The Logarithmic Sobolev Constant of The Lamplighter

We give estimates on the logarithmic Sobolev constant of some finite lamplighter graphs in terms of the spectral gap of the underlying base. Also, we give examples of application

An innovative therapeutic educational program to support older drivers with cognitive disorders: Description of a randomized controlled trial study protocol

Older drivers face the prospect of having to adjust their driving habits because of health problems, which can include neurocognitive disorders. Self-awareness of driving difficulties and the interaction between individual with neurocognitive disorders and natural caregiver seem to be important levers for the implementation of adaptation strategies and for the subsequent voluntary cessation of driving when the cognitive disorders become too severe. This study aims to evaluate an educational program for patient/natural caregiver dyads who wish to implement self-regulation strategies in driving activity, and to improve self-awareness of driving ability. The ACCOMPAGNE program is based on seven group workshops, which target the dyad. The workshops deal with the impact of cognitive, sensory and iatrogenic disorders on driving. They tackle questions about responsibility, and about autonomy and social life. They also provide alternative solutions aimed at maintaining outward-looking activities even if driving is reduced or stopped. A randomized controlled trial is planned to evaluate the effectiveness of the program 2 months and 6 months after inclusion, and to compare this to the effectiveness of conventional approaches. The main outcome of this trial (i.e., the implementation of self-regulated driving strategies), will be measured based on scores on the “Current Self-Regulatory Practices” subscale of the Driver Perception and Practices Questionnaire. The Driving Habits Questionnaire will be used to measure secondary outcomes (indicators of driving changes; indicators of changes in mood, quality of life and caregiver burden; and self-awareness of driving abilities). Indicators will be collected for both patients and natural caregivers. This cognitive, social and psychological program should allow older individuals with cognitive disorders to drive more safely, and help to maintain the quality of life and mood of both patient and natural caregiver despite driving limitations. The patient's care path would be optimized, as he/she would become an actor in the process of giving up driving, which will, most certainly, be needed at some point in the progress of neurocognitive disorders. This process ranges from becoming aware of driving difficulties, to implementing self-regulation strategies, through to complete cessation of driving when necessary.Clinical trial registration numberNCT04493957

Hepatic Stem-like Phenotype and Interplay of Wnt/β-Catenin and Myc Signaling in Aggressive Childhood Liver Cancer

SummaryHepatoblastoma, the most common pediatric liver cancer, is tightly linked to excessive Wnt/β-catenin signaling. Here, we used microarray analysis to identify two tumor subclasses resembling distinct phases of liver development and a discriminating 16-gene signature. β-catenin activated different transcriptional programs in the two tumor types, with distinctive expression of hepatic stem/progenitor markers in immature tumors. This highly proliferating subclass was typified by gains of chromosomes 8q and 2p and upregulated Myc signaling. Myc-induced hepatoblastoma-like tumors in mice strikingly resembled the human immature subtype, and Myc downregulation in hepatoblastoma cells impaired tumorigenesis in vivo. Remarkably, the 16-gene signature discriminated invasive and metastatic hepatoblastomas and predicted prognosis with high accuracy

Etude pilote sur l'efficacité du programme d'accompagnement des patients avec trouble cognitif dans le maintien ou le processus d'arrêt de la conduite automobile en Gériatrie et Neurologie (ACCOMPAGNE): résultats préliminaires

38ème Congrès annuel des hôpitaux de jour gériatriques, COLMAR, FRANCE, 07-/06/2018 - 08/06/2018Les gériatres et neurologues sont régulièrement confrontés à la question du maintien ou de l'arrêt de la conduite automobile chez des patients présentant un Trouble Neuro- Cognitif (TNC). Des stratégies de compensation, apprises au cours d'ateliers de prévention, peuvent être utilisées pour réduire le risque d'accident en cas de TNC et maintenir transitoirement la conduite automobile avant son arrêt définitif. Le projet ACCOMPAGNE est un programme de prévention de sécurité routière. Il est composé de différents ateliers : atelier de présentation, atelier cognitif, atelier représentation psychologiques, atelier législation, atelier foire aux questions, atelier solutions. Ce programme est destiné aux patients et aux aidants

Oral Administration of Lactobacillus helveticus LA401 and Lactobacillus gasseri LA806 Combination Attenuates Oesophageal and Gastrointestinal Candidiasis and Consequent Gut Inflammation in Mice

