12794
2013
eng
e1003212
3
9
article
1
2016-02-25
--
--
Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk
BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 x 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 x 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 x 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2 x 10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.
PLOS Genetics
10.1371/journal.pgen.1003212
1553-7404
urn:nbn:de:bvb:20-opus-127947
PLoS Genetics 9(3): e1003212. doi:10.1371/journal.pgen.1003212
223175
Fergus J. Couch
Xianshu Wang
Lesley McGuffog
Andrew Lee
Curtis Olswold
Karoline B. Kuchenbaecker
Penny Soucy
Zachary Fredericksen
Daniel Barrowdale
Joe Dennis
Mia M. Gaudet
Ed Dicks
Matthew Kosel
Sue Healey
Olga M. Sinilnikova
Adam Lee
Françios Bacot
Daniel Vincent
Frans B. L. Hogervorst
Susan Peock
Dominique Stoppa-Lyonnet
Anna Jakubowska
Paolo Radice
Rita Katharina Schmutzler
Susan M. Domchek
Marion Piedmonte
Christian F. Singer
Eitan Friedman
Mads Thomassen
Thomas V. O. Hansen
Susan L. Neuhausen
Csilla I. Szabo
Ingnacio Blanco
Mark H. Greene
Beth Y. Karlan
Judy Garber
Catherine M. Phelan
Jeffrey N. Weitzel
Marco Montagna
Edith Olah
Irene L. Andrulis
Andrew K. Godwin
Drakoulis Yannoukakos
David E. Goldgar
Trinidad Caldes
Heli Nevanlinna
Ana Osorio
Mary Beth Terry
Mary B. Daly
Elisabeth J. van Rensburg
Ute Hamann
Susan J. Ramus
Amanda Ewart Toland
Maria A. Caligo
Olufunmilayo I. Olopade
Nadine Tung
Kathleen Claes
Mary S. Beattie
Melissa C. Southey
Evgeny N. Imyanitov
Marc Tischkowitz
Ramunas Janavicius
Esther M. John
Ava Kwong
Orland Diez
Ava Kwong
Judith Balmaña
Rosa B. Barkardottir
Banu K. Arun
Gad Rennert
Soo-Hwang Teo
Patricia A. Ganz
Ian Campbell
Annemarie H. van der Hout
Carolien H. M. van Deurzen
Caroline Seynaeve
Encarna B. Gómez Garcia
Flora E. van Leeuwen
Hanne E. J. Meijers-Heijboer
Johannes J. P. Gille
Magreet G. E. M. Ausems
Marinus J. Blok
Marjolinjin J. L. Ligtenberg
Matti A. Rookus
Peter Devilee
Senno Verhoef
Theo A. M. van Os
Juul T. Wijnen
Debra Frost
Steve Ellis
Elena Fineberg
Radke Platte
D. Gareth Evans
Luise Izatt
Rosalind A. Eeles
Julian Adlard
Diana M. Eccles
Jackie Cook
Carole Brewer
Fiona Douglas
Shirley Hodgson
Patrick J. Morrison
Lucy E. Side
Alan Donaldson
Catherine Houghton
Mark T. Rogers
Huw Dorkins
Jacqueline Eason
Helen Gregory
Emma McCann
Alex Murray
Alain Calender
Agnès Hardouin
Pascaline Berthet
Capucine Delnatte
Catherine Nogues
Christine Lasset
Claude Houdayer
Dominique Leroux,
Etienne Rouleau
Fabienne Prieur
Francesca Damiola
Hagay Sobol
Isabelle Coupier
Laurence Venat-Bouvet
Laurent Castera
Marion Gauthier-Villars
Mélanie Léoné
Pascal Pujol
Sylvie Mazoyer
Yves-Jean Bignon
Elzbieta Zlowocka-Perlowska
Jacek Gronwald
Jan Lubinski,
Katarzyna Durda
Katarzyna Jaworska
Tomasz Huzarski
Amanda B. Spurdle
Alessandra Viel
Bernhard Peissel
Bernardo Bonanni
Guilia Melloni
Laura Ottini
Laura Papi
Liliana Varesco
Maria Grazia Tibiletti
Paolo Peterlongo
Sara Volorio
Siranoush Manoukian
Valeria Pensotti
Norbert Arnold
Christoph Engel
Helmut Deissler
Dorothea Gadzicki
Andrea Gehrig
Karin Kast
Kerstin Rhiem
Alfons Meindl
Dieter Niederacher
Nina Ditsch
Hansjoerg Plendl
Sabine Preisler-Adams
Stefanie Engert
Christian Sutter
Raymenda Varon-Mateeva
Barbara Wappenschmidt
Bernhard H. F. Weber
Brita Arver
Marie Stenmark-Askmalm
Niklas Loman
Richard Rosenquist
Zakaria Einbeigi
Katherine L. Nathanson
Timothy R. Rebbeck
Stephanie V. Blank
David E. Cohn
Gustavo C. Rodriguez
Laurie Small
Michael Friedlander
Victoria L. Bae-Jump
Anneliese Fink-Retter
Christine Rappaport
Daphne Gschwantler-Kaulich
Georg Pfeiler
Muy-Kheng Tea
Noralane M. Lindor
Bella Kaufman
Shani Shimon Paluch
Yael Laitman
Anne-Bine Skytte
Anne-Marie Gerdes
Inge Sokilde Pedersen
Sanne Traasdahl Moeller
Torben A. Kruse
Uffe Birk Jensen
Joseph Vijai
Kara Sarrel
Mark Robson
Noah Kauff
Anna Marie Mulligan
Gord Glendon
Hilmi Ozcelik
Bent Ejlertsen
Finn C. Nielsen
Lars Jønson
Mette K. Andersen
Yuan Chun Ding
Linda Steele
Lenka Foretova
Alex Teulé
Conxi Lazaro
Joan Brunet
Miquel Angel Pujana
Phuong L. Mai
Jennifer T. Loud
Christine Walsh
Jenny Lester
Sandra Orsulic
Steven A. Narod
Josef Herzog
Sharon R. Sand
Silvia Tognazzo
Simona Agata
Tibor Vaszko
Joellen Weaver
Alexandra V. Stravropoulou
Saundra S. Buys
Atocha Romero
Miguel de la Hoya
Kristiina Aittomäki
Taru A. Muranen
Mercedes Duran
Wendy K. Chung
Adriana Lasa
Cecilia M. Dorfling
Alexander Miron
Javier Benitez
Leigha Senter
Dezheng Huo
Salina B. Chan
Anna P. Sokolenko
Jocelyne Chiquette
Laima Tihomirova
Tara M. Friebel
Bjarne A. Agnarsson
Karen H. Lu
Flavio Lejbkowicz
Paul A. James
Per Hall
Alison M. Dunning
Daniel Tessier
Julie Cunningham
Susan L. Slager
Wang Chen
Steven Hart
Kristen Stevens
Jacques Simard
Tomi Pastinen
Vernon S. Pankratz
Kenneth Offit
Douglas F. Easton
Georgia Chenevix-Trench
Antonis C. Antoniou
eng
uncontrolled
common variants
eng
uncontrolled
susceptibility alleles
eng
uncontrolled
genetic variants
eng
uncontrolled
modifiers
eng
uncontrolled
ZNF365
eng
uncontrolled
investigators
eng
uncontrolled
population
eng
uncontrolled
consortium
eng
uncontrolled
selection
eng
uncontrolled
subtypes
Inzidenz und Prävention von Krankheiten
open_access
Institut für Humangenetik
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12794/063_Couch_Plos_Genetics.pdf
13044
2012
eng
R33
14
article
CIMBA; SWE-BRCA; HEBON; EMBRACE; GEMO Study Collaborators; kConFab Investigators
1
2016-03-22
--
--
Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers
Introduction: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2).
Methods: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework.
Results: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 x 10\(^{-4}\)). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 x 10\(^{-5}\), P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df P = 0.007; rs1292011 2df P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 x 10\(^{-5}\)) and there was marginal evidence of association with ER- negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049).
Conclusions: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers.
Breast Cancer Research
10.1186/bcr3121
urn:nbn:de:bvb:20-opus-130449
Breast Cancer Research 2012, 14:R33. DOI:10.1186/bcr3121
223175
Antonis C. Antoniou
Karoline B. Kuchenbaecker
Penny Soucy
Jonathan Beesley
Xiaoqing Chen
Lesley McGuffog
Andrew Lee
Daniel Barrowdale
Sue Healey
Olga M. Sinilnikova
Maria A. Caligo
Niklas Loman
Katja Harbst
Annika Lindblom
Brita Arver
Richard Rosenquist
Per Karlsson
Kate Nathanson
Susan Domchek
Tim Rebbeck
Anna Jakubowska
Jan Lubinski
Katarzyna Jaworska
Katarzyna Durda
Elżbieta Zlowowcka-Perłowska
Ana Osorio
Mercedes Durán
Raquel Andrés
Javier Benítez
Ute Hamann
Frans B. Hogervorst
Theo A. van Os
Senno Verhoef
Hanne E. J. Meijers-Heijboer
Juul Wijnen
Encarna B. Gómez Garcia
Marjolijn J. Ligtenberg
Mieke Kriege
Margriet Collée
Margreet G. E. M. Ausems
Jan C. Oosterwijk
Susan Peock
Debra Frost
Steve D. Ellis
Radka Platte
Elena Fineberg
D. Gareth Evans
Fiona Lalloo
Chris Jacobs
Ros Eeles
Julian Adlard
Rosemarie Davidson
Trevor Cole
Jackie Cook
Joan Paterson
Fiona Douglas
Carole Brewer
Shirley Hodgson
Patrick J. Morrison
Lisa Walker
Mark T. Rogers
Alan Donaldson
Huw Dorkins
Andrew K. Godwin
Betsy Bove
Dominique Stoppa-Lyonnet
Claude Houdayer
Bruno Buecher
Antoine de Pauw
Sylvie Mazoyer
Alain Calender
Mélanie Léoné
Brigitte Bressac-de Paillerets
Olivier Caron
Hagay Sobol
Marc Frenay
Fabienne Prieur
Sandra Fert Ferrer
Isabelle Mortemousque
Saundra Buys
Mary Daly
Alexander Miron
Mary Beth Terry
John L. Hopper
Esther M. John
Melissa Southey
David Goldgar
Christian F. Singer
Anneliese Fink-Retter
Tea Muy-Kheng
Daphne Geschwantler Kaulich
Thomas V. O. Hansen
Finn C. Nielsen
Rosa B. Barkardottir
Mia Gaudet
Tomas Kirchhoff
Vijai Joseph
Ana Dutra-Clarke
Kenneth Offit
Marion Piedmonte
Judy Kirk
David Cohn
Jean Hurteau
John Byron
James Fiorica
Amanda E. Toland
Marco Montagna
Cristina Oliani
Evgeny Imyanitov
Claudine Isaacs
Laima Tihomirova
Ignacio Blanco
Conxi Lazaro
Alex Teulé
J. Del Valle
Simon A. Gayther
Kunle Odunsi
Jenny Gross
Beth Y. Karlan
Edith Olah
Soo-Hwang Teo
Patricia A. Ganz
Mary S. Beattie
Cecelia M. Dorfling
Elizabeth Jansen van Rensburg
Orland Diez
Ava Kwong
Rita K. Schmutzler
Barbara Wappenschmidt
Christoph Engel
Alfons Meindl
Nina Ditsch
Norbert Arnold
Simone Heidemann
Dieter Niederacher
Sabine Preisler-Adams
Dorothea Gadzicki
Raymonda Varon-Mateeva
Helmut Deissler
Andrea Gehrig
Christian Sutter
Karin Kast
Britta Fiebig
Dieter Schäfer
Trinidad Caldes
Miguel de la Hoya
Heli Nevanlinna
Taru A. Muranen
Bernard Lespérance
Amanda B. Spurdle
Susan L. Neuhausen
Yuan C. Ding
Xianshu Wang
Zachary Fredericksen
Vernon S. Pankratz
Noralane M. Lindor
Paulo Peterlongo
Siranoush Manoukian
Bernard Peissel
Daniela Zaffaroni
Bernardo Bonanni
Loris Bernard
Riccardo Dolcetti
Laura Papi
Laura Ottini
Paolo Radice
Mark H. Greene
Jennifer T. Loud
Irene L. Andrulis
Hilmi Ozcelik
Anna Marie Mulligan
Gord Glendon
Mads Thomassen
Anne-Marie Gerdes
Uffe B. Jensen
Anne-Bine Skytte
Torben A. Kruse
Georgia Chenevix-Trench
Fergus J. Couch
Jacques Simard
Douglas F. Easton
eng
uncontrolled
investigators
eng
uncontrolled
genetic modifiers
eng
uncontrolled
mammographic density
eng
uncontrolled
susceptibility loci
eng
uncontrolled
ovarian cancer
eng
uncontrolled
hormone-related protein
eng
uncontrolled
genome-wide association
eng
uncontrolled
tumor subtypes
eng
uncontrolled
alleles
eng
uncontrolled
consortium
Menschliche Anatomie, Zytologie, Histologie
open_access
Institut für Humangenetik
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13044/Antoniou_A10.1186-Fbcr3121.pdf
28176
2022
eng
14
14
article
1
--
2022-07-11
--
Uncovering the contribution of moderate-penetrance susceptibility genes to breast cancer by whole-exome sequencing and targeted enrichment sequencing of candidate genes in women of European ancestry
Rare variants in at least 10 genes, including BRCA1, BRCA2, PALB2, ATM, and CHEK2, are associated with increased risk of breast cancer; however, these variants, in combination with common variants identified through genome-wide association studies, explain only a fraction of the familial aggregation of the disease. To identify further susceptibility genes, we performed a two-stage whole-exome sequencing study. In the discovery stage, samples from 1528 breast cancer cases enriched for breast cancer susceptibility and 3733 geographically matched unaffected controls were sequenced. Using five different filtering and gene prioritization strategies, 198 genes were selected for further validation. These genes, and a panel of 32 known or suspected breast cancer susceptibility genes, were assessed in a validation set of 6211 cases and 6019 controls for their association with risk of breast cancer overall, and by estrogen receptor (ER) disease subtypes, using gene burden tests applied to loss-of-function and rare missense variants. Twenty genes showed nominal evidence of association (p-value < 0.05) with either overall or subtype-specific breast cancer. Our study had the statistical power to detect susceptibility genes with effect sizes similar to ATM, CHEK2, and PALB2, however, it was underpowered to identify genes in which susceptibility variants are rarer or confer smaller effect sizes. Larger sample sizes would be required in order to identify such genes.
Cancers
2072-6694
10.3390/cancers14143363
urn:nbn:de:bvb:20-opus-281768
2022-08-03T11:57:22+00:00
sword
swordwue
attachment; filename=deposit.zip
4e4675a09a24bc2701fd9f04c78ac863
Cancers (2022) 14:14, 3363. https://doi.org/10.3390/cancers14143363
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Martine Dumont
Nana Weber-Lassalle
Charles Joly-Beauparlant
Corinna Ernst
Arnaud Droit
Bing-Jian Feng
Stéphane Dubois
Annie-Claude Collin-Deschesnes
Penny Soucy
Maxime Vallée
Frédéric Fournier
Audrey Lemaçon
Muriel A. Adank
Jamie Allen
Janine Altmüller
Norbert Arnold
Margreet G. E. M. Ausems
Riccardo Berutti
Manjeet K. Bolla
Shelley Bull
Sara Carvalho
Sten Cornelissen
Michael R. Dufault
Alison M. Dunning
Christoph Engel
Andrea Gehrig
Willemina R. R. Geurts-Giele
Christian Gieger
Jessica Green
Karl Hackmann
Mohamed Helmy
Julia Hentschel
Frans B. L. Hogervorst
Antoinette Hollestelle
Maartje J. Hooning
Judit Horváth
M. Arfan Ikram
Silke Kaulfuß
Renske Keeman
Da Kuang
Craig Luccarini
Wolfgang Maier
John W. M. Martens
Dieter Niederacher
Peter Nürnberg
Claus-Eric Ott
Annette Peters
Paul D. P. Pharoah
Alfredo Ramirez
Juliane Ramser
Steffi Riedel-Heller
Gunnar Schmidt
Mitul Shah
Martin Scherer
Antje Stäbler
Tim M. Strom
Christian Sutter
Holger Thiele
Christi J. van Asperen
Lizet van der Kolk
Rob B. van der Luijt
Alexander E. Volk
Michael Wagner
Quinten Waisfisz
Qin Wang
Shan Wang-Gohrke
Bernhard H. F. Weber
Peter Devilee
Sean Tavtigian
Gary D. Bader
Alfons Meindl
David E. Goldgar
Irene L. Andrulis
Rita K. Schmutzler
Douglas F. Easton
Marjanka K. Schmidt
Eric Hahnen
Jacques Simard
eng
uncontrolled
breast cancer
eng
uncontrolled
genetic susceptibility
eng
uncontrolled
whole-exome sequencing
eng
uncontrolled
moderate-penetrance genes
Medizin und Gesundheit
open_access
Institut für Humangenetik
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/28176/cancers-14-03363-v2.pdf
23434
2021
eng
14
article
1
--
--
--
International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020)
Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice.
Frontiers in Human Neuroscience
1662-5161
10.3389/fnhum.2020.568051
urn:nbn:de:bvb:20-opus-234346
2021-04-12T16:08:35+00:00
sword
swordwue
attachment; filename=deposit.zip
7c32ee28b56dfb62089aa3c20ca8ef11
Frontiers in Human Neuroscience 2021, 14:568051. DOI: 10.3389/fnhum.2020.568051
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Adam D. Farmer
Adam Strzelczyk
Alessandra Finisguerra
Alexander V. Gourine
Alireza Gharabaghi
Alkomiet Hasan
Andreas M. Burger
Andrés M. Jaramillo
Ann Mertens
Arshad Majid
Bart Verkuil
Bashar W. Badran
Carlos Ventura-Bort
Charly Gaul
Christian Beste
Christopher M. Warren
Daniel S. Quintana
Dorothea Hämmerer
Elena Freri
Eleni Frangos
Eleonora Tobaldini
Eugenijus Kaniusas
Felix Rosenow
Fioravante Capone
Fivos Panetsos
Gareth L. Ackland
Gaurav Kaithwas
Georgia H. O'Leary
Hannah Genheimer
Heidi I. L. Jacobs
Ilse Van Diest
Jean Schoenen
Jessica Redgrave
Jiliang Fang
Jim Deuchars
Jozsef C. Széles
Julian F. Thayer
Kaushik More
Kristl Vonck
Laura Steenbergen
Lauro C. Vianna
Lisa M. McTeague
Mareike Ludwig
Maria G. Veldhuizen
Marijke De Couck
Marina Casazza
Marius Keute
Marom Bikson
Marta Andreatta
Martina D'Agostini
Mathias Weymar
Matthew Betts
Matthias Prigge
Michael Kaess
Michael Roden
Michelle Thai
Nathaniel M. Schuster
Nicola Montano
Niels Hansen
Nils B. Kroemer
Peijing Rong
Rico Fischer
Robert H. Howland
Roberta Sclocco
Roberta Sellaro
Ronald G. Garcia
Sebastian Bauer
Sofiya Gancheva
Stavros Stavrakis
Stefan Kampusch
Susan A. Deuchars
Sven Wehner
Sylvain Laborde
Taras Usichenko
Thomas Polak
Tino Zaehle
Uirassu Borges
Vanessa Teckentrup
Vera K. Jandackova
Vitaly Napadow
Julian Koenig
eng
uncontrolled
transcutaneous vagus nerve stimulation
eng
uncontrolled
minimum reporting standards
eng
uncontrolled
guidelines & recommendations
eng
uncontrolled
transcutaneous auricular vagus nerve stimulation
eng
uncontrolled
transcutaneous cervical vagus nerve stimulation
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie
Institut für Psychologie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/23434/fnhum-14-568051.pdf
https://opus.bibliothek.uni-wuerzburg.de/files/23434/fnhum-14-568051-g0001.tif
https://opus.bibliothek.uni-wuerzburg.de/files/23434/fnhum-14-568051-g0002.tif
13151
2013
eng
e229
3
article
1
2016-04-07
--
--
A common variant in Myosin-18B contributes to mathematical abilities in children with dyslexia and intraparietal sulcus variability in adults
The ability to perform mathematical tasks is required in everyday life. Although heritability estimates suggest a genetic contribution, no previous study has conclusively identified a genetic risk variant for mathematical performance. Research has shown that the prevalence of mathematical disabilities is increased in children with dyslexia. We therefore correlated genome-wide data of 200 German children with spelling disability, with available quantitative data on mathematic ability. Replication of the top findings in additional dyslexia samples revealed that rs133885 was a genome-wide significant marker for mathematical abilities\((P_{comb}=7.71 x 10^{-10}, n=699)\), with an effect size of 4.87%. This association was also found in a sample from the general population (P=0.048, n=1080), albeit with a lower effect size. The identified variant encodes an amino-acid substitution in MYO18B, a protein with as yet unknown functions in the brain. As areas of the parietal cortex, in particular the intraparietal sulcus (IPS), are involved in numerical processing in humans, we investigated whether rs133885 was associated with IPS morphology using structural magnetic resonance imaging data from 79 neuropsychiatrically healthy adults. Carriers of the MYO18B risk-genotype displayed a significantly lower depth of the right IPS. This validates the identified association between rs133885 and mathematical disability at the level of a specific intermediate phenotype.
