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Decadal trends (2013–2023) in PM<sub>10</sub> sources and oxidative potential at a European urban supersite (Grenoble, France)
No full textInternational audienceThe identification of particulate matter (PM) sources and the quantification of their contribution to the urban environment is a necessary input for policymakers to reduce the air pollution impacts. The association between the PM sources and the oxidative potential (OP) is also a key indicator for evaluating the ability of PM sources to induce in-vivo oxidative stress and lead to adverse health effects, which becomes an emerging metric in the Directive on ambient air quality (22024/2881/EU). Most studies in Europe have focused on PM and OP sources in the short term, for only 1 or 2 years. However, the efficiency of reduction policies, trends, and epidemiological impacts cannot be properly evaluated with such short-term studies due to a lack of statistical robustness. Here, long-term PM10 filter sampling at the Grenoble (France) urban background supersite and detailed chemical analyses were used to investigate decadal trends of the main PM sources and related OP metrics. Positive matrix factorization (PMF) analyses were conducted on the corresponding 11-year dataset (January 2013 to May 2023, n=1570), enlightening the contributions of 10 PM sources: mineral dust, sulfate-rich, primary traffic, biomass burning, primary biogenic, nitrate-rich, MSA-rich, aged sea salt, industrial and chloride-rich. The stability of the chemical profile of these sources was validated by comparison with the profiles retrieved from shorter-term (3 years) successive PMF analyses. A Seasonal-Trend using LOESS decomposition was then applied to evaluate the trends of these PM10 sources, which revealed a substantial decrease in PM10 (−0.73 µgm-3yr-1) as well as that of many of the PM10 sources. Specifically, negative trends for primary traffic and biomass burning sources are detected, with a reduction of 0.30 and 0.11 µgm-3yr-1, respectively. The OP PM10 source apportionment in 11 years confirmed the high redox activity of the anthropogenic sources, including biomass burning, industrial, and primary traffic. Eventually, downward trends were also observed for OPAA and OPDTT, mainly driven by the reduction of residential heating and transport emissions, respectively
Subcutaneous infliximab in inflammatory bowel disease: bridging the gap between theory and practice.
No full textInternational audienceBackground: At the end of the past century, infliximab (IFX), the first-in-class biological therapy approved in inflammatory bowel disease (IBD), dramatically modified the therapeutic armamentarium. The recent development of subcutaneous (SC) formulations of IFX offers a promising alternative, with the potential to improve patient convenience, adherence, and overall outcomes. This review explores the clinical evidence supporting the initiation of SC IFX and the transition from intravenous (IV) to SC IFX.Methods: Comprehensive review using MEDLINE (source PUBMED).Results: Comparative studies have shown that SC IFX is associated with higher IFX serum concentration levels than IV, fewer neutralizing antibodies and similar levels of remission. Real-world studies have confirmed that switching from IV to SC IFX 120 mg is well accepted with a low risk of relapse. The ease of at-home administration has been associated with improved patient satisfaction and reduced healthcare burdens. The adoption of SC IFX could profoundly change the therapeutic landscape, offering a more patient-centered approach to long-term disease control but some questions remain, particularly about the place of IFX in certain populations.Conclusion: In this article, we reviewed the known and unknown data on SC IFX to provide a comprehensive summary and assist IBD physicians in integrating this knowledge into everyday clinical practice
Alternatives to Synthetic Midurethral Slings in the Surgical Management of Female Stress Urinary Incontinence: Results of a National Survey