International audienceCandida albicans is an opportunistic pathogen that causes mucosal gastrointestinal (GI) candidiasis tightly associated with gut inflammatory status. The emergence of drug resistance, the side effects of currently available antifungals and the high frequency of recurrent candidiasis indicate that new and improved therapeutics are needed. Probiotics have been suggested as a useful alternative for the management of candidiasis. We demonstrated that oral administration of Lactobacillus gasseri LA806 alone or combined with Lactobacillus helveticus LA401 in Candida albicans-infected mice decrease the Candida colonization of the oesophageal and GI tract, highlighting a protective role for these strains in C. albicans colonization. Interestingly, the probiotic combination significantly modulates the composition of gut microbiota towards a protective profile and consequently dampens inflammatory and oxidative status in the colon. Moreover, we showed that L. helveticus LA401 and/or L. gasseri LA806 orient macrophages towards a fungicidal phenotype characterized by a C-type lectin receptors signature composed of Dectin-1 and Mannose receptor. Our findings suggest that the use of the LA401 and LA806 combination might be a promising strategy to manage GI candidiasis and the inflammation it causes by inducing the intrinsic antifungal activities of macrophages. Thus, the probiotic combination is a good candidate for managing GI candidiasis by inducing fungicidal functions in macrophages while preserving the GI integrity by modulating the microbiota and inflammation

S36 - Implication des récepteurs Dectine-1 et Mannose des macrophages dans les maladies inflammatoires chroniques de l’intestin

International audienceIntroductionLes macrophages (Mφ) intestinaux jouent un rôle important dans l’homéostasie du tube digestif. Ils sont fortement recrutés au niveau de la muqueuse intestinale de patients atteints de Maladies Inflammatoires Chroniques de l’Intestin (MICI) telles que la rectocolite hémorragique (RCH) et la maladie de Crohn (MC). Ces cellules présentent une large plasticité phénotypique et fonctionnelle en fonction de leur microenvironnement. Ainsi, les Mφ activés classiquement dits M1 ont un rôle pro-inflammatoire alors que les Mφ alternativement activés dit M2 peuvent être anti ou pro-inflammatoires, anti ou pro-tumoraux et réparateurs selon le microenvironnement. Ainsi, il apparait important de comprendre comment les Mφ jouent un rôle dans le développement des MICI. De plus, ces différents sous-types de Mφ sont caractérisés par l’expression spécifique de marqueurs, dont notamment des récepteurs de surface tels que les Pattern Recognition Receptors, qui ont été décrits comme étant des facteurs impliqués dans la pathogenèse des MICI. Le rôle de deux récepteurs appartenant à la famille des récepteurs lectine de type C (CLRs), Dectine-1 et le récepteur mannose (RM), est controversé dans des modèles murins et n’est pas décrit chez l’Homme. Dans ce contexte, l’objectif de ce projet a été de définir le rôle de la différenciation des Mφ et l’implication de Dectine-1 et du RM dans le développement des MICI

nSMase2 (Type 2-Neutral Sphingomyelinase) Deficiency or Inhibition by GW4869 Reduces Inflammation and Atherosclerosis in Apoe −/− Mice

International audienceObjective: Atherosclerosis is a chronic multifactorial and inflammatory disease of large and medium arteries and the leading cause of cardiovascular diseases worldwide. The aim of this study was to investigate whether and how the nSMase2 (type 2-neutral sphingomyelinase), a key enzyme of sphingolipid metabolism, may contribute to the development of atherosclerotic lesions.Approach and results: The role of nSMase2 in atherosclerosis was investigated in Apoe-/-;Smpd3fro/fro mice, mutant for nSMase2, and in Apoe-/-;Smpd3+/+ mice intraperitoneally injected with GW4869, a pharmacological nSMase2 inhibitor. The defect or inhibition of nSMase2 resulted in a reduction of atherosclerotic lesions and a decrease in macrophage infiltration and lipid deposition, although cholesterolemia remained unchanged. nSMase2 inhibition decreased the inflammatory response of murine endothelial cells to oxLDL (oxidized low-density lipoprotein), as assessed by the significant reduction of MCP-1 (monocyte chemoattractant protein 1), ICAM-1 (intercellular adhesion molecule-1), and VCAM-1 (vascular cell adhesion molecule-1) mRNA expressions and macrophage recruitment. Likewise, in RAW264.7 or in macrophages isolated from Apoe-/-/Smpd3fro/fro or Apoe-/-/Smpd3+/+ mice stimulated by lipopolysaccharides, nSMase2 inhibition resulted in a decrease in the expression of inflammatory molecules. Mechanistically, the anti-inflammatory response resulting from nSMase2 inhibition involves Nrf2 (nuclear factor [erythroid-derived 2]-like 2 or NF-E2-related factor-2) activation in both endothelial cells and macrophages, as assessed by the lack of protective effect of GW4869 in endothelial cells silenced for Nrf2 by small interfering RNAs, and in lipopolysaccharide-stimulated macrophages issued from Nrf2-KO mice.Conclusions: The genetic deficiency or inhibition of nSMase2 strongly decreases the development of atherosclerotic lesions in Apoe-/- mice, by reducing inflammatory responses through a mechanism involving the Nrf2 pathway. Inhibitors of nSMase2 may, therefore, constitute a novel approach to slow down atherosclerosis progression