The type I interferon signature in leukocyte subsets from peripheral blood of patients with early arthritis: a major contribution by granulocytes

The type I interferon (IFN) signature in rheumatoid arthritis (RA) has shown clinical relevance in relation to disease onset and therapeutic response. Identification of the cell type(s) contributing to this IFN signature could provide insight into the signature's functional consequences. The aim of this study was to investigate the contribution of peripheral leukocyte subsets to the IFN signature in early arthritis. Blood was collected from 26 patients with early arthritis and lysed directly or separated into peripheral blood mononuclear cells (PBMCs) and polymorphonuclear granulocytes (PMNs). PBMCs were sorted into CD4(+) T cells, CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes by flow cytometry. Messenger RNA expression of three interferon response genes (IRGs RSAD2, IFI44L, and MX1) and type I interferon receptors (IFNAR1 and IFNAR2) was determined in whole blood and blood cell subsets by quantitative polymerase chain reaction. IRG expression was averaged to calculate an IFN score for each sample. Patients were designated "IFN(high)" (n = 8) or "IFN(low)" (n = 18) on the basis of an IFN score cutoff in whole peripheral blood from healthy control subjects. The difference in IFN score between IFN(high) and IFN(low) patients was remarkably large for the PMN fraction (mean 25-fold) compared with the other subsets (mean 6- to 9-fold), indicating that PMNs are the main inducers of IRGs. Moreover, the relative contribution of the PMN fraction to the whole-blood IFN score was threefold higher than expected from its abundance in blood (p = 0.008), whereas it was three- to sixfold lower for the other subsets (p ≤ 0.063), implying that the PMNs are most sensitive to IFN signaling. Concordantly, IFNAR1 and IFNAR2 were upregulated compared with healthy controls selectively in patient PMNs (p ≤ 0.0077) but not in PBMCs. PMNs are the main contributors to the whole-blood type I IFN signature in patients with early arthritis, which seems due to increased sensitivity of these cells to type I IFN signaling. Considering the well-established role of neutrophils in the pathology of arthritis, this suggests a role of type I IFN activity in the disease as wel

Dynamics of the Type I Interferon Response During Immunosuppressive Therapy in Rheumatoid Arthritis

Objective: The type I interferon (IFN) response in rheumatoid arthritis (RA) has been extensively studied in relation to therapy with biological DMARDs (bDMARDs). However, the effect of conventional synthetic (cs)DMARDs and glucocorticoids (GCs) on IFN response gene (IRG) expression remains largely unknown, even though csDMARDS are used throughout all disease phases, including simultaneously with biologic therapy. This study was aimed to determine the dynamics of IFN response upon immunosuppressive treatment.Methods: Whole blood was collected in PAXgene tubes from 35 RA patients who received either COBRA therapy (combination of prednisone, initially 60 mg, methotrexate and sulfasalazine) (n = 14) or COBRA-light therapy (prednisone, initially 30 mg, and methotrexate) (n = 21). Expression of 10 IRGs was determined by real-time PCR at baseline (T0), after 4 weeks (T4), and 13 weeks (T13) of treatment. IRG selection was based on the differential presence of transcription factor binding sites (TFBS), in order to study the therapy effect on different pathway components involved in IFN signaling.Results: Seven of the 10 IRGs displayed significant changes during treatment (p ≤ 0.016). These 7 IRGs all displayed a particularly pronounced decrease between T0 and T4 (≥1.6-fold, p ≤ 0.0059). The differences between IRG sensitivity to the treatment appeared related to the presence of TFBS for STAT1 and IRF proteins within the genes. The extent of the decreases between T0 and T4 was similar for the COBRA- and COBRA-light-treated group, despite the differences in drug combination and doses in those groups. Between T4 and T13, however, IRG expression in the COBRA-light-treated group displayed a significant increase, whereas it remained stable or decreased even further in most COBRA-treated patients (comparison of mean fold changes, p = 0.011). A significant association between IRG dynamics and clinical response to therapy was not detected.Conclusions: Immunosuppressive treatment with csDMARDs, in this case a combination of prednisolone, methotrexate and sulfasalazine, substantially downregulates the IFN response in RA patients. The dynamics of this downregulation were partly dependent on the presence of TFBS within the IRGs and the combination and dosages of agents, but they were irrespective of the clinical response to therapy

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Figure S3. Line plot of the absolute number of cells per lymphocyte subset in 68 non-converting and 17 converting patients with arthralgia. The non-converting patients are depicted from the time point of inclusion. The converting patients are depicted from the time point of conversion and the time before conversion. (TIF 1784 kb

Interventions to Promote Healthy Eating, Physical Activity and Smoking in Low-Income Groups: a Systematic Review with Meta-Analysis of Behavior Change Techniques and Delivery/Context

Purpose Healthy eating, physical activity and smoking interventions for low-income groups may have small, positive effects. Identifying effective intervention components could guide intervention development. This study investigated which content and delivery components of interventions were associated with increased healthy behavior in randomised controlled trials (RCTs) for low-income adults. Method Data from a review showing intervention effects in 35 RCTs containing 45 interventions with 17,000 participants were analysed to assess associations with behavior change techniques (BCTs) and delivery/context components from the template for intervention description and replication (TIDieR) checklist. The associations of 46 BCTs and 14 delivery/context components with behavior change (measures of healthy eating, physical activity and smoking cessation) were examined using random effects subgroup meta-analyses. Synergistic effects of components were examined using classification and regression trees (meta-CART) analyses based on both fixed and random effects assumptions. Results For healthy eating, self-monitoring, delivery through personal contact, and targeting multiple behaviors were associated with increased effectiveness. Providing feedback, information about emotional consequences, or using prompts and cues were associated with reduced effectiveness. In synergistic analyses, interventions were most effective without feedback, or with selfmonitoring excluding feedback. More effective physical activity interventions included behavioral practice/rehearsal or instruction, focussed solely on physical activity or took place in home/community settings. Information about antecedents was associated with reduced effectiveness. In synergistic analyses, interventions were most effective in home/community settings with instruction. No associations were identified for smoking. Conclusion This study identified BCTs and delivery/context components, individually and synergistically, linked to increased and reduced effectiveness of healthy eating and physical activity interventions. The identified components should be subject to further experimental study to help inform the development effective behavior change interventions for low-income groups to reduce health inequalities

Affordance : théorie, caractérisation et perspectives pour l'ergonomie

International audienceThe affordance concept is a cornerstone of the ecological approach to perception and action. Popularized at the end of the eighties among the design community, it received a resounding welcome within the field of ergonomics, especially for human-computer interactions (HCI). We come back to this notion of affordance and address more specifically affordances characterization, which involves describing the environment in units intrinsic to the individual, that is, taken in reference to one’s body and action systems. After giving a short reminder of some founding principles and a definition of the concept, we detail classical formalization of affordance by reviewing some of the major findings from the literature on affordances. We conclude by discussing some of the perspectives the affordance concept and its formal description offer to ergonomics, well beyond the scope of HCI.Le concept d’affordance est l’un des piliers de l’approche écologique de la perception et de l’action. Popularisé à la fin des années quatre-vingt auprès de la communauté du design, il a connu un écho retentissant en ergonomie, principalement dans le domaine de la conception d’interfaces homme-machine (IHM). Nous revenons sur cette notion d’affordance et plus particulièrement sur la caractérisation des affordances, qui repose sur une description de l’environnement dans une unité intrinsèque à l’individu, c’est-à-dire en référence à son corps ou à ses systèmes d’action. Après un bref rappel de quelques principes fondateurs et une définition du concept, nous détaillons le formalisme classiquement employé pour caractériser une affordance, jusqu’à ses évolutions récentes, au travers de quelques résultats majeurs de la littérature sur les affordances. Enfin, nous discutons des perspectives qu’offrent, bien au-delà des IHM, la notion d’affordance et son formalisme en ergonomie

Assistance vibrotactile à l'interception locomotrice de cibles mobiles : étude de faisabilité

Organisateurs : Université de Genève (Germain Poizat, Raphaël Maion, Simon Flandin), Haute Ecole Spécialisée de Suisse Occidentale (Carole Baudin, Bruno Parent, Rafaël Weissbrodt), Centre universitaire de médecine générale et de santé publique (Claire Bauduin), Centre hospitalier universitaire vaudois (Vera Bustamante) Hopitaux Universitaire de Genève (Christine Villaret), Optimance (David Bozier).International audienceCan we assist the locomotor actions of intercepting moving targets in the absence of visionusing a tactile sensory augmentation system? When the target to be intercepted is visible, a person canadjust their walking speed so as to null the rate of change of the angle between their direction and thetarget (maintaining constant bearing angle, CBA). We present technological developments and afeasibility study evaluating the usability of a tactile sensory augmentation device intended to assist thelocomotor actions of interception. Our results suggest that CBA coupling, which is naturally observedwhen vision is available, can be maintained when using our device, after a training period. We discussthe preliminary results of this study in the light of the experimental changes we will introduce into ourscientific program in the future.Peut-on assister les actions locomotrices d'interception de cibles mobiles en absence de vision grâce à un dispositif de suppléance sensorielle tactile ? Lorsque la cible à intercepter est visible, une personne peut ajuster sa vitesse de déplacement de façon à annuler le taux de changement de l'angle entre sa direction de déplacement et celle de la cible (constant bearing angle, CBA). Nous présentons ici les développements technologiques et une étude de faisabilité visant à évaluer l'utilisabilité d'un dispositif de suppléance sensorielle tactile destiné à assister les actions locomotrices d'interception. Nos résultats suggèrent que moyennant une période d'apprentissage, le couplage CBA, naturellement observé lorsque la vision est disponible peut être maintenu lors de l'utilisation de notre dispositif. Nous discutons les résultats préliminaires de cette étude au regard des changements expérimentaux que nous introduirons à l'avenir dans notre programme scientifique

Assistance vibrotactile à l'interception locomotrice de cibles mobiles : étude de faisabilité

International audiencePeut-on assister les actions locomotrices d'interception de cibles mobiles en absence de vision grâce à un dispositif de suppléance sensorielle tactile ? Lorsque la cible à intercepter est visible, une personne peut ajuster sa vitesse de déplacement de façon à annuler le taux de changement de l'angle entre sa direction de déplacement et celle de la cible (constant bearing angle, CBA). Nous présentons ici les développements technologiques et une étude de faisabilité visant à évaluer l'utilisabilité d'un dispositif de suppléance sensorielle tactile destiné à assister les actions locomotrices d'interception. Nos résultats suggèrent que moyennant une période d'apprentissage, le couplage CBA, naturellement observé lorsque la vision est disponible peut être maintenu lors de l'utilisation de notre dispositif. Nous discutons les résultats préliminaires de cette étude au regard des changements expérimentaux que nous introduirons à l'avenir dans notre programme scientifique

Spatiotemporal influences on the recognition of two-dimensional vibrotactile patterns on the abdomen

International audienceSpatial and temporal factors are known to highly influence tactile perception, but their role has been largely unexplored in the case of two-dimensional (2D) pattern recognition. We investigated whether recognition is facilitated by the spatial and/or temporal separation of pattern elements, or by conditions known to favor perceptual integration, such as the ones eliciting apparent movement. 2D vibrotactile patterns were presented to the abdomen of novice participants. In Experiment 1, we manipulated the spatial (inter-tactor distance) and temporal (burst duration and inter-burst interval) parameters applied to the tracing mode (sequential activation of pattern elements). In Experiment 2, we compared display modes differing in their level of temporal overlap in the presentation of pattern elements: the static mode (simultaneous activation of pattern elements), the slit-scan mode (pattern revealed line by line), and the tracing mode. The results of both experiments reveal that (a) recognition performance increases with the isolation of pattern elements in space and/or in time, (b) spatial and temporal factors interact in pattern recognition, and (c) conditions leading to apparent movement tend to be associated with lower recognition accuracy. These results further our understanding of tactile perception and provide guidance for the design of future vibrotactile communication systems