No full textInternational audienceIntroduction and hypothesis: The midurethral sling (MUS) is the surgical reference treatment for female stress urinary incontinence (SUI). Concerns regarding MUS safety have led to their authorization in France being questioned. A survey was conducted to investigate alternatives to MUS.Methods: An online questionnaire was distributed via three scientific societies. It explored the characteristics of the respondents, their experience with MUS, and alternatives.Results: A total of 173 practitioners responded to the survey: 85% were gynecologists and 15% urologists. Nearly 70% had more than 10 years of experience, and 39% reported dedicating more than half of their activity to urogynecology. The use of MUS remained predominant: 65% regularly performed transobturator tape, and 61% tension-free vaginal tape procedures. Among surgical alternatives, 52% of practitioners had never performed a Bulkamid® injection. Among users, half performed fewer than 10 procedures per year. Over 90% considered this procedure less effective, but also less risky than MUS in the long term. Colposuspension had never been performed by 46% of respondents. Among those who had performed it, 20% performed between 1 and 5 per year, and 73% no longer performed it. It was considered less effective by 71% of respondents, and less prone to complications by 45%. Finally, 73% of practitioners had never performed an autologous sling. It was perceived as less effective by 68% of respondents, and less risky than MUS by 44%.Conclusion: This survey highlights the current fragility of surgical alternatives in the management of female SUI among French urologists and gynecologists
La mitochondrie : un acteur clé dans les déséquilibres intestinaux de l’obésité
No full textNational audienceMetabolic complications of obesity are associated with a loss of intestinal homeostasis and low-grade chronic inflammation. As the energy powerhouses of enterocytes, mitochondria play a key role in maintaining this homeostasis. We investigated whether mitochondrial alterations could contribute to the intestinal hyperpermeability observed in obesity. In mice, excess dietary lipids caused the accumulation of lipid droplets in enterocytes, leading to a reduction in mitochondrial number and activity, associated with a loss of mature epithelial phenotype and barrier function. In murine jejunal organoids, decreased mitochondrial activity limited the differentiation of progenitors into mature enterocytes, potentially promoting hyperpermeability. In the colon, a high-fat diet also induced mitochondrial dysfunction and epithelial hyperpermeability linked to dysbiosis characterized by an abundance of Desulfovibrionaceae and sulfides, inhibitors of mitochondrial complex IV. These findings highlight the key role of mitochondria in intestinal imbalance associated with obesity and open new therapeutic avenues.Les complications métaboliques de l’obésité sont associées à une perte d’homéostasie intestinale et à une inflammation chronique de bas grade. Centrales énergétiques des entérocytes, les mitochondries jouent un rôle clé dans le maintien de cette homéostasie. Nous avons évalué si leur altération pouvait contribuer à l’hyperperméabilité intestinale observée dans l’obésité. Chez la souris, un excès de lipides alimentaires provoque une accumulation de gouttelettes lipidiques dans les entérocytes, entraînant une baisse du nombre et de l’activité mitochondriale, associée à une perte du phénotype mature et de la fonction de barrière. Dans les organoïdes jéjunaux murins, la réduction de l’activité mitochondriale limite la différenciation des progéniteurs en entérocytes matures, pouvant favoriser l’hyperperméabilité. Dans le côlon, le régime hyperlipidique induit aussi une dysfonction mitochondriale et une hyperperméabilité liée à une dysbiose marquée par les Desulfovibrionaceae et les sulfures, inhibiteurs du complexe IV mitochondrial. Ces travaux soulignent le rôle clé des mitochondries dans les déséquilibres intestinaux liés à l’obésité et ouvrent de nouvelles pistes thérapeutiques
Pesticide reduction in the French wine industry and its effect on production risk
No full textPesticide reduction in the French wine industry and its effect on production risk
Exploring Pinus nigra's induced defense arsenal against Diplodia sapinea through gene and metabolic pathway analysis
