Differential impact of genetic deletion of TIGIT or PD-1 on melanoma-specific T-lymphocytes.

Immune checkpoint (IC) blockade and adoptive transfer of tumor-specific T-cells (ACT) are two major strategies to treat metastatic melanoma. Their combination can potentiate T-cell activation in the suppressive tumor microenvironment, but the autoimmune adverse effects associated with systemic injection of IC blockers persist with this strategy. ACT of tumor-reactive T-cells defective for IC expression would overcome this issue.

Micromolding-based encapsulation of mesenchymal stromal cells in alginate for intraarticular injection in osteoarthritis.

Osteoarthritis (OA) is an inflammatory joint disease that affects cartilage, subchondral bone, and joint tissues. Undifferentiated Mesenchymal Stromal Cells are a promising therapeutic option for OA due to their ability to release anti-inflammatory, immuno-modulatory, and pro-regenerative factors. They can be embedded in hydrogels to prevent their tissue engraftment and subsequent differentiation.

Standardized and axially vascularized calcium phosphate-based implants for segmental mandibular defects: A promising proof of concept.

The reconstruction of massive segmental mandibular bone defects (SMDs) remains challenging even today; the current gold standard in human clinics being vascularized bone transplantation (VBT). As alternative to this onerous approach, bone tissue engineering strategies have been widely investigated. However, they displayed limited clinical success, particularly in failing to address the essential problem of quick vascularization of the implant.

Development and characterization of a humanized mouse model of osteoarthritis.

Objective: In light of the role of immune cells in OA pathogenesis, the development of sophisticated animal models closely mimicking the immune dysregulation during the disease development and progression could be instrumental for the preclinical evaluation of novel treatments. Among these models, immunologically humanized mice may represent a relevant system, particularly for testing immune-interacting DMOADs or cell therapies before their transfer to the clinic. Our objective, therefore, was to develop an experimental model of OA by destabilization of the medial meniscus (DMM) in humanized mice.

A partially demineralized allogeneic bone graft: in vitro osteogenic potential and preclinical evaluation in two different intramembranous bone healing models.

In skeletal surgical procedures, bone regeneration in irregular and hard-to-reach areas may present clinical challenges. In order to overcome the limitations of traditional autologous bone grafts and bone substitutes, an extrudable and easy-to-handle innovative partially demineralized allogenic bone graft in the form of a paste has been developed. In this study, the regenerative potential of this paste was assessed and compared to its clinically used precursor form allogenic bone particles.

Tailored Three-Dimensionally Printed Triply Periodic Calcium Phosphate Implants: A Preclinical Study for Craniofacial Bone Repair.

Finding alternative strategies for the regeneration of craniofacial bone defects (CSD), such as combining a synthetic ephemeral calcium phosphate (CaP) implant and/or active substances and cells, would contribute to solving this reconstructive roadblock. However, CaP's architectural features (i.e.

Combined electrochemical/chemical methods for the synthesis and the molecular diversifying of isoindolinone-based heterocyclic scaffolds.

By means of C-H acids activation on Pt-cathode, an electrochemically initiated strategy aimed to developing a diversity-oriented synthesis based on the isoindolinone nucleus has been established. Conveniently, the achievement of a small library of new heterocycle-fused isoindolinone compounds with potential interest for drug design was carried out by using tandem reactions and one-pot sequential processes.

Determining a clinically relevant strategy for bone tissue engineering: an "all-in-one" study in nude mice.

Purpose: Autologous bone grafting (BG) remains the standard reconstruction strategy for large craniofacial defects. Calcium phosphate (CaP) biomaterials, such as biphasic calcium phosphate (BCP), do not yield consistent results when used alone and must then be combined with cells through bone tissue engineering (BTE). In this context, total bone marrow (TBM) and bone marrow-derived mesenchymal stem cells (MSC) are the primary sources of cellular material used with biomaterials.

Chiral sulfoxides in the enantioselective allylation of aldehydes with allyltrichlorosilane: a kinetic study.

The mechanism of the allylation of aldehydes in the presence of allyltrichlorosilane employing the commercially available (R)-methyl p-tolyl sulfoxide as a Lewis base has been investigated. The combination of kinetic measurements, conductivity analysis and quantum chemical calculations indicates that the reaction proceeds through a dissociative pathway in which an octahedral cationic complex with two sulfoxides is involved. The lack of turnover is ascribed to the formation of neutral sulfurane derivatives.

Socio-demographic and lifestyle factors associated with overweight in a representative sample of 11-15 year olds in France: results from the WHO-Collaborative Health Behaviour in School-aged Children (HBSC) cross-sectional study.

Background: The prevalence of overweight in children and adolescents is high and overweight is associated with poor health outcomes over short- and long-term. Lifestyle factors can interact to influence overweight. Comprehensive studies linking overweight concomitantly with several demographic and potentially-modifiable lifestyle factors and health-risk behaviours are limited in adolescents--an age-group characterized by changes in lifestyle behaviours and high prevalence of overweight.

Improving attitudes towards children with disabilities in a school context: a cluster randomized intervention study.

Aim: although inclusive education of disabled children is now an accepted practice, it is often challenged by negative peer attitudes. We undertook an interventional study aimed at improving students' attitudes towards their disabled peers.

Method: the participants were students from the 7th grade of twelve paired schools (1509 students from 62 classes; age 12-13y), randomly allocated to an intervention group (205 males, 285 females) or a control group (132 males, 165 females).

Determinants of students' attitudes towards peers with disabilities.

Aim: To explore factors associated with students' attitudes towards their peers with disabilities.

