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Echocardiographic Outcomes After Transcatheter Edge-to-Edge Repair in Patients With Isolated Tricuspid Regurgitation: The Tri.Fr Trial
No full textInternational audienceBackground: The relationships among tricuspid regurgitation (TR) reduction after tricuspid transcatheter edge-to-edge repair (T-TEER), changes in right-sided heart function, and outcomes are poorly explored.Objectives: This study aims to explore the relationship between functional remodeling and subsequent outcomes and the associations among T-TEER, residual TR, and outcomes.Methods: Changes in echocardiographic parameters from baseline to 1 year, overall and according to TR reduction were evaluated by a centralized echocardiographic core laboratory in patients included in the Tri.Fr (Evaluation of Tricuspid Valve Percutaneous Repair System in the Treatment of Severe Secondary Tricuspid Disorders) trial.Results: A total of 300 patients (aged 78 ± 5 years; 53.7% women) were enrolled; 152 patients were allocated to the T-TEER + guideline-directed medical therapy (GDMT) group, and 148 were allocated to the GDMT group. Patients in the T-TEER + GDMT group demonstrated a significant decrease in most of parameters of right ventricular (RV) function, whereas patients in the GDMT group exhibited no significant changes in RV metrics at 1 year. The clinical composite score improved progressively with each successive grade of TR reduction. The positive effect of T-TEER on the composite clinical score was observed irrespective of baseline right atrial volume but only in patients with normal RV-pulmonary artery coupling (defined by a tricuspid annular plane systolic excursion-to-systolic pulmonary artery pressure ratio ≥0.40). At 1 year, patients with an improved clinical composite score had a lower right atrial volume index compared with patients whose clinical score remained unchanged or worsened (median 112 mL/m2 [Q1-Q3: 78.0-146 mL/m2] vs median 141 mL/m2 [Q1-Q3: 107-173 mL/m2]; P = 0.004).Conclusions: Although T-TEER can decrease TR severity, its impact on conventional RV function parameters and RV-pulmonary artery coupling remains limited. RV functional recovery has a smaller influence on clinical outcomes at 1 year compared with achieving optimal reduction in TR severity. (Evaluation of Tricuspid Valve Percutaneous Repair System in the Treatment of Severe Secondary Tricuspid Disorders [Tri.Fr]; NCT04646811)
Inhibition of IRAK4 by microbial trimethylamine blunts metabolic inflammation and ameliorates glycemic control
No full textInternational audienceAbstract The global type 2 diabetes epidemic is a major health crisis. Although the microbiome has roles in the onset of insulin resistance (IR), low-grade inflammation and diabetes, the microbial compounds controlling these processes remain to be discovered. Here, we show that the microbial metabolite trimethylamine (TMA) decouples inflammation and IR from diet-induced obesity by inhibiting interleukin-1 receptor-associated kinase 4 (IRAK4), a central kinase in the Toll-like receptor pathway sensing danger signals. TMA blunts TLR4 signalling in primary human hepatocytes and peripheral blood monocytic cells and rescues mouse survival after lipopolysaccharide-induced septic shock. Genetic deletion and chemical inhibition of IRAK4 result in metabolic and immune improvements in high-fat diets. Remarkably, our results suggest that TMA—unlike its liver co-metabolite trimethylamine N -oxide, which is associated with cardiovascular disease—improves immune tone and glycemic control in diet-induced obesity. Altogether, this study supports the emerging role of the kinome in the microbial–mammalian chemical crosstalk
A multicellular star-shaped actin network underpins epithelial organization and connectivity
No full textInternational audienceEpithelial tissues withstand external stresses while maintaining structural stability. Bicellular junctions and the actomyosin network support epithelial integrity, packing and remodelling.While their role in development and disease are well studied, their synergistic impact on maintaining tissue organization remains unclear. Here, we identify a tissue-scale actomyosin network in adult murine intestinal villi, as well as in an ex vivo organoid-based epithelium model. This actomyosin network consists of repeated units of actin starsradial actin structures at the base of hexagonal cells-linked via bicellular junctions into multicellular array.Functionally, actin stars maintain epithelial morphological stability by preserving cell shape and packing. Laser ablation experiments support a modified vertex model, linking tension along actin star branches to epithelial arrangement. Additionally, actin stars act as basal locks, limiting protrusive activity, and hindering cell migration and tissue disruption. Together, these findings reveal the star-shaped supracellular actin network as a pivotal biomechanical system governing epithelial layer coordination.</p
