Sagittal knee laxity is often quantified using arthrometers. Adding rotational laxity and compliance measurementsis relatively new and could bring new information for anterior cruciate ligament (ACL) injury diagnosis....Sagittal knee laxity is often quantified using arthrometers. Adding rotational laxity and compliance measurementsis relatively new and could bring new information for anterior cruciate ligament (ACL) injury diagnosis. TheDYNEELAX® is a new knee arthrometer able to evaluate simultaneously tibial translation and rotation. Thepurpose is to assess the sensitivity, reproducibility and repeatability of the DYNEELAX® with a prototype leg toprovide accurate instructions before using it in clinical practice. Sensitivity is studied by varying 7 parameters(positioning and sensors), and reproducibility by repeating measurement series with a group of two experiencedoperators and a group of two non-experienced operators. Repeatability is assessed throughout the study. Theresults showed that DYNEELAX® is poorly sensitive to the angle and the position of the displacement sensor, andthe angle of the rotation sensor. It is a bit sensitive to positioning of patella and ankle supports. It is very sensitiveto the tightening of the patella and ankle supports. It exists a significant difference only between groups (p <0.001), but there is no significant difference between the two experienced operators (p > 0.215), or between thetwo non-experienced operators (p > 0.229). Variation coefficients for intra-series are on average inferior to 5% fortranslation and rotation tests. Then, the DYNEELAX® presented encouraging results with a good accuracy and agood reliability but operators must be careful about positioning.展开更多
The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given th...The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularl展开更多
Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through PIK3CA.Venous malformations are assoc...Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through PIK3CA.Venous malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening situations.No authorized medical treatment exists for patients with venous malformations.Here,we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient phenotypes.We showed that these malformations only partially signal through AKT proteins.We compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a PI3Kαinhibitor at improving the lesions seen in the mouse model.We demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging survival.Considering these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying PIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous sclerotherapies.We assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each patient.Alpelisib demonstrated improvement in all 25 patients.Vascular malformations previously considered intractable were reduced and clinical symptoms were attenuated.MRI showed a decrease of 33.4%and 27.8%in the median volume of PIK3CA and TEK malformations respectively,over 6 months on alpelisib.In conclusion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.展开更多
Excavation with tunnel boring machine(TBM)can generate vibrations,causing damages to neighbouring buildings and disturbing the residents or the equipment.This problem is particularly challenging in urban areas,where T...Excavation with tunnel boring machine(TBM)can generate vibrations,causing damages to neighbouring buildings and disturbing the residents or the equipment.This problem is particularly challenging in urban areas,where TBMs are increasingly large in diameter and shallow in depth.In response to this problem,four experimental campaigns were carried out in different geotechnical contexts in France.The vibration measurements were acquired on the surface and inside the TBMs.These measurements are also complemented by few data in the literature.An original methodology of signal processing is pro-posed to characterize the amplitude of the particle velocities,as well as the frequency content of the signals to highlight the most energetic bands.The levels of vibrations are also compared with the thresholds existing in various European regulations concerning the impact on neighbouring structures and the disturbance to local residents.展开更多
Objective: Dehydroepiandrosterone (DHEA) has been previously reported to improve ovarian response in IVF for poor responders. Its effect remains uncertain. The purpose of this study was to evaluate the effect of DHEA ...Objective: Dehydroepiandrosterone (DHEA) has been previously reported to improve ovarian response in IVF for poor responders. Its effect remains uncertain. The purpose of this study was to evaluate the effect of DHEA given during two years in our unit, in order to build hypothesis for a future randomized controlled trial. Design: Cohort of exposed and non-exposed DHEA study. Patient(s): 224 patients with AMH under 1.6 ng/ml undergoing IVF with a short antagonist protocol adding FSH and LH rec were enrolled for 327 IVF cycles. 176 patients had been treated with DHEA before IVF, and 151 had not. Intervention(s): None. Main Outcome Measure(s): Cancellation cycle rate, amount of gonadotrophins used, estradiol level on day six of stimulation, number of oocytes retrieved, metaphase II oocytes, blastocysts and frozen embryos, clinical pregnancy rate and miscarriage rate. Results: The cancellation rate was significantly higher in the group without DHEA (29.8% versus 13.1%, p = 0.002). The amount of gonadotrophins used for stimulation, the estradiol level on day six of stimulation, the number of oocytes retrieved, metaphase II oocytes, blastocysts, frozen embryos and miscarriage rate were not different in both groups. The clinical pregnancy rate per included patient in the DHEA group was 17.1% versus 8.6% in the non-treated group (p = 0.02). Conclusion: DHEA appears to improve clinical pregnancy rate by decreasing the cancellation rate.展开更多
