Synthesis, physicochemical characterisation and biological evaluation of polymer-functionalised gold nanoparticles for cancer treatment

Most of the chemotherapeutics employed today are facing important limitations, including the inability to provide targeted therapy and intracellular drug degradation within the lysosomal compartments. These explain why the average survival rate, throughout all cancer types, is still as low as 50%. The aim of the present thesis is to develop multifunctional AuNPs for intracellular delivery. PEGylated AuNPs were prepared via grafting poly(ethylene glycol) onto the AuNP surface. The influence of the PEG chain length and grafting densities on the colloidal stability, the grafted polymer conformation, the stealth character and the interparticle interactions have been extensively investigated. Longer chain lengths favoured the stability of the colloids in aqueous solution and the preparation of long-range and ordered assemblies via “flexible” interparticle interactions whereas shorter chain lengths led to denser layers and “hard-to-contact” spheres. Highly stable biocompatible pH-responsive AuNPs were obtained through the grafting with the anionic poly(L-lysine isophthalamide) (PLP) conjugated with L-phenylalanine at 75 mol% (PP75). The polymer pH dependent coil-to-globule conformational change was retained between pH 5-6, tuned to the endosomal pH. The AuNPs@PP75 nanohybrids demonstrated a quick and highly reversible agglomeration-deagglomeration cycle. Doxorubicin was loaded at 0.6 wt% onto the nanohybrids without compromising the overall stability in biological media and was effectively delivered into drug-resistant human uterus sarcoma cell line. The synergistic effect of the chemotherapy with photothermal treatment increased the killing efficiency by 6 folds compared to the conventional free drug. The nanohybrids were finally entrapped into pH-responsive PLP hydrogels. The composite hydrogels retained a high pH-responsive swelling behaviour and demonstrated improved mechanical properties compared to the bare hydrogel. Controlled drug release ability and biocompatibility confirmed their suitability as potential cancer therapeutics via oral administration.Open Acces

Le silence des Sirènes : Franz Kafka

La nouvelle de Kafka, une page écrite le 23 octobre 1917, est une réécriture du passage de l’Odyssée d’Homère1 dans lequel Circé avertit Ulysse qu’il va passer au large de l’île des Sirènes. Ces êtres hybrides, mifemmes mioiseaux, attirent irrésistiblement les marins par leur chant et provoquent leur naufrage ce dont témoigne le rivage couvert d’ossements. Circé indique aussi à Ulysse le moyen d’échapper à ce sort funeste: il devra boucher les oreilles de ses compagnons avec de la cire; lui seul, solidement attaché au mât, pourra jouir de la voix des Sirènes

La voix du castrat ou le sexe de l’ange

Ce texte a été écrit en hommage à l’Italie, un pays si nourri d’art en général, si amoureux des belles voix en particulier, qu’il a toléré pendant au moins deux siècles, en particulier au 17ème et 18ème siècles, l’âge baroque, la mutilation d’environ 3000 à 4000 jeunes garçons chaque année, afin de créer les plus étranges de toutes les voix de chanteurs, les voix de castrats

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

Human Muscle Satellite Cells as Targets of Chikungunya Virus Infection

BACKGROUND: Chikungunya (CHIK) virus is a mosquito-transmitted alphavirus that causes in humans an acute infection characterised by fever, polyarthralgia, head-ache, and myalgia. Since 2005, the emergence of CHIK virus was associated with an unprecedented magnitude outbreak of CHIK disease in the Indian Ocean. Clinically, this outbreak was characterized by invalidating poly-arthralgia, with myalgia being reported in 97.7% of cases. Since the cellular targets of CHIK virus in humans are unknown, we studied the pathogenic events and targets of CHIK infection in skeletal muscle. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistology on muscle biopsies from two CHIK virus-infected patients with myositic syndrome showed that viral antigens were found exclusively inside skeletal muscle progenitor cells (designed as satelllite cells), and not in muscle fibers. To evaluate the ability of CHIK virus to replicate in human satellite cells, we assessed virus infection on primary human muscle cells; viral growth was observed in CHIK virus-infected satellite cells with a cytopathic effect, whereas myotubes were essentially refractory to infection. CONCLUSIONS/SIGNIFICANCE: This report provides new insights into CHIK virus pathogenesis, since it is the first to identify a cellular target of CHIK virus in humans and to report a selective infection of muscle satellite cells by a viral agent in humans

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Vécu de la grossesse des femmes dépendantes aux opiacés

Introduction : La dépendance aux opiacés rend les grossesses à très haut risque médico-social. De nombreuses études descriptives ont été réalisées sur ces grossesses, notamment en milieu hospitalier et du point de vue du soignant. L’objectif de l’étude est de documenter le vécu des patientes dépendantes aux opiacés au regard d’une grossesse passée ou en cours, de décrire les points essentiels de leurs trajectoires, de leurs stratégies psycho-sociales afin d’améliorer la compréhension de leur expérience de la maternité à partir de leur propre point de vue. Méthodologie : Notre étude qualitative par entretiens semi-dirigés a permis l’interview de 11 femmes dépendantes aux opiacés. Résultats et discussion : Ces mères ont témoigné de leur combat réussi, bien souvent grâce à leur (s) enfant (s). La culpabilité éprouvée par ces femmes est au coeur des entretiens. Leur rapport aux opiacés, la présence de leur entourage, le syndrome de sevrage du nouveau-né sont, entre autres, des thèmes qui ont été développés. Ces femmes se sont montrées en quête de reconnaissance d’un statut de bonne mère. Elles ont aussi révélé la nécessité pour les professionnels de santé de se comporter de façon empathique. Un suivi attentif et personnalisé de la grossesse chez les femmes toxicomanes, ainsi qu'un soutien médical et psychosocial semblent primordial. Conclusion : Une politique d'attention et de considération envers ces patientes doit être au coeur de l'action. Le développement d’un travail en réseau multidisciplinaire doit être maintenu

La population mastocytaire du poumon de cobaye : caracterisation cytochimique, evolution par rapport a la puberte, influence de la sensibilisation et de la provocation, effet d'une corticotherapie

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc