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Targeting α-synuclein by PD03 AFFITOPE■ and Anle 138b rescues neurodegenerative pathology in a model of multiple system atrophy:clinical relevance

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Translational Neurodegeneration 2020年第3期9卷 484-497页

作者： Miguel Lemos Serena Venezia Violetta Refolo Antonio Heras-Gavin Sabine Schmidhuber Armin Giese Andrei Leonov Sergey Ryazanov Christian Griesinger Gergana Galabova Guenther Safer gregor karl wenning Nadia Stefanova Division of Neurobiology Department of NeurologyInnsbruck Medical University6020 InnsbruckAustria AFFIRIS AG ViennaAustria Center for Neuropathology and Prion Research Ludwig-Maximilians-UniversityMunichGermany Max Planck Institute for Biophysical Chemistry GottingenGermany Present Address:Origenis GmbH MunichGermany

Background:Misfolded oligomeric α-synuclein plays a pivotal role in the pathogenesis of a-synucleinopathies including Parkinson's disease and multiple system atrophy,and its detection parallels activation of microglia and a loss of neurons in the substantia nigra pars *** we aimed to analyze the therapeutic efficacy of PD03,a new AFFITOPE■ immunotherapy approach,either alone or in combination with Anle138b,in a PLP-α-syn mouse ***:The PLP-α-syn mice were treated with PD03 immunotherapy,Anle138b,or a combination of *** months after study initiation,the mice underwent behavioral testing and were sacrificed for neuropathological *** treatment groups were compared to the vehicle group with regard to motor performance,nigral neuronal loss,microglial activation and α-synuclein ***:The PLP-α-syn mice receiving the PD03 or Anle138b single therapy showed improvement of gait deficits and preservation of nigral dopaminergic neurons associated with the reduced α-synuclein oligomer levels and decreased microglial *** combined therapy with Anle138b and PD03 resulted in lower lgG binding in the brain as compared to the single immunotherapy with ***:PD03 and Anle138b can selectively target oligomeric α-synuclein,resulting in attenuation of neurodegeneration in the PLP-α-syn *** approaches are potential therapies that should be developed further for disease modification in α-synucleinopathies.

关键词： α-Synuclein Immunotherapy Oligomer modulation Target engagement Substantia nigra Microglia

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Current position of ALPPS in the surgical landscape of CRLM treatment proposals

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World Journal of Gastroenterology 2013年第39期19卷 6548-6554页

作者： Marcello Donati gregor A Stavrou karl J Oldhafer Department of General and Abdominal Surgery Asklepios Hospital Barmbek22291 HamburgGermany Department of Surgery General and Oncologic Surgery UnitVittorio-Emanuele University Hospital of Catania95122 CataniaItaly

The Authors summarize problems,criticisms but also advantages and indications regarding the recent surgical proposal of associating liver partition and portal vein ligation(PVL)for staged hepatectomy(ALPPS)for the surgical management of colorectal liver *** at published data,the technique,when compared with other traditional and well established methods such as PVL/portal vein embolisation(PVE),seems to give real advantages in terms of volumetric gain of future liver ***,major concerns are raised in the literature and some questions remain unanswered,preliminary experiences seem to be *** method has been adopted all over the world over the last 2 years,even if oncological long-term results remain unknown,and benefit for patients is *** prospective studies comparing traditional methods(PVE,PVL or classical 2 staged hepatectomy)with ALPPS are available to *** reinterpretations of the original method were also proposed in order to enhance feasability and increase safety of the *** data about morbidity and mortality are also *** real role of ALPPS is,to date,still to be *** clinical studies,even if,for ethical reasons,in well selected cohorts of patients,are expected to better define the indications for this new surgical strategy.