No full textInternational audienceThe European black pine (Pinus nigra J. F. Arnold) is a conifer of high economic and ecological importance and is considered a potential alternative to several forest tree species in Central Europe to support adaptation to global climate warming. However, the fungus Diplodia sapinea (Fr.) Fuckel is causing severe damage and world-wide economic loss to this and other Pinus host species. The lack of genomic resources and the scarce knowledge of the tree´s molecular defense mechanisms limit any breeding perspectives. Here, we report the results of a controlled infection experiment in which the transcriptomic and metabolomic profiles of mock and infected P. nigra saplings from two provenances were compared over a period of 21 days. This combined approach suggests that P. nigra response to D. sapinea infection is activated between 8 and 21 days post-inoculation when key plant defense signaling hormones such as jasmonic acid, abscisic acid and salicylic acid increased. This concurred with high differential gene expression, including the activation of major plant defense-related pathways, leading to the induction of several phytoalexins and defense-related proteins. Furthermore, some of these responses were provenance-specific. Finally, this study identified key genes and metabolic pathways involved in the defense response of P. nigra to D. sapinea, providing a solid basis for further exploration of genetic variation among natural populations (provenances) of different subspecies with varying constitutive and induced defense responses. This deeper understanding will aid in elucidating resistance mechanisms and guiding the selection of plant reproductive material for future forest plantations
Étude des communautés microbiennes des sols et des racines des chênes de la forêt de Chantilly RAPPORT FINAL
No full textDans le cadre du projet « Sauvons la forêt de Chantilly » portant sur les causes et les solutions à apporter au problème de dépérissement de la forêt de Chantilly, l’étude réalisée ici vise à analyser l’état du microbiote des sols et des arbres de la forêt de Chantilly. Le microbiote est un acteur clé du fonctionnement des écosystèmes forestiers en contribuant à la nutrition hydrominérale des arbres et au recyclage de la matière organique. Cependant, le microbiote peut aussi être source de maladies et de dépérissement lorsque des agents pathogènes se développent de manière épidémique. Dans ce contexte, il semble crucial, pour comprendre le phénomène de dépérissement en cours dans la forêt de Chantilly, d’établir une étude approfondie du microbiote de la forêt de Chantilly. Pour ce faire, deux séries d’échantillonnages ont été réalisées en 2022 et 2023 : l’une visant à réaliser un diagnostic intensif du microbiote du sol sur les 60 placettes-laboratoires pour avoir un état des lieux de « l’état de santé » du microbiote du sol (2023), l’autre visant à comparer les microbiotes des arbres sains à ceux des arbres en dépérissement pour identifier les microbiotes bénéfiques et d’éventuels bioindicateurs de ce dépérissement (2022). Les résultats suggèrent que le microbiote de la forêt de Chantilly est riche et diversifié aussi bien pour les champignons que les bactéries et ne présente pas de dysbiose majeure. En effet, la proportion d’agents pathogènes est faible. Toutefois, il existe une nette diminution du taux de champignons symbiotiques impliqués dans la nutrition des arbres dans les placettes en dépérissement tandis que les champignons opportunistes susceptibles d’induire des maladies lorsque les arbres sont affaiblis sontplus présents dans les sols des placettes en dépérissement. Cet effet est plus marqué sur certains types de sols, suggérant que le microbiote de certaines parcelles pourrait être plus sensible au phénomène de dépérissement et nécessiter une gestion sylvicole adaptée liée au type de sol. Enfin, les modifications de la composition des communautés liées au dépérissement semblent avoir peu d’effet à ce stade sur les activités de dégradation de la matière organique. Ainsi, le microbiote n’est donc très probablement pas responsable directement du dépérissement observé en forêt de Chantilly mais certains membres du microbiote pourraientcontribuer à l’affaiblissement des arbres, même si ce processus n’est probablement pas majeur
Health-related quality of life after second-line axi-cel in transplant-ineligible patients with large B-cell lymphoma
