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Sequencing of high-efficacy disease-modifying therapies in multiple sclerosis： perspectives and approaches

Neural Regeneration Research 2018年第11期13卷 1871-1874页

作者： francois Grand'Maison Michael Yeung Sarah A. Morrow Liesly Lee francois Emond Brian J. Ward pierre Laneuville Robyn Schecter Neuro Rive-Sud Hospital Charles LeMoyne Greenfield Park Quebec Canada Clinical Neurosciences Foothills Medical Centre Calgary Alberta Canada London Health Sciences Center (LHSC) Western University London Ontario Canada Department of Neurology Sunnybrook Health Sciences Centre Toronto Ontario Canada Centre Hospitalier Universitaire de Quebec - hospital de l'Enfant-Jesus Quebec City Quebec Canada Research Institute of the McGill University Health Centre Montreal Quebec Canada Department of Medicine McGill University Montreal Quebec Canada Novartis Pharmaceuticals Canada Inc. Dotal Quebec Canada

Multiple sclerosis（MS） is characterized by chronic inflammation in conjunction with neurodegeneration within the central nervous system. Most individuals with MS begin with a relapsing remitting course that later transitions to secondary progressive MS. Currently available disease-modifying therapies（DMTs） for relapsing MS have been demonstrated to reduce disease activity, however most patients require a change in therapy over the course of their disease. Treatment goals include the prevention of relapses and disability accumulation and to achieve this objective requires careful planning. Sequencing of DMTs for individual patients should be designed in such a way to maximize disease control and minimize risk based on the mechanism of action, pharmacokinetic and pharmacodynamic properties of each therapy. This includes the DMT patients are being switched from to those they are being switched to. The reversibility of immune system effects should be a key consideration for DMT sequence selection. This feature varies across DMTs and should factor more prominently in decision making as newer treatments become available for the prevention of disability accumulation in patients with progressive MS. In this short review, we discuss the landscape of existing therapies with an eye to the future when planning for optimal DMT sequencing. While no cure exists for MS, efforts are being directed toward research in neuroregeneration with the hope for positive outcomes.

关键词： relapsing multiple sclerosis high efficacy disease-modifying therapies treatment optimization treatment sequencing therapeutic inertia sub-optimal treatment progressive disease immune effects

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Facilitated Fe Nutrition by Phenolic Compounds Excreted by the Arabidopsis ABCG37/PDR9 Transporter Requires the IRT1/FRO2 High-Affinity Root Fe^2＋ Transport System

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Molecular Plant 2016年第3期9卷 485-488页

作者： pierre Fourcroy Nicolas Tissot Frederic Gaymard Jean-francois Briat Christian Dubos Biochimie et Physiologie Moldculaire des Plantes Centre National de la Recherche Scientifique Institut National de la Recherche Agronomique Universite Montpellier SupAgro Bat 7 2 place Viala 34060 Montpellier Cedex 1 France

Iron （Fe） is an essential metal nutrient for plant productivity and plant product quality （Briat et al., 2015）. Fe exists under two forms, ferrous （Fe^2＋） or ferric （Fe^3＋）, and is very reactive with oxygen, explaining why Fe plant nutrition is dependent upon both Fe chelation and Fe reduction. Fe availability in the soil is pH dependent, this metal being particularly insoluble in its ferric form in calcareous soils, representing one-third of the world＇s cultivated soils. Consequently, plants grown on these soils, in particular non-graminaceous plants, often suffer from Fe deficiency, which alters their growth.

