73 research outputs found
Frequency, pressure, and strain dependence of nonlinear elasticity in Berea Sandstone
No full textAcoustoelasticity measurements in a sample of room dry Berea sandstone are conducted at
various loading frequencies to explore the transition between the quasi-static (f → 0) and dynamic (few
kilohertz) nonlinear elastic response. We carry out these measurements at multiple confining pressures and
perform a multivariate regression analysis to quantify the dependence of the harmonic content on strain
amplitude, frequency, and pressure. The modulus softening (equivalent to the harmonic at 0f) increases
by a factor 2–3 over 3 orders of magnitude increase in frequency. Harmonics at 2f, 4f, and 6f exhibit
similar behaviors. In contrast, the harmonic at 1f appears frequency independent. This result corroborates
previous studies showing that the nonlinear elasticity of rocks can be described with a minimum of two
physical mechanisms. This study provides quantitative data that describes the rate dependency of nonlinear
elasticity. These findings can be used to improve theories relating the macroscopic elastic response to
microstructural feature
Therapeutic innovation in adult-onset Still’s disease (and other rare inflammatory disorders): how to secure evidence-based medicine?
No full textComprehensive description of adult-onset Still's disease after COVID-19 vaccination
No full textCases of adult-onset Still's disease (AOSD) have been reported after COVID-19 vaccination. Here we provide a comprehensive description and analysis of all cases of AOSD reported in the literature and in pharmacovigilance databases through April 2022. Disproportionality analyses of pharmacovigilance data were performed in order to further explore the association between vaccination and AOSD. We included 159 patients, 144 from the World Health Organization pharmacovigilance database and 15 from the literature. Detailed clinical characteristics were described for the cases from the literature and from the French pharmacovigilance database (n = 9). The cases of AOSD after COVID-19 vaccination concerned women in 52.2% of cases. The median age was 43.4 years. More than 80% of AOSD reports occurred during the first three weeks and concerned mostly the BNT162b2 mRNA vaccine. We identified 14.5% of disease flare with a median time-to-onset of AOSD flare-up significantly shorter than for the new onset form. More than 90% patients received steroids. Although all cases were considered serious and required hospitalization, most cases presented a favorable outcome (67.1%) with a good response to corticosteroid therapy with a mean time to recovery of 7.2 days. Disproportionality analyses suggested that AOSD was associated with COVID-19 vaccines as well as other vaccines. AOSD was nearly five times more frequently reported with COVID-19 vaccines than with all other drugs. Clinicians should be informed about the potential risk of AOSD onset or flare following COVID vaccines and the importance of its early detection to optimize its management
The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases
No full textThe SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article
Adult onset Still's disease (AOSD) in the era of biologic therapies: Dichotomous view for cytokine and clinical expressions
No full textInternational audienceAdult onset Still's disease (AOSD) is a rare inflammatory disorder characterized by hectic spiking fever, evanescent rash and joint involvement. Prognosis is highly variable upon disease course and specific involvements, ranging from benign and limited outcome to chronic destructive polyarthritis and/or life-threatening events in case of visceral complications or reactive hemophagocytic lymphohistiocytosis (RHL). AOSD remains a debatable entity at the frontiers of autoimmune diseases and autoinflammatory disorders. The pivotal role of macrophage cell activation leading to a typical Th1 cytokine storm is now well established in AOSD, and confirmed by the benefits using treatments targeting TNF-α, IL-1β or IL-6 in refractory patients. However, it remains difficult to determine predictive factors of outcome and to draw guidelines for patient management. Herein, reviewing literature and relying on our experience in a series of 8 refractory AOSD patients, we question nosology and postulate that different cytokine patterns could underlie contrasting clinical expressions, as well as responses to targeted therapies. We therefore propose to dichotomize AOSD according to its clinical presentation. On the one hand, 'systemic AOSD' patients, exhibiting the highest inflammation process driven by excessive IL-18, IL-1β and IL-6 production, would be at risk of life-threatening complications (such as multivisceral involvements and RHL), and would preferentially respond to IL-1β and IL-6 antagonists. On the other hand, 'rheumatic AOSD' patients, exhibiting pre-eminence of joint involvement driven by IL-8 and IFN-γ production, would be at risk of articular destructions, and would preferentially respond to TNF-α blockers
