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Intestinal in vitro model mimicking tissue microstructuration and dynamics
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Pregnancy and neonatal outcome following in utero exposure to CFTR modulators: A multicentre prospective case series
No full textInternational audienceBackground: Clinical data regarding in utero exposure to CFTR modulators (CFTRm) are limited. Our objective was to describe pregnancy outcomes, with particular attention to malformations, and neonatal adverse outcomes among prospective pregnancies exposed to CFTRm, using clinical data from the French Network of Pharmacovigilance Centres and the Teratology Information Service CRAT (Centre de Reference sur les Agents Tératogènes).Methods: An observational multicentre study was performed on the reported CFTRm-exposed pregnancies with an expected delivery date between 2018 and 2023. We described prospective cases, defined as pregnancies for which the outcome was unknown and no adverse prenatal outcome was diagnosed at the time of first contact with the healthcare professional. Major congenital anomalies (MCA) were classified according to criteria of the European Registration of Congenital Anomalies and Twins.Results: Fifty-eight pregnancies were included, mainly exposed to elezacaftor/tezacaftor/ivacaftor throughout pregnancy (87.9 %).There were 53 live births, four spontaneous abortions and one medical abortion (fetus with cystic fibrosis). One atrial septal defect and one acrania/anencephaly were observed, resulting in a MCA prevalence of 3.4 % (IC95 %: 0.4- 11.9). There were three neonatal adverse outcomes without a clearly identified cause: one sudden massive alveolar hemorrhage, one delayed respiratory distress and one delayed transient hypotonia. No cataract was found in children who had an ophthalmological examination (n = 10).Conclusions: This prospective case series - the largest to date - does not suggest a high rate of MCA or neonatal adverse outcomes in CFTRm-exposed pregnancies. Further studies including long-term follow-up of in utero exposed children are needed to confirm these findings
Challenges of dipeptide identification for a better characterization of nutritional quality of food and derivatives
No full textInternational audienceBioactive peptides (2 to 20 amino acids (AAs)) from food sources are typically inactive within the sequence of the parent protein but, after being released through enzymatic proteolysis, can exert a range of physiological functions. Bioactive peptides derived from agri-food industry products or byproducts exhibit a wide range of biological activities, such as antihypertensive, antioxidative, antibacterial... BIOPEP is one of the most comprehensive databases of bioactive peptides, referencing more than 5,000 peptides. Nearly 45% of these latter are ultra-short- peptides (USPs, composed of 2 to 5 AAs)—comprising 581 dipeptides, 754 tripeptides, 385 tetrapeptides, and 511 pentapeptides, totaling 2,231 USPs. However, while analytical methods are efficient for larger peptides, USPs still present characterization challenges due to their “metabolomic” nature.First, 209 molecular descriptors were computed from the SMILES of all 400 L-dipeptides and used for principal component analysis (PCA) and heatmap visualization to select 25 representative dipeptides based on their descriptor-based heterogeneity. Each AA appears at least once in this model dipeptide set. Second, dipeptide analyses were performed using both C18 and HILIC HPLC columns, coupled with an ESI-QTOF-MS.This work illustrates the bioinformatic strategy employed for dipeptide selection and highlights the importance of chromatographic phase orthogonality. Furthermore, we present the strategy envisioned for annotating USPs, leveraging the maximum amount of information extracted from MS/MS data. Although manual identification of dipeptides in a standard mixture is feasible under the described peptidomic conditions, current metabolomics- and peptidomics-dedicated software lacks the capability for accurate and automated dipeptide annotation. Optimizing HPLC conditions (e.g., column type, temperature) or leveraging amino acid-specific fragment ions could enhance dipeptide identification
Prévalence de Salmonella et Escherichia coli dans les élevages de porcs de Yopougon (Côte d'Ivoire)
No full textInternational audienceMicrobiological contamination of pork is a growing concern as its consumption increases. This study aims to examine the microbiological contamination of pork by bacteria of the genus Salmonella and Escherichia in a pig production environment. To this end, forty (40) faecal samples from pigs raised in pens on four (04) farms in the commune of Yopougon were collected and analysed. Conventional microbiological methods, including enrichment, pre-enrichment, selective culture, isolation on plain agar and biochemical tests, were used to identify the specific biochemical characteristics of each bacterium. The overall prevalence of the genus Escherichia was 80% with no significant variation between farms (p=0.946) or according to animal status (p=0.614). In addition, the prevalence of Salmonella species was 12.5%, also with no significant difference between groups.These preliminary data suggest significant circulation of E. coli and, to a lesser extent, Salmonella in the farms studied. Further studies are needed to assess the pathogenic potential of the identified strains and optimise biosecurity measures among stakeholders in the pig farming sector in Côte d'Ivoire.La contamination microbiologique de la viande de porc est une préoccupation de plus en plus importante à mesure que sa consommation augmente. Cette étude vise à examiner la contamination microbiologique de la viande de porc par les bactéries du genre Salmonella et Escherichia dans un environnement de production porcine. A cet effet, quarante (40) échantillons fécaux de porcs élevés en enclos dans quatre (04) fermes de la commune de Yopougon ont été collectés et analysés. Les méthodes microbiologiques classiques, y compris l'enrichissement, le pré-enrichissement, la culture sur milieu sélectif, l'isolement sur gélose ordinaire et les tests biochimiques, ont été utilisées pour identifier les caractéristiques biochimiques spécifiques de chaque bactérie. La prévalence globale du genre Escherichia était de 80 % sans variation significative entre les fermes (p=0,946) ou selon le statut des animaux (p=0,614). En outre, la prévalence des espèces de Salmonella était de 12,5 % également sans différence significative entre les groupes.Ces données préliminaires suggèrent une circulation importante d'E. coli et, dans une moindre mesure, de Salmonella dans les élevages étudiés. Des études complémentaires sont nécessaires pour évaluer le potentiel pathogène des souches identifiées et optimiser les mesures de biosécurité au niveau des acteurs du secteur de l'élevage porcin en Côte d’Ivoire
