Severe asthma exacerbation:Changes in patient characteristics,management,and outcomes from 1997 to 2016 in 40 ICUs in the greater Paris area

Background Despite advances in asthma treatments,severe asthma exacerbation(SAE)remains a life-threatening condition in adults,and there is a lack of data derived from adult patients admitted to intensive care units(ICUs)for SAE.The current study investigated changes in adult patient characteristics,management,and outcomes of SAE over a 20-year period in 40 ICUs in the greater Paris area.Methods In this retrospective observational study,admissions to 40 ICUs in the greater Paris area for SAE from January 1,1997,to December 31,2016 were analyzed.The primary outcome was the proportion of ICU admissions for SAE during 5-year periods.Secondary outcomes were ICU and hospital mortality,and the use of mechanical ventilation and catecholamine.Multivariate analysis was performed to assess factors associated with ICU mortality.Results A total of 7049 admissions for SAE were recorded.For each 5-year period,the proportion decreased over time,with SAE accounting for 2.84%of total ICU admissions(n=2841)between 1997 and 2001,1.76%(n=1717)between 2002 and 2006,1.05%(n=965)between 2007 and 2011,and 1.05%(n=1526)between 2012 and 2016.The median age was 46 years(interquartile range[IQR]:32–59 years),55.41%were female,the median Simplified Acute Physiology Score II was 20(IQR:13–28),and 19.76%had mechanical ventilation.The use of mechanical ventilation remained infrequent throughout the 20-year period,whereas the use of catecholamine decreased.ICU and hospital mortality rates decreased.Factors associated with ICU mortality were renal replacement therapy,catecholamine,cardiac arrest,pneumothorax,acute respiratory distress syndrome,sepsis,and invasive mechanical ventilation(IMV).Non-survivors were older,had more severe symptoms,and were more likely to have received IMV.Conclusion ICU admission for SAE remains uncommon,and the proportion of cases decreased over time.Despite a slight increase in symptom severity during a 20-year period,ICU and hospital mortality decreased.Patients requiring IMV had a higher mortality rate.

Evaluating pediatric ureteropelvic junction obstruction:Dynamic magnetic resonance urography vs renal scintigraphy 99mtechnetium mercaptoacetyltriglycine

BACKGROUND Ureteropelvic junction obstruction(UPJO)is a common congenital urinary tract disorder in children.It can be diagnosed as early as in utero due to the presence of hydronephrosis or later in life due to symptomatic occurrence.AIM To evaluate the discrepancy between dynamic contrast-enhanced magnetic resonance urography(dMRU)and scintigraphy 99m-technetium mercaptoacetyltriglycine(MAG-3)for the functional evaluation of UPJO.METHODS Between 2016 and 2020,126 patients with UPJO underwent surgery at Robert DebréHospital.Of these,83 received a prenatal diagnosis,and 43 were diagnosed during childhood.Four of the 126 patients underwent surgery based on the clinical situation and postnatal ultrasound findings without undergoing functional imaging evaluation.Split renal function was evaluated preoperatively using scintigraphy MAG-3(n=28),dMRU(n=53),or both(n=40).In this study,we included patients who underwent surgery for UPJO and scintigraphy MAG-3+dMRU but excluded those who underwent only scintigraphy MAG-3 or dMRU.The patients were divided into groups A(<10%discrepancy)and B(>10%discrepancy).We examined the discrepancy in split renal function between the two modalities and investigated the possible risk factors.RESULTS The split renal function between the two kidneys was compared in 40 patients(28 boys and 12 girls)using scintigraphy MAG-3 and dMRU.Differential renal function,as determined using both modalities,showed a difference of<10%in 31 children and>10%in 9 children.Calculation of the relative renal function using dMRU revealed an excellent correlation coefficient with renal scintigraphy MAG-3 for both kidneys.CONCLUSION Our findings demonstrated that dMRU is equivalent to scintigraphy MAG-3 for evaluating split renal function in patients with UPJO.