关键词： explaining dependent calcareous

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Value of intravascular ultrasound imaging in following up patients with replacement of the ascending aorta for acute type A aortic dissection

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Chinese Medical Journal 2008年第21期121卷 2139-2143页

作者： HU Wei francois Schiele Nicolas Meneveau Marie-France Seronde pierre Legalery Fiona Caulfield Jean-Frangois Bonneville Sidney Chocron Jean-pierre Bassand Department of Cardiology Min Hang Central Hospital Shanghai 201100 China Department of Cardiology Jean Minjoz Hospital Besancon 25000 France Department of Radiology Jean Minjoz Hospital Besancon 25000 France Department of Cardiac Surgery Jean Minjoz Hospital Besancon 25000 France

Background The value of intravascular ultrasound （IVUS） imaging in patients with replacement of the ascending aorta for acute type A aortic dissection （AD） is unknown. The purpose of this study was to assess the potential use of IVUS imaging in this setting. Methods From September 2002 to July 2005, IVUS imaging with a 9 MHz probe was performed in a series of 16 consecutive patients with suspected or established AD. This study focused on 5 of them with replacement of the ascending aorta for acute type A AD. Among these 5 patients, other imaging modalities including aortography, spiral computed tomography, magnetic resonance imaging and transesophageal echocardiography were performed in 5, 3, 3 and 1 patients, respectively. Results There were no complications related to IVUS imaging. For the replaced graft, as other imaging modalities, IVUS could identify all 5 grafts, the proximal and the distal anastomoses, and the ostia of the reimplanted coronary arteries. In 2 cases, IVUS detected 2 peri-graft pseudo-aneurysms （1 per case）, which were also detected by magnetic resonance imaging but omitted by aortography. For the residual dissection, IVUS had similar findings as other imaging modalities in detecting the patency （5/5）, the longitudinal and the circumferential extent, the thrombus （4/5）, the recurrent dissection （1/5） and an aneurysm distal to the graft （5 in 4 patients）. However, it detected more intimal tears and side branch involvements than other imaging modalities （15 vs 10 and 3 vs 1, respectively）. Conclusions In following-up patients with replacement of the ascending aorta for acute type A AD, IVUS imaging can provide complete information of the replaced graft and the residual dissection. So, IVUS imaging may be considered when the four current frequently used imaging modalities can not supply sufficient information or there are some discrepancies between them.

关键词： intravascular ultrasound aortic dissection graft

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Reliability and sensitivity to change of IW-TSE versus DESS magnetic resonance imaging sequences in the assessment of bone marrow lesions in knee osteoarthritis patients: Longitudinal data from the Osteoarthritis Initiative (OAI) cohort

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Journal of Biomedical Science and Engineering 2013年第3期6卷 337-345页

作者： Jean-pierre Raynauld Lukas martin Wildi francois Abram Thomas Moser Jean-pierre Pelletier Johanne Martel-Pelletier Osteoarthritis Research Unit University of Montreal Hospital Research Center(CRCHUM)MontrealCanada Department of Rheumatology University Hospital of ZurichZurichSwitzerland Imaging Research&Development ArthroLab Inc.MontrealCanada Department of Radiology University of Montreal Hospital Centre(CHUM)MontrealCanada

Background: Bone marrow lesions (BMLs) are associated with osteoarthritis (OA). We assessed the performance of two commonly used MRI sequences, IW-TSE and DESS, for reliability in the detection of BMLs and sensitivity to estimate change over time. We suggested that the IW-TSE would demonstrate higher sensitivity to change than DESS in the assessment of BML prevalence and change over time. This study was performed using a subset of the Osteoarthritis Initiative (OAI) cohort. Methods: A sub-group of 144 patients was selected from the OAI progression cohort who all had IW-TSE and DESS MRI acquisitions at baseline and 24 months. BMLs were assessed using a semi-quantitative scale in the global knee, medial and lateral compartments, and subregions. Intra-reader reliability was assessed on a subset of 51 patients. Results: Intra-reader reliability was substantial for the global knee ≥ 0.64, medial ≥ 0.70, and lateral ≥ 0.63 compartments for IW-TSE and DESS. The prevalence of BML detected at baseline was only slightly greater for IW-TSE compared to DESS. The mean BML score at baseline was significantly higher (p ≤ 0.006) for the IW-TSE than the DESS. However, mean change at 24 months was similar for both sequences for all regions except the medial compartment (p = 0.034) and medial femur (p = 0.015) where they were significantly higher for DESS than IW-TSE. Moreover, the prevalence of BML change at 24 months was similar in all regions except the global knee (p = 0.047) and the lateral tibial plateau (p = 0.031). Conclusion: This study does not suggest superior sensitivity to change of one sequence over the other for almost all the regions. The only difference is a higher BML mean change over time detected by the DESS sequence in the medial compartment and femur. These data bring into perspective that both sequences seem equivalent regarding their use for the assessment of BML in clinical trials.

