HAL-Inserm
Not a member yet
90480 research outputs found
Sort by
Intubation of obese patients in the operating room with or without bag-mask ventilation: study protocol for a randomized multicenter trial (VENT OR NOT)
No full textInternational audienceBackground: Almost two-thirds of the adults in Europe are overweight or obese. Obese patients are at higher risk of complications, especially during intubation. Therefore, the management of general anesthesia is crucial. Regarding intubation, there is no consensus among anesthesiologists between the two strategies: standard sequence intubation (i.e., with bag-mask ventilation between induction and intubation) vs. rapid sequence intubation (i.e., without bag-mask ventilation between induction and intubation) assuming that these patients are at high risk of inhalation and desaturation during apnea. This study aims to compare the incidence of intubation-related complications between these two strategies in severely obese patients undergoing elective surgery.Methods: The VENT OR NOT study is a prospective, multicenter, open-label, randomized trial including obese patients with a body mass index ≥ 35 kg/m2 requiring tracheal intubation before scheduled surgery. We will assess the superiority of the standard sequence intubation (\"VENT strategy\") compared with the rapid sequence intubation (\"NO VENT strategy\") to prevent intubation-related complications in 702 obese patients. Enrolment started in September 2023 in 13 French academic and nonacademic hospitals and is expected to finish in September 2025. The primary outcome is a composite criterion of complications occurring from the induction of general anesthesia up to 10 min after intubation including: oxygen desaturation < 95%, intubation failure on the first attempt, aspiration or regurgitation, and severe hypotension defined as a systolic blood pressure < 80 mmHg. The VENT OR NOT trial began after ethics committee approval has been obtained and is carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines.Discussion: The VENT OR NOT trial is the first randomized controlled trial designed to investigate whether the \"VENT strategy\" reduces the risk of intubation-related complications compared with the \"NO VENT strategy\" for elective surgery.Trial registration: ClinicalTrials.gov NCT05930678. Registered on June 1, 2023
Unraveling the neurophysiological correlates of phase-specific enhancement of motor memory consolidation via slow-wave closed-loop targeted memory reactivation
No full textInternational audienceMemory consolidation can be enhanced during sleep using targeted memory reactivation (TMR) and closed-loop (CL) acoustic stimulation on the up-phase of slow oscillations (SOs). Here, we test whether applying TMR at specific phases of the SOs (up vs. down vs. no reactivation) can influence the behavioral and neural correlates of motor memory consolidation in healthy young adults. Results show that up- (as compared to down-) state cueing results in greater performance improvement. Sleep electrophysiological data indicate that up- (as compared to down-) stimulated SOs exhibits higher amplitude and greater peak-nested sigma power. Task-related functional magnetic resonance images reveal that up-state cueing strengthens activity in - and segregation of - striato-motor and hippocampal networks; and that these modulations are related to the beneficial effect of TMR on sleep features and performance. Overall, these findings highlight the potential of CL-TMR to induce phase-specific modulations of motor performance, sleep oscillations and brain responses during motor memory consolidation
High-Pressure Intrusion of Saline Solutions in Hydrophobic STT-Type Zeosil
No full textInternational audienceHigh-pressure intrusion of water and LiCl aqueous solutions at different concentrations in hydrophobic STT-type zeosil was studied for possible applications in absorption and storage of mechanical energy. The water is intruded at a pressure of 35 MPa and remains trapped in the pores after pressure release, which corresponds to bumper behavior with total energy absorption. The use of LiCl solution leads to a change in system behavior, regardless of the concentration investigated (10, 15, or 20 M). Its intrusion is mainly reversible, but a small part of the intruded liquid remains in the pores after the first intrusion–extrusion cycle, which corresponds to a mixed behavior of bumper and shock absorber. The intrusion pressure rises strongly with an increase in salt concentration and reaches 227 MPa for a LiCl 20 M solution; the stored energy of 27 J/g can be achieved. The characterization of STT-type zeosil before and after intrusion–extrusion tests by structural and physicochemical methods shows that silanol defects are formed both under the intrusion of water and LiCl solutions. The relationship between zeosil structure and intrusion–extrusion characteristics is discussed by comparing the results obtained with those of other structural types of zeosils
Inflammatory Signatures in VEXAS Syndrome, Myelodysplasia Cutis, and Sweet Syndrome