Background: A large number of studies have addressed whiplash injury, and many meta-analyses have sought to highlight chronicity factors;the implicated processes, however, remain a matter of debate. The present study ...Background: A large number of studies have addressed whiplash injury, and many meta-analyses have sought to highlight chronicity factors;the implicated processes, however, remain a matter of debate. The present study used data from the ESPARR cohort (an on-going prospective study of a representative cohort of road accident victims in the Rh?ne administrative département of France). The objectives were to describe the consequences of whiplash injury and to determine prognostic factors for poor recovery and persistent pain at 1 year post-accident. Methods: The cohort included 255 “pure” whiplash victims, 173 of whom responded to the 1-year follow-up questionnaire. Correlations between explanatory variables and health and pain status were explored by modified Poisson regression to provide adjusted relative risk (RR) values. Results: Half of the victims had not fully recovered health status by 1 year. The main factor associated with non-recovery was pain (RR = 1.3;1.0-1.7). A birth in the family preceding the accident emerged as another factor (RR=1.5;1.2-1.9). Victims responsible for their accident were twice as likely to report being free of pain as those not responsible (RR = 0.5;0.3-0.8). No correlation emerged with accident-related characteristics or PTSD. Conclusions: The present results extend our understand- ing of whiplash injury. Residual pain is the fundamental factor causing whiplash victims to feel that they have not recovered good health. Our findings suggest this may be bound up with physical factors (gender susceptibility);external factors such as having to carry weights (such as a baby) and with perceiving oneself as a victim are not incompatible with this hypothesis.展开更多
Evidence suggests that the structure of psychosis-proneness in the general population may involve three distinct related dimensions. Therefore we conducted a study, using a wider range of measures, to explore the fact...Evidence suggests that the structure of psychosis-proneness in the general population may involve three distinct related dimensions. Therefore we conducted a study, using a wider range of measures, to explore the factorial structure of schizotypy assessed by a mixed self-report Schizotypal Traits Questionnaire (mSTQ) in young French healthy individuals. Raine’s Schizotypal Personality Questionnaire [SPQ] and four of the Chapman’s scales [Magical Ideation Scale-MIS;Perceptual Aberration Scale-PAS;Revised Physical Anhedonia Scale-PhA and Revised Social Anhedonia Scale-SA] were combined to form a mSTQ which was administered to 232 French undergraduate students aged from 18 to 25 years old. A Principal Component Analysis [PCA] was carried out on scores for each scale to examine the factorial structure of schizotypal traits in this sample. PCA evidenced a three-factor model of schizotypy in the sample as a whole and even in the lower score sub-sample. The three factors were “positive or cognitive-perceptual”, “negative or social-interpersonal” and “disorganization” latent. Schizotypy, as assessed by these scales, is a multidimensional construct composed by at least three dimensions in this nonclinical sample. This factorial structure is similar to those of schizophrenia symptoms which raise the hypothesis of a continuum from normality to schizophrenia via schizotypal展开更多
Obsessive-compulsive disorder(OCD)is a severe mental illness characterized by persistent,intrusive and distressing obsessions and/or compulsions.Such symptoms have been conceptualized as resulting from a failure in so...Obsessive-compulsive disorder(OCD)is a severe mental illness characterized by persistent,intrusive and distressing obsessions and/or compulsions.Such symptoms have been conceptualized as resulting from a failure in sourcemonitoring processes,suggesting that patients with OCD fail to distinguish actions they perform from those they just imagine doing.In this study,we aimed to provide an updated and exhaustive review of the literature examining the relationship between source-monitoring and OCD.A systematic search in the literature through January 2019 allowed us to identify 13 relevant publications investigating source-monitoring abilities in patients with OCD or participants with subclinical compulsive symptoms.Most of the retrieved studies did not report any source-monitoring deficits in clinical and subclinical subjects compared with healthy volunteers.However,most of the studies reported that patients with OCD and subclinical subjects displayed reduced confidence in source-monitoring judgments or global cognitive confidence compared to controls.The present review highlighted some methodological and statistical limitations.Consequently,further studies are needed to explore source monitoring with regard to the subcategories of OCD symptoms(i.e.,symmetryordering,contamination-washing,hoarding,aggressive obsession-checking,sexual-religious thoughts)and to clarify the relationship between sourcemonitoring subtypes(i.e.,reality or internal source-monitoring)and confidence in these populations.展开更多
Red blood cells(RBCs)can act as carriers for therapeutic agents and can substantially improve the safety,pharmacokinetics,and pharmacodynamics of many drugs.Maintaining RBCs integrity and lifespan is important for the...Red blood cells(RBCs)can act as carriers for therapeutic agents and can substantially improve the safety,pharmacokinetics,and pharmacodynamics of many drugs.Maintaining RBCs integrity and lifespan is important for the efficacy of RBCs as drug carrier.We investigated the impact of drug encapsulation by hypotonic dialysis on RBCs physiology and integrity.Several parameters were compared between processed RBCs loaded with l-asparaginase(“eryaspase”),processed RBCs without drug and non-processed RBCs.Processed RBCs were less hydrated and displayed a reduction of intracellular content.We observed a change in the metabolomic but not in the proteomic profile of processed RBCs.Encapsulation process caused moderate morphological changes and was accompanied by an increase of RBCs-derived Extracellular Vesicles release.Despite a decrease in deformability,processed RBCs were not mechanically retained in a spleen-mimicking device and had increased surface-to-volume ratio and osmotic resistance.Processed RBCs half-life was not significantly affected in a mouse model and our previous phase 1 clinical study showed that encapsulation of asparaginase in RBCs prolonged its in vivo half-life compared to free forms.Our study demonstrated that encapsulation by hypotonic dialysis may affect certain characteristics of RBCs but does not significantly affect the in vivo longevity of RBCs or their drug carrier function.展开更多