关键词： Portal ligation In situ split Liver resections Colorectal metastases Liver metastases

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Anxiety and depression in adult patients with celiac disease on a gluten-free diet

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World Journal of Gastroenterology 2010年第22期16卷 2780-2787页

作者： Winfried Huser karl-Heinz Janke Bodo Klump Michael gregor Andreas Hinz Department of Internal Medicine I Klinikum Saarbrücken Winterberg 1 D-66119 Saarbrücken and Department of Psychosomatic Medicine and Psychotherapie Technische Universitt München Baden-Württemberg State Health Office District Government Stuttgart Gastroenterology and Gastrointestinal Cancer St. Anna Hospital Obere Waiblinger Starβe 101 D-70374 Stuttgart Germany and Department of Internal Medicine 1 Universittskliniken Tübingen Department of Internal Medicine 1 Universittskliniken Tübingen Department of Medical Psychology and Medical Sociology Universitt Leipzig

AIM: To compare anxiety and depression levels in adult patients with celiac disease (CD) on a gluten-free diet (GFD) with ***: The levels of anxiety, depression and of a probable anxiety or depressive disorder were assessed by the Hospital Anxiety and Depression Scale in 441 adult patients with CD recruited by the German Celiac Society, in 235 age-and sex-matched patients with inflammatory bowel disease (IBD) in remission or with slight disease activity, and in 441 adult persons of a representative German general population sample (GP). Potential demographic (age, sex, social class, family status) and disease-related (latency to diagnosis, duration of GFD, compliance with GFD, thyroid disease) predictors of anxiety and depression in CD were tested for by regression analyses. RESULTS: The level of anxiety in CD patients was predicted (R 2 = 0.07) by female gender (P = 0.01). Female sex (OR = 3.6, 95% CI: 1.3-9.4, P = 0.01) was associated with a probable anxiety disorder. Living alone (OR = 0.5, 95% CI: 0.2-0.9, P = 0.05) was associated with a reduced risk of an anxiety disorder. The level of depression and a probable depressive disorder were not predicted by any of the demographic and medical variables tested for. The levels of anxiety in patients with CD (6.6 ± 3.4) and with IBD (6.9 ± 3.7) were higher than those of persons in the GP (4.6 ± 3.3) (both P < 0.001). The levels of depression in persons with CD (4.2 ± 3.4), IBD (4.6 ± 3.4) and of the GP (4.2 ± 3.8) did not differ (P = 0.3). The prevalence of a probable anxiety disorder in persons with CD (16.8%) and IBD (14.0%) was higher than that of the GP (5.7%) (P < 0.001). The prevalence of a probable depressive disorder did not differ significantly between the three groups (P = 0.1). CONCLUSION: Anxiety in adult German female celiacs on a GFD is higher than in persons of the GP. Female celiacs on a GFD should be screened for anxiety.

关键词： Celiac disease Anxiety Depression Gender

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Multimodal nonlinear endomicroscopic imaging probe using a double-core double-clad fiber and focus-combining micro-optical concept

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Light(Science & Applications) 2021年第11期10卷 2173-2183页

作者： Ekaterina Pshenay-Severin Hyeonsoo Bae karl Reichwald gregor Matz Jörg Bierlich Jens Kobelke Adrian Lorenz Anka Schwuchow Tobias Meyer-Zedler Michael Schmitt Bernhard Messerschmidt Juergen Popp GRINTECH GmbH Schillerstr.107745JenaGermany Leibniz Institute of Photonic Technology Member of Leibniz Health TechnologiesAlbert-Einstein-Str.907745JenaGermany Institute of Physical Chemistry and Abbe Center of Photonics Friedrich Schiller University JenaHelmholtzweg 407743JenaGermany

Multimodal non-linear microscopy combining coherent anti-Stokes Raman scattering,second harmonic generation,and two-photon excited fluorescence has proved to be a versatile and powerful tool enabling the label-free investigation of tissue structure,molecular composition,and correlation with function and disease *** a routine medical application,the implementation of this approach into an in vivo imaging endoscope is ***,this is a difficult task due to the requirements of a multicolour ultrashort laser delivery from a compact and robust laser source through a fiber with low losses and temporal synchronization,the efficient signal collection in epi-direction,the need for small-diameter but highly corrected endomicroobjectives of high numerical aperture and compact ***,we introduce an ultra-compact fiber-scanning endoscope platform for multimodal non-linear endomicroscopy in combination with a compact four-wave mixing based fiber *** heart of this fiber-scanning endoscope is an in-house custom-designed,single mode,double clad,double core pure silica fiber in combination with a 2.4 mm diameter NIR-dual-waveband corrected endomicroscopic objective of 0.55 numerical aperture and 180µm field of view for non-linear imaging,allowing a background free,low-loss,high peak power laser delivery,and an efficient signal collection in backward direction.A linear diffractive optical grating overlays pump and Stokes laser foci across the full field of view,such that diffraction-limited performance is demonstrated for tissue imaging at one frame per second with sub-micron spatial resolution and at a high transmission of 65%from the laser to the specimen using a distal resonant fiber scanner.

