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Alcohol Rehabilitation Within 3 Months after Alcohol Hepatitis and Survival - A National Analysis
No full textInternational audienceBackground and aimsThere is limited understanding of the benefits of alcohol rehabilitation after alcohol hepatitis (AH).MethodsWe conducted a 2012-2021 national longitudinal study involving adult inpatients diagnosed with AH in France. We assessed the primary outcome of liver transplantation or death within one year after AH, including in its complicated form (CAH) defined as ≥ 2 hepatic or extrahepatic complications within 4 weeks after AH. The primary exposure was in-hospital alcohol rehabilitation within 3 months following AH. Patients who died (6.5%, n=5,282) or were censored (12.5%, n=10,180) ≤ 4 weeks after AH were excluded. We measured adjusted hazard ratios (aHR) and odds ratios (aOR) within the full cohort and propensity-matched samples.ResultsAmong 65,737 patients (median age 52; IQR 44–60; 76% male), 12% died or underwent liver transplantation. In-hospital alcohol rehabilitation was noted for 25% of patients (15.2% among CAH patients) and was the primary discharge diagnosis for 13.3%. The one-year transplant-free survival rates were 94% (95% CI: 94% to 95%) for rehabilitated patients, compared to 85% (85% to 86%) for those without [aHR 0.62 (0.57 to 0.69) p < 0.001]. Among CAH patients, transplant-free survival was 78% (76% to 81%) with rehabilitation versus 70% (69% to 71%) without [aHR 0.82 (0.68 to 0.98) p = 0.025]. In propensity-matched samples, rehabilitation was linked to an aOR of 0.54 (0.49 to 0.55, p < 0.001) overall, and 0.73 (0.60 to 0.89, p = 0.002) among matched CAH patients.ConclusionsIn-hospital alcohol rehabilitation within 3-months after AH and CAH improve transplant-free survival rate but remain underutilized
Study of the prebiotic properties of wood-hemicellulose oligosaccharides
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How social pharmaceutical innovations are addressing problems of availability, accessibility and affordability of drugs for rare diseases
No full textInternational audienceBackgroundThe current organization of the pharmaceutical innovation system poses three major challenges for rare disease patients in terms of availability, accessibility and affordability of treatments. While some changes have emerged in the European Union to address some of these challenges, their impacts are not experienced uniformly across member states nor around the world. We have observed niche initiatives that are actively working to address those challenges within their local contexts. In a position paper in this journal, we characterized such initiatives as “social pharmaceutical innovation” (or SPIN): novel collaborations involving diverse sets of actors that break with conventional pharmaceutical innovation practices to develop interventions that address unmet societal needs of rare disease patients and that are not primarily market driven.ResultsHere we report on 15 cases of SPIN across Brazil, Canada, France and the Netherlands that we studied through semi-structured qualitative interviews (n = 151) with players involved in those cases. Our findings show how SPIN initiatives are reconfiguring pharmaceutical innovation networks to include a wider range of actors in redistributed and differentiated roles within innovation processes. Further, we find that SPINs are associated with changes in the ways data is gathered (often in clinical contexts rather than in conventional trials), and how evidence is assembled to improve access to the treatments. Finally, we demonstrate how SPINs are providing new routes for patients to access treatments for rare diseases, often at more affordable prices.ConclusionsWhile promising, SPINs are not perfect solutions for rare disease patients or the broader challenges to the pharmaceutical innovation system. SPINs are specific solutions adapted to the particulars of local framing, institutions, national policy and care contexts of rare diseases, and should be developed as such. Our findings support these recommendations for SPIN: use local knowledge and expertise in crafting SPINs; develop comprehensive strategies for data governance, access and ownership; and explore new economic models to recoup investments and/or sustain future initiatives. We invite collaboration on these topics and emerging SPIN initiatives so as to support efforts at addressing challenges of availability, accessibility and affordability of treatments for rare diseases patients
The FMDV_PersIstOmics project: From proteogenomic host response signatures of persistent foot-and-mouth disease virus (FMDV) infection to diagnostic markers and therapeutic control
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Advancing Genotoxicity Assessment by Building a Global AOP Network
