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1. Milk oligosaccharide-driven persistence of Bifidobacterium pseudocatenulatum modulates local and systemic microbial metabolites upon synbiotic treatment in conventionally colonized mice

Author

Jules A. Larke, Britta E. Heiss, Amy M. Ehrlich, Diana H. Taft, Helen E. Raybould, David A. Mills, and Carolyn M. Slupsky

Subjects
Probiotic, Prebiotic, Colonization, HMO, Human milk oligosaccharide, 2′-FL, Microbial ecology, QR100-130
Abstract

Abstract Background Bifidobacteria represent an important gut commensal in humans, particularly during initial microbiome assembly in the first year of life. Enrichment of Bifidobacterium is mediated though the utilization of human milk oligosaccharides (HMOs), as several human-adapted species have dedicated genomic loci for transport and metabolism of these glycans. This results in the release of fermentation products into the gut lumen which may offer physiological benefits to the host. Synbiotic pairing of probiotic species with a cognate prebiotic delivers a competitive advantage, as the prebiotic provides a nutrient niche. Methods To determine the fitness advantage and metabolic characteristics of an HMO-catabolizing Bifidobacterium strain in the presence or absence of 2′-fucosyllactose (2′-FL), conventionally colonized mice were gavaged with either Bifidobacterium pseudocatenulatum MP80 (B.p. MP80) (as the probiotic) or saline during the first 3 days of the experiment and received water or water containing 2′-FL (as the prebiotic) throughout the study. Results 16S rRNA gene sequencing revealed that mice provided only B.p. MP80 were observed to have a similar microbiota composition as control mice throughout the experiment with a consistently low proportion of Bifidobacteriaceae present. Using 1H NMR spectroscopy, similar metabolic profiles of gut luminal contents and serum were observed between the control and B.p. MP80 group. Conversely, synbiotic supplemented mice exhibited dramatic shifts in their community structure across time with an overall increased, yet variable, proportion of Bifidobacteriaceae following oral inoculation. Parsing the synbiotic group into high and moderate bifidobacterial persistence based on the median proportion of Bifidobacteriaceae, significant differences in gut microbial diversity and metabolite profiles were observed. Notably, metabolites associated with the fermentation of 2′-FL by bifidobacteria were significantly greater in mice with a high proportion of Bifidobacteriaceae in the gut suggesting metabolite production scales with population density. Moreover, 1,2-propanediol, a fucose fermentation product, was only observed in the liver and brain of mice harboring high proportions of Bifidobacteriaceae. Conclusions This study reinforces that the colonization of the gut with a commensal microorganism does not guarantee a specific functional output. Video Abstract

Published
2023
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2. Bifidobacterium catabolism of human milk oligosaccharides overrides endogenous competitive exclusion driving colonization and protection

Author

Britta E. Heiss, Amy M. Ehrlich, Maria X. Maldonado-Gomez, Diana H. Taft, Jules A. Larke, Michael L. Goodson, Carolyn M. Slupsky, Daniel J. Tancredi, Helen E. Raybould, and David A. Mills

Subjects
gut microbiota, human milk oligosaccharides, bifidobacterium, colonization, probiotics, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Understanding how exogenous microbes stably colonize the animal gut is essential to reveal mechanisms of action and tailor effective probiotic treatments. Bifidobacterium species are naturally enriched in the gastrointestinal tract of breast-fed infants. Human milk oligosaccharides (HMOs) are associated with this enrichment. However, direct mechanistic proof of the importance of HMOs in this colonization is lacking given milk contains additional factors that impact the gut microbiota. This study examined mice supplemented with the HMO 2ʹfucosyllactose (2ʹFL) together with a 2ʹFL-consuming strain, Bifidobacterium pseudocatenulatum MP80. 2ʹFL supplementation creates a niche for high levels of B.p. MP80 persistence, similar to Bifidobacterium levels seen in breast-fed infants. This synergism impacted gut microbiota composition, activated anti-inflammatory pathways and protected against chemically-induced colitis. These results demonstrate that bacterial-milk glycan interactions alone drive enrichment of beneficial Bifidobacterium and provide a model for tunable colonization thus facilitating insight into mechanisms of health promotion by bifidobacteriain neonates.

Published
2021
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4. Optogenetic activation of striatal cholinergic interneurons regulates L-dopa-induced dyskinesias

Author

Tanuja Bordia, Xiomara A. Perez, Jaime E. Heiss, Danhui Zhang, and Maryka Quik

Subjects
ChAT-Cre, ChR2, Dyskinesias, Nicotinic, Optogenetics, Parkinson's disease, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

L-dopa-induced dyskinesias (LIDs) are a serious complication of L-dopa therapy for Parkinson's disease. Emerging evidence indicates that the nicotinic cholinergic system plays a role in LIDs, although the pathways and mechanisms are poorly understood. Here we used optogenetics to investigate the role of striatal cholinergic interneurons in LIDs. Mice expressing cre-recombinase under the control of the choline acetyltransferase promoter (ChAT-Cre) were lesioned by unilateral injection of 6-hydroxydopamine. AAV5-ChR2-eYFP or AAV5-control-eYFP was injected into the dorsolateral striatum, and optical fibers implanted. After stable virus expression, mice were treated with L-dopa. They were then subjected to various stimulation protocols for 2 h and LIDs rated. Continuous stimulation with a short duration optical pulse (1–5 ms) enhanced LIDs. This effect was blocked by the general muscarinic acetylcholine receptor (mAChR) antagonist atropine indicating it was mAChR-mediated. By contrast, continuous stimulation with a longer duration optical pulse (20 ms to 1 s) reduced LIDs to a similar extent as nicotine treatment (~50%). The general nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine blocked the decline in LIDs with longer optical pulses showing it was nAChR-mediated. None of the stimulation regimens altered LIDs in control-eYFP mice. Lesion-induced motor impairment was not affected by optical stimulation indicating that cholinergic transmission selectively regulates LIDs. Longer pulse stimulation increased the number of c-Fos expressing ChAT neurons, suggesting that changes in this immediate early gene may be involved. These results demonstrate that striatal cholinergic interneurons play a critical role in LIDs and support the idea that nicotine treatment reduces LIDs via nAChR desensitization.

Published
2016
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6. Bioinspired polymer microstructures for directional transport of oily liquids

Author

C. Plamadeala, F. Hischen, R. Friesenecker, R. Wollhofen, J. Jacak, G. Buchberger, E. Heiss, T.A. Klar, W. Baumgartner, and J. Heitz

Subjects
biomimetics, two-photon lithography, directional transport, Science
Abstract

Nature has always served as an inspiration for scientists, helping them to solve a large diversity of technical problems. In our case, we are interested in the directional transport of oily liquids and as a model for this application we used the flat bug Dysodius lunatus. In this report, we present arrays of drops looking like polymer microstructures produced by the two-photon polymerization technique that mimic the micro-ornamentation from the bug's cuticle. A good directionality of oil transport was achieved, directly controlled by the direction of the pointed microstructures at the surface. If the tips of the drop-like microstructures are pointing towards the left side, the liquid front moves to the right and vice versa. Similar effects could be expected for the transport of oily lubricants. These results could, therefore, be interesting for applications in friction and wear reduction.

Published
2017
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7. UeMS training requirements for angiology/Vascular Medicine: european Standards of Postgraduate Medical Specialist training (2022 Updated Version)

Author

Wautrecht, J.-C. Olinic, D.-M. Catalano, M. Baines, C. Belch, J. Blinc, A. Buschmann, I. Celovska, D. Colgan, M.-P. Dimakakos, E. Heiss, C. Kolossvary, E. Kozak, M. Kroon, B. Mazzolai, L. Marakomichelakis, G. Pecsvarady, Z. Pias Canedo, M.A. Quere, I. Roztocil, K. Schernthaner, G.H. Sieron, A. Spaak, J. Sprynger, M. Stanek, A. Staub, D. Vasic, D. Visona, A. Willfort-Ehringer, A. and Wautrecht, J.-C. Olinic, D.-M. Catalano, M. Baines, C. Belch, J. Blinc, A. Buschmann, I. Celovska, D. Colgan, M.-P. Dimakakos, E. Heiss, C. Kolossvary, E. Kozak, M. Kroon, B. Mazzolai, L. Marakomichelakis, G. Pecsvarady, Z. Pias Canedo, M.A. Quere, I. Roztocil, K. Schernthaner, G.H. Sieron, A. Spaak, J. Sprynger, M. Stanek, A. Staub, D. Vasic, D. Visona, A. Willfort-Ehringer, A.

Published
2022

9. Fucosylated Human Milk Oligosaccharide Foraging within the Species Bifidobacterium pseudocatenulatum Is Driven by Glycosyl Hydrolase Content and Specificity

Author

Chad F. Masarweh, Amr El-Hawiet, John S. Klassen, Carlito B. Lebrilla, David A. Mills, Carolyn M. Slupsky, Linh Nguyen, Nick M Jensen, Britta E. Heiss, Jennifer L Hoeflinger, Jasmine C.C. Davis, Jules A. Larke, Guy Shani, Elisha Goonatilleke, Saumya Wickramasinghe, and Dudley, Edward G

Subjects
Glycan, Hydrolases, Bifidobacterium pseudocatenulatum, substrate-binding protein, Oligosaccharides, Microbiology, Applied Microbiology and Biotechnology, fucosylated HMO, Hydrolase, Gene cluster, Humans, Fucosidase, Gene, health care economics and organizations, Nutrition, Pediatric, chemistry.chemical_classification, alpha-L-Fucosidase, fucosidases, Ecology, biology, Milk, Human, Catabolism, strain specificity, Infant, α-fucosidase, glycan metabolism, Oligosaccharide, alpha-fucosidase, Milk, chemistry, biology.protein, Food Microbiology, milk oligosaccharides, Female, Bifidobacterium, Human, Food Science, Biotechnology
Abstract

Human milk enriches members of the genus Bifidobacterium in the infant gut. One species, Bifidobacterium pseudocatenulatum, is found in the gastrointestinal tracts of adults and breastfed infants. In this study, B. pseudocatenulatum strains were isolated and characterized to identify genetic adaptations to the breastfed infant gut. During growth on pooled human milk oligosaccharides (HMOs), we observed two distinct groups of B. pseudocatenulatum, isolates that readily consumed HMOs and those that did not, a difference driven by variable catabolism of fucosylated HMOs. A conserved gene cluster for fucosylated HMO utilization was identified in several sequenced B. pseudocatenulatum strains. One isolate, B. pseudocatenulatum MP80, which uniquely possessed GH95 and GH29 α-fucosidases, consumed the majority of fucosylated HMOs tested. Furthermore, B. pseudocatenulatum SC585, which possesses only a single GH95 α-fucosidase, lacked the ability to consume the complete repertoire of linkages within the fucosylated HMO pool. Analysis of the purified GH29 and GH95 fucosidase activities directly on HMOs revealed complementing enzyme specificities with the GH95 enzyme preferring 1-2 fucosyl linkages and the GH29 enzyme favoring 1-3 and 1-4 linkages. The HMO-binding specificities of the family 1 solute-binding protein component linked to the fucosylated HMO gene cluster in both SC585 and MP80 are similar, suggesting differential transport of fucosylated HMO is not a driving factor in each strain's distinct HMO consumption pattern. Taken together, these data indicate the presence or absence of specific α-fucosidases directs the strain-specific fucosylated HMO utilization pattern among bifidobacteria and likely influences competitive behavior for HMO foraging in situ. IMPORTANCE Often isolated from the human gut, microbes from the bacterial family Bifidobacteriaceae commonly possess genes enabling carbohydrate utilization. Isolates from breastfed infants often grow on and possess genes for the catabolism of human milk oligosaccharides (HMOs), glycans found in human breast milk. However, catabolism of structurally diverse HMOs differs between bifidobacterial strains. This study identifies key gene differences between Bifidobacterium pseudocatenulatum isolates that may impact whether a microbe successfully colonizes an infant gut. In this case, the presence of complementary α-fucosidases may provide an advantage to microbes seeking residence in the infant gut. Such knowledge furthers our understanding of how diet drives bacterial colonization of the infant gut.

Published
2022

10. Bifidobacterium catabolism of human milk oligosaccharides overrides endogenous competitive exclusion driving colonization and protection

Author

Carolyn M. Slupsky, David A. Mills, Michael L. Goodson, Amy M. Ehrlich, Britta E. Heiss, Jules A. Larke, Daniel J. Tancredi, Maria X. Maldonado-Gomez, Diana H. Taft, and Helen E. Raybould

Subjects
Male, Bifidobacterium pseudocatenulatum, Oligosaccharides, RC799-869, Gut flora, bifidobacterium, Inbred C57BL, law.invention, Probiotic, Feces, Mice, fluids and secretions, law, 2.1 Biological and endogenous factors, Colonization, Aetiology, Bifidobacterium, Pediatric, Gastrointestinal tract, biology, Gastroenterology, Diseases of the digestive system. Gastroenterology, Colitis, Infectious Diseases, Milk, Breast Feeding, Female, Research Article, Research Paper, Human, Microbiology (medical), Gut microbiota, digestive system, Microbiology, Complementary and Integrative Health, medicine, Animals, Humans, Nutrition, gut microbiota, Catabolism, biology.organism_classification, medicine.disease, colonization, Gastrointestinal Microbiome, Gastrointestinal Tract, probiotics, human milk oligosaccharides, Digestive Diseases
Abstract

Understanding how exogenous microbes stably colonize the animal gut is essential to reveal mechanisms of action and tailor effective probiotic treatments. Bifidobacterium species are naturally enriched in the gastrointestinal tract of breast-fed infants. Human milk oligosaccharides (HMOs) are associated with this enrichment. However, direct mechanistic proof of the importance of HMOs in this colonization is lacking given milk contains additional factors that impact the gut microbiota. This study examined mice supplemented with the HMO 2ʹfucosyllactose (2ʹFL) together with a 2ʹFL-consuming strain, Bifidobacterium pseudocatenulatum MP80. 2ʹFL supplementation creates a niche for high levels of B.p. MP80 persistence, similar to Bifidobacterium levels seen in breast-fed infants. This synergism impacted gut microbiota composition, activated anti-inflammatory pathways and protected against chemically-induced colitis. These results demonstrate that bacterial-milk glycan interactions alone drive enrichment of beneficial Bifidobacterium and provide a model for tunable colonization thus facilitating insight into mechanisms of health promotion by bifidobacteriain neonates.