关键词： fiber double scanner

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非典型性帕金森样病

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中国现代神经疾病杂志 2011年第1期11卷 7-14页

作者：黄越陈生弟 gregor wenning Lawrence Golbe 王少石王拥军赵钢吕佩源陈彪 Jun Yu Christine Song Andrew Lees Irene Litvan 王晓民 Glenda Halliday 澳大利亚悉尼新南威尔士大学澳大利亚神经科学院中国上海交通大学医学院附属瑞金医院神经科奥地利因斯布鲁克医科大学附属医院神经内科美国新泽西州罗伯伍强森医学院中国上海市第四人民医院神经内科中国首都医科大学附属北京天坛医院神经内科中国西安第四军医大学西京医院神经内科中国河北省人民医院神经内科中国北京首都医科大学宣武医院神经内科英国伦敦大学丽拉韦斯顿学院神经病学研究所美国肯塔基州路易斯维尔大学附属医院神经内科中国北京首都医科大学教育部神经变性病学重点实验室

非典型性帕金森样病亦称帕金森综合征，为一组临床表现多样的疾病症候群，除了覆盖原发性帕金森病（PD）的主要临床症状[静止性震颤、肌强直、运动不能和（或）运动迟缓、姿势反射障碍外，还具有进展迅速、对左旋多巴反应不佳或其他特... 详细信息

非典型性帕金森样病亦称帕金森综合征，为一组临床表现多样的疾病症候群，除了覆盖原发性帕金森病（PD）的主要临床症状[静止性震颤、肌强直、运动不能和（或）运动迟缓、姿势反射障碍外，还具有进展迅速、对左旋多巴反应不佳或其他特征性表现，如疾病早期易跌倒。

关键词：帕金森障碍神经变性疾病脑血管基底神经节疾病综述文献

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Development and internal validation of the Comprehensive ALPPS Preoperative Risk Assessment(CAPRA)score:is the patient suitable for Associating Liver Partition and Portal vein ligation for Staged hepatectomy(ALPPS)?

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Hepatobiliary Surgery and Nutrition 2022年第1期11卷 52-66,I0007,I0008页

作者： Ivan Capobianco karl J.Oldhafer Mohammed-Hossein Fard-Aghaie Ricardo Robles-Campos Roberto Brusadin Henrik Petrowsky Michael Linecker Arianeb Mehrabi Katrin Hoffmann Jun Li Asmus Heumann Roberto Hernandez-Alejandro Mauro Enrique Tun-Abraham Elio Jovine Matteo Serenari Bergthor Bjornsson Per Sandström Ruslan Alikhanov Mikhail Efanov Paolo Muiesan Andrea Schlegel Thomas M.van Gulik Pim B.Olthof gregor Alexander Stavrou Lina Maria Serna-Higuita Alfred Königsrainer Silvio Nadalin Department of General Visceral and Transplant SurgeryUniversity Hospital TübingenTübingenGermany Department of General and Abdominal Surgery Asklepios Hospital BarmbekHamburgGermany Department of Surgery Virgen de la Arrixaca Clinic and University HospitalMurciaSpain Swiss HPB and Transplantation Center Department of SurgeryZurich University HospitalZurichSwitzerland Department of General Visceraland Transplantation SurgeryUniversity of HeidelbergHeidelbergGermany General Visceral and Thoracic Surgery Department and ClinicHamburg-Eppendorf University Medical CenterHamburgGermany Division of Transplantation and Hepatobiliary Surgery University of RochesterRochesterNYUSA Division of HPB Surgery and Liver Transplantation Department of SurgeryLondon Health Sciences CentreLondonCanada General and Emergency Surgery Unit Azienda Ospedaliero-Universitaria di BolognaMaggiore HospitalBolognaItaly General Surgery and Transplantation Unit Azienda Ospedaliero-Universitaria di BolognaSant’Orsola-Malpighi HospitalBolognaItaly Department of Surgery in Linköping and Department of Biomedical and Clinical SciencesLinköping UniversityLinköpingSweden Department of Hepatopancreatobiliary Surgery Moscow Clinical Scientific CenterMoscowRussia Liver Unit Queen Elizabeth Hospital BirminghamUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUK Department of Surgery Amsterdam UMC(Location AMC)University of AmsterdamAmsterdamThe Netherlands Department of General Abdominal and Thoracic SurgerySurgical OncologySaarbruecken General HospitalSaarbrueckenGermany Department of Clinical Epidemiology and Applied Biometry University of TübingenTübingenGermany