Impaired serum neutralization and death in Omicron-infected critically ill patients: insights from the French SEVARVIR prospective, multicenter cohort study
No full textInternational audienceBackgroundDespite advances in treatment, critically ill COVID-19 patients requiring intensive care unit (ICU) admission continue to comprise a substantial proportion of cases. However, the factors influencing poor prognosis in this population remain poorly understood. To address this knowledge gap, we conducted a prospective analysis of serum neutralizing activity against SARS-CoV-2 in 49 non-selected, critically ill COVID-19 patients enrolled in the multicenter SEVARVIR cohort between October 2022 and May 2024.MethodsThis a substudy of the SEVARVIR prospective multicenter observational cohort study (NCT05162508). We included 49 critically ill COVID-19 patients hospitalized in four French intensive care units between October 2022 and May 2024 from the 827 patients enrolled in the multicenter, prospective SEVARVIR study. Serum neutralizing titers of authentic SARS-CoV-2 isolates were measured using the S-Fuse assay and patients categorized as neutralizers if they had an anti-spike serum neutralization titer against the infecting variant > 15 and non-neutralizers if ≤ 15. Full-length SARS-CoV-2 genomes from all included patients were sequenced by means of next-generation sequencing.ResultsMedian age was 73 years (59–75) and 34.7% of patients (n = 17/49) were female. Half of the patients (53.1%, n = 26/49) had immunosuppressive comorbidities. A large proportion of individuals lacked the capacity to neutralize their infecting variant (57.1%, n = 28/49). Neutralizing titers were significantly higher in 28-day survivors than in deceased patients (p = 0.0212) and neutralizers had a significantly lower 28-day mortality than non-neutralizers (5.0%, n = 1/21 vs. 32.1%, n = 9/28; p = 0.0312). Nine out of the ten patients who succumbed to the disease within 28 days of admission had undetectable serum neutralizing capacity, which was significantly more prevalent than in survivors (p = 0.03), irrespective of immunosuppression status. The sole patient who died despite having detectable neutralizing antibodies against SARS-CoV-2, was found to have anti-interferon auto-antibodies.ConclusionThese findings underscore the potential benefits of early therapeutic interventions aimed at enhancing neutralization, which may improve survival outcomes in both immunocompetent and immunocompromised critically ill COVID-19 patients
Hoeffding-type decomposition for U-statistics on bipartite networks
No full textInternational audienc
Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses (ICTV) from the Animal dsRNA and ssRNA(−) Viruses Subcommittee, 2025
No full textInternational audienceRNA viruses are ubiquitous in the environment and are important pathogens of humans, animals and plants. In 2024, the International Committee on Taxonomy of Viruses Animal dsRNA and ssRNA(−) Viruses Subcommittee submitted 18 taxonomic proposals for consideration. These proposals expanded the known virosphere by classifying 9 new genera and 88 species for newly detected virus genomes. Of note, newly established species expand the large family of Rhabdoviridae to 580 species. A new species in the family Arenaviridae includes a virus detected in Antarctic fish with a unique split nucleoprotein ORF. Additionally, four new species were established for historically isolated viruses with previously unsequenced genomes. Furthermore, three species were abolished due to incomplete genome sequence information, and one family was moved from being unassigned in the phylum Negarnaviricota into a subphylum and order. Herein, we summarize the 18 ratified taxonomic proposals and the general features of the current taxonomy, thereby supporting public and animal health responses
