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« Faire intimité » en migration
No full textInternational audienceDrawing on a literature review of diverse conceptions of intimacy in migration, this introduction underscores that intimacy, while inherently tied to a sense of interiority, is shaped by social norms, institutional directives and relational dynamics. As such, intimacy serves as an analytical lens for exploring the process of subjectivation and their room of manoeuvre within migratory regimes – shedding light on how migrants “do intimacy”. The aim of the special issue, as outlined in this introduction, is to examine the plurality of attachment forms and identity reconfigurations within migrants’ intimate spheres. In doing so, it strikes the delicate balance between exposing the oppressions experienced in migration and emphasising the everyday possibilities of forging intimate spaces.A partir de una reseña de la literatura sobre las diferentes concepciones de la intimidad en el contexto de la migración, esta introducción resalta que la intimidad, aunque vinculada a una dimensión de interioridad, está profundamente moldeada por normas sociales, mandatos institucionales y dinámicas relacionales. De este modo, lo intimo puede convertirse en una herramienta analítica para explorar los procesos de subjetivación de los individuos y su capacidad de maniobra frente a los regímenes migratorios, permitiendo comprender cómo los migrantes dan forma à lo intimo. El objetivo de este dossier, según se expone en la introducción, es describir la diversidad de formas de apego y las reconfiguraciones identitarias que emergen en la esfera íntima de los migrantes, trazando así una línea sutil entre visibilizar las opresiones que enfrentan en el proceso migratorio e insistir en las posibilidades cotidianas de constuir espacios íntimos.À partir d’une revue de littérature sur les différentes conceptions de l’intimité en migration, cette introduction insiste sur le fait que l’intimité, tout en restant liée à une forme d’intériorité, est façonnée par des normes sociales, des injonctions institutionnelles et des dynamiques relationnelles. L’intimité peut alors constituer un outil conceptuel pour explorer la subjectivation des personnes et leurs marges de manœuvre face aux régimes migratoires, et comprendre comment les personnes migrantes « font intimité ». L’objectif du dossier, présenté dans cette introduction, est de décrire la pluralité des formes d’attachement et de reconfiguration identitaire qui existe au sein de la sphère intime des migrant·es. Ce faisant, il s’agira pour l’analyse de se tenir sur une ligne de crête entre la mise en lumière des oppressions vécues en migration et l’insistance sur les possibilités quotidiennes de se forger des sphères intimes saisies par les migrant·es
Real‐Time PCR Helicobacter pylori Test in Comparison With Culture and Histology for Helicobacter pylori Detection and Identification of Resistance to Clarithromycin: A Single‐Center Real‐Life Study
No full textInternational audienceABSTRACT Background In our center, RT‐PCR was integrated as a routine method to diagnose Helicobacter pylori due to its higher availability after COVID‐19 pandemics. The objective of this study was to assess the feasibility and performance of systematically performed RT‐PCR for H. pylori detection and clarithromycin (CLA) resistance in a real‐life clinical practice. Materials and Methods One hundred consecutive patients underwent an upper digestive endoscopy during which at least four biopsies (two from the antrum and two from the corpus) were obtained for RT‐PCR and culture with antibiogram and four additional biopsies for histology. The results of H. pylori detection were compared among RT‐PCR, histology, and bacterial culture, and the results of CLA susceptibility were compared between culture‐based antibiogram and RT‐PCR. Results Out of 100 patients, 64 were positive for H. pylori by RT‐PCR, 66 by histology, and 53 by culture, with no statistically significant difference among the three methods ( p > 0.05). CLA resistance was found in 8 out of 45 patients (17.7%) by culture and in 12 out of 64 patients (18.7%) by PCR. In 8 H. pylori ‐positive patients by culture, the antibiogram could not be realized due to lack of viability of the strains. In one patient, after a double checking, discrepant results were observed, requiring a complementary molecular analysis by the French National Reference Center for Helicobacters, which confirmed the existence of a double population of H. pylori strains within biopsies, with and without CLA resistance. Conclusions Our study demonstrates that in real‐life clinical practice, RT‐PCR is feasible and comparable in the ability to detect H. pylori and its resistance to CLA to bacterial culture with antibiogram and histology. Given its rapidity and limited dependence on the operator's interpretation, it appears preferable to the other methods
A T 1 MRI detectable hyaluronic acid hydrogel for in vivo tracking after intracerebral injection in stroke