Translational Psychiatry
10.1038/tp.2012.148
urn:nbn:de:bvb:20-opus-131513
Supplementary Information accompanies the paper on the Translational Psychiatry website (http://www.nature.com/tp).
Translational Psychiatry (2013) 3, e229; doi:10.1038/tp.2012.148
018696
K. U. Ludwig
P. Sämann
M. Alexander
J. Becker
J. Bruder
K. Moll
D. Spieler
M. Czisch
A. Warnke
S. J. Docherty
O. S. P. Davis
R. Plomin
M. M. Nöthen
K. Landerl
B. Müller-Myhsok
P. Hoffmann
J. Schumacher
G. Schulte-Körne
D. Czamara
eng
uncontrolled
disability
eng
uncontrolled
sulcal morphology
eng
uncontrolled
prelevance
eng
uncontrolled
identification
eng
uncontrolled
brain
eng
uncontrolled
cancer
eng
uncontrolled
association
eng
uncontrolled
developmental dyscalculia
eng
uncontrolled
tumor-suppressor gene
eng
uncontrolled
correlate
eng
uncontrolled
disorders
eng
uncontrolled
dyscalculia
eng
uncontrolled
dyslexia
eng
uncontrolled
genomic imaging
eng
uncontrolled
mathematics
eng
uncontrolled
quantitative trait
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13151/107_Ludwig_Translational_Psychiatry.pdf
16540
2016
eng
2073-2079
7
6
article
1
2018-07-23
--
--
Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients
Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117), despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.93–1.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility.
G3: Genes Genomes Genetics
10.1534/g3.116.030841
urn:nbn:de:bvb:20-opus-165405
G3: Genes Genomes Genetics, 2016, Vol. 6(7), p 2073-2079
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
A. Dessa Sadovnick
Anthony L. Traboulsee
Cecily Q. Bernales
Jay P. Ross
Amanda L. Forwell
Irene M. Yee
Lena Guillot-Noel
Bertrand Fontaine
Isabelle Cournu-Rebeix
Antonio Alcina
Maria Fedetz
Guillermo Izquierdo
Fuencisla Matesanz
Kelly Hilven
Bénédicte Dubois
An Goris
Ianire Astobiza
Iraide Alloza
Alfredo Antigüedad
Koen Vandenbroeck
Denis A. Akkad
Orhan Aktas
Paul Blaschke
Mathias Buttmann
Andrew Chan
Joerg T. Epplen
Lisa-Ann Gerdes
Antje Kroner
Christian Kubisch
Tania Kümpfel
Peter Lohse
Peter Rieckmann
Uwe K. Zettl
Frauke Zipp
Lars Bertram
Christina M. Lill
Oscar Fernandez
Patricia Urbaneja
Laura Leyva
Jose Carlos Alvarez-Cermeño
Rafael Arroyo
Aroa M. Garagorri
Angel García-Martínez
Luisa M. Villar
Elena Urcelay
Sunny Malhotra
Xavier Montalban
Manuel Comabella
Thomas Berger
Franz Fazekas
Markus Reindl
Mascha C. Schmied
Alexander Zimprich
Carles Vilariño-Güell
eng
uncontrolled
multiple sclerosis
eng
uncontrolled
genetics
eng
uncontrolled
linkage
eng
uncontrolled
association
eng
uncontrolled
plasminogen
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16540/068_Sadovnick_G3-GENES GENOMES GENETICS.pdf
11725
2014
eng
347-357
3
6
article
1
2015-08-04
--
--
Heteropathogenic virulence and phylogeny reveal phased pathogenic metamorphosis in Escherichia coli O2:H6
Extraintestinal pathogenic and intestinal pathogenic (diarrheagenic) Escherichia coli differ phylogenetically and by virulence profiles. Classic theory teaches simple linear descent in this species, where non-pathogens acquire virulence traits and emerge as pathogens. However, diarrheagenic Shiga toxin-producing E.coli (STEC) O2:H6 not only possess and express virulence factors associated with diarrheagenic and uropathogenic E.coli but also cause diarrhea and urinary tract infections. These organisms are phylogenetically positioned between members of an intestinal pathogenic group (STEC) and extraintestinal pathogenic E.coli. STEC O2:H6 is, therefore, a 'heteropathogen,' and the first such hybrid virulent E.coli identified. The phylogeny of these E.coli and the repertoire of virulence traits they possess compel consideration of an alternate view of pathogen emergence, whereby one pathogroup of E.coli undergoes phased metamorphosis into another. By understanding the evolutionary mechanisms of bacterial pathogens, rational strategies for counteracting their detrimental effects on humans can be developed.
EMBO Molecular Medicine
10.1002/emmm.201303133
1757-4684
24413188
urn:nbn:de:bvb:20-opus-117254
EMBO Molecular Medicine 2014 6(3):347-57. doi: 10.1002/emmm.201303133
Martina Bielaszewska
Roswitha Schiller
Lydia Lammers
Andreas Bauwens
Angelika Fruth
Barbara Middendorf
M. Alexander Schmidt
Phillip I. Tarr
Ulrich Dobrindt
Helge Karch
Alexander Mellmann
eng
uncontrolled
phased metamorphosis
eng
uncontrolled
phylogeny
eng
uncontrolled
heteropathogenicity
eng
uncontrolled
Shiga toxin-producing Escherichia coli
eng
uncontrolled
hemolytic-uremic syndrome
eng
uncontrolled
urinary-tract-infection
eng
uncontrolled
cytolethal distending toxin
eng
uncontrolled
shiga toxin
eng
uncontrolled
Crohns-disease
eng
uncontrolled
outbreak
eng
uncontrolled
genes
eng
uncontrolled
island
eng
uncontrolled
strains
eng
uncontrolled
parallel evolution
eng
uncontrolled
uropathogenic Escherichia coli
Medizin und Gesundheit
open_access
Institut für Molekulare Infektionsbiologie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11725/114_Bielaszewska_Embo_Molecular_Medicine.pdf
26481
2022
eng
141–151
1
32
article
1
--
--
--
Safety and Effectiveness of the New Generation APERIO® Hybrid Stent-retriever Device in Large Vessel Occlusion Stroke
Background
It is unknown whether technological advancement of stent-retriever devices influences typical observational indicators of safety or effectiveness.
Methods
Observational retrospective study of APERIO® (AP) vs. new generation APERIO® Hybrid (APH) (Acandis®, Pforzheim, Germany) stent-retriever device (01/2019–09/2020) for mechanical thrombectomy (MT) in large vessel occlusion (LVO) stroke. Primary effectiveness endpoint was successful recanalization eTICI (expanded Thrombolysis In Cerebral Ischemia) ≥ 2b67, primary safety endpoint was occurrence of hemorrhagic complications after MT. Secondary outcome measures were time from groin puncture to first pass and successful reperfusion, and the total number of passes needed to achieve the final recanalization result.
Results
A total of 298 patients with LVO stroke who were treated by MT matched the inclusion criteria: 148 patients (49.7%) treated with AP vs. 150 patients (50.3%) treated with new generation APH. Successful recanalization was not statistically different between both groups: 75.7% for AP vs. 79.3% for APH; p = 0.450. Postinterventional hemorrhagic complications and particularly subarachnoid hemorrhage as the entity possibly associated with stent-retriever device type was significantly less frequent in the group treated with the APH: 29.7% for AP and 16.0% for APH; p = 0.005; however, rates of symptomatic hemorrhage with clinical deterioration and in domo mortality were not statistically different. Neither the median number of stent-retriever passages needed to achieve final recanalization, time from groin puncture to first pass, time from groin puncture to final recanalization nor the number of cases in which successful recanalization could only be achieved by using a different stent-retriever as bail-out device differed between both groups.
Conclusion
In the specific example of the APERIO® stent-retriever device, we observed that further technological developments of the new generation device were not associated with disadvantages with respect to typical observational indicators of safety or effectiveness.
Clinical Neuroradiology
10.1007/s00062-021-01122-1
urn:nbn:de:bvb:20-opus-264817
publish
Clinical Neuroradiology 2022, 32(1):141–151. DOI: 10.1007/s00062-021-01122-1
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Marius L. Vogt
Alexander M. Kollikowski
Franziska Weidner
Marc Strinitz
Jörn Feick
Fabian Essig
Herrmann Neugebauer
Karl Georg Haeusler
Mirko Pham
Alexander Maerz
eng
uncontrolled
APERIO Hybrid
eng
uncontrolled
mechanical thrombectomy
eng
uncontrolled
stent-retriever device
eng
uncontrolled
stroke
eng
uncontrolled
APERIO
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie)
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/26481/Vogt_Clinical.pdf
22793
2018
eng
18
article
1
2021-02-28
--
--
Sequential treatment of ADHD in mother and child (AIMAC study): importance of the treatment phases for intervention success in a randomized trial
Background
The efficacy of parent-child training (PCT) regarding child symptoms may be reduced if the mother has attention-deficit/hyperactivity disorder (ADHD). The AIMAC study (ADHD in Mothers and Children) aimed to compensate for the deteriorating effect of parental psychopathology by treating the mother (Step 1) before the beginning of PCT (Step 2). This secondary analysis was particularly concerned with the additional effect of the Step 2 PCT on child symptoms after the Step 1 treatment.
Methods
The analysis included 143 mothers and children (aged 6–12 years) both diagnosed with ADHD. The study design was a two-stage, two-arm parallel group trial (Step 1 treatment group [TG]: intensive treatment of the mother including psychotherapy and pharmacotherapy; Step 1 control group [CG]: supportive counseling only for mother; Step 2 TG and CG: PCT). Single- and multi-group analyses with piecewise linear latent growth curve models were applied to test for the effects of group and phase. Child symptoms (e.g., ADHD symptoms, disruptive behavior) were rated by three informants (blinded clinician, mother, teacher).
Results
Children in the TG showed a stronger improvement of their disruptive behavior as rated by mothers than those in the CG during Step 1 (Step 1: TG vs. CG). In the CG, according to reports of the blinded clinician and the mother, the reduction of children’s disruptive behavior was stronger during Step 2 than during Step 1 (CG: Step 1 vs. Step 2). In the TG, improvement of child outcome did not differ across treatment steps (TG: Step 1 vs. Step 2).
Conclusions
Intensive treatment of the mother including pharmacotherapy and psychotherapy may have small positive effects on the child’s disruptive behavior. PCT may be a valid treatment option for children with ADHD regarding disruptive behavior, even if mothers are not intensively treated beforehand.
Trial registration
ISRCTN registry ISRCTN73911400. Registered 29 March 2007.
BMC Psychiatry
10.1186/s12888-018-1963-9
urn:nbn:de:bvb:20-opus-227930
publish
BMC Psychiatry (2018) 18:388. https://doi.org/10.1186/s12888-018-1963-9
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Christopher Hautmann
Manfred Döpfner
Josepha Katzmann
Stephanie Schürmann
Tanja Wolff Metternich-Kaizman
Charlotte Jaite
Viola Kappel
Julia Geissler
Andreas Warnke
Christian Jacob
Klaus Hennighausen
Barbara Haack-Dees
Katja Schneider-Momm
Alexandra Philipsen
Swantje Matthies
Michael Rösler
Wolfgang Retz
Alexander von Gontard
Esther Sobanski
Barbara Alm
Sarah Hohmann
Alexander Häge
Luise Poustka
Michael Colla
Laura Gentschow
Christine M. Freitag
Katja Becker
Thomas Jans
eng
uncontrolled
mothers
eng
uncontrolled
children
eng
uncontrolled
adult treatment
eng
uncontrolled
parent training
eng
uncontrolled
efficacy
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/22793/s12888-018-1963-9.pdf
27019
2022
eng
364–369
3
13
article
1
--
--
--
Platelet Activation and Chemokine Release Are Related to Local Neutrophil-Dominant Inflammation During Hyperacute Human Stroke
Experimental evidence has emerged that local platelet activation contributes to inflammation and infarct formation in acute ischemic stroke (AIS) which awaits confirmation in human studies. We conducted a prospective observational study on 258 consecutive patients undergoing mechanical thrombectomy (MT) due to large-vessel-occlusion stroke of the anterior circulation (08/2018-05/2020). Intraprocedural microcatheter aspiration of 1 ml of local (occlusion condition) and systemic arterial blood samples (self-control) was performed according to a prespecified protocol. The samples were analyzed for differential leukocyte counts, platelet counts, and plasma levels of the platelet-derived neutrophil-activating chemokine C-X-C-motif ligand (CXCL) 4 (PF-4), the neutrophil attractant CXCL7 (NAP-2), and myeloperoxidase (MPO). The clinical-biological relevance of these variables was corroborated by specific associations with molecular-cellular, structural-radiological, hemodynamic, and clinical-functional parameters. Seventy consecutive patients fulfilling all predefined criteria entered analysis. Mean local CXCL4 (+ 39%: 571 vs 410 ng/ml, P = .0095) and CXCL7 (+ 9%: 693 vs 636 ng/ml, P = .013) concentrations were higher compared with self-controls. Local platelet counts were lower (- 10%: 347,582 vs 383,284/µl, P = .0052), whereas neutrophil counts were elevated (+ 10%: 6022 vs 5485/µl, P = 0.0027). Correlation analyses revealed associations between local platelet and neutrophil counts (r = 0.27, P = .034), and between CXCL7 and MPO (r = 0.24, P = .048). Local CXCL4 was associated with the angiographic degree of reperfusion following recanalization (r = - 0.2523, P = .0479). Functional outcome at discharge correlated with local MPO concentrations (r = 0.3832, P = .0014) and platelet counts (r = 0.288, P = .0181). This study provides human evidence of cerebral platelet activation and platelet-neutrophil interactions during AIS and points to the relevance of per-ischemic thrombo-inflammatory mechanisms to impaired reperfusion and worse functional outcome following recanalization.
Translational Stroke Research
1868-601X
10.1007/s12975-021-00938-w
34455571
urn:nbn:de:bvb:20-opus-270194
publish
Translational Stroke Research 2022, 13(3):364–369. DOI: 10.1007/s12975-021-00938-w
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Alexander M. Kollikowski
Mirko Pham
Alexander G. März
Lena Papp
Bernhard Nieswandt
Guido Stoll
Michael K. Schuhmann
eng
uncontrolled
chemokines
eng
uncontrolled
CXCL4
eng
uncontrolled
PF4
eng
uncontrolled
CXCL7
eng
uncontrolled
NAP-2
eng
uncontrolled
ischemic stroke
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Rudolf-Virchow-Zentrum
Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie)
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/27019/Kollikowski_Translational.pdf
28428
2021
eng
17
22
article
1
--
2021-08-25
--
Immune cells invade the collateral circulation during human stroke: prospective replication and extension
It remains unclear if principal components of the local cerebral stroke immune response can be reliably and reproducibly observed in patients with acute large-vessel-occlusion (LVO) stroke. We prospectively studied a large independent cohort of n = 318 consecutive LVO stroke patients undergoing mechanical thrombectomy during which cerebral blood samples from within the occluded anterior circulation and systemic control samples from the ipsilateral cervical internal carotid artery were obtained. An extensive protocol was applied to homogenize the patient cohort and to standardize the procedural steps of endovascular sample collection, sample processing, and laboratory analyses. N = 58 patients met all inclusion criteria. (1) Mean total leukocyte counts were significantly higher within the occluded ischemic cerebral vasculature (I) vs. intraindividual systemic controls (S): +9.6%, I: 8114/µL ± 529 vs. S: 7406/µL ± 468, p = 0.0125. (2) This increase was driven by neutrophils: +12.1%, I: 7197/µL ± 510 vs. S: 6420/µL ± 438, p = 0.0022. Leukocyte influx was associated with (3) reduced retrograde collateral flow (R\(^2\) = 0.09696, p = 0.0373) and (4) greater infarct extent (R\(^2\) = 0.08382, p = 0.032). Despite LVO, leukocytes invade the occluded territory via retrograde collateral pathways early during ischemia, likely compromising cerebral hemodynamics and tissue integrity. This inflammatory response can be reliably observed in human stroke by harvesting immune cells from the occluded cerebral vascular compartment.
International Journal of Molecular Sciences
1422-0067
10.3390/ijms22179161
urn:nbn:de:bvb:20-opus-284281
2022-09-03T18:40:03+00:00
sword
swordwue
attachment; filename=deposit.zip
0ba702d5e2f3f5bef62a838d20b3a3ba
International Journal of Molecular Sciences (2021) 22:17, 9161. https://doi.org/10.3390/ijms22179161
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Marc Strinitz
Mirko Pham
Alexander G. März
Jörn Feick
Franziska Weidner
Marius L. Vogt
Fabian Essig
Hermann Neugebauer
Guido Stoll
Michael K. Schuhmann
Alexander M. Kollikowski
eng
uncontrolled
ischemic stroke
eng
uncontrolled
cerebral ischemia
eng
uncontrolled
mechanical thrombectomy
eng
uncontrolled
large vessel occlusion
eng
uncontrolled
leukocytes
eng
uncontrolled
neutrophils
eng
uncontrolled
collateral circulation
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie)
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/28428/ijms-22-09161-v2.pdf
12126
2014
eng
2480-92
9
137
article
on behalf of the International Parkinson’s Disease Genomics Consortium and UCL-exomes consortium
1
2015-10-28
--
--
Parkinson’s disease in GTP cyclohydrolase 1 mutation carriers
GTP cyclohydrolase 1, encoded by the GCH1 gene, is an essential enzyme for dopamine production in nigrostriatal cells. Loss-of-function mutations in GCH1 result in severe reduction of dopamine synthesis in nigrostriatal cells and are the most common cause of DOPA-responsive dystonia, a rare disease that classically presents in childhood with generalized dystonia and a dramatic long-lasting response to levodopa. We describe clinical, genetic and nigrostriatal dopaminergic imaging ([(123)I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane single photon computed tomography) findings of four unrelated pedigrees with DOPA-responsive dystonia in which pathogenic GCH1 variants were identified in family members with adult-onset parkinsonism. Dopamine transporter imaging was abnormal in all parkinsonian patients, indicating Parkinson's disease-like nigrostriatal dopaminergic denervation. We subsequently explored the possibility that pathogenic GCH1 variants could contribute to the risk of developing Parkinson's disease, even in the absence of a family history for DOPA-responsive dystonia. The frequency of GCH1 variants was evaluated in whole-exome sequencing data of 1318 cases with Parkinson's disease and 5935 control subjects. Combining cases and controls, we identified a total of 11 different heterozygous GCH1 variants, all at low frequency. This list includes four pathogenic variants previously associated with DOPA-responsive dystonia (Q110X, V204I, K224R and M230I) and seven of undetermined clinical relevance (Q110E, T112A, A120S, D134G, I154V, R198Q and G217V). The frequency of GCH1 variants was significantly higher (Fisher's exact test P-value 0.0001) in cases (10/1318 = 0.75%) than in controls (6/5935 = 0.1%; odds ratio 7.5; 95% confidence interval 2.4-25.3). Our results show that rare GCH1 variants are associated with an increased risk for Parkinson's disease. These findings expand the clinical and biological relevance of GTP cycloydrolase 1 deficiency, suggesting that it not only leads to biochemical striatal dopamine depletion and DOPA-responsive dystonia, but also predisposes to nigrostriatal cell loss. Further insight into GCH1-associated pathogenetic mechanisms will shed light on the role of dopamine metabolism in nigral degeneration and Parkinson's disease.
Brain
10.1093/brain/awu179
24993959
urn:nbn:de:bvb:20-opus-121268
Brain 2014: 137; 2480–2492. doi:10.1093/brain/awu179
Niccoló E. Mencacci
Ioannis U. Isaias
Martin M. Reich
Christos Ganos
Vincent Plagnol
James M. Polke
Jose Bras
Joshua Hersheson
Maria Stamelou
Alan M. Pittman
Alastair J. Noyce
Kin Y. Mok
Thomas Opladen
Erdmute Kunstmann
Sybille Hodecker
Alexander Münchau
Jens Volkmann
Samuel Samnick
Katie Sidle
Tina Nanji
Mary G. Sweeney
Henry Houlden
Amit Batla
Anna L. Zecchinelli
Gianni Pezzoli
Giorgio Marotta
Andrew Lees
Paulo Alegria
Paul Krack
Florence Cormier-Dequaire
Suzanne Lesage
Alexis Brice
Peter Heutink
Thomas Gasser
Steven J. Lubbe
Huw R. Morris
Pille Taba
Sulev Koks
Elisa Majounie
J. Raphael Gibbs
Andrew Singleton
John Hardy
Stephan Klebe
Kailash P. Bhatia
Nicholas W. Wood
eng
uncontrolled
DOPA-responsive-dystonia
eng
uncontrolled
GCH1
eng
uncontrolled
Parkinson's disease
eng
uncontrolled
dopamine
eng
uncontrolled
exome sequencing
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12126/035_Mencacci_Brain.pdf
13375
2011
eng
e1002292
9
7
article
1
2016-05-20
--
--
Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD
Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR < 60ml/min/1.73m(2) at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression.
PLoS Genetics
10.1371/journal.pgen.1002292
urn:nbn:de:bvb:20-opus-133758
PLoS Genet 7(9): e1002292. doi:10.1371/journal.pgen.1002292
false
true
CC 0: Public Domain Dedication
Böger Carsten A.
Mathias Gorski
Man Li
Michael M. Hoffmann
Chunmei Huang
Qiong Yang
Alexander Teumer
Vera Krane
Conall M. O'Seaghdha
Zoltán Kutalik
H.-Erich Wichmann
Thomas Haak
Eva Boes
Stefan Coassin
Josef Coresh
Barbara Kollerits
Margot Haun
Bernhard Paulweber
Anna Köttgen
Guo Li
Michael G. Shlipak
Neil Powe
Shih-Jen Hwang
Abbas Dehghan
Fernando Rivadeneira
André Uitterlinden
Albert Hofman
Jacques S. Beckmann
Bernhard K. Krämer
Jacqueline Witteman
Murielle Bochud
David Siscovick
Rainer Rettig
Florian Kronenberg
Christoph Wanner
Ravi I. Thadhani
Iris M. Heid
Caroline S. Fox
W.H. Kao
eng
uncontrolled
Chronic Kidney-disease
eng
uncontrolled
Stage renal-disease
eng
uncontrolled
Glomerular-filtration-rate
eng
uncontrolled
Diabetic-nephropathy
eng
uncontrolled
General-population
eng
uncontrolled
African-americans
eng
uncontrolled
Risk
eng
uncontrolled
Progression
eng
uncontrolled
Mortality
eng
uncontrolled
Variants
Medizin und Gesundheit
open_access
Medizinische Klinik und Poliklinik I
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13375/012_Boeger_PLoS-Genetic.PDF
27076
2022
eng
8
14
article
1
--
2022-04-13
--
Sorafenib versus lenvatinib-based sequential systemic therapy for advanced hepatocellular carcinoma: a real-world analysis
The optimal treatment sequence of tyrosine kinase inhibitor (TKI)-based therapy in patients with hepatocellular carcinoma (HCC) remains unclear. Therefore, sequential systemic therapy after first-line therapy with sorafenib or lenvatinib was compared in a retrospective real-world cohort. In total, 164 patients with HCC were included. Child B cirrhosis was present in 26 patients (16.5%), whereas 132 patients (83.5%) had preserved liver function. In total, 72 patients (44%) discontinued systemic therapy after first-line therapy while 51 (31%) and 31 (19%) patients received 2 or more treatment lines. Most notably, median overall survival (mOS) was influenced by liver functional status and patient performance status at the beginning of first-line therapy. Patients receiving a sequential therapy regimen had significantly longer mOS compared to patients that discontinued systemic therapy after omitting first-line treatment. The choice of the initial TKI did not impact mOS. A clear deterioration of liver function could be observed during the course of TKI-based treatment.
Cancers
2072-6694
10.3390/cancers14081975
urn:nbn:de:bvb:20-opus-270765
2022-05-09T06:43:39+00:00
sword
swordwue
attachment; filename=deposit.zip
9d979fc499b6af935cc54630748e2613
Cancers (2022) 14:8, 1975. https://doi.org/10.3390/cancers14081975
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Catherine Leyh
Ursula Ehmer
Daniel Roessler
Alexander B. Philipp
Florian P. Reiter
Petia Jeliazkova
Leonie S. Jochheim
Matthias Jeschke
Janina Hammig
Johannes M. Ludwig
Jens M. Theysohn
Andreas Geier
Christian M. Lange
eng
uncontrolled
hepatocellular carcinoma
eng
uncontrolled
systemic therapy
eng
uncontrolled
tyrosine-kinase inhibitor
Medizin und Gesundheit
open_access
Medizinische Klinik und Poliklinik II
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/27076/cancers-14-01975-v3.pdf
5641
2010
eng
article
1
2012-03-02
--
--
Post-Stroke Inhibition of Induced NADPH Oxidase Type 4 Prevents Oxidative Stress and Neurodegeneration
Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox42/2) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox42/2 mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy.
urn:nbn:de:bvb:20-opus-68416
6841
PLOS BIOLOGY (2010) 8, 9, DOI: 10.1371/journal.pbio.1000479
Christoph Kleinschnitz
Henrike Grund
Kirstin Wingler
Melanie E. Armitage
Emma Jones
Manish Mittal
David Barit
Tobias Schwarz
Christian Geis
Peter Kraft
Konstanze Barthel
Michael K. Schuhmann
Alexander M. Herrmann
Sven G. Meuth
Guido Stoll
Sabine Meurer
Anja Schrewe
Lore Becker
Valerie Gailus-Durner
Helmut Fuchs
Thomas Klopstock
Martin Hrabe de Angelis
Karin Jandeleit-Dahm
Ajay M. Shah
Norbert Weissmann
Harald H. H. W. Schmidt
deu
swd
Schlaganfall
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5641/Kleinschnitz_journal.pbio.1000479.pdf
29734
2022
eng
22
11
article
1
--
2022-11-18
--
Pumpless extracorporeal hemadsorption technique (pEHAT): a proof-of-concept animal study
Background: Extracorporeal hemadsorption eliminates proinflammatory mediators in critically ill patients with hyperinflammation. The use of a pumpless extracorporeal hemadsorption technique allows its early usage prior to organ failure and the need for an additional medical device. In our animal model, we investigated the feasibility of pumpless extracorporeal hemadsorption over a wide range of mean arterial pressures (MAP). Methods: An arteriovenous shunt between the femoral artery and femoral vein was established in eight pigs. The hemadsorption devices were inserted into the shunt circulation; four pigs received CytoSorb\(^®\) and four Oxiris\(^®\) hemadsorbers. Extracorporeal blood flow was measured in a range between mean arterial pressures of 45–85 mmHg. Mean arterial pressures were preset using intravenous infusions of noradrenaline, urapidil, or increased sedatives. Results: Extracorporeal blood flows remained well above the minimum flows recommended by the manufacturers throughout all MAP steps for both devices. Linear regression resulted in CytoSorb\(^®\) blood flow [mL/min] = 4.226 × MAP [mmHg] − 3.496 (R-square 0.8133) and Oxiris\(^®\) blood flow [mL/min] = 3.267 × MAP [mmHg] + 57.63 (R-square 0.8708), respectively. Conclusion: Arteriovenous pumpless extracorporeal hemadsorption resulted in sufficient blood flows through both the CytoSorb\(^®\) and Oxiris\(^®\) devices over a wide range of mean arterial blood pressures and is likely an intriguing therapeutic option in the early phase of septic shock or hyperinflammatory syndromes.
Journal of Clinical Medicine
2077-0383
10.3390/jcm11226815
urn:nbn:de:bvb:20-opus-297347
2022-12-15T14:03:49+00:00
sword
swordwue
attachment; filename=deposit.zip
eb36493e8e05d13b810c11d2fd39b9da
Journal of Clinical Medicine (2022) 11:22, 6815. https://doi.org/10.3390/jcm11226815
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Mascha O. Fiedler
Ralf M. Muellenbach
Caroline Rolfes
Christopher Lotz
Felix Nickel
Beat P. Müller-Stich
Alexander Supady
Philipp M. Lepper
Markus A. Weigand
Patrick Meybohm
Armin Kalenka
Christian Reyher
eng
uncontrolled
blood purification
eng
uncontrolled
extracorporeal hemadsorption
eng
uncontrolled
cytokines
eng
uncontrolled
adsorption
eng
uncontrolled
animal model
eng
uncontrolled
immunosorbents
eng
uncontrolled
septic shock
eng
uncontrolled
endotoxin
eng
uncontrolled
extracorporeal techniques in hemadsorption therapy
eng
uncontrolled
arteriovenous extracorporeal hemadsorption technique
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Anästhesiologie (ab 2004)
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/29734/jcm-11-06815.pdf
14591
2016
eng
1-17
12
article
1
2017-03-21
--
--
Functional and structural characterization of axonal opioid receptors as targets for analgesia
Background
Opioids are the gold standard for the treatment of acute pain despite serious side effects in the central and enteric nervous system. µ-opioid receptors (MOPs) are expressed and functional at the terminals of sensory axons, when activated by exogenous or endogenous ligands. However, the presence and function of MOP along nociceptive axons remains controversial particularly in naïve animals. Here, we characterized axonal MOPs by immunofluorescence, ultrastructural, and functional analyses. Furthermore, we evaluated hypertonic saline as a possible enhancer of opioid receptor function.
Results
Comparative immunolabeling showed that, among several tested antibodies, which all provided specific MOP detection in the rat central nervous system (CNS), only one monoclonal MOP-antibody yielded specificity and reproducibility for MOP detection in the rat peripheral nervous system including the sciatic nerve. Double immunolabeling documented that MOP immunoreactivity was confined to calcitonin gene-related peptide (CGRP) positive fibers and fiber bundles. Almost identical labeling and double labeling patterns were found using mcherry-immunolabeling on sciatic nerves of mice producing a MOP-mcherry fusion protein (MOP-mcherry knock-in mice). Preembedding immunogold electron microscopy on MOP-mcherry knock-in sciatic nerves indicated presence of MOP in cytoplasm and at membranes of unmyelinated axons. Application of [D-Ala\(^2\), N-MePhe\(^4\), Gly-ol]-enkephalin (DAMGO) or fentanyl dose-dependently inhibited depolarization-induced CGRP release from rat sciatic nerve axons ex vivo, which was blocked by naloxone. When the lipophilic opioid fentanyl was applied perisciatically in naïve Wistar rats, mechanical nociceptive thresholds increased. Subthreshold doses of fentanyl or the hydrophilic opioid DAMGO were only effective if injected together with hypertonic saline. In vitro, using β-arrestin-2/MOP double-transfected human embryonic kidney cells, DAMGO as well as fentanyl lead to a recruitment of β-arrestin-2 to the membrane followed by a β-arrestin-2 reappearance in the cytosol and MOP internalization. Pretreatment with hypertonic saline prevented MOP internalization.
Conclusion
MOPs are present and functional in the axonal membrane from naïve animals. Hypertonic saline acutely decreases ligand-induced internalization of MOP and thereby might improve MOP function. Further studies should explore potential clinical applications of opioids together with enhancers for regional analgesia.
Molecular Pain
10.1177/1744806916628734
urn:nbn:de:bvb:20-opus-145917
Molecular Pain, Volume 12: 1–17 (2016). DOI:10.1177/1744806916628734
Egle M. Mambretti
Katrin Kistner
Stefanie Mayer
Dominique Massotte
Brigitte L. Kieffer
Carsten Hoffmann
Peter W. Reeh
Alexander Brack
Esther Asan
Heike L. Rittner
eng
uncontrolled
µ-Opioid receptor
eng
uncontrolled
hypertonic solution
eng
uncontrolled
fentanyl
eng
uncontrolled
calcitonin gene-related peptide
eng
uncontrolled
DAMGO
eng
uncontrolled
internalization
eng
uncontrolled
peripheral nerve
eng
uncontrolled
ultrastructure
Chirurgie und verwandte medizinische Fachrichtungen
open_access
Institut für Pharmakologie und Toxikologie
Institut für Anatomie und Zellbiologie
Klinik und Poliklinik für Anästhesiologie (ab 2004)
Rudolf-Virchow-Zentrum
Förderzeitraum 2016
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14591/Mambretti_1744806916628734.pdf
6242
2010
eng
article
1
2012-11-10
--
--
Spatial, temporal and interindividual epigenetic variation of functionally important DNA methylation patterns
DNA methylation is an epigenetic modification that plays an important role in gene regulation. It can be influenced by stochastic events, environmental factors and developmental programs. However, little is known about the natural variation of genespecific methylation patterns. In this study, we performed quantitative methylation analyses of six differentially methylated imprinted genes (H19, MEG3, LIT1, NESP55, PEG3 and SNRPN), one hypermethylated pluripotency gene (OCT4) and one hypomethylated tumor suppressor gene (APC) in chorionic villus, fetal and adult cortex, and adult blood samples. Both average methylation level and range of methylation variation depended on the gene locus, tissue type and/or developmental stage. We found considerable variability of functionally important methylation patterns among unrelated healthy individuals and a trend toward more similar methylation levels in monozygotic twins than in dizygotic twins. Imprinted genes showed relatively little methylation changes associated with aging in individuals who are >25 years. The relative differences in methylation among neighboring CpGs in the generally hypomethylated APC promoter may not only reflect stochastic fluctuations but also depend on the tissue type. Our results are consistent with the view that most methylation variation may arise after fertilization, leading to epigenetic mosaicism.
urn:nbn:de:bvb:20-opus-68371
6837
In: Nucleic Acids Research (2010) 38, 12, 3880-3890, DOI: 10.1093/nar/gkq126
Eberhard Schneider
Galyna Pliushch
Nady El Hajj
Danuta Galetzka
Alexander Puhl
Martin Schorsch
Katrin Frauenknecht
Thomas Riepert
Achim Tresch
Annette M. Mueller
Wiltrud Coerdt
Ulrich Zechner
Thomas Haaf
deu
swd
Medizin
Medizin und Gesundheit
open_access
Institut für Humangenetik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/6242/Haaf062_3880.full.pdf
12204
2013
eng
25
14
article
DIACORE Study Group
1
2015-11-18
--
--
Study design of DIACORE (DIAbetes COhoRtE) - a cohort study of patients with diabetes mellitus type 2
Background: Diabetes mellitus type 2 (DM2) is highly associated with increased risk for chronic kidney disease (CKD), end stage renal disease (ESRD) and cardiovascular morbidity. Epidemiological and genetic studies generate hypotheses for innovative strategies in DM2 management by unravelling novel mechanisms of diabetes complications, which is essential for future intervention trials. We have thus initiated the DIAbetes COhoRtE study (DIACORE).
Methods: DIACORE is a prospective cohort study aiming to recruit 6000 patients of self-reported Caucasian ethnicity with prevalent DM2 for at least 10 years of follow-up. Study visits are performed in University-based recruiting clinics in Germany using standard operating procedures. All prevalent DM2 patients in outpatient clinics surrounding the recruiting centers are invited to participate. At baseline and at each 2-year follow-up examination, patients are subjected to a core phenotyping protocol. This includes a standardized online questionnaire and physical examination to determine incident micro-and macrovascular DM2 complications, malignancy and hospitalization, with a primary focus on renal events. Confirmatory outcome information is requested from patient records. Blood samples are obtained for a centrally analyzed standard laboratory panel and for biobanking of aliquots of serum, plasma, urine, mRNA and DNA for future scientific use. A subset of the cohort is subjected to extended phenotyping, e. g. sleep apnea screening, skin autofluorescence measurement, non-mydriatic retinal photography and non-invasive determination of arterial stiffness.
Discussion: DIACORE will enable the prospective evaluation of factors involved in DM2 complication pathogenesis using high-throughput technologies in biosamples and genetic epidemiological studies.
BMC Medical Genetics
10.1186/1471-2350-14-25
1471-2350
urn:nbn:de:bvb:20-opus-122040
BMC Medical Genetics 2013, 14:25. doi:10.1186/1471-2350-14-25
Lena Dörhöfer
Alexander Lammert
Vera Krane
Mathias Gorski
Bernhard Banas
Christoph Wanner
Bernhard K. Krämer
Iris M. Heid
Carsten A. Böger
eng
uncontrolled
chronic kidney-disease
eng
uncontrolled
stage renal-disease
eng
uncontrolled
glomerular-filtration-rate
eng
uncontrolled
genome-wide association
eng
uncontrolled
blood-glucose control
eng
uncontrolled
genetics
eng
uncontrolled
serum creatinine
eng
uncontrolled
cardiovascular disease
eng
uncontrolled
replacement therapy
eng
uncontrolled
United States
eng
uncontrolled
risk factors
eng
uncontrolled
diabetes mellitus type 2
eng
uncontrolled
diabetic nephropathy
eng
uncontrolled
end stage renal disease
eng
uncontrolled
cardiovascular morbidity
eng
uncontrolled
diabetes complications
eng
uncontrolled
epidemiology
Krankheiten
open_access
Medizinische Klinik und Poliklinik I
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12204/011_Doerhoefer_BMC_Medical_Grenetics.pdf
12076
2014
eng
2686-96
3
8
article
1
2015-10-21
--
--
Drug-Induced Morphology Switch in Drug Delivery Systems Based on Poly(2-oxazoline)s
Defined aggregates of polymers such as polymeric micelles are of great importance in the development of pharmaceutical formulations. The amount of drug that can be formulated by a drug delivery system is an important issue, and most drug delivery systems suffer from their relatively low drug-loading capacity. However, as the loading capacities increase, i.e., promoted by good drug–polymer interactions, the drug may affect the morphology and stability of the micellar system. We investigated this effect in a prominent system with very high capacity for hydrophobic drugs and found extraordinary stability as well as a profound morphology change upon incorporation of paclitaxel into micelles of amphiphilic ABA poly(2-oxazoline) triblock copolymers. The hydrophilic blocks A comprised poly(2-methyl-2-oxazoline), while the middle blocks B were either just barely hydrophobic poly(2-n-butyl-2-oxazoline) or highly hydrophobic poly(2-n-nonyl-2-oxazoline). The aggregation behavior of both polymers and their formulations with varying paclitaxel contents were investigated by means of dynamic light scattering, atomic force microscopy, (cryogenic) transmission electron microscopy, and small-angle neutron scattering. While without drug, wormlike micelles were present, after incorporation of small amounts of drugs only spherical morphologies remained. Furthermore, the much more hydrophobic poly(2-n-nonyl-2-oxazoline)-containing triblock copolymer exhibited only half the capacity for paclitaxel than the poly(2-n-butyl-2-oxazoline)-containing copolymer along with a lower stability. In the latter, contents of paclitaxel of 8 wt % or higher resulted in a raspberry-like micellar core.
ACS Nano
10.1021/nn406388t
24548260
urn:nbn:de:bvb:20-opus-120766
This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html), which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
ACS Nano VOL. 8, NO. 3, 2686–2696. DOI:10.1021/nn406388t
Anita Schulz
Sebastian Jaksch
Rene Schubel
Erik Wegener
Zhenyu Di
Yingchao Han
Annette Meister
Jörg Kressler
Alexander V. Kabanov
Robert Luxenhofer
Christine M. Papadakis
Rainer Jordan
eng
uncontrolled
amphiphilic poly(2-oxazoline)s
eng
uncontrolled
paclitaxel
eng
uncontrolled
drug delivery
eng
uncontrolled
rod-to-sphere transition
Chemie und zugeordnete Wissenschaften
open_access
Institut für Funktionsmaterialien und Biofabrikation
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12076/006_Schulz_ACS_Nano.pdf
2666
1981
eng
article
1
2009-01-07
--
--
On the origin of the H1N1 (A/USSR/90/77) influenza virus
The influenza virus H1N1 (the A/USSR/90/77 strain) that reappeared in 1977 after the H1N1 influenza viruses had disappeared from the human population, is compared with the A/FM/1/47 and the A/FW/1/50 influenza viruses by the method of oligonucleotide mapping of individual segments of the viral RNAs. Seven genes of the A/USSR/90/77 virus appear to be very similar to the corresponding genes of the A/FW/1/50 virus, whereas the gene coding for the M protein displays considerable homology to the corresponding gene of the A/FM/1/47 virus. The data demonstrate that the A/USSR/90/77 strain is a recombinant virus.
urn:nbn:de:bvb:20-opus-32556
3255
In: Journal of general virology (1981), 56, 437-440
J. V. Kozlov
Valentin G. Gorboulev
A. G. Kurmanova
Alexander A. Bayev
A. A. Shilov
V. M. Zhdanov
eng
uncontrolled
influenza virus ; virion RNA segments ; oligonucleotide mapping ; gene reassortment
Medizin und Gesundheit
open_access
Institut für Anatomie und Zellbiologie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/2666/Gorboulev_H1N1.pdf
11524
2014
eng
302-310
5
7
article
1
2015-07-04
--
--
Rats Fed Diets with Different Energy Contribution from Fat Do Not Differ in Adiposity
Objective: To determine whether rats reaching the same body mass, having been fed either a low-fat (LFD) or a high-fat diet (HFD), differ in white adipose tissue (WAT) deposition. Methods: In experiment 1, 22 Sprague-Dawley rats of the same age were divided into 11 rats with body mass below the batch median and fed a HFD, and 11 above the median and fed a LFD. In experiment 2, 20 Sprague-Dawley rats of the same age and starting body mass were randomised to either a HFD or LFD. When all groups reached similar final body mass, WAT was quantified using magnetic resonance imaging (MRI), dissection, and plasma leptin. Results: In experiment 1, both groups reached similar final body mass at the same age; in experiment 2 the HFD group reached similar final body mass earlier than the LFD group. There were no significant differences in WAT as assessed by MRI or leptin between the HFD and LFD groups in both experiments. Dissection revealed a trend for higher retroperitoneal and epididymal adiposity in the HFD groups in both experiments. Conclusions: We conclude that at similar body mass, adiposity is independent of the macronutrient composition of the feeding regimen used to achieve it. (C) 2014 S Karger GmbH, Freiburg
OBESITY FACTS
10.1159/000368622
25277969
urn:nbn:de:bvb:20-opus-115249
Obesity Facts 2014;7:302–310. DOI: 10.1159/000368622
241592
Alexander D. Miras
Florian Seyfried
Alkystis Phinikaridou
Marcelo E. Andia
Ioannis Christakis
Alan C. Spector
Rene M. Botnar
Carel W. le Roux
eng
uncontrolled
Leptin
eng
uncontrolled
body fat
eng
uncontrolled
induced obesity
eng
uncontrolled
visceral fat
eng
uncontrolled
isocaloric intake
eng
uncontrolled
mass
eng
uncontrolled
tissue
eng
uncontrolled
weight-gain
eng
uncontrolled
metabolism
eng
uncontrolled
expenditure
eng
uncontrolled
accumulation
eng
uncontrolled
High-fat diet
eng
uncontrolled
Low-fat diet
eng
uncontrolled
MRI
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I)
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11524/037_Miras_OBESITY_FACTS.pdf
9661
2013
eng
article
1
--
--
--
High-Resolution Transcriptome Maps Reveal Strain-Specific Regulatory Features of Multiple Campylobacter jejuni Isolates
Campylobacter jejuni is currently the leading cause of bacterial gastroenteritis in humans. Comparison of multiple Campylobacter strains revealed a high genetic and phenotypic diversity. However, little is known about differences in transcriptome organization, gene expression, and small RNA (sRNA) repertoires. Here we present the first comparative primary transcriptome analysis based on the differential RNA–seq (dRNA–seq) of four C. jejuni isolates. Our approach includes a novel, generic method for the automated annotation of transcriptional start sites (TSS), which allowed us to provide genome-wide promoter maps in the analyzed strains. These global TSS maps are refined through the integration of a SuperGenome approach that allows for a comparative TSS annotation by mapping RNA–seq data of multiple strains into a common coordinate system derived from a whole-genome alignment. Considering the steadily increasing amount of RNA–seq studies, our automated TSS annotation will not only facilitate transcriptome annotation for a wider range of pro- and eukaryotes but can also be adapted for the analysis among different growth or stress conditions. Our comparative dRNA–seq analysis revealed conservation of most TSS, but also single-nucleotide-polymorphisms (SNP) in promoter regions, which lead to strain-specific transcriptional output. Furthermore, we identified strain-specific sRNA repertoires that could contribute to differential gene regulation among strains. In addition, we identified a novel minimal CRISPR-system in Campylobacter of the type-II CRISPR subtype, which relies on the host factor RNase III and a trans-encoded sRNA for maturation of crRNAs. This minimal system of Campylobacter, which seems active in only some strains, employs a unique maturation pathway, since the crRNAs are transcribed from individual promoters in the upstream repeats and thereby minimize the requirements for the maturation machinery. Overall, our study provides new insights into strain-specific transcriptome organization and sRNAs, and reveals genes that could modulate phenotypic variation among strains despite high conservation at the DNA level.