Prevention of Hemorrhage After Implantation of Mechanical Circulatory Support With a Purified Von Willebrand Factor Concentrate: results of the early terminated randomized controlled PHAM trial
No full textInternational audienceBackground: Bleeding complications are frequent under left ventricular assist device (LVAD) support. LVAD-associated high shear stress induces increased proteolysis of circulating von Willebrand factor (VWF), which may contribute to this high bleeding rate.Objectives: To assess if a prophylactic administration of a VWF-concentrate could reduce bleeding rate in LVAD-patients METHODS: In this multicentre open-label randomized controlled study, we investigated the efficacy, safety and pharmacokinetic of a plasma-derived VWF-concentrate (WILFACTIN®, LFB, France), administered prophylactically twice-weekly at 50 IU.kg-1 for 3 months after LVAD-implantation, compared to standard of care (SOC). The efficacy end points were the difference in the incidence rate of any, clinically significant or major bleeding post-randomization. Bleeding and thrombotic events were reviewed at week-1, -2 and then every 2 weeks. The study ended prematurely due to deficient recruitment and drug supply constraints, leading to prioritization of prescriptions for VWD-patients. We present the available data.Results: Twenty-nine adult patients (166 planned) were randomized and analyzed. VWF-prophylaxis resulted in a non-significant 55% reduction in bleeding incidence rate compared to SOC (risk ratio, 0.45; 95%CI: 0.18 to 1.04; p=0.06). Accordingly, there was a similar reduction of clinically relevant and major bleeding in VWF-arm. Severe adverse events were similar post-randomization between VWF- and control-arm including deaths (2 and 4 respectively) and thrombotic events (2 in each arm). In pharmacokinetic analysis, a rapid degradation of WILFACTIN® occurred within 24 hours.Conclusions: The lack of observed therapeutic efficacy of VWF-prophylaxis in LVAD-setting is likely due to a short-lived prohemostatic effect due to rapid degradation of VWF-concentrate
The 33 rd Ion Channels Meeting, September 2024, Sète, France
No full textInternational audienceThe 33rd Ion Channels Meeting has been held in Sète, France, from September 8th to 11th. The congress gathered together senior and junior researchers from almost all over the world working on different fields of biology and pathophysiology. The colloquium opened with the plenary lecture on the action mechanisms of α2δ proteins in the trafficking of calcium channels and how these proteins can modulate the channels functional properties, given by Prof. Annette Dolphin. The five symposia of this edition were focused not only on several techniques for studying ion channels and their environment but also on ion channels and their involvement in cancer. Two symposia have been totally dedicated to genetic channelopathies, and the last one was devoted to glutamate receptors. All the presentations of the symposia are reported and summarized in this report meeting article
Clé d'identification des espèces de Toxorhynchites (Diptera : Culicidae), femelles, Région Afrotropicale
No full textClé dichotomique commentée, en français, pour l'identification des espèces de moustiques du genre Toxorhynchites (DIPTERA : Culicidae) de la région afrotropicale. Elle traduit, reprend ou adapte des travaux antérieurs, notamment: Ribeiro H. Systematics and identification of Afrotropical Toxorhynchitinae (Diptera: Culicidae). J Med Entomol. 2005;42: 953–958. doi:10.1093/jmedent/42.6.953 Service MW. Handbook to the Afrotropical Toxorhynchitine and Culicine Mosquitoes, Excepting Aedes and Culex. British Museum (Natural History); 1990. Baldacchino F, Paupy C, Rahola N. Clé de détermination des Culicidae présents en Afrique Centrale et au GABON (document de travail). 2014. Robert V, Ndiaye EH, Rahola N, Le Goff G, Boussès P, Diallo D, et al. Clés dichotomiques illustrées d’identification des femelles et des larves de moustiques (Diptera : Culicidae) du Burkina Faso, Cap-Vert, Gambie, Mali, Mauritanie, Niger, Sénégal et Tchad. Montpellier: IRD; 2022. Available: https://doi.org/10.23708/fdi:010084866 [accessed 30 Sep 2025]Clé dichotomique commentée, en français, pour l'identification des espèces de moustiques du genre Toxorhynchites (DIPTERA : Culicidae) de la région afrotropicale. La clé est valide pour l'identification des femelles. Elle traduit, reprend ou adapte des travaux antérieurs, notamment: Ribeiro H. Systematics and identification of Afrotropical Toxorhynchitinae (Diptera: Culicidae). J Med Entomol. 2005;42: 953–958. doi:10.1093/jmedent/42.6.953 Service MW. Handbook to the Afrotropical Toxorhynchitine and Culicine Mosquitoes, Excepting Aedes and Culex. British Museum (Natural History); 1990. Baldacchino F, Paupy C, Rahola N. Clé de détermination des Culicidae présents en Afrique Centrale et au GABON (document de travail). 2014. Robert V, Ndiaye EH, Rahola N, Le Goff G, Boussès P, Diallo D, et al. Clés dichotomiques illustrées d’identification des femelles et des larves de moustiques (Diptera : Culicidae) du Burkina Faso, Cap-Vert, Gambie, Mali, Mauritanie, Niger, Sénégal et Tchad. Montpellier: IRD; 2022. Available: https://doi.org/10.23708/fdi:010084866 [accessed 30 Sep 2025
Development of explicit definitions of potentially inappropriate prescriptions for antidiabetic drugs in people with type 2 diabetes: A Delphi survey and consensus meeting.