Environmental controls on the distribution of brGDGTs and brGMGTs across the Seine River basin (NW France): implications for bacterial tetraethers as a proxy for riverine runoff
No full textInternational audienceBranched glycerol dialkyl glycerol tetraethers (brGDGTs) are bacterial lipids that have been widely used as environmental proxies in continental paleorecords. Another group of related lipids, branched glycerol monoalkyl glycerol tetraethers (brGMGTs), has recently been proposed as a potential paleotemperature proxy. Nevertheless, the sources and environmental dependencies of both brGDGTs and brGMGTs along the river–sea continuum are still poorly understood, complicating their application as paleoenvironmental proxies in some aquatic settings. In this study, the sources of brGDGTs and brGMGTs and the potential factors controlling their distributions are explored across the Seine River basin (NW France), which encompasses the freshwater-to-seawater continuum. BrGDGTs and brGMGTs were analyzed in soils, suspended particulate matter (SPM), and sediments (n=237) collected along the land–sea continuum of the Seine basin. Both types of compounds (i.e., brGDGTs and brGMGTs) are shown to be produced in situ, in freshwater and saltwater, based on their high concentrations and distinct distributions in aquatic settings (SPM and sediments) vs. soils. Redundancy analysis further shows that both salinity and nitrogen dominantly control the brGDGT distributions. Furthermore, the relative abundance of 6-methyl vs. that of 5-methyl brGDGTs (the IR6Me ratio), the total nitrogen (TN), the δ15N, and the chlorophyll a concentration co-vary in a specific geographical zone with low salinity, suggesting that 6-methyl brGDGTs are preferentially produced under low-salinity and high-productivity conditions. In contrast to brGDGTs, the brGMGT distribution appears to be primarily regulated by salinity, with a distinct influence on the individual homologues. Salinity is positively correlated with homologues H1020a and H1020b and negatively correlated with compounds H1020c and H1034b in SPM. This suggests that bacteria living in freshwater preferentially produce compounds H1020c and H1034b, whereas bacteria that primarily grow in saltwater appear to be predominantly responsible for the production of homologues H1020a and H1020b. Based on the abundance ratio of the freshwater-derived compounds (H1020c and H1034b) vs. their saltwater-derived homologues (H1020a and H1020b), a novel proxy, the Riverine IndeX (RIX), is proposed to trace riverine organic matter inputs, with high values (>0.5) indicating a higher riverine contribution. We successfully applied RIX to the Godavari River basin (India) and a paleorecord across the upper Paleocene and lower Eocene from the Arctic Coring Expedition at Lomonosov Ridge, showing its potential applicability to both modern samples and paleorecords
Extracellular Vesicles Are More Potent Than Adipose Mesenchymal Stromal Cells to Exert an Anti-Fibrotic Effect in an In Vitro Model of Systemic Sclerosis
No full textInternational audienceSystemic sclerosis (SSc) is a complex disorder resulting from dysregulated interactions between the three main pathophysiological axes: fibrosis, immune dysfunction, and vasculopathy, with no specific treatment available to date. Adipose tissue-derived mesenchymal stromal cells (ASCs) and their extracellular vesicles (EVs) have proved efficacy in pre-clinical murine models of SSc. However, their precise action mechanism is still not fully understood. Because of the lack of availability of fibroblasts isolated from SSc patients (SSc-Fb), our aim was to determine whether a TGFβ1-induced model of human myofibroblasts (Tβ-Fb) could reproduce the characteristics of SSc-Fb and be used to evaluate the anti-fibrotic function of ASCs and their EVs. We found out that Tβ-Fb displayed the main morphological and molecular features of SSc-Fb, including the enlarged hypertrophic morphology and expression of several markers associated with the myofibroblastic phenotype. Using this model, we showed that ASCs were able to regulate the expression of most myofibroblastic markers on Tβ-Fb and SSc-Fb, but only when pre-stimulated with TGFβ1. Of interest, ASC-derived EVs were more effective than parental cells for improving the myofibroblastic phenotype. In conclusion, we provided evidence that Tβ-Fb are a relevant model to mimic the main characteristics of SSc fibroblasts and investigate the mechanism of action of ASCs. We further reported that ASC-EVs are more effective than parental cells suggesting that the TGFβ1-induced pro-fibrotic environment may alter the function of ASCs