No full textInternational audienceCurrent genotoxicity testing strategies face several challenges, including a high incidence of misleading positive results that lead to unnecessary animal testing, limited mechanistic insights, insufficient integration of innovative methodologies, and a lack of quantitative assessment. Despite rapid advancements in technology and scientific understanding, genotoxicity testing batteries have remained largely unchanged for years. To modernize genotoxicity assessment and incorporate innovative approaches, the development of Integrated Approaches for Testing and Assessment (IATAs) is essential. These frameworks combine existing knowledge with data from New Approach Methodologies (NAMs) aiming to reduce or eliminate reliance on in vivo testing. Genotoxicity is particularly well‐suited for IATA development as numerous cutting‐edge, non‐animal methods have emerged in recent years, including 3D test systems, Prediscreen, MultiFlow, ToxTracker, and transcriptomic‐based biomarkers such as GENOMARK and TGx‐DDI. However, the integration of NAMs into IATAs must be systematic and scientifically robust. In this process, the Adverse Outcome Pathway (AOP) framework plays a crucial role by linking molecular‐level events to adverse health effects, thereby supporting the structured selection of NAMs. This article explores the key challenges and gaps within the current European regulatory frameworks for chemical compound genotoxicity assessment and discusses how an AOP‐based IATA can address these issues. Additionally, we present a global AOP network for permanent DNA damage, designed to guide IATA development and improve regulatory decision‐making. This integrated approach has the potential to enhance the accuracy, efficiency, and ethical standards of genotoxicity assessment while reducing reliance on animal testing
Corrigendum to “Epidemiology of Staphylococcus aureus food isolates: Comparison of conventional methods with whole genome sequencing typing methods” [Food Microbiol. volume 125, January 2025, 104625]
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Emergence of Neuroendocrine Tumors in Patients Treated with Androgen Receptor Pathway Inhibitors for Metastatic Prostate Cancer: A Systematic Review and Meta-analysis
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First report of Diaphorina citri and 'Candidatus Liberibacter asiaticus' associated with the Huanglongbing disease on Citrus spp. in French Guiana
No full textSource Agritrop Cirad (https://agritrop.cirad.fr/615528/)International audienceHuanglongbing (HLB) is a disease on citrus associated with three unculturable phloem-limited gram-negative bacterial species transmitted through grafting or by two psyllids: Diaphorina citri (ACP) and Trioza erytreae (Bové 2006). HLB is considered the worst constraint on citrus worldwide, where major active epidemics involve 'Candidatus Liberibacter asiaticus' (CLas) and ACP. In the French West Indies, ACP was detected in Guadeloupe (1998) and Martinique (2012), followed by CLas detection in 2012 and 2013, respectively. In French Guiana, under the direction of the French Ministry of Agriculture regional services (DEAAF), FREDON Guyane has been monitoring HLB and its psyllid vectors since 2016. The first detection of D. citri occurred on 22 July 2021 in the Madeleine district of Cayenne within the Murraya paniculata sentinel network and on various Citrus spp. Species identification was confirmed morphologically on 2 August 2021 by the French National Reference Laboratory for Insects (ANSES, Plant Health Laboratory, Entomology and Botany Unit), but no Liberibacter sp. test was done. At this stage, citrus trees did not show clear HLB symptoms (blotchy mottle patterns and yellow islands on leaves). Suspicious plant samples of M. paniculata and Citrus spp. were regularly transmitted to the National Reference Laboratory for bacteria on citrus and tropical plants (ANSES, Plant Health Laboratory, Tropical Pests and Diseases Unit, Reunion Island) for analysis, using the official French method ANSES/LSV/MA 068 based on the Li et al. (2006) real-time PCR. DNA extractions (DNeasy Plant Mini Kit, Qiagen) were performed on leaf midribs, along with a negative control (Citrus paradisi 'Star Rubis'). Amplifications were performed on two wells, giving an average Cq value. In September 2021, typical amplification curves were obtained on one sample of M. paniculata (Cq = 34.36; SD = 0.314). The same scenario occurred in March 2022 on a sample from an old citrus tree (Cq = 31.27; SD = 0.241) collected in a private courtyard in Sinnamary and in July 2023 on a citrus tree (Cq = 31.83; SD = 0.074) from an orchard in Kourou. This last sample's positive status was further confirmed through the real-time PCR protocols from Morgan et al. (2012) (Cq = 33.25; SD = 0.027), Zheng et al. (2016) (Cq = 33.05; SD = 0.237), and de Chaves et al. (2023) (Cq = 34.19; SD = 0.850). Following the impossibility to characterize the species of 'Ca. Liberibacter spp.' detected (40 out of 352 samples since 2022), hampered by its in planta low titer, a field survey was organized in November 2024. CLas was detected on one sample of citrus tree from a private courtyard in Kourou (Cq = 26.31; SD = 0.288), confirmed by the method of de Chaves et al. (2023) (Cq = 27.507; SD = 0.07). Higher in planta titer allowed for the CLas species characterization through conventional PCR (CLas observed band of 703 bp) (Hocquellet et al. 1999; Teixeira et al. 2005). Sanger sequencing (Genewiz U.K., 678 bp) of this amplicon (Genbank no. PV018783) showed 100% identity (BLASTn) with the CLas strain CP131152. To our knowledge, this is the first report of the presence of HLB in French Guiana, involving the CLas species and the vector D. citri. All year long, high heat could explain in planta HLB low titer. The introduction events remain unclear. This report highlights the importance of plant certification, psyllid population control, and surveillance of territories close to French Guiana