关键词： Osteoarthritis Magnetic Resonance Imaging Bone Marrow Lesions

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The methanolic extract ofGuibourtia tessmannii(Caesalpiniaceae)improves sexual parameters in high fat diet-induced obese sexually sluggish rats

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Asian pacific Journal of Reproduction 2017年第5期6卷 202-211页

作者： Patrick Brice Deeh Defo Modeste Wankeu-Nya Esther Ngadjui Georges Romeo Bonsou Fozin francois Xavier Kemka Albert Kamanyi pierre Kamtchouing pierre Watcho Animal Physiology and Phytopharmacology Laboratory University of DschangBox 67 DschangCameroon Department of Animal Organisms Biology University of Douala-Cameroon Department of Animal Biology and Physiology University of Yaoundé1YaoundéCameroon

Objective:To evaluate the effects of the methanolic extract ofGuibourtia tessmannii (G. tesmannii) on sperm parameters, lipid profile and testosterone level in obese ***: A total of 193 male Wistar rats were fed either with palm oil diet (n=185) or standard diet (n=8) for 16 wk. At the end of this feeding period, 90 obese rats were selected and randomly divided into 18 groups of five rats each and treated with distilled water (10 mL/kg), vitamin E (75 mg/kg), clomiphene citrate (2 mg/kg) or methanolic extract ofG. tessmannii (55, 110 or 220 mg/kg) for 7, 21 or 56 d. At the end of each treatment period, sperm parameters, lipid profile and testosterone level were evaluated. Data were analyzed using ANOVA for repeated measures followed by post-hoc Tukey HSD (P<0.05) for multiple ***: Feeding of rats for 16 wk with palm oil diet significantly damaged sperm parameters. The methanolic extract ofG. tesmannii improved sperm viability, motility and normality after 21 or 56 d of treatment. The sperm normality increased significantly in rats treated with the methanolic extract ofG. tesmannii for 7 (110 mg/kg,P<0.01) and 56 d (110 and 220 mg/kg,P<0.05) compared to control group. Triglycerids, total cholesterol, low and very low density lipoproteins cholesterol levels were lower in rats treated with the plant extract for 56 d.G. tesmannii also significantly increased the high density lipoprotein cholesterol and testosterone levels in the plasma after 56 d of ***: The methanolic extract ofG. tesmannii can improve sperm parameters, lipid profile and testosterone level in obese rats. These findings may justify the folkloric use ofG. tesmannii as a reproductive performance enhancer.

关键词： Guibourtia tessmannii Palm oil diet Sperm parameters Lipid profile Testosterone

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MAPPING HUMAN BRAIN FUNCTION WITH MRI AT 7 TESLA

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波谱学杂志 2002年第1期19卷 90-91页

作者： Xiaoping HU Essa YACOUB Josef PFEUFFER Amir SCHUMEL pierre francois Van de MOORTELE Gregor ADRIANY Kamil UGURBIL University of Minnesota Center for Magnetic Resonance Research2021 Sixth Street SEMinneapolisMN 55455

In the past decade, the most significant development in MRI is the introduction of fMRI, which permits the mapping of human brain function with exquisite details noninvasively. Functional mapping can be achieved by... 详细信息

关键词： MRI MAPPING HUMAN BRAIN FUNCTION WITH MRI AT 7 TESLA AT

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An Immersed Method Based on Cut-Cells for the Simulation of 2D Incompressible Fluid Flows Past Solid Structures

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Computer Modeling in Engineering & Sciences 2019年第4期119卷 165-184页

作者： francois Bouchon Thierry Dubois Nicolas James Université Clermont Auvergne CNRSLMBPF-63000 CLERMONT-FERRANDFrance Laboratoire de Mathématiques et Applications UMR 7348 Universitéde PoitiersTéléport 2-B.P.30179Boulevard Marie et Pierre Curie86962 Futuroscope Chasseneuil CedexFrance