Potential impacts of climate and anthropogenic-induced changes on DOM dynamics among the major Chinese rivers

Dissolved organic matter (DOM) is closely linked to human activities in drainage basins and plays a crucial role in maintaining ecosystem functioning and reflecting environmental quality. However, the impacts of climate and anthropogenic-induced changes on DOM in riverine systems under increasingly warming conditions still need to be better understood, particularly at large regional scales. To address this knowledge gap, we analyzed a dataset containing 386 published measurements for nine major Chinese river systems, examining dissolved organic carbon (DOC) concentrations and optical properties of chromophoric DOM (CDOM) under diverse envi- ronmental conditions, including mean air temperature, precipitation, surface solar radiation, population density, and land use. Our findings indicate that riverine DOC concentrations are significantly higher in northern China (at ∼46.8%) than in the south. This disparity is primarily due to the high input of soil erosion-induced DOM from drying-affected lands (57.0%), farmland (49.1%), and forests in the north. The high temperate and strong hydrological conditions would lead to DOM degradation easily in the riverine system in the south of China. Our study highlights that various climatic and anthropogenic factors, such as agriculture, vegetation coverage, soil erosion, surface solar radiation, and precipitation, individually or in combination, can affect DOM dynamics in river systems. Therefore, considering alterations in DOM dynamics resulting from climate and environmental changes is crucial for carbon-neutral policies and sustainable river ecosystem assessments.

All-dielectric χ^(2) metasurfaces: recent progress

Optical metasurfaces,i.e.arrays of nanoantennas with sub-wavelength size and separation,enable the manipulation of light-matter interactions in miniaturized optical components with no classical counterparts.Six decades after the first ob-servation of the second harmonic generation(SHG)in bulk crystals,these devices are expected to break new ground in the field of nonlinear optics,shifting the focus from the phase matching approach achieved within long propagation dis-tances to that of near-field resonances interplay in leaky nanocavities.Here we review the recent progress in SHG with all-dielectric metasurfaces.We discuss the most used technological platforms which underpinned such advances and analyze different SHG control approaches.We finally compare their performances with other well-established technolo-gies,with the hope to delineate the current state-of-the-art and figure out a few scenarios in which these devices might soon offer unprecedented opportunities.

Vanadium-dependent activation of glucose transport in adipocytes by catecholamines is not mediated via adrenoceptor stimulation or monoamine oxidase activity

BACKGROUND Benzylamine and methylamine activate glucose uptake in adipocytes.For tyramine,this effect has even been extended to cardiomyocytes.AIM To investigate the effects of catecholamines and other amines on glucose uptake.METHODS A screening compared 25 biogenic amines on 2-deoxyglucose(2-DG)uptake activation in rat adipocytes.Pharmacological approaches and transgenic mouse models were then used to decipher the mode of action of several hits.RESULTS In rat adipocytes,insulin stimulation of 2-DG uptake was reproduced with catecholamines.100μmol/L or 1 mmol/L adrenaline,noradrenaline,dopamine and deoxyepinephrine,maximally activated hexose transport only when sodium orthovanadate was added at 100μmol/L.Such activation was similar to that already reported for benzylamine,methylamine and tyramine,well-recognized substrates of semicarbazide-sensitive amine oxidase(SSAO)and monoamine oxidase(MAO).Several,but not all,tested agonists ofβ-adrenoreceptors(β-ARs)also activated glucose transport whileα-AR agonists were inactive.Lack of blockade byα-andβ-AR antagonists indicated that catecholamine-induced 2-DG uptake was not mediated by AR stimulation.Adipocytes from mice lackingβ1-,β2-andβ3-ARs(triple KO)also responded to millimolar doses of adrenaline or noradrenaline by activating hexose transport in the presence of 100μmol/L vanadate.The MAO blocker pargyline,and SSAO inhibitors did not block the effects of adrenaline or noradrenaline plus vanadate,which were blunted by antioxidants.CONCLUSION Catecholamines exert unexpected insulin-like actions in adipocytes when combined with vanadium.For limiting insulin resistance by activating glucose consumption at least in fat stores,we propose that catecholamine derivatives combined with vanadium can generate novel complexes that may have low toxicity and promising anti-diabetic properties.

Metabolic syndrome and non-alcoholic fatty liver disease in liver surgery: The new scourges?

The aim of this topic highlight is to review relevant evidence regarding the influence of the metabolic syndrome(MS) and its associated liver manifestation, non-alcoholic fatty liver disease(NAFLD), on the development of liver cancer as well as their impact on the results of major liver surgery. MS and NAFLD, whose incidences are significantly increasing in Western countries, are leading to a changing profile of the patients undergoing liver surgery. A MEDLINE search was performed for relevant articles using the key words "metabolic syndrome", "liver resection", "liver transplantation", "non alcoholic fatty liver disease", "non-alcoholic steatohepatitis" and "liver cancer". On one hand, the MS favors the development of primary liver malignancies(hepatocellular carcinoma and cholangiocarcinoma)either through NAFLD liver parenchymal alterations(steatosis, steatohepatitis, fibrosis) or in the absence of significant underlying liver parenchyma changes. Also, the existence of NAFLD may have a specific impact on colorectal liver metastases recurrence. On the other hand, the postoperative period following partial liver resection and liver transplantation is at increased risk of both postoperative complications and mortality. These deleterious effects seem to be related to the existence of liver specific complications but also higher cardio-vascular sensitivity in a setting of MS/NAFLD. Finally, the long-term prognosis after curative surgery joins that of patients operated on with other types of underlying liver diseases. An increased rate of patients with MS/NAFLD referred to hepatobiliary units has to be expected. The higher operative risk observed in this subset of patients will require specific improvements in their perioperative management.

Characterization of two rat models of cystic fibrosis—KO and F508del CFTR—Generated by Crispr-Cas9

Background: Genetically engineered animals are essential for gaining a proper understanding of the disease mechanisms of cystic fibrosis(CF). The rat is a relevant laboratory model for CF because of its zootechnical capacity, size, and airway characteristics, including the presence of submucosal glands.Methods: We describe the generation of a CF rat model(F508 del) homozygous for the p.Phe508 del mutation in the transmembrane conductance regulator(Cftr) gene. This model was compared to new Cftr-/-rats(CFTR KO). Target organs in CF were examined by histological staining of tissue sections and tooth enamel was quantified by micro-computed tomography. The activity of CFTR was evaluated by nasal potential difference(NPD) and short-circuit current measurements. The effect of VX-809 and VX-770 was analyzed on nasal epithelial primary cell cultures from F508 del rats.Results: Both newborn F508 del and Knock out(KO) animals developed intestinal obstruction that could be partly compensated by special diet combined with an osmotic laxative. The two rat models exhibited CF phenotypic anomalies such as vas deferens agenesis and tooth enamel defects. Histology of the intestine, pancreas, liver, and lungs was normal. Absence of CFTR function in KO rats was confirmed ex vivo by short-circuit current measurements on colon mucosae and in vivo by NPD, whereas residual CFTR activity was observed in F508 del rats. Exposure of F508 del CFTR nasal primary cultures to a combination of VX-809 and VX-770 improved CFTR-mediated Cl-transport.Conclusions: The F508 del rats reproduce the phenotypes observed in CFTR KO animals and represent a novel resource to advance the development of CF therapeutics.

Locoregional therapies and their effects on the tumoral microenvironment of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma(PDAC) is expected to become the second leading cause of death from cancer by 2030. Despite intensive research in the field of therapeutics, the 5-year overall survival is approximately 8%, with only 20% of patients eligible for surgery at the time of diagnosis. The tumoral microenvironment(TME) of the PDAC is one of the main causes for resistance to antitumoral treatments due to the presence of tumor vasculature, stroma, and a modified immune response. The TME of PDAC is characterized by high stiffness due to fibrosis, with hypo microvascular perfusion, along with an immunosuppressive environment that constitutes a barrier to effective antitumoral treatment. While systemic therapies often produce severe side effects that can alter patients’ quality of life, locoregional therapies have gained attention since their action is localized to the pancreas and can thus alleviate some of the barriers to effective antitumoral treatment due to their physical effects. Local hyperthermia using radiofrequency ablation and radiation therapy-most commonly using a local high single dose-are the two main modalities holding promise for clinical efficacy. Recently, irreversible electroporation and focused ultrasound-derived cavitation have gained increasing attention. To date, most of the data are limited to preclinical studies, but ongoing clinical trials may help better define the role of these locoregional therapies in the management of PDAC patients.