Published
2021

12. Yuri Popov — as we remember him

Author

Dmitri E. Shcherbakov, A. Ponomarenko, R. Wootton, Dany Azar, M. Mostovski, R. T. Schuh, Ch. Hoffeins, N. Ponomarenko, L. Medvedev, Viktor B. Golub, C. Soriano, E. Heiss, W. P. Wgierek, Hans-Werner Hoffeins, and S. Golovatch

Subjects
Biography, entomologists, Insect Science, Personalia, paleontologists, In memoriam, Ecology, Evolution, Behavior and Systematics
Abstract

Dr. Yuri Popov, born 5 March 1936, passed away 16 November 2016. Upon graduation from the Entomology Department of Moscow State University, he joined the Arthropoda Lab of the Paleontological Institute, where he studied fossil and living true bugs and their kin and became a major expert in that area. He was a man of many talents and had lots of friends all over the world. The few flashbacks collected here are but a small tribute to his memory.

Published
2017
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13. Optogenetic activation of striatal cholinergic interneurons regulates L-dopa-induced dyskinesias

Author

Maryka Quik, Tanuja Bordia, Jaime E. Heiss, Xiomara A. Perez, and Danhui Zhang

Subjects
0301 basic medicine, Dyskinesia, Drug-Induced, Nicotine, genetic structures, Parkinson's disease, Stimulation, Striatum, Nicotinic, Article, Choline O-Acetyltransferase, lcsh:RC321-571, Levodopa, Mice, 03 medical and health sciences, 0302 clinical medicine, Interneurons, Muscarinic acetylcholine receptor, Mecamylamine, medicine, Animals, Nicotinic Agonists, ChR2, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, ChAT-Cre, Dyskinesias, Chemistry, Choline acetyltransferase, Corpus Striatum, eye diseases, Neostriatum, Optogenetics, Nicotinic acetylcholine receptor, 030104 developmental biology, Nicotinic agonist, Neurology, nervous system, Cholinergic, sense organs, Neuroscience, 030217 neurology & neurosurgery, medicine.drug
Abstract

L-dopa-induced dyskinesias (LIDs) are a serious complication of L-dopa therapy for Parkinson's disease. Emerging evidence indicates that the nicotinic cholinergic system plays a role in LIDs, although the pathways and mechanisms are poorly understood. Here we used optogenetics to investigate the role of striatal cholinergic interneurons in LIDs. Mice expressing cre-recombinase under the control of the choline acetyltransferase promoter (ChAT-Cre) were lesioned by unilateral injection of 6-hydroxydopamine. AAV5-ChR2-eYFP or AAV5-control-eYFP was injected into the dorsolateral striatum, and optical fibers implanted. After stable virus expression, mice were treated with L-dopa. They were then subjected to various stimulation protocols for 2 h and LIDs rated. Continuous stimulation with a short duration optical pulse (1-5 ms) enhanced LIDs. This effect was blocked by the general muscarinic acetylcholine receptor (mAChR) antagonist atropine indicating it was mAChR-mediated. By contrast, continuous stimulation with a longer duration optical pulse (20 ms to 1 s) reduced LIDs to a similar extent as nicotine treatment (~50%). The general nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine blocked the decline in LIDs with longer optical pulses showing it was nAChR-mediated. None of the stimulation regimens altered LIDs in control-eYFP mice. Lesion-induced motor impairment was not affected by optical stimulation indicating that cholinergic transmission selectively regulates LIDs. Longer pulse stimulation increased the number of c-Fos expressing ChAT neurons, suggesting that changes in this immediate early gene may be involved. These results demonstrate that striatal cholinergic interneurons play a critical role in LIDs and support the idea that nicotine treatment reduces LIDs via nAChR desensitization.