PLoS Genetics
10.1371/journal.pgen.1003495
urn:nbn:de:bvb:20-opus-96610
Research Center for Infectious Diseases (ZINF), University of Wuerzburg, Wuerzburg, Germany,
In: PLoS Genetics (2013) 9: 5, doi:10.1371/journal.pgen.1003495
Cynthia M. Sharma
Gaurav Dugar
Alexander Herbig
Konrad U. Förstner
Nadja Heidrich
Richard Reinhardt
Kay Nieselt
eng
uncontrolled
bacterial genomics
eng
uncontrolled
CRISPRs
eng
uncontrolled
genome annotation
eng
uncontrolled
campylobacter
eng
uncontrolled
genomic libraries
eng
uncontrolled
genomic library construction
eng
uncontrolled
sequence motif analysis
eng
uncontrolled
transcriptome analysis
Medizin und Gesundheit
open_access
Institut für Molekulare Infektionsbiologie
Förderzeitraum 2013
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/9661/Sharma_journal.pgen.1003495.pdf
6699
2012
deu
article
1
2013-07-09
--
--
Cover contact graphs
We study problems that arise in the context of covering certain geometric objects called seeds (e.g., points or disks) by a set of other geometric objects called cover (e.g., a set of disks or homothetic triangles). We insist that the interiors of the seeds and the cover elements are pairwise disjoint, respectively, but they can touch. We call the contact graph of a cover a cover contact graph (CCG). We are interested in three types of tasks, both in the general case and in the special case of seeds on a line: (a) deciding whether a given seed set has a connected CCG, (b) deciding whether a given graph has a realization as a CCG on a given seed set, and (c) bounding the sizes of certain classes of CCG’s. Concerning (a) we give efficient algorithms for the case that seeds are points and show that the problem becomes hard if seeds and covers are disks. Concerning (b) we show that this problem is hard even for point seeds and disk covers (given a fixed correspondence between graph vertices and seeds). Concerning (c) we obtain upper and lower bounds on the number of CCG’s for point seeds.
urn:nbn:de:bvb:20-opus-78845
7884
In: Journal of Computational Geometry (2012) 3(1), 102-131; http://jocg.org/index.php/jocg/article/view/66
Nieves Atienza
Natalia de Castro
Carmen Cortés
M. Ángeles Garrido
Clara I. Grima
Gregorio Hernández
Alberto Márquez
Auxiliadora Moreno-González
Martin Nöllenburg
José Ramón Portillo
Pedro Reyes
Jesús Valenzuela
Maria Trinidad Villar
Alexander Wolff
deu
swd
Informatik
Datenverarbeitung; Informatik
open_access
Institut für Informatik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/6699/091_jocg_3_1.pdf
26556
2021
eng
20
22
article
1
2022-04-04
--
--
High mobility group box 1 protein in cerebral thromboemboli
High-mobility group box 1 protein (HMGB1) is a damage-associated molecular pattern (DAMP) involved in neutrophil extracellular trap (NET) formation and thrombosis. NETs are regularly found in cerebral thromboemboli. We here analyzed associated HMGB1 expression in human thromboemboli retrieved via mechanical thrombectomy from 37 stroke patients with large vessel occlusion. HMGB1 was detected in all thromboemboli, accounting for 1.7% (IQR 0.6–6.2%) of the total thromboemboli area and was found to be colocalized with neutrophils and NETs and in spatial proximity to platelets. Correlation analysis revealed that the detection of HMGB1 was strongly related to the number of neutrophils (r = 0.58, p = 0.0002) and platelets (r = 0.51, p = 0.001). Our results demonstrate that HMGB1 is a substantial constituent of thromboemboli causing large vessel occlusion stroke.
International Journal of Molecular Sciences
10.3390/ijms222011276
urn:nbn:de:bvb:20-opus-265568
1422-0067
publish
International Journal of Molecular Sciences (2021) 22:20, 11276. https://doi.org/10.3390/ijms222011276
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Fabian Essig
Lilith Babilon
Christoph Vollmuth
Alexander M. Kollikowski
Mirko Pham
László Solymosi
Karl Georg Haeusler
Peter Kraft
Guido Stoll
Michael K. Schuhmann
eng
uncontrolled
acute ischemic stroke
eng
uncontrolled
thromboemboli
eng
uncontrolled
HMGB1
eng
uncontrolled
neutrophils
eng
uncontrolled
platelets
eng
uncontrolled
immunohistochemistry
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie)
Förderzeitraum 2021
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/26556/ijms-22-11276-v2.pdf
23958
2021
eng
10
13
article
1
--
2021-05-12
--
Factors influencing the adjuvant therapy decision: results of a real-world multicenter data analysis of 904 melanoma patients
Adjuvant treatment of melanoma patients with immune-checkpoint inhibition (ICI) and targeted therapy (TT) significantly improved recurrence-free survival. This study investigates the real-world situation of 904 patients from 13 German skin cancer centers with an indication for adjuvant treatment since the approval of adjuvant ICI and TT. From adjusted log-binomial regression models, we estimated relative risks for associations between various influence factors and treatment decisions (adjuvant therapy yes/no, TT vs. ICI in BRAF mutant patients). Of these patients, 76.9% (95% CI 74–80) opted for a systemic adjuvant treatment. The probability of starting an adjuvant treatment was 26% lower in patients >65 years (RR 0.74, 95% CI 68–80). The most common reasons against adjuvant treatment given by patients were age (29.4%, 95% CI 24–38), and fear of adverse events (21.1%, 95% CI 16–28) and impaired quality of life (11.9%, 95% CI 7–16). Of all BRAF-mutated patients who opted for adjuvant treatment, 52.9% (95% CI 47–59) decided for ICI. Treatment decision for TT or ICI was barely associated with age, gender and tumor stage, but with comorbidities and affiliated center. Shortly after their approval, adjuvant treatments have been well accepted by physicians and patients. Age plays a decisive role in the decision for adjuvant treatment, while pre-existing autoimmune disease and regional differences influence the choice between TT or ICI.
Cancers
2072-6694
10.3390/cancers13102319
urn:nbn:de:bvb:20-opus-239583
2021-06-11T13:00:27+00:00
sword
swordwue
attachment; filename=deposit.zip
7243a460afe95bdf3dec8fbcdb2dccfe
Cancers (2021) 13:10, 2319. https://doi.org/10.3390/cancers13102319
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Georg Lodde
Andrea Forschner
Jessica Hassel
Lena M. Wulfken
Friedegund Meier
Peter Mohr
Katharina Kähler
Bastian Schilling
Carmen Loquai
Carola Berking
Svea Hüning
Kerstin Schatton
Christoffer Gebhardt
Julia Eckardt
Ralf Gutzmer
Lydia Reinhardt
Valerie Glutsch
Ulrike Nikfarjam
Michael Erdmann
Andreas Stang
Bernd Kowall
Alexander Roesch
Selma Ugurel
Lisa Zimmer
Dirk Schadendorf
Elisabeth Livingstone
eng
uncontrolled
melanoma
eng
uncontrolled
adjuvant treatment
eng
uncontrolled
checkpoint blocker
eng
uncontrolled
targeted therapy
eng
uncontrolled
BRAF
eng
uncontrolled
PD-1
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/23958/cancers-13-02319-v2.pdf
19316
2019
eng
2593
11
11
article
1
--
2019-10-28
--
Clinical Characteristics of Inpatients with Childhood vs. Adolescent Anorexia Nervosa
We aimed to compare the clinical data at first presentation to inpatient treatment of children (<14 years) vs. adolescents (≥14 years) with anorexia nervosa (AN), focusing on duration of illness before hospital admission and body mass index (BMI) at admission and discharge, proven predictors of the outcomes of adolescent AN. Clinical data at first admission and at discharge in 289 inpatients with AN (children: n = 72; adolescents: n = 217) from a German multicenter, web-based registry for consecutively enrolled patients with childhood and adolescent AN were analyzed. Inclusion criteria were a maximum age of 18 years, first inpatient treatment due to AN, and a BMI <10th BMI percentile at admission. Compared to adolescents, children with AN had a shorter duration of illness before admission (median: 6.0 months vs. 8.0 months, p = 0.004) and higher BMI percentiles at admission (median: 0.7 vs. 0.2, p = 0.004) as well as at discharge (median: 19.3 vs. 15.1, p = 0.011). Thus, in our study, children with AN exhibited clinical characteristics that have been associated with better outcomes, including higher admission and discharge BMI percentile. Future studies should examine whether these factors are actually associated with positive long-term outcomes in children.
Nutrients
2072-6643
10.3390/nu11112593
urn:nbn:de:bvb:20-opus-193160
Nutrients 2019, 11(11), 2593; https://doi.org/10.3390/nu11112593
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Charlotte Jaite
Katharina Bühren
Brigitte Dahmen
Astrid Dempfle
Katja Becker
Christoph U. Correll
Karin M. Egberts
Stefan Ehrlich
Christian Fleischhaker
Alexander von Gontard
Freia Hahn
David Kolar
Michael Kaess
Tanja Legenbauer
Tobias J. Renner
Ulrike Schulze
Judith Sinzig
Ellen Thomae
Linda Weber
Ida Wessing
Gisela Antony
Johannes Hebebrand
Manuel Föcker
Beate Herpertz-Dahlmann
eng
uncontrolled
anorexia nervosa
eng
uncontrolled
children
eng
uncontrolled
adolescents
eng
uncontrolled
clinical characteristics
eng
uncontrolled
BMI
eng
uncontrolled
outcome
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/19316/nutrients-11-02593.pdf
22504
2019
eng
1-13
150
9
article
1
2021-02-17
--
--
A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders
Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (r(g) approximate to 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We (h(SNP)(2)) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and estimated the variance in therapy outcomes that could be explained by common genetic variants learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h(SNP)(2) could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.
Translational Psychiatry
10.1038/s41398-019-0481-y
urn:nbn:de:bvb:20-opus-225048
publish
Translational Psychiatry (2019) 9:150
true
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Christopher Rayner
Jonathan R. I. Coleman
Kirstin L. Purves
John Hodsoll
Kimberley Goldsmith
Georg W. Alpers
Evelyn Andersson
Volker Arolt
Julia Boberg
Susan Bögels
Cathy Creswell
Peter Cooper
Charles Curtis
Jürgen Deckert
Katharina Domschke
Samir El Alaoui
Lydia Fehm
Thomas Fydrich
Alexander L. Gerlach
Anja Grocholewski
Kurt Hahlweg
Alfons Hamm
Erik Hedman
Einar R. Heiervang
Jennifer L. Hudson
Peter Jöhren
Robert Keers
Tilo Kircher
Thomas Lang
Catharina Lavebratt
Sang-hyuck Lee
Kathryn J. Lester
Nils Lindefors
Jürgen Margraf
Maaike Nauta
Christiane A. Pané-Farré
Paul Pauli
Ronald M. Rapee
Andreas Reif
Winfried Rief
Susanna Roberts
Martin Schalling
Silvia Schneider
Wendy K. Silverman
Andreas Ströhle
Tobias Teismann
Mikael Thastum
Andre Wannemüller
Heike Weber
Hans-Ulrich Wittchen
Christiane Wolf
Christian Rück
Gerome Breen
Thalia C. Eley
eng
uncontrolled
Human behaviour
eng
uncontrolled
Personalized medicine
eng
uncontrolled
Prognostic markers
eng
uncontrolled
Psychiatric disorders
Psychologie
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Institut für Psychologie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/22504/A_genome-wide_association.pdf
25015
2021
eng
12
12
article
1
--
2021-11-30
--
Water availability controls the biomass increment of Melia dubia in South India
Farmland tree cultivation is considered an important option for enhancing wood production. In South India, the native leaf-deciduous tree species Melia dubia is popular for short-rotation plantations. Across a rainfall gradient from 420 to 2170 mm year\(^{–1}\), we studied 186 farmland woodlots between one and nine years in age. The objectives were to identify the main factors controlling aboveground biomass (AGB) and growth rates. A power-law growth model predicts an average stand-level AGB of 93.8 Mg ha\(^{–1}\) for nine-year-old woodlots. The resulting average annual AGB increment over the length of the rotation cycle is 10.4 Mg ha\(^{–1}\) year\(^{–1}\), which falls within the range reported for other tropical tree plantations. When expressing the parameters of the growth model as functions of management, climate and soil variables, it explains 65% of the variance in AGB. The results indicate that water availability is the main driver of the growth of M. dubia. Compared to the effects of water availability, the effects of soil nutrients are 26% to 60% smaller. We conclude that because of its high biomass accumulation rates in farm forestry, M. dubia is a promising candidate for short-rotation plantations in South India and beyond.
Forests
1999-4907
10.3390/f12121675
urn:nbn:de:bvb:20-opus-250150
2021-12-01T17:28:19+00:00
sword
swordwue
attachment; filename=deposit.zip
739b4d6102266dbd3cbf90424563ffad
Forests (2021) 12:12, 1675. https://doi.org/10.3390/f12121675
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Alexander Röll
Mundre N. Ramesha
Roman M. Link
Dietrich Hertel
Bernhard Schuldt
Shekhargouda L. Patil
Dirk Hölscher
eng
uncontrolled
aboveground biomass
eng
uncontrolled
climatological water deficit
eng
uncontrolled
farm forestry
eng
uncontrolled
farmland woodlots
eng
uncontrolled
rainfall gradient
eng
uncontrolled
soil
eng
uncontrolled
wood production
Pflanzen (Botanik)
open_access
Julius-von-Sachs-Institut für Biowissenschaften
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/25015/forests-12-01675-v2.pdf
26671
2021
eng
2287–2294
12
141
article
1
--
--
--
An insert with less than spherical medial conformity causes a loss of passive internal rotation after calipered kinematically aligned TKA
Introduction
In total knee arthroplasty (TKA), the level of conformity, a medial stabilized (MS) implant, needs to restore native (i.e., healthy) knee kinematics without over-tensioning the flexion space when the surgeon chooses to retain the posterior cruciate ligament (PCL) is unknown. Whether an insert with a medial ball-in-socket conformity and lateral flat surface like the native knee or a less than spherical medial conformity restores higher and closer to native internal tibial rotation without anterior lift-off, an over-tension indicator, when implanted with calipered kinematic alignment (KA), is unknown.
Methods and Materials
Two surgeons treated 21 patients with calipered KA and a PCL retaining MS implant. Validated verification checks that restore native tibial compartment forces in passive flexion without release of healthy ligaments were used to select the optimal insert thickness. A goniometer etched onto trial inserts with the ball-in-socket and the less than spherical medial conformity measured the tibial rotation relative to the femoral component at extension and 90° and 120° flexion. The surgeon recorded the incidence of anterior lift-off of the insert.
Results
The insert with the medial ball-in-socket and lateral flat surface restored more internal tibial rotation than the one with less than spherical medial conformity, with mean values of 19° vs. 17° from extension to 90° flexion (p < 0.01), and 23° vs. 20°-120° flexion (p < 0.002), respectively. There was no anterior lift-off of the insert at 90° and 120° flexion.
Conclusion
An MS insert with a medial ball-in-socket and lateral flat surface that matches the native knee's spherical conformity restores native tibial internal rotation when implanted with calipered KA and PCL retention without over-tensioning the flexion space.
Archives of Orthopaedic and Trauma Surgery
1434-3916
10.1007/s00402-021-04054-0
34264381
urn:nbn:de:bvb:20-opus-266710
publish
Archives of Orthopaedic and Trauma Surgery 2021, 141(12): 10.1007/s00402-021-04054-0
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Alexander J. Nedopil
Adithya Shekhar
Stephen M. Howell
Maury L. Hull
eng
uncontrolled
calipered
eng
uncontrolled
medial stabilized
eng
uncontrolled
spherical
eng
uncontrolled
conforming
eng
uncontrolled
insert
eng
uncontrolled
rotation
eng
uncontrolled
total knee arthroplasty
eng
uncontrolled
total knee replacement
eng
uncontrolled
kinematic alignment
Medizin und Gesundheit
open_access
Lehrstuhl für Orthopädie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/26671/Nedopil_Archives.pdf
17182
2017
eng
2
12
article
1
2018-11-15
--
--
Local versus global aortic pulse wave velocity in early atherosclerosis: An animal study in ApoE\(^{-/-}\) mice using ultrahigh field MRI
Increased aortic stiffness is known to be associated with atherosclerosis and has a predictive value for cardiovascular events. This study aims to investigate the local distribution of early arterial stiffening due to initial atherosclerotic lesions. Therefore, global and local pulse wave velocity (PWV) were measured in ApoE\(^{-/-}\) and wild type (WT) mice using ultrahigh field MRI. For quantification of global aortic stiffness, a new multi-point transit-time (TT) method was implemented and validated to determine the global PWV in the murine aorta. Local aortic stiffness was measured by assessing the local PWV in the upper abdominal aorta, using the flow/area (QA) method. Significant differences between age matched ApoE\(^{-/-}\) and WT mice were determined for global and local PWV measurements (global PWV: ApoE\(^{-/-}\): 2.7 ±0.2m/s vs WT: 2.1±0.2m/s, P<0.03; local PWV: ApoE\(^{-/-}\): 2.9±0.2m/s vs WT: 2.2±0.2m/s, P<0.03). Within the WT mouse group, the global PWV correlated well with the local PWV in the upper abdominal aorta (R\(^2\) = 0.75, P<0.01), implying a widely uniform arterial elasticity.
In ApoE\(^{-/-}\) animals, however, no significant correlation between individual local and global PWV was present (R\(^2\) = 0.07, P = 0.53), implying a heterogeneous distribution of vascular stiffening in early atherosclerosis. The assessment of global PWV using the new multi-point TT measurement technique was validated against a pressure wire measurement in a vessel
phantom and showed excellent agreement. The experimental results demonstrate that vascular stiffening caused by early atherosclerosis is unequally distributed over the length of large vessels. This finding implies that assessing heterogeneity of arterial stiffness by multiple local measurements of PWV might be more sensitive than global PWV to identify early atherosclerotic lesions.