No full textInternational audienceThe phase 2 ALYCANTE trial aimed to evaluate the investigator-assessed complete metabolic response at 3 months from the axicabtagene ciloleucel (axi-cel) infusion as a primary end point in patients with high-risk relapsed/refractory large B-cell lymphoma who are ineligible for autologous stem cell transplantation (ASCT). This study showed a significant improvement in complete metabolic response rate at 3 months based on historical controls. This study reports the health-related quality of life (HRQoL) results as a secondary end point. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) cancer-specific questionnaire, the Quality of Life Questionnaire high-grade non-Hodgkin lymphoma 29 (QLQ-NHL-HG29) , and the EuroQol Quality of Life Scale-5 dimensions-5 levels of severity (EQ-5D-5L) generic questionnaire at baseline and 1, 3, 6, and 12 months after axi-cel infusion. Among the 62 patients included, 60 (97%) completed a baseline and at least 1 postbaseline HRQoL assessment. At 1 month infusion, adjusted mean change in HRQoL scores from baseline showed a clinically significant deterioration (greater than the clinical threshold) in physical, role, social functioning, and fatigue. However, all HRQoL dimensions recovered by 3 months after infusion and remained stable or continued to improve by 12 months. In an exploratory analysis, adjusted mean change in HRQoL score from baseline in ALYCANTE was similar to or better than in ASCT-eligible patients who received axi-cel in the phase 3 ZUMA-7 trial. Finally, the global health status and fatigue scores of the ALYCANTE population improved to levels comparable to the general French population of similar age by 3 months after infusion. These findings indicate that axi-cel improves HRQoL regardless of transplant eligibility, supporting its use across a broad patient population. This trial was registered at www.clinicaltrials.gov as #NCT04531046
Prise en charge thérapeutique des grossesses extra-utérines tubaires. Recommandations pour la pratique clinique du CNGOF et de la SCGP
No full textInternational audience• Ectopic Pregnancy is defined as the presence of a pregnancy or pregnancy residue outside the uterine cavity, with a prevalence of approximately 2%. Tubal ectopic pregnancy is defined as the presence of a pregnancy or pregnancy residue in the extra-myometrial portion of the fallopian tube (isthmus, ampulla, or fimbriae), and accounts for 96 to 99% of ectopic pregnancy locations. Management of tubal ectopic pregnancy should depend on both its activity and whether it is symptomatic or not. • Regarding emergency management of tubal ectopic pregnancy, it is recommended not to consider expectant management for patients with symptomatic tubal ectopic pregnancy, nor for patients with active tubal ectopic pregnancy (Strong recommendation, low quality of evidence). It is recommended to offer expectant management as an alternative to medical treatment with MTX (methotrexate) for patients with non-active and asymptomatic tubal ectopic pregnancy (Strong recommendation, low quality of evidence). It is recommended to offer expectant management as an alternative to surgical treatment for patients with non-active and asymptomatic tubal ectopic pregnancy (Strong recommendation, very low quality of evidence). In cases of expectant management of tubal ectopic pregnancy, it is strongly recommended to systematically re-evaluate the patient clinically and biologically at 48 hours (Strong recommendation, low quality of evidence). If hCG levels decrease by more than 15% at 48 hours, it is recommended to continue monitoring weekly until negativity, provided there are no signs of symptomatic tubal ectopic pregnancy (Strong recommendation, very low quality of evidence). If an expectant approach is chosen, and there is an increase in hCG levels of more than 15% at 48 hours or the tubal ectopic pregnancy becomes symptomatic, it is recommended to discontinue expectant management (Strong recommendation, low quality of evidence). • Regarding medical treatment of tubal ectopic pregnancy, it is recommended not to favor a multi-dose protocol over a single-dose protocol to increase the success rate of MTX treatment (Strong recommendation, moderate quality of evidence). It is recommended to prefer the single-dose MTX protocol over the multi-dose protocol to limit the risk of adverse effects (Strong recommendation, high quality of evidence). It is also recommended not to systematically combine mifepristone treatment with an MTX injection to improve the efficacy of medical treatment for tubal ectopic pregnancy (Strong recommendation, high quality of evidence). • Regarding surgical management, in a patient with tubal ectopic pregnancy, it is recommended to perform either salpingotomy or salpingectomy with regard to fertility (Strong recommendation, high quality of evidence). It is recommended not to perform tubal expression