Published
2016

14. Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data

Author

Bruce C V Campbell, Charles B L M Majoie, Gregory W Albers, Bijoy K Menon, Nawaf Yassi, Gagan Sharma, Wim H van Zwam, Robert J van Oostenbrugge, Andrew M Demchuk, Francis Guillemin, Philip White, Antoni Dávalos, Aad van der Lugt, Kenneth S Butcher, Aboubaker Cherifi, Henk A Marquering, Geoffrey Cloud, Juan M Macho Fernández, Jeremy Madigan, Catherine Oppenheim, Geoffrey A Donnan, Yvo B W E M Roos, Jai Shankar, Hester Lingsma, Alain Bonafé, Hélène Raoult, María Hernández-Pérez, Aditya Bharatha, Reza Jahan, Olav Jansen, Sébastien Richard, Elad I Levy, Olvert A Berkhemer, Marc Soudant, Lucia Aja, Stephen M Davis, Timo Krings, Marie Tisserand, Luis San Román, Alejandro Tomasello, Debbie Beumer, Scott Brown, David S Liebeskind, Serge Bracard, Keith W Muir, Diederik W J Dippel, Mayank Goyal, Jeffrey L Saver, Tudor G Jovin, Michael D Hill, Peter J Mitchell, Puck SS Fransen, Lucie A van den Berg, Hester F Lingsma, Albert J Yoo, Wouter J Schonewille, Jan Albert Vos, Paul J Nederkoorn, Marieke JH Wermer, Marianne AA van Walderveen, Julie Staals, Jeannette Hofmeijer, Jacques A. van Oostayen, Geert J. Lycklama à Nijeholt, Jelis Boiten, Patrick A. Brouwer, Bart J. Emmer, Sebastiaan F. de Bruijn, Lukas C. van Dijk, Jaap Kappelle, Rob H Lo, Ewoud J. van Dijk, Joost de Vries, Paul L.M. de Kort, Willem Jan J. van Rooij, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Marieke C. Visser, Joseph C.J. Bot, Patrick C. Vroomen, Omid Eshghi, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Alexander V. Tielbeek, Heleen M. den Hertog, Dick G. Gerrits, Renske M. van den Berg-Vos, Giorgos B. Karas, Ewout W. Steyerberg, Zwenneke Flach, Henk A. Marquering, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, Ludo F.M. Beenen, René van den Berg, Peter J. Koudstaal, Wim H. van Zwam, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Charles B.L.M. Majoie, Diederik W.J. Dippel, Martin M. Brown, Thomas Liebig, Theo Stijnen, Tommy Andersson, Heinrich Mattle, Nils Wahlgren, Esther van der Heijden, Naziha Ghannouti, Nadine Fleitour, Imke Hooijenga, Corina Puppels, Wilma Pellikaan, Annet Geerling, Annemieke Lindl-Velema, Gina van Vemde, Ans de Ridder, Paut Greebe, José de Bont-Stikkelbroeck, Joke de Meris, Kirsten Janssen, Willy Struijk, Silvan Licher, Nikki Boodt, Adriaan Ros, Esmee Venema, Ilse Slokkers, Raymie-Jayce Ganpat, Maxim Mulder, Nawid Saiedie, Alis Heshmatollah, Stefanie Schipperen, Stefan Vinken, Tiemen van Boxtel, Jeroen Koets, Merel Boers, Emilie Santos, Jordi Borst, Ivo Jansen, Manon Kappelhof, Marit Lucas, Ralph Geuskens, Renan Sales Barros, Roeland Dobbe, Marloes Csizmadia, MD Hill, M Goyal, AM Demchuk, BK Menon, M Eesa, KJ Ryckborst, MR Wright, NR Kamal, L Andersen, PA Randhawa, T Stewart, S Patil, P Minhas, M Almekhlafi, S Mishra, F Clement, T Sajobi, A Shuaib, WJ Montanera, D Roy, FL Silver, TG Jovin, DF Frei, B Sapkota, JL Rempel, J Thornton, D Williams, D Tampieri, AY Poppe, D Dowlatshahi, JH Wong, AP Mitha, S Subramaniam, G Hull, MW Lowerison, M Salluzzi, M Maxwell, S Lacusta, E Drupals, K Armitage, PA Barber, EE Smith, WF Morrish, SB Coutts, C Derdeyn, B Demaerschalk, D Yavagal, R Martin, R Brant, Y Yu, RA Willinsky, A Weill, C Kenney, H Aram, PK Stys, TW Watson, G Klein, D Pearson, P Couillard, A Trivedi, D Singh, E Klourfeld, O Imoukhuede, D Nikneshan, S Blayney, R Reddy, P Choi, M Horton, T Musuka, V Dubuc, TS Field, J Desai, S Adatia, A Alseraya, V Nambiar, R van Dijk, NJ Newcommon, B Schwindt, KS Butcher, T Jeerakathil, B Buck, K Khan, SS Naik, DJ Emery, RJ Owen, TB Kotylak, RA Ashforth, TA Yeo, D McNally, M Siddiqui, M Saqqur, D Hussain, H Kalashyan, A Manosalva, M Kate, L Gioia, S Hasan, A Mohammad, M Muratoglu, A Cullen, P Brennan, A O'Hare, S Looby, D Hyland, S Duff, M McCusker, B Hallinan, S Lee, J McCormack, A Moore, M O'Connor, C Donegan, L Brewer, A Martin, S Murphy, K O'Rourke, S Smyth, P Kelly, T Lynch, T Daly, P O'Brien, A O'Driscoll, M Martin, R Collins, T Coughlan, D McCabe, D O'Neill, M Mulroy, O Lynch, T Walsh, M O'Donnell, T Galvin, J Harbison, P McElwaine, K Mulpeter, C McLoughlin, M Reardon, E Harkin, E Dolan, M Watts, N Cunningham, C Fallon, S Gallagher, P Cotter, M Crowe, R Doyle, I Noone, M Lapierre, VA Coté, S Lanthier, C Odier, A Durocher, J Raymond, N Daneault, Y Deschaintre, B Jankowitz, L Baxendell, L Massaro, C Jackson-Graves, S Decesare, P Porter, K Armbruster, A Adams, J Billigan, J Oakley, A Ducruet, A Jadhav, D-V Giurgiutiu, A Aghaebrahim, V Reddy, M Hammer, M Starr, V Totoraitis, L Wechsler, S Streib, S Rangaraju, D Campbell, M Rocha, D Gulati, T Krings, L Kalman, A Cayley, J Williams, R Wiegner, LK Casaubon, C Jaigobin, JM del Campo, E Elamin, JD Schaafsma, R Agid, R Farb, K ter Brugge, BL Sapkoda, BW Baxter, K Barton, A Knox, A Porter, A Sirelkhatim, T Devlin, C Dellinger, N Pitiyanuvath, J Patterson, J Nichols, S Quarfordt, J Calvert, H Hawk, C Fanale, A Bitner, A Novak, D Huddle, R Bellon, D Loy, J Wagner, I Chang, E Lampe, B Spencer, R Pratt, R Bartt, S Shine, G Dooley, T Nguyen, M Whaley, K McCarthy, J Teitelbaum, W Poon, N Campbell, M Cortes, C Lum, R Shamloul, S Robert, G Stotts, M Shamy, N Steffenhagen, D Blacquiere, M Hogan, M AlHazzaa, G Basir, H Lesiuk, D Iancu, M Santos, H Choe, DC Weisman, K Jonczak, A Blue-Schaller, Q Shah, L MacKenzie, B Klein, K Kulandaivel, O Kozak, DJ Gzesh, LJ Harris, JS Khoury, J Mandzia, D Pelz, S Crann, L Fleming, K Hesser, B Beauchamp, B Amato-Marzialli, M Boulton, P Lopez- Ojeda, M Sharma, S Lownie, R Chan, R Swartz, P Howard, D Golob, D Gladstone, K Boyle, M Boulos, J Hopyan, V Yang, L Da Costa, CA Holmstedt, AS Turk, R Navarro, E Jauch, S Ozark, R Turner, S Phillips, J Shankar, J Jarrett, G Gubitz, W Maloney, R Vandorpe, M Schmidt, J Heidenreich, G Hunter, M Kelly, R Whelan, L Peeling, PA Burns, A Hunter, I Wiggam, E Kerr, M Watt, A Fulton, P Gordon, I Rennie, P Flynn, G Smyth, S O'Leary, N Gentile, G Linares, P McNelis, K Erkmen, P Katz, A Azizi, M Weaver, C Jungreis, S Faro, P Shah, H Reimer, V Kalugdan, G Saposnik, A Bharatha, Y Li, P Kostyrko, T Marotta, W Montanera, D Sarma, D Selchen, J Spears, JH Heo, K Jeong, DJ Kim, BM Kim, YD Kim, D Song, K-J Lee, J Yoo, OY Bang, S Rho, J Lee, P Jeon, KH Kim, J Cha, SJ Kim, S Ryoo, MJ Lee, S-I Sohn, C-H Kim, H-G Ryu, J-H Hong, H-W Chang, C-Y Lee, J Rha, Bruce CV Campbell, Leonid Churilov, Bernard Yan, Richard Dowling, Thomas J Oxley, Teddy Y Wu, Gabriel Silver, Amy McDonald, Rachael McCoy, Timothy J Kleinig, Rebecca Scroop, Helen M Dewey, Marion Simpson, Mark Brooks, Bronwyn Coulton, Martin Krause, Timothy J Harrington, Brendan Steinfort, Kenneth Faulder, Miriam Priglinger, Susan Day, Thanh Phan, Winston Chong, Michael Holt, Ronil V Chandra, Henry Ma, Dennis Young, Kitty Wong, Tissa Wijeratne, Hans Tu, Elizabeth Mackay, Sherisse Celestino, Christopher F Bladin, Poh Sien Loh, Amanda Gilligan, Zofia Ross, Skye Coote, Tanya Frost, Mark W Parsons, Ferdinand Miteff, Christopher R Levi, Timothy Ang, Neil Spratt, Lara Kaauwai, Monica Badve, Henry Rice, Laetitia de Villiers, P. Alan Barber, Ben McGuinness, Ayton Hope, Maurice Moriarty, Patricia Bennett, Andrew Wong, Alan Coulthard, Andrew Lee, Jim Jannes, Deborah Field, Simon Salinas, Elise Cowley, Barry Snow, John Kolbe, Richard Stark, John King, Richard Macdonnell, John Attia, Cate D'Este, Hans-Christoph Diener, Elad I. Levy, Vitor Mendes Pereira, Gregory W. Albers, Christophe Cognard, David J. Cohen, Werner Hacke, Tudor G. Jovin, Heinrich P. Mattle, Raul G. Nogueira, Adnan H. Siddiqui, Dileep R. Yavagal, Rüdiger von Kummer, Wade Smith, Francis Turjman, Scott Hamilton, Richard Chiacchierini, Arun Amar, Nerses Sanossian, Yince Loh, B Baxter, VK Reddy, A Horev, M Star, A Siddiqui, LN Hopkins, K Snyder, R Sawyer, S Hall, V Costalat, C Riquelme, P Machi, E Omer, C Arquizan, I Mourand, M Charif, X Ayrignac, N Menjot de Champfleur, N Leboucq, G Gascou, M Moynier, R du Mesnil de Rochemont, O Singer, J Berkefeld, C Foerch, M Lorenz, W Pfeilschifer, E Hattingen, M Wagner, SJ You, S Lescher, H Braun, S Dehkharghani, SR Belagaje, A Anderson, A Lima, M Obideen, D Haussen, R Dharia, M Frankel, V Patel, K Owada, A Saad, L Amerson, C Horn, S Doppelheuer, K Schindler, DK Lopes, M Chen, R Moftakhar, C Anton, M Smreczak, JS Carpenter, S Boo, A Rai, T Roberts, A Tarabishy, L Gutmann, C Brooks, J Brick, J Domico, G Reimann, K Hinrichs, M Becker, E Heiss, C Selle, A Witteler, S Al-Boutros, M-J Danch, A Ranft, S Rohde, K Burg, C Weimar, V Zegarac, C Hartmann, M Schlamann, S Göricke, A Ringlestein, I Wanke, C Mönninghoff, M Dietzold, R Budzik, T Davis, G Eubank, WJ Hicks, P Pema, N Vora, J Mejilla, M Taylor, W Clark, A Rontal, J Fields, B Peterson, G Nesbit, H Lutsep, H Bozorgchami, R Priest, O Ologuntoye, S Barnwell, A Dogan, K Herrick, C Takahasi, N Beadell, B Brown, S Jamieson, MS Hussain, A Russman, F Hui, D Wisco, K Uchino, Z Khawaja, I Katzan, G Toth, E Cheng-Ching, M Bain, S Man, A Farrag, P George, S John, L Shankar, A Drofa, R Dahlgren, A Bauer, A Itreat, A Taqui, R Cerejo, A Richmond, P Ringleb, M Bendszus, M Möhlenbruch, T Reiff, H Amiri, J Purrucker, C Herweh, M Pham, O Menn, I Ludwig, I Acosta, C Villar, W Morgan, C Sombutmai, F Hellinger, E Allen, M Bellew, R Gandhi, E Bonwit, J Aly, RD Ecker, D Seder, J Morris, M Skaletsky, J Belden, C Baker, LS Connolly, P Papanagiotou, C Roth, A Kastrup, M Politi, F Brunner, M Alexandrou, H Merdivan, C Ramsey, C Given II, S Renfrow, V Deshmukh, K Sasadeusz, F Vincent, JT Thiesing, J Putnam, A Bhatt, A Kansara, D Caceves, T Lowenkopf, L Yanase, J Zurasky, S Dancer, B Freeman, T Scheibe-Mirek, J Robison, J Roll, D Clark, M Rodriguez, B-FM Fitzsimmons, O Zaidat, JR Lynch, M Lazzaro, T Larson, L Padmore, E Das, A Farrow-Schmidt, A Hassan, W Tekle, C Cate, O Jansen, C Cnyrim, F Wodarg, C Wiese, A Binder, C Riedel, A Rohr, N Lang, H Laufs, S Krieter, L Remonda, M Diepers, J Añon, K Nedeltchev, T Kahles, S Biethahn, M Lindner, V Chang, C Gächter, C Esperon, M Guglielmetti, JF Arenillas Lara, M Martínez Galdámez, AI Calleja Sanz, E Cortijo Garcia, P Garcia Bermejo, S Perez, P Mulero Carrillo, E Crespo Vallejo, M Ruiz Piñero, L Lopez Mesonero, FJ Reyes Muñoz, C Brekenfeld, J-H Buhk, A Krützelmann, G Thomalla, B Cheng, C Beck, J Hoppe, E Goebell, B Holst, U Grzyska, G Wortmann, S Starkman, G Duckwiler, R Jahan, N Rao, S Sheth, K Ng, A Noorian, V Szeder, M Nour, M McManus, J Huang, J Tarpley, S Tateshima, N Gonzalez, L Ali, D Liebeskind, J Hinman, M Calderon-Arnulphi, C Liang, J Guzy, S Koch, K DeSousa, G Gordon-Perue, M Elhammady, E Peterson, V Pandey, S Dharmadhikari, P Khandelwal, A Malik, R Pafford, P Gonzalez, K Ramdas, G Andersen, D Damgaard, P Von Weitzel-Mudersbach, C Simonsen, N Ruiz de Morales Ayudarte, M Poulsen, L Sørensen, S Karabegovich, M Hjørringgaard, N Hjort, T Harbo, K Sørensen, E Deshaies, D Padalino, A Swarnkar, JG Latorre, E Elnour, Z El-Zammar, M Villwock, H Farid, A Balgude, L Cross, K Hansen, M Holtmannspötter, D Kondziella, J Hoejgaard, S Taudorf, H Soendergaard, A Wagner, M Cronquist, T Stavngaard, M Cortsen, LH Krarup, T Hyldal, H-P Haring, S Guggenberger, M Hamberger, J Trenkler, M Sonnberger, K Nussbaumer, C Dominger, E Bach, BD Jagadeesan, R Taylor, J Kim, K Shea, R Tummala, H Zacharatos, D Sandhu, M Ezzeddine, A Grande, D Hildebrandt, K Miller, J Scherber, A Hendrickson, M Jumaa, S Zaidi, T Hendrickson, V Snyder, M Killer-Oberpfalzer, J Mutzenbach, F Weymayr, E Broussalis, K Stadler, A Jedlitschka, A Malek, N Mueller-Kronast, P Beck, C Martin, D Summers, J Day, I Bettinger, W Holloway, K Olds, S Arkin, N Akhtar, C Boutwell, S Crandall, M Schwartzman, C Weinstein, B Brion, S Prothmann, J Kleine, K Kreiser, T Boeckh-Behrens, H Poppert, S Wunderlich, ML Koch, V Biberacher, A Huberle, G Gora-Stahlberg, B Knier, T Meindl, D Utpadel-Fischler, M Zech, M Kowarik, C Seifert, B Schwaiger, A Puri, S Hou, A Wakhloo, M Moonis, N Henninger, R Goddeau, F Massari, A Minaeian, JD Lozano, M Ramzan, C Stout, A Patel, A Tunguturi, S Onteddu, R Carandang, M Howk, M Ribó, E Sanjuan, M Rubiera, J Pagola, A Flores, M Muchada, P Meler, E Huerga, S Gelabert, P Coscojuela, A Tomasello, D Rodriguez, E Santamarina, O Maisterra, S Boned, L Seró, A Rovira, CA Molina, M Millán, L Muñoz, N Pérez de la Ossa, M Gomis, L Dorado, E López-Cancio, E Palomeras, J Munuera, P García Bermejo, S Remollo, C Castaño, R García-Sort, P Cuadras, P Puyalto, M Hernández-Pérez, M Jiménez, A Martínez-Piñeiro, G Lucente, A Dávalos, A Chamorro, X Urra, V Obach, A Cervera, S Amaro, L Llull, J Codas, M Balasa, J Navarro, H Ariño, A Aceituno, S Rudilosso, A Renu, JM Macho, L San Roman, J Blasco, A López, N Macías, P Cardona, H Quesada, F Rubio, L Cano, B Lara, MA de Miquel, L Aja, J Serena, E Cobo, Kennedy R Lees, J Arenillas, R Roberts, F Al-Ajlan, L Zimmel, S Patel, J Martí-Fàbregas, M Salvat-Plana, S Bracard, Xavier Ducrocq, René Anxionnat, Pierre-Alexandre Baillot, Charlotte Barbier, Anne-Laure Derelle, Jean-Christophe Lacour, Yves Samson, Nader Sourour, Flore Baronnet-Chauvet, Frédéric Clarencon, Sophie Crozier, Sandrine Deltour, Federico Di Maria, Raphael Le Bouc, Anne Leger, Gurkan Mutlu, Charlotte Rosso, Zoltan Szatmary, Marion Yger, Chiara Zavanone, Serge Bakchine, Laurent Pierot, Nathalie Caucheteux, Laurent Estrade, Krzysztof Kadziolka, Alexandre Leautaud, Céline Renkes, Isabelle Serre, Hubert Desal, Benoît Guillon, Claire Boutoleau-Bretonniere, Benjamin Daumas-Duport, Solène De Gaalon, Pascal Derkinderen, Sarah Evain, Fanny Herisson, David-Axel Laplaud, Thibaud Lebouvier, Alina Lintia-Gaultier, Hélène Pouclet-Courtemanche, Tiphaine Rouaud, Violaine Rouaud Jaffrenou, Aurélia Schunck, Mathieu Sevin-Allouet, Frederique Toulgoat, Sandrine Wiertlewski, Jean-Yves Gauvrit, Thomas Ronziere, Vincent Cahagne, Jean-Christophe Ferre, Jean-François Pinel, Jean-Louis Mas, Jean-François Meder, Amen-Adam Al Najjar-Carpentier, Julia Birchenall, Eric Bodiguel, David Calvet, Valérie Domigo, Sylvie Godon-Hardy, Vincent Guiraud, Catherine Lamy, Loubna Majhadi, Ludovic Morin, Olivier Naggara, Denis Trystram, Guillaume Turc, Jérôme Berge, Igor Sibon, Patrice Menegon, Xavier Barreau, François Rouanet, Sabrina Debruxelles, Annabelle Kazadi, Pauline Renou, Olivier Fleury, Anne Pasco-Papon, Frédéric Dubas, Jildaz Caroff, Sophie Godard Ducceschi, Marie-Aurélie Hamon, Alderic Lecluse, Guillaume Marc, Maurice Giroud, Frédéric Ricolfi, Yannick Bejot, Adrien Chavent, Arnaud Gentil, Apolline Kazemi, Guy-Victor Osseby, Charlotte Voguet, Marie-Hélène Mahagne, Jacques Sedat, Yves Chau, Laurent Suissa, Sylvain Lachaud, Emmanuel Houdart, Christian Stapf, Frédérique Buffon Porcher, Hugues Chabriat, Pierre Guedin, Dominique Herve, Eric Jouvent, Jérôme Mawet, Jean-Pierre Saint-Maurice, Hans-Martin Schneble, Norbert Nighoghossian, Nadia-Nawel Berhoune, Françoise Bouhour, Tae-Hee Cho, Laurent Derex, Sandra Felix, Hélène Gervais-Bernard, Benjamin Gory, Luis Manera, Laura Mechtouff, Thomas Ritzenthaler, Roberto Riva, Fabrizio Salaris Silvio, Caroline Tilikete, Raphael Blanc, Michaël Obadia, Mario Bruno Bartolini, Antoine Gueguen, Michel Piotin, Silvia Pistocchi, Hocine Redjem, Jacques Drouineau, Jean-Philippe Neau, Gaelle Godeneche, Matthias Lamy, Emilia Marsac, Stephane Velasco, Pierre Clavelou, Emmanuel Chabert, Nathalie Bourgois, Catherine Cornut-Chauvinc, Anna Ferrier, Jean Gabrillargues, Betty Jean, Anna-Raquel Marques, Nicolas Vitello, Olivier Detante, Marianne Barbieux, Kamel Boubagra, Isabelle Favre Wiki, Katia Garambois, Florence Tahon, Vasdev Ashok, Oguzhan Coskun, Georges Rodesch, Bertrand Lapergue, Frédéric Bourdain, Serge Evrard, Philippe Graveleau, Jean Pierre Decroix, Adrien Wang, François Sellal, Guido Ahle, Gabriela Carelli, Marie-Hélène Dugay, Claude Gaultier, Ariel Pablo Lebedinsky, Lavinia Lita, Raul Mariano Musacchio, Catherine Renglewicz-Destuynder, Alain Tournade, Françis Vuillemet, Francisco Macian Montoro, Charbel Mounayer, Frederic Faugeras, Laetitia Gimenez, Catherine Labach, Géraldine Lautrette, Christian Denier, Guillaume Saliou, Olivier Chassin, Claire Dussaule, Elsa Melki, Augustin Ozanne, Francesco Puccinelli, Marina Sachet, Mariana Sarov, Jean-François Bonneville, Thierry Moulin, Alessandra Biondi, Elisabeth De Bustos Medeiros, Fabrice Vuillier, Patrick Courtheoux, Fausto Viader, Marion Apoil-Brissard, Mathieu Bataille, Anne-Laure Bonnet, Julien Cogez, Emmanuel Touze, Xavier Leclerc, Didier Leys, Mohamed Aggour, Pierre Aguettaz, Marie Bodenant, Charlotte Cordonnier, Dominique Deplanque, Marie Girot, Hilde Henon, Erwah Kalsoum, Christian Lucas, Jean-Pierre Pruvo, Paolo Zuniga, Caroline Arquizan, Vincent Costalat, Paolo Machi, Isabelle Mourand, Carlos Riquelme, Pierre Bounolleau, Charles Arteaga, Anthony Faivre, Marc Bintner, Patrice Tournebize, Cyril Charlin, Françoise Darcel, Pascale Gauthier-Lasalarie, Marcia Jeremenko, Servane Mouton, Jean-Baptiste Zerlauth, Chantal Lamy, Deramond Hervé, Hosseini Hassan, André Gaston, Francis-Guy Barral, Pierre Garnier, Rémy Beaujeux, Valérie Wolff, Denis Herbreteau, Séverine Debiais, Alicia Murray, Gary Ford, Andy Clifton, Janet Freeman, Ian Ford, Hugh Markus, Joanna Wardlaw, Andy Molyneux, Thompson Robinson, Steff Lewis, John Norrie, Fergus Robertson, Richard Perry, Anand Dixit, Andrew Clifton, Christine Roffe, Sanjeev Nayak, Kyriakos Lobotesis, Craig Smith, Amit Herwadkar, Naga Kandasamy, Tony Goddard, John Bamford, Ganesh Subramanian, Rob Lenthall, Edward Littleton, Sal Lamin, Kelley Storey, Rita Ghatala, Azra Banaras, John Aeron-Thomas, Bath Hazel, Holly Maguire, Emelda Veraque, Louise Harrison, Rekha Keshvara, James Cunningham, Clinical Neurophysiology, Weimar, Christian (Beitragende*r), Radiology and nuclear medicine, Rheumatology, ACS - Atherosclerosis & ischemic syndromes, RS: Carim - B05 Cerebral small vessel disease, RS: CARIM - R3.03 - Cerebral small vessel disease, RS: Carim - B06 Imaging, Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: CARIM - R3.11 - Imaging, MUMC+: MA Neurologie (3), Klinische Neurowetenschappen, MUMC+: MA AIOS Neurologie (9), The Royal Melbourne Hospital, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Stanford University, University of Calgary, The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University [Maastricht], Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Neuroscience [Newcastle] (ION), Newcastle University [Newcastle], Universitat Autònoma de Barcelona (UAB), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Alberta, Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), Monash University [Melbourne], St George’s University Hospitals, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dalhousie University [Halifax], Neuroradiologie [Hôpital Gui de Chauliac], Hôpital Gui de Chauliac [Montpellier], Service de Neuroradiologie [Rennes], CHU Pontchaillou [Rennes], St. Michael's Hospital, University of California [Los Angeles] (UCLA), University of California, University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY), Toronto Western Hospital, Hôpital Foch [Suresnes], Vall d'Hebron University Hospital [Barcelona], Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University of Glasgow, Queen Elizabeth University Hospital (Glasgow), David Geffen School of Medicine [Los Angeles], University of California-University of California, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Radiology & Nuclear Medicine, Public Health, Neurology, Radiology and Nuclear Medicine, ACS - Microcirculation, ANS - Neurovascular Disorders, ACS - Amsterdam Cardiovascular Sciences, Graduate School, ACS - Pulmonary hypertension & thrombosis, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, ARD - Amsterdam Reproduction and Development, Biomedical Engineering and Physics, APH - Personalized Medicine, APH - Quality of Care, and AMS - Restoration & Development

Subjects
SELECTION, COMPUTED TOMOGRAPHIC PERFUSION, Medizin, Perfusion scanning, 030204 cardiovascular system & hematology, Brain Ischemia, 0302 clinical medicine, Modified Rankin Scale, REPERFUSION, Stroke, ComputingMilieux_MISCELLANEOUS, Thrombectomy, Aged, 80 and over, medicine.diagnostic_test, Penumbra, Endovascular Procedures, Brain, Middle Aged, Magnetic Resonance Imaging, 3. Good health, Treatment Outcome, Cerebral blood flow, Tissue Plasminogen Activator, INFARCT, Cardiology, Female, TRIAL, CT, medicine.medical_specialty, Perfusion Imaging, Neuroimaging, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, Fibrinolytic Agents, ALTEPLASE, Internal medicine, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Aged, business.industry, MECHANICAL THROMBECTOMY, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Magnetic resonance imaging, Odds ratio, medicine.disease, Neurology (clinical), business, Tomography, X-Ray Computed, 030217 neurology & neurosurgery, Fibrinolytic agent, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome.Methods In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1,2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 mu m(2)/s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0-2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered.Findings We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0.47 [95% CI 0.30-0.72], p=0.0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0.77 [0.69-0.86] per 10 mL, p(interaction)=0.29; diffusion MRI OR 0.87 [0.81-0.94] per 10 mL, p(interaction)=0.94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low.Interpretation Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imagingto-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions. Copyright (C) 2018 Elsevier Ltd. All rights reserved.