AIM:To describe and analyse factors associated with Clostridium difficile infection(CDI)severity in hospitalised medical intensive care unit patients.METHODS:We performed a retrospective cohort study of 40 patients wi...AIM:To describe and analyse factors associated with Clostridium difficile infection(CDI)severity in hospitalised medical intensive care unit patients.METHODS:We performed a retrospective cohort study of 40 patients with CDI in a medical intensive care unit(MICU)at a French university hospital.We include patients hospitalised between January 1,2007and December 31,2011.Data on demographics characteristics,past medical history,CDI description was collected.Exposure to risk factors associated with CDI within 8 wk before CDI was recorded,including previous hospitalisation,nursing home residency,antibiotics,antisecretory drugs,and surgical procedures.RESULTS:All included cases had their first episode of CDI.The mean incidence rate was 12.94 cases/1000admitted patients,and 14.93,8.52,13.24,19.70,and8.31 respectively per 1000 admitted patients annually from 2007 to 2011.Median age was 62.9[interquartile range(IQR)55.4-72.40]years,and 13(32.5%)were women.Median length of MICU stay was 14.0d(IQR 5.0-22.8).In addition to diarrhoea,the clinical symptoms of CDI were fever(>38℃)in 23 patients,abdominal pain in 15 patients,and ileus in 1 patient.The duration of diarrhoea was 13.0(8.0-19.5)d.In addition to diarrhoea,the clinical symptoms of CDI were fever(>38℃)in 23 patients,abdominal pain in 15 patients,and ileus in 1 patient.Prior to CDI,38patients(95.0%)were exposed to antibiotics,and 12(30%)received at least 4 antibiotics.Fluoroquinolones,3rdgeneration cephalosporins,coamoxiclav and tazocillin were prescribed most frequently(65%,55%,40%and 37.5%,respectively).The majority of cases were hospital-acquired(n=36,90%),with 5 cases(13.9%)being MICU-acquired.Fifteen patients had severe CDI.The crude mortality rate within 30 d after diagnosis was 40%(n=16),with 9 deaths(9 over 16;56.3%)related to CDI.Of our 40 patients,15(37.5%)had severe CDI.Multivariate logistic regression showed that male gender[odds ratio(OR):8.45;95%CI:1.06-67.16,P=0.044],rising serum C-reactive protein levels(OR=1.11;95%CI:1.02-1.21,P=0.021),and previous e展开更多
A critical cognitive symptom that is commonly involved in social anxiety and depression is attentional deficit. However, the functional relationship between attentional deficit and these two disorders remains poorly u...A critical cognitive symptom that is commonly involved in social anxiety and depression is attentional deficit. However, the functional relationship between attentional deficit and these two disorders remains poorly understood. Here, we behaviorally disentangled the three key attentional components(alerting, orienting, and executive control) using the established attentional network task(ANT) to investigate how social anxiety and depression are related to deficits in these attention components. We identified a double dissociation between the symptoms of social anxiety and depression and the attentional component deficits when processing non-emotional stimuli. While individuals vulnerable to social anxiety exhibited deficits in the orienting component, individuals vulnerable to depression were impaired in the executive control component. Our findings showed that social anxiety and depression were associated with deficits in different attentional components, which are not specific to emotional information.展开更多
On-board measurements of unit emissions of CO,HC,NOx and CO2 were conducted on 17 private cars powered by different types of fuels including gasoline,dual gasoline–liquefied petroleum gas（LPG）,gasoline,and diesel. ...On-board measurements of unit emissions of CO,HC,NOx and CO2 were conducted on 17 private cars powered by different types of fuels including gasoline,dual gasoline–liquefied petroleum gas（LPG）,gasoline,and diesel. The tests performed revealed the effect of LPG injection technology on unit emissions and made it possible to compare the measured emissions to the European Artemis emission model. A sequential multipoint injection LPG kit with no catalyst installed was found to be the most efficient pollutant reduction device for all of the pollutants,with the exception of the NOx. Specific test results for a sub-group of LPG vehicles revealed that LPG-fueled engines with no catalyst cannot compete with catalyzed gasoline and diesel engines. Vehicle age does not appear to be a determining parameter with regard to vehicle pollutant emissions. A fuel switch to LPG offers many advantages as far as pollutant emissions are concerned,due to LPG＇s intrinsic characteristics.However,these advantages are being rapidly offset by the strong development of both gasoline and diesel engine technologies and catalyst converters. The LPG＇s performance on a chassis dynamometer under real driving conditions was better than expected. The enforcement of pollutant emission standards in developing countries is an important step towards introducing clean technology and reducing vehicle emissions.展开更多
Aircraft pollutant emissions are an important part of sources of pollution that directly or indirectly affect human health and ecosystems. This research suggests an Artificial Neural Network model to determine the hea...Aircraft pollutant emissions are an important part of sources of pollution that directly or indirectly affect human health and ecosystems. This research suggests an Artificial Neural Network model to determine the healthy risk level around Soekarno Hatta International Airport-Cengkareng Indonesia. This ANN modeling is a flexible method, which enables to recognize highly complex non-linear correlations. The network was trained with real measurement data and updated with new measurements, enhancing its quality and making it the ideal method for this research. Measurements of aircraft pollutant emissions are carried out with the aim to be used as input data and to validate the developed model. The obtained results concerned the improved ANN architecture model based on pollutant emissions as input variables. ANN model processes variables—hidden layers—and gives an output variable corresponding to a healthy risk level. This model is characterized by a 4-10-1 scheme. Based on ANN criteria, the best validation performance is achieved at epoch 28 from 34 epochs with the Mean Squared Error (MSE) of 9 × 10-3. The correlation between targets and outputs is confirmed. It validated a close relationship between targets and outputs. The network output errors value approaches zero. Further research is needed with the aim to enlarge the scheme of the ANN model by increasing its input variables. This is one of the major key defining environmental capacities of an airport that should be applied by Indonesian airport authorities. These would institute policies to manage or reduce pollutant emissions considering population and income growth to be socially positive.展开更多