Method: All 7th grade students (aged 12-13y) from 12 schools in the Toulouse area were invited to participate (n=1509). Attitudes were measured using the Chedoke-McMaster Attitudes Towards Children with Handicaps (CATCH) questionnaire (affective, behavioural, cognitive, and total scores).

A multilevel analysis of condom use among adolescents in the European Union.

Objectives: This study examined which individual and national factors affect condom use among adolescents.

Study Design: Multilevel analysis.

Methods: This study reviewed the data on bullying, alcohol use and condom use provided by 18 European countries and subnational entities in the Health Behaviour in School-Aged Children survey.

Measuring children's attitudes towards peers with disabilities: a review of instruments.

This study aimed to identify instruments for measuring children's attitudes towards their peers with disabilities that are suitable for use in epidemiological studies and to report on their psychometric properties. A literature review was conducted to identify instruments measuring at least one of the three components of children's attitudes (affective, behavioural, or cognitive measures) towards peers with disabilities and which are intended for self-completion by children. Criteria used to appraise these instruments were appropriateness, acceptability, validity, reliability, internal consistency, and test-retest reliability.

[Factors associated with early sexual initiation in girls: French data from the international survey Health Behaviour in School-aged Children (HBSC)/WHO].

Objective: Inspite of unquestionable progress, the protection of girls at first sexual intercourse is still not perfect. The main risks are well known (sexually transmitted infections [STIs], unwanted pregnancies, psychological consequences) and seem to be higher in the case of early sexual initiation. The aim of this epidemiological study is to analyse factors associated with early heterosexual intercourse (age 15 or before) among girls, considered as risk factors for pregnancies and STIs.

Contraceptive use by 15-year-old students at their last sexual intercourse: results from 24 countries.

Objectives: To identify and report cross-national patterns in contraceptive use among sexually active adolescents.

Design: A cross-national cross-sectional survey.

Setting: Data were collected in 2002 by self-report questionnaire from students in school classrooms.

[Schooling of young people with cancer].

The schooling of young people with cancer poses various problems, similar to those experienced by disabled or chronically ill children. Published data on this subject in the medical literature comes mainly from studies carried out in the USA and the UK. Cancer and its treatment can cause both direct (learning difficulties or other disabilities.

Expression of tryptophan hydroxylase in developing mouse taste papillae.

Gustatory papillae and associated taste buds receive and process chemical information from the environment. In mammals, their development takes place during the late phase of embryogenesis. However, the cellular factors that regulate the differentiation of taste papillae remain largely unknown.

Effects of a large-scale industrial disaster on rates of symptoms consistent with posttraumatic stress disorders among schoolchildren in toulouse.

Background: Posttraumatic stress disorder (PTSD) has been studied largely among adults and in the context of intentional, collective experiences such as war and terrorism. Far less is known about PTSD among adolescents and resulting from massive industrial accidents. Such an accident in Toulouse, France, 10 days after the World Trade Center disaster, provided an opportunity to examine its effects among adolescents already sensitized by media coverage of the World Trade Center disaster.

The role of TNF-related activation-induced cytokine-receptor activating NF-kappa B interaction in acute allograft rejection and CD40L-independent chronic allograft rejection.

We analyzed the role of TNF-related activation-induced cytokine (TRANCE), a member of the TNF family expressed on activated T cells that shares functional properties with CD40L, and its receptor-activating NF-kappaB (RANK) which is mostly expressed on mature dendritic cells, during allogenic responses in vivo using a rodent heart allograft model. TRANCE mRNA was strongly up-regulated in acutely rejected allografts on days 4 and 5 posttransplantation whereas RANK was detected as early as day 1 but did not show further up-regulation during the first week. Immunofluoresence analyses of heart allografts showed that 80 and 100% of TRANCE and RANK-expressing cells were T cells and APCs, respectively.

Inhibitors of vacuolar H+-ATPase impair the preferential accumulation of daunomycin in lysosomes and reverse the resistance to anthracyclines in drug-resistant renal epithelial cells.

It has been suggested that the inappropriate sequestration of weak-base chemotherapeutic drugs in acidic vesicles by multidrug-resistance (MDR) cells contributes to the mechanisms of drug resistance. The function of the acidic lysosomes can be altered in MDR cells, and so we investigated the effects of lysosomotropic agents on the secretion of lysosomal enzymes and on the intracellular distribution of the weak-base anthracycline daunomycin in drug-resistant renal proximal tubule PKSV-PR(col50) cells and their drug-sensitive PKSV-PR cell counterparts. Imaging studies using pH-dependent lysosomotropic dyes revealed that drug-sensitive and drug-resistant cells exhibited a similar acidic lysosomal pH (around 5.

Anti-TCR Vbeta-specific DNA vaccination prolongs heart allograft survival in adult rats.

Allospecific T cells are known to play a central role in the process of allograft rejection. Recently, it has been shown that T cell function could be specifically targeted using DNA vaccination. In our model, PCR analysis of the TCR-beta chain repertoire of T cells infiltrating rejected allografts showed specific expansions of the Vbeta13 and Vbeta2 families.

Anti-TCR-specific DNA vaccination demonstrates a role for a CD8+ T cell clone in the induction of allograft tolerance by donor-specific blood transfusion.

Donor-specific allograft tolerance can be induced in the adult rat by pregraft donor-specific blood transfusion (DST). This tolerance appeared to be mediated by regulatory cells and to the production of the suppressive cytokine TGF-beta1. A potential immunoregulatory CD8+ clone bearing a Vbeta18-Dbeta1-Jbeta2.