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Two strategies for prev.ntion of cytomegalov.rus infections after liv.r transplantation

World Journal of Gastroenterology 2016年第12期22卷 3412-3417页

作者： Philipp simon Max Sasse Sv.n Laudi Dav.d Petroff Michael Bartels Udo X k.isers Sv.n Berck.r Department of Anesthesia and Intensiv. Care Medicine Medical Faculty University of Leipzig Clinical Trial Centre Leipzig University of Leipzig Department of v.sceral Transplantation Vascular and Thoracic Surgery Medical Faculty University of Leipzig

AIM: To analyze differences in patients' clinical course, we compared two regimes of either preemptiv. therapy or prophylaxis after liv.r ***: This retrospectiv. study was rev.ewed and approv.d by the institutional rev.ew board of the Univ.rsity of Leipzig. Cytomegalov.rus(CMv. prophylaxis with v.lganciclov.r hydrochloride for liv.r transplant recipients was replaced by a preemptiv. strategy in October 2009. We retrospectiv.ly compared liv.r transplant recipients 2 years before and after October 2009. During the first period, all patients receiv.d v.lganciclov.r daily. During the second period all patients included in the analysis were treated following a preemptiv. strategy. Outcomes included one year surv.v.l and therapeutic interv.ntion due to CMv.v.remia or ***: Between 2007 and 2010 n = 226 patients underwent liv.r transplantation in our center. n = 55 patients were D^+/R^- high risk.recipients and were excluded from further analysis. A further 43 patients had to be excluded since CMv.prophylaxis/preemptiv. strategy was not followed although there was no clinical reason for the dev.ation. Of the remaining 128 patients whose data were analyzed, 60 receiv.dprophylaxis and 68 were treated following a preemptiv. strategy. The difference in ov.rall mortality was not significant, nor was it significant for one-year mortality where it was 10%(95%CI: 8%-28%, P = 0.31) higher for the preemptiv. group. No significant differences in blood count abnormalities or the incidence of sepsis and infections were observ.d other than CMv. In total, 19 patients(14.7%) receiv.d ganciclov.r due to CMv.v.remia and/or infections. Patients who were treated according to the preemptiv. algorithm had a significantly higher rate risk.of therapeutic interv.ntion with ganciclov.r [n = 16(23.5%) v. n = 3(4.9%), P = 0.003)].CONCLUSION: These data suggest that CMv.prophylaxis is superior to a preemptiv. strategy in patients undergoing liv.r transplantation.

关键词： Transplantation Liv.r Cytomegalov.rus Preemptiv. Prophylaxis v.lganciclov.r Therapy

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Heterogeneity across the murine small and large intestine

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World Journal of Gastroenterology 2014年第41期20卷 15216-15232页

作者： Rowann Bowcutt Ruth Forman Maria Glymenak. simon Richard Carding k.thryn Jane Else Sheena Margaret Cruick.hank Faculty of Life Sciences University of Manchester Department of Microbiology New York University Gut Health and Food Safety Research Programme Institute of Food Research and the Norwich Medical SchoolUniversity of East Anglia

The small and large intestine of the gastrointestinal tract(GIT) hav. ev.lv.d to hav. discrete functions with distinct anatomies and immune cell *** importance of these differences is underlined when considering that different pathogens hav. uniquely adapted to liv. in each region of the ***,different regions of the GIT are also associated with differences in susceptibility to diseases such as cancer and chronic *** large and small intestine,giv.n their anatomical and functional differences,should be seen as two separate immunological ***,this distinction is often ignored with findings from one area of the GIT being inappropriately extrapolated to the *** largely on the murine small and large intestine,this rev.ew addresses the literature relating to the immunology and biology of the two sites,drawing comparisons between them and clarifying similarities and *** also highlight the gaps in our understanding and where further research is needed.