We read with great interest the paper by Miyata et al.entitled:The Impact of Histologic Liver Inflammation on Oncology and the Prognosis of Patients Undergoing Hepatectomy for Hepatocellular Carcinoma(1).In this singl...We read with great interest the paper by Miyata et al.entitled:The Impact of Histologic Liver Inflammation on Oncology and the Prognosis of Patients Undergoing Hepatectomy for Hepatocellular Carcinoma(1).In this single center retrospective study,the authors included 500 patients undergoing curative surgical liver resection for primary hepatocellular carcinoma(HCC)without any neoadjuvant treatment.All liver specimen underwent postoperative pathological analysis to identify fibrosis but also lymphocyte infiltration and hepatocyte necrosis as surrogate marker for hepatic inflammation.Histological hepatic inflammation was graded from A0:no necro-inflammatory reaction,to A3:severe necro-inflammatory reaction.Median follow-up was 47.3 months.Overall,19.4%of the patients had severe liver inflammation A3(n=97)and presented with higher postoperative morbidity and reduced overall and recurrence-free survival compared to patients with none to moderate inflammation A0-A2(n=403).Furthermore,inflammation grade A3 was an independent predictor of HCC recurrence independent of underlying liver disease and fibrosis grade.展开更多
In order to investigate the evolution of the venous patch blood inter face after implantation, an experimental model utilizing an autologous venous patch to repair an infrarenal abdominal aortic defect in rats was dev...In order to investigate the evolution of the venous patch blood inter face after implantation, an experimental model utilizing an autologous venous patch to repair an infrarenal abdominal aortic defect in rats was developed. A small piece of both the jugular vein and the aorta were first excised. After implantation and reestablishment of blood flow, the animals were subsequently sacrificed in groups of 3 at the following intervals: 10 seconds, 1, 10, 30 minutes, 1, 6, 12, 24 hours, 7, 30 and 90 days. All the patches and adjacent aortae were collected and studied using scanning electron microscopy. The results of our present show that: 1) the extensive endothelial lesion of both the autologous vein patch and the adjacent aorta is presented before implantation due to operative manipulation; 2) after blood flow reestablishment, the patch and the adjacent aortic interface are reactive to platelets and other blood cells; 3) the new cellular lining begins to appear from the 7th day after implantation, but it is not complete at 3 months; 4)from the model, the endothelial repair of autologous venous patch and its adjacent aorta is a very slow process.展开更多
AIM:To analyze the impact of previous cyst-enterostomy of patients underwent congenital bile duct cysts(BDC)resection.METHODS:A multicenter European retrospective study between 1974 and 2011 were conducted by the Fren...AIM:To analyze the impact of previous cyst-enterostomy of patients underwent congenital bile duct cysts(BDC)resection.METHODS:A multicenter European retrospective study between 1974 and 2011 were conducted by the French Surgical Association.Only Todani subtypes I and IVb were included.Diagnostic imaging studies and operative and pathology reports underwent central revision.Patients with and without a previous history of cystenterostomy(CE)were compared.RESULTS:Among 243 patients with Todani types I and IVb BDC,16 had undergone previous CE(6.5%).Patients with a prior history of CE experienced a greater incidence of preoperative cholangitis(75%vs 22.9%,P<0.0001),had more complicated presentations(75%vs 40.5%,P=0.007),and were more likely to have synchronous biliary cancer(31.3%vs 6.2%,P=0.004)than patients without a prior CE.Overall morbidity(75%vs 33.5%;P<0.0008),severe complications(43.8%vs 11.9%;P=0.0026)and reoperation rates(37.5%vs 8.8%;P=0.0032)were also significantly greater in patients with previous CE,and their Mayo Risk Score,during a median follow-up of 37.5 mo(range:4-372 mo)indicated significantly more patients with fair and poor results(46.1%vs 15.6%;P=0.0136).CONCLUSION:This is the large series to show that previous CE is associated with poorer short-and longterm results after Todani types I and IVb BDC resection.展开更多
In this study, we followed the biodegradation of ultra-small superparamagnetic iron oxide nanoparticles injected intravenously at clinical doses in mice. An advanced fitting procedure for magnetic susceptibility curve...In this study, we followed the biodegradation of ultra-small superparamagnetic iron oxide nanoparticles injected intravenously at clinical doses in mice. An advanced fitting procedure for magnetic susceptibility curves and low- temperature hysteresis loops was used to fully characterize the magnetic size distribution as well as the magnetic anisotropy energy of the injected P904 nano- particles （Guerbet Laboratory）. Additional magnetometry measurements and transmission electronic microscopy observations were systematically performed to examine dehydrated samples from the spleen and liver of healthy C57B16 mice after nanoparticle injection, with sacrifice of the mice for up to 14 months. At 3 months after injection, the magnetic properties of the spleen and liver were dramatically different. While the liver showed no magnetic signals other than those also present in the reference species, the spleen showed an increased magnetic signal attributed to ferritin. This surplus of ferritin remained constant up to 14 months after injection.展开更多
Background:NANOG is a core transcription factor(TF)in embryonic stem cells(ESCs)and primordial germ cells(PGCs).Regulation of the NANOG gene by TFs,epigenetic factors,and autoregulatory factors is well characterized i...Background:NANOG is a core transcription factor(TF)in embryonic stem cells(ESCs)and primordial germ cells(PGCs).Regulation of the NANOG gene by TFs,epigenetic factors,and autoregulatory factors is well characterized in ESCs,and transcriptional regulation of NANOG is well established in these cells.Although NANOG plays a key role in germ cells,the molecular mechanism underlying its transcriptional regulation in PGCs has not been studied.Therefore,we investigated the mechanism that regulates transcription of the chicken NANOG(cNANOG)gene in PGCs and ESCs.Results:We first identified the transcription start site of cNANOG by 5′-rapid amplification of cDNA ends PCR analysis.Then,we measured the promoter activity of various 5′flanking regions of cNANOG in chicken PGCs and ESCs using the luciferase reporter assay.cNANOG expression required transcriptional regulatory elements,which were positively regulated by POU5F3(OCT4)and SOX2 and negatively regulated by TP53 in PGCs.The proximal region of the cNANOG promoter contains a positive transcriptional regulatory element(CCAAT/enhancer-binding protein(CEBP)-binding site)in ESCs.Furthermore,small interfering RNA-mediated knockdown demonstrated that POU5F3,SOX2,and CEBP played a role in cell type-specific transcription of cNANOG.Conclusions:We show for the first time that different trans-regulatory elements control transcription of cNANOG in a cell type-specific manner.This finding might help to elucidate the mechanism that regulates cNANOG expression in PGCs and ESCs.展开更多
基金The ethics committee of our institution approved our study protocol and amendments(n°22.04729.000226).
