181 results on '"Tönges L"'
Search Results
2. Implications of dopaminergic medication withdrawal in Parkinson’s disease
- Author
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Koschel, J., Ray Chaudhuri, K., Tönges, L., Thiel, M., Raeder, V., and Jost, W. H.
- Published
- 2022
- Full Text
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3. L-DOPA administration shifts the stability-flexibility balance towards attentional capture by distractors during a visual search task
- Author
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Riedel, P., Domachowska, I. M., Lee, Y., Neukam, P. T., Tönges, L., Li, S. C., Goschke, T., and Smolka, M. N.
- Published
- 2022
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4. Die Auswirkungen der Pandemie auf die neurologische Lehre: Not macht erfinderisch!
- Author
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Biesalski, Anne-Sophie, Peters, L., Tönges, L., Klebe, S., Fincke, F., Bornkamm, K., Brich, J., and Schmidt-Graf, F.
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- 2022
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5. Charakteristika und Dynamik der stationären Behandlung von Parkinson-Patienten in Deutschland: Analyse von 1,5 Mio. Patientenfällen aus den Jahren 2010 bis 2015
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Tönges, L., Bartig, D., Muhlack, S., Jost, W., Gold, R., and Krogias, C.
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- 2019
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6. Disease modifying treatment trials in Parkinson’s disease: how to balance expectations and interests of patients, physicians and industry partners?
- Author
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Berg, D., Eggert, K., Haslinger, B., Kassubek, J., Mollenhauer, B., Reetz, K., Rogge, A., Schaeffer, E., Tönges, L., and Zeuner, K. E.
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- 2020
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7. P-99 Nerve conduction studies in a cohort of patients with Parkinson[StQuote]s disease, multiple system atrophy and progressive supranuclear palsy
- Author
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Bieber, A., primary, Müller, K., additional, Kools, S., additional, Hilker, L., additional, Ebner, L., additional, Kirchgässler, A., additional, Rohmann, R., additional, Kleinz, T., additional, Ortmann, L., additional, Basner, L., additional, Kühn, E., additional, Averdunk, P., additional, Schmitz, F., additional, Bulut, Y., additional, Huckemann, S., additional, Scholz, L., additional, Fisse, A.L., additional, Motte, J., additional, Grüter, T., additional, Kwon, E., additional, Schneider-Gold, C., additional, Gold, R., additional, Tönges, L., additional, and Pitarokoili, K., additional
- Published
- 2023
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- View/download PDF
8. Die Auswirkungen der Pandemie auf die neurologische Lehre: Not macht erfinderisch!
- Author
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Biesalski, Anne-Sophie, Peters, L., Tönges, L., Klebe, S., Fincke, F., Bornkamm, K., Brich, J., and Schmidt-Graf, F.