Etude de l’alimentation totale française 3 (EAT3) - Rapport méthode
No full textCitation suggérée : Anses. (2025). Etude de l’alimentation totale française 3 (EAT3) - Rapport méthode. (saisine2019-SA-0010). Maisons-Alfort : Anses, 90 p
RAGE contributes to persistent sepsis-induced muscle and mitochondrial alterations
No full textInternational audienceAbstract A majority of patients surviving sepsis develop muscle weakness. However, the underlying cellular and molecular pathways remain largely unexplored. To determine whether sepsis leads to long-term persistent muscular consequences and to identify the underlying mechanisms, we used a murine model of reanimated sepsis induced by intraperitoneal injection of a heterologous stool slurry. Muscles were analyzed 3 months later. The oxidative muscle exhibited reduced fatigue resistance and decreased mitochondrial respiration, without a corresponding reduction in mitochondrial OXPHOS proteins. Glycolytic and mixed muscle fibres were atrophied. Markers of oxidative and mitochondrial stress, as well as genes involved in mitochondrial fission, remained present 3 months after sepsis. Low-grade, but significant, muscular inflammation was also measured. Specifically, both the NLRP3 inflammasome and the receptor of Advanced Glycation End-products (RAGE) axis were upregulated. Interestingly, long-term sepsis-induced muscular consequences were not observed in RAGE knockout mice. Overall, we describe for the first time in mice that sepsis causes long-lasting muscle dysfunction after recovery, including mitochondrial alterations and low-grade inflammation, and that RAGE may represent a promising target to mitigate long-term muscle alterations induced by sepsis
Fast ultra-selective 1H-15N 1D NMR spectroscopy unlocks atom-resolved dynamics of low-complexity protein regions
No full textInsight into the conformational dynamics of proteins is essential towards understanding their function at a molecular level. The motions experienced by individual atoms in the protein can be precisely quantified through NMR relaxation rates, but their measurement requires well-resolved spectral responses. Two-dimensional 1H-15N correlation spectra are the standard approach to resolve amide signals in protein NMR, but come with an excessive cost in experimental time when spectra are heavily congested due to limited 15N chemical shift dispersions. This limitation often thwarts complete characterization of dynamics for intrinsically disordered proteins, especially when they feature low-complexity or homopolymer amino acid sequences. Here, we introduce an ultra-selective 1H-15N NMR method that allows high-quality measurement of individual 15N spinrelaxation constants using fast 1D NMR spectra, even when 15N resonances are merely 6-8 Hz apart. We demonstrate the new experiment by characterizing, for the first time, pico-to nanosecond dynamics along a 16-residue polyglutamine stretch within the protein huntingtin, the causal agent of Huntington's disease, as well as millisecond conformational exchange in the SH3GL3 protein. The new experiment will find wide application in the study of conformational dynamics of intrinsically disordered proteins or any other biomacromolecule that features highly dense 1H-15N 2D spectra
Cell wall arabinogalactan is responsible for Fungitell® cross reactivity in nocardiosis
No full textInternational audienceNocardiosis is a serious infection in immunosuppressed patients, especially transplant recipients. The slow-growing phenotype of the bacterium and the variety of symptoms complicate diagnosis and delay antimicrobial therapy, resulting in high mortality rates despite effective treatments. A further complication is that some nocardiosis patients test positive in fungal diagnostics that detect (1,3)-β-D-glucan (the Fungitell® assay), but the basis for this cross-reactivity remains unknown. We demonstrate that nocardial cell wall arabinogalactan is a cryptic antigen responsible for cross-reactivity in the Fungitell® assay and that this antigen is revealed in vivo following bacterial cell lysis. We further show that the reactivity results from a β-glucose substitution of the galactan domain, a modification specific to nocardia, and identify the optimal antigen as a tetramer of the trisaccharide repeating unit. By providing structural evidence for Fungitell® cross-reactivity during nocardiosis, this work paves the way for developing specific diagnostic tools that are currently lacking