文摘Sagittal knee laxity is often quantified using arthrometers. Adding rotational laxity and compliance measurementsis relatively new and could bring new information for anterior cruciate ligament (ACL) injury diagnosis. TheDYNEELAX® is a new knee arthrometer able to evaluate simultaneously tibial translation and rotation. Thepurpose is to assess the sensitivity, reproducibility and repeatability of the DYNEELAX® with a prototype leg toprovide accurate instructions before using it in clinical practice. Sensitivity is studied by varying 7 parameters(positioning and sensors), and reproducibility by repeating measurement series with a group of two experiencedoperators and a group of two non-experienced operators. Repeatability is assessed throughout the study. Theresults showed that DYNEELAX® is poorly sensitive to the angle and the position of the displacement sensor, andthe angle of the rotation sensor. It is a bit sensitive to positioning of patella and ankle supports. It is very sensitiveto the tightening of the patella and ankle supports. It exists a significant difference only between groups (p <0.001), but there is no significant difference between the two experienced operators (p > 0.215), or between thetwo non-experienced operators (p > 0.229). Variation coefficients for intra-series are on average inferior to 5% fortranslation and rotation tests. Then, the DYNEELAX® presented encouraging results with a good accuracy and agood reliability but operators must be careful about positioning.
基金supported by a grant from the French Society of Sleep Research and Medicine(to LS)The China Scholarship Council(to HL)The CNRS,INSERM,Claude Bernard University Lyon1(to LS)。
文摘The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularl
基金supported by the European Research Council(CoG 2020 grant number 101000948 awarded to GC)the Agence Nationale de la Recherche-Programme d’Investissements d’Avenir(ANR-18-RHUS-005 to GC)+1 种基金the Agence Nationale de la Recherche-Programme de Recherche Collaborative(19-CE14-0030-01 to GC)supported by the CLOVES SYNDROME COMMUNITY(West Kennebunk,USA),Association Syndrome de CLOVES(Nantes,France),Fondation d’entreprise IRCEM(Roubaix,France),Fonds de dotation Emmanuel BOUSSARD(Paris,France),the Fondation DAY SOLVAY(Paris,France),the Fondation TOURRE(Paris,France)to GC,the Fondation BETTENCOURT SCHUELLER(Paris,France)to GC,the Fondation Simone et Cino DEL DUCA(Paris,France),the Fondation Line RENAUD-Loulou GASTE(Paris,France,the Fondation Schlumberger pour l’Education et la Recherche(Paris,France),the Association Robert Debrépour la Recherche.
文摘Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through PIK3CA.Venous malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening situations.No authorized medical treatment exists for patients with venous malformations.Here,we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient phenotypes.We showed that these malformations only partially signal through AKT proteins.We compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a PI3Kαinhibitor at improving the lesions seen in the mouse model.We demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging survival.Considering these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying PIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous sclerotherapies.We assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each patient.Alpelisib demonstrated improvement in all 25 patients.Vascular malformations previously considered intractable were reduced and clinical symptoms were attenuated.MRI showed a decrease of 33.4%and 27.8%in the median volume of PIK3CA and TEK malformations respectively,over 6 months on alpelisib.In conclusion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.
文摘Excavation with tunnel boring machine(TBM)can generate vibrations,causing damages to neighbouring buildings and disturbing the residents or the equipment.This problem is particularly challenging in urban areas,where TBMs are increasingly large in diameter and shallow in depth.In response to this problem,four experimental campaigns were carried out in different geotechnical contexts in France.The vibration measurements were acquired on the surface and inside the TBMs.These measurements are also complemented by few data in the literature.An original methodology of signal processing is pro-posed to characterize the amplitude of the particle velocities,as well as the frequency content of the signals to highlight the most energetic bands.The levels of vibrations are also compared with the thresholds existing in various European regulations concerning the impact on neighbouring structures and the disturbance to local residents.
文摘Objective: Dehydroepiandrosterone (DHEA) has been previously reported to improve ovarian response in IVF for poor responders. Its effect remains uncertain. The purpose of this study was to evaluate the effect of DHEA given during two years in our unit, in order to build hypothesis for a future randomized controlled trial. Design: Cohort of exposed and non-exposed DHEA study. Patient(s): 224 patients with AMH under 1.6 ng/ml undergoing IVF with a short antagonist protocol adding FSH and LH rec were enrolled for 327 IVF cycles. 176 patients had been treated with DHEA before IVF, and 151 had not. Intervention(s): None. Main Outcome Measure(s): Cancellation cycle rate, amount of gonadotrophins used, estradiol level on day six of stimulation, number of oocytes retrieved, metaphase II oocytes, blastocysts and frozen embryos, clinical pregnancy rate and miscarriage rate. Results: The cancellation rate was significantly higher in the group without DHEA (29.8% versus 13.1%, p = 0.002). The amount of gonadotrophins used for stimulation, the estradiol level on day six of stimulation, the number of oocytes retrieved, metaphase II oocytes, blastocysts, frozen embryos and miscarriage rate were not different in both groups. The clinical pregnancy rate per included patient in the DHEA group was 17.1% versus 8.6% in the non-treated group (p = 0.02). Conclusion: DHEA appears to improve clinical pregnancy rate by decreasing the cancellation rate.