No full textInternational audienceInjectable hydrogels have emerged as a promising strategy for treating stroke and neurodegenerative diseases, but their effectiveness depends on precise injection, defect filling, and long-term retention at the target site. While MRI can help visualize hydrogels, distinguishing them from fluid-filled spaces, like a post-stroke cavity at a chronic stage, is challenging owing to their high water content and similar MR properties. In this study, a T1 MRI detectable hyaluronic acid (HA) hydrogel that is injectable and self-healing was developed for in vivo tracking after intracerebral injection in stroke. This HA hydrogel was functionalized with a thermodynamically stable and kinetically inert gadolinium(III) complex for monitoring its long-term fate in the brain with T1-contrast enhanced MRI. The dynamic covalent cross-links based on boronate ester bonds in the hydrogel network ensured precise injection and instantaneous self-healing. The HA network did not induce adverse tissue response and was biocompatible with therapeutic cells (human adipose stromal/stem cells). Furthermore, this labeling strategy enabled accurate tracking of hydrogel distribution and degradation in stroke condition, allowing a better assessment of efficacy and safety. This MRI-visible hydrogel has significant potential as a scaffold for stem cells, growth factors, and/or drugs, paving the way for more effective treatments for brain disorders
Geometric construction of gravitation
No full textThe equations of classical mechanics derive from Kepler's laws as interpreted by Isaac Newton. Relativistic solid rotation makes it possible to rehabilitate René Descartes's vision of gravitation and to give it a geometric construction in an Euclidian space. The profoundly relativistic nature of Newton's gravitation law is recovered
Iron‑sulfur cluster biogenesis and function in Apicomplexa parasites
No full textInternational audienceIron‑sulfur cluster are ubiquitous and ancient protein cofactors that support a wide array of essential cellular functions. In eukaryotes, their assembly requires specific and dedicated machineries in each subcellular compartment. Apicomplexans are parasitic protists that are collectively responsible for a significant burden on the health of humans and other animals, and most of them harbor two organelles of endosymbiotic origin: a mitochondrion, and a plastid of high metabolic importance called the apicoplast. Consequently, apicomplexan parasites have distinct iron‑sulfur cluster assembly machineries located to their endosymbiotic organelles, as well as a cytosolic pathway. Recent findings have not only shown the importance of iron‑sulfur cluster assembly for the fitness of these parasites, but also highlighted parasite-specific features that may be promising for the development of targeted anti-parasitic strategies
Knowledge and application of ESC / HFA guidelines in the management of advanced heart failure
No full textInternational audienceAims Management of advanced heart failure (HF) remains challenging despite specific sections in the 2021 European Society of Cardiology/Heart Failure Association (ESC/HFA) guidelines, with delays in referrals exacerbating the issue. This study aimed to evaluate the awareness and implementation of these guidelines among cardiologists and identify barriers to effective referral. Methods and results From June to October 2023, an online survey was disseminated through the ESC mailing list, targeting cardiologists across Europe. The survey investigated four areas: guideline awareness, healthcare network organization, clinical case management, and perceptions of mechanical circulatory support (MCS) outcomes. Respondents were categorized into heart failure cardiologists (HFCs), general cardiologists (GCs), and other participants (OPs). Among 497 respondents, 25% were heart HFCs, 40% were GCs, and 35% were OPs. A total of 84% of HFCs reported a high level of guideline knowledge, compared to 57% of GCs and 62% of OPs ( p < 0.001). Additionally, 76% of HFCs ‘regularly or always’ used ESC/HFA criteria to identify advanced HF, compared to 44% of GCs and 48% of OPs ( p < 0.001). Correct responses regarding the recommendation class for heart transplantation were 84%, 55%, and 60% ( p < 0.0001), and for MCS as a bridge to transplantation, 69%, 65%, and 55% ( p = 0.018) among HFCs, GCs, and OPs, respectively. Referring patients with severe HF to a tertiary centre team was found to be ‘very difficult’ or ‘difficult’ by 8.4% of HFCs, 19.6% of GCs, and 18.2% of OPs ( p = 0.0005). Conclusion The study highlights significant disparities in knowledge and application of advanced HF guidelines among cardiologists, revealing an opportunity for educational initiatives. The difficulty in referring patients to tertiary centres underscores the need to improve the referral pathway for advanced HF patients
Prevalence of Liver Steatosis and Fibrosis in Adults With Primary Hypobetaliproteinemia: Results From the HYPOCHOL Study
No full textInternational audienceNo abstract availabl
Subunit protein CD40.SARS.CoV2 vaccine induces SARS-CoV-2-specific stem cell-like memory CD8+ T cells
No full textInternational audienceBackground: Ideally, vaccination should induce protective long-lived humoral and cellular immunity. Current licensed COVID-19 mRNA vaccines focused on the spike (S) region induce neutralizing antibodies that rapidly wane.Methods: Herein, we show that a subunit vaccine (CD40.CoV2) targeting spike and nucleocapsid antigens to CD40-expressing cells elicits broad specific human (hu)Th1 CD4 + and CD8 + T cells in humanized mice.Findings: CD40.CoV2 vaccination selectively enriched long-lived spike-and nucleocapsid-specific CD8 + progenitors with stem-cell-like memory (Tscm) properties, whereas mRNA BNT162b2 induced effector memory CD8 + T cells. CD8 + Tscm cells produced IFNγ and TNF upon antigenic restimulation and showed a high proliferation rate. We demonstrate that CD40 activation is specifically required for the generation of huCD8 + Tscm cells.Interpretation: These results support the development of a CD40-vaccine platform capable of eliciting long-lasting T-cell immunity.Funding: This work was supported by Inserm, Université Paris-Est Créteil, and the Investissements d'Avenir program, Vaccine Research Institute (VRI), managed by the ANR