We present a cut-cell method for the simulation of 2D incompressible flows past *** consists in using the MAC scheme on cartesian grids and imposing Dirchlet boundary conditions for the velocity field on the boundary of solid structures following the Shortley-Weller *** order to ensure local conservation properties,viscous and convecting terms are discretized in a finite volume *** scheme is second order implicit in time for the linear part,the linear systems are solved by the use of the capacitance matrix method for non-moving *** results of flows around an impulsively started circular cylinder are presented which confirm the efficiency of the method,for Reynolds numbers 1000 and *** example of flows around a moving rigid body at Reynolds number 800 is also shown,a solver using the PETSc-Library has been prefered in this context to solve the linear systems.

关键词： Immersed boundary methods cutt-cell methods incompressible viscous flows

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冲绳海槽200ka的孢粉记录及冰期-间冰期旋回古环境重建

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中国科学：地球科学 2013年第10期43卷 1231-1248页

作者：郑卓黄康有邓韫曹玲珑余少华 Jean-pierre SUC Serge BERNE francois GUICHARD 中山大学地球科学系广州510275 Paleoenvironnements et Paleobiosphere Universite Claude Bernard-Lyonl Villeurbanne 69622 France 国家海洋局南海海洋工程勘察与环境研究院广州510300 Institut des Sciences de la Terre Paris Université P. et M. Curie Pads 75005 France Université de Perpignan Via Domitia Perpignan 66860 France Laboratoire des Sciences du Climat et de l'Environnement Gif-sur-Yvette 91191 France

本文对冲绳海槽中部MD982194钻孔29.78m近200kaBP的岩芯进行了孢粉研究.结果表明,孢粉组合主要表现为裸子植物与草本植物花粉之间的交替.带气囊类的松属、铁杉在间冰期的1,3,5和7氧同位素期显著增高,而草本则在冰期阶段占优,两者的含量... 详细信息

本文对冲绳海槽中部MD982194钻孔29.78m近200kaBP的岩芯进行了孢粉研究.结果表明,孢粉组合主要表现为裸子植物与草本植物花粉之间的交替.带气囊类的松属、铁杉在间冰期的1,3,5和7氧同位素期显著增高,而草本则在冰期阶段占优,两者的含量变化显示出对冰期-间冰期环境变化的敏感响应.本钻孔发现莎草科花粉在冰期阶段含量大幅度增加,伴随蒿属、禾本科、菊科、藜科和淡水藻类的显著升高.它们与轨道尺度的海平面变化呈现十分吻合的负相关关系.草本花粉总量的周期性变化可以作为该区域海平面变化的替代性指标.末次盛冰期的海平面下降导致陆地与冲绳海槽的距离大幅缩小,源于长江的物质随河流进入大陆架后因流速急剧降低发生沉降,导致上游物质难以被远距离搬运到海槽.因此,冰期阶段冲绳海槽的孢粉物质可能主体来自于大陆架前缘的地表植被,而间冰期带气囊类花粉的比例增大与海岸距离较远和风力搬运物质的比例增加有关.钻孔的孢粉组分更替与气候变化也有显著的对应关系,反映出氧同位素7,5和1期木本含量高,并与东亚夏季风增强和降雨量增大有关.其中MIS5.3,MIS5.1和MIS3.3段的松属花粉峰值可能与轨道和亚轨道周期的地表太阳辐射和季风增强有密切联系.研究认为,盛冰期的东海陆架平原的气温和降雨量都有较明显的下降,但低海面时期裸露的大陆架平原可能并非由半干旱的地带性草原所覆盖,而是以疏林草地及密布的隐域性植被(河流补给淡水湖沼和湿地)组成.海平面变化引起的海岸距离伸缩和源区气候变化对陆源物质通量和孢粉组分更替起到联合制约的作用,而冲绳海槽冰期-间冰期尺度的海岸线距离变化在孢粉信号中的表现要明显强于陆源区域的气候变化.