Published
2019
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15. 6‐Dihydroparadol, a Ginger Constituent, Enhances Cholesterol Efflux from THP‐1‐Derived Macrophages

Author

Verena M. Dirsch, Franz Bucar, Atanas G. Atanasov, Simone Latkolik, Angela Ladurner, Verena Hiebl, Dongdong Wang, and E Heiß

Subjects
0301 basic medicine, ATP‐binding cassette transporter A1, Probucol, Pharmacology, 03 medical and health sciences, chemistry.chemical_compound, Western blot, medicine, Research Articles, medicine.diagnostic_test, biology, Cholesterol, Reverse cholesterol transport, cardiovascular diseases, 3. Good health, 030104 developmental biology, chemistry, ABCG1, ABCA1, biology.protein, ATP‐binding cassette transporter G1, lipids (amino acids, peptides, and proteins), Apolipoprotein A1, Efflux, atherosclerosis, cholesterol efflux, Research Article, Food Science, Biotechnology, medicine.drug
Abstract

Scope Ginger is reported to be used for the prevention and treatment of cardiovascular diseases (CVD). Cholesterol efflux from macrophage foam cells is an important process in reverse cholesterol transport, whose increase may help to prevent or treat CVD. In this study, we investigated the effects of 6‐dihydroparadol from ginger on macrophage cholesterol efflux. Methods and results We show that 6‐dihydroparadol concentration‐dependently enhances both apolipoprotein A1‐ and human plasma–mediated cholesterol efflux from cholesterol‐loaded THP‐1‐derived macrophages using macrophage cholesterol efflux assay. 6‐Dihydroparadol increases protein levels of both ATP‐binding cassette transporters A1 and G1 (ATP‐binding cassette transporter A1 [ABCA1] and ATP‐binding cassette transporter G1 [ABCG1]) according to Western blot analysis. The ABCA1 inhibitor probucol completely abolishes 6‐dihydroparadol‐enhanced cholesterol efflux. Furthermore, increased ABCA1 protein levels in the presence of 6‐dihydroparadol were associated with both increased ABCA1 mRNA levels and increased ABCA1 protein stability. Enhanced ABCG1 protein levels were only associated with increased protein stability. Increased ABCA1 protein stability appeared to be the result of a reduced proteasomal degradation of the transporter in the presence of 6‐dihydroparadol. Conclusion We identified 6‐dihydroparadol from ginger as a novel promoter of cholesterol efflux from macrophages that increases both ABCA1 and ABCG1 protein abundance. This newly identified bioactivity might contribute to the antiatherogenic effects of ginger.

Published
2018
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17. Generation of expression constructs to identify ER retention motifs in the Human Herpesvirus 7 U20 protein

Author

Britta E. Heiss and Christine L. Schneider

Subjects
Signal peptide, Genetics, education.field_of_study, Immune system, Membrane protein, Endoplasmic reticulum, Population, General Engineering, ER retention, Biology, education, Gene, Transmembrane protein
Abstract

The long coevolution of β-herpesviruses with humans has resulted in the acquisition of a large variety of immune evasion strategies by these viruses. Presumably immune evasion genes are necessary for each herpesvirus to establish a life-long infection in their host. Human herpesvirus 7 (HHV-7) is a relatively understudied virus, likely because it does not typically pose significant health concerns. HHV-7 establishes a life-long infection in approximately 90% of the population before the age of 3 suggesting it likely possesses significant immune evasion strategies. Several genes found in a cluster near a known immune evasion gene, U21, may possibly encode novel immune evasion proteins. In an attempt to determine the function of one of these genes, U20, we previously expressed the protein in a variety of cell types. As predicted, U20 is a type I membrane protein targeted to the secretory system through a predicted N-terminal signal sequence. Interestingly, although U20 does not possess any predicted endoplasmic reticulum (ER) retention motifs, the exogenously expressed protein remained localized to the ER in all cell types examined. Here we describe a cloning project to generate constructs that will be used to examine the role of each domain (lumenal, transmembrane, or cytoplasmic) of U20 in ER retention.

Published
2015
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18. Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Author

