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Effects of frequent or massive sediment supplies on sediment redox dynamics: a microcosm simulation
No full textInternational audienceMarine coastal environments are subject to depositional events generated for instance by turbidites, spring tidesand estuarine floods. Biogeochemical stability in sediments was already shown to be disrupted following thedeposition of a new sediment layer. The present study aims to understand the successive recovery stages of earlydiagenetic processes following sediment deposition events of varying intensity and frequency, using microcosmssimulations. Over a five-week period with weekly sampling, high spatial resolution methods were applied tocharacterize the behavior of oxygen, nitrogen, manganese and iron in response to i) a single 2.7 cm sedimentdeposit (“one-time high volume”; OHV) and ii) a series of weekly 0.4 cm thick deposit (“frequent low volume”;FLV), compared to an undisturbed control microcosm. Results indicate that oxygen, ammonium and nitriteconcentration in porewaters exhibited similar vertical distributions in FLV and control microcosms. In the OHVmicrocosm, oxygen penetration depth was returned to control levels after 3 weeks, whereas denitrification frontswithin the newly deposited sediments reestablished within one week after disturbance. Regarding manganeseand iron, both OHV and FLV treatments showed that the Mn/Fe oxide-enriched surface layer became anoxic aftersediment deposition, triggering bacterial reduction of these oxides. Dissolved manganese production occurredone week before dissolved iron production, highlighting preferential organic matter remineralization pathways.These findings suggest that the transient biogeochemical response to sediment deposition can therefore beappreciated through manganese and iron cycling
1578 Pushing the boundaries of SBRT in irradiated territories for nodal oligorecurrent prostate cancer: outcomes of the CYGNUS retrospective study
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Le rôle de la plante hôte dans les interactions entre Alternaria brassicicola et des champignons antagonistes chez des Brassicacées sauvages
No full textTo develop alternative methods to conventional fungicides, exploring non cultivated plant species and their microbiota can lead to the identification of antagonistic microorganisms and bioactive compounds. Using Alternaria brassicicola, a necrotrophic seed-transmitted fungal pathogen as example, four wild Brassicaceae species (Arabidopsis thaliana, Capsella bursa-pastoris, Cardamine hirsuta, and Draba verna) described as resistant to A. brassicicola, were selected. These species produce some phytoalexins and phytoanticipins known to inhibit the growth of the pathogen. To identify potential antagonistic fungi, from seeds collected in different populations, 490 fungal strains were isolated, and 18% inhibited A. brassicicola mycelial growth in vitro by at least 25%. Furthermore, at the rosette stage, vegetative rosettes of Capsella bursa-pastoris produced a phytoalexin that triggered an high resistance towards A. brassicicola. However, while A. brassicicola can be transmitted to C. bursa-pastoris seeds, co-inoculation of a Trichoderma viridarium strain reduced the transmission of the pathogen in planta by nearly 70%. Finally, all defense compounds could enhance the antagonistic effects of some of the isolated strains on A. brassicicola mycelial growth in vitro. The host plant can therefore impact the interactions between pathogenic and antagonistic fungi, a crucial aspect to consider when developing new biocontrol strategies.Afin de proposer des méthodes de lutte alternatives aux fongicides conventionnels, l’exploration des espèces végétales non cultivées et de leur microbiote peut conduire à l’identification de micro-organismes antagonistes et de composés aux propriétés biocides. En prenant pour exemple Alternaria brassicicola, champignon pathogène nécrotrophe transmis par les graines, quatre espèces de Brassicacées sauvages (Arabidopsis thaliana, Capsella bursa-pastoris, Cardamine hirsuta et Draba verna) décrites comme résistantes à A. brassicicola, ont été sélectionnées. Ces espèces synthétisent des phytoalexines et des phytoanticipines connues pour leur capacité à inhiber la croissance du champignon pathogène in vitro. Afin d’identifier des souches antagonistes, à partir de graines collectées dans différentes populations, 490 champignons ont été isolés, et 18% d’entre eux inhibent la croissance mycélienne d’A. brassicicola d’au moins 25% in vitro. Capsella bursa-pastoris est également source d’une phytoalexine responsable d’une forte résistance vis-à-vis d’A. brassicicola sur rosettes. Cependant, A. brassicicola peut se transmettre aux graines de C. bursa-pastoris mais la co inoculation avec une souche de Trichoderma viridarium réduit cette transmission in planta de près de 70 %. Enfin, l’inhibition de la croissance in vitro d’A. brassicicola par les filtrats fongiques de T. viridarium ou d’autres souches antagonistes a été amplifiée par des effets synergiques en présence de certains composés de défense. La plante hôte peut donc impacter les interactions entre champignons pathogènes et antagonistes, ce qui est crucial à considérer pour développer de nouvelles stratégies de biocontrôle