文摘Background: A large number of studies have addressed whiplash injury, and many meta-analyses have sought to highlight chronicity factors;the implicated processes, however, remain a matter of debate. The present study used data from the ESPARR cohort (an on-going prospective study of a representative cohort of road accident victims in the Rh?ne administrative département of France). The objectives were to describe the consequences of whiplash injury and to determine prognostic factors for poor recovery and persistent pain at 1 year post-accident. Methods: The cohort included 255 “pure” whiplash victims, 173 of whom responded to the 1-year follow-up questionnaire. Correlations between explanatory variables and health and pain status were explored by modified Poisson regression to provide adjusted relative risk (RR) values. Results: Half of the victims had not fully recovered health status by 1 year. The main factor associated with non-recovery was pain (RR = 1.3;1.0-1.7). A birth in the family preceding the accident emerged as another factor (RR=1.5;1.2-1.9). Victims responsible for their accident were twice as likely to report being free of pain as those not responsible (RR = 0.5;0.3-0.8). No correlation emerged with accident-related characteristics or PTSD. Conclusions: The present results extend our understand- ing of whiplash injury. Residual pain is the fundamental factor causing whiplash victims to feel that they have not recovered good health. Our findings suggest this may be bound up with physical factors (gender susceptibility);external factors such as having to carry weights (such as a baby) and with perceiving oneself as a victim are not incompatible with this hypothesis.
基金grants from the “Progamme Hospitalier de Recherche Clinique” (PHRC) the “Université Lyon 1” (BQR) the “Conseil Scientifique de la Recherche, CH Le Vinatier”
文摘Evidence suggests that the structure of psychosis-proneness in the general population may involve three distinct related dimensions. Therefore we conducted a study, using a wider range of measures, to explore the factorial structure of schizotypy assessed by a mixed self-report Schizotypal Traits Questionnaire (mSTQ) in young French healthy individuals. Raine’s Schizotypal Personality Questionnaire [SPQ] and four of the Chapman’s scales [Magical Ideation Scale-MIS;Perceptual Aberration Scale-PAS;Revised Physical Anhedonia Scale-PhA and Revised Social Anhedonia Scale-SA] were combined to form a mSTQ which was administered to 232 French undergraduate students aged from 18 to 25 years old. A Principal Component Analysis [PCA] was carried out on scores for each scale to examine the factorial structure of schizotypal traits in this sample. PCA evidenced a three-factor model of schizotypy in the sample as a whole and even in the lower score sub-sample. The three factors were “positive or cognitive-perceptual”, “negative or social-interpersonal” and “disorganization” latent. Schizotypy, as assessed by these scales, is a multidimensional construct composed by at least three dimensions in this nonclinical sample. This factorial structure is similar to those of schizophrenia symptoms which raise the hypothesis of a continuum from normality to schizophrenia via schizotypal
文摘Obsessive-compulsive disorder(OCD)is a severe mental illness characterized by persistent,intrusive and distressing obsessions and/or compulsions.Such symptoms have been conceptualized as resulting from a failure in sourcemonitoring processes,suggesting that patients with OCD fail to distinguish actions they perform from those they just imagine doing.In this study,we aimed to provide an updated and exhaustive review of the literature examining the relationship between source-monitoring and OCD.A systematic search in the literature through January 2019 allowed us to identify 13 relevant publications investigating source-monitoring abilities in patients with OCD or participants with subclinical compulsive symptoms.Most of the retrieved studies did not report any source-monitoring deficits in clinical and subclinical subjects compared with healthy volunteers.However,most of the studies reported that patients with OCD and subclinical subjects displayed reduced confidence in source-monitoring judgments or global cognitive confidence compared to controls.The present review highlighted some methodological and statistical limitations.Consequently,further studies are needed to explore source monitoring with regard to the subcategories of OCD symptoms(i.e.,symmetryordering,contamination-washing,hoarding,aggressive obsession-checking,sexual-religious thoughts)and to clarify the relationship between sourcemonitoring subtypes(i.e.,reality or internal source-monitoring)and confidence in these populations.
基金funds from the FEDER through the Operational Programme for Competitiveness Factors and Employment 2007-2013 (France)from the Cancérop?le Ile de France (France)
文摘Red blood cells(RBCs)can act as carriers for therapeutic agents and can substantially improve the safety,pharmacokinetics,and pharmacodynamics of many drugs.Maintaining RBCs integrity and lifespan is important for the efficacy of RBCs as drug carrier.We investigated the impact of drug encapsulation by hypotonic dialysis on RBCs physiology and integrity.Several parameters were compared between processed RBCs loaded with l-asparaginase(“eryaspase”),processed RBCs without drug and non-processed RBCs.Processed RBCs were less hydrated and displayed a reduction of intracellular content.We observed a change in the metabolomic but not in the proteomic profile of processed RBCs.Encapsulation process caused moderate morphological changes and was accompanied by an increase of RBCs-derived Extracellular Vesicles release.Despite a decrease in deformability,processed RBCs were not mechanically retained in a spleen-mimicking device and had increased surface-to-volume ratio and osmotic resistance.Processed RBCs half-life was not significantly affected in a mouse model and our previous phase 1 clinical study showed that encapsulation of asparaginase in RBCs prolonged its in vivo half-life compared to free forms.Our study demonstrated that encapsulation by hypotonic dialysis may affect certain characteristics of RBCs but does not significantly affect the in vivo longevity of RBCs or their drug carrier function.