Theobroma cacao improves bone growth by modulating defective ciliogenesis in a mouse model of achondroplasia

A gain-of-function mutation in the fibroblast growth factor receptor 3 gene(FGFR3)results in achondroplasia(ACH),the most frequent form of dwarfism.Constitutive activation of FGFR3 impairs bone formation and elongation and many signal transduction pathways.Identification of new and relevant compounds targeting the FGFR3 signaling pathway is of broad importance for the treatment of ACH,and natural plant compounds are prime drug candidate sources.Here,we found that the phenolic compound(-)-epicatechin,isolated from Theobroma cacao,effectively inhibited FGFR3’s downstream signaling pathways.Transcriptomic analysis in an Fgfr3 mouse model showed that ciliary mRNA expression was modified and influenced significantly by the Indian hedgehog and PKA pathways.(-)-Epicatechin is able to rescue mRNA expression impairments that control both the structural organization of the primary cilium and ciliogenesis-related genes.In femurs isolated from a mouse model(Fgfr3^(Y367C/+))of ACH,we showed that(-)-epicatechin eliminated bone growth impairment during 6 days of ex vivo culture.In vivo,we confirmed that daily subcutaneous injections of(-)-epicatechin to Fgfr3^(Y367C/+) mice increased bone elongation and rescued the primary cilium defects observed in chondrocytes.This modification to the primary cilia promoted the typical columnar arrangement of flat proliferative chondrocytes and thus enhanced bone elongation.The results of the present proof-of-principle study support(-)-epicatechin as a potential drug for the treatment of ACH.

High doses of catecholamines activate glucose transport in human adipocytes independently from adrenoceptor stimulation or vanadium addition

BACKGROUND When combined with vanadium salts,catecholamines strongly activate glucose uptake in rat and mouse adipocytes.AIM To test whether catecholamines activate glucose transport in human adipocytes.METHODS The uptake of 2-deoxyglucose(2-DG)was measured in adipocytes isolated from pieces of abdominal subcutaneous tissue removed from women undergoing reconstructive surgery.Pharmacological approaches with amine oxidase inhibitors,adrenoreceptor agonists and antioxidants were performed to unravel the mechanisms of action of noradrenaline or adrenaline(also named epinephrine).RESULTS In human adipocytes,45-min incubation with 100μmol/L adrenaline or noradrenaline activated 2-DG uptake up to more than one-third of the maximal response to insulin.This stimulation was not reproduced with millimolar doses of dopamine or serotonin and was not enhanced by addition of vanadate to the incubation medium.Among various natural amines and adrenergic agonists tested,no other molecule was more efficient than adrenaline and noradrenaline in stimulating 2-DG uptake.The effect of the catecholamines was not impaired by pargyline and semicarbazide,contrarily to that of benzylamine or methylamine,which are recognized substrates of semicarbazide-sensitive amine oxidase.Hydrogen peroxide at 1 mmol/L activated hexose uptake but not pyrocatechol or benzoquinone,and only the former was potentiated by vanadate.Catalase and the phosphoinositide 3-kinase inhibitor wortmannin inhibited adrenaline-induced activation of 2-DG uptake.CONCLUSION High doses of catecholamines exert insulin-like actions on glucose transport in human adipocytes.At submillimolar doses,vanadium did not enhance this catecholamine activation of glucose transport.Consequently,this dismantles our previous suggestion to combine the metal ion with catecholamines to improve the benefit/risk ratio of vanadium-based antidiabetic approaches.

Dental pulp stem cells as a promising model to study imprinting diseases

Parental imprinting is an epigenetic process leading to monoallelic expression of certain genes depending on their parental origin.Imprinting diseases are characterized by growth and metabolic issues starting from birth to adulthood.They are mainly due to methylation defects in imprinting control region that drive the abnormal expression of imprinted genes.We currently lack relevant animal or cellular models to unravel the pathophysiology of growth failure in these diseases.We aimed to characterize the methylation of imprinting regions in dental pulp stem cells and during their differentiation in osteogenic cells(involved in growth regulation)to assess the interest of this cells in modeling imprinting diseases.We collected dental pulp stem cells from five controls and four patients(three with Silver-Russell syndrome and one with Beckwith-Wiedemann syndrome).Methylation analysis of imprinting control regions involved in these syndromes showed a normal profile in controls and the imprinting defect in patients.These results were maintained in dental pulp stem cells cultured under osteogenic conditions.Furthermore,we confirmed the same pattern in six other loci involved in imprinting diseases in humans.We also confirmed monoallelic expression of H19(an imprinted gene)in controls and its biallelic expression in one patient.Extensive imprinting control regions methylation analysis shows the strong potential of dental pulp stem cells in modeling imprinting diseases,in which imprinting regions are preserved in culture and during osteogenic differentiation.This will allow to perform in vitro functional and therapeutic tests in cells derived from dental pulp stem cells and generate other cell-types.

Neoarchean atmospheric chemistry and the preservation of S-MIF in sediments from the São Francisco Craton

Sulfur mass-independent fractionation(S-MIF)preserved in Archean sedimentary pyrite is interpreted to reflect atmospheric chemistry.Small ranges in Δ^(33)S that expanded into larger fractionations leading up to the Great Oxygenation Event(GOE;2.45–2.2 Ga)are disproportionately represented by sequences from the Kaapvaal and Pilbara Cratons.These patterns of S-MIF attenuation and enhancement may differ from the timing and magnitude of minor sulfur isotope fractionations reported from other cratons,thus obscuring local for global sulfur cycling dynamics.By expanding the Δ^(33)S record to include the relatively underrepresented São Francisco Craton in Brazil,we suggest that marine biogeochemistry affected S-MIF preservation prior to the GOE.In an early Neoarchean sequence(2763–2730 Ma)from the Rio das Velhas Greenstone Belt,we propose that low δ^(13)Corg(<-30‰)and dampened Δ^(33)S(-0.4‰to-0.7‰)in banded iron formation reflect the marine diagenetic process of anaerobic methane oxidation.The overlying black shale(TOC up to 7.8%)with higher δ^(13)Corg(-33.4‰to-19.2‰)and expanded Δ^(33)S(2.3‰±0.8‰),recorded oxidative sulfur cycling that resulted in enhance preservation of S-MIF input from atmospheric sources of elemental sulfur.The sequence culminates in a metasandstone,where concomitant changes to more uniform δCorg(-30‰to--25‰),potentially associated with the RuBisCO I enzyme,and near-zero Δ^(33)S(-0.04‰to 0.38‰)is mainly interpreted as evidence for local oxygen production.When placed in the context of other sequences worldwide,the Rio das Velhas helps differentiate the influences of global atmospheric chemistry and local marine diagenesis in Archean biogeochemical processes.Our data suggest that prokaryotic sulfur,iron,and methane cycles might have an underestimated role in pre-GOE sulfur minor isotope records.

Comment on “Locating the source field lines of Jovian decametric radio emissions” by YuMing Wang et al.

In this comment on the article“Locating the source field lines of Jovian decametric radio emissions”by Wang YM et al.,2020,we discuss the assumptions used by the authors to compute the beaming angle of Jupiter’s decametric emissions induced by the moon Io.Their method,relying on multi-point radio observations,was applied to a single event observed on 14th March 2014 by Wind and both STEREO A/B spacecraft from~5 to~16 MHz.They have erroneously identified the emission as a northern(Io-B type)instead of a southern one(Io-D type).We encourage the authors to update their results with the correct hemisphere of origin and to test their method on a larger sample of Jupiter-Io emissions.

QUANTIZATION COMMUTES WITH REDUCTION,A SURVEY

We review the themes relating to the proposition that“quantization commutes with reduction”([Q,R]=0),from symplectic manifolds to Cauchy-Riemann manifolds.

From Solar System to Exoplanets:What can we learn from Planetary Spectroscopy?