No full textInternational audienceImportance VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a monogenic disease caused by UBA1 somatic variants in hematopoietic progenitor cells, mostly involving adult men. It is associated with inflammatory-related symptoms, frequently involving the skin and hematological disorders. Recently described myelodysplasia cutis (MDS-cutis) is a cutaneous manifestation of myelodysplasia in which clonal myelodysplastic cells infiltrate the skin. In both cases, skin lesions are driven by the infiltration of clonal mutated myeloid cells and may clinically and histologically mimic Sweet syndrome (SS), a neutrophilic skin disease. Objective To decipher the underlying mechanisms driving these 3 myeloid-related skin diseases (ie, VEXAS, MDS-cutis, and SS) compared with leukemia cutis (LC), a neoplastic blastic myeloid-related skin condition, and healthy control skin samples. Design, Setting, and Participants This multicenter translational study on formaldehyde-fixed paraffin-embedded lesional skin samples of VEXAS syndrome, MDS-cutis, idiopathic SS, LC, and healthy controls using bulk RNA sequencing analyses was conducted in France. Patients included had cutaneous lesions of VEXAS syndrome, MDS-cutis, idiopathic SS, or LC. The data were analyzed from June 2023 to March 2024. Main Outcomes and Measures Differentially expressed genes between conditions were studied. These genes were used to characterize the enrichment in activated inflammatory pathways in each condition using Gene Set Enrichment Analysis and Ingenuity Pathway Analysis. Results Twenty patients with skin conditions (median [range] age, 67 [43-88] years; 10 [50%] men) were included. Six had cutaneous lesions of VEXAS syndrome, 4 had MDS-cutis, 5 had idiopathic SS, and 5 had LC. They were compared with 5 healthy control skin samples. Bulk RNA sequencing analysis reveals that MDS-cutis and VEXAS syndrome lesions display closely related transcriptomic profiles, highly imprinted by cytokine responses, interferon signatures, and activation of the apoptosis pathway. A shared inflammatory environment between MDS-cutis, VEXAS syndrome, and idiopathic SS was observed, mostly relying on a type 1 immune response led by type 1 and 2 interferons, along with the activation of tumor necrosis factor and interleukin (IL)–1β pathways. Conversely, LC showed an isolated transcriptomic profile mainly enriched in cell cycle pathways. Conclusions and Relevance The findings of this translational study highlight a common inflammatory pattern shared between VEXAS syndrome, MDS-cutis, and refractory idiopathic SS skin samples. This suggests the potential therapeutic targeting of interferon pathways in patients affected with refractory nonblastic myeloid-related skin diseases
Splenic stiffness does not predict esophageal varices in children with portal hypertension
No full textInternational audienceObjective : To investigate ultrasound parameters, particularly splenic stiffness, as predictors of pediatric esophageal varices.Methods : We included all children aged 0–19 years who underwent esophagogastroduodenoscopy, for variceal screening or surveillance, and abdominopelvic ultrasound with splenic elastography measurement. We also recorded biological parameters (platelets count, albumin) to determine a clinical prediction rule (CPR). Derivation and validation cohorts were defined according to measurement date. Receiver-operating characteristic (ROC) statistics and sensitivity, specificity, positive predictive value, and negative predictive value for the optimal threshold value were calculated, and used to assess the performance of each parameter.Results : Eighty derivation cohort children and 58 validation cohort children formed the study sample. Cohort characteristics did not differ for age, sex, distribution of varices but differ for some etiologies, abdominal surgery, spleen size, splenic stiffness measurement (SSM), ascites, and the presence of spontaneous portosystemic shunts. In the derivation cohort, splenic stiffness was the best independent predictor of esophageal varices, with an area under the ROC curve (AUC) of 0.83, a sensitivity of 0.90, and specificity of 0.73 at a threshold of 22 kPa. In the validation cohort, SSM was no longer significantly associated with esophageal varices at endoscopy, had a lower sensitivity of 0.26, and no other threshold could be found. Liver stiffness measurement (LSM) and CPR had a correct predictive value (AUC 0.70 for LSM; 0.78 for CPR in the derivation cohort and 0.64 for LSM; 0.71 for CPR in the validation cohort) for esophageal varices.Conclusions : SSM cannot be used as a single parameter to predict esophageal varices. LSM and CPR despite their lower AUC appear to much more robust measures with consistent results across cohorts
Predicted Structures of Ceduovirus Adhesion Devices Highlight Unique Architectures Reminiscent of Bacterial Secretion System VI
No full textInternational audienceBacteriophages, or phages, are sophisticated nanomachines that efficiently infect bacteria. Their infection of lactic acid bacteria (LAB) used in fermentation can lead to significant industrial losses. Among phages that infect monoderm bacteria, those with siphovirion morphology characterized by a long, non-contractile tail are predominant. The initial stage of phage infection involves precise host recognition and binding. To achieve this, phages feature host adhesion devices (HADs) located at the distal end of their tails, which have evolved to recognize specific proteinaceous or saccharidic receptors on the host cell wall. Ceduovirus represents a group of unique lytic siphophages that specifically infect the LAB Lactococcus lactis by targeting proteinaceous receptors. Despite having compact genomes, most of their structural genes are poorly annotated and the architecture and function of their HADs remain unknown. Here we used AlphaFold3 to explore the Ceduovirus HADs and their interaction with the host. We show that Ceduovirus HADs exhibit unprecedented features among bacteriophages infecting Gram + , share structural similarities with bacterial secretion system VI, and combine both saccharide and proteinbinding modules. Moreover, we could annotate the majority of Ceduovirus genes encoding structural proteins by leveraging their predicted structures, highlighting AlphaFold's significant contribution to phage genome annotation