关键词：冲绳海槽孢粉分析东海陆架海平面陆源植被气候变化

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Intracoronary stent implantation under intracoronary ultrasound guidance with aspirin and ticlopidine therapy

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Chinese Medical Journal 2001年第3期114卷 38-41,105页

作者：张大东蔡煦沈卫峰上海第二医科大学附属瑞金医院心脏科上海200025

目的　对 4 1例冠心病患者病变冠状动脉 (冠脉 )在血管内超声 (IVUS)指导下置入支架 ,并评价造影和IVUS及一个月临床结果。方法　本文采用支架置入IVUS标准 :支架内截面积≥近端和远端相关血管腔截面积平均值的 80 % ,结合抗血小板药以... 详细信息

目的　对 4 1例冠心病患者病变冠状动脉 (冠脉 )在血管内超声 (IVUS)指导下置入支架 ,并评价造影和IVUS及一个月临床结果。方法　本文采用支架置入IVUS标准 :支架内截面积≥近端和远端相关血管腔截面积平均值的 80 % ,结合抗血小板药以防支架内亚急性血栓形成。结果　支架置入后 2 5例达到标准 ,不需再扩张 ;14例IVUS不满意者 (造影结果良好 )过扩张支架 ,支架内截面积增加 2 5 7% (P <0 0 5) ;2例因超声导管未跨过支架无超声资料。最终 35例 (90 % )得到满意IVUS(支架内最小截面积 8 5± 2 2mm2 ) ,结合阿司匹林和噻氯匹定治疗 ,无一例死亡、心肌梗死和支架内血栓形成。

关键词：经皮经腔冠状动脉成形术冠状动脉内支架术冠状动脉内超声

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Relationship of preoperative androgen levels and metabolic syndrome with quality of life and erectile function in patients who are to undergo radical prostatectomy

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Asian Journal of Andrology 2021年第5期23卷 520-526页

作者： Yann Neuzillet Jean-francois Dreyfus Jean-pierre Raynaud Mathieu Rouanne Marc Schneider Morgan Roupret Sarah Drouin Marc Galiano Xavier Cathelineau Thierry Lebret Henry Botto Department of Urology Hopital FochUVSQ-Paris-Saclay UniversitySuresnes 92150France Department of Clinical Research and Innovation Hopital FochUVSQ-Paris-Saclay UniversitySuresnes 92150France Sorbonne University Paris 75013France Department of Urology Hfipital Louis PasteurColmar 68000France Department of Urology Hopital Pitie-SalpetriereAssistance Publique-Hopitaux de ParisSorbonne UniversityParis 75013France Department of Urology Institut Mutualiste MontsourisParis-Descartes UniversityParis 75014France

This study aims to investigate whether clinical and biological preoperative characteristics of patients who were to undergo radical prostatectomy were associated with impairment in patient-reported quality of life(QoL)and erectile dysfunction immediately before *** evaluated patient-reported outcomes among 1019 patients(out of 1343)of the AndroCan study,willing to score the Aging Male Symptom(AMS)and the International Index of Erectile Function 5-item(IIEF-5)*** linear regression and robust multiple regression were used to ascertain the relationship between demographic,clinical,and hormonal parameters and global AMS or IIEF-5 *** a result,most patients(85.1%)of the Androcan cohort agreed to complete *** higher IIEF-5 global scores were found in non-Caucasian and obese patients,with larger waist circumference,metabolic syndrome,diabetes mellitus,cardiovascular disease,hypertension,high blood sugar,concomitant medications,and hypogonadism,while the AMS global score was significantly higher in patients with larger waist circumference,metabolic syndrome,high blood pressure,raised glycemia,and concomitant *** IIEF-5 global score was correlated to age,dehydroepiandrosterone(DHEA),fat mass percentage,and androstenediol(D5).The AMS global score was significantly correlated to DHEA,D5,and DHEA ***,the multivariate models showed that QoL and erectile function were significantly affected,before surgery,by symptoms and signs that are usually considered as pertaining to the metabolic syndrome,while sexual hormones are essentially correlated to erectile dysfunction.

关键词： erectile function metabolic syndrome quality of life radical prostatectomy testosterone

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