in order to reduce morbidity compared to salpingotomy (Strong recommendation, very low quality of evidence).La Grossesse Extra-Utérine (GEU) est définie par la présence d’une grossesse ou d’un résidu de grossesse en dehors de la cavité utérine sa prévalence est d’environ 2%. La GEU tubaire est définie comme la présence d’une grossesse ou d’un résidu de grossesse dans la portion extra-myométriale de la trompe (isthme, ampoule ou pavillon) et représente 96 à 99% des localisations de GEU. La prise en charge de la GEU tubaire doit dépendre à la fois de son activité et de son caractère symptomatique ou non. Concernant la prise en charge en urgence d’une GEU tubaire, Il est recommandé de ne pas envisager une attitude expectative pour des patientes présentant une GEU tubaire symptomatique, ni pour pour des patientes présentant une GEU tubaire active (Recommandation forte, qualité de la preuve basse). Il est recommandé de proposer une attitude expectative comme alternative au traitement médical par méthotrexate (MTX) aux patientes présentant une GEU tubaire non active et asymptomatique (Recommandation forte, qualité de la preuve basse). Il est recommandé de proposer une attitude expectative comme alternative au traitement chirurgical aux patientes présentant une GEU tubaire non active et asymptomatique ( Recommandation forte, qualité de la preuve très basse). Il est recommandé, en cas de prise en charge d’une GEU tubaire par expectative, de réévaluer systématiquement cliniquement et biologiquement la patiente à 48 heures (Recommandation forte, qualité de la preuve basse) et en cas de décroissance des HCG >15% à 48h, il est recommandé de poursuivre la surveillance de la décroissance une fois par semaine jusqu’à négativation en l’absence de signes de GEU tubaire symptomatique (Recommandation forte, qualité de la preuve très basse), Si une attitude d’expectative est retenue, en cas d’augmentation des HCG > 15% à 48h ou en cas de GEU tubaire devenant symptomatique, il est recommandé de ne pas poursuivre l’attitude expectative (Recommandation forte, qualité de la preuve basse). Concernant les modalités du traitement médical de la GEU tubaire, Il est recommandé de ne pas privilégier un protocole multidose par rapport à un protocole monodose afin d’augmenter le taux de succès d’un traitement par MTX. (Recommandation forte, qualité de la preuve modérée). Il est recommandé de privilégier le traitement monodose de MTX au protocole multidose afin de limiter le risque d’effets indésirables (Recommandation forte, qualité de la preuve élévée). . il est recommandé de ne pas associer systématiquement un traitement par mifépristone à une injection de MTX pour augmenter l’efficacité du traitement médical d’une GEU tubaire (Recommandation forte, qualité de la preuve élevée). Concernant la prise en charge chirurgicale, chez une patiente présentant une GEU tubaire, il est recommandé de réaliser soit une salpingotomie soit une salpingectomie pour la fertilité. (Recommandation forte, qualité de la preuve élévée). Il est recommandé de ne pas pratiquer une expression tubaire pour diminuer la morbidité par rapport à la salpingotomie (Recommandation forte, qualité de la preuve très basse)
‘Tidy data for clean pastures’: bureaucratic control of shrub encroachment and farmers’ environmental subjectivities
No full textInternational audienceIn recent decades, environmental and agricultural administrations have increasingly relied on geospatial tools, such as GIS and satellite imagery. Within European agricultural policy, this digitalisation of nature serves both environmental conservation and budgetary discipline agendas. This article links the critical analysis of GIS instruments to the study of environmental subjectivities. Drawing on interviews with advisers, inspectors and farmers in southwestern France, I show how new forms of quantifying abandoned and grazed marginal lands shape farmers' environmental subjectivities related to shrub encroachment. Intended to integrate non-herbaceous resources into area-based subsidies, the procedure studied perpetuates the local distaste and the systematic mechanised removal of this type of vegetation. Therefore, it reinforces land control by increasingly capitalised farms instead of the emerging small-scale pastoral systems. These results contribute to the study of government spatial technologies and how they become entangled with local environmental subjectivities and related power dynamics