No full textInternational audienceIntroductionExplicit definitions for potentially inappropriate prescriptions (PIPs) are useful for optimizing drug use. The objective of the present study was to validate a list of definitions of PIPs for antidiabetic drugs in a Delphi survey with general practitioners, diabetologists, community pharmacists, hospital pharmacists and pharmacologists from mainland France, Belgium, and Switzerland.MethodsThe experts gave their opinion on each explicit definition and could suggest new definitions. Definitions with a 1-to-9 Likert score of between 7 and 9 from at least 75% of the participants were validated. The results were discussed during consensus meetings after each round.Results46 participants were recruited, and 38 (82.6%) completed the survey. The Delphi survey resulted in a consensus list of 41 explicit definitions of PIPs for antidiabetic drugs in four groups: (i) the need to temporarily discontinue a medication in the event of acute illness (n = 9; 22%), (ii) the need to review and adjust the dosing regimen (n = 26; 36.6%), (iii) the initiation of an inappropriate drug (n = 3; 7.3%), and (iv) the need for further monitoring of a people with type 2 diabetes (n = 3; 7.3%).ConclusionsThe list is specific for antidiabetic drugs (other than insulin) for people with type 2 diabetes. This explicit list could be implemented in a clinical decision support system for the automatic detection of PIPs and might help healthcare professionals involved in the management of people living with type 2 diabetes
Effect of Copper-Catalyzed Oxidation on the Aggregation of the Islet Amyloid Polypeptide
No full textInternational audienceThe islet amyloid polypeptide (IAPP) is a 37-residue peptide hormone secreted by pancreatic β-cells that is known to aggregate into amyloid fibrils. These fibrils accumulate in the pancreatic islets of individuals afflicted with type 2 diabetes and are implicated in β-cell dysfunction. Metal ions such as copper and zinc are known to modulate IAPP fibrillization, yet the role of metal-induced oxidative modifications in this process remains largely unexplored. This study examines the non-enzymatic post-translational oxidation of IAPP and its effects on aggregation using the biologically relevant Cu/O2/ascorbate system. Mass spectrometry identified residues within the amyloidogenic region (residues 20–29) as the primary targets of oxidation. These oxidative modifications impaired the formation of cross-β-sheet amyloid fibrils and promoted the accumulation of amorphous aggregates. The H18A IAPP derivative, lacking the key metal-binding histidine, was also examined to assess the impact of sequence variation on oxidation and aggregation. Copper-mediated oxidation of H18A resulted in a broader distribution of oxidation sites and impacts fibril formation. These findings provide preliminary mechanistic insights into copper-induced oxidation and its impact on IAPP aggregation pathways
Beyond boundaries: unveiling the art of blockchain-enshrined molecules through xSublimatio
No full textInternational audienceIn 2023, the xSublimatio project showcased a fusion of art and science, presenting an interactive platform where molecules were transformed into digital artworks within the blockchain. This innovative concept leveraged advanced artificial intelligence predictions to bridge empirical precision with creative expression, offering a unique exploration of scientific data through artistic interpretation.The creation of xSublimatio involved meticulous selection and representation of molecules, blending scientific accuracy with aesthetic appeal. Through AlphaFold-inspired insights, the project reimagined molecular design, transcending traditional boundaries.During its presentation at the GDR ChemBio conference in Strasbourg, xSublimatio sparked insightful discussions within the French chemistry community. This article explores its technical implementation, its potential for introducing blockchain and non-fungible token concepts to diverse communities, and its broader implications for interdisciplinary collaboration and decentralized science