PLoS ONE
10.1371/journal.pone.0171603
28207773
urn:nbn:de:bvb:20-opus-171824
PLoS ONE (2017) 12(2): e0171603. https://doi.org/10.1371/journal.pone.0171603
true
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Alexander Gotschy
Wolfgang R. Bauer
Patrick Winter
Peter Nordbeck
Eberhard Rommel
Peter M. Jakob
Volker Herold
eng
uncontrolled
MRI
eng
uncontrolled
Atherosclerosis
eng
uncontrolled
Aorta
eng
uncontrolled
Stiffness
eng
uncontrolled
Measurement
eng
uncontrolled
Time measurement
eng
uncontrolled
Magnetic resonance imaging
eng
uncontrolled
Mouse models
eng
uncontrolled
Systole
Medizin und Gesundheit
open_access
Physikalisches Institut
Medizinische Klinik und Poliklinik I
Deutsches Zentrum für Herzinsuffizienz (DZHI)
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17182/Gotschy_pone.0171603.pdf
17347
2017
eng
7
article
1
2018-12-03
--
--
miR-16 and miR-103 impact 5-HT4 receptor signalling and correlate with symptom profile in irritable bowel syndrome
Irritable bowel syndrome (IBS) is a gut-brain disorder involving alterations in intestinal sensitivity and motility. Serotonin 5-HT4 receptors are promising candidates in IBS pathophysiology since they regulate gut motor function and stool consistency, and targeted 5-HT4R selective drug intervention has been proven beneficial in subgroups of patients. We identified a single nucleotide polymorphism (SNP) (rs201253747) c.*61 T > C within the 5-HT4 receptor gene \(HTR4\) to be predominantly present in diarrhoea-IBS patients (IBS-D). It affects a binding site for the miR-16 family and miR-103/miR-107 within the isoforms \({HTR4b/i}\) and putatively impairs \(HTR4\) expression. Subsequent miRNA profiling revealed downregulation of miR-16 and miR-103 in the jejunum of IBS-D patients correlating with symptoms. \(In\) \(vitro\) assays confirmed expression regulation via three 3′UTR binding sites. The novel isoform \(HTR4b\_2\) lacking two of the three miRNA binding sites escapes miR-16/103/107 regulationin SNP carriers. We provide the first evidence that \(HTR4\) expression is fine-tuned by miRNAs, and that this regulation is impaired either by the SNP c.*61 T > C or bydiminished levels of miR-16 and miR-103 suggesting that \(HTR4\) might be involved in the development of IBS-D.
Scientific Reports
10.1038/s41598-017-13982-0
29089619
urn:nbn:de:bvb:20-opus-173478
Scientific Reports (2017) 7:14680. https://doi.org/10.1038/s41598-017-13982-0
true
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Carolin Wohlfarth
Stefanie Schmitteckert
Janina D. Härtle
Lesley A. Houghton
Harsh Dweep
Marina Fortea
Ghazaleh Assadi
Alexander Braun
Tanja Mederer
Sarina Pöhner
Philip P. Becker
Christine Fischer
Martin Granzow
Hubert Mönnikes
Emeran A. Mayer
Gregory Sayuk
Guy Boeckxstaens
Mira M. Wouters
Magnus Simrén
Greger Lindberg
Bodil Ohlsson
Peter Thelin Schmidt
Aldona Dlugosz
Lars Agreus
Anna Andreasson
Mauro D'Amato
Barbara Burwinkel
Justo Lorenzo Bermejo
Ralph Röth
Felix Lasitschka
Maria Vicario
Marco Metzger
Javier Santos
Gudrun A. Rappold
Cristina Martinez
Beate Niesler
eng
uncontrolled
Medicine
eng
uncontrolled
Gene regulation
eng
uncontrolled
Irritable bowel syndrome
Medizin und Gesundheit
open_access
Lehrstuhl für Tissue Engineering und Regenerative Medizin
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17347/Wohlfahrt_s41598-017-13982-0.pdf
16550
2016
eng
11626
7
article
1
2018-07-24
--
--
Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells
Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein–kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells. Immune activation by FXII is mediated by dendritic cells in a CD87-dependent manner and involves alterations in intracellular cyclic AMP formation. Our study demonstrates that a member of the plasmatic coagulation cascade is a key mediator of autoimmunity. FXII inhibition may provide a strategy to combat MS and other immune-related disorders.
Nature Communications
10.1038/ncomms11626
urn:nbn:de:bvb:20-opus-165503
Nature Communications, 2015, 7:11626. DOI: 10.1038/ncomms11626
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Kerstin Göbel
Susann Pankratz
Chloi-Magdalini Asaridou
Alexander M. Herrmann
Stefan Bittner
Monika Merker
Tobias Ruck
Sarah Glumm
Friederike Langhauser
Peter Kraft
Thorsten F. Krug
Johanna Breuer
Martin Herold
Catharina C. Gross
Denise Beckmann
Adelheid Korb-Pap
Michael K. Schuhmann
Stefanie Kuerten
Ioannis Mitroulis
Clemens Ruppert
Marc W. Nolte
Con Panousis
Luisa Klotz
Beate Kehrel
Thomas Korn
Harald F. Langer
Thomas Pap
Bernhard Nieswandt
Heinz Wiendl
Triantafyllos Chavakis
Christoph Kleinschnitz
Sven G. Meuth
eng
uncontrolled
blood coagulation
eng
uncontrolled
factor XII
eng
uncontrolled
neuroinflammation
eng
uncontrolled
dendric cells
Biowissenschaften; Biologie
Medizin und Gesundheit
open_access
Institut für Anatomie und Zellbiologie
Neurologische Klinik und Poliklinik
Rudolf-Virchow-Zentrum
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16550/Goebel_Nature_Communications.pdf
26209
2022
eng
2
12
article
1
--
2022-02-18
--
Excellent and good results treating stiffness with early and late manipulation after unrestricted caliper-verified kinematically aligned TKA
Manipulation under anesthesia (MUA) for stiffness within 6 to 12 weeks after mechanically aligned total knee arthroplasty (TKA) generally yields better outcome scores than an MUA performed later. However, the timing of MUA after unrestricted, caliper-verified, kinematically aligned (KA) TKA remains uncertain. A retrospective review identified 82 of 3558 (2.3%) KA TKA patients treated with an MUA between 2010 and 2017. Thirty patients treated with an MUA within 3 months of the TKA (i.e., early) and 24 in the late group (i.e., >3 months) returned a questionnaire after a mean of 6 years and 5 years, respectively. Mean outcome scores for the early vs. late group were 78 vs. 62 for the Forgotten Joint Score (FJS) (p = 0.023) and 42 vs. 39 for the Oxford Knee Score (OKS) (p = 0.037). Subjectively, the early vs. late group responses indicated that 83% vs. 67% walked without a limp, 73% vs. 54% had normal extension, and 43% vs. 25% had normal flexion. An MUA within 3 months after unrestricted KA TKA provided excellent FJS and OKS at final follow-up relative to a late MUA. A late MUA performed after 3 months is worth consideration because of the good FJS and OKS scores, albeit with a risk of a persistent limp and limitation in knee extension and flexion.
Journal of Personalized Medicine
2075-4426
10.3390/jpm12020304
urn:nbn:de:bvb:20-opus-262094
2022-03-28T07:39:31+00:00
sword
swordwue
attachment; filename=deposit.zip
2d7f415971e00d29020e8d7debe23d82
Journal of Personalized Medicine (2022) 12:2, 304. https://doi.org/10.3390/jpm12020304
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Adithya Shekhar
Stephen M. Howell
Alexander J. Nedopil
Maury L. Hull
eng
uncontrolled
reoperation
eng
uncontrolled
revision
eng
uncontrolled
implant survival
eng
uncontrolled
forgotten joint score
eng
uncontrolled
Oxford knee score
Medizin und Gesundheit
open_access
Lehrstuhl für Orthopädie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/26209/jpm-12-00304.pdf
17309
2015
eng
e0131456
7
10
article
1
2018-11-28
--
--
Analysis of a multi-component multi-stage malaria vaccine candidate—tackling the cocktail challenge
Combining key antigens from the different stages of the P. falciparum life cycle in the context of a multi-stage-specific cocktail offers a promising approach towards the development of a malaria vaccine ideally capable of preventing initial infection, the clinical manifestation as well as the transmission of the disease. To investigate the potential of such an approach we combined proteins and domains (11 in total) from the pre-erythrocytic, blood and sexual stages of P. falciparum into a cocktail of four different components recombinantly produced in plants. After immunization of rabbits we determined the domain-specific antibody titers as well as component-specific antibody concentrations and correlated them with stage specific in vitro efficacy. Using purified rabbit immune IgG we observed strong inhibition in functional in vitro assays addressing the pre-erythrocytic (up to 80%), blood (up to 90%) and sexual parasite stages (100%). Based on the component-specific antibody concentrations we calculated the IC50 values for the pre-erythrocytic stage (17–25 μg/ml), the blood stage (40–60 μg/ml) and the sexual stage (1.75 μg/ml). While the results underline the feasibility of a multi-stage vaccine cocktail, the analysis of component-specific efficacy indicates significant differences in IC50 requirements for stage-specific antibody concentrations providing valuable insights into this complex scenario and will thereby improve future approaches towards malaria vaccine cocktail development regarding the selection of suitable antigens and the ratios of components, to fine tune overall and stage-specific efficacy.
PLoS ONE
10.1371/journal.pone.0131456
urn:nbn:de:bvb:20-opus-173092
PLoS ONE 10(7): e0131456 (2015). DOI: 10.1371/journal.pone.0131456
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Alexander Boes
Holger Spiegel
Nadja Voepel
Gueven Edgue
Veronique Beiss
Stephanie Kapelski
Rolf Fendel
Matthias Scheuermayer
Gabriele Pradel
Judith M. Bolscher
Marije C. Behet
Koen J. Dechering
Cornelus C. Hermsen
Robert W. Sauerwein
Stefan Schillberg
Andreas Reimann
Rainer Fischer
eng
uncontrolled
malaria
eng
uncontrolled
vaccines
eng
uncontrolled
antibodies
eng
uncontrolled
P. falciparum
Krankheiten
open_access
Institut für Molekulare Infektionsbiologie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17309/084_Boes_PLoS_ONE.PDF
26529
2022
eng
948–957
3
30
article
1
--
--
--
Reoperations are few and confined to the most valgus phenotypes 4 years after unrestricted calipered kinematically aligned TKA
Purpose
The present study determined the postoperative phenotypes after unrestricted calipered kinematically aligned (KA) total knee arthroplasty (TKA), whether any phenotypes were associated with reoperation, implant revision, and lower outcome scores at 4 years, and whether the proportion of TKAs within each phenotype was comparable to those of the nonarthritic contralateral limb.
Methods
From 1117 consecutive primary TKAs treated by one surgeon with unrestricted calipered KA, an observer identified all patients (N = 198) that otherwise had normal paired femora and tibiae on a long-leg CT scanogram. In both legs, the distal femur–mechanical axis angle (FMA), proximal tibia–mechanical axis angle (TMA), and the hip–knee–ankle angle (HKA) were measured. Each alignment angle was assigned to one of Hirschmann’s five FMA, five TMA, and seven HKA phenotype categories.
Results
Three TKAs (1.5%) underwent reoperation for anterior knee pain or patellofemoral instability in the subgroup of patients with the more valgus phenotypes. There were no implant revisions for component loosening, wear, or tibiofemoral instability. The median Forgotten Joint Score (FJS) was similar between phenotypes. The median Oxford Knee Score (OKS) was similar between the TMA and HKA phenotypes and greatest in the most varus FMA phenotype. The phenotype proportions after calipered KA TKA were comparable to the contralateral leg.
Conclusion
Unrestricted calipered KA’s restoration of the wide range of phenotypes did not result in implant revision or poor FJS and OKS scores at a mean follow-up of 4 years. The few reoperated patients had a more valgus setting of the prosthetic trochlea than recommended for mechanical alignment. Designing a femoral component specifically for KA that restores patellofemoral kinematics with all phenotypes, especially the more valgus ones, is a strategy for reducing reoperation risk.
Knee Surgery, Sports Traumatology, Arthroscopy
10.1007/s00167-021-06473-3
urn:nbn:de:bvb:20-opus-265291
publish
Knee Surgery, Sports Traumatology, Arthroscopy 2022, 30(3):948–957. DOI: 10.1007/s00167-021-06473-3
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Stephen M. Howell
Manpreet Gill
Trevor J. Shelton
Alexander J. Nedopil
eng
uncontrolled
phenotype
eng
uncontrolled
total knee arthroplasty
eng
uncontrolled
total knee replacement
eng
uncontrolled
kinematic alignment
eng
uncontrolled
calipered
eng
uncontrolled
reoperation
Medizin und Gesundheit
open_access
Lehrstuhl für Orthopädie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/26529/Howell_Knee.pdf
20101
2019
eng
397
38
article
1
2020-03-10
--
--
IFN-gamma-induced PD-L1 expression in melanoma depends on p53 expression
Background
Immune checkpoint inhibition and in particular anti-PD-1 immunotherapy have revolutionized the treatment of advanced melanoma. In this regard, higher tumoral PD-L1 protein (gene name: CD274) expression is associated with better clinical response and increased survival to anti-PD-1 therapy. Moreover, there is increasing evidence that tumor suppressor proteins are involved in immune regulation and are capable of modulating the expression of immune checkpoint proteins. Here, we determined the role of p53 protein (gene name: TP53) in the regulation of PD-L1 expression in melanoma.
Methods
We analyzed publicly available mRNA and protein expression data from the cancer genome/proteome atlas and performed immunohistochemistry on tumors with known TP53 status. Constitutive and IFN-ɣ-induced PD-L1 expression upon p53 knockdown in wildtype, TP53-mutated or JAK2-overexpressing melanoma cells or in cells, in which p53 was rendered transcriptionally inactive by CRISPR/Cas9, was determined by immunoblot or flow cytometry. Similarly, PD-L1 expression was investigated after overexpression of a transcriptionally-impaired p53 (L22Q, W23S) in TP53-wt or a TP53-knockout melanoma cell line. Immunoblot was applied to analyze the IFN-ɣ signaling pathway.
Results
For TP53-mutated tumors, an increased CD274 mRNA expression and a higher frequency of PD-L1 positivity was observed. Interestingly, positive correlations of IFNG mRNA and PD-L1 protein in both TP53-wt and -mutated samples and of p53 and PD-L1 protein suggest a non-transcriptional mode of action of p53. Indeed, cell line experiments revealed a diminished IFN-ɣ-induced PD-L1 expression upon p53 knockdown in both wildtype and TP53-mutated melanoma cells, which was not the case when p53 wildtype protein was rendered transcriptionally inactive or by ectopic expression of p53\(^{L22Q,W23S}\), a transcriptionally-impaired variant, in TP53-wt cells. Accordingly, expression of p53\(^{L22Q,W23S}\) in a TP53-knockout melanoma cell line boosted IFN-ɣ-induced PD-L1 expression. The impaired PD-L1-inducibility after p53 knockdown was associated with a reduced JAK2 expression in the cells and was almost abrogated by JAK2 overexpression.
Conclusions
While having only a small impact on basal PD-L1 expression, both wildtype and mutated p53 play an important positive role for IFN-ɣ-induced PD-L1 expression in melanoma cells by supporting JAK2 expression. Future studies should address, whether p53 expression levels might influence response to anti-PD-1 immunotherapy.
Journal of Experimental & Clinical Cancer Research
10.1186/s13046-019-1403-9
urn:nbn:de:bvb:20-opus-201016
Journal of Experimental & Clinical Cancer Research (2019) 38:397. https://doi.org/10.1186/s13046-019-1403-9
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Alexander Thiem
Sonja Hesbacher
Hermann Kneitz
Teresa di Primio
Markus V. Heppt
Heike M. Hermanns
Matthias Goebeler
Svenja Meierjohann
Roland Houben
David Schrama
eng
uncontrolled
Melanoma
eng
uncontrolled
PD-L1
eng
uncontrolled
CD274
eng
uncontrolled
p53
eng
uncontrolled
TP53
eng
uncontrolled
JAK2
Medizin und Gesundheit
open_access
Theodor-Boveri-Institut für Biowissenschaften
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Medizinische Klinik und Poliklinik II
Förderzeitraum 2019
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/20101/Thiem_JournalOfExperimental&ClinicalCancerResearch__2019.pdf
21245
2020
eng
14
article
1
--
--
--
Diabetic Polyneuropathy Is Associated With Pathomorphological Changes in Human Dorsal Root Ganglia: A Study Using 3T MR Neurography
Diabetic neuropathy (DPN) is one of the most severe and yet most poorly understood complications of diabetes mellitus. In vivo imaging of dorsal root ganglia (DRG), a key structure for the understanding of DPN, has been restricted to animal studies. These have shown a correlation of decreased DRG volume with neuropathic symptom severity. Our objective was to investigate correlations of DRG morphology and signal characteristics at 3 Tesla (3T) magnetic resonance neurography (MRN) with clinical and serological data in diabetic patients with and without DPN. In this cross-sectional study, participants underwent 3T MRN of both L5 DRG using an isotropic 3D T2-weighted, fat-suppressed sequence with subsequent segmentation of DRG volume and analysis of normalized signal properties. Overall, 55 diabetes patients (66 ± 9 years; 32 men; 30 with DPN) took part in this study. DRG volume was smaller in patients with severe DPN when compared to patients with mild or moderate DPN (134.7 ± 21.86 vs 170.1 ± 49.22; p = 0.040). In DPN patients, DRG volume was negatively correlated with the neuropathy disability score (r = −0.43; 95%CI = −0.66 to −0.14; p = 0.02), a measure of neuropathy severity. DRG volume showed negative correlations with triglycerides (r = −0.40; 95%CI = −0.57 to −0.19; p = 0.006), and LDL cholesterol (r = −0.33; 95%CI = −0.51 to −0.11; p = 0.04). There was a strong positive correlation of normalized MR signal intensity (SI) with the neuropathy symptom score in the subgroup of patients with painful DPN (r = 0.80; 95%CI = 0.46 to 0.93; p = 0.005). DRG SI was positively correlated with HbA1c levels (r = 0.30; 95%CI = 0.09 to 0.50; p = 0.03) and the triglyceride/HDL ratio (r = 0.40; 95%CI = 0.19 to 0.57; p = 0.007). In this first in vivo study, we found DRG morphological degeneration and signal increase in correlation with neuropathy severity. This elucidates the potential importance of MR-based DRG assessments in studying structural and functional changes in DPN.
Frontiers in Neuroscience
10.3389/fnins.2020.570744
urn:nbn:de:bvb:20-opus-212459
swordwue
2020-10-01T19:52:37+00:00
attachment; filename=deposit.zip
d31996ce6a428ff2f5a34862fbadcfe2
Frontiers in Neuroscience 2020, 14:570744. DOI: 10.3389/fnins.2020.570744
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Johann M. E. Jende
Zoltan Kender
Christian Rother
Lucia Alvarez-Ramos
Jan B. Groener
Mirko Pham
Jakob Morgenstern
Dimitrios Oikonomou
Artur Hahn
Alexander Juerchott
Jennifer Kollmer
Sabine Heiland
Stefan Kopf
Peter P. Nawroth
Martin Bendszus
Felix T. Kurz
eng
uncontrolled
diabetic polyneuropathy
eng
uncontrolled
dorsal root ganglion
eng
uncontrolled
magnetic resonance neurography
eng
uncontrolled
neuropathic pain
eng
uncontrolled
peripheral nervous system
Medizin und Gesundheit
open_access
Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie)
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/21245/fnins-14-570744.pdf
18661
2016
eng
2499-2504
12
263
article
1
2019-08-30
--
--
Importance of cerebrospinal fluid analysis in the era of McDonald 2010 criteria: a German-Austrian retrospective multicenter study in patients with a clinically isolated syndrome
The majority of patients presenting with a first clinical symptom suggestive of multiple sclerosis (MS) do not fulfill the MRI criteria for dissemination in space and time according to the 2010 revision of the McDonald diagnostic criteria for MS and are thus classified as clinically isolated syndrome (CIS). To re-evaluate the utility of cerebrospinal fluid (CSF) analysis in the context of the revised McDonald criteria from 2010, we conducted a retrospective multicenter study aimed at determining the prevalence and predictive value of oligoclonal IgG bands (OCBs) in patients with CIS. Patients were recruited from ten specialized MS centers in Germany and Austria. We collected data from 406 patients; at disease onset, 44/406 (11 %) fulfilled the McDonald 2010 criteria for MS. Intrathecal IgG OCBs were detected in 310/362 (86 %) of CIS patients. Those patients were twice as likely to convert to MS according to McDonald 2010 criteria as OCB-negative individuals (hazard ratio = 2.1, p = 0.0014) and in a shorter time period of 25 months (95 % CI 21-34) compared to 47 months in OCB-negative individuals (95 % CI 36-85). In patients without brain lesions at first attack and presence of intrathecal OCBs (30/44), conversion rate to MS was 60 % (18/30), whereas it was only 21 % (3/14) in those without OCBs. Our data confirm that in patients with CIS the risk of conversion to MS substantially increases if OCBs are present at onset. CSF analysis definitely helps to evaluate the prognosis in patients who do not have MS according to the revised McDonald criteria.