The purpose of this paper is to address the question:Using our knowledge of infrared planetary spectroscopy,what can we learn about the atmospheres of exoplanets?In a first part,a simplified classification of exoplanets,assuming thermochemical equilibrium,is presented,based on their masses and their equilibrium temperatures,in order to propose some possible estimations about their atmospheric composition.In the second part,infrared spectra of planets are discussed,in order to see what lessons can be drawn for exoplanetary spectroscopy.In the last part,we consider the solar system as it would appear from a star located in the ecliptic plane.It first appears that the solar system(except in a few specific cases)would not be seen as a multiple system,because,contrary to many exoplanetary systems,the planets are too far from the Sun and the inclinations of their orbits with respect to the ecliptic plane are too high.Primary transit synthetic spectra of solar system planets are used to discuss the relative merits of transmission and direct emission spectroscopy for probing exoplanetary atmospheres.

Radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma

Gastric mucosa-associated lymphoid tissue(MALT)lymphoma is a rare disease which is often associated with Helicobacter pylori(H.pylori)infection.First-line treatment of stage IE and IIE localized gastric MALT lymphoma is based on the eradication of H.pylori.The presence of H.pylori resistance factors such as translocation t(11;18),peri-gastric lymph node involvement and the degree of tumor infiltration of the gastric wall;or lack of response to antibiotic therapy are two main indications to treat with definitive radiotherapy(RT).RT is an effective treatment in localized gastric MALT lymphoma.A moderate dose of 30 Gy allows a high cure rate while being well tolerated.After treatment,regular gastric endoscopic follow-up is necessary to detect a potential occurrence of gastric adenocarcinoma.

Pulmonary Perfusion Asymmetry in Patients after Repair of Tetralogy of Fallot: A 4D Flow MRI-Based Study

Background:Repaired Tetralogy of Fallot(rTOF)patients may have residual lesions such as main(MPA)and branch pulmonary artery stenosis(BPAS).While MPA stenosis is well studied,few data are available on BPAS in rTOF.We aimed to describe pulmonary perfusion in a large paediatric cohort of rTOF and its impact on right ventricular and outflow-tract hemodynamics using 4D flow CMR.Methods:130 consecutive patients(mean age at CMR 14.3±4.6 years)were retrospectively reviewed.96 patients had transannular patch without valve preservation while 34 patients had conserved annulus or valved conduit.A pulmonary blood flow ratio(right pulmonary artery(RPA)/left pulmonary artery(LPA))between 0.75 and 1.56 was considered normal.Results:Asymmetric pulmonary perfusion was present in 59/130 patients(45%),with 54/59(91%)having left lung hypoperfusion(blood flow ratio>1.56).RPA/LPA perfusion ratio in the whole cohort was independently associated with the LPA Z-score(−0.053,p=0.007),the RPA regurgitant fraction(RF)(0.013,p=0.011)and previous LPA stenting(0.648,p=0.004).Decreasing LPA%perfusion(and conversely increasing RPA%perfusion)was significantly associated with higher MPA diameter Z-score(−0.06,p=0.007).On multivariate analysis,MPA Z-score was independently associated with pulmonary RF(0.48,p<0.001)and with right ventricular indexed volumes(coefficient 3.6,p=0.023).In patients with transannular patch repair,asymmetric pulmonary flow was an independent predictor of right ventricular ejection fraction(RVEF)(−3.66,p=0.04).Conclusions:Pulmonary perfusion asymmetry is frequent in rTOF and is associated with abnormal right ventricular and outflow-tract hemodynamics,including MPA dilatation and decreased RVEF in patients after transannular patch.

