to a mismatch between the variation of volume voiced by speakers and the range of volume expected by listeners. Together, this suggests that the stress level of the speaker affects judgments made by the receiver. In Study 2, we demonstrate that participants who were induced with a feeling of stress before carrying out an emotional prosody recognition task performed worse than non-stressed participants. Overall, findings suggest detrimental effects of induced stress on interpersonal sensitivity

Effectiveness and costs of implementation strategies to reduce acid suppressive drug prescriptions: a systematic review

<p>Abstract</p> <p>Background</p> <p>Evaluation of evidence for the effectiveness of implementation strategies aimed at reducing prescriptions for the use of acid suppressive drugs (ASD).</p> <p>Methods</p> <p>A systematic review of intervention studies with a design according to research quality criteria and outcomes related to the effect of reduction of ASD medication retrieved from Medline, Embase and the Cochrane Library. Outcome measures were the strategy of intervention, quality of methodology and results of treatment to differences of ASD prescriptions and costs.</p> <p>Results</p> <p>The intervention varied from a single passive method to multiple active interactions with GPs. Reports of study quality had shortcomings on subjects of data-analysis. Not all outcomes were calculated but if so rction of prescriptions varied from 8% up to 40% and the cost effectiveness was in some cases negative and in others positive. Few studies demonstrated good effects from the interventions to reduce ASD.</p> <p>Conclusion</p> <p>Poor quality of some studies is limiting the evidence for effective interventions. Also it is difficult to compare cost-effectiveness between studies. However, RCT studies demonstrate that active interventions are required to reduce ASD volume. Larger multi-intervention studies are necessary to evaluate the most successful intervention instruments.</p