Journal of Neurology
10.1007/s00415-016-8302-1
urn:nbn:de:bvb:20-opus-186619
Journal of Neurology (2016) 263:12, 2499-2504. https://doi.10.1007/s00415-016-8302-1
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
André M. Huss
Steffen Halbgebauer
Patrick Öckl
Corinna Trebst
Annette Spreer
Nadja Borisow
Andrea Harrer
Isabel Brecht
Bettina Balint
Oliver Stich
Sabine Schlegel
Nele Retzlaff
Alexander Winkelmann
Romy Roesler
Florian Lauda
Özlem Yildiz
Elke Voß
Rainer Muche
Sebastian Rauer
Florian Then Bergh
Markus Otto
Friedemann Paul
Brigitte Wildemann
Jörg Kraus
Klemens Ruprecht
Martin Stangel
Mathias Buttmann
Uwe K. Zettl
Hayrettin Tumani
eng
uncontrolled
multiple sklerosis
eng
uncontrolled
MRI criteria
eng
uncontrolled
conversion
eng
uncontrolled
MS
eng
uncontrolled
CSF
eng
uncontrolled
biomarker
eng
uncontrolled
OCB
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/18661/Huss_JournalOfNeurology_2016.pdf
24099
2021
eng
6
11
article
1
--
2021-06-04
--
Restoring the patient's pre-arthritic posterior slope is the correct target for maximizing internal tibial rotation when implanting a PCL retaining TKA with calipered kinematic alignment
Introduction: The calipered kinematically-aligned (KA) total knee arthroplasty (TKA) strives to restore the patient's individual pre-arthritic (i.e., native) posterior tibial slope when retaining the posterior cruciate ligament (PCL). Deviations from the patient's individual pre-arthritic posterior slope tighten and slacken the PCL in flexion that drives tibial rotation, and such a change might compromise passive internal tibial rotation and coupled patellofemoral kinematics. Methods: Twenty-one patients were treated with a calipered KA TKA and a PCL retaining implant with a medial ball-in-socket and a lateral flat articular insert conformity that mimics the native (i.e., healthy) knee. The slope of the tibial resection was set parallel to the medial joint line by adjusting the plane of an angel wing inserted in the tibial guide. Three trial inserts that matched and deviated 2°> and 2°< from the patient's pre-arthritic slope were 3D printed with goniometric markings. The goniometer measured the orientation of the tibia (i.e., trial insert) relative to the femoral component. Results: There was no difference between the radiographic preoperative and postoperative tibial slope (0.7 ± 3.2°, NS). From extension to 90° flexion, the mean passive internal tibial rotation with the pre-arthritic slope insert of 19° was greater than the 15° for the 2°> slope (p < 0.000), and 15° for the 2°< slope (p < 0.000). Discussion: When performing a calipered KA TKA with PCL retention, the correct target for setting the tibial component is the patient's individual pre-arthritic slope within a tolerance of ±2°, as this target resulted in a 15–19° range of internal tibial rotation that is comparable to the 15–18° range reported for the native knee from extension to 90° flexion.
Journal of Personalized Medicine
2075-4426
10.3390/jpm11060516
urn:nbn:de:bvb:20-opus-240996
2021-07-03T16:18:34+00:00
sword
swordwue
attachment; filename=deposit.zip
0866a82843acbc233f18d1bd68e092d4
Journal of Personalized Medicine (2021) 11:6, 516. https://doi.org/10.3390/jpm11060516
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Alexander J. Nedopil
Connor Delman
Stephen M. Howell
Maury L. Hull
eng
uncontrolled
total knee replacement
eng
uncontrolled
total knee arthroplasty
eng
uncontrolled
kinematic alignment
eng
uncontrolled
slope
eng
uncontrolled
rotation
Medizin und Gesundheit
open_access
Lehrstuhl für Orthopädie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/24099/jpm-11-00516.pdf
31233
2023
eng
13
29
article
1
--
--
--
IR/UV Double Resonance Study of the 2‐Phenylallyl Radical and its Pyrolysis Products
Isolated 2‐phenylallyl radicals (2‐PA), generated by pyrolysis from a nitrite precursor, have been investigated by IR/UV ion dip spectroscopy using free electron laser radiation. 2‐PA is a resonance‐stabilized radical that is considered to be involved in the formation of polycyclic aromatic hydrocarbons (PAH) in combustion, but also in interstellar space. The radical is identified based on its gas‐phase IR spectrum. Furthermore, a number of bimolecular reaction products are identified, showing that the self‐reaction as well as reactions with unimolecular decomposition products of 2‐PA form several PAH efficiently. Possible mechanisms are discussed and the chemistry of 2‐PA is compared with the one of the related 2‐methylallyl and phenylpropargyl radicals.
Chemistry – A European Journal
10.1002/chem.202202943
urn:nbn:de:bvb:20-opus-312338
2023-04-19T20:24:48+00:00
sword
swordwue
attachment; filename=deposit.zip
3d03d6496cd46bafe92890439692fb85
Chemistry – A European Journal 2023, 29(13):e202202943. DOI: 10.1002/chem.202202943
654148
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Tobias Preitschopf
Floriane Sturm
Iuliia Stroganova
Alexander K. Lemmens
Anouk M. Rijs
Ingo Fischer
eng
uncontrolled
free electron laser
eng
uncontrolled
free jet
eng
uncontrolled
IR spectroscopy
eng
uncontrolled
PAH formation
eng
uncontrolled
radical reactions
Chemie und zugeordnete Wissenschaften
open_access
Institut für Physikalische und Theoretische Chemie
OpenAIRE
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/31233/Preitschopf_Chemistry.pdf
20255
2020
eng
1-16
1
10
article
1
2020-04-01
--
--
\(^{18}\)F-labeled, PSMA-targeted radiotracers: leveraging the advantages of radiofluorination for prostate cancer molecular imaging
Prostate-specific membrane antigen (PSMA)-targeted PET imaging for prostate cancer with \(^{68}\)Ga-labeled compounds has rapidly become adopted as part of routine clinical care in many parts of the world. However, recent years have witnessed the start of a shift from \(^{68}\)Ga- to \(^{18}\)F-labeled PSMA-targeted compounds. The latter imaging agents have several key advantages, which may lay the groundwork for an even more widespread adoption into the clinic. First, facilitated delivery from distant suppliers expands the availability of PET radiopharmaceuticals in smaller hospitals operating a PET center but lacking the patient volume to justify an onsite \(^{68}\)Ge/\(^{68}\)Ga generator. Thus, such an approach meets the increasing demand for PSMA-targeted PET imaging in areas with lower population density and may even lead to cost-savings compared to in-house production. Moreover, \(^{18}\)F-labeled radiotracers have a higher positron yield and lower positron energy, which in turn decreases image noise, improves contrast resolution, and maximizes the likelihood of detecting subtle lesions. In addition, the longer half-life of 110 min allows for improved delayed imaging protocols and flexibility in study design, which may further increase diagnostic accuracy. Moreover, such compounds can be distributed to sites which are not allowed to produce radiotracers on-site due to regulatory issues or to centers without access to a cyclotron. In light of these advantageous characteristics, \(^{18}\)F-labeled PSMA-targeted PET radiotracers may play an important role in both optimizing this transformative imaging modality and making it widely available. We have aimed to provide a concise overview of emerging \(^{18}\)F-labeled PSMA-targeted radiotracers undergoing active clinical development. Given the wide array of available radiotracers, comparative studies are needed to firmly establish the role of the available \(^{18}\)F-labeled compounds in the field of molecular PCa imaging, preferably in different clinical scenarios.
Theranostics
10.7150/thno.37894
1838-7640
urn:nbn:de:bvb:20-opus-202559
Thermostatics (2020) 10:1, 1-16. https://doi.org/10.7150/thno.37894
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Rudolf A. Werner
Thorsten Derlin
Constantin Lapa
Sara Sheikbahaei
Takahiro Higuchi
Frederik L. Giesel
Spencer Behr
Alexander Drzezga
Hiroyuki Kimura
Andreas K. Buck
Frank M. Bengel
Martin G. Pomper
Michael A. Gorin
Steven P. Rowe
eng
uncontrolled
Radiofluorine
eng
uncontrolled
prostate-specific membrane antigen
eng
uncontrolled
prostate cancer
eng
uncontrolled
\(^{18}\)F
eng
uncontrolled
PSMA
eng
uncontrolled
\(^{68}\)Ga
eng
uncontrolled
theranostics
eng
uncontrolled
radioligand therapy
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Förderzeitraum 2019
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/20255/Werner_Theranostics_2020.pdf
23619
2020
eng
19
21
article
1
2021-04-29
--
--
Immunohistological analysis of neutrophils and neutrophil extracellular traps in human thrombemboli causing acute ischemic stroke
Ischemic stroke caused by thromboembolic occlusion of large cerebral arteries, such as the internal carotid (ICA) and/or the middle cerebral artery (MCA), is treated by mechanical thrombectomy (MT). MT allows salvage of the vessel-occluding thrombemboli, which most frequently originate from the left atrium or the left ventricle of the heart or from sites of plaque rupture within large arteries above the heart. Clot composition may influence the efficacy of (intravenous) thrombolysis and MT, respectively. We analyzed 37 human thrombemboli obtained from acute ischemic stroke patients during MT with special emphasis on histological staining of neutrophils and neutrophil extracellular traps (NETs). We found neutrophils as the main cellular component of cerebral thrombemboli but encountered considerable morphological heterogeneity. Neutrophils accumulated in the border region of fibrin-rich structures indicating possible interaction of neutrophils with distinct structural thrombembolus components. Web-like NETs were found in 35 of 37 thrombemboli in varying amounts. NETs were almost exclusively found within fibrin-rich areas. Importantly, stroke etiology, age and present oral anticoagulation was associated with morphological patterns and the amount of neutrophils. Correlation of histological data and imaging data revealed that relative Hounsfield units of cerebral thrombemboli positively correlated with the amount of red blood cells. In summary, our results demonstrate that neutrophils and NETs are substantial constituents of cerebral thrombemboli and contribute to their structural complexity.
International Journal of Molecular Sciences
10.3390/ijms21197387
urn:nbn:de:bvb:20-opus-236192
1422-0067
publish
International Journal of Molecular Sciences (2020) 21:19, 7387. https://doi.org/10.3390/ijms21197387
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Fabian Essig
Alexander M. Kollikowski
Mirko Pham
László Solymosi
Guido Stoll
Karl Georg Haeusler
Peter Kraft
Michael K. Schuhmann
eng
uncontrolled
acute ischemic stroke
eng
uncontrolled
thrombemboli
eng
uncontrolled
neutrophils
eng
uncontrolled
NETs
eng
uncontrolled
immunohistochemistry
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie)
Förderzeitraum 2020
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/23619/ijms-21-07387.pdf
26217
2022
eng
4
14
article
1
--
2022-02-09
--
Concepts and outcomes of perioperative therapy in stage IA-III pancreatic cancer — a cross-validation of the National Cancer Database (NCDB) and the German Cancer Registry Group of the Society of German Tumor Centers (GCRG/ADT)
(1) Background: The aim of this study is to assess perioperative therapy in stage IA-III pancreatic cancer cross-validating the German Cancer Registry Group of the Society of German Tumor Centers — Network for Care, Quality, and Research in Oncology, Berlin (GCRG/ADT) and the National Cancer Database (NCDB). (2) Methods: Patients with clinical stage IA-III PDAC undergoing surgery alone (OP), neoadjuvant therapy (TX) + surgery (neo + OP), surgery+adjuvantTX (OP + adj) and neoadjuvantTX + surgery + adjuvantTX (neo + OP + adj) were identified. Baseline characteristics, histopathological parameters, and overall survival (OS) were evaluated. (3) Results: 1392 patients from the GCRG/ADT and 29,081 patients from the NCDB were included. Patient selection and strategies of perioperative therapy remained consistent across the registries for stage IA-III pancreatic cancer. Combined neo + OP + adj was associated with prolonged OS as compared to neo + OP alone (17.8 m vs. 21.3 m, p = 0.012) across all stages in the GCRG/ADT registry. Similarly, OS with neo + OP + adj was improved as compared to neo + OP in the NCDB registry (26.4 m vs. 35.4 m, p < 0.001). (4) Conclusion: The cross-validation study demonstrated similar concepts and patient selection criteria of perioperative therapy across clinical stages of PDAC. Neoadjuvant therapy combined with adjuvant therapy is associated with improved overall survival as compared to either therapy alone.
Cancers
2072-6694
10.3390/cancers14040868
urn:nbn:de:bvb:20-opus-262174
2022-03-28T07:40:24+00:00
sword
swordwue
attachment; filename=deposit.zip
de2eaa7499dab4962f126bcc962840d5
Cancers (2022) 14:4, 868. https://doi.org/10.3390/cancers14040868
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Louisa Bolm
Sergii Zemskov
Maria Zeller
Taisuke Baba
Jorge Roldan
Jon M. Harrison
Natalie Petruch
Hiroki Sato
Ekaterina Petrova
Hryhoriy Lapshyn
Ruediger Braun
Kim C. Honselmann
Richard Hummel
Oleksii Dronov
Alexander V. Kirichenko
Monika Klinkhammer-Schalke
Kees Kleihues-van Tol
Sylke R. Zeissig
Dirk Rades
Tobias Keck
Carlos Fernandez-del Castillo
Ulrich F. Wellner
Rodney E. Wegner
eng
uncontrolled
pancreatic cancer
eng
uncontrolled
perioperative therapy
eng
uncontrolled
neoadjuvant therapy
eng
uncontrolled
pancreatic surgery
Medizin und Gesundheit
open_access
Institut für Klinische Epidemiologie und Biometrie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/26217/cancers-14-00868-v2.pdf
20170
2019
eng
8
20
article
1
2020-03-16
--
--
Targeting platelet GPVI plus rt-PA administration but not α2β1-mediated collagen binding protects against ischemic brain damage in mice
Platelet collagen interactions at sites of vascular injuries predominantly involve glycoprotein VI (GPVI) and the integrin α2β1. Both proteins are primarily expressed on platelets and megakaryocytes whereas GPVI expression is also shown on endothelial and integrin α2β1 expression on epithelial cells. We recently showed that depletion of GPVI improves stroke outcome without increasing the risk of cerebral hemorrhage. Genetic variants associated with higher platelet surface integrin α2 (ITGA2) receptor levels have frequently been found to correlate with an increased risk of ischemic stroke in patients. However until now, no preclinical stroke study has addressed whether platelet integrin α2β1 contributes to the pathophysiology of ischemia/reperfusion (I/R) injury. Focal cerebral ischemia was induced in C57BL/6 and Itga2\(^{−/−}\) mice by a 60 min transient middle cerebral artery occlusion (tMCAO). Additionally, wild-type animals were pretreated with anti-GPVI antibody (JAQ1) or Fab fragments of a function blocking antibody against integrin α2β1 (LEN/B). In anti-GPVI treated animals, intravenous (IV) recombinant tissue plasminogen activator (rt-PA) treatment was applied immediately prior to reperfusion. Stroke outcome, including infarct size and neurological scoring was determined on day 1 after tMCAO. We demonstrate that targeting the integrin α2β1 (pharmacologic; genetic) did neither reduce stroke size nor improve functional outcome on day 1 after tMCAO. In contrast, depletion of platelet GPVI prior to stroke was safe and effective, even when combined with rt-PA treatment. Our results underscore that GPVI, but not ITGA2, is a promising and safe target in the setting of ischemic stroke.
International Journal of Molecular Science
10.3390/ijms20082019
urn:nbn:de:bvb:20-opus-201700
1422-0067
International Journal of Molecular Science (2019) 20:8, 2019. https://doi.org/10.3390/ijms20082019
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Michael K. Schuhmann
Peter Kraft
Michael Bieber
Alexander M. Kollikowski
Harald Schulze
Bernhard Nieswandt
Mirko Pham
David Stegner
Guido Stoll
eng
uncontrolled
ischemic stroke
eng
uncontrolled
integrin α2
eng
uncontrolled
glycoprotein VI
eng
uncontrolled
recombinant tissue-type plasminogen activator
eng
uncontrolled
intracranial bleeding
eng
uncontrolled
transient middle cerebral artery occlusion
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Rudolf-Virchow-Zentrum
Institut für Experimentelle Biomedizin
Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie)
Förderzeitraum 2019
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/20170/Schuhmann_ijms-20-02019.pdf
30105
2022
eng
1
12
article
1
--
--
--
Motivations underlying self-infliction of pain during thinking for pleasure
Previous research suggested that people prefer to administer unpleasant electric shocks to themselves rather than being left alone with their thoughts because engagement in thinking is an unpleasant activity. The present research examined this negative reinforcement hypothesis by giving participants a choice of distracting themselves with the generation of electric shock causing no to intense pain. Four experiments (N = 254) replicated the result that a large proportion of participants opted to administer painful shocks to themselves during the thinking period. However, they administered strong electric shocks to themselves even when an innocuous response option generating no or a mild shock was available. Furthermore, participants inflicted pain to themselves when they were assisted in the generation of pleasant thoughts during the waiting period, with no difference between pleasant versus unpleasant thought conditions. Overall, these results question that the primary motivation for the self-administration of painful shocks is avoidance of thinking. Instead, it seems that the self-infliction of pain was attractive for many participants, because they were curious about the shocks, their intensities, and the effects they would have on them.
Scientific Reports
10.1038/s41598-022-14775-w
urn:nbn:de:bvb:20-opus-301059
@articleEder.2022, author = Eder, Andreas B. and Maas, Franzisca and Schubmann, Alexander and Krishna, Anand and Erle, Thorsten M., year = 2022, title = Motivations underlying self-infliction of pain during thinking for pleasure, pages = 11247, volume = 12, number = 1, journal = Scientific reports, doi = 10.1038/s41598-022-14775-w,
md5:c3d06cb4036bc52db0ac00e0234bdc85
2023-01-24T14:30:49+00:00
/tmp/php6cbma4
bibtex
63cfeb99251858.21475481
Scientific Reports 2022. 12(1):11247. DOI: 10.1038/s41598-022-14775-w
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Andreas B. Eder
Franzisca Maas
Alexander Schubmann
Anand Krishna
Thorsten M. Erle
eng
uncontrolled
pain
eng
uncontrolled
self-infliction
eng
uncontrolled
thinking
Psychologie
open_access
Institut für Psychologie
Institut Mensch - Computer - Medien
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/30105/Scientific_Reports_Eder.pdf
21216
2020
eng
466-479
3
87
article
1
--
2020-02-15
--
Local Leukocyte Invasion during Hyperacute Human Ischemic Stroke
Objective
Bridging the gap between experimental stroke and patients by ischemic blood probing during the hyperacute stage of vascular occlusion is crucial to assess the role of inflammation in human stroke and for the development of adjunct treatments beyond recanalization.
Methods
We prospectively observed 151 consecutive ischemic stroke patients with embolic large vessel occlusion of the anterior circulation who underwent mechanical thrombectomy. In all these patients, we attempted microcatheter aspiration of 3 different arterial blood samples: (1) within the core of the occluded vascular compartment and controlled by (2) carotid and (3) femoral samples obtained under physiological flow conditions. Subsequent laboratory analyses comprised leukocyte counting and differentiation, platelet counting, and the quantification of 13 proinflammatory human chemokines/cytokines.
Results
Forty patients meeting all clinical, imaging, interventional, and laboratory inclusion criteria could be analyzed, showing that the total number of leukocytes significantly increased under the occlusion condition. This increase was predominantly driven by neutrophils. Significant increases were also apparent for lymphocytes and monocytes, accompanied by locally elevated plasma levels of the T‐cell chemoattractant CXCL‐11. Finally, we found evidence that short‐term clinical outcome (National Institute of Health Stroke Scale at 72 hours) was negatively associated with neutrophil accumulation.
Interpretation
We provide the first direct human evidence that neutrophils, lymphocytes, and monocytes, accompanied by specific chemokine upregulation, accumulate in the ischemic vasculature during hyperacute stroke and may affect outcome. These findings strongly support experimental evidence that immune cells contribute to acute ischemic brain damage and indicate that ischemic inflammation initiates already during vascular occlusion. Ann Neurol 2020;87:466–479
Annals of Neurology
10.1002/ana.25665
urn:nbn:de:bvb:20-opus-212168
Annals of Neurology 2020, 87: 466-479. doi:10.1002/ana.25665
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Alexander M. Kollikowski
Michael K. Schuhmann
Bernhard Nieswandt
Wolfgang Müllges
Guido Stoll
Mirko Pham
eng
uncontrolled
neurology
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Rudolf-Virchow-Zentrum
Institut für Experimentelle Biomedizin
Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie)
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/21216/ANA_ANA25665.pdf
25917
2021
eng
46
1
18
article
1
2022-03-03
--
--
Platelets and lymphocytes drive progressive penumbral tissue loss during middle cerebral artery occlusion in mice
Background
In acute ischemic stroke, cessation of blood flow causes immediate tissue necrosis within the center of the ischemic brain region accompanied by functional failure in the surrounding brain tissue designated the penumbra. The penumbra can be salvaged by timely thrombolysis/thrombectomy, the only available acute stroke treatment to date, but is progressively destroyed by the expansion of infarction. The underlying mechanisms of progressive infarction are not fully understood.
Methods
To address mechanisms, mice underwent filament occlusion of the middle cerebral artery (MCAO) for up to 4 h. Infarct development was compared between mice treated with antigen-binding fragments (Fab) against the platelet surface molecules GPIb (p0p/B Fab) or rat immunoglobulin G (IgG) Fab as control treatment. Moreover, Rag1\(^{−/−}\) mice lacking T-cells underwent the same procedures. Infarct volumes as well as the local inflammatory response were determined during vessel occlusion.
Results
We show that blocking of the platelet adhesion receptor, glycoprotein (GP) Ibα in mice, delays cerebral infarct progression already during occlusion and thus before recanalization/reperfusion. This therapeutic effect was accompanied by decreased T-cell infiltration, particularly at the infarct border zone, which during occlusion is supplied by collateral blood flow. Accordingly, mice lacking T-cells were likewise protected from infarct progression under occlusion.
Conclusions
Progressive brain infarction can be delayed by blocking detrimental lymphocyte/platelet responses already during occlusion paving the way for ultra-early treatment strategies in hyper-acute stroke before recanalization.