Adult human liver slice cultures:Modelling of liver fibrosis and evaluation of new anti-fibrotic drugs

BACKGROUND Liver fibrosis can result in end-stage liver failure and death.AIM To examine human liver fibrogenesis and anti-fibrotic therapies,we evaluated the three dimensional ex vivo liver slice(LS)model.METHODS Fibrotic liver samples(F0 to F4 fibrosis stage according to the METAVIR score)were collected from patients after liver resection.Human liver slices(HLS)were cultivated for up to 21 days.Hepatitis C virus(HCV)infection,alcohol(ethanol stimulation)and steatosis(palmitate stimulation)were examined in fibrotic(F2 to F4)liver slices infected(or not)with HCV.F0-F1 HLS were used as controls.At day 0,either ursodeoxycholic acid(choleretic and hepatoprotective properties)and/or α-tocopherol(antioxidant properties)were added to standard of care on HLS and fibrotic liver slices,infected(or not)with HCV.Expression of the biomarkers of fibrosis and the triglyceride production were checked by quantitative reverse transcription polymerase chain reaction and/or enzymelinked immunosorbent assay.RESULTS The cultures were viable in vitro for 21 days allowing to study fibrosis inducers and to estimate the effect of anti-fibrotic drugs.Expression of the biomarkers of fibrosis and the progression to steatosis(estimated by triglycerides production)was increased with the addition of HCV and/or ethanol or palmitate.From day 15 of the follow-up studies,a significant decrease of both transforming growth factorβ-1 and Procol1A1 expression and triglycerides production was observed when a combined anti-fibrotic treatment was applied on HCV infected F2-F4 LS cultures.CONCLUSION These results show that the human three dimensional ex vivo model effectively reflects the in vivo processes in damaged human liver(viral,alcoholic,nonalcoholic steatohepatitis liver diseases)and provides the proof of concept that the LS examined model permits a rapid evaluation of new anti-fibrotic therapies when used alone or in combination.

Unraveling one billion years of geological evolution of the southeastern Amazonia Craton from detrital zircon analyses

Despite representing one of the largest cratons on Earth,the early geological evolution of the Amazonia Craton remains poorly known due to relatively poor exposure and because younger metamorphic and tectonic events have obscured initial information.In this study,we investigated the sedimentary archives of the Carajás Basin to unravel the early geological evolution of the southeastern Amazonia Craton.The Carajás Basin contains sedimentary rocks that were deposited throughout a long period spanning more than one billion years from the Mesoarchean to the Paleoproterozoic.The oldest archives preserved in this basin consist of a few ca.3.6 Ga detrital zircon grains showing that the geological roots of the Amazonia Craton were already formed by the Eoarchean.During the Paleoarchean or the early Mesoarchean(<3.1 Ga),the Carajás Basin was large and rigid enough to sustain the formation and preservation of the Rio Novo Group greenstone belt.Later,during the Neoarchean,at ca.2.7 Ga,the southeastern Amazonia Craton witnessed the emplacement of the Parauapebas Large Igneous Province(LIP)that probably covered a large part of the craton and was associated with the deposition of some of the world largest iron formations.The emplacement of this LIP immediately preceded a period of continental extension that formed a rift infilled first by iron formations followed by terrigenous sediments.This major change of sedimentary regime might have been controlled by the regional tectonic evolution of the Amazonia Craton and its emergence above sea-level.During the Paleoproterozoic,at ca.2.1 Ga,the Rio Fresco Group,consisting of terrigenous sediments from the interior of the Amazonia Craton,was deposited in the Carajás Basin.At that time,the Amazonian lithosphere could have either underwent thermal subsidence forming a large intracratonic basin or could have been deformed by long wavelength flexures that induced the formation of basins and swells throughout the craton under the influence of the growing Transamazonian mountain belt.

French Spine Surgery Society guidelines for management of spinal surgeries during COVID-19 pandemic

Since the outbreak of coronavirus disease 2019(COVID-19)in December 2019 in China,various measures have been adopted in order to attenuate the impact of the virus on the population.With regard to spine surgery,French physicians are devoted to take place in the national plan against COVID-19,the French Spine Surgery Society therefore decided to elaborate specific guidelines for management of spinal disorders during COVID-19 pandemic in order to prioritize management of patients.A three levels stratification was elaborated with Level I:Urgent surgical indications,Level II:Surgical indications associated to a potential loss of chance for the patient and Level III:Non-urgent surgical indications.We also report French experience in a COVID-19 cluster region illustrated by two clinical cases.We hope that the guidelines formulated by the French Spine Surgery Society and the experience of spine surgeons from a cluster region will be helpful in order optimizing the management of patients with urgent spinal conditions during the pandemic.