Nacre, a natural, multi-use, and timely biomaterial for bone graft substitution

International audienceDuring the past two decades, with a huge and rapidly increasing clinical need for bone regeneration and repair, bone substitutes are more and more seen as a potential solution. Major innovation efforts are being made to develop such substitutes , some having advanced even to clinical practice. It is now time to turn to natural biomaterials. Nacre, or mother-of-pearl, is an organic matrix-calcium carbonate coupled shell structure produced by molluscs. In vivo and in vitro studies have revealed that nacre is osteoinductive, osteoconductive, biocompatible, and biodegradable. With many other outstanding qualities, nacre represents a natural and multi-use biomaterial as a bone graft substitute. This review aims at summarising the current needs in orthopaedic clinics and the challenges for the development of bone substitutes; most of all, we systematically review the physiological characteristics and biological evidence of nacre's effects centred on osteogen-esis, and finally we put forward the potential use of nacre as a bone graft substitute

La dyspareunie féminine, not a simple functional disorder !.

editorial reviewedDyspareunia is defined as pain during sexual intercourse. It will be qualified as superficial if it occurs during the vaginal penetration and as deep when it appears in the lower abdomen or further in the vagina. It concerns between 10 and 28 % of women during their lifetime and will have a significant impact on their quality of life. Multidisciplinary care will allow an accurate diagnosis and optimal treatment. The collaboration between general practitioner, gynecologist, physiotherapist and psychologist is mandatory in order to improve the quality of life of patients.La dyspareunie se définit par une douleur lors du rapport sexuel. Elle sera qualifiée de superficielle si elle survient lors de la pénétration du vagin, et de profonde lorsqu’elle apparaît lors de la pénétration complète et est décrite dans le bas du ventre ou dans le fond du vagin. Elle concerne entre 10 et 28 % des femmes au cours de leur vie et impactera de manière importante leur qualité de vie. Une prise en charge multidisciplinaire permettra un diagnostic précis et un traitement optimal. La collaboration entre médecin traitant, gynécologue, physiothérapeute et psychologue est une condition sine qua non pour l’amélioration de la qualité de vie des patientes

Evaluating the impact of curfews and other measures on SARS-CoV-2 transmission in French Guiana.

While general lockdowns have proven effective to control SARS-CoV-2 epidemics, they come with enormous costs for society. It is therefore essential to identify control strategies with lower social and economic impact. Here, we report and evaluate the control strategy implemented during a large SARS-CoV-2 epidemic in June-July 2020 in French Guiana that relied on curfews, targeted lockdowns, and other measures. We find that the combination of these interventions coincided with a reduction in the basic reproduction number of SARS-CoV-2 from 1.7 to 1.1, which was sufficient to avoid hospital saturation. We estimate that thanks to the young demographics, the risk of hospitalisation following infection was 0.3 times that of metropolitan France and that about 20% of the population was infected by July. Our model projections are consistent with a recent seroprevalence study. The study showcases how mathematical modelling can be used to support healthcare planning in a context of high uncertainty

‘Content to be sad’ or ‘runaway apprentice’? The psychological contract and career agency of young scientists in the entrepreneurial university

This article examines employee agency in psychological contracts by exploring how young scientists proactively shape their careers in response to unmet expectations induced by academic entrepreneurialism. It uses the lens of social exchange to examine their relationships with the professors engaged in two types of activities: collaborative research characterized by diffuse/reciprocal exchange, and commercial ventures, by restricted/negotiated exchange. These two categories show how career agency varies in orientation, form and behavioural outcome depending on the relational context within which their psychological contracts evolve. Those involved in collaborative research experienced a relational psychological contract and responded to unfulfilled career promises by ‘extended investment’ in their current jobs. They use ‘proxy agency’ by enlisting the support of their professors. However, some become ‘trapped’ in perennial temporary employment and are ‘content to be sad’. By contrast, those involved in research commercialization experienced a transactional contract and assert ‘personal agency’ by crafting their own entrepreneurial careers. They are ‘runaways’ who seek autonomy. The evidence is based on interviews with 24 doctoral/postdoctoral researchers and 16 professors from three leading UK universities. The study extends psychological contract theory by incorporating career agency and sheds new light on changing academic careers

Loss-of-function alleles of P2RX7 and TLR4 fail to affect the response to chemotherapy in non-small cell lung cancer

The success of anticancer chemotherapy relies at least in part on the induction of an immune response against tumor cells. Thus, tumors growing on mice that lack the pattern recognition receptor TLR4 or the purinergic receptor P2RX7 fail to respond to chemotherapy with anthracyclins or oxaliplatin in conditions in which the same neoplasms growing on immunocompetent mice would do so. Similarly, the therapeutic efficacy (measured as progression-free survival) of adjuvant chemotherapy with anthracyclins is reduced in breast cancer patients bearing loss-of-function alleles of TLR4 or P2RX7. TLR4 loss-of-function alleles also have a negative impact on the therapeutic outcome of oxaliplatin in colorectal cancer patients. Here, we report that loss-of-function TLR4 and P2RX7 alleles do not affect overall survival in non-small cell lung cancer (NSCLC) patients, irrespective of the administration and type of chemotherapy. The intrinsic characteristics of NSCLC (which near-to-always is chemoresistant and associated with poor prognosis) and/or the type of therapy that is employed to treat this malignancy (which near-to-always is based on cisplatin) may explain why two genes that affect the immune response to dying cells fail to influence the clinical progression of NSCLC patients