Phase 3 Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis
No full textInternational audienceBackground: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia caused by autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), which alveolar macrophages require to clear surfactant. Molgramostim is a formulation of inhaled recombinant human GM-CSF, but its efficacy and safety in patients with aPAP have not been studied sufficiently.Methods: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned patients with aPAP to receive molgramostim at a dose of 300 μg or placebo once daily for 48 weeks. The primary end point was the change from baseline to week 24 in the diffusing capacity of the lungs for carbon monoxide (DLCO), which was adjusted for hemoglobin concentration and expressed as a percentage of the predicted value. Secondary end points adjusted for multiplicity were the change from baseline in DLCO at 48 weeks and the change from baseline in the St. George's Respiratory Questionnaire total (SGRQ-T) and activity (SGRQ-A) scores (scores range from 0 to 100, with lower scores indicating better quality of life) and in exercise capacity at 24 and 48 weeks.Results: A total of 164 patients underwent randomization: 81 were assigned to receive molgramostim and 83 to receive placebo. The least-squares mean change in DLCO from baseline to week 24 was 9.8 percentage points (95% confidence interval [CI], 7.3 to 12.3) with molgramostim and 3.8 percentage points (95% CI, 1.4 to 6.3) with placebo (estimated treatment difference, 6.0 percentage points; 95% CI, 2.5 to 9.4; P<0.001). The least-squares mean change in DLCO from baseline to week 48 was 11.6 percentage points (95% CI, 8.7 to 14.5) with molgramostim and 4.7 percentage points (95% CI, 1.8 to 7.6) with placebo (P<0.001), and the least-squares mean change in the SGRQ-T score at week 24 was -11.5 points (95% CI, -15.0 to -8.0) and -4.9 points (95% CI, -8.3 to -1.5), respectively (P = 0.007). No significant between-group difference in the change in SGRQ-A score was observed at 24 weeks, so no statistical inference was drawn with respect to subsequent secondary end points. The percentage of patients with at least one adverse event and the percentage with at least one serious adverse event were similar in the two groups.Conclusions: Once-daily inhaled molgramostim led to a greater increase in pulmonary gas transfer than placebo in patients with aPAP. (Funded by Savara; IMPALA-2 ClinicalTrials.gov number, NCT04544293; European Union Clinical Trials Information System number, 2024-511052-41-00.)
Occupational Exposure to Engine Exhausts and Prostate Cancer Risk
No full textInternational audienceBackground: Some engine exhausts (EEs) have been classified as carcinogens and/or can have hormone-modulating properties that could play a role in prostate cancer development.Objective: We investigated associations between lifetime occupational exposure to various EEs and prostate cancer risk, overall and for aggressive cancers.Methods: In a population-based case-control study conducted in Montreal, Canada, 1,924 incident histologically-confirmed prostate cancer cases (436 aggressive) and 1,989 population controls were recruited. Socio-demographics, lifestyle factors and a detailed occupational history were collected during in-person interviews. Industrial hygienists conducted evaluations of intensity, frequency and reliability of exposure to EEs resulting from the combustion of several fuels (any diesel, light- and heavy-duty diesel, leaded and unleaded gasoline, propane and jet fuel) in each job held ≥ 2 years. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated for exposure to each EE, in association with prostate cancer risk, adjusting for age and then for potential lifestyle and occupational confounders, accounting for a 5-year latency period. As most associations were not linear, we fitted functions for changes in percentile distributions based on natural cubic splines.Results: There was no evidence of associations between exposure to the various EEs and overall prostate cancer. However, for high-grade cancers, based on the fully-adjusted model, a change from the 25th to the 75th percentile of the exposure distribution of any diesel EE yielded an OR of 1.24 (95%CI 0.96-1.61), and of 1.27 (95% CI 0.80-2.01) for a change from the 75th to the 95th percentile. These increases reflected exposure to diesel EE from light-duty vehicles, associated with similar ORs. For leaded gasoline EE, a change from the 75th to the 95th percentile resulted in an age-adjusted OR of 1.36 (95%CI 0.88-2.11), which was attenuated to 1.12 (95%CI 0.63-2.02) after full adjustment. There were no associations with EE from unleaded gasoline, diesel from heavy-duty vehicles, jet fuel and propane.Conclusion: There was suggestive evidence for a deleterious role of occupational exposure to EE resulting from the combustion of any diesel, light-duty diesel and from leaded gasoline in the development of aggressive prostate cancer. Results were independent from prostate cancer screening patterns