Improving Sortase A-mediated transpeptidation reactions by electrostatically-assisted capture
No full textInternational audienceSortase A (SrtA) is a widely used transpeptidase for protein modification. However, the reversible nature of the SrtA-catalyzed transpeptidation reactions provides limited yields. In this study, we report a substrate engineering strategy that extends the LPxTG recognition motif with a positively charged poly-arginine peptide module. This enables sequence-specific capture of the released peptide via electrostatically-assisted aminolysis of a negatively charged thioester, thus shifting the equilibrium toward product formation. The approach is traceless, selective, operates under mild conditions, and improves SrtA efficiency with only a moderate excess of substrate
Dialogue inclusif avec les communautés locales : pratiques parmi les professionnels et le combat pour l'équité et l'engagement des publics dans les musées et centres de science
No full textInternational audienceThis study aimed to understand the actions carried out for dialog between science centers and science museums with the public of local communities living in a situation of socioeconomic vulnerability. The study adopted a quantitative and qualitative approach and the theoretical framework of science communication, of the exercise of citizenship and of engagement with science, using concepts such as Technoscientific Citizenship, Social Appropriation of Science and Technology, and Science Capital. Also, a few previous visitor studies on the same purpose of inclusion and social equity were considered. The methodology involved the participation of professionals who work in Brazilian institutions, in two stages of data collection, both carried out online. Initially, a questionnaire was answered by 69 professionals, of whom nine took part in in‐depth interviews. The qualitative data was analyzed using the Discourse of the Collective Subject (DCS) method, from which the results have been presented in three Categories and twelve Synthesis‐Speeches. The establishment of a dialog with a broader public involves taking on a long‐term institutional commitment, developing broad access mechanisms with respect to cultural differences. It is fundamental to make constant and careful efforts to welcome a diverse public and meet the challenge of breaking down prejudices. The implementation of the social role of science centers and science museums not only democratize knowledge but promotes a freedom feeling and the raise of self‐esteem of those who engage in its activities. The results corroborated previous studies, stating that to build a legacy and to foster significant changes in the profile of the audience, the social exclusion needs to be treated as a structural, complex, and multifaceted issue.Cette étude visait à comprendre les actions menées pour favoriser le dialogue entre les musées des sciences et les centres des sciences avec le public des quartier vivant dans une situation de vulnérabilité socio-économique. L'étude a adopté une approche quantitative et qualitative et le cadre théorique de la communication scientifique, de l'exercice de la citoyenneté et de l'engagement envers la science, en utilisant des concepts tels que la citoyenneté technoscientifique, l'appropriation sociale de la science et de la technologie, et le capital scientifique. En outre, quelques études antérieures sur les visiteurs ayant le même objectif d'inclusion et d'équité sociale ont été prises en compte. La méthodologie a impliqué la participation de professionnels travaillant dans des institutions brésiliennes, en deux étapes de collecte de données, toutes deux réalisées en ligne. Dans un premier temps, un questionnaire a été rempli par 69 professionnels, dont neuf ont participé à des entretiens approfondis. Les données qualitatives ont été analysées à l'aide de la méthode du Discours du Sujet Collectif (DCS), à partir de laquelle les résultats ont été présentés en trois catégories et douze discours de synthèse. L'établissement d'un dialogue avec un public plus large implique de prendre un engagement institutionnel à long terme, en développant des mécanismes d'accès larges et respectueux des différences culturelles. Il est fondamental de faire des efforts constants et minutieux pour accueillir un public diversifié et relever le défi de briser les préjugés. La mise en œuvre du rôle social des centres des sciences et des musées des sciences permet non seulement de démocratiser les savoirs, mais aussi de promouvoir un sentiment de liberté et d'améliorer l'estime de soi de ceux qui participent à leurs activités. Les résultats corroborent les études précédentes, qui affirment que pour construire un héritage et favoriser des changements significatifs dans le profil du public, l'exclusion sociale doit être traitée comme une question structurelle, complexe et multiforme