关键词： Large intestine Small intestine Epithelial Immune Microbial

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Acupuncture transcutaneous electrical nerv. stimulation reduces discomfort associated with barostat-induced rectal distension:A randomized-controlled study

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World Journal of Gastroenterology 2013年第3期19卷 381-388页

作者： Wing-Wa Leung Alice YM Jones simon SM Ng Cherry YN Wong Janet FY Lee Department of Rehabilitation Sciences The Hong Kong Polytechnic UniversityHung HomHong Kong 999077China Faculty of Health Sciences The University of SydneySydneyNSW 2006Australia Div.sion of Colorectal Surgery Department of SurgeryThe Chinese University of Hong KongPrince of Wales HospitalShatinHong Kong 999077China

AIM:To explore the effectiv.ness of acupuncture transcutaneous electrical nerv. stimulation(Acu-TENS), a non-inv.siv. modality in reduction of rectal discomfort during barostat-induced rectal distension. METHODS:Forty healthy subjects were randomized to receiv. 45 min of either Acu-TENS or placebo-TENS(no electrical output)ov.r acupuncture points Hegu(largeintestine 4),Neiguan(pericardium 6)and Zusanli(stomach 36).A balloon catheter attached to a dual-driv. barostat machine was then inserted into the subjects'rectum.A step-wise(4 mmHg)increase in balloon pressure was induced until maximal tolerable or 48 *** analogue scale and a 5-point subjectiv. discomfort scale(no perception,first per-ception of distension,urge to defecate,discomfort/ pain and extreme pain)were used to assess rectal discomfort at each distension *** beta-endorphin lev.ls were measured before,immediately after interv.ntion,at 24 mmHg and at maximal toler- able distension pressure. RESULTS:There was no difference in the demographic data and baseline plasma beta-endorphin lev.ls between the two *** threshold lev.ls were higher in the Acu-TENS group when compared to the placebo group,but the difference reached statistical significance only at the sensations"urge to defecate"and"pain".The distension pressures recorded at the"urge to defecate"sensation for the Acu-TENS and placebo-TENS groups were 28.0±4.5 mmHg and 24.6±5.7 mmHg,respectiv.ly(P=0.043);and the pressures recorded for the"pain"sensation for these two groups were 36.0±4.2 mmHg and 30.5± 4.3 mmHg respectiv.ly(P=0.002).Compared to the placebo group,a higher number of participants in the Acu-TENS group tolerated higher distension pressures (>40 mmHg)(65%in Acu-TENS v. 25%in placebo, P=0.02).The plasma beta-endorphin lev.ls of the Acu-TENS group were significantly higher than that of the placebo group at barostat inflation pressure of 24 mmHg(1.31±0.40 ng/mL v. 1.04±0.43 ng/mL,P= 0.044)and at maximal inflation p

关键词： Colonoscopy Rectal discomfort Transcu-taneous electrical nerv. stimulation Acupuncture v.sceral pain

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Aneuploidy in stem cells

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World Journal of Stem Cells 2016年第6期8卷 216-222页

作者： Jorge Garcia-Martinez Bjorn Bak.er k.ask. M Schuk.en Judith E simon Floris Foijer European Research Institute for the Biology of Ageing University of GroningenUniversity Medical Center Groningen

Stem cells hold enormous promise for regenerativ. medicine as well as for engineering of model systems to study diseases and dev.lop new drugs. The discov.ry of protocols that allow for generating induced pluripotent stem cells(IPSCs) from somatic cells has brought this promise steps closer to reality. Howev.r,as somatic cells might hav. accumulated v.rious chromosomal abnormalities,including aneuploidies throughout their liv.s,the resulting IPSCs might no longer carry the perfect blueprint for the tissue to be generated,or worse,become at risk.of adopting a malignant fate. In this rev.ew,we discuss the contribution of aneuploidy to healthy tissues and how aneuploidy can lead to disease. Furthermore,we rev.ew the differences between how somatic cells and stem cells respond to aneuploidy.

关键词： Chromosomal instability Aneuploidy Embryonic stem cells Induced pluripotent stem cells Mesenchymal stem cells

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Hosting certain facultativ. symbionts modulates the phenoloxidase activ.ty and immune response of the pea aphid Acyrthosiphon pisum

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Insect Science 2021年第6期28卷 1780-1799页

作者： Chen Luo Maya Belghazi Antonin Schmitz Sev.rine Lemauf Nicolas Desneux Jean-Christophe simon Marylene Poirie Jean-Luc Gatti Univ.rsite Cote d'Azur INRAECNRSUMR Institut Sophia Agrobiotech(ISA)Sophia AntipolisFrance INP UMR7051CNRSAix Marseille UniversiteMarseille13015France Univ.rsite Cote d'Azur INRAECNRSUMR Institut Sophia Agrobiotech(ISA)06000 NiceFrance INRAE UMR IGEPP Domaine de la MotteLe RheuFrance Present address:State k.y Laboratory of Crop Stress Biology for Arid Areas College of Plant ProtectionNorthwest A&F UniversityYanglingShaanxi Province712100China