基金Supported by A grant for her PhD from Sanofi Pasteur,France,to Khanafer N
文摘AIM:To describe and analyse factors associated with Clostridium difficile infection(CDI)severity in hospitalised medical intensive care unit patients.METHODS:We performed a retrospective cohort study of 40 patients with CDI in a medical intensive care unit(MICU)at a French university hospital.We include patients hospitalised between January 1,2007and December 31,2011.Data on demographics characteristics,past medical history,CDI description was collected.Exposure to risk factors associated with CDI within 8 wk before CDI was recorded,including previous hospitalisation,nursing home residency,antibiotics,antisecretory drugs,and surgical procedures.RESULTS:All included cases had their first episode of CDI.The mean incidence rate was 12.94 cases/1000admitted patients,and 14.93,8.52,13.24,19.70,and8.31 respectively per 1000 admitted patients annually from 2007 to 2011.Median age was 62.9[interquartile range(IQR)55.4-72.40]years,and 13(32.5%)were women.Median length of MICU stay was 14.0d(IQR 5.0-22.8).In addition to diarrhoea,the clinical symptoms of CDI were fever(>38℃)in 23 patients,abdominal pain in 15 patients,and ileus in 1 patient.The duration of diarrhoea was 13.0(8.0-19.5)d.In addition to diarrhoea,the clinical symptoms of CDI were fever(>38℃)in 23 patients,abdominal pain in 15 patients,and ileus in 1 patient.Prior to CDI,38patients(95.0%)were exposed to antibiotics,and 12(30%)received at least 4 antibiotics.Fluoroquinolones,3rdgeneration cephalosporins,coamoxiclav and tazocillin were prescribed most frequently(65%,55%,40%and 37.5%,respectively).The majority of cases were hospital-acquired(n=36,90%),with 5 cases(13.9%)being MICU-acquired.Fifteen patients had severe CDI.The crude mortality rate within 30 d after diagnosis was 40%(n=16),with 9 deaths(9 over 16;56.3%)related to CDI.Of our 40 patients,15(37.5%)had severe CDI.Multivariate logistic regression showed that male gender[odds ratio(OR):8.45;95%CI:1.06-67.16,P=0.044],rising serum C-reactive protein levels(OR=1.11;95%CI:1.02-1.21,P=0.021),and previous e
基金supported by the National Natural Science Foundation of China (31930053, 31671168, 31421003)Beijing Municipal Science and Technology Commission (Z181100001518002)。
文摘A critical cognitive symptom that is commonly involved in social anxiety and depression is attentional deficit. However, the functional relationship between attentional deficit and these two disorders remains poorly understood. Here, we behaviorally disentangled the three key attentional components(alerting, orienting, and executive control) using the established attentional network task(ANT) to investigate how social anxiety and depression are related to deficits in these attention components. We identified a double dissociation between the symptoms of social anxiety and depression and the attentional component deficits when processing non-emotional stimuli. While individuals vulnerable to social anxiety exhibited deficits in the orienting component, individuals vulnerable to depression were impaired in the executive control component. Our findings showed that social anxiety and depression were associated with deficits in different attentional components, which are not specific to emotional information.
文摘On-board measurements of unit emissions of CO,HC,NOx and CO2 were conducted on 17 private cars powered by different types of fuels including gasoline,dual gasoline–liquefied petroleum gas（LPG）,gasoline,and diesel. The tests performed revealed the effect of LPG injection technology on unit emissions and made it possible to compare the measured emissions to the European Artemis emission model. A sequential multipoint injection LPG kit with no catalyst installed was found to be the most efficient pollutant reduction device for all of the pollutants,with the exception of the NOx. Specific test results for a sub-group of LPG vehicles revealed that LPG-fueled engines with no catalyst cannot compete with catalyzed gasoline and diesel engines. Vehicle age does not appear to be a determining parameter with regard to vehicle pollutant emissions. A fuel switch to LPG offers many advantages as far as pollutant emissions are concerned,due to LPG＇s intrinsic characteristics.However,these advantages are being rapidly offset by the strong development of both gasoline and diesel engine technologies and catalyst converters. The LPG＇s performance on a chassis dynamometer under real driving conditions was better than expected. The enforcement of pollutant emission standards in developing countries is an important step towards introducing clean technology and reducing vehicle emissions.
文摘Aircraft pollutant emissions are an important part of sources of pollution that directly or indirectly affect human health and ecosystems. This research suggests an Artificial Neural Network model to determine the healthy risk level around Soekarno Hatta International Airport-Cengkareng Indonesia. This ANN modeling is a flexible method, which enables to recognize highly complex non-linear correlations. The network was trained with real measurement data and updated with new measurements, enhancing its quality and making it the ideal method for this research. Measurements of aircraft pollutant emissions are carried out with the aim to be used as input data and to validate the developed model. The obtained results concerned the improved ANN architecture model based on pollutant emissions as input variables. ANN model processes variables—hidden layers—and gives an output variable corresponding to a healthy risk level. This model is characterized by a 4-10-1 scheme. Based on ANN criteria, the best validation performance is achieved at epoch 28 from 34 epochs with the Mean Squared Error (MSE) of 9 × 10-3. The correlation between targets and outputs is confirmed. It validated a close relationship between targets and outputs. The network output errors value approaches zero. Further research is needed with the aim to enlarge the scheme of the ANN model by increasing its input variables. This is one of the major key defining environmental capacities of an airport that should be applied by Indonesian airport authorities. These would institute policies to manage or reduce pollutant emissions considering population and income growth to be socially positive.