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- 2024
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- View/download PDF
9. Die Auswirkungen der Pandemie auf die neurologische Lehre: Not macht erfinderisch!
- Author
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Biesalski, Anne-Sophie, primary, Peters, L., additional, Tönges, L., additional, Klebe, S., additional, Fincke, F., additional, Bornkamm, K., additional, Brich, J., additional, and Schmidt-Graf, F., additional
- Published
- 2021
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- View/download PDF
10. P 51. Sonographical study on morphological alterations of the peripheral nerves in a cohort of patients with Parkinson's Disease
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Scholz, L., primary, Huckemann, S., additional, Müller, K., additional, Kools, S., additional, Hilker, L., additional, Ebner, L., additional, Kirchgässler, A., additional, Kühn, E., additional, Averdunk, P., additional, Gold, R., additional, Tönges, L., additional, and Pitarokoili, K., additional
- Published
- 2021
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- View/download PDF
11. P 35. Nerve conduction studies and their clinical relevance in a cohort of patients with Parkinson's disease
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Müller, K., primary, Scholz, L., additional, Huckemann, S., additional, Kools, S., additional, Hilker, L., additional, Kirchgässler, A., additional, Ebner, L., additional, Bulut, Y., additional, Motte, J., additional, Fisse, A.L., additional, Tönges, L., additional, Gold, R., additional, Schneider-Gold, C., additional, and Pitarokoili, K., additional
- Published
- 2021
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12. FV 7. Cross-sectional area of the vagus nerve correlates with parasympathetic dysfunction in Parkinson's Disease
- Author
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Huckemann, S., primary, Müller, K., additional, Averdunk, P., additional, Kühn, E., additional, Hilker, L., additional, Kools, S., additional, Scholz, L., additional, Bulut, Y., additional, Brünger, J., additional, Grüter, T., additional, Fisse, A.L., additional, Motte, J., additional, Yoon, M.S., additional, Gold, R., additional, Schneider-Gold, C., additional, Tönges, L., additional, and Pitarokoili, K., additional
- Published
- 2021
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13. Implications of dopaminergic medication withdrawal in Parkinson’s disease
- Author
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Koschel, J., primary, Ray Chaudhuri, K., additional, Tönges, L., additional, Thiel, M., additional, Raeder, V., additional, and Jost, W. H., additional
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- 2021
- Full Text
- View/download PDF
14. Parkinson-Versorgungs-Netzwerke in Deutschland: Eine Bestandsaufnahme
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van Munster, M, Tönges, L, Loewenbrück, KF, Warnecke, T, Eggers, C, van Munster, M, Tönges, L, Loewenbrück, KF, Warnecke, T, and Eggers, C
- Published
- 2021
15. Association of Blood Pressure with Outcomes in Acute Stroke Thrombectomy
- Author
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Malhotra, K. Goyal, N. Katsanos, A.H. Filippatou, A. Mistry, E.A. Khatri, P. Anadani, M. Spiotta, A.M. Sandset, E.C. Sarraj, A. Magoufis, G. Krogias, C. Tönges, L. Safouris, A. Elijovich, L. Goyal, M. Arthur, A. Alexandrov, A.V. Tsivgoulis, G.
- Abstract
Limited data exist evaluating the effect of blood pressure (BP) on clinical outcomes among patients with acute ischemic stroke with large vessel occlusion treated with mechanical thrombectomy (MT). We sought to evaluate the association of BP levels on clinical outcomes among patients with acute ischemic stroke with large vessel occlusion treated with MT. Studies were identified that reported the association of systolic BP (SBP) or diastolic BP levels before, during, or after MT on the outcomes of patients with acute ischemic stroke treated with MT. Unadjusted and adjusted analyses of studies reporting odds ratios (ORadj) per 10 mm Hg BP increment were performed. Our analysis included 25 studies comprising 6474 patients. Higher pre-MT mean SBP (P=0.008) and post-MT maximum SBP (P=0.009) levels were observed in patients who died within 3 months. Patients with 3-month functional independence were noted to have lower pre-MT (P
- Published
- 2020
16. Rho kinase inhibition with Fasudil in SOD1(G93A) mouse model of Amyotrophic Lateral Sclerosis - symptomatic treatment potential after diesease onset
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Günther, R., Balck, A., Koch, J., Nientiedt, T., Sereda, M., Bähr, M., Lingor, P., and Tönges, L.