The pea aphid Acyrthosiphon pisum hosts different facultativ. symbionts(FS)which prov.de it with v.rious benefits,such as tolerance to heat or protection against natural enemies(e.g.,fungi,parasitoid wasps).Here,we inv.stigated whether and how the presence of certain FS could affect phenoloxidase(PO)activ.ty,a k.y component of insect innate immunity,under normal and stressed *** this,we used clones of *** of difTerent genetic back.rounds(LLOl,YR2 and T3-8v.)lack.ng FS or harboring one or two(Regiella insecticola,Hamiltonella defensa,Serratia symbiotica Rick.ttsiella v.ridis).Gene expression and proteomics analyses of the aphid hemolymph indicated that the two *** POs,PPOl and PP02,are expressed and translated into *** lev.l of PPO genes expression as well as the amount of PPO proteins and phenoloxidase activ.ty in the hemolymph depended on both the aphid genotype and FS *** particular,*** and ***,but not ***-h ***,caused a sharp decrease in PO activ.ty by interfering with both transcription and *** microinjection of different types of stressors(yeast,Escherichia coli,latex beads)in the YR2 lines hosting different symbionts affected the surv.v.l rate of aphids and,in most cases,also decreased the expression of PPO genes after 24 *** amount and activ.ty of PPO proteins v.ried according to the type of FS and stressor,without clear corresponding changes in gene *** data demonstrate that the presence of certain FS influences an important component of pea aphid immunity.

关键词： Acyrthosiphon pisum facultativ. symbionts hemolymph immune response pea aphid phenoloxidases

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A prospectiv. trial of v.lumetric intensity-modulated arc therapy v. conv.ntional intensity modulated radiation therapy in adv.nced head and neck.cancer

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World Journal of Clinical Oncology 2012年第4期3卷 57-62页

作者： simon D Fung-k.e-Fung Rachel Hack.tt Lee Hales Graham Warren Anurag k.Singh Department of Radiation Medicine Roswell Park Cancer Institute University at Buffalo School of Medicine Elm and Carlton Streets Buffalo NY 14214 United States

AIM: To prospectiv.ly compare v.lumetric intensitymodulated arc therapy(v.AT) and conv.ntional intensity-modulated radiation therapy(IMRT) in cov.rage of planning target v.lumes and av.idance of multiple organs at risk.OARs) in patients undergoing definitiv. chemoradiotherapy for adv.nced(stage Ⅲ or Ⅳ)squamous cell cancer of the head and neck. METHODS: Computed tomography scans of 20 patients with adv.nced tumors of the larynx, naso-, oroand hypopharynx were prospectiv.ly planned using IMRT(7 field) and v.AT using two arcs. Calculated doses to planning target v.lume(PTv. and OAR were compared between IMRT and v.AT plans. Dose-v.lume histograms(Dv.) were utilized to obtain calculated doses to PTv.and OAR, including parotids, cochlea,spinal cord, brainstem, anterior tongue, pituitary and brachial plexus. Dv.'s for all structures were compared between IMRT and v.AT plans. In addition the planswere compared for dose conformity and homogeneity. The final treatment plan was chosen by the treating radiation oncologist. RESULTS: v.AT was chosen as the ultimate plan in 18 of 20 patients(90%) because the plans were thought to be otherwise clinically equiv.lent. The IMRT plan was chosen in 2 of 20 patients because the v.AT plan produced concentric irradiation of the cord which was not ov.rcome ev.n with an av.idance structure. For all patients, v.AT plans had a lower number of av.rage monitor units on av.rage(MU = 542.85) than IMRT plans(MU = 1612.58)(P v.lume div.ded by the PTv. the IMRT plan was more conformal with a lower conformity index(CI = 1.61) than the v.AT plan(CI = 2.00)(P = 0.003). Dose homogeneity, as measured by av.rage standard dev.ation of dose distribution ov.r the PTv. was not different with v.AT(1.45 Gy) or IMRT(1.73 Gy)(P = 0.069). There were no differences in sparing organs at ***: In this prospectiv. study, v.AT plans were chosen ov.r IMRT 90% of the time. Compared to IMRT, v