Journal of Neuroinflammation
10.1186/s12974-021-02095-1
urn:nbn:de:bvb:20-opus-259172
publish
Journal of Neuroinflammation (2021) 18:46. doi:10.1186/s12974-021-02095-1
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Michael K. Schuhmann
Michael Bieber
Maximilian Franke
Alexander M. Kollikowski
David Stegner
Katrin G. Heinze
Bernhard Nieswandt
Mirko Pham
Guido Stoll
eng
uncontrolled
ischemic penumbra
eng
uncontrolled
glycoprotein receptor Ib
eng
uncontrolled
T-cells
eng
uncontrolled
ischemic stroke
eng
uncontrolled
thrombo-inflammation
eng
uncontrolled
middle cerebral artery occlusion
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Rudolf-Virchow-Zentrum
Institut für Experimentelle Biomedizin
Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie)
Förderzeitraum 2021
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/25917/s12974-021-02095-1.pdf
24963
2021
eng
12
article
1
--
2021-11-08
--
Reduced Programming Time and Strong Symptom Control Even in Chronic Course Through Imaging-Based DBS Programming
Objectives: Deep brain stimulation (DBS) programming is based on clinical response testing. Our clinical pilot trial assessed the feasibility of image-guided programing using software depicting the lead location in a patient-specific anatomical model.
Methods: Parkinson's disease patients with subthalamic nucleus-DBS were randomly assigned to standard clinical-based programming (CBP) or anatomical-based (imaging-guided) programming (ABP) in an 8-week crossover trial. Programming characteristics and clinical outcomes were evaluated.
Results: In 10 patients, both programs led to similar motor symptom control (MDS-UPDRS III) after 4 weeks (medicationOFF/stimulationON; CPB: 18.27 ± 9.23; ABP: 18.37 ± 6.66). Stimulation settings were not significantly different, apart from higher frequency in the baseline program than CBP (p = 0.01) or ABP (p = 0.003). Time spent in a program was not significantly different (CBP: 86.1 ± 29.82%, ABP: 88.6 ± 29.0%). Programing time was significantly shorter (p = 0.039) with ABP (19.78 ± 5.86 min) than CBP (45.22 ± 18.32).
Conclusion: Image-guided DBS programming in PD patients drastically reduces programming time without compromising symptom control and patient satisfaction in this small feasibility trial.
Frontiers in Neurology
1664-2295
10.3389/fneur.2021.785529
urn:nbn:de:bvb:20-opus-249634
2021-11-24T13:12:08+00:00
sword
swordwue
attachment; filename=deposit.zip
ef3c7332931edc9522d14e6585a6e88b
Frontiers in Neurology (2021) 12:785529. doi: 10.3389/fneur.2021.785529
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Florian Lange
Frank Steigerwald
Tobias Malzacher
Gregor Alexander Brandt
Thorsten Michael Odorfer
Jonas Roothans
Martin M. Reich
Patrick Fricke
Jens Volkmann
Cordula Matthies
Philipp D. Capetian
eng
uncontrolled
directional deep brain stimulation
eng
uncontrolled
image-guided programming
eng
uncontrolled
subthalamic nucleus
eng
uncontrolled
chronic stimulation
eng
uncontrolled
randomized controlled double-blind study
eng
uncontrolled
Parkinson's disease
Medizin und Gesundheit
open_access
Neurochirurgische Klinik und Poliklinik
Neurologische Klinik und Poliklinik
Import
Förderzeitraum 2021
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/24963/fneur-12-785529.pdf
19813
2020
eng
3090
10
article
1
--
2020-01-15
--
Lymphoid aggregates in the CNS of progressive multiple sclerosis patients lack regulatory T cells
In gray matter pathology of multiple sclerosis, neurodegeneration associates with a high degree of meningeal inflammatory activity. Importantly, ectopic lymphoid follicles (eLFs) were identified at the inflamed meninges of patients with progressive multiple sclerosis. Besides T lymphocytes, they comprise B cells and might elicit germinal center (GC)-like reactions. GC reactions are controlled by FOXP3+ T-follicular regulatory cells (TFR), but it is unknown if they participate in autoantibody production in eLFs. Receiving human post-mortem material, gathered from autopsies of progressive multiple sclerosis patients, indeed, distinct inflammatory infiltrates enriched with B cells could be detected in perivascular areas and deep sulci. CD35+ cells, parafollicular CD138+ plasma cells, and abundant expression of the homing receptor for GCs, CXCR5, on lymphocytes defined some of them as eLFs. However, they resembled GCs only in varying extent, as T cells did not express PD-1, only few cells were positive for the key transcriptional regulator BCL-6 and ongoing proliferation, whereas a substantial number of T cells expressed high NFATc1 like GC-follicular T cells. Then again, predominant cytoplasmic NFATc1 and an enrichment with CD3+CD27+ memory and CD4+CD69+ tissue-resident cells implied a chronic state, very much in line with PD-1 and BCL-6 downregulation. Intriguingly, FOXP3+ cells were almost absent in the whole brain sections and CD3+FOXP3+ TFRs were never found in the lymphoid aggregates. This also points to less controlled humoral immune responses in those lymphoid aggregates possibly enabling the occurrence of CNS-specific autoantibodies in multiple sclerosis patients.
Frontiers in Immunology
1664-3224
10.3389/fimmu.2019.03090
urn:nbn:de:bvb:20-opus-198130
Frontiers in Immunology 10:3090. doi: 10.3389/fimmu.2019.03090
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Luisa Bell
Alexander Lenhart
Andreas Rosenwald
Camelia M. Monoranu
Friederike Berberich-Siebelt
eng
uncontrolled
ectopic lymphoid follicle
eng
uncontrolled
lymphoid aggregate
eng
uncontrolled
T-follicular regulatory cell
eng
uncontrolled
meningeal inflammation
eng
uncontrolled
NFATc1
eng
uncontrolled
progressive multiple sclerosis
Medizin und Gesundheit
open_access
Pathologisches Institut
Import
Förderzeitraum 2019
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/19813/fimmu-10-03090.pdf
20612
2019
eng
12601-12610
54
25
article
1
2020-06-15
--
--
Ultra-high to ultra-low drug loaded micelles: Probing host-guest interactions by fluorescence spectroscopy
Polymer micelles are an attractive means to solubilize water insoluble compounds such as drugs. Drug loading, formulations stability and control over drug release are crucial factors for drug‐loaded polymer micelles. The interactions between the polymeric host and the guest molecules are considered critical to control these factors but typically barely understood. Here, we compare two isomeric polymer micelles, one of which enables ultra‐high curcumin loading exceeding 50 wt.%, while the other allows a drug loading of only 25 wt.%. In the low capacity micelles, steady‐state fluorescence revealed a very unusual feature of curcumin fluorescence, a high energy emission at 510 nm. Time‐resolved fluorescence upconversion showed that the fluorescence life time of the corresponding species is too short in the high‐capacity micelles, preventing an observable emission in steady‐state. Therefore, contrary to common perception, stronger interactions between host and guest can be detrimental to the drug loading in polymer micelles.
Chemistry - A European Journal
10.1002/chem.201902619
urn:nbn:de:bvb:20-opus-206128
Chemistry - A European Journal (2019) 25:54, 12601-12610. https://doi.org/10.1002/chem.201902619
false
true
CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International
Michael M. Lübtow
Henning Marciniak
Alexander Schmiedel
Markus Roos
Christoph Lambert
Robert Luxenhofer
eng
uncontrolled
curcumin
eng
uncontrolled
drug delivery
eng
uncontrolled
fluorenscence
eng
uncontrolled
poly(2-oxazine)
eng
uncontrolled
pol(2-oxazoline)
deu
swd
Polymer-drug interaction
deu
swd
upconversion
Chemie und zugeordnete Wissenschaften
open_access
Institut für Organische Chemie
Institut für Funktionsmaterialien und Biofabrikation
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/20612/luebtow_chemistry_a_european_journal_2019.pdf
28184
2022
eng
7
12
article
1
--
2022-07-16
--
A surgeon that switched to unrestricted kinematic alignment with manual instruments has a short learning curve and comparable resection accuracy and outcomes to those of an experienced surgeon
After starting an orthopedic practice, a surgeon with a fellowship in mechanically aligned (MA) TKA initiated this study to characterize their learning curve after they switched to unrestricted kinematic alignment (KA) TKA using manual instruments. Accordingly, the present study determined for the inexperienced (IE) surgeon the number of cases required to achieve consistent femoral resections and operating times, and whether the femoral resection accuracy, patient-reported outcome measures (PROMs), and component alignment were different from an experienced (E) surgeon. This prospective cohort study analyzed the IE surgeon's first 30 TKAs, all performed with KA, and 30 consecutive KA TKAs performed by an E surgeon. The resection accuracy or deviation was the calipered thickness of the distal and posterior medial and lateral femoral resections minus the planned resection thickness, which was the thickness of the corresponding condyle of the femoral component, minus 2 mm for cartilage wear, and 1 mm for the kerf of the blade. Independent observers recorded the femoral resection thickness, operative times, PROMs, and alignment. For each femoral resection, the deviation between three groups of patients containing ten consecutive KA TKAs, was either insignificant (p = 0.695 to 1.000) or within the 0.5 mm resolution of the caliper, which indicated no learning curve. More than three groups were needed to determine the learning curve for the operative time; however, the IE surgeon's procedure dropped to 77 min for the last 10 patients, which was 20 min longer than the E surgeon. The resection deviations of the IE and E surgeon were comparable, except for the posterolateral femoral resection, which the IE surgeon under-resected by a mean of −0.8 mm (p < 0.0001). At a mean follow-up of 9 and 17 months, the Forgotten Joint Score, Oxford Knee Score, KOOS, and the alignment of the components and limbs were not different between the IE and E surgeon (p ≥ 0.6994). A surgeon that switches to unrestricted KA with manual instruments can determine their learning curve by computing the deviation of the distal and posterior femoral resections from the planned resection. Based on the present study, an IE surgeon could have resection accuracy, post-operative patient outcomes, and component alignment comparable to an E surgeon.
Journal of Personalized Medicine
2075-4426
10.3390/jpm12071152
urn:nbn:de:bvb:20-opus-281842
2022-08-03T14:03:56+00:00
sword
swordwue
attachment; filename=deposit.zip
4b1072bd5f6b15bc59c120612785b770
Journal of Personalized Medicine (2022) 12:7, 1152. https://doi.org/10.3390/jpm12071152
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Alexander J. Nedopil
Anand Dhaliwal
Stephen M. Howell
Maury L. Hull
eng
uncontrolled
total knee arthroplasty
eng
uncontrolled
kinematic alignment
eng
uncontrolled
learning curve
eng
uncontrolled
accuracy
eng
uncontrolled
efficiency
Medizin und Gesundheit
open_access
Lehrstuhl für Orthopädie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/28184/jpm-12-01152-v2.pdf
29029
2022
eng
11
12
article
1
--
2022-10-26
--
Central serotonin/noradrenaline transporter availability and treatment success in patients with obesity
Serotonin (5-hydroxytryptamine, 5-HT) as well as noradrenaline (NA) are key modulators of various fundamental brain functions including the control of appetite. While manipulations that alter brain serotoninergic signaling clearly affect body weight, studies implicating 5-HT transporters and NA transporters (5-HTT and NAT, respectively) as a main drug treatment target for human obesity have not been conclusive. The aim of this positron emission tomography (PET) study was to investigate how these central transporters are associated with changes of body weight after 6 months of dietary intervention or Roux-en-Y gastric bypass (RYGB) surgery in order to assess whether 5-HTT as well as NAT availability can predict weight loss and consequently treatment success. The study population consisted of two study cohorts using either the 5-HTT-selective radiotracer [\(^{11}\)C]DASB to measure 5-HTT availability or the NAT-selective radiotracer [\(^{11}\)C]MRB to assess NAT availability. Each group included non-obesity healthy participants, patients with severe obesity (body mass index, BMI, >35 kg/m\(^2\)) following a conservative dietary program (diet) and patients undergoing RYGB surgery within a 6-month follow-up. Overall, changes in BMI were not associated with changes of both 5-HTT and NAT availability, while 5-HTT availability in the dorsal raphe nucleus (DRN) prior to intervention was associated with substantial BMI reduction after RYGB surgery and inversely related with modest BMI reduction after diet. Taken together, the data of our study indicate that 5-HTT and NAT are involved in the pathomechanism of obesity and have the potential to serve as predictors of treatment outcomes.
Brain Sciences
2076-3425
10.3390/brainsci12111437
urn:nbn:de:bvb:20-opus-290294
2022-11-04T10:26:28+00:00
sword
swordwue
attachment; filename=deposit.zip
f73402400d6bab03dab8b41d31d2a88d
Brain Sciences (2022) 12:11, 1437. https://doi.org/10.3390/brainsci12111437
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Nora-Isabell Griebsch
Johanna Kern
Jonas Hansen
Michael Rullmann
Julia Luthardt
Stephanie Helfmeyer
Franziska J. Dekorsy
Marvin Soeder
Mohammed K. Hankir
Franziska Zientek
Georg-Alexander Becker
Marianne Patt
Philipp M. Meyer
Arne Dietrich
Matthias Blüher
Yu-Shin Ding
Anja Hilbert
Osama Sabri
Swen Hesse
eng
uncontrolled
obesity
eng
uncontrolled
serotonin
eng
uncontrolled
noradrenaline
eng
uncontrolled
serotonin transporter
eng
uncontrolled
noradrenaline transporter
eng
uncontrolled
Roux-en-Y gastric bypass surgery
eng
uncontrolled
body mass index (BMI; kg/m\(^2\))
eng
uncontrolled
radiotracer
eng
uncontrolled
PET
eng
uncontrolled
PET imaging
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I)
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/29029/brainsci-12-01437.pdf
31921
2023
eng
6
11
article
1
--
2023-05-31
--
Insulin resistance is the main characteristic of metabolically unhealthy obesity (MUO) associated with NASH in patients undergoing bariatric surgery
(1) Background: Metabolically healthy obesity (MHO) is a concept that applies to obese patients without any elements of metabolic syndrome (metS). In turn, metabolically unhealthy obesity (MUO) defines the presence of elements of metS in obese patients. The components of MUO can be divided into subgroups regarding the elements of inflammation, lipid and glucose metabolism and cardiovascular disease. MUO patients appear to be at greater risk of developing non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) compared to MHO patients. The aim of this study was to evaluate the influence of different MUO components on NAFLD and NASH in patients with morbid obesity undergoing bariatric surgery. (2) Methods: 141 patients undergoing bariatric surgery from September 2015 and October 2021 at RWTH Aachen university hospital (Germany) were included. Patients were evaluated pre-operatively for characteristics of metS and MUO (HbA1c, HOMA, CRP, BMI, fasting glucose, LDL, TG, HDL and the presence of arterial hypertension). Intraoperatively, a liver biopsy was taken from the left liver lobe and evaluated for the presence of NAFLD or NASH. In ordinal regression analyses, different factors were evaluated for their influence on NAFLD and NASH. (3) Results: Mean BMI of the patients was 52.3 kg/m\(^2\) (36–74.8, SD 8.4). Together, the parameters HbA1c, HOMA, CRP, BMI, fasting glucose, LDL, TG, HDL and the presence of arterial hypertension accounted for a significant amount of variance in the outcome, with a likelihood ratio of χ\(^2\) (9) = 41.547, p < 0.001, for predicting the presence of NASH. Only HOMA was an independent predictor of NASH (B = 0.102, SE = 0.0373, p = 0.007). Evaluation of steatosis showed a similar trend (likelihood ratio χ\(^2\) (9) = 40.272, p < 0.001). Independent predictors of steatosis were HbA1c (B = 0.833, SE = 0.343, p = 0.015) and HOMA (B = 0.136, SE = 0.039, p < 0.001). (4) Conclusions: The above-mentioned model, including components of MUO, was significant for diagnosing NASH in patients with morbid obesity undergoing bariatric surgery. Out of the different subitems, HOMA independently predicted the presence of NASH and steatosis, while HbA1c independently predicted steatosis and fibrosis. Taken together, the parameter of glucose metabolism appears to be more accurate for the prediction of NASH than the parameters of lipid metabolism, inflammation or the presence of cardiovascular disease.
Biomedicines
2227-9059
10.3390/biomedicines11061595
urn:nbn:de:bvb:20-opus-319213
2023-06-07T08:45:00+00:00
sword
swordwue
attachment; filename=deposit.zip
06329dd8642993839c33bc5350b4d4a3
Biomedicines (2023) 11:6, 1595. https://doi.org/10.3390/biomedicines11061595
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Sophia M. Schmitz
Sebastian Storms
Alexander Koch
Christine Stier
Andreas Kroh
Karl P. Rheinwalt
Sandra Schipper
Karim Hamesch
Tom F. Ulmer
Ulf P. Neumann
Patrick H. Alizai
eng
uncontrolled
NAFLD
eng
uncontrolled
metabolically unhealthy obesity
eng
uncontrolled
obesity surgery
eng
uncontrolled
insulin resistance
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I)
Medizinische Klinik und Poliklinik I
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/31921/biomedicines-11-01595.pdf
28614
2022
eng
8
12
article
1
--
2022-08-03
--
A TKA insert with a lateral flat articular surface maximizes external and internal tibial orientations without anterior lift-off relative to low- and ultracongruent surfaces
Background: In total knee arthroplasty (TKA), inserts can have different levels of medial and lateral congruency determined by the acuteness of the upslopes of the anterior and posterior articular surfaces. The present study evaluated an insert with different levels of lateral congruency and a medial ball-in-socket congruency to test the hypothesis that a lateral flat (F) insert maximizes external tibial orientation at extension and internal orientation at 90° flexion and lowers the incidence of anterior lift-off relative to low-congruent (LC) and ultracongruent (UC) lateral inserts. Methods: Two surgeons treated 23 patients with unrestricted caliper-verified kinematic alignment (KA) and posterior cruciate ligament (PCL) retention. They randomly trialed inserts with a medial radial dial that functioned as a built-in goniometer by measuring the tibial orientation relative to a sagittal line on the femoral trial component. Anterior lift-off of the insert from the baseplate indicated PCL tightness. Results: The F insert’s mean of 9° of external tibial orientation was higher than that of the LC (5°, p < 0.0001) and UC inserts (2°, p < 0.0001). The −13° of internal tibial orientation at 90° flexion was higher than that of the LC (−9°, p < 0.0001) and UC inserts (−7°, p < 0.0001). The 0% incidence of anterior lift-off was less than that of the LC (26%) and UC inserts (57%) (p < 0.0001). Conclusions: Surgeons and implant manufacturers should know that adding congruency to the lateral articular surface limits external tibial orientation in extension and internal tibial orientation at 90° flexion and overtightens the PCL. These rotational limitations and flexion space tightness can adversely affect patellofemoral tracking and knee flexion.
Journal of Personalized Medicine
2075-4426
10.3390/jpm12081274
urn:nbn:de:bvb:20-opus-286142
2022-09-07T16:41:47+00:00
sword
swordwue
attachment; filename=deposit.zip
4a587d8ecb4a796c8d860229cb23d9e6
Journal of Personalized Medicine (2022) 12:8, 1274. https://doi.org/10.3390/jpm12081274
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Alexander J. Nedopil
Stephen M. Howell
Maury L. Hull
eng
uncontrolled
total knee arthroplasty
eng
uncontrolled
kinematic alignment
eng
uncontrolled
implant design
eng
uncontrolled
PCL retention
eng
uncontrolled
congruency
Medizin und Gesundheit
open_access
Lehrstuhl für Orthopädie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/28614/jpm-12-01274.pdf
28623
2022
eng
9
12
article
1
--
2022-08-31
--
Measurement of tibial orientation helps select the optimal insert thickness to personalize PCL tension in a medial ball-in-socket TKA
As the conformity of a medial ball-in-socket total knee arthroplasty (TKA) provides intrinsic anterior-posterior (A-P) stability, surgeons cannot rely on the manual examination of sagittal laxity to identify the optimal insert thickness. Instead, the present study determined whether measuring tibial axial orientation in extension and 90° flexion with an insert goniometer could identify the optimal thickness that, when implanted, provides high postoperative function. In twenty-two patients that underwent unrestricted caliper-verified kinematic alignment (KA) with a PCL retaining implant, two surgeons measured tibial orientation in extension and 90° flexion with 10, 11, 12, and 13 mm thick insert goniometers. Each TKA had one insert thickness that restored either the maximum external tibial orientation in extension, the maximum internal tibial orientation at 90° flexion, or both relative to 1 mm thinner and thicker inserts. In addition, the 6-month median [interquartile range] Forgotten Joint Score of 73 (54–87) and Oxford Knee Score of 42 (38–45) indicated high satisfaction and function. In conclusion, surgeons using a medial ball-in-socket TKA design can measure external tibial orientation in extension and internal tibial orientation at 90° flexion with an insert goniometer. Furthermore, implanting an insert with the thickness that provided the maximum orientation values resulted in high postoperative function, thereby personalizing PCL tension.