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- 2017
17. Charakteristika und Dynamik der stationären Behandlung von Parkinson-Patienten in Deutschland
- Author
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Tönges, L., primary, Bartig, D., additional, Muhlack, S., additional, Jost, W., additional, Gold, R., additional, and Krogias, C., additional
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- 2018
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18. High-Resolution Nerve Ultrasound and Electrophysiological Findings in Restless Legs Syndrome
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Pitarokoili, K., primary, Fels, M., additional, Kerasnoudis, A., additional, Tönges, L., additional, Gold, R., additional, and Yoon, M.-S., additional
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- 2018
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19. Alpha-synuclein affects neurite morphology, autophagy, vesicle transport and axonal degeneration in CNS neurons
- Author
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Koch, J C, Bitow, F, Haack, J, d'Hedouville, Z, Zhang, J-N, Tönges, L, Michel, U, Oliveira, L M A, Jovin, T M, Liman, J, Tatenhorst, L, Bähr, M, and Lingor, P
- Subjects
Dopamine ,Dopaminergic Neurons ,animal diseases ,Parkinson Disease ,Axons ,Rats ,nervous system diseases ,Substantia Nigra ,αSyn, alpha-Synuclein ,A30P, Alanin to Prolin at amino-acid 30 point mutation of αSyn ,A53T, Alanin to Threonin at amino-acid 53 point mutation of αSyn ,AAD, Acute axonal degeneration ,AAV, Adeno-associated viral vector ,AIR, Axonal integrity ratio ,ANOVA, Analysis of variance ,CNS, Central nervous system ,DIV, Day in vitro ,EGFP, Enhanced green fluorescent protein ,GAP43, Growth associated protein 43 ,ICC, Immunocytochemistry ,LB, Lewy body ,LC3, Microtubule-associated protein 1 light chain 3 ,mTOR, Mammalian target of rapamycin ,PD, Parkinson’s disease ,PFA, Paraformaldehyde ,PMN, Primary midbrain neurons ,TH, Tyrosine hydroxylase ,TOM20, Translocase of outer mitochondrial membrane 20 kDa subunit ,TU, Transforming units ,WT, Wildtype ,Amino Acid Substitution ,Gene Expression Regulation ,nervous system ,Nerve Degeneration ,Autophagy ,Neurites ,alpha-Synuclein ,Animals ,Humans ,Original Article - Abstract
Many neuropathological and experimental studies suggest that the degeneration of dopaminergic terminals and axons precedes the demise of dopaminergic neurons in the substantia nigra, which finally results in the clinical symptoms of Parkinson disease (PD). The mechanisms underlying this early axonal degeneration are, however, still poorly understood. Here, we examined the effects of overexpression of human wildtype alpha-synuclein (alpha Syn-WT), a protein associated with PD, and its mutant variants alpha Syn-A30P and -A53T on neurite morphology and functional parameters in rat primary midbrain neurons (PMN). Moreover, axonal degeneration after overexpression of alpha Syn-WT and -A30P was analyzed by live imaging in the rat optic nerve in vivo. We found that overexpression of alpha Syn-WT and of its mutants A30P and A53T impaired neurite outgrowth of PMN and affected neurite branching assessed by Sholl analysis in a variant-dependent manner. Surprisingly, the number of primary neurites per neuron was increased in neurons transfected with alpha Syn. Axonal vesicle transport was examined by live imaging of PMN co-transfected with EGFP-labeled synaptophysin. Overexpression of all alpha Syn variants significantly decreased the number of motile vesicles and decelerated vesicle transport compared with control. Macroautophagic flux in PMN was enhanced by alpha Syn-WT and -A53T but not by alpha Syn-A30P. Correspondingly, colocalization of alpha Syn and the autophagy marker LC3 was reduced for alpha Syn-A30P compared with the other alpha Syn variants. The number of mitochondria colocalizing with LC3 as a marker for mitophagy did not differ among the groups. In the rat optic nerve, both alpha Syn-WT and -A30P accelerated kinetics of acute axonal degeneration following crush lesion as analyzed by in vivo live imaging. We conclude that alpha Syn overexpression impairs neurite outgrowth and augments axonal degeneration, whereas axonal vesicle transport and autophagy are severely altered.
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- 2015
20. Galectin-1-expression and effect on proliferation and migration of glioma cells
- Author
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Strik, H.M., Schmidt, K., Lingor, P., Tönges, L., Wischhusen, J., Weller, M., and Bähr, M.