Bruce C V Campbell, Wim H van Zwam, Mayank Goyal, Bijoy K Menon, Diederik W J Dippel, Andrew M Demchuk, Serge Bracard, Philip White, Antoni Dávalos, Charles B L M Majoie, Aad van der Lugt, Gary A Ford, Natalia Pérez de la Ossa, Michael Kelly, Romain Bourcier, Geoffrey A Donnan, Yvo B W E M Roos, Oh Young Bang, Raul G Nogueira, Thomas G Devlin, Lucie A van den Berg, Frédéric Clarençon, Paul Burns, Jeffrey Carpenter, Olvert A Berkhemer, Dileep R Yavagal, Vitor Mendes Pereira, Xavier Ducrocq, Anand Dixit, Helena Quesada, Jonathan Epstein, Stephen M Davis, Olav Jansen, Marta Rubiera, Xabier Urra, Emilien Micard, Hester F Lingsma, Olivier Naggara, Scott Brown, Francis Guillemin, Keith W Muir, Robert J van Oostenbrugge, Jeffrey L Saver, Tudor G Jovin, Michael D Hill, Peter J Mitchell, Puck SS Fransen, Debbie Beumer, Albert J Yoo, Wouter J Schonewille, Jan Albert Vos, Paul J Nederkoorn, Marieke JH Wermer, Marianne AA van Walderveen, Julie Staals, Jeannette Hofmeijer, Jacques A. van Oostayen, Geert J. Lycklama à Nijeholt, Jelis Boiten, Patrick A. Brouwer, Bart J. Emmer, Sebastiaan F. de Bruijn, Lukas C. van Dijk, Jaap Kappelle, Rob H Lo, Ewoud J. van Dijk, Joost de Vries, Paul L.M. de Kort, Willem Jan J. van Rooij, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Marieke C. Visser, Joseph C.J. Bot, Patrick C. Vroomen, Omid Eshghi, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Alexander V. Tielbeek, Heleen M. den Hertog, Dick G. Gerrits, Renske M. van den Berg-Vos, Giorgos B. Karas, Ewout W. Steyerberg, Zwenneke Flach, Henk A. Marquering, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, Ludo F.M. Beenen, René van den Berg, Peter J. Koudstaal, Wim H. van Zwam, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Charles B.L.M. Majoie, Diederik W.J. Dippel, Martin M. Brown, Thomas Liebig, Theo Stijnen, Tommy Andersson, Heinrich Mattle, Nils Wahlgren, Esther van der Heijden, Naziha Ghannouti, Nadine Fleitour, Imke Hooijenga, Corina Puppels, Wilma Pellikaan, Annet Geerling, Annemieke Lindl-Velema, Gina van Vemde, Ans de Ridder, Paut Greebe, José de Bont-Stikkelbroeck, Joke de Meris, Kirsten Janssen, Willy Struijk, Silvan Licher, Nikki Boodt, Adriaan Ros, Esmee Venema, Ilse Slokkers, Raymie-Jayce Ganpat, Maxim Mulder, Nawid Saiedie, Alis Heshmatollah, Stefanie Schipperen, Stefan Vinken, Tiemen van Boxtel, Jeroen Koets, Merel Boers, Emilie Santos, Jordi Borst, Ivo Jansen, Manon Kappelhof, Marit Lucas, Ralph Geuskens, Renan Sales Barros, Roeland Dobbe, Marloes Csizmadia, MD Hill, M Goyal, AM Demchuk, BK Menon, M Eesa, KJ Ryckborst, MR Wright, NR Kamal, L Andersen, PA Randhawa, T Stewart, S Patil, P Minhas, M Almekhlafi, S Mishra, F Clement, T Sajobi, A Shuaib, WJ Montanera, D Roy, FL Silver, TG Jovin, DF Frei, B Sapkota, JL Rempel, J Thornton, D Williams, D Tampieri, AY Poppe, D Dowlatshahi, JH Wong, AP Mitha, S Subramaniam, G Hull, MW Lowerison, M Salluzzi, M Maxwell, S Lacusta, E Drupals, K Armitage, PA Barber, EE Smith, WF Morrish, SB Coutts, C Derdeyn, B Demaerschalk, D Yavagal, R Martin, R Brant, Y Yu, RA Willinsky, A Weill, C Kenney, H Aram, PK Stys, TW Watson, G Klein, D Pearson, P Couillard, A Trivedi, D Singh, E Klourfeld, O Imoukhuede, D Nikneshan, S Blayney, R Reddy, P Choi, M Horton, T Musuka, V Dubuc, TS Field, J Desai, S Adatia, A Alseraya, V Nambiar, R van Dijk, NJ Newcommon, B Schwindt, KS Butcher, T Jeerakathil, B Buck, K Khan, SS Naik, DJ Emery, RJ Owen, TB Kotylak, RA Ashforth, TA Yeo, D McNally, M Siddiqui, M Saqqur, D Hussain, H Kalashyan, A Manosalva, M Kate, L Gioia, S Hasan, A Mohammad, M Muratoglu, A Cullen, P Brennan, A O'Hare, S Looby, D Hyland, S Duff, M McCusker, B Hallinan, S Lee, J McCormack, A Moore, M O'Connor, C Donegan, L Brewer, A Martin, S Murphy, K O'Rourke, S Smyth, P Kelly, T Lynch, T Daly, P O'Brien, A O'Driscoll, M Martin, R Collins, T Coughlan, D McCabe, D O'Neill, M Mulroy, O Lynch, T Walsh, M O'Donnell, T Galvin, J Harbison, P McElwaine, K Mulpeter, C McLoughlin, M Reardon, E Harkin, E Dolan, M Watts, N Cunningham, C Fallon, S Gallagher, P Cotter, M Crowe, R Doyle, I Noone, M Lapierre, VA Coté, S Lanthier, C Odier, A Durocher, J Raymond, N Daneault, Y Deschaintre, B Jankowitz, L Baxendell, L Massaro, C Jackson-Graves, S Decesare, P Porter, K Armbruster, A Adams, J Billigan, J Oakley, A Ducruet, A Jadhav, D-V Giurgiutiu, A Aghaebrahim, V Reddy, M Hammer, M Starr, V Totoraitis, L Wechsler, S Streib, S Rangaraju, D Campbell, M Rocha, D Gulati, T Krings, L Kalman, A Cayley, J Williams, R Wiegner, LK Casaubon, C Jaigobin, JM del Campo, E Elamin, JD Schaafsma, R Agid, R Farb, K ter Brugge, BL Sapkoda, BW Baxter, K Barton, A Knox, A Porter, A Sirelkhatim, T Devlin, C Dellinger, N Pitiyanuvath, J Patterson, J Nichols, S Quarfordt, J Calvert, H Hawk, C Fanale, A Bitner, A Novak, D Huddle, R Bellon, D Loy, J Wagner, I Chang, E Lampe, B Spencer, R Pratt, R Bartt, S Shine, G Dooley, T Nguyen, M Whaley, K McCarthy, J Teitelbaum, W Poon, N Campbell, M Cortes, C Lum, R Shamloul, S Robert, G Stotts, M Shamy, N Steffenhagen, D Blacquiere, M Hogan, M AlHazzaa, G Basir, H Lesiuk, D Iancu, M Santos, H Choe, DC Weisman, K Jonczak, A Blue-Schaller, Q Shah, L MacKenzie, B Klein, K Kulandaivel, O Kozak, DJ Gzesh, LJ Harris, JS Khoury, J Mandzia, D Pelz, S Crann, L Fleming, K Hesser, B Beauchamp, B Amato-Marzialli, M Boulton, P Lopez- Ojeda, M Sharma, S Lownie, R Chan, R Swartz, P Howard, D Golob, D Gladstone, K Boyle, M Boulos, J Hopyan, V Yang, L Da Costa, CA Holmstedt, AS Turk, R Navarro, E Jauch, S Ozark, R Turner, S Phillips, J Shankar, J Jarrett, G Gubitz, W Maloney, R Vandorpe, M Schmidt, J Heidenreich, G Hunter, M Kelly, R Whelan, L Peeling, PA Burns, A Hunter, I Wiggam, E Kerr, M Watt, A Fulton, P Gordon, I Rennie, P Flynn, G Smyth, S O'Leary, N Gentile, G Linares, P McNelis, K Erkmen, P Katz, A Azizi, M Weaver, C Jungreis, S Faro, P Shah, H Reimer, V Kalugdan, G Saposnik, A Bharatha, Y Li, P Kostyrko, T Marotta, W Montanera, D Sarma, D Selchen, J Spears, JH Heo, K Jeong, DJ Kim, BM Kim, YD Kim, D Song, K-J Lee, J Yoo, OY Bang, S Rho, J Lee, P Jeon, KH Kim, J Cha, SJ Kim, S Ryoo, MJ Lee, S-I Sohn, C-H Kim, H-G Ryu, J-H Hong, H-W Chang, C-Y Lee, J Rha, Bruce CV Campbell, Leonid Churilov, Bernard Yan, Richard Dowling, Nawaf Yassi, Thomas J Oxley, Teddy Y Wu, Gabriel Silver, Amy McDonald, Rachael McCoy, Timothy J Kleinig, Rebecca Scroop, Helen M Dewey, Marion Simpson, Mark Brooks, Bronwyn Coulton, Martin Krause, Timothy J Harrington, Brendan Steinfort, Kenneth Faulder, Miriam Priglinger, Susan Day, Thanh Phan, Winston Chong, Michael Holt, Ronil V Chandra, Henry Ma, Dennis Young, Kitty Wong, Tissa Wijeratne, Hans Tu, Elizabeth Mackay, Sherisse Celestino, Christopher F Bladin, Poh Sien Loh, Amanda Gilligan, Zofia Ross, Skye Coote, Tanya Frost, Mark W Parsons, Ferdinand Miteff, Christopher R Levi, Timothy Ang, Neil Spratt, Lara Kaauwai, Monica Badve, Henry Rice, Laetitia de Villiers, P. Alan Barber, Ben McGuinness, Ayton Hope, Maurice Moriarty, Patricia Bennett, Andrew Wong, Alan Coulthard, Andrew Lee, Jim Jannes, Deborah Field, Gagan Sharma, Simon Salinas, Elise Cowley, Barry Snow, John Kolbe, Richard Stark, John King, Richard Macdonnell, John Attia, Cate D'Este, Hans-Christoph Diener, Elad I. Levy, Alain Bonafé, Reza Jahan, Gregory W. Albers, Christophe Cognard, David J. Cohen, Werner Hacke, Tudor G. Jovin, Heinrich P. Mattle, Raul G. Nogueira, Adnan H. Siddiqui, Dileep R. Yavagal, Rüdiger von Kummer, Wade Smith, Francis Turjman, Scott Hamilton, Richard Chiacchierini, Arun Amar, Nerses Sanossian, Yince Loh, B Baxter, VK Reddy, A Horev, M Star, A Siddiqui, LN Hopkins, K Snyder, R Sawyer, S Hall, V Costalat, C Riquelme, P Machi, E Omer, C Arquizan, I Mourand, M Charif, X Ayrignac, N Menjot de Champfleur, N Leboucq, G Gascou, M Moynier, R du Mesnil de Rochemont, O Singer, J Berkefeld, C Foerch, M Lorenz, W Pfeilschifer, E Hattingen, M Wagner, SJ You, S Lescher, H Braun, S Dehkharghani, SR Belagaje, A Anderson, A Lima, M Obideen, D Haussen, R Dharia, M Frankel, V Patel, K Owada, A Saad, L Amerson, C Horn, S Doppelheuer, K Schindler, DK Lopes, M Chen, R Moftakhar, C Anton, M Smreczak, JS Carpenter, S Boo, A Rai, T Roberts, A Tarabishy, L Gutmann, C Brooks, J Brick, J Domico, G Reimann, K Hinrichs, M Becker, E Heiss, C Selle, A Witteler, S Al-Boutros, M-J Danch, A Ranft, S Rohde, K Burg, C Weimar, V Zegarac, C Hartmann, M Schlamann, S Göricke, A Ringlestein, I Wanke, C Mönninghoff, M Dietzold, R Budzik, T Davis, G Eubank, WJ Hicks, P Pema, N Vora, J Mejilla, M Taylor, W Clark, A Rontal, J Fields, B Peterson, G Nesbit, H Lutsep, H Bozorgchami, R Priest, O Ologuntoye, S Barnwell, A Dogan, K Herrick, C Takahasi, N Beadell, B Brown, S Jamieson, MS Hussain, A Russman, F Hui, D Wisco, K Uchino, Z Khawaja, I Katzan, G Toth, E Cheng-Ching, M Bain, S Man, A Farrag, P George, S John, L Shankar, A Drofa, R Dahlgren, A Bauer, A Itreat, A Taqui, R Cerejo, A Richmond, P Ringleb, M Bendszus, M Möhlenbruch, T Reiff, H Amiri, J Purrucker, C Herweh, M Pham, O Menn, I Ludwig, I Acosta, C Villar, W Morgan, C Sombutmai, F Hellinger, E Allen, M Bellew, R Gandhi, E Bonwit, J Aly, RD Ecker, D Seder, J Morris, M Skaletsky, J Belden, C Baker, LS Connolly, P Papanagiotou, C Roth, A Kastrup, M Politi, F Brunner, M Alexandrou, H Merdivan, C Ramsey, C Given II, S Renfrow, V Deshmukh, K Sasadeusz, F Vincent, JT Thiesing, J Putnam, A Bhatt, A Kansara, D Caceves, T Lowenkopf, L Yanase, J Zurasky, S Dancer, B Freeman, T Scheibe-Mirek, J Robison, J Roll, D Clark, M Rodriguez, B-FM Fitzsimmons, O Zaidat, JR Lynch, M Lazzaro, T Larson, L Padmore, E Das, A Farrow-Schmidt, A Hassan, W Tekle, C Cate, O Jansen, C Cnyrim, F Wodarg, C Wiese, A Binder, C Riedel, A Rohr, N Lang, H Laufs, S Krieter, L Remonda, M Diepers, J Añon, K Nedeltchev, T Kahles, S Biethahn, M Lindner, V Chang, C Gächter, C Esperon, M Guglielmetti, JF Arenillas Lara, M Martínez Galdámez, AI Calleja Sanz, E Cortijo Garcia, P Garcia Bermejo, S Perez, P Mulero Carrillo, E Crespo Vallejo, M Ruiz Piñero, L Lopez Mesonero, FJ Reyes Muñoz, C Brekenfeld, J-H Buhk, A Krützelmann, G Thomalla, B Cheng, C Beck, J Hoppe, E Goebell, B Holst, U Grzyska, G Wortmann, S Starkman, G Duckwiler, R Jahan, N Rao, S Sheth, K Ng, A Noorian, V Szeder, M Nour, M McManus, J Huang, J Tarpley, S Tateshima, N Gonzalez, L Ali, D Liebeskind, J Hinman, M Calderon-Arnulphi, C Liang, J Guzy, S Koch, K DeSousa, G Gordon-Perue, M Elhammady, E Peterson, V Pandey, S Dharmadhikari, P Khandelwal, A Malik, R Pafford, P Gonzalez, K Ramdas, G Andersen, D Damgaard, P Von Weitzel-Mudersbach, C Simonsen, N Ruiz de Morales Ayudarte, M Poulsen, L Sørensen, S Karabegovich, M Hjørringgaard, N Hjort, T Harbo, K Sørensen, E Deshaies, D Padalino, A Swarnkar, JG Latorre, E Elnour, Z El-Zammar, M Villwock, H Farid, A Balgude, L Cross, K Hansen, M Holtmannspötter, D Kondziella, J Hoejgaard, S Taudorf, H Soendergaard, A Wagner, M Cronquist, T Stavngaard, M Cortsen, LH Krarup, T Hyldal, H-P Haring, S Guggenberger, M Hamberger, J Trenkler, M Sonnberger, K Nussbaumer, C Dominger, E Bach, BD Jagadeesan, R Taylor, J Kim, K Shea, R Tummala, H Zacharatos, D Sandhu, M Ezzeddine, A Grande, D Hildebrandt, K Miller, J Scherber, A Hendrickson, M Jumaa, S Zaidi, T Hendrickson, V Snyder, M Killer-Oberpfalzer, J Mutzenbach, F Weymayr, E Broussalis, K Stadler, A Jedlitschka, A Malek, N Mueller-Kronast, P Beck, C Martin, D Summers, J Day, I Bettinger, W Holloway, K Olds, S Arkin, N Akhtar, C Boutwell, S Crandall, M Schwartzman, C Weinstein, B Brion, S Prothmann, J Kleine, K Kreiser, T Boeckh-Behrens, H Poppert, S Wunderlich, ML Koch, V Biberacher, A Huberle, G Gora-Stahlberg, B Knier, T Meindl, D Utpadel-Fischler, M Zech, M Kowarik, C Seifert, B Schwaiger, A Puri, S Hou, A Wakhloo, M Moonis, N Henninger, R Goddeau, F Massari, A Minaeian, JD Lozano, M Ramzan, C Stout, A Patel, A Tunguturi, S Onteddu, R Carandang, M Howk, M Ribó, E Sanjuan, M Rubiera, J Pagola, A Flores, M Muchada, P Meler, E Huerga, S Gelabert, P Coscojuela, A Tomasello, D Rodriguez, E Santamarina, O Maisterra, S Boned, L Seró, A Rovira, CA Molina, M Millán, L Muñoz, N Pérez de la Ossa, M Gomis, L Dorado, E López-Cancio, E Palomeras, J Munuera, P García Bermejo, S Remollo, C Castaño, R García-Sort, P Cuadras, P Puyalto, M Hernández-Pérez, M Jiménez, A Martínez-Piñeiro, G Lucente, A Dávalos, A Chamorro, X Urra, V Obach, A Cervera, S Amaro, L Llull, J Codas, M Balasa, J Navarro, H Ariño, A Aceituno, S Rudilosso, A Renu, JM Macho, L San Roman, J Blasco, A López, N Macías, P Cardona, H Quesada, F Rubio, L Cano, B Lara, MA de Miquel, L Aja, J Serena, E Cobo, Gregory W Albers, Kennedy R Lees, J Arenillas, R Roberts, F Al-Ajlan, L Zimmel, S Patel, J Martí-Fàbregas, M Salvat-Plana, S Bracard, René Anxionnat, Pierre-Alexandre Baillot, Charlotte Barbier, Anne-Laure Derelle, Jean-Christophe Lacour, Sébastien Richard, Yves Samson, Nader Sourour, Flore Baronnet-Chauvet, Frédéric Clarencon, Sophie Crozier, Sandrine Deltour, Federico Di Maria, Raphael Le Bouc, Anne Leger, Gurkan Mutlu, Charlotte Rosso, Zoltan Szatmary, Marion Yger, Chiara Zavanone, Serge Bakchine, Laurent Pierot, Nathalie Caucheteux, Laurent Estrade, Krzysztof Kadziolka, Alexandre Leautaud, Céline Renkes, Isabelle Serre, Hubert Desal, Benoît Guillon, Claire Boutoleau-Bretonniere, Benjamin Daumas-Duport, Solène De Gaalon, Pascal Derkinderen, Sarah Evain, Fanny Herisson, David-Axel Laplaud, Thibaud Lebouvier, Alina Lintia-Gaultier, Hélène Pouclet-Courtemanche, Tiphaine Rouaud, Violaine Rouaud Jaffrenou, Aurélia Schunck, Mathieu Sevin-Allouet, Frederique Toulgoat, Sandrine Wiertlewski, Jean-Yves Gauvrit, Thomas Ronziere, Vincent Cahagne, Jean-Christophe Ferre, Jean-François Pinel, Hélène Raoult, Jean-Louis Mas, Jean-François Meder, Amen-Adam Al Najjar-Carpentier, Julia Birchenall, Eric Bodiguel, David Calvet, Valérie Domigo, Sylvie Godon-Hardy, Vincent Guiraud, Catherine Lamy, Loubna Majhadi, Ludovic Morin, Denis Trystram, Guillaume Turc, Jérôme Berge, Igor Sibon, Patrice Menegon, Xavier Barreau, François Rouanet, Sabrina Debruxelles, Annabelle Kazadi, Pauline Renou, Olivier Fleury, Anne Pasco-Papon, Frédéric Dubas, Jildaz Caroff, Sophie Godard Ducceschi, Marie-Aurélie Hamon, Alderic Lecluse, Guillaume Marc, Maurice Giroud, Frédéric Ricolfi, Yannick Bejot, Adrien Chavent, Arnaud Gentil, Apolline Kazemi, Guy-Victor Osseby, Charlotte Voguet, Marie-Hélène Mahagne, Jacques Sedat, Yves Chau, Laurent Suissa, Sylvain Lachaud, Emmanuel Houdart, Christian Stapf, Frédérique Buffon Porcher, Hugues Chabriat, Pierre Guedin, Dominique Herve, Eric Jouvent, Jérôme Mawet, Jean-Pierre Saint-Maurice, Hans-Martin Schneble, Norbert Nighoghossian, Nadia-Nawel Berhoune, Françoise Bouhour, Tae-Hee Cho, Laurent Derex, Sandra Felix, Hélène Gervais-Bernard, Benjamin Gory, Luis Manera, Laura Mechtouff, Thomas Ritzenthaler, Roberto Riva, Fabrizio Salaris Silvio, Caroline Tilikete, Raphael Blanc, Michaël Obadia, Mario Bruno Bartolini, Antoine Gueguen, Michel Piotin, Silvia Pistocchi, Hocine Redjem, Jacques Drouineau, Jean-Philippe Neau, Gaelle Godeneche, Matthias Lamy, Emilia Marsac, Stephane Velasco, Pierre Clavelou, Emmanuel Chabert, Nathalie Bourgois, Catherine Cornut-Chauvinc, Anna Ferrier, Jean Gabrillargues, Betty Jean, Anna-Raquel Marques, Nicolas Vitello, Olivier Detante, Marianne Barbieux, Kamel Boubagra, Isabelle Favre Wiki, Katia Garambois, Florence Tahon, Vasdev Ashok, Oguzhan Coskun, Georges Rodesch, Bertrand Lapergue, Frédéric Bourdain, Serge Evrard, Philippe Graveleau, Jean Pierre Decroix, Adrien Wang, François Sellal, Guido Ahle, Gabriela Carelli, Marie-Hélène Dugay, Claude Gaultier, Ariel Pablo Lebedinsky, Lavinia Lita, Raul Mariano Musacchio, Catherine Renglewicz-Destuynder, Alain Tournade, Françis Vuillemet, Francisco Macian Montoro, Charbel Mounayer, Frederic Faugeras, Laetitia Gimenez, Catherine Labach, Géraldine Lautrette, Christian Denier, Guillaume Saliou, Olivier Chassin, Claire Dussaule, Elsa Melki, Augustin Ozanne, Francesco Puccinelli, Marina Sachet, Mariana Sarov, Jean-François Bonneville, Thierry Moulin, Alessandra Biondi, Elisabeth De Bustos Medeiros, Fabrice Vuillier, Patrick Courtheoux, Fausto Viader, Marion Apoil-Brissard, Mathieu Bataille, Anne-Laure Bonnet, Julien Cogez, Emmanuel Touze, Xavier Leclerc, Didier Leys, Mohamed Aggour, Pierre Aguettaz, Marie Bodenant, Charlotte Cordonnier, Dominique Deplanque, Marie Girot, Hilde Henon, Erwah Kalsoum, Christian Lucas, Jean-Pierre Pruvo, Paolo Zuniga, Caroline Arquizan, Vincent Costalat, Paolo Machi, Isabelle Mourand, Carlos Riquelme, Pierre Bounolleau, Charles Arteaga, Anthony Faivre, Marc Bintner, Patrice Tournebize, Cyril Charlin, Françoise Darcel, Pascale Gauthier-Lasalarie, Marcia Jeremenko, Servane Mouton, Jean-Baptiste Zerlauth, Chantal Lamy, Deramond Hervé, Hosseini Hassan, André Gaston, Francis-Guy Barral, Pierre Garnier, Rémy Beaujeux, Valérie Wolff, Denis Herbreteau, Séverine Debiais, Alicia Murray, Gary Ford, Martin M Brown, Andy Clifton, Janet Freeman, Ian Ford, Hugh Markus, Joanna Wardlaw, Andy Molyneux, Thompson Robinson, Steff Lewis, John Norrie, Fergus Robertson, Richard Perry, Geoffrey Cloud, Andrew Clifton, Jeremy Madigan, Christine Roffe, Sanjeev Nayak, Kyriakos Lobotesis, Craig Smith, Amit Herwadkar, Naga Kandasamy, Tony Goddard, John Bamford, Ganesh Subramanian, Rob Lenthall, Edward Littleton, Sal Lamin, Kelley Storey, Rita Ghatala, Azra Banaras, John Aeron-Thomas, Bath Hazel, Holly Maguire, Emelda Veraque, Louise Harrison, Rekha Keshvara, James Cunningham, University of Melbourne, University of Calgary, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University of Amsterdam [Amsterdam] (UvA), Universitat Autònoma de Barcelona (UAB), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), ANS - Neurovascular Disorders, Radiology and Nuclear Medicine, ACS - Amsterdam Cardiovascular Sciences, Neurology, Graduate School, Other Research, APH - Personalized Medicine, APH - Quality of Care, Biomedical Engineering and Physics, ARD - Amsterdam Reproduction and Development, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Microcirculation, ACS - Atherosclerosis & ischemic syndromes, ACS - Pulmonary hypertension & thrombosis, Radiology & Nuclear Medicine, Public Health, Weimar, Christian (Beitragende*r), Molecular cell biology and Immunology, Pathology, Radiology and nuclear medicine, Amsterdam Neuroscience - Neurovascular Disorders, Rheumatology, Beeldvorming, RS: CARIM - R3.03 - Cerebral small vessel disease, RS: CARIM - R3.11 - Imaging, MUMC+: DA BV Medisch Specialisten Radiologie (9), Klinische Neurowetenschappen, and MUMC+: MA Neurologie (3)

