ATHLETIQUE: interest of an adapted physical activity program in patients with juvenile idiopathic arthritis: a feasibility and preliminary effectiveness study

BackgroundJuvenile Idiopathic Arthritis (JIA) is associated with joint inflammation, pain and limited joint mobility, impacting the practice of physical activities. Adapted Physical Activities (APA) are an increasingly used method of rehabilitation, but additional studies are needed to define the nature of the most appropriate physical activity for patients with JIA. The “ATHLETIQUE” project aims to evaluate the impact of a program integrating APA sessions with use of a pedometer watch, on disease activity in patients with JIA.MethodsThis study will be a randomized, multicenter, open-label, controlled clinical trial with 2 parallel arms. The patients included in this study will be children and adolescents with JIA, aged 6 to 17 years. The experimental group (30 patients) will participate in an APA program for 3 months and will use a pedometer watch for one year. We will evaluate and compare the change in disease activity measurements (primary objective), fatigue, pain, quality of life, level of physical activity, functional capacities, and muscle strength (secondary objectives) after 14, 26 and 50 weeks. The control group (10 patients) will undergo the same evaluations as the experimental group but will not participate in the APA program and will not wear the pedometer watch.Expected resultsThe APA program may help to promote an active lifestyle with regular physical activity, preventing comorbidities and motor disability. Promising results on disease activity, functional capacities and quality of life would enable us to envisage a larger research program with a view to optimizing and assessing APA for children with JIA.DiscussionThis study will be conducted in the short and medium-term, with one-year follow-up, including 3 months of APA sessions for the experimental group. The sessions proposed during the APA program will mainly be aerobic and bodyweight exercises. Furthermore, in contrast to previous studies on this topic, our study will integrate a novel element, namely the use of a pedometer watch. This watch will help to implement strategies to address motivation. This study aims to improve physical and mental well-being, provide a basis for the design of a larger study, and propose recommendations adapted to children with JIA.Trial registrationRegistered with ClinicalTrials.gov under the number NCT0557242

Trust and Trustworthiness in a Sequential Bargaining Game

We use a two-person extensive form bargaining game to examine individuals? trusting and reciprocal behavior and how those relate to their scores on a trust survey. In keeping with prior research, we find that the ?self-interested? outcome is rejected by a majority of individuals. People who score high on the trust survey are both trusting and are also trustworthy, in that they reciprocate others? trust. But, people with low trust scores often exhibit trust but are not trustworthy. These ?inconsistent trusters? seem to be interested in exploiting the trust and trustworthiness of others in increasing their own payoff

ATHLETIQUE: interest of an adapted physical activity program in patients with juvenile idiopathic arthritis: a feasibility and preliminary effectiveness study

Background Juvenile Idiopathic Arthritis (JIA) is associated with joint inflammation, pain and limited joint mobility, impacting the practice of physical activities. Adapted Physical Activities (APA) are an increasingly used method of rehabilitation, but additional studies are needed to define the nature of the most appropriate physical activity for patients with JIA. The “ATHLETIQUE” project aims to evaluate the impact of a program integrating APA sessions with use of a pedometer watch, on disease activity in patients with JIA. Methods This study will be a randomized, multicenter, open-label, controlled clinical trial with 2 parallel arms. The patients included in this study will be children and adolescents with JIA, aged 6 to 17 years. The experimental group (30 patients) will participate in an APA program for 3 months and will use a pedometer watch for one year. We will evaluate and compare the change in disease activity measurements (primary objective), fatigue, pain, quality of life, level of physical activity, functional capacities, and muscle strength (secondary objectives) after 14, 26 and 50 weeks. The control group (10 patients) will undergo the same evaluations as the experimental group but will not participate in the APA program and will not wear the pedometer watch. Expected results The APA program may help to promote an active lifestyle with regular physical activity, preventing comorbidities and motor disability. Promising results on disease activity, functional capacities and quality of life would enable us to envisage a larger research program with a view to optimizing and assessing APA for children with JIA. Discussion This study will be conducted in the short and medium-term, with one-year follow-up, including 3 months of APA sessions for the experimental group. The sessions proposed during the APA program will mainly be aerobic and bodyweight exercises. Furthermore, in contrast to previous studies on this topic, our study will integrate a novel element, namely the use of a pedometer watch. This watch will help to implement strategies to address motivation. This study aims to improve physical and mental well-being, provide a basis for the design of a larger study, and propose recommendations adapted to children with JIA. Trial registration Registered with ClinicalTrials.gov under the number NCT0557242

Optogenetically controlled inflammasome activation demonstrates two phases of cell swelling during pyroptosis

International audienceInflammasomes are multiprotein platforms that control caspase-1 activation, which process the inactive precursor forms of the inflammatory cytokines IL-1β and IL-18, leading to an inflammatory type of programmed cell death called pyroptosis. Studying inflammasome-driven processes, such as pyroptosis-induced cell swelling, under controlled conditions remains challenging because the signals that activate pyroptosis also stimulate other signaling pathways. We designed an optogenetic approach using a photo-oligomerizable inflammasome core adapter protein, apoptosis-associated speck–like containing a caspase recruitment domain (ASC), to temporally and quantitatively manipulate inflammasome activation. We demonstrated that inducing the light-sensitive oligomerization of ASC was sufficient to recapitulate the classical features of inflammasomes within minutes. This system showed that there were two phases of cell swelling during pyroptosis. This approach offers avenues for biophysical investigations into the intricate nature of cellular volume control and plasma membrane rupture during cell death

Le biais d'auto-évaluation de compétence scolaire Risque ou opportunité pour la réussite des élèves ?

Beliefs about competence can be a limitation for some students and an asset for others in acquiring the basic knowledge that is essential for their academic and social future. The SchoolBias program focused on students' judgments of their academic competence, in particular the difference between their actual potential and the way they evaluate their competence. This difference reflects the self- evaluation bias of academic competence. This bias can be positive (overestimation of competence) or negative (underestimation of competence). The program consisted of two distinct levels of analysis. At an intra-individual level (student), the aim was to gather information about the dynamics of positive and negative self-evaluation biases, and their effects on basic learning at different levels of schooling. At an inter-individual level (teacher judgment), we investigated how teachers judged students who had either positively or negatively biased assessments of their academic competence. Lastly, we extended the study of the impact of these perceptions to other cultures.Twenty-two studies were conducted in ordinary classroom situations. They involved more than 5000 students of various grades in elementary and junior high schools, and more than 200 teachers. They combined longitudinal (developmental trajectory analyses) and cross-sectional approaches as well as experimental and correlational designs. A method of structured cognitive interviews adapted for children was also used to analyze the thinking patterns of positively and negatively biased students. The study of students' competence beliefs in different cultures (China, France, Canada-Quebec, and Russia) also required a specific methodology for cross-cultural validation of the scales and the material used.First of all, the results of the trajectory analyses showed that as early as the middle of elementary school, students can present a self-evaluation bias in one fundamental subject, without necessarily presenting a bias in other subjects. These results therefore underline the importance of not only considering the self-evaluation bias of academic competence at a general or global level, but also at a specific one. They also indicate that overestimating one's academic competence is beneficial to the student, whereas underestimating it is detrimental to their academic adjustment throughout their schooling. At the intra-individual level, students who overestimate themselves are more motivated, self-regulate well, are more actively involved in their learning, and perform better than their negativelybiased peers. At the inter-individual level, since they appear to be more in line with schoolexpectations, teachers judge them better than others. This pattern is also found in other cultural systems. Finally, we observed that teachers lack the ability to correctly identify positively and negatively biased students.In conclusion, the results of this research program should encourage education professionals to better understand the complexity of student self-evaluations of competence, and how they impact the learning process and teacher judgment. It also opens up avenues of reflection for better handling of students with unrealistic negative self-perceptions.Les croyances de compétence peuvent être chez certains élèves un frein et chez d’autres un atout pour l’acquisition des apprentissages fondamentaux indispensables à leur avenir scolaire et social. Le programme SchoolBias s’est focalisé sur les jugements que les élèves ont de leur propre compétence scolaire, en particulier sur la différence entre leur potentiel réel et l’évaluation qu’il font de leur compétence. Cette différence rend compte du biais d’auto-évaluation de compétence scolaire. Ce biais peut être positif (surestimation de sa compétence scolaire) ou négatif (sous-estimation). Le programme comprend deux niveaux d'analyse distincts. A un niveau intra-individuel (élève), il s’agissait de recueillir des informations sur la dynamique des biais d’auto-évaluation de compétence scolaire(positif et négatif) et leurs effets sur les apprentissages fondamentaux à différents niveaux de la scolarité. A un niveau inter-individuel (jugement de l'enseignant), nous avons étudié comment les enseignants jugeaient les élèves ayant une évaluation biaisée, positive ou négative, de leur compétence scolaire. Enfin, nous avons étendu l’examen de l’impact de ces croyances à d’autres cultures.Vingt-deux études, toutes conduites en situation ordinaire de classe, ont été réalisées. Ces études ont impliqué plus de 5000 élèves de niveaux scolaires variés (de l’école élémentaire au collège) et plus de 200 enseignants. Elles ont combiné aussi bien des approches longitudinales (analyses de trajectoires développementales) et transversales que des devis expérimentaux et corrélationnels. Une méthode d’entretiens cognitifs structurés adaptée aux enfants a aussi été utilisé afin d’analyser les schémas de pensée des élèves biaisés positivement et négativement. L’examen des croyances de compétence desélèves dans différentes cultures (Chine, France, Québec et Russie) a également nécessité de mobiliser une méthodologie de validation transculturelle des échelles et plus largement du matériel utilisé. Les résultats des analyses de trajectoires montrent d’abord clairement que, dès le milieu d’école élémentaire, les élèves peuvent présenter un biais d’auto-évaluation dans une matière fondamentale, sans fatalement le présenter dans d’autres matières. Ils soulignent donc l’importance de considérer, non seulement, le biais d’auto-évaluation de compétence scolaire à un niveau global mais aussi spécifique. Ils indiquent ensuite que, toutes choses égales par ailleurs, surévaluer sa compétence scolaire est bénéfique à l’élève alors que la sous-estimer est délétère pour son ajustement scolaire, et ce tout au long de la scolarité. Au niveau intra-individuel, les élèves qui se surestiment sont plus motivés, s’auto-régulent bien, sont plus actifs dans leurs apprentissages et réussissent mieux que leurspairs biaisés négativement. Au niveau inter-individuel, apparaissant plus en conformité avec les attentes du système scolaire, les enseignants leur accordent une plus-value et les jugent mieux que les autres. Ce pattern se retrouve aussi dans d’autres systèmes culturels. Enfin, on observe un manque de discernement des enseignants quant aux élèves biaisés positivement et négativement qu’ils ont du mal à identifier correctement.En conclusion, ce travail invite les acteurs du milieu éducatif à mieux saisir la complexité des évaluations de soi des élèves et leur implication dans les apprentissages des élèves et le jugement des enseignants. Il ouvre aussi des pistes de réflexions pour améliorer la prise en charge des élèves ayant des perceptions irréalistes négatives d’eux-mêmes