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- 2024
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21. ROCK2 is a major regulator of axonal degeneration, neuronal death and axonal regeneration in the CNS
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Koch, J. C., Tönges, L., Barski, E., Michel, U., Bähr, M., and Lingor, P.
- Subjects
ROCK2 ,LIMK1 ,axonal degeneration ,regeneration ,retinal ganglion cells ,optic nerve crush - Abstract
he Rho/ROCK/LIMK pathway is central for the mediation of repulsive environmental signals in the central nervous system. Several studies using pharmacological Rho-associated protein kinase (ROCK) inhibitors have shown positive effects on neurite regeneration and suggest additional pro-survival effects in neurons. However, as none of these drugs is completely target specific, it remains unclear how these effects are mediated and whether ROCK is really the most relevant target of the pathway. To answer these questions, we generated adeno-associated viral vectors to specifically downregulate ROCK2 and LIM domain kinase (LIMK)-1 in rat retinal ganglion cells (RGCs) in vitro and in vivo. We show here that specific knockdown of ROCK2 and LIMK1 equally enhanced neurite outgrowth of RGCs on inhibitory substrates and both induced substantial neuronal regeneration over distances of more than 5 mm after rat optic nerve crush (ONC) in vivo. However, only knockdown of ROCK2 but not LIMK1 increased survival of RGCs after optic nerve axotomy. Moreover, knockdown of ROCK2 attenuated axonal degeneration of the proximal axon after ONC assessed by in vivo live imaging. Mechanistically, we demonstrate here that knockdown of ROCK2 resulted in decreased intraneuronal activity of calpain and caspase 3, whereas levels of pAkt and collapsin response mediator protein 2 and autophagic flux were increased. Taken together, our data characterize ROCK2 as a specific therapeutic target in neurodegenerative diseases and demonstrate new downstream effects of ROCK2 including axonal degeneration, apoptosis and autophagy. Open-Access-Publikationsfonds 2014 peerReviewed
- Published
- 2014
22. EPV 1. Coronal examination plane in transcranial sonography improves the discrimination between Parkinson’s disease and essential tremor. Additional benefits by sonographic determination of the tremor frequency
- Author
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Richter, D., primary, Woitalla, D., additional, Muhlack, S., additional, Gold, R., additional, Tönges, L., additional, and Krogias, C., additional
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- 2016
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23. EP 100. Observational study: Long-term course of Botulinum Neurotoxin (BoNT) in patients with facial or focal dystonia, spasticity and hyperhydrosis
- Author
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Schmidt, H., primary, Tönges, L., additional, Koch, J., additional, Bielig, J., additional, and Blocher, J., additional
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- 2016
- Full Text
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24. Measurement of the bottom-strange meson mixing phase in the full CDF data set
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Aaltonen, T., Alvarez, González, Amerio, B., Amidei, S., Anastassov, D., Annovi, A., Antos, A., Apollinari, J., Appel, G., J. A., Arisawa, Artikov, T., Asaadi, A., Ashmanskas, J., Auerbach, W., Aurisano, B., Azfar, A., Badgett, F., Bae, W., Barbaro, Galtieri, Barnes, A., V. E., Barnett, B. A., Barria, Bartos, P., Bauce, P., Bedeschi, M., Behari, F., Bellettini, S., Bellinger, G., Benjamin, J., Beretvas, D., Bhatti, A., Bisello, A., Bizjak, D., Bland, I., K. R., Blumenfeld, Bocci, B., Bodek, A., Bortoletto, A., Boudreau, D., Boveia, J., Brigliadori, A., Bromberg, L., Brucken, C., Budagov, E., Budd, J., H. S., Burkett, Busetto, K., Bussey, G., Buzatu, P., Calamba, A., Calancha, A., Camarda, C., Campanelli, S., Campbell, M., Canelli, M., Carls, F., Carlsmith, B., Carosi, D., Carrillo, R., Carron, S., Casal, S., Casarsