Implication of medical therapists in the introduction of innovative technologies: Specification of S’TIM, a rehabilitation serious game on a touch table case

International audienc

Un Nouveau Dispositif de Rééducation dans l’Univers des Troubles « Dys » : S’TIM, le Serious-Game Persuasif Thérapeutique Conçu pour les Patients Dysexécutifs

Dans l’univers des troubles «dys», les personnes atteintes de troubles dysexécutifs sont en attente de nouvelles solutions pour leur rééducation. A partir d’une analyse approfondie de la littérature, un consortium multidisciplinaire a été créé afin de spécifier et de développer un Serious-Game qui immerge les patients dans un monde virtuel à travers un scénario élaboré et des missions variées. Il s’utilise sur une table tactile robotisée de 48’ facile à appréhender. Ce dispositif a trois enjeux majeurs. Tout d’abord la levée de l’anosognosie ainsi que le passage à une motivation intrinsèque des patients afin qu’ils soient acteurs de leur rééducation. Ensuite, l’atteinte d’une métacognition suffisante pour qu’ils puissent développer des stratégies qui leurs sont propres et qu’ils sélectionnent la plus appropriée dans chaque contexte. Enfin, la facilitation du transfert de ces stratégies dans la vie quotidienne. Des changements dans l’organisation des thérapeutes sont également attendus

Un Nouveau Dispositif de Rééducation dans l’Univers des Troubles « Dys » : S’TIM, le Serious-Game Persuasif Thérapeutique Conçu pour les Patients Dysexécutifs

Dans l’univers des troubles «dys», les personnes atteintes de troubles dysexécutifs sont en attente de nouvelles solutions pour leur rééducation. A partir d’une analyse approfondie de la littérature, un consortium multidisciplinaire a été créé afin de spécifier et de développer un Serious-Game qui immerge les patients dans un monde virtuel à travers un scénario élaboré et des missions variées. Il s’utilise sur une table tactile robotisée de 48’ facile à appréhender. Ce dispositif a trois enjeux majeurs. Tout d’abord la levée de l’anosognosie ainsi que le passage à une motivation intrinsèque des patients afin qu’ils soient acteurs de leur rééducation. Ensuite, l’atteinte d’une métacognition suffisante pour qu’ils puissent développer des stratégies qui leurs sont propres et qu’ils sélectionnent la plus appropriée dans chaque contexte. Enfin, la facilitation du transfert de ces stratégies dans la vie quotidienne. Des changements dans l’organisation des thérapeutes sont également attendus

Implication of medical therapists in the introduction of innovative technologies: Specification of S’TIM, a rehabilitation serious game on a touch table case

International audienc

Un Nouveau Dispositif de Rééducation dans l’Univers des Troubles « Dys » : S’TIM, le Serious-Game Persuasif Thérapeutique Conçu pour les Patients Dysexécutifs

Dans l’univers des troubles «dys», les personnes atteintes de troubles dysexécutifs sont en attente de nouvelles solutions pour leur rééducation. A partir d’une analyse approfondie de la littérature, un consortium multidisciplinaire a été créé afin de spécifier et de développer un Serious-Game qui immerge les patients dans un monde virtuel à travers un scénario élaboré et des missions variées. Il s’utilise sur une table tactile robotisée de 48’ facile à appréhender. Ce dispositif a trois enjeux majeurs. Tout d’abord la levée de l’anosognosie ainsi que le passage à une motivation intrinsèque des patients afin qu’ils soient acteurs de leur rééducation. Ensuite, l’atteinte d’une métacognition suffisante pour qu’ils puissent développer des stratégies qui leurs sont propres et qu’ils sélectionnent la plus appropriée dans chaque contexte. Enfin, la facilitation du transfert de ces stratégies dans la vie quotidienne. Des changements dans l’organisation des thérapeutes sont également attendus

Specification, Use and Impact of the Persuasive Serious Game S'TIM in a Rehabilitation Process for Patients with Dysexecutive Syndrome