Le biais d'auto-évaluation de compétence scolaire Risque ou opportunité pour la réussite des élèves ?

Beliefs about competence can be a limitation for some students and an asset for others in acquiring the basic knowledge that is essential for their academic and social future. The SchoolBias program focused on students' judgments of their academic competence, in particular the difference between their actual potential and the way they evaluate their competence. This difference reflects the self- evaluation bias of academic competence. This bias can be positive (overestimation of competence) or negative (underestimation of competence). The program consisted of two distinct levels of analysis. At an intra-individual level (student), the aim was to gather information about the dynamics of positive and negative self-evaluation biases, and their effects on basic learning at different levels of schooling. At an inter-individual level (teacher judgment), we investigated how teachers judged students who had either positively or negatively biased assessments of their academic competence. Lastly, we extended the study of the impact of these perceptions to other cultures.Twenty-two studies were conducted in ordinary classroom situations. They involved more than 5000 students of various grades in elementary and junior high schools, and more than 200 teachers. They combined longitudinal (developmental trajectory analyses) and cross-sectional approaches as well as experimental and correlational designs. A method of structured cognitive interviews adapted for children was also used to analyze the thinking patterns of positively and negatively biased students. The study of students' competence beliefs in different cultures (China, France, Canada-Quebec, and Russia) also required a specific methodology for cross-cultural validation of the scales and the material used.First of all, the results of the trajectory analyses showed that as early as the middle of elementary school, students can present a self-evaluation bias in one fundamental subject, without necessarily presenting a bias in other subjects. These results therefore underline the importance of not only considering the self-evaluation bias of academic competence at a general or global level, but also at a specific one. They also indicate that overestimating one's academic competence is beneficial to the student, whereas underestimating it is detrimental to their academic adjustment throughout their schooling. At the intra-individual level, students who overestimate themselves are more motivated, self-regulate well, are more actively involved in their learning, and perform better than their negativelybiased peers. At the inter-individual level, since they appear to be more in line with schoolexpectations, teachers judge them better than others. This pattern is also found in other cultural systems. Finally, we observed that teachers lack the ability to correctly identify positively and negatively biased students.In conclusion, the results of this research program should encourage education professionals to better understand the complexity of student self-evaluations of competence, and how they impact the learning process and teacher judgment. It also opens up avenues of reflection for better handling of students with unrealistic negative self-perceptions.Les croyances de compétence peuvent être chez certains élèves un frein et chez d’autres un atout pour l’acquisition des apprentissages fondamentaux indispensables à leur avenir scolaire et social. Le programme SchoolBias s’est focalisé sur les jugements que les élèves ont de leur propre compétence scolaire, en particulier sur la différence entre leur potentiel réel et l’évaluation qu’il font de leur compétence. Cette différence rend compte du biais d’auto-évaluation de compétence scolaire. Ce biais peut être positif (surestimation de sa compétence scolaire) ou négatif (sous-estimation). Le programme comprend deux niveaux d'analyse distincts. A un niveau intra-individuel (élève), il s’agissait de recueillir des informations sur la dynamique des biais d’auto-évaluation de compétence scolaire(positif et négatif) et leurs effets sur les apprentissages fondamentaux à différents niveaux de la scolarité. A un niveau inter-individuel (jugement de l'enseignant), nous avons étudié comment les enseignants jugeaient les élèves ayant une évaluation biaisée, positive ou négative, de leur compétence scolaire. Enfin, nous avons étendu l’examen de l’impact de ces croyances à d’autres cultures.Vingt-deux études, toutes conduites en situation ordinaire de classe, ont été réalisées. Ces études ont impliqué plus de 5000 élèves de niveaux scolaires variés (de l’école élémentaire au collège) et plus de 200 enseignants. Elles ont combiné aussi bien des approches longitudinales (analyses de trajectoires développementales) et transversales que des devis expérimentaux et corrélationnels. Une méthode d’entretiens cognitifs structurés adaptée aux enfants a aussi été utilisé afin d’analyser les schémas de pensée des élèves biaisés positivement et négativement. L’examen des croyances de compétence desélèves dans différentes cultures (Chine, France, Québec et Russie) a également nécessité de mobiliser une méthodologie de validation transculturelle des échelles et plus largement du matériel utilisé. Les résultats des analyses de trajectoires montrent d’abord clairement que, dès le milieu d’école élémentaire, les élèves peuvent présenter un biais d’auto-évaluation dans une matière fondamentale, sans fatalement le présenter dans d’autres matières. Ils soulignent donc l’importance de considérer, non seulement, le biais d’auto-évaluation de compétence scolaire à un niveau global mais aussi spécifique. Ils indiquent ensuite que, toutes choses égales par ailleurs, surévaluer sa compétence scolaire est bénéfique à l’élève alors que la sous-estimer est délétère pour son ajustement scolaire, et ce tout au long de la scolarité. Au niveau intra-individuel, les élèves qui se surestiment sont plus motivés, s’auto-régulent bien, sont plus actifs dans leurs apprentissages et réussissent mieux que leurspairs biaisés négativement. Au niveau inter-individuel, apparaissant plus en conformité avec les attentes du système scolaire, les enseignants leur accordent une plus-value et les jugent mieux que les autres. Ce pattern se retrouve aussi dans d’autres systèmes culturels. Enfin, on observe un manque de discernement des enseignants quant aux élèves biaisés positivement et négativement qu’ils ont du mal à identifier correctement.En conclusion, ce travail invite les acteurs du milieu éducatif à mieux saisir la complexité des évaluations de soi des élèves et leur implication dans les apprentissages des élèves et le jugement des enseignants. Il ouvre aussi des pistes de réflexions pour améliorer la prise en charge des élèves ayant des perceptions irréalistes négatives d’eux-mêmes