Subjects
Male, medicine.medical_specialty, Sedation, Medizin, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030204 cardiovascular system & hematology, Anesthesia, General, CONTROLLED-TRIAL, THERAPY, law.invention, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Randomized controlled trial, law, Modified Rankin Scale, Journal Article, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Medicine, Humans, General anaesthesia, Stroke, Aged, Randomized Controlled Trials as Topic, Thrombectomy, Aged, 80 and over, business.industry, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Odds ratio, MR, Middle Aged, Outcome and Process Assessment (Health Care), medicine.disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], 3. Good health, Surgery, Outcome and Process Assessment, Health Care, Meta-analysis, Observational study, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Meta-Analysis
Abstract

BACKGROUND: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care.METHODS: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered.FINDINGS: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09-2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75-3·10, pINTERPRETATION: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons.FUNDING: Medtronic.

Published
2018
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19. Bilirubin Decreases Macrophage Cholesterol Efflux and ABCA1 Protein Expression

Author

E Heiß, Atanas G. Atanasov, Andrew C. Bulmer, Karl-Heinz Wagner, Christine Mölzer, Verena M. Dirsch, Marlies Wallner, Anela Tosevska, Dongdong Wang, and Angela Ladurner

Subjects
medicine.medical_specialty, Bilirubin, Cholesterol, business.industry, Physiology, chemistry.chemical_compound, Endocrinology, chemistry, ABCA1 Protein, Internal medicine, medicine, Macrophage, Efflux, business
Published
2017
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21. New flatbug (Hemiptera: Heteroptera: Aradidae) records from the Middle Eocene Messel Maar, Germany

Author

Sonja Wedmann, Torsten Wappler, and E Heiss

Subjects
Subfamily, Extant taxon, Aradidae, Ecology, Heteroptera, Mezirinae, Paleontology, Biology, biology.organism_classification, Southern Hemisphere, Hemiptera, Maar
Abstract

Three new species of the flat bug family Aradidae from the Eocene Messel Maar are described and illustrated. Aneurus ? incertus n. sp. is a new species belonging to the extant subfamily Aneurinae. Mezira petrificata n. sp. and M. parapetrificata n. sp. are two new species belonging to the extant subfamily Mezirinae. They are compared with the specimens so far described from Messel, as well as with related extant taxa. Additionally, a male probably belonging to M. eocenica and a female of M. petrificata are reported. Even though the aradids represent less than 0.05 % in the taphocoenosis from Messel, and are one of the smallest groups among the recorded heteropterans, the presence of six species among eight preserved specimens indicates an unexpected high diversity among flat bugs from Messel. Especially well-represented are members of the subfamily Mezirinae that today occur in all major biogeographic regions but seem to be concentrated in the Southern Hemisphere.

Published
2014
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22. A role for cortical nNOS/NK1 neurons in coupling homeostatic sleep drive to EEG slow wave activity

Author

Dmitry Gerashchenko, Ravi K. Pasumarthi, Stephen R. Morairty, Lars Dittrich, Daniel Valladao, Jaime E. Heiss, and Thomas S. Kilduff

Subjects
medicine.medical_specialty, Sleep spindle, Nitric Oxide Synthase Type I, Non-rapid eye movement sleep, Interneurons, Internal medicine, mental disorders, medicine, Biological neural network, Animals, Neuroscience of sleep, Cerebral Cortex, Multidisciplinary, musculoskeletal, neural, and ocular physiology, Biological Sciences, Brain Waves, Sleep in non-human animals, nervous system diseases, Sleep deprivation, Endocrinology, nervous system, medicine.symptom, Sleep onset, Sleep, Psychology, K-complex, Neuroscience, psychological phenomena and processes
Abstract

Although the neural circuitry underlying homeostatic sleep regulation is little understood, cortical neurons immunoreactive for neuronal nitric oxide synthase (nNOS) and the neurokinin-1 receptor (NK1) have been proposed to be involved in this physiological process. By systematically manipulating the durations of sleep deprivation and subsequent recovery sleep, we show that activation of cortical nNOS/NK1 neurons is directly related to non-rapid eye movement (NREM) sleep time, NREM bout duration, and EEG δ power during NREM sleep, an index of preexisting homeostatic sleep drive. Conversely, nNOS knockout mice show reduced NREM sleep time, shorter NREM bouts, and decreased power in the low δ range during NREM sleep, despite constitutively elevated sleep drive. Cortical NK1 neurons are still activated in response to sleep deprivation in these mice but, in the absence of nNOS, they are unable to up-regulate NREM δ power appropriately. These findings support the hypothesis that cortical nNOS/NK1 neurons translate homeostatic sleep drive into up-regulation of NREM δ power through an NO-dependent mechanism.

Published
2013
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23. Simultaneous Bayesian Estimation of Excitatory and Inhibitory Synaptic Conductances by Exploiting Multiple Recorded Trials

Author

Taro Toyoizumi, Jaime E. Heiss, Milad Lankarany, and Ilan Lampl

Subjects
0301 basic medicine, excitatory and inhibitory synaptic inputs, Computer science, Bayesian probability, Neuroscience (miscellaneous), Machine learning, computer.software_genre, Inhibitory postsynaptic potential, in-vivo, lcsh:RC321-571, current clamp, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Expectation–maximization algorithm, Biological neural network, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Original Research, Bayes estimator, business.industry, Kalman filter, synaptic conductance, in vivo, 030104 developmental biology, Excitatory postsynaptic potential, barrel cortex, Artificial intelligence, Biological system, Particle filter, business, computer, 030217 neurology & neurosurgery, Neuroscience
Abstract

Advanced statistical methods have enabled trial-by-trial inference of the underlying excitatory and inhibitory synaptic conductances of the membrane potential recordings. Simultaneous inference of both excitatory and inhibitory conductances sheds light into the neural circuits underlying the neural activity and advances our understanding on neural information processing. Conventional Bayesian methods can infer excitatory and inhibitory synaptic conductances based on a single trial of observed membrane potential. However, if multiple recorded trials are available, this typically leads to suboptimal estimation because they neglect common statistics (of synaptic inputs) across trials. Here, we establish a new expectation maximization (EM) algorithm that improves such single-trial Bayesian methods by exploiting multiple recorded trials to extract common synaptic input statistics across the trials. In this paper, the proposed EM algorithm is embedded in parallel Kalman filters (KFs) and Particle filters (PFs) for multiple recorded trials to integrate their outputs to iteratively update the common synaptic input statistics. These statistics are then used to infer the excitatory and inhibitory synaptic conductances of individual trials. We demonstrate the superior performance of these multiple-trial Kalman Filter (MtKF) and Particle Filter (MtPF) methods relative to the corresponding single-trial methods. While relative estimation error of excitatory and inhibitory conductances is known to depend on the level of current injection into a cell, our numerical simulations using MtKF show that both excitatory and inhibitory condutances are reliably inferred using an optimal level of current injection. Finally, we validate the robustness and applicability of our technique through simulation studies and apply the MtKF algorithm to in-vivo data recorded from rat barrel cortex.

Published
2016

24. Aneurussp. from the early Miocene Foulden Maar, New Zealand: the first Southern Hemisphere record of fossil Aradidae (Insecta: Hemiptera: Heteroptera)

Author

Uwe Kaulfuss, E Heiss, Torsten Wappler, and M-C Larivière

Subjects
Paleontology, Multidisciplinary, biology, Aradidae, Genus, Fauna, Heteroptera, Rainforest, biology.organism_classification, Hemiptera, Southern Hemisphere, Geology, Maar
Abstract

The first specimen of fossil Heteroptera (Aradidae, Aneurinae) from New Zealand is figured and described. The ventrally preserved specimen from early Miocene lake sediments at Foulden Maar, Otago is assigned to Aneurus, a flat-bug genus that is represented by six species in the modern New Zealand fauna. Aneurus sp. from Foulden Maar represents the first Southern Hemisphere fossil record of the family Aradidae. Its occurrence at Foulden Maar indicates that the genus has been present in the Australasian region at least since the early Miocene and supports previous suggestions of a long evolutionary history of New Zealand aradids closely linked to rainforest habitats.

Published
2011
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25. New taxa and systematic assignments of Madagascan Aradidae(Hemiptera: Heteroptera)

Author

E. Heiss

Subjects
Taxon, Aradidae, biology, Heteroptera, Zoology, Animal Science and Zoology, biology.organism_classification, Hemiptera, Ecology, Evolution, Behavior and Systematics
Abstract

In this paper the flat bug genera Jarmilaia Hoberlandt 1957 and Bergrothista Kiritshenko 1959, recorded from Madagascar, are revised. As both genera share distinct metathoracic scent gland canals, a basic character for the classification for the subfamily Mezirinae, these genera, to date treated as Carventinae, are transferred to Mezirinae. Two new species of Jarmilaia, rabitschi n. sp. and zetteli n. sp., and two species of Bergrothista, maculipennis n. sp. and andasibensis n. sp., are recognized and described. For Bergrothista mollis (Hoberlandt 1957) the new genus Parabergrothista n. gen. is erected and a new species P. secunda described and also placed in Mezirinae. A new genus Neobergrothista n. gen. with the species N. rotundiventris n. sp. belongs also to Mezirinae. All taxa are illustrated by colour photographs.

Published
2019
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26. Parallel Arousal Pathways in the Lateral Hypothalamus

Author

Thomas S. Kilduff, Jaime E. Heiss, and Akihiro Yamanaka

Subjects
Male, medicine.medical_specialty, Lateral hypothalamus, Population, Mice, Transgenic, Inhibitory postsynaptic potential, Mice, Internal medicine, Acetamides, medicine, Animals, Wakefulness, education, Clozapine, Neurons, Orexins, education.field_of_study, Chemistry, General Neuroscience, General Medicine, Isoquinolines, Orexin receptor, Anti-Bacterial Agents, Orexin, Mice, Inbred C57BL, Endocrinology, medicine.anatomical_structure, nervous system, Doxycycline, Hypothalamic Area, Lateral, Female, Orexin Receptor Antagonists, Neuron, Almorexant, Arousal, Sleep, Antipsychotic Agents, medicine.drug
Abstract

Until recently, hypocretin (Hcrt) neurons were the only known wake-promoting neuronal population in the lateral hypothalamus (LH), but subpopulations of inhibitory neurons in this area and glutamatergic neurons in the nearby supramammillary nucleus (SuM) have recently been found that also promote wakefulness. We performed chemogenetic excitation of LH neurons in mice and observed increased wakefulness that lasted more than 4 h without unusual behavior or EEG anomalies. The increased wakefulness was similar in the presence or absence of the dual orexin receptor blocker almorexant (ALM). Analysis of hM3Dq transfection and c-FOS expression in LH inhibitory neurons and in the SuM failed to confirm that the increased wakefulness was due to these wake-promoting populations, although this possibility cannot be completely excluded. To evaluate the relationship to the Hcrt system, we repeated the study inOrexin-tTAmice in the presence or absence of dietary doxycycline (DOX), which enabled us to manipulate the percentage of Hcrt neurons that expressed hM3Dq. In DOX-fed mice, 18% of Hcrt neurons as well as many other LH neurons expressed hM3Dq; these mice showed a profound increase in wake after hM3Dq activation even in the presence of ALM. In mice switched to normal chow, 62% of Hcrt neurons expressed hM3Dq along with other LH cells; chemogenetic activation produced even more sustained arousal which could be reduced to previous levels by ALM treatment. Together, these results indicate an LH neuron population that promotes wakefulness through an Hcrt-independent pathway that can act synergistically with the Hcrt system to prolong arousal.

Published
2018
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27. Alterations in High-Frequency Neuronal Oscillations in a Cynomolgus Macaque Test of Sustained Attention Following NMDA Receptor Antagonism

Author

Edilio Borroni, Courtney Glavis-Bloom, Daniela Alberati, Gerhard Trube, Tanya L. Wallace, Jaime E. Heiss, and Anushka V. Goonawardena

Subjects
0301 basic medicine, Male, Phencyclidine, Electroencephalography, Receptors, N-Methyl-D-Aspartate, 03 medical and health sciences, 0302 clinical medicine, Parietal Lobe, Gamma Rhythm, medicine, Animals, Attention, Pharmacology, N100, medicine.diagnostic_test, Dose-Response Relationship, Drug, Parietal lobe, medicine.disease, Frontal Lobe, Psychiatry and Mental health, Macaca fascicularis, 030104 developmental biology, Frontal lobe, Schizophrenia, NMDA receptor, Original Article, Psychology, Neuroscience, Excitatory Amino Acid Antagonists, 030217 neurology & neurosurgery, medicine.drug
Abstract

A growing body of evidence indicates that neuronal oscillations in the gamma frequency range (30-80 Hz) are disturbed in schizophrenic patients during cognitive processes and may represent an endophenotype of the disease. N-methyl-D-aspartate (NMDA) receptor antagonists have been used experimentally to induce schizophrenia-like symptoms including cognitive deficits in animals and humans. Here we characterized neuronal oscillations and event-related potentials (ERPs) in Cynomolgus macaques fully trained to perform a continuous performance test (CPT) in the presence and absence of the NMDA antagonist phencyclidine (PCP). Macaques (n=8) were trained to touch 'target' stimuli and ignore 'distractor' stimuli presented randomly on a touchscreen. Subsequently, all subjects were implanted with epidural EEG electrodes over frontal (FC) and parietal cortices (PC) and later tested under vehicle (saline, i.m.) or acute PCP (0.1-0.3 mg/kg, i.m.) conditions. Compared with vehicle treatment, PCP produced a significant dose-dependent decrease in CPT performance accuracy and increased reaction times. Furthermore, PCP elevated the amplitudes of 'low' (30-50 Hz) and 'high' (51-80 Hz) gamma oscillations in FC and PC around target presentations for all correct responses. The CPT accuracy was inversely correlated with the gamma band amplitude in the presence of PCP. Additionally, PCP delayed the N100 peak latency in FC, and prolonged and suppressed the cognitively relevant P300 component of mean ERPs in FC and PC, respectively. The NMDA receptor antagonist-induced alteration in neuronal oscillations and ERPs may contribute to the observed cognitive deficits in macaques, and enhance our understanding of EEG recordings as a translatable biomarker.

Published
2015

29. Zur Pathogenese des peritumoralen Ödems bei Meningeomen

Author

Uwe Seeger, Karsten Voigt, Uwe Klose, E. Heiss, Michael Bitzer, and Thomas Nägele

Subjects
Tumor size, business.industry, Ischemia, Brain tissue, medicine.disease, Meningioma, Gliosis, Edema, Parenchyma, medicine, Radiology, Nuclear Medicine and imaging, Neurology (clinical), medicine.symptom, business, Nuclear medicine, Peritumoral Brain Edema
Abstract

In order to study the role of ischemia for induction of peritumoral brain edema in meningiomas, we examined postoperative MR images to evaluate reversible and persisting changes of peritumoral brain tissue after meningioma extirpation.We examined 14 patients with 17 meningiomas pre- and postoperatively by MRI. The postoperative examinations were performed half a year or more after surgery. Patients with postoperative complications (bleeding, ischemia, etc.) were excluded. Postoperative MRI was mainly based on a inversion-recovery-sequence. We considered persisting hyperintense white matter changes (HMV) and complete parenchyma defects (PD) isointense to CSF.Persisting HMVs showed a close spatial correlation with preoperative peritumoral edema, while PD's were found mainly in the preoperative tumor region. We found a significant correlation between the size of preoperative peritumoral edema and postoperative HMV (p≤0.02) and between preoperative tumor size and postoperative PD (p≤0..0001).Our results suggest that ischemic processes may occur in peritumoral edema of meningiomas, but are rather secondary and may lead to postischemic gliosis. Complete tissue necrosis, however, seems to be caused rather by direct tumor compression than by edema.

Published
1999
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30. Zur Pathogenese des peritumoralen Ödems bei Meningeomen

Author

Karsten Voigt, Thomas Nägele, Dietmar Seitz, Uwe Klose, Uwe Seeger, E. Heiss, and Michael Bitzer

Subjects
Gynecology, medicine.medical_specialty, business.industry, Brain edema, medicine, Radiology, Nuclear Medicine and imaging, Neurology (clinical), business
Abstract

Um die Bedeutung von ischamischen Vorgangen bei der Pathogenese des peritumoralen Hirnodems bei Meningeomen zu klaren, sollten postoperative Kernspintomogramme auf reversible und persistierende Hirnparenchymveranderungen nach Meningeomentfernung untersucht werden. Untersucht wurden 14 Patienten mit 17 intrakraniellen Meningeomen mit einer pra- und postoperativen Kernspintomographie. Die postoperativen MR-Untersuchungen wurden ein halbes Jahr oder langer nach der Operation durchgefuhrt. Es durfte keine intraoperative Komplikation und auch keine relevante postoperative Nachblutung vorgelegen haben. Die postoperative MR-Untersuchung erfolgte mit einer hochauflosenden Inversion-Recovery-Sequenz. Die postoperativen Aufnahmen wurden auf persistierende hyperintense Marklagerveranderungen (HMV) und auf komplette liquorisointense Parenchymdefekte (PD) untersucht. Persistierende HMV wiesen eine enge raumliche Ubereinstimmung mit dem praoperativen peritumoralen Odern auf. Komplette Parenchymdefekte ihrerseits zeigten eine enge raumliche Beziehung mit der praoperativen Lage des Tumors. Ferner fanden sich statistisch signifikante Korrelationen zwischen der Grose des praoperativen Odems und den postoperativen HMV (p≤0,02) und zwischen der praoperativen Tumorgrose und den postoperativen PD (p≤0,0001). Unsere Ergebnisse legen nahe, das ischamische Prozesse in peritumoralen Hirnodemen bei Meningeomen ablaufen konnen, aber als sekundare und fakultative Veranderungen anzusehen sind. Dabei konnen als Endzustand des Odems postischamische Glioseareale verbleiben. Komplette Kolliquationsnekrosen sind in der Regel Folge einer direkten mechanischen Kornpression durch den Tumor selbst und nicht durch das odem.

Published
1999
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31. Die Bedeutung von morphologischen Veränderungen der Hirn-Tumor-Grenze für die Pathogenese des Hirnödems bei Meningeomen: Magnetresonanztomographie und intraoperative Untersuchungen

Author

Dirk Freudenstein, Karsten Voigt, Thomas Nägele, P. M. Mundinger, E. Heiss, Michael Bitzer, and Uwe Klose

Subjects
Pathology, medicine.medical_specialty, business.industry, Brain edema, Slice thickness, Inversion recovery, medicine.disease, Cerebral edema, Meningioma, medicine.anatomical_structure, Edema, medicine, Radiology, Nuclear Medicine and imaging, medicine.symptom, Subarachnoid space, Nuclear medicine, business, Peritumoral Brain Edema
Abstract

Ziel: Es wurde uberpruft, ob makroskopische Veranderungen der Hirn-Tumor-Grenze mit der Entstehung von Hirnodemen bei Meningeomen korrelieren. Methoden: In einer prospektiven Studie wurden praoperativ mit einer optimierten Inversion-Recovery(IR)-Sequenz 27 Meningeome untersucht. Nach i.v. Gabe von 0,2 mmol Gd-DTPA/kg erfolgte eine luckenlose Bildakquisition axial und koronar (SL = 2 mm). Bei der Auswertung wurden an der Hirn-Tumor-Grenze Distanzen von signalveranderter Hirnrinde und von Obliterationen des Subarachnoidalraumes (SAR) gemessen, mit dem Tumorumfang in Beziehung gesetzt und daraus ein Rinden- und SAR-Index berechnet. Intraoperativ wurde die Hirn-Tumor-Grenze von 25 Meningeomen folgendermasen beurteilt: 0: SAR komplett erhalten, 1: SAR teilweise aufgehoben, 2: Rindenband aufgehoben, 3: Hirninfiltration des Tumors. Ergebnisse: Meningeome mit Odem zeigten im Vergleich zu jenen ohne Odem signifikante Erhohungen (p = 0,0001) des SAR-Index (0,47 vs. 0,07) und des Rindenindex (0,45 vs. 0,0). Intraoperativ zeigten 95% der odemassoziierten Meningeome eine Obliteration des SAR, odemfreie Meningeome nur in 50%. Schlusfolgerungen: Peritumorale Adharenzen der Arachnoidea mit obliteriertem SAR scheinen bei der Odeminduktion von Meningeomen relevant zu sein. Purpose: The aim of the study was to verify a possible correlation between macroscopic changes of the brain-tumor interface (BTI) and the development of a peritumoral brain edema in meningiomas. Methods: 27 meningiomas were investigated in this prospective study using an optimized inversion-recovery (IR) sequence. After i.v. administration of 0.2 mmol Gd-DTPA/kg axial and coronary images were acquired (slice thickness = 2 mm). The distances of signal altered cortex and obliterations of the subarachnoid space (SAS) were measured at the BTI and related to the pial tumor circumference (cortical-index and SAS-index). Intraoperatively the BTI was divided into the following categories: 0: SAS not obliterated, 1: SAS partially obliterated, 2: direct contact between tumor and white matter, 3: tumor infiltration into brain. Results: Edema-associated meningiomas showed a significantly (p = 0.0001) increased SAS-index (0.47 vs. 0.07) and cortical index (0.45 vs. 0.0) compared to cases without edema. Intraoperatively 95 % of meningiomas with brain edema showed SAS-obliterations, compared to 50 % of cases without an edema. Conclusions: Arachnoid adhesions at the BTI with obliteration of the SAS seem to play an essential role in the induction of brain edema in meningiomas.

Published
1999
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33. Five Scales in Search of a Construct: Exploring Continued Attachment to Parents in College Students

Author

Glen E. Heiss, William H. Berman, and Michael B. Sperling

Subjects
Health, Toxicology and Mutagenesis, media_common.quotation_subject, Construct validity, Validity, Test validity, Developmental psychology, Clinical Psychology, Arts and Humanities (miscellaneous), Convergent validity, Personality, Personality test, Psychology, Construct (philosophy), Attachment measures, media_common
Abstract

The multitude of measures and differences across self-report indices of continued parental attachment raise questions regarding the validity and meaning of these scales. The purpose of this study was to examine the convergent and construct validity of 5 measures of continued parental attachment. Five attachment scales and 6 personality scales were administered to 216 undergraduate students. Factor analyses and correlational analyses indicate that the 5 attachment measures differentiate healthy from pathological bonding with parents, the construct being assessed has multiple dimensions, and scores on these attachment measures are correlated with personify variables as would be expected. These attachment scales appear to assess a construct that is related to attachment, although they may be more illustrative of the general affective quality of relationships. Subsequent assessment efforts should employ more specific ratings and measure concrete behavioral manifestations of attachment to most effectively examine the construct.

Published
1996
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34. Walnut leaves against diabetes mellitus? Potential mechanism and active principle

Author

E Heiß, S Glasl-Tazreiter, Anna Pitschmann, Martin Zehl, and Verena M. Dirsch

Subjects
Pharmacology, business.industry, Active principle, Organic Chemistry, Pharmaceutical Science, medicine.disease, Analytical Chemistry, Complementary and alternative medicine, Diabetes mellitus, Drug Discovery, Molecular Medicine, Medicine, business, Potential mechanism
Published
2012
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35. Cortical nNOS neurons co-express the NK1 receptor and are depolarized by Substance P in multiple mammalian species

Author

Thomas S. Kilduff, Maryka Quik, Lars Dittrich, Deepti R Warrier, Jaime E. Heiss, and Xiomara A. Perez

Subjects
Cognitive Neuroscience, neurogliaform, Neuroscience (miscellaneous), sleep homeostasis, Substance P, Biology, Nitric Oxide, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Cortex (anatomy), medicine, Original Research Article, Patch clamp, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, 030304 developmental biology, Cerebral Cortex, 0303 health sciences, bNOS, Depolarization, Neuropeptide Y receptor, tac1, Sensory Systems, tac1r, medicine.anatomical_structure, NOS-1, chemistry, nervous system, Cerebral cortex, Tetrodotoxin, GABAergic, Neuroscience, 030217 neurology & neurosurgery, NOS1
Abstract

We have previously demonstrated that Type I neuronal Nitric Oxide Synthase (nNOS)-expressing neurons are sleep-active in the cortex of mice, rats and hamsters. These neurons are known to be GABAergic, to express Neuropeptide Y and, in rats, to co-express the Substance P (SP) receptor NK1, suggesting a possible role for SP in sleep/wake regulation. To evaluate the degree of co-expression of nNOS and NK1 in the cortex among mammals, we used double immunofluorescence for nNOS and NK1 and determined the anatomical distribution in mouse, rat, and squirrel monkey cortex. Type I nNOS neurons co-expressed NK1 in all three species although the anatomical distribution within the cortex was species-specific. We then performed in vitro patch clamp recordings in cortical neurons in mouse and rat slices using the SP conjugate tetramethylrhodamine-SP (TMR-SP) to identify NK1-expressing cells and evaluated the effects of SP on these neurons. Bath application of SP (0.03-1 µM) resulted in a sustained increase in firing rate of these neurons; depolarization persisted in the presence of tetrodotoxin. These results suggest a conserved role for SP in the regulation of cortical sleep-active neurons in mammals.

Published
2012
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36. Measuring Continued Attachment to Parents: The Continued Attachment Scale—Parent Version

Author

Michael B. Sperling, Glen E. Heiss, and William H. Berman

Subjects
Psychometrics, media_common.quotation_subject, 05 social sciences, Closeness, 050301 education, 050109 social psychology, Cognition, Developmental psychology, Distress, Scale (social sciences), Personality, 0501 psychology and cognitive sciences, Psychology, Construct (philosophy), 0503 education, General Psychology, Autonomy, media_common
Abstract

Continued attachment to parents has correlated with measures of adjustment in both school and peer situations at least through the transition to college. The measurement of parental attachment has relied primarily on self-reports of the quality of the parental relationship in terms of support, encouragement, autonomy, and dependency. Bowlby's original theory and research relied more on reactions to separation, which Berman called “attachment distress” in adults. The present study examined the psychometric properties of the Continued Attachment Scale—Parent version which measures cognitive and emotional responses to the perceived separation from parents. Data from 216 college students were collected on the scale as well as several scales selected to evaluate convergent and construct validities. The scale showed good reliability. Scores were highly correlated with attachment scale scores that measure support, encouragement, and closeness. Correlations with measures of emotional state and personality differed for men and women but generally suggested that the scale assesses a distinct domain of experience related to continued closeness to parents and to depression.