Journal of Personalized Medicine
2075-4426
10.3390/jpm12091427
urn:nbn:de:bvb:20-opus-286232
2022-09-07T19:57:04+00:00
sword
swordwue
attachment; filename=deposit.zip
f4053154d3bdb86556bf42ac808bc0b5
Journal of Personalized Medicine (2022) 12:9, 1427. https://doi.org/10.3390/jpm12091427
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Alexander J. Nedopil
Stephen M. Howell
Maury L. Hull
eng
uncontrolled
posterior cruciate ligament
eng
uncontrolled
tibial rotation
eng
uncontrolled
medial pivot
eng
uncontrolled
total knee arthroplasty
eng
uncontrolled
kinematic alignment
Medizin und Gesundheit
open_access
Lehrstuhl für Orthopädie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/28623/jpm-12-01427.pdf
28818
2022
eng
9
12
article
1
--
2022-09-07
--
Six commonly used postoperative radiographic alignment parameters do not predict clinical outcome scores after unrestricted caliper-verified kinematically aligned TKA
Background: Unrestricted caliper-verified kinematically aligned (KA) TKA restores patient’s prearthritic coronal and sagittal alignments, which have a wide range containing outliers that concern the surgeon practicing mechanical alignment (MA). Therefore, knowing which radiographic parameters are associated with dissatisfaction could help a surgeon decide whether to rely on them as criteria for revising an unhappy patient with a primary KA TKA using MA principles. Hence, we determined whether the femoral mechanical angle (FMA), hip–knee–ankle angle (HKAA), tibial mechanical angle (TMA), tibial slope angle (TSA), and the indicators of patellofemoral tracking, including patella tilt angle (PTA) and the lateral undercoverage of the trochlear resection (LUCTR), are associated with clinical outcome scores. Methods: Forty-three patients with a CT scan and skyline radiograph after a KA TKA with PCL retention and medial stabilized design were analyzed. Linear regression determined the strength of the association between the FMA, HKA angle, PTS, PTA, and LUCTR and the forgotten joint score (FJS), Oxford knee score (OKS), and KOOS Jr score obtained at a mean of 23 months. Results: There was no correlation between the FMA (range 2° varus to −10° valgus), HKAA (range 10° varus to −9° valgus), TMA (range 10° varus to −0° valgus), TSA (range 14° posterior to −4° anterior), PTA (range, −10° medial to 14° lateral), and the LUCTR resection (range 2 to 9 mm) and the FJS (median 83), the OKS (median 44), and the KOOS Jr (median 85) (r = 0.000 to 0.079). Conclusions: Surgeons should be cautious about using postoperative FMA, HKAA, TMA, TSA, PTA, and LUCTR values within the present study’s reported ranges to explain success and dissatisfaction after KA TKA.
Journal of Personalized Medicine
2075-4426
10.3390/jpm12091468
urn:nbn:de:bvb:20-opus-288186
2022-10-06T13:14:21+00:00
sword
swordwue
attachment; filename=deposit.zip
b1543bbd90e0e3804eced0698709926e
Journal of Personalized Medicine (2022) 12:9, 1468. https://doi.org/10.3390/jpm12091468
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Anand Dhaliwal
Tomas Zamora
Alexander J. Nedopil
Stephen M. Howell
Maury L. Hull
eng
uncontrolled
total knee arthroplasty
eng
uncontrolled
kinematic alignment
eng
uncontrolled
reoperation
eng
uncontrolled
revision
eng
uncontrolled
phenotype
Medizin und Gesundheit
open_access
Lehrstuhl für Orthopädie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/28818/jpm-12-01468.pdf
28621
2022
eng
17
19
article
1
--
2022-08-31
--
Birth order, Caesarean section, or daycare attendance in relation to child- and adult-onset type 1 diabetes: results from the German National Cohort
(1) Background: Global incidence of type 1 diabetes (T1D) is rising and nearly half occurred in adults. However, it is unclear if certain early-life childhood T1D risk factors were also associated with adult-onset T1D. This study aimed to assess associations between birth order, delivery mode or daycare attendance and type 1 diabetes (T1D) risk in a population-based cohort and whether these were similar for childhood- and adult-onset T1D (cut-off age 15); (2) Methods: Data were obtained from the German National Cohort (NAKO Gesundheitsstudie) baseline assessment. Self-reported diabetes was classified as T1D if: diagnosis age ≤ 40 years and has been receiving insulin treatment since less than one year after diagnosis. Cox regression was applied for T1D risk analysis; (3) Results: Analyses included 101,411 participants (100 childhood- and 271 adult-onset T1D cases). Compared to “only-children”, HRs for second- or later-born individuals were 0.70 (95% CI = 0.50–0.96) and 0.65 (95% CI = 0.45–0.94), respectively, regardless of parental diabetes, migration background, birth year and perinatal factors. In further analyses, higher birth order reduced T1D risk in children and adults born in recent decades. Caesarean section and daycare attendance showed no clear associations with T1D risk; (4) Conclusions: Birth order should be considered in both children and adults’ T1D risk assessment for early detection.
International Journal of Environmental Research and Public Health
1660-4601
10.3390/ijerph191710880
urn:nbn:de:bvb:20-opus-286216
2022-09-07T19:52:11+00:00
sword
swordwue
attachment; filename=deposit.zip
4398e18a78186f4449cd7d927c2e1fb5
International Journal of Environmental Research and Public Health (2022) 19:17, 10880. https://doi.org/10.3390/ijerph191710880
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Justine Tanoey
Christina Baechle
Hermann Brenner
Andreas Deckert
Julia Fricke
Kathrin Günther
André Karch
Thomas Keil
Alexander Kluttig
Michael Leitzmann
Rafael Mikolajczyk
Nadia Obi
Tobias Pischon
Tamara Schikowski
Sabine M. Schipf
Matthias B. Schulze
Anja Sedlmeier
Ilais Moreno Velásquez
Katharina S. Weber
Henry Völzke
Wolfgang Ahrens
Sylvia Gastell
Bernd Holleczek
Karl-Heinz Jöckel
Verena Katzke
Wolfgang Lieb
Karin B. Michels
Börge Schmidt
Henning Teismann
Heiko Becher
eng
uncontrolled
perinatal
eng
uncontrolled
adult-onset
eng
uncontrolled
late-onset
eng
uncontrolled
autoimmune
eng
uncontrolled
delivery mode
eng
uncontrolled
sex
eng
uncontrolled
offspring
eng
uncontrolled
NAKO
Medizin und Gesundheit
open_access
Institut für Klinische Epidemiologie und Biometrie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/28621/ijerph-19-10880-v2.pdf
28814
2022
eng
18
19
article
1
--
2022-09-16
--
Oral-health-related quality of life in patients with medication-related osteonecrosis of the jaw: a prospective clinical study
Medication-related osteonecrosis of the jaw (MRONJ) represents an adverse side effect of antiresorptive and antiangiogenic medications. It is associated with impaired quality of life, oral health, and oral function and can be classified into various stages. The purpose of this prospective clinical study is to evaluate the impact of stages I and II MRONJ on oral-health-related quality of life (OHRQoL) and related parameters. Patients’ OHRQoL, satisfaction with life, oral discomfort, and oral health were assessed using the German version of the Oral Health Impact Profile (OHIP-G49), visual analog scales (VAS), and Satisfaction with Life Scale (SWLS) at baseline (T0), 10 days (T1), and 3 months after treatment (T2) in 36 patients. Data were analyzed using Kolmogorov–Smirnov test, two-way mixed ANOVAs, and follow-up Mann–Whitney U tests. The impact of treatment effects on the original seven OHIP domain structures and the recently introduced four-dimensional OHIP structure were evaluated using linear regression analysis. Thirty-six patients received surgical MRONJ treatment. Before treatment, patients’ perceived OHRQoL, oral discomfort, oral health, and satisfaction with life were negatively affected by MRONJ. Surgical treatment significantly improved OHRQoL and related parameters (all p ≤ 0.012). This improvement was greater in patients with higher impairment at T0. OHRQoL and oral restrictions were still impaired after treatment in patients who needed prosthetic treatment. The four-dimensional structure revealed valuable information beyond the standard seven OHIP domains. Increased awareness of MRONJ risks and an interdisciplinary treatment approach for MRONJ patients are needed.
International Journal of Environmental Research and Public Health
1660-4601
10.3390/ijerph191811709
urn:nbn:de:bvb:20-opus-288141
2022-10-06T12:47:25+00:00
sword
swordwue
attachment; filename=deposit.zip
1f6ce57bb25e60fbb07f4538bab7e3da
International Journal of Environmental Research and Public Health (2022) 19:18, 11709. doi:10.3390/ijerph191811709
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Anna Winter
Stefan M. Schulz
Marc Schmitter
Roman C. Brands
Anton Straub
Alexander Kübler
Anna Borgmann
Stefan Hartmann
eng
uncontrolled
oral-health-related quality of life
eng
uncontrolled
satisfaction with life
eng
uncontrolled
oral health
eng
uncontrolled
medication-related osteonecrosis of the jaw
eng
uncontrolled
treatment benefit
eng
uncontrolled
OHIP-49
eng
uncontrolled
SWLS
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Mund-, Kiefer- und Plastische Gesichtschirurgie
Poliklinik für Zahnärztliche Prothetik
Import
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/28814/ijerph-19-11709-v2.pdf
29048
2022
eng
10
12
article
1
--
2022-10-16
--
The trochlear groove of a femoral component designed for kinematic alignment is lateral to the quadriceps line of force and better laterally covers the anterior femoral resection than a mechanical alignment design
Background: A concern about kinematically aligned (KA) total knee arthroplasty (TKA) is that it relies on femoral components designed for mechanical alignment (MAd-FC) that could affect patellar tracking, in part, because of a trochlear groove orientation that is typically 6° from vertical. KA sets the femoral component coincident to the patient’s pre-arthritic distal and posterior femoral joint lines and restores the Q-angle, which varies widely. Relative to KA and the native knee, aligning the femoral component with MA changes most distal joint lines and Q-angles, and rotates the posterior joint line externally laterally covering the anterior femoral resection. Whether switching from a MAd- to a KAd-FC with a wider trochlear groove orientation of 20.5° from vertical results in radiographic measures known to promote patellar tracking is unknown. The primary aim was to determine whether a KAd-FC sets the trochlear groove lateral to the quadriceps line of force (QLF), better laterally covers the anterior femoral resection, and reduces lateral patella tilt relative to a MAd-FC. The secondary objective was to determine at six weeks whether the KAd-FC resulted in a higher complication rate, less knee extension and flexion, and lower clinical outcomes. Methods: Between April 2019 and July 2022, two surgeons performed sequential bilateral unrestricted caliper-verified KA TKA with manual instruments on thirty-six patients with a KAd- and MAd-FC in opposite knees. An observer measured the angle between a line best-fit to the deepest valley of the trochlea and a line representing the QLF that indicated the patient’s Q-angle. When the trochlear groove was lateral or medial relative to the QLF, the angle is denoted + or −, and the femoral component included or excluded the patient’s Q-angle, respectively. Software measured the lateral undercoverage of the anterior femoral resection on a Computed Tomography (CT) scan, and the patella tilt angle (PTA) on a skyline radiograph. Complications, knee extension and flexion measurements, Oxford Knee Score, KOOS Jr, and Forgotten Joint Score were recorded pre- and post-operatively (at 6 weeks). A paired Student’s T-test determined the difference between the KA TKAs with a KAd-FC and MAd-FC with a significance set at p < 0.05. Results: The final analysis included thirty-five patients. The 20.5° trochlear groove of the KAd-FC was lateral to the QLF in 100% (15 ± 3°) of TKAs, which was greater than the 69% (1 ± 3°) lateral to the QLF with the 6° trochlear groove of the MAd-FC (p < 0.001). The KAd-FC’s 2 ± 1.9 mm lateral undercoverage of the anterior femoral resection was less than the 4.4 ± 1.5 mm for the MAd-FC (p < 0.001). The PTA, complication rate, knee extension and flexion, and clinical outcome measures did not differ between component designs. Conclusions: The KA TKA with a KAd-FC resulted in a trochlear groove lateral to the QLF that included the Q-angle in all patients, and negligible lateral undercoverage of the anterior femoral resection. These newly described radiographic parameters could be helpful when investigating femoral components designed for KA with the intent of promoting patellofemoral kinematics.
Journal of Personalized Medicine
2075-4426
10.3390/jpm12101724
urn:nbn:de:bvb:20-opus-290482
2022-11-04T14:02:18+00:00
sword
swordwue
attachment; filename=deposit.zip
41dfe3da99d3aae3101d9b8ba74de3a5
Journal of Personalized Medicine (2022) 12:10, 1724. https://doi.org/10.3390/jpm12101724
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Elliot Sappey-Marinier
Stephen M. Howell
Alexander J. Nedopil
Maury L. Hull
eng
uncontrolled
total knee arthroplasty
eng
uncontrolled
lateral trochlear undercoverage
eng
uncontrolled
prosthetic design
eng
uncontrolled
kinematic alignment
eng
uncontrolled
patellofemoral relationship
Medizin und Gesundheit
open_access
Lehrstuhl für Orthopädie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/29048/jpm-12-01724-v2.pdf
30499
2023
eng
2
12
article
1
--
2023-01-11
--
Vasoactive soluble endoglin: a novel biomarker indicative of reperfusion after cerebral large-vessel occlusion
Now that mechanical thrombectomy has substantially improved outcomes after large-vessel occlusion stroke in up to every second patient, futile reperfusion wherein successful recanalization is not followed by a favorable outcome is moving into focus. Unfortunately, blood-based biomarkers, which identify critical stages of hemodynamically compromised yet reperfused tissue, are lacking. We recently reported that hypoxia induces the expression of endoglin, a TGF-β co-receptor, in human brain endothelium in vitro. Subsequent reoxygenation resulted in shedding. Our cell model suggests that soluble endoglin compromises the brain endothelial barrier function. To evaluate soluble endoglin as a potential biomarker of reperfusion (-injury) we analyzed its concentration in 148 blood samples of patients with acute stroke due to large-vessel occlusion. In line with our in vitro data, systemic soluble endoglin concentrations were significantly higher in patients with successful recanalization, whereas hypoxia alone did not induce local endoglin shedding, as analyzed by intra-arterial samples from hypoxic vasculature. In patients with reperfusion, higher concentrations of soluble endoglin additionally indicated larger infarct volumes at admission. In summary, we give translational evidence that the sequence of hypoxia and subsequent reoxygenation triggers the release of vasoactive soluble endoglin in large-vessel occlusion stroke and can serve as a biomarker for severe ischemia with ensuing recanalization/reperfusion.
Cells
2073-4409
10.3390/cells12020288
urn:nbn:de:bvb:20-opus-304995
2023-03-14T06:03:44+00:00
sword
swordwue
attachment; filename=deposit.zip
b913dabd5119af2a402a9e367c45c3b3
Cells (2023) 12:2, 288. https://doi.org/10.3390/cells12020288
Klinische Studienzentrale (Universitätsklinikum)
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Axel Haarmann
Christoph Vollmuth
Alexander M. Kollikowski
Peter U. Heuschmann
Mirko Pham
Guido Stoll
Hermann Neugebauer
Michael K. Schuhmann
eng
uncontrolled
endoglin
eng
uncontrolled
brain endothelium
eng
uncontrolled
stroke
eng
uncontrolled
shedding
eng
uncontrolled
mechanical thrombectomy
eng
uncontrolled
hypoxia
eng
uncontrolled
reperfusion injury
eng
uncontrolled
biomarker
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Institut für Klinische Epidemiologie und Biometrie
Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie)
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/30499/cells-12-00288-v2.pdf
28512
2018
eng
1
19
article
1
--
2018-01-11
--
Protein activity of the \(Fusarium\) \(fujikuroi\) rhodopsins CarO and OpsA and their relation to fungus−plant interaction
Fungi possess diverse photosensory proteins that allow them to perceive different light wavelengths and to adapt to changing light conditions in their environment. The biological and physiological roles of the green light-sensing rhodopsins in fungi are not yet resolved. The rice plant pathogen Fusarium fujikuroi exhibits two different rhodopsins, CarO and OpsA. CarO was previously characterized as a light-driven proton pump. We further analyzed the pumping behavior of CarO by patch-clamp experiments. Our data show that CarO pumping activity is strongly augmented in the presence of the plant hormone indole-3-acetic acid and in sodium acetate, in a dose-dependent manner under slightly acidic conditions. By contrast, under these and other tested conditions, the Neurospora rhodopsin (NR)-like rhodopsin OpsA did not exhibit any pump activity. Basic local alignment search tool (BLAST) searches in the genomes of ascomycetes revealed the occurrence of rhodopsin-encoding genes mainly in phyto-associated or phytopathogenic fungi, suggesting a possible correlation of the presence of rhodopsins with fungal ecology. In accordance, rice plants infected with a CarO-deficient F. fujikuroi strain showed more severe bakanae symptoms than the reference strain, indicating a potential role of the CarO rhodopsin in the regulation of plant infection by this fungus.
International Journal of Molecular Sciences
1422-0067
10.3390/ijms19010215
urn:nbn:de:bvb:20-opus-285125
2022-09-05T19:03:22+00:00
sword
swordwue
attachment; filename=deposit.zip
b6a93a82ad902c57d24bf47e49dd32ba
International Journal of Molecular Sciences (2018) 19:1, 215. https://doi.org/10.3390/ijms19010215
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Alexander Adam
Stephan Deimel
Javier Pardo-Medina
Jorge García-Martínez
Tilen Konte
M. Carmen Limón
Javier Avalos
Ulrich Terpitz
eng
uncontrolled
fungal rhodopsins
eng
uncontrolled
CarO
eng
uncontrolled
OpsA
eng
uncontrolled
Fusarium fujikuroi
eng
uncontrolled
Oryza sativa
eng
uncontrolled
rice–plant infection
eng
uncontrolled
green light perception
eng
uncontrolled
indole-3-acetic acid (IAA)
eng
uncontrolled
bakanae
eng
uncontrolled
patch-clamp
Biowissenschaften; Biologie
open_access
Theodor-Boveri-Institut für Biowissenschaften
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/28512/ijms-19-00215.pdf
13933
2011
eng
R21
13
article
1
2016-10-14
--
--
Expression of K\(_2\)\(_P\)5.1 potassium channels on CD4\(^+\)T lymphocytes correlates with disease activity in rheumatoid arthritis patients
Introduction
CD4+ T cells express K2P5.1 (TWIK-related acid-sensitive potassium channel 2 (TASK2); KCNK5), a member of the two-pore domain potassium channel family, which has been shown to influence T cell effector functions. Recently, it was shown that K2P5.1 is upregulated upon (autoimmune) T cell stimulation. The aim of this study was to correlate expression levels of K2P5.1 on T cells from patients with rheumatoid arthritis (RA) to disease activity in these patients.
Methods
Expression levels of K2P5.1 were measured by RT-PCR in the peripheral blood of 58 patients with RA and correlated with disease activity parameters (C-reactive protein levels, erythrocyte sedimentation rates, disease activity score (DAS28) scores). Twenty patients undergoing therapy change were followed-up for six months. Additionally, synovial fluid and synovial biopsies were investigated for T lymphocytes expressing K2P5.1.
Results
K2P5.1 expression levels in CD4+ T cells show a strong correlation to DAS28 scores in RA patients. Similar correlations were found for serological inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein). In addition, K2P5.1 expression levels of synovial fluid-derived T cells are higher compared to peripheral blood T cells. Prospective data in individual patients show a parallel behaviour of K2P5.1 expression to disease activity parameters during a longitudinal follow-up for six months.
Conclusions
Disease activity in RA patients correlates strongly with K2P5.1 expression levels in CD4+ T lymphocytes in the peripheral blood in cross-sectional as well as in longitudinal observations. Further studies are needed to investigate the exact pathophysiological mechanisms and to evaluate the possible use of K2P5.1 as a potential biomarker for disease activity and differential diagnosis.
Arthritis Research & Therapy
10.1186/ar3245
urn:nbn:de:bvb:20-opus-139334
Arthritis Research & Therapy 2011 13:R21.
Stefan Bittner
Nicole Bobak
Martin Feuchtenberger
Alexander M Herrmann
Kerstin Göbel
Raimund W Kinne
Anker J Hansen
Thomas Budde
Christoph Kleinschnitz
Oliver Frey
Hans-Peter Tony
Heinz Wiendl
Sven G Meuth
eng
uncontrolled
neurology
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Medizinische Klinik und Poliklinik II
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13933/050_Bittner_Arthritis-Research-and-Therapy.pdf
16614
2016
eng
11540
7
article
1
2018-07-31
--
--
Giant photon bunching, superradiant pulse emission and excitation trapping in quantum-dot nanolasers
Light is often characterized only by its classical properties, like intensity or coherence. When looking at its quantum properties, described by photon correlations, new information about the state of the matter generating the radiation can be revealed. In particular the difference between independent and entangled emitters, which is at the heart of quantum mechanics, can be made visible in the photon statistics of the emitted light. The well-studied phenomenon of superradiance occurs when quantum–mechanical correlations between the emitters are present. Notwithstanding, superradiance was previously demonstrated only in terms of classical light properties. Here, we provide the missing link between quantum correlations of the active material and photon correlations in the emitted radiation. We use the superradiance of quantum dots in a cavity-quantum electrodynamics laser to show a direct connection between superradiant pulse emission and distinctive changes in the photon correlation function. This directly demonstrates the importance of quantum–mechanical correlations and their transfer between carriers and photons in novel optoelectronic devices.
Nature Communications
10.1038/ncomms11540
urn:nbn:de:bvb:20-opus-166144
Nature Communications 2016, 7:11540. DOI: 10.1038/ncomms11540
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Frank Jahnke
Christopher Gies
Marc Aßmann
Manfred Bayer
H.A.M. Leymann
Alexander Foerster
Jan Wiersig
Christian Schneider
Martin Kamp
Sven Höfling
eng
uncontrolled
photon bunching
eng
uncontrolled
quantum mechanics
eng
uncontrolled
superradiant pulse emission
Physik
open_access
Physikalisches Institut
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16614/Jahnke_Nature_Communications.pdf