International audienceThe aim of this multidisciplinary study is to specify and develop aSerious-Game (SG) to immerge patients with a dysexecutive syn-drome in a virtual word. With an elaborate scenario and variouschallenges, the SG we named S’TIM is used on a robotised andeasy-to-use touch table. The high stakes for patients are firstly tobreak anosognosia and intrinsically motivate patients to implicatethem in their rehabilitation; Secondly to enable them to reach asufficient metacognition level to develop their own strategy andselect the most relevant in each context. Finally, to facilitate thesestrategies transfer in daily-life. Changes in organisations will alsobe observed

Epidemiology and genetic diversity of Anaplasma ovis in goats in Corsica, France

Background Anaplasma ovis is a major cause of small ruminant anaplasmosis, a tick-borne disease mainly affecting small ruminants in tropical and subtropical regions of the world. Due to health and production problems in dairy goat flocks in Corsica, France, and the demonstration of A. ovis infection in some animals, an extensive survey was conducted in the island in spring 2016. The aim of the survey was to determine the prevalence and geographical distribution of A. ovis infections in goats and ticks as well as possible relationships with anaemia and other health indicators. In addition, the genetic diversity of A. ovis was evaluated. Methods Blood and faecal samples were collected in 55 clinically healthy flocks (10 goats per flock) for A. ovis qPCR, haematocrit determination, paratuberculosis ELISA seropositivity and gastrointestinal nematode egg excretion quantification. Ticks were collected, identified and processed for A. ovis DNA detection. Results A high prevalence of A. ovis DNA detection was found at the individual (52.0%) and flock levels (83.6%) with a within-flock prevalence ranging between 0–100%. Rhipicephalus bursa was the only tick species collected on goats (n = 355) and the detection rate of A. ovis DNA in ticks was 20.3%. Anaplasma ovis DNA prevalence was higher in flocks located at an altitude above 168 m, in goats of Corsican/crossbred breed and in goats > 3 years-old. No relationship was found between A. ovis DNA detection at the individual or flock level and haematocrit, paratuberculosis seropositivity or gastrointestinal parasites. Positive A. ovis goat samples were used for amplification of gltA and msp4 genes for species confirmation and strain identification, respectively. Sequence and phylogenetic analysis of these genes confirmed the detection of A. ovis and allowed identification of six different strains of this pathogen (named Corsica 1-6 (COR1-6). While the msp4 sequence of strain COR1 had 100% identity with strains previously reported, COR2 to 6 were found to be novel strains. The strain COR1 was the most represented, corresponding to 94.6% of the msp4 sequences obtained. Conclusions The results showed a relatively high genetic diversity of A. ovis associated with high bacterial prevalence in goats

Epigenomic mapping identifies an enhancer repertoire that regulates cell identity in bladder cancer through distinct transcription factor networks

International audienceAbstract Muscle-invasive bladder cancer (BLCA) is an aggressive disease. Consensus BLCA transcriptomic subtypes have been proposed, with two major Luminal and Basal subgroups, presenting distinct molecular and clinical characteristics. However, how these distinct subtypes are regulated remains unclear. We hypothesized that epigenetic activation of distinct super-enhancers could drive the transcriptional programs of BLCA subtypes. Through integrated RNA-sequencing and epigenomic profiling of histone marks in primary tumours, cancer cell lines, and normal human urothelia, we established the first integrated epigenetic map of BLCA and demonstrated the link between subtype and epigenetic control. We identified the repertoire of activated super-enhancers and highlighted Basal, Luminal and Normal-associated SEs. We revealed super-enhancer-regulated networks of candidate master transcription factors for Luminal and Basal subgroups including FOXA1 and ZBED2, respectively. FOXA1 CRISPR-Cas9 mutation triggered a shift from Luminal to Basal phenotype, confirming its role in Luminal identity regulation and induced ZBED2 overexpression. In parallel, we showed that both FOXA1 and ZBED2 play concordant roles in preventing inflammatory response in cancer cells through STAT2 inhibition. Our study furthers the understanding of epigenetic regulation of muscle-invasive BLCA and identifies a co-regulated network of super-enhancers and associated transcription factors providing potential targets for the treatment of this aggressive disease

PPARγ is a tumor suppressor in basal bladder tumors offering new potential therapeutic opportunities

PPARactivation is a critical event in luminal muscle-invasive bladder cancer (MIBC) tumorigenesis, favoring both tumor cell growth and microenvironment modulation toward tumor immune escape. Conversely, the down-regulation of PPARactivity in basal MIBC suggests tumor suppressive effects in this subgroup. Here, we report genetic, epigenetic and functional evidence to support the tumor suppressor role for PPAR in basal bladder tumors. We identified hemizygous deletions, DNA hyper-methylation and loss-of-function mutations of PPARin basal MIBC, associated with PPAR under-expression and its decreased activity. Re-expression of PPARin basal tumor cells resulted in the activation of PPAR-dependent transcription program that modulated fatty acid metabolism and cell differentiation and decreased cell growth, which could partly rely on EGFR down-regulation. Structure-function studies of two PPAR mutant revealed a destabilization of a region important for coactivator recruitment and should help develop potent molecules to activate PPAR as a therapeutic strategy for basal MIBC. The identification of this subtype-dependent dual role of PPAR in MIBC strengthens the critical role of PPAR in bladder tumorigenesis and reinforces the interest in stratified medicine based on tumor molecular subtyping

FGFR3 Mutational Activation Can Induce Luminal-like Papillary Bladder Tumor Formation and Favors a Male Sex Bias

International audienceBackground: Bladder cancer (BCa) is more common in men and presents differences in molecular subtypes based on sex. Fibroblast growth factor receptor 3 (FGFR3) mutations are enriched in the luminal papillary muscle-invasive BCa (MIBC) and non-MIBC subtypes.Objective: To determine whether FGFR3 mutations initiate BCa and impact BCa male sex bias.Design, setting, and participants: We developed a transgenic mouse model expressing the most frequent FGFR3 mutation, FGFR3-S249C, in urothelial cells. Bladder tumorigenesis was monitored in transgenic mice, with and without carcinogen exposure. Mouse and human BCa transcriptomic data were compared.Intervention: Mutant FGFR3 overexpression in mouse urothelium and siRNA knockdown in cell lines, and N-butyl-N(4-hydroxybutyl)-nitrosamine (BBN) exposure.Outcome measurements and statistical analysis: Impact of transgene dosage on tumor frequency, synergy with BBN treatment, and FGFR3 pathway activation were analyzed. The sex-specific incidence of FGFR3-mutated tumors was evaluated in mice and humans. FGFR3 expression in FGFR3-S249C mouse urothelium and in various human epithelia was measured. Mutant FGFR3 regulation of androgen (AR) and estrogen (ESR1) receptor activity was evaluated, through target gene expression (regulon) and reporter assays.Results and limitations: FGFR3-S249C expression in mice induced low-grade papillary BCa resembling human luminal counterpart at histological, genomic, and transcriptomic levels, and promoted BBN-induced basal BCa formation. Mutant FGFR3 expression levels impacted tumor incidence in mice, and mutant FGFR3–driven human tumors were restricted to epithelia presenting high normal FGFR3 expression levels. BCa male sex bias, also found in our model, was even higher in human FGFR3-mutated tumors compared with wild-type tumors and was associated with higher AR and lower ESR1 regulon activity. Mutant FGFR3 expression inhibited both ESR1 and AR activity in mouse tumors and human cell lines, demonstrating causation only between FGFR3 activation and low ESR1 activity in tumors.Conclusions: Mutant FGFR3 initiates luminal papillary BCa formation and favors BCa male sex bias, potentially through FGFR3-dependent ESR1 downregulation. Patients with premalignant lesions or early-stage BCa could thus potentially benefit from FGFR3 targeting. FGFR3 expression level in epithelia could account for FGFR3-driven carcinoma tissue specificity