NLRP3 controls ATM activation in response to DNA damage

The DNA damage response (DDR) is essential to preserve genomic integrity and acts as a barrier to cancer. The ATM pathway orchestrates the cellular response to DNA double strand breaks (DSBs), and its attenuation is frequent during tumorigenesis. Here, we show that NLRP3, a Pattern Recognition Receptor known for its role in the inflammasome complex formation, interacts with the ATM kinase to control the early phase of DDR, independently of its inflammasome activity. NLRP3 down-regulation in human bronchial epithelial cells impairs ATM pathway activation as shown by an altered ATM substrate phosphorylation profile, and due to impaired p53 activation, confers resistance to acute genomic stress. Moreover, we found that NLRP3 is down-regulated in Non-Small Cell Lung Cancer (NSCLC) tissues and NLRP3 expression is correlated with patient overall survival. NLRP3 re-expression in NSCLC cells restores appropriate ATM signaling. Our findings identify a non-immune function for NLRP3 in genome integrity surveillance and strengthen the concept of a functional link between innate immunity and DNA damage sensing pathways

Inflammasome-independent NLRP3 function enforces ATM activity in response to genotoxic stress

NLRP3 is a pattern recognition receptor with a well-documented role in inducing inflammasome assembly in response to cellular stress. Deregulation of its activity leads to many inflammatory disorders including gouty arthritis, Alzheimer disease, and cancer. Whereas its role in the context of cancer has been mostly explored in the immune compartment, whether NLRP3 exerts functions unrelated to immunity in cancer development remains unexplored. Here, we demonstrate that NLRP3 interacts with the ATM kinase to control the activation of the DNA damage response, independently of its inflammasome activity. NLRP3 down-regulation in both broncho- and mammary human epithelial cells significantly impairs ATM pathway activation, leading to lower p53 activation, and provides cells with the ability to resist apoptosis induced by acute genotoxic stress. Interestingly, NLRP3 expression is down-regulated in non-small cell lung cancers and breast cancers, and its expression positively correlates with patient overall survival. Our findings identify a novel non-immune function for NLRP3 in maintaining genome integrity and strengthen the concept of a functional link between innate immunity and DNA damage sensing pathways to maintain cell integrity