Background:Preoperative patient selection in Associating Liver Partition and Portal vein ligation for Staged hepatectomy(ALPPS)is not always reliable with currently available scores,particularly in patients with primary liver *** study aims to(I)to determine whether comorbidities and patients characteristics are a risk factor in ALPPS and(II)to create a score predicting 90-day mortality ***:Thirteen high-volume centers participated in this retrospective multicentric study.A risk analysis based on patient characteristics,underlying disease and procedure type was performed to identify risk factors and model the Comprehensive ALPPS Preoperative Risk Assessment(CAPRA)score.A nonparametric receiver operating characteristic analysis was performed to estimate the predictive ability of our score against the Charlson Comorbidity Index(CCI),the age-adjusted CCI(aCCI),the ALPPS risk score before Stage 1(ALPPS-RS1)and Stage 2(ALPPS-RS2).The model was internally validated applying ***:A total of 451 patients were *** was 14.4%.The CAPRA score is calculated based on the following formula:(0.1×age)−(2×BSA)+1(in the presence of primary liver tumor)+1(in the presence of severe cardiovascular disease)+2(in the presence of moderate or severe diabetes)+2(in the presence of renal disease)+2(if classic ALPPS is planned).The predictive ability was 0.837 for the CAPRA score,0.443 for CCI,0.519 for aCCI,0.693 for ALPPS-RS1 and 0.807 for *** 1,000 cycles of bootstrapping the C statistic was *** accuracy plot revealed a cut-off for optimal prediction of postoperative mortality of ***:Comorbidities play an important role in ALPPS and should be carefully considered when planning the *** assessing the patient’s preoperative condition in relation to ALPPS,the CAPRA score has a very good ability to predict postoperative mortality.

关键词： Associating Liver Partition and Portal vein ligation for Staged hepatectomy(ALPPS) comorbidity mortality prediction model patient selection

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左旋多巴的临床应用(下)

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中华医学信息导报 2005年第19期20卷 13-13页

作者： gregor K.wenning Werner Poewe 苏雅茹蒋雨平 Department of Neurology 上海华山医院

目前人们普遍认识到左旋多巴明显改善了帕金森病运动不能的进展和病死率，但在对左旋多巴抵抗的不典型帕金森综合征患者中无此结果。Hoehn比较了左旋多巴出现前后每5年间的病死率和致残率（Hoehn＆Yahr评分Ⅳ和Ⅴ级）的差异，结果发现... 详细信息

目前人们普遍认识到左旋多巴明显改善了帕金森病运动不能的进展和病死率，但在对左旋多巴抵抗的不典型帕金森综合征患者中无此结果。Hoehn比较了左旋多巴出现前后每5年间的病死率和致残率（Hoehn＆Yahr评分Ⅳ和Ⅴ级）的差异，结果发现，左旋多巴减少同期患者运动不能的发生率多达50％。然而，在治疗和未治疗的患者间，疾病的进展差异无显著性。该结果表明左旋多巴并不阻止帕金森病的进展。此外，左旋多巴不能影响肢体受累的模式，包括从一侧上肢或下肢随时间进展累及到对侧或其他肢体。

关键词：左旋多巴临床应用帕金森综合征运动不能帕金森病 Hoehn 病死率患者不典型

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