Development of a potential nano-based delivery system combining Colchicine-loaded lipid nanocapsules and BIOT-NFL-peptide to target glioblastoma
No full textInternational audiencePeptide conjugated-nanodrug is one of the most studied new treatment options in the field of cancer, including glioblastoma (GBM). This tumour, GBM, is a difficult to treat brain tumour mainly due to its location and the complexity of targeting tumour cells. A promising GBM-targeting peptide (NFL-TBS.40-63) is a cell penetrating peptide (CPP) that has previously demonstrated selectivity against GBM cells and also a capacity to damage their microtubule network at appropriate concentrations. Here, a potential nano-based delivery system was developed by coupling the biotinylated-NFL-peptide (BIOT-NFL) with lipid nanocapsules (LNCs) loaded with Colchicine (Col), an anti-microtubule agent with potent anticancer activity. The effect of BIOT-NFL and free Colchicine was first evaluated on GBM cells. Colchicine was then loaded in lipid nanocapsules (Col-loaded LNCs) and the obtained nanocapsules were characterized for particle size, morphology, encapsulation efficiency and in vitro release, and then coupled with the BIOT-NFL-peptide. Interestingly, a potential nanosystem composed of peptidenanofibers (formed from BIOT-NFL) decorated with Col-LNCs was observed by electron microscopic examination. Finally, the effects of this BIOT-NFL coupled to Col-LNCs were evaluated in vitro on GBM cells. This new nanosystem may offer a promising strategy for GBM targeted therapy.</div
Ergodicité exponentielle de dynamiques de Langevin de champ moyen par couplage synchrone
No full textAs an example of the nonlinear Fokker-Planck equation, the mean field Langevin dynamics recently attracts attention due to its connection to (noisy) gradient descent on infinitely wide neural networks in the mean field regime, and hence the convergence property of the dynamics is of great theoretical interest. In this paper, In the continuity of [1, 2], we are interested by the long-time behavior and uniform in time propagation of chaos by synchronous coupling for mean-field Langevin dynamics (over- and under-damped).À titre d'exemple de l'équation de Fokker-Planck non linéaire, la dynamique de Langevin de champ moyen a récemment retenu l'attention en raison de son lien avec la descente de gradient (stochastique) sur des réseaux de neurones infiniment larges en régime de champ moyen. La propriété de convergence de cette dynamique présente donc un grand intérêt théorique. Dans cet article, dans la continuité de [1, 2], nous nous intéressons au comportement à long terme et à la propagation uniforme du chaos par couplage synchrone pour la dynamique de Langevin en champ moyen (sur- et sous-amortie)
High level of infection-related hospitalizations in the 2019-2020 French national dialysis cohort
No full textInternational audienceBackground: Dialysis patients experience a high rate of hospitalizations for infection. This work aimed to study the frequency of hospitalizations for infections and the associated risk factors in a nationwide dialysis cohort during 2019-2020.Methods: This was an observational, retrospective study using two national databases. We included 59 585 patients undergoing dialysis from 1 January 2019 to 31 December 2020. Hospitalization rates (per 1000 patient-years) were calculated from all hospital discharges with a principal or related diagnosis of infection. Infections were classified into 14 categories. The association between individual risk factors and incidence of infection-related hospitalizations was estimated with multilevel Poisson models with patients as random effects.Results: The incidence rate was 245 (95% confidence intervals (CI) 242-249) hospitalizations per 1000 patient-years, 241 (236-246) and 249 (244-254) in 2019 and 2020. After excluding COVID-19-related hospitalizations, the 2020 incidence was 197 (192-201). The main source of infection-related hospitalizations was pulmonary [93 (91-96)] followed by sepsis [33 (32-34)], digestive excluding peritonitis [25 (24-26)], cutaneous [24 (23-26)], urinary [18 (17-19)], and osteoarticular [9 (8-9)]. Except for pulmonary infection lower in 2020, attributed to barrier measures