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured

Les assemblées citoyennes

Si l'actualité des assemblées citoyennes est relativement récente en France, avec la Convention citoyenne pour le climat, cette technique s'appuie sur de nombreuses et anciennes expériences dans d'autres États. L'étude de ces assemblées a également fait l'objet de nombreux travaux issus de la science politique en France comme à l'étranger. Les juristes demeurent, encore aujourd'hui, largement étrangers à cette réflexion, aussi bien dans sa dimension pratique, l'étude de la pratique des assemblées citoyennes, que dans sa dimension théorique, sous l'angle de l'étude des concepts de démocratie délibérative et de démocratie participative. Dans un tel contexte, le présent ouvrage, Les assemblées citoyennes : nouvelle utopie démocratique ?, résultat d'un colloque international pluridisciplinaire, permet de dresser un état des lieux, sous un angle critique, de ce qu'il convient de penser des assemblées citoyennes. Les assemblées citoyennes constituent-elles le remède miracle à la crise du régime représentatif ? Tel est, sans doute le fil rouge de toutes les questions soulevées au cours de cette journée d'études. Quel est le sens des « assemblées citoyennes » ? À quelle théorie politique est-il possible de les rattacher ? Quelles en sont les expressions concrètes et les différentes expériences pratiques ? Telles sont les différentes questions sur lesquelles les contributions de cet ouvrage ont apporté un éclairage pluridisciplinaire, contemporain et critique. La multiplication des regards disciplinaires, science politique et droit pour l'essentiel, permet ainsi de croiser les regards sur cet objet d'études, de déplacer, parfois, les frontières et, surtout, de penser de manière globale le phénomène des assemblées citoyennes

Identification of natural killer markers associated with fatal outcome in COVID-19 patients

IntroductionIncreasing evidence has shown that coronavirus disease 19 (COVID-19) severity is driven by a dysregulated immunological response. Previous studies have demonstrated that natural killer (NK) cell dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of NK cell markers as a driver of death in the most critically ill patients.MethodsWe enrolled 50 non-vaccinated hospitalized patients infected with the initial virus or the alpha variant of SARS-CoV-2 with moderate or severe illness, to evaluate phenotypic and functional features of NK cells.ResultsHere, we show that, consistent with previous studies, evolution NK cells from COVID-19 patients are more activated, with the decreased activation of natural cytotoxicity receptors and impaired cytotoxicity and IFN-γ production, in association with disease regardless of the SARS-CoV-2 strain. Fatality was observed in 6 of 17 patients with severe disease; NK cells from all of these patients displayed a peculiar phenotype of an activated memory-like phenotype associated with massive TNF-α production.DiscussionThese data suggest that fatal COVID-19 infection is driven by an uncoordinated inflammatory response in part mediated by a specific subset of activated NK cells

Epstein-Barr Virus and immune status imprint the immunogenomics of non-Hodgkin lymphomas occurring in immune-suppressed environments

Non-Hodgkin lymphomas (NHL) commonly occur in immune-deficient (ID) patients, both HIV-infected and transplanted, and are often EBV-driven with cerebral localization, raising the question of tumor immunogenicity, a critical issue for treatment responses. We investigated the immunogenomics of 68 lymphoproliferative disorders from 51 ID (34 posttransplant, 17 HIV+) and 17 immunocompetent patients. Overall, 72% were Large B Cells Lymphoma (LBCL) and 25% were primary central-nervous-system lymphoma (PCNSL) while 40% were EBV-positive. Tumor whole-exome and RNA sequencing, along with a bioinformatics pipeline allowed analysis of tumor mutational burden (TMB), tumor landscape and microenvironment (TME) and prediction of tumor neoepitopes. Both TMB (2.2 vs 3.4/Mb, p=0.001) and neoepitopes numbers (40 vs 200, p=0.00019) were lower in EBVpositive than in EBV-negative NHL, regardless of the immune status. In contrast both EBV and the immune status influenced the tumor mutational profile, with HNRNPF and STAT3 mutations exclusively observed in EBV-positive and ID NHL, respectively. Peripheral blood T-cell responses against tumor neoepitopes were detected in all EBV-negative cases but in only half EBV-positive ones, including responses against IgH-derived MHC-class-II restricted neoepitopes. The TME analysis showed higher CD8 T cell infiltrates in EBVpositive vs EBV-negative NHL, together with a more tolerogenic profile composed of Tregs, type-M2 macrophages and an increased expression of negative immune-regulators. Our results highlight that the immunogenomics of NHL in patients with immunodeficiency primarily relies on the tumor EBV status, while T cell recognition of tumor- and IgH-specific neoepitopes is conserved in EBV-negative patients, offering potential opportunities for future T cell-based immune therapies