Published
1994
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37. New genera and species of Carventinae from New Caledonia (Hemiptera: Heteroptera: Aradidae)

Author

E. Heiss

Subjects
Aradidae, Insecta, biology, Arthropoda, Ecology, Heteroptera, Biodiversity, biology.organism_classification, Hemiptera, Taxon, Key (lock), Animalia, Animal Science and Zoology, Ecology, Evolution, Behavior and Systematics, Taxonomy
Abstract

Only a few taxa of Aradidae were described from the Pacific island of New Caledonia to date. Based on recently collected material, 3 new genera (Kanakaptera n. gen., Rugicarventus n. gen., and Paracaraptera n. gen.) and 7 new species (Ka- nakaptera laticeps n. sp., K. montdoa n. sp., K.heimiana n. sp., K. carininota n. sp.; Rugicarventus pygmaeus n. sp.; Paracaraptera schuhiana n. sp., and Nesiaptera picea n. sp.) are described in this paper. All species are illustrated by colour photographs and a key is provided for the species of Kanakaptera n. gen.

Published
2011

38. Who Rides These Things?

Author

Jack E. Heiss

Subjects
Service (business), education.field_of_study, Engineering, business.industry, Population, Investment (macroeconomics), Supply and demand, Transport engineering, Product (business), Identification (information), Revenue, Train, education, business
Abstract

While planners and politicians alike go about kicking the tires of various trains, and traveling abroad on fact-finding missions about HSR, the question remains whether Americans will patronize high-speed rail in sufficient number to justify the investment. A common practice is to identify an existing or abandoned rail line as the candidate route that connects population centers, identify the former stations for rehabilitation, select a technology, and then perform an investment-grade ridership study to determine whether sufficient revenues will be generated. This approach may prove sufficient in the upgrading of an existing conventional service, or re-establishing a previous service in those areas of the country with a long history of passenger rail. When approaching newer developed areas such as the Sunbelt cities, the inter-relationship of development patterns and fixed-guideway passenger services is not established. Those development patterns were influenced by the automobile, not by guideway-based transportation. A different approach is needed when history is not a guide. While the selection of the population centers to be served at the outset is appropriate and makes for a basic identification of the market to be served, it does not reveal the actual destinations that are interest to the travelers. The next step is to more thoroughly investigate travel between those points. That investigation should include surveys to determine trip purpose, identify the main attractors in the markets, the demographics of the travelers and how time is valued by the travelers. Finally, estimates must be made of the absolute numbers of those traveling. Additionally, examination of the current travel patterns through the patronage of existing services can provide clues to the market demand. The acquisition of this market information then allows the planners to design a transportation product that will appeal to the potential customers and make a determination of potential revenue. Even when certain parameters of a system are set because of geography or availability of infrastructure, market information can guide improvements to maximize market capture. This paper will examine those data that are important to a high-speed rail plan and how some system decisions directly affect the ability of the transportation product offered to satisfy the needs of the traveling public. “Build it and they will come” cannot be trusted to repay the massive investment required by high-speed rail.Copyright © 2010 by ASME

Published
2010
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39. Screening of 35 plants used in Austrian folk medicine for PPAR-α and -γ activation and NFkB inhibition

Author

E Heiß, S Vogl, Nanang Fakhrudin, Verena M. Dirsch, Atanas G. Atanasov, Christoph Wawrosch, Gottfried Reznicek, P Picker, Johannes Saukel, and B. Kopp

Subjects
Pharmacology, Folk medicine, Complementary and alternative medicine, Traditional medicine, business.industry, Organic Chemistry, Drug Discovery, Pharmaceutical Science, Molecular Medicine, Medicine, business, Analytical Chemistry
Published
2009
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40. Influence of chlorophyll and tannins in plant extracts on cell-based luciferase reporter gene assays

Author

Johannes Saukel, Christoph Wawrosch, B. Kopp, Verena M. Dirsch, E Heiß, Atanas G. Atanasov, Nanang Fakhrudin, Gottfried Reznicek, S Vogl, and P Picker

Subjects
Pharmacology, Organic Chemistry, Pharmaceutical Science, Biology, Molecular biology, Analytical Chemistry, chemistry.chemical_compound, Complementary and alternative medicine, chemistry, Chlorophyll, Drug Discovery, Molecular Medicine, Luciferase reporter gene, Cell based
Published
2009
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41. Shift in the Balance between Excitation and Inhibition during Sensory Adaptation of S1 Neurons

Author

Elad Ganmor, Ilan Lampl, Yonatan Katz, and Jaime E. Heiss

Subjects
Patch-Clamp Techniques, Action Potentials, Sensory system, Stimulation, Inhibitory postsynaptic potential, Synaptic Transmission, Physical Stimulation, Animals, Patch clamp, Trigeminal Nerve, Rats, Wistar, Neurons, Sensory Adaptation, Afferent Pathways, Chemistry, General Neuroscience, Excitatory Postsynaptic Potentials, Neural Inhibition, Articles, Somatosensory Cortex, Barrel cortex, Adaptation, Physiological, Cortex (botany), Rats, Inhibitory Postsynaptic Potentials, Touch, Sensory Thresholds, Vibrissae, Neuroscience, Mechanoreceptors
Abstract

Sustained stimulation of sensory organs results in adaptation of the neuronal response along the sensory pathway. Whether or not cortical adaptation affects equally excitation and inhibition is poorly understood. We examined this question using patch recordings of neurons in the barrel cortex of anesthetized rats while repetitively stimulating the principal whisker. We found that inhibition adapts more than excitation, causing the balance between them to shift toward excitation. A comparison of the latency of thalamic firing and evoked excitation and inhibition in the cortex strongly suggests that adaptation of inhibition results mostly from depression of inhibitory synapses rather than adaptation in the firing of inhibitory cells. The differential adaptation of the evoked conductances that shifts the balance toward excitation may act as a gain mechanism which enhances the subthreshold response during sustained stimulation, despite a large reduction in excitation.

Published
2008

43. Extracting fuzzy rules from polysomnographic recordings for infant sleep classification

Author

Jaime E. Heiss, Claudio A. Perez, M. Garrido, Cecilia Algarín, Pablo A. Estevez, Patricio Peirano, and C.M. Held

Subjects
Male, Sleep state, Computer science, Polysomnography, Biomedical Engineering, Infant sleep, Machine learning, computer.software_genre, Fuzzy logic, Pattern Recognition, Automated, Knowledge extraction, Fuzzy Logic, Humans, Diagnosis, Computer-Assisted, Adaptive neuro fuzzy inference system, Training set, business.industry, Infant, Pattern recognition, Knowledge acquisition, Test set, Wakefulness, Female, Artificial intelligence, Sleep Stages, business, Classifier (UML), computer, Algorithms
Abstract

A neuro-fuzzy classifier (NFC) of sleep-wake states and stages has been developed for healthy infants of ages 6 mo and onward. The NFC takes five input patterns previously identified on 20-s epochs from polysomnographic recordings and assigns them to one out of five possible classes: Wakefulness, REM-Sleep, Non-REM Sleep Stage 1, Stage 2, and Stage 3-4. The definite criterion for a sleep state or stage to be established is duration of at least 1 min. The data set consisted of a total of 14 continuous recordings of naturally occurring naps (average duration: 143plusmn39 min), corresponding to a total of 6021 epochs. They were divided in a training, a validation and a test set with 7, 2, and 5 recordings, respectively. During supervised training, the system determined the fuzzy concepts associated to the inputs and the rules required for performing the classification, extracting knowledge from the training set, and pruning nonrelevant rules. Results on an independent test set achieved 83.9plusmn0.4% of expert agreement. The fuzzy rules obtained from the training examples without a priori information showed a high level of coincidence with the crisp rules stated by the experts, which are based on internationally accepted criteria. These results show that the NFC can be a valuable tool for implementing an automated sleep-wake classification system

Published
2006

46. Classification of sleep stages in infants: a neuro fuzzy approach

Author

Pablo A. Estevez, Jaime E. Heiss, Claudio A. Perez, Juan P. Perez, C.M. Held, and Carsten Holzmann

Subjects
Fuzzy classification, Neuro-fuzzy, Computer science, Polysomnography, Biomedical Engineering, Expert Systems, computer.software_genre, Machine learning, Fuzzy logic, Sensitivity and Specificity, Pattern Recognition, Automated, Fuzzy Logic, Artificial Intelligence, Humans, Diagnosis, Computer-Assisted, Wakefulness, Cluster analysis, Sleep Stages, Adaptive neuro fuzzy inference system, Artificial neural network, business.industry, Supervised learning, Infant, Reproducibility of Results, Pattern recognition, General Medicine, Perceptron, Expert system, Error function, Data mining, Artificial intelligence, Neural Networks, Computer, business, computer, Algorithms
Abstract

An ANFIS based neuro-fuzzy classifier with a pruning algorithm was implemented and applied to the classification of sleep-waking states-stages in infants, using the sleep pattern detection system of P.A. Estevez (2002) to generate the inputs. Including artifacted pages, an average of 88.2% of expert agreement was achieved for testing data. As a result of the training process and pruning, rules and parameters that defined a fuzzy classification system were also determined. Analyzing the rules obtained for sleep-stage NREM-1, it was found that the main rule matched the expert rule to classify NREM-1. Additional rules were discovered that complement the classification and may provide additional information about the characteristics of this sleep stage. This is a promissory result, and further research is needed in this topic. Future work includes implementation of a clustering algorithm to determine the initial parameters of the system, training the system with a different objective function, such as the max-type error function described in J.S.R. Jang and C.T. Sun (1993), and evaluating the performance of different T-norms at layer 2 in Figure 1. The development of a general methodology for rule discovery and interpretation is also of interest.

Published
2002

47. Polysomnographic pattern recognition for automated classification of sleep-waking states in infants

Author

M. Garrido, Claudio A. Perez, Pablo A. Estevez, Patricio Peirano, Jaime E. Heiss, Jeanette Pérez, Carsten Holzmann, and C.M. Held

Subjects
Male, medicine.medical_specialty, Polysomnography, Biomedical Engineering, Sleep spindle, Audiology, Electroencephalography, Pattern Recognition, Automated, Muscle tone, medicine, Humans, Sleep Stages, medicine.diagnostic_test, business.industry, Electromyography, Infant, Signal Processing, Computer-Assisted, Sleep in non-human animals, Computer Science Applications, Electrooculography, medicine.anatomical_structure, Wakefulness, Female, Artificial intelligence, Psychology, business, Kappa, Algorithms
Abstract

A robust, automated pattern recognition system for polysomnography data targeted to the sleep-waking state and stage identification is presented. Five patterns were searched for: slow-delta and theta wave predominance in the background electro-encephalogram (EEG) activity; presence of sleep spindles in the EEG; presence of rapid eye movements in an electro-oculogram; and presence of muscle tone in an electromyogram. The performance of the automated system was measured indirectly by evaluating sleep staging, based on the experts' accepted methodology, to relate the detected patterns in infants over four months of post-term age. The set of sleep-waking classes included wakefulness, REM sleep and non-REM sleep stages I, II, and III-IV. Several noise and artifact rejection methods were implemented, including filters, fuzzy quality indices, windows of variable sizes and detectors of limb movements and wakefulness. Eleven polysomnographic recordings of healthy infants were studied. The ages of the subjects ranged from 6 to 13 months old. Six recordings counting 2665 epochs were included in the training set. Results on a test set (2,369 epochs from five recordings) show an overall agreement of 87.7% (kappa 0.840) between the automated system and the human expert. These results show significant improvements compared with previous work.

Published
2002

49. The yeast SEC20 gene is required for N- and O-glycosylation in the Golgi. Evidence that impaired glycosylation does not correlate with the secretory defect

Author

I, Schleip, E, Heiss, and L, Lehle

Subjects
Glycosylation, Membrane Glycoproteins, Saccharomyces cerevisiae Proteins, Glycoside Hydrolases, beta-Fructofuranosidase, Cell Membrane, Chitinases, Golgi Apparatus, Carboxypeptidases, Saccharomyces cerevisiae, Qb-SNARE Proteins, Endoplasmic Reticulum, Tritium, Mannosyltransferases, Fungal Proteins, Protein Transport, Phenotype, Mutation, Mannose, Plasmids, Subcellular Fractions
Abstract

The Golgi plays a fundamental role in posttranslational glycosylation, transport, and sorting of proteins. The mechanism of protein transport through the Golgi has been seen as controversial in recent years. During the characterization of N-glycosylation-defective mutants (ngd) previously isolated by this laboratory, it was found that ngd20 is allelic to sec20. SEC20 was reported to be required for transport from endoplasmic reticulum to Golgi, but its precise function remains to be determined. We show now that SEC20 is also required for N- and O-glycosylation in the Golgi but not in the ER, in a cargo-specific manner, and that the glycosylation defect does not correlate with the secretory defect. By pulse-chase labeling experiments in combination with mannose linkage-specific antibodies, invertase and carboxypeptidase were found to be efficiently secreted to their final compartment, even upon shift to the nonpermissive temperature, while glycosylation in the Golgi was severely impaired. Using microsomal membranes isolated from ngd20, we found that mannosyl transfer from GDP-Man to various mannose-oligosaccharides, indicative for Golgi mannosylation, was strongly diminished. Analysis of the carbohydrate component of chitinase, an exclusively O-mannosylated protein, or of the bulk mannoprotein indicates that O-mannosylation is also reduced. The results demonstrate that in addition to secretion SEC20 also affects glycosylation in the Golgi, presumably because it exerts a more general role in maintenance and function of the Golgi compartments.

Published
2001

50. [The significance of morphological changes in the brain-tumor border area for the pathogenesis of brain edema in meningiomas: magnetic resonance tomographic and intraoperative studies]

Author

M, Bitzer, U, Klose, T, Nägele, P, Mundinger, D, Freudenstein, E, Heiss, and K, Voigt

Subjects
Adult, Gadolinium DTPA, Male, Intraoperative Care, Time Factors, Brain, Contrast Media, Brain Edema, Middle Aged, Magnetic Resonance Imaging, Preoperative Care, Meningeal Neoplasms, Humans, Female, Prospective Studies, Meningioma, Aged
Abstract

The aim of the study was to verify a possible correlation between macroscopic changes of the brain-tumor interface (BTI) and the development of a peritumoral brain edema in meningiomas.27 meningiomas were investigated in this prospective study using an optimized inversion-recovery (IR) sequence. After i.v. administration of 0.2 mmol Gd-DTPA/kg axial and coronary images were acquired (slice thickness = 2 mm). The distances of signal altered cortex and obliterations of the subarachnoid space (SAS) were measured at the BTI and related to the pial tumor circumference (cortical-index and SAS-index). Intraoperatively the BTI was divided into the following categories: 0: SAS not obliterated, 1: SAS partially obliterated, 2: direct contact between tumor and white matter, 3: tumor infiltration into brain.Edema-associated meningiomas showed a significantly (p = 0.0001) increased SAS-index (0.47 vs. 0.07) and cortical index (0.45 vs. 0.0) compared to cases without edema. Intraoperatively 95% of meningiomas with brain edema showed SAS-obliterations, compared to 50% of cases without an edema.Arachnoid adhesions at the BTI with obliteration of the SAS seem to play an essential role in the induction of brain edema in meningiomas.

Published
1999

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