and lockdowns, there were no major discrepancies in incidence between 2019 and 2020. The main factors associated with risk of infection were male gender; low albumin level; presence of diabetes, chronic respiratory failure, heart failure, and lower-limb arteritis; cirrhosis stage; walking disability; and presence of active cancer. The risk of infection-related hospitalization was increased for patients with tunneled catheters and arteriovenous grafts and those under peritoneal dialysis compared with patients with arteriovenous fistula [1.63 (95% CI 1.52-1.76), 1.30 (1.11-1.53) and 1.73 (1.53-1.96); all P < .001].Conclusion: The risk of hospitalization for infection is high in dialysis patients, which calls for intensified prevention measures. Lockdown and shielding barriers were efficient to decrease the incidence of pulmonary infections but not other infections
Prevalence, risk and protective factors of postpartum depression and anxiety symptoms in the Allada district, Benin
No full textInternational audiencePurpose: Postpartum depression symptoms (PPDS) and postpartum anxiety symptoms (PPAS) are a major global public health issue, especially in low-resource settings. This study aimed to determine the prevalence of PPDS and PPAS in Benin, Sub-Saharan Africa, at one year postpartum and to identify associated risk and protective factors.Methods: Pregnant women were recruited for a longitudinal mother-child cohort in the Allada District of Benin, and a cross-sectional analysis was performed on data collected at one-year postpartum. Maternal depression and anxiety symptoms were assessed one year postpartum using the Edinburgh Postnatal Depression Scale (EPDS)-validated in Benin and translated into Fon-and its anxiety subscale (EPDS-3 A). Cut-off scores for high depressive and anxiety symptoms were ≥ 13 and ≥ 6, respectively. Potential risk and protective factors including maternal, child characteristics, socioeconomic status, and social support were analyzed using multivariable-adjusted logistic regression models.Results: At one year postpartum, 13% of 742 mothers had PPDS, and 21% PPAS. Risk factors for PPDS included recent alcohol consumption (previous three months) (aOR = 1.88; 95%CI: 1.17-3.02) and food insecurity (aOR = 4.47; 95%CI: 1.29-17.4), while partner cohabitation reduced PPDS odds (aOR = 0.45; 95%CI: 0.26-0.80). PPAS risk factors included recent alcohol consumption (aOR = 2.17; 95%CI: 1.44-3.28) and regular child care support from 3 + childcare providers (aOR = 2.91; 95%CI: 1.50-5.68). Protective factors for PPAS included the minority Aizo ethnicity (aOR = 0.58; 95%CI: 0.36-0.93) and living in an individual house (aOR = 0.45; 95%CI: 0.24-0.85).Conclusion: This study sheds light on the prevalence of PPDS and PPAS at one year postpartum in the Beninese context, as well as associated factors. Findings underscore the importance of establishing postpartum psychological follow-up and targeted strategies to support maternal mental health in low-resource settings, addressing both socioeconomic vulnerabilities and social support structures
Chrysin-Loaded Extracellular Vesicles Attenuate LPS-Induced Neuroinflammation in BV2 Microglial Cells In Vitro: A Novel Neuroprotective Strategy
No full textInternational audienceNeuroinflammation, driven by activated microglia, contributes to the progression of neurodegenerative diseases. Extracellular vesicles mediate intercellular communication and influence immune responses. Chrysin, a natural flavone found in fruits and propolis, has demonstrated anti-inflammatory effects. This study explored the immunomodulatory potential of chrysin-loaded EVs (EVs-Chry) derived from BV2 microglial cells. BV2 cells were treated with chrysin for 24 h to assess cytotoxicity and proliferation. EVs were isolated from treated and untreated cells, characterized by nanoparticle tracking analysis, and applied to naïve BV2 cells prior to LPS stimulation. Effects on cell morphology, migration, cytokine expression (IL-1β, IL-6), inflammasome activity (caspase-1), and apoptosis-related protein Bcl-xL were investigated. Our results show that EVs-Chry significantly reduced LPS-induced cell proliferation, restored resting microglial morphology, and reduced migratory capacity. Furthermore, co-treatment with EVs-Chry and LPS reduced pro-inflammatory cytokines such as IL-1β, IL-6, and caspase-1 expression while enhancing anti-apoptotic Bcl-xL levels, indicating a shift toward an anti-inflammatory, neuroprotective micro-glial phenotype. Together, our results demonstrated that EVs-Chry have neuroprotective effects on LPS-induced microglial activation and modulate microglial responses to inflammatory stimuli, attenuating pro-inflammatory signaling and promoting cellular homeostasis. These findings support the therapeutic potential of EVs-Chry in the context of neuroinflammatory and neurodegenerative disorders