Long-term home parenteral nutrition in systemic sclerosis-related intestinal failure is feasible but unveils occult cardiac disease
No full textInternational audienceObjective: The aim of this study was to compare safety and efficacy of long-term home parenteral nutrition between patients with systemic sclerosis and intestinal failure (IF) and controls with IF from another etiology.Methods: A retrospective study was conducted in a referral center for systemic sclerosis (SSc) in Montpellier, France. Patients followed between 1985 and 2020 with SSc-related IF were included and compared with control patients with IF from another etiology. The patients included had to be treated for 4 wk by home parenteral nutrition (HPN). Primary outcome was occurrence of HPN-related complications. Secondary outcomes included duration of parenteral nutrition, body mass index at 12 mo, and survival.Results: Cumulative duration of HPN was 23 397 catheter days. HPN resulted in body mass index increase in both groups. There was no statistical difference regarding catheter-related bloodstream infections and thrombosis between the groups, despite use of immunosuppressive drugs and autologous hematopoietic stem cell transplantation in patients with SSc. However, the patients with SSc had significantly more HPN- related cardiac overload than the controls (P < 0.0001). Overloads occurred in SSc patients with and without cardiac disease, arguing for comprehensive hemodynamic screening in this condition.Conclusion: Long-term HPN in SSc-related IF is feasible but unveils occult cardiac disease
Lung Fibrosis Is Improved by Extracellular Vesicles from IFNγ-Primed Mesenchymal Stromal Cells in Murine Systemic Sclerosis
No full textBackground: Systemic sclerosis (SSc) is a severe autoimmune disease for which mesenchymal stromal cells (MSCs)-based therapy was reported to reduce SSc-related symptoms in pre-clinical studies. Recently, extracellular vesicles released by MSCs (MSC-EVs) were shown to mediate most of their therapeutic effect. Here, we aimed at improving their efficacy by increasing the MSC-EV dose or by IFNγ-priming of MSCs. Methods: small size (ssEVs) and large size EVs (lsEVs) were recovered from murine MSCs that were pre-activated using 1 or 20 ng/mL of IFNγ. In the HOCl-induced model of SSc, mice were treated with EVs at day 21 and sacrificed at day 42. Lung and skin samples were collected for histological and molecular analyses. Results: increasing the dose of MSC-EVs did not add benefit to the dose previously reported to be efficient in SSc. By contrast, IFNγ pre-activation improved MSC-EVs-based treatment, essentially in the lungs. Low doses of IFNγ decreased the expression of fibrotic markers, while high doses improved remodeling and anti-inflammatory markers. IFNγ pre-activation upregulated iNos, IL1ra and Il6 in MSCs and ssEVs and the PGE2 protein in lsEVs. Conclusion: IFNγ-pre-activation improved the therapeutic effect of MSC-EVs preferentially in the lungs of SSc mice by modulating anti-inflammatory and anti-fibrotic markers
Mesenchymal stromal cells-derived extracellular vesicles alleviate systemic sclerosis via miR-29a-3p
No full textInternational audienceSystemic sclerosis (SSc) is a potentially lethal disease with no curative treatment. Mesenchymal stromal cells (MSCs) have proved efficacy in SSc but no data is available on MSC-derived extracellular vesicles (EVs) in this multi-organ fibrosis disease. Small size (ssEVs) and large size EVs (lsEVs) were isolated from murine MSCs or human adipose tissue-derived MSCs (ASCs). Control antagomiR (Ct) or antagomiR-29a-3p (A29a) were transfected in MSCs and ASCs before EV production. EVs were injected in the HOCl-induced SSc model at day 21 and euthanasized at day 42. We found that both ssEVs and lsEVs were effective to slow-down the course of the disease. All disease parameters improved in skin and lungs. Interestingly, down-regulating miR-29a-3p in MSCs totally abolished therapeutic efficacy. Besides, we demonstrated a similar efficacy of human ASC-EVs and importantly, EVs from A29a-transfected ASCs failed to improve skin fibrosis. We identified Dnmt3a, Pdgfrbb, Bcl2, Bcl-xl as target genes of miR-29a-3p whose regulation was associated with skin fibrosis improvement. Our study highlights the therapeutic role of miR-29a-3p in SSc and the importance of regulating methylation and apoptosis
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