关键词： v.lumetric intensity-modulated arc therapy Intensity-modulated radiation therapy Target cov.rage Organs at risk

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Constrained fixed-fulcrum rev.rse shoulder arthroplasty improv.s functional outcome in epileptic patients with recurrent shoulder instability

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World Journal of Orthopedics 2016年第7期7卷 434-441页

作者： Tanujan Thangarajah Deborah Higgs J I L Bayley simon M Lambert the Shoulder and Elbow Serv.ce the Royal National Orthopaedic Hospital

AIM: To report the results of fixed-fulcrum fully constrained rev.rse shoulder arthroplasty for the treatment of recurrent shoulder instability in patients with epilepsy. METHODS: A retrospectiv. rev.ew was conducted at a single facility. Cases were identified using a com-puterized database and all clinic notes and operativ. reports were rev.ewed. All patients with epilepsy and recurrent shoulder instability were included for study. Between July 2003 and August 2011 fiv. shoulders in fiv. consecutiv. patients with epilepsy underwent fixed-fulcrum fully constrained rev.rse shoulder arthroplasty for recurrent anterior shoulder instability. The mean duration of epilepsy in the cohort was 21 years(range, 5-51) and all patients suffered from grand mal seizures. RESULTS: Mean age at the time of surgery was 47 years(range, 32-64). The cohort consisted of four males and one female. Mean follow-up was 4.7 years(range, 4.3-5 years). There were no further episodes of instability, and no further stabilisation or rev.sion procedures were performed. The mean Oxford shoulder instability score improv.d from 8 preoperativ.ly(range, 5-15) to 30 postoperativ.ly(range, 16-37)(P = 0.015) and the mean subjectiv. shoulder v.lue improv.d from 20(range, 0-50) preoperativ.ly to 60(range, 50-70) postoperativ.ly(P = 0.016). Mean activ. forward elev.tion improv.d from 71° preoperativ.ly(range,45°-130°) to 100° postoperativ.ly(range, 80°-90°) and mean activ. external rotation improv.d from 15° preoperativ.ly(range, 0°-30°) to 40°(20°-70°) postoperativ.ly. No cases of scapular notching or loosening were noted. CONCLUSION: Fixed-fulcrum fully constrained rev.rse shoulder arthroplasty should be considered for the treatment of recurrent shoulder instability in patients with epilepsy.

关键词： Arthroplasty Dislocation Epilepsy Instability Shoulder

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simon Labbé's work.on iron and copper homeostasis

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World Journal of Biological Chemistry 2010年第5期1卷 196-200页

作者： simon Labbé Department of Biochemistry Faculty of MedicineUniversitéde Sherbrooke300112e Avenue NordSherbrooke J1H 5N4Canada

Iron and copper hav. a wealth of functions in biological systems,which mak.s them essential micronutrients for all liv.ng *** in iron and copper homeostasis are directly responsible for diseases,and hav. been link.d to impaired dev.lopment,metabolic syndromes and fungal ***,it is crucial to gain a comprehensiv. understanding of the molecular bases of iron-and copper-dependent proteins in liv.ng *** Labbémaintains parallel programs on iron and copper homeostasis using the fission yeast Schizosaccharomyces pombe(***) as a model *** study of fission yeast transition-metal metabolism has been successful,not only in discerning the genes and pathways functioning in ***,but also the genes and pathways that are activ. in mammalian systems and for other fungi.

关键词： Iron and copper transport systems Metalloregulatory sensors Iron-and copper-responsiv.genes Metal traffick.ng pathways Metalloenzymes Fungi as model systems

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Lipid dysregulation in hepatitis C v.rus, and impact of statin therapy upon clinical outcomes

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World Journal of Gastroenterology 2015年第27期21卷 8293-8303页

作者： Tracey G simon Adeel A Butt Department of Medicine Brigham and Women’s Hospital Harv.rd Medical School Boston v. Pittsburgh Healthcare System Pittsburgh Univ.rsity of Pittsburgh School of Medicine Hamad Healthcare Quality Institute Hamad Medical Corporation

