Transitional B Cells and TLR9 Responses Are Defective in Selective IgA Deficiency.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesSelective IgA deficiency (IgAD) is the most common primary antibody deficiency in the western world with affected individuals suffering from an increased burden of autoimmunity, atopic diseases and infections. It has been shown that IgAD B cells can be induced with germinal center mimicking reactions to produce IgA. However, IgA is the most prevalent antibody in mucosal sites, where antigen-independent responses are important. Much interest has recently focused on the role of TLR9 in both naïve and mature B cell differentiation into IgA secreting plasma cells. Here, we analyze the phenotype and function of T and B cells in individuals with IgAD following IgA-inducing CpG-TLR9 stimulations. The IgAD individuals had significantly lower numbers of transitional B cells (CD19+CD24hiCD38hi) and class-switched memory B cells (CD20+CD27+IgD-) ex vivo. However, proportions of T cell populations ex vivo as well as in vitro induced T effector cells and T regulatory cells were comparable to healthy controls. After CpG stimulation, the transitional B cell defect was further enhanced, especially within its B regulatory subset expressing IL-10. Finally, CpG stimulation failed to induce IgA production in IgAD individuals. Collectively, our results demonstrate a defect of the TLR9 responses in IgAD that leads to B cell dysregulation and decreased IgA production.Icelandic Research Fund University hospital of Iceland research fun

Exploring user experience and technology acceptance for a fall prevention system: results from a randomized clinical trial and a living lab

Background: Falls are common in older adults and can result in serious injuries. Due to demographic changes, falls and related healthcare costs are likely to increase over the next years. Participation and motivation of older adults in fall prevention measures remain a challenge. The iStoppFalls project developed an information and communication technology (ICT)-based system for older adults to use at home in order to reduce common fall risk factors such as impaired balance and muscle weakness. The system aims at increasing older adults’ motivation to participate in ICT-based fall prevention measures. This article reports on usability, user-experience and user-acceptance aspects affecting the use of the iStoppFalls system by older adults. Methods: In the course of a 16-week international multicenter study, 153 community-dwelling older adults aged 65+ participated in the iStoppFalls randomized controlled trial, of which half used the system in their home to exercise and assess their risk of falling. During the study, 60 participants completed questionnaires regarding the usability, user experience and user acceptance of the iStoppFalls system. Usability was measured with the System Usability Scale (SUS). For user experience the Physical Activity Enjoyment Scale (PACES) was applied. User acceptance was assessed with the Dynamic Acceptance Model for the Re-evaluation of Technologies (DART). To collect more detailed data on usability, user experience and user acceptance, additional qualitative interviews and observations were conducted with participants. Results: Participants evaluated the usability of the system with an overall score of 62 (Standard Deviation, SD 15.58) out of 100, which suggests good usability. Most users enjoyed the iStoppFalls games and assessments, as shown by the overall PACES score of 31 (SD 8.03). With a score of 0.87 (SD 0.26), user acceptance results showed that participants accepted the iStoppFalls system for use in their own home. Interview data suggested that certain factors such as motivation, complexity or graphical design were different for gender and age. Conclusions: The results suggest that the iStoppFalls system has good usability, user experience and user acceptance. It will be important to take these along with factors such as motivation, gender and age into consideration when designing and further developing ICT-based fall prevention systems

Which dressing do donor site wounds need?: study protocol for a randomized controlled trial

Donor site wounds after split-skin grafting are rather 'standard' wounds. At present, lots of dressings and topical agents for donor site wounds are commercially available. This causes large variation in the local care of these wounds, while the optimum 'standard' dressing for local wound care is unclear. This protocol describes a trial in which we investigate the effectiveness of various treatment options for these donor site wounds. A 14-center, six-armed randomized clinical trial is being carried out in the Netherlands. An a-priori power analysis and an anticipated dropout rate of 15% indicates that 50 patients per group are necessary, totaling 300 patients, to be able to detect a 25% quicker mean time to complete wound healing. Randomization has been computerized to ensure allocation concealment. Adult patients who need a split-skin grafting operation for any reason, leaving a donor site wound of at least 10 cm2 are included and receive one of the following dressings: hydrocolloid, alginate, film, hydrofiber, silicone dressing, or paraffin gauze. No combinations of products from other intervention groups in this trial are allowed. Optimum application and changes of these dressings are pursued according to the protocol as supplied by the dressing manufacturers. Primary outcomes are days to complete wound healing and pain (using a Visual Analogue Scale). Secondary outcomes are adverse effects, scarring, patient satisfaction, and costs. Outcome assessors unaware of the treatment allocation will assess whether or not an outcome has occurred. Results will be analyzed according to the intention to treat principle. The first patient was randomized October 1, 2009. This study will provide comprehensive data on the effectiveness of different treatment options for donor site wounds. The dressing(s) that will prevail in effectiveness, satisfaction and costs will be promoted among clinicians dealing with such patients. Thus, we aim to contribute a well-designed trial, relevant to all clinicians involved in the care for donor site wounds, which will help enhance uniformity and quality of care for these patients. http://www.trialregister.nl, NTR1849. Date registered: June 9, 200

HDL Interfere with the Binding of T Cell Microparticles to Human Monocytes to Inhibit Pro-Inflammatory Cytokine Production