The socioeconomic environment and access to care affect the survival of patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma
No full textInternational audienceBackground: The socioeconomic environment and access to care may influence the prognosis of patients with primary liver cancer. We aimed to study the effects of the socioeconomic environment and access to care on the net survival of patients with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (iCCA).Methods: All patients with HCC or iCCA who were diagnosed between 2013 and 2015 within the French network of cancer registries were included, with follow-up until June 2018. The socioeconomic environment and access to care were assessed using the European Deprivation Index and the Spatial Accessibility Multiscalar (SCALe) index. The excess hazard ratios (EHR) were estimated and modelled using flexible parametric survival models with multidimensional penalized splines.Results: In total, 6137 patients were included (4931 with HCC and 1206 with iCCA). The 5-year net survival rates for men and women with HCC were 19.7% (95% confidence interval (CI) [18.1; 21.3]) and 20.0% (95% CI [16.2; 24.1]), respectively, and the 5-year net survival rates for men and women with iCCA were 10.4% (95% CI [7.5;14.0]) and 10.3% (95% CI [7.4;13.8]), respectively. A socioeconomic gradient was identified between the most and the least deprived areas for men with HCC (EHR 1.16 (95% CI [1.04;1.29]). Difficult access to care negatively affected the net survival of women with HCC (EHR 1.36 (95% CI [1.10;1.68]) corresponding to the 3rd quintile of distribution) and women with iCCA (EHR 1.37 (95% CI [1.07;1.76]) for the most isolated quintile compared with the least isolated quintile).Conclusions: This study provides distinct net survival analyses for patients with HCC and iCCA. The net survival of patients with HCC is twice as high as that of patients with iCCA. The social environment adversely affects the net survival of men with HCC, whereas the geographical environment adversely affects that of women with HCC and iCCA
Multimode ultrastrong coupling in three-dimensional photonic-crystal cavities
No full textInternational audienceAbstract Recent theoretical studies have highlighted how spatially varying cavity electromagnetic fields enable novel cavity quantum electrodynamics phenomena, such as the Dicke superradiant phase transition. Three-dimensional photonic-crystal cavities, which exhibit discrete in-plane translational symmetry, overcome this limitation, but fabrication challenges have hindered the achievement of strong coupling. Here, we demonstrate multimode ultrastrong coupling between cavity modes of a three-dimensional photonic-crystal cavity at terahertz frequencies and the cyclotron resonance of a Landau-quantized two-dimensional electron gas in gallium arsenide. The multimode coupling depends on the spatial profiles of the cavity modes, resulting in distinct coupling scenarios based on probe polarization. Our results align with an extended multimode Hopfield model that accounts for spatial field variations. Guided by the model, we discuss possible strong ground-state correlations between cavity modes and introduce relevant figures of merit for multimode ultrastrong coupling. Our findings highlight the crucial role of spatial inhomogeneity in multimode ultrastrong coupling
Development of potent Affitin-based bispecific NK cell engagers for the therapy of MSLN-expressing cancers
No full textInternational audienceWell-characterized tumor associated antigens (TAA) represent targets of interest in many anti-cancer therapeutic strategies. Even though the use of monoclonal antibodies has led this field for years, the development of smaller molecules, with improved properties, holds great potential for specific anticancer applications. Affitins are a type of small (7 kDa), thermostable and high affinity non-immunoglobulin protein scaffolds derived from archaea. Using ribosome display and next generation sequencing, we isolated the first Affitins specific for human mesothelin (hMSLN), a TAA over-expressed in many solid cancers and targeted currently in clinical trials. The homodimerization of the most promising Affitin (N13) allowed to improve affinity by 60-fold (from 35 nM to 0.57 nM). The high specificity of N13 was demonstrated on cell co-cultures under static or dynamic conditions. This Affitin, monomeric or dimeric, was also stable under a wide range of temperatures and upon repeated freeze/thaw cycles. Finally, Bispecific natural killer (NK) cell Engagers (BiKE) composed of an anti-CD16 VHH fused to a monomer or a dimer of N13 Affitins were constructed. Using a cytotoxicity assay, we showed the specific lysis of hMSLN expressing cells in the presence of BiKE and NK cells supporting the potential therapeutic application of these affinity agents
Fundamental Neurochemistry Review: Sphingolipids and Ceramides in Brain Development
No full textInternational audienceLipids are emerging as key players in regulating neural stem cells and their progeny. Recent lipidomic profiling studies clearly illustrate the significance of lipids across cerebral cortical development and evolution. In this review, we identify the existing knowledge concerning the importance of lipids in cortex development and neurogenesis processes, with a special emphasis on ceramide-based sphingolipids. We then discuss the lipidation of factors that are relevant for cortex development and how their interaction with ceramides facilitates certain intracellular processes. We further summarize the importance of ceramides in different intracellular compartments and organelles, and finally discuss the alterations of sphingolipid metabolism in neurological disorders, particularly of neurodevelopmental origin.</div