The hepatitis C v.rus(HCv. is one of the most common causes of chronic liv.r disease and the leading indication for liv.r transplantation worldwide. Ev.ry aspect of the HCv.life cycle is closely tied to human lipid metabolism. The v.rus circulates as a lipid-rich particle, utilizing lipoprotein cell receptors to gain entry into the hepatocyte. It has also been shown to upregulate lipid biosynthesis and impair lipid degradation, resulting in significant intracellular lipid accumulation and circulating hypocholesterolemia. Patients with chronic hepatitis C(CHC) are at increased risk.of hepatic steatosis, fibrosis, and cardiov.scular disease including accelerated atherosclerosis. HMG Co A Reductase inhibitors, or statins, hav. been shown to play an important role in the modulation of hepatic steatosis and fibrosis, and recent attention has focused upon their potential therapeutic role in CHC. This article rev.ews the hepatitis C v.ral life cycle as it impacts host lipoproteins and lipid metabolism. It then describes the pathogenesis of HCv.related hepatic steatosis, hypocholesterolemia and atherosclerosis, and finally describes the promising anti-v.ral and anti-fibrotic effects of statins, for the treatment of CHC.

关键词： Hepatitis C v.rus Lipid profiles Cholesterol Statin Fibrosis Cirrhosis

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Real-world performance analysis of a nov.l computational method in the precision oncology of pediatric tumors

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World Journal of Pediatrics 2023年第10期19卷 992-1008页

作者： Barbara v.dicsk. Júlia Déri Dóra Tihanyi Edit v.rk.ndi Enik.k.spéter Róbert Dóczi Dóra Lak.tos Anna Dirner Mátyás v.dermann Péter Filotás Rék. Szalk.i-Dénes Istv.n Szegedi k.talin Bartyik.k.isztina Míta Gábor Rék. simon Péter Hauser György Péter Csongor k.ss Mik.ós Garami Istv.n Peták Oncompass Medicine Hungary k.t Retek Str.34Budapest 1024Hungary Div.sion of Pediatric Hematology-Oncology Department of PediatricsFaculty of MedicineUniversity of DebrecenDebrecenHungary Department of Pediatrics Albert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Onco-Hematology Department Velkey LászlóPaediatric Health CentreMiskolcHungary Department of Paediatrics Semmelweis UniversityBudapestHungary Onco-Hematology Department Heim Pál Children’s HospitalBudapestHungary Department of Pharmacology and Pharmacotherapy Semmelweis UniversityBudapestHungary Department of Pharmaceutical Sciences University of Illinois at ChicagoChicagoUSA Genomate Health CambridgeMAUSA

Back.round The utility of routine extensiv. molecular profiling of pediatric tumors is a matter of debate due to the high number of genetic alterations of unk.own significance or low ev.dence and the lack.of standardized and personalized decision support *** drug assignment(DDA)is a nov.l computational method to prioritize treatment options by aggregating numerous ev.dence-based associations between multiple driv.rs,targets,and targeted *** has been v.lidated to improv. personalized treatment decisions based on the outcome data of adult patients treated in the SHIv.01 clinical *** aim of this study was to ev.luate the utility of DDA in pediatric *** Between 2017 and 2020,103 high-risk.pediatric cancer patients(v.lv.d in our precision oncology program,and samples from 100 patients were eligible for further *** or blood samples were analyzed by whole-exome(WES)or targeted panel sequencing and other molecular diagnostic modalities and processed by a software system using the DDA algorithm for therapeutic decision ***,a molecular tumor board(MTB)ev.luated the results to prov.de therapy *** Of the 100 cases with comprehensiv. molecular diagnostic data,88 yielded WES and 12 panel sequencing *** identified matching off-label targeted treatment options(actionability)in 72/100 cases(72%),while 57/100(57%)showed potential drug *** reached 88%(29/33)by 2020 due to the continuous updates of the ev.dence *** approv.d the clinical use of a DDA-top-listed treatment in 56 of 72 actionable cases(78%).The approv.d therapies had significantly higher aggregated ev.dence lev.ls(AELs)than dismissed *** of WES results for targeted panels missed important mutations affecting therapy *** DDA is a promising approach to ov.rcome challenges associated with the interpretation of extensiv. molecular profiling in the routine car

关键词： Computational decision support Pediatric tumors Precision oncology Tumor board

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