BACKGROUND: Direct cellular contact with stimulated T cells is a potent mechanism that induces cytokine production in human monocytes in the absence of an infectious agent. This mechanism is likely to be relevant to T cell-mediated inflammatory diseases such as rheumatoid arthritis and multiple sclerosis. Microparticles (MP) generated by stimulated T cells (MPT) display similar monocyte activating ability to whole T cells, isolated T cell membranes, or solubilized T cell membranes. We previously demonstrated that high-density lipoproteins (HDL) inhibited T cell contact- and MPT-induced production of IL-1beta but not of its natural inhibitor, the secreted form of IL-1 receptor antagonist (sIL-1Ra). METHODOLOGY/PRINCIPAL FINDINGS: Labeled MPT were used to assess their interaction with monocytes and T lymphocytes by flow cytometry. Similarly, interactions of labeled HDL with monocytes and MPT were assessed by flow cytometry. In parallel, the MPT-induction of IL-1beta and sIL-1Ra production in human monocytes and the effect of HDL were assessed in cell cultures. The results show that MPT, but not MP generated by activated endothelial cells, bond monocytes to trigger cytokine production. MPT did not bind T cells. The inhibition of IL-1beta production by HDL correlated with the inhibition of MPT binding to monocytes. HDL interacted with MPT rather than with monocytes suggesting that they bound the activating factor(s) of T cell surface. Furthermore, prototypical pro-inflammatory cytokines and chemokines such as TNF, IL-6, IL-8, CCL3 and CCL4 displayed a pattern of production induced by MPT and inhibition by HDL similar to IL-1beta, whereas the production of CCL2, like that of sIL-1Ra, was not inhibited by HDL. CONCLUSIONS/SIGNIFICANCE: HDL inhibit both MPT binding to monocytes and the MPT-induced production of some but not all cytokines, shedding new light on the mechanism by which HDL display their anti-inflammatory functions

Associations between medical student empathy and personality: A Multi-institutional study

Background: More empathetic physicians are more likely to achieve higher patient satisfaction, adherence to treatments, and health outcomes. In the context of medical education, it is thus important to understand how personality might condition the empathetic development of medical students. Single institutional evidence shows associations between students' personality and empathy. This multi-institutional study aimed to assess such associations across institutions, looking for personality differences between students with high empathy and low empathy levels. Methods: Participants were 472 students from three medical schools in Portugal. They completed validated adaptations to Portuguese of self-report measures of the NEO-Five Factor Inventory(NEO-FFI) and the Jefferson Scale of Physician Empathy(JSPE-spv). Students were categorized into two groups: "Bottom" (low empathy, N = 165) and "Top" (high empathy, N = 169) according to their empathy JSPE-spv total score terciles. Correlation analysis, binary logistic regression analysis and ROC curve analysis were conducted. Results: A regression model with gender, age and university had a predictive power (pseudo R2) for belonging to the top or bottom group of 6.4%. The addition of personality dimensions improved the predictive power to 16.8%. Openness to experience and Agreeableness were important to predict top or bottom empathy scores when gender, age and university were considered." Based on the considered predictors the model correctly classified 69.3% of all students. Conclusions: The present multi-institutional cross-sectional study in Portugal revealed across-school associations between the Big5 dimensions Agreeableness and Openness to experience and the empathy of medical students and that personality made a significant contribution to identify the more empathic students. Therefore, medical schools may need to pay attention to the personality of medical students to understand how to enhance the empathy of medical students

Effect of TENS on pain in relation to central sensitization in patients with osteoarthritis of the knee: study protocol of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Central sensitization has recently been documented in patients with knee osteoarthritis (OAk). So far, the presence of central sensitization has not been considered as a confounding factor in studies assessing the pain inhibitory effect of tens on osteoarthritis of the knee. The purpose of this study is to explore the pain inhibitory effect of burst tens in OAk patients and to explore the prognostic value of central sensitization on the pain inhibitory effect of tens in OAk patients.</p> <p>Methods</p> <p>Patients with knee pain due to OAk will be recruited through advertisements in local media. Temporal summation, before and after a heterotopic noxious conditioning stimulation, will be measured. In addition, pain on a numeric rating score, WOMAC subscores for pain and function and global perceived effect will be assessed. Patients will be randomly allocated to one of two treatment groups (tens, sham tens). Follow-up measurements will be scheduled after a period of 6 and 12 weeks.</p> <p>Discussion</p> <p>Tens influences pain through the electrical stimulation of low-threshold A-beta cutaneous fibers. The responsiveness of central pain-signaling neurons of centrally sensitized OAk patients may be augmented to the input of these electrical stimuli. This would encompass an adverse therapy effect of tens. To increase treatment effectiveness it might be interesting to identify a subgroup of symptomatic OAk patients, i.e., non-sensitized patients, who are likely to benefit from burst tens.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01390285">NCT01390285</a></p

Consumers' experiences and values in conventional and alternative medicine paradigms: a problem detection study (PDS)

Background: This study explored consumer perceptions of complementary and alternative medicine (CAM) and relationships with CAM and conventional medicine practitioners. A problem detection study (PDS) was used. The qualitative component to develop the questionnaire used a CAM consumer focus group to explore conventional and CAM paradigms in healthcare. 32 key issues, seven main themes, informed the questionnaire (the quantitative PDS component - 36 statements explored using five-point Likert scales.