文摘We read with great interest the paper by Miyata et al.entitled:The Impact of Histologic Liver Inflammation on Oncology and the Prognosis of Patients Undergoing Hepatectomy for Hepatocellular Carcinoma(1).In this single center retrospective study,the authors included 500 patients undergoing curative surgical liver resection for primary hepatocellular carcinoma(HCC)without any neoadjuvant treatment.All liver specimen underwent postoperative pathological analysis to identify fibrosis but also lymphocyte infiltration and hepatocyte necrosis as surrogate marker for hepatic inflammation.Histological hepatic inflammation was graded from A0:no necro-inflammatory reaction,to A3:severe necro-inflammatory reaction.Median follow-up was 47.3 months.Overall,19.4%of the patients had severe liver inflammation A3(n=97)and presented with higher postoperative morbidity and reduced overall and recurrence-free survival compared to patients with none to moderate inflammation A0-A2(n=403).Furthermore,inflammation grade A3 was an independent predictor of HCC recurrence independent of underlying liver disease and fibrosis grade.
文摘In order to investigate the evolution of the venous patch blood inter face after implantation, an experimental model utilizing an autologous venous patch to repair an infrarenal abdominal aortic defect in rats was developed. A small piece of both the jugular vein and the aorta were first excised. After implantation and reestablishment of blood flow, the animals were subsequently sacrificed in groups of 3 at the following intervals: 10 seconds, 1, 10, 30 minutes, 1, 6, 12, 24 hours, 7, 30 and 90 days. All the patches and adjacent aortae were collected and studied using scanning electron microscopy. The results of our present show that: 1) the extensive endothelial lesion of both the autologous vein patch and the adjacent aorta is presented before implantation due to operative manipulation; 2) after blood flow reestablishment, the patch and the adjacent aortic interface are reactive to platelets and other blood cells; 3) the new cellular lining begins to appear from the 7th day after implantation, but it is not complete at 3 months; 4)from the model, the endothelial repair of autologous venous patch and its adjacent aorta is a very slow process.
文摘AIM:To analyze the impact of previous cyst-enterostomy of patients underwent congenital bile duct cysts(BDC)resection.METHODS:A multicenter European retrospective study between 1974 and 2011 were conducted by the French Surgical Association.Only Todani subtypes I and IVb were included.Diagnostic imaging studies and operative and pathology reports underwent central revision.Patients with and without a previous history of cystenterostomy(CE)were compared.RESULTS:Among 243 patients with Todani types I and IVb BDC,16 had undergone previous CE(6.5%).Patients with a prior history of CE experienced a greater incidence of preoperative cholangitis(75%vs 22.9%,P<0.0001),had more complicated presentations(75%vs 40.5%,P=0.007),and were more likely to have synchronous biliary cancer(31.3%vs 6.2%,P=0.004)than patients without a prior CE.Overall morbidity(75%vs 33.5%;P<0.0008),severe complications(43.8%vs 11.9%;P=0.0026)and reoperation rates(37.5%vs 8.8%;P=0.0032)were also significantly greater in patients with previous CE,and their Mayo Risk Score,during a median follow-up of 37.5 mo(range:4-372 mo)indicated significantly more patients with fair and poor results(46.1%vs 15.6%;P=0.0136).CONCLUSION:This is the large series to show that previous CE is associated with poorer short-and longterm results after Todani types I and IVb BDC resection.
文摘In this study, we followed the biodegradation of ultra-small superparamagnetic iron oxide nanoparticles injected intravenously at clinical doses in mice. An advanced fitting procedure for magnetic susceptibility curves and low- temperature hysteresis loops was used to fully characterize the magnetic size distribution as well as the magnetic anisotropy energy of the injected P904 nano- particles （Guerbet Laboratory）. Additional magnetometry measurements and transmission electronic microscopy observations were systematically performed to examine dehydrated samples from the spleen and liver of healthy C57B16 mice after nanoparticle injection, with sacrifice of the mice for up to 14 months. At 3 months after injection, the magnetic properties of the spleen and liver were dramatically different. While the liver showed no magnetic signals other than those also present in the reference species, the spleen showed an increased magnetic signal attributed to ferritin. This surplus of ferritin remained constant up to 14 months after injection.
基金This work was supported by a National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIP)[2015R1A3A2033826]and[2018R1D1A1B07049376].
文摘Background:NANOG is a core transcription factor(TF)in embryonic stem cells(ESCs)and primordial germ cells(PGCs).Regulation of the NANOG gene by TFs,epigenetic factors,and autoregulatory factors is well characterized in ESCs,and transcriptional regulation of NANOG is well established in these cells.Although NANOG plays a key role in germ cells,the molecular mechanism underlying its transcriptional regulation in PGCs has not been studied.Therefore,we investigated the mechanism that regulates transcription of the chicken NANOG(cNANOG)gene in PGCs and ESCs.Results:We first identified the transcription start site of cNANOG by 5′-rapid amplification of cDNA ends PCR analysis.Then,we measured the promoter activity of various 5′flanking regions of cNANOG in chicken PGCs and ESCs using the luciferase reporter assay.cNANOG expression required transcriptional regulatory elements,which were positively regulated by POU5F3(OCT4)and SOX2 and negatively regulated by TP53 in PGCs.The proximal region of the cNANOG promoter contains a positive transcriptional regulatory element(CCAAT/enhancer-binding protein(CEBP)-binding site)in ESCs.Furthermore,small interfering RNA-mediated knockdown demonstrated that POU5F3,SOX2,and CEBP played a role in cell type-specific transcription of cNANOG.Conclusions:We show for the first time that different trans-regulatory elements control transcription of cNANOG in a cell type-specific manner.This finding might help to elucidate the mechanism that regulates cNANOG expression in PGCs and ESCs.