The background sodium leak channel NALCN is a major controlling factor in pituitary cell excitability
No full textInternational audienceThe pituitary gland produces and secretes a variety of hormones that are essential to life, such as for the regulation of growth and development, metabolism, reproduction, and the stress response. This is achieved through an intricate signalling interplay between the brain and peripheral feedback signals that shape pituitary cell excitability by regulating the ion channel properties of these cells. In addition, endocrine anterior pituitary cells spontaneously fire action potentials to regulate the intracellular calcium ([Ca2+]i) level, an essential signalling conduit for hormonal secretion. To this end, pituitary cells must regulate their resting membrane potential (RMP) close to the firing threshold, but the molecular identity of the ionic mechanisms responsible for this remains largely unknown. Here, we revealed that the sodium leak channel NALCN, known to modulate neuronal excitability elsewhere in the brain, regulates excitability in the mouse anterior endocrine pituitary cells. Using viral transduction combined with powerful electrophysiology methods and calcium imaging, we show that NALCN forms the major Na+ leak conductance in these cells, appropriately tuning cellular RMP for sustaining spontaneous firing activity. Genetic depletion of NALCN channel activity drastically hyperpolarised these cells, suppressing their firing and [Ca2+]i oscillations. Remarkably, despite this profound function of NALCN conductance in controlling pituitary cell excitability, it represents a very small fraction of the total cell conductance. Because NALCN responds to hypothalamic hormones, our results also provide a plausible mechanism through which hormonal feedback signals from the brain and body could powerfully affect pituitary activity to influence hormonal function. KEY POINTS: Pituitary hormones are essential to life as they regulate important physiological processes, such as growth and development, metabolism, reproduction and the stress response. Pituitary hormonal secretion relies on the spontaneous electrical activity of pituitary cells and co-ordinated inputs from the brain and periphery. This appropriately regulates intracellular calcium signals in pituitary cells to trigger hormonal release. Using viral transduction in combination with electrophysiology and calcium imaging, we show that the activity of the background leak channel NALCN is a major controlling factor in eliciting spontaneous electrical activity and intracellular calcium signalling in pituitary cells. Remarkably, our results revealed that a minute change in NALCN activity could have a major influence on pituitary cell excitability. Our study provides a plausible mechanism through which the brain and body could intricately control pituitary activity to influence hormonal function
Risk score stratification of cutaneous melanoma patients based on whole slide images analysis by deep learning
No full textInternational audienceBackground There is a need to improve risk stratification of primary cutaneous melanomas to better guide adjuvant therapy. Taking into account that haematoxylin and eosin (HE)‐stained tumour tissue contains a huge amount of clinically unexploited morphological informations, we developed a weakly‐supervised deep‐learning approach, SmartProg‐MEL, to predict survival outcomes in stages I to III melanoma patients from HE‐stained whole slide image (WSI). Methods We designed a deep neural network that extracts morphological features from WSI to predict 5‐y overall survival (OS), and assign a survival risk score to each patient. The model was trained and validated on a discovery cohort of primary cutaneous melanomas (IHP‐MEL‐1, n = 342). Performance was tested on two external and independent datasets (IHP‐MEL‐2, n = 161; and TCGA cohort n = 63). It was compared with well‐established prognostic factors. Concordance index (c‐index) was used as a metric. Results On the discovery cohort, the SmartProg‐MEL predicts the 5‐y OS with a c‐index of 0.78 on the cross‐validation data and of 0.72 on the cross‐testing series. In the external cohorts, the model achieved a c‐index of 0.71 and 0.69 for the IHP‐MEL‐2 and TCGA dataset respectively. Furthermore, SmartProg‐MEL was an independent and the most powerful prognostic factor in multivariate analysis (HR = 1.84, p ‐value < 0.005). Finally, the model was able to dichotomize patients in two groups—a low and a high‐risk group—each associated with a significantly different 5‐y OS ( p ‐value < 0.001 for IHP‐MEL‐1 and p ‐value = 0.01 for IHP‐MEL‐2). Conclusion The performance of our fully automated SmartProg‐MEL model outperforms the current clinicopathological factors in terms of prediction of 5‐y OS and risk stratification of cutaneous melanoma patients. Incorporation of SmartProg‐MEL in the clinical workflow could guide the decision‐making process by improving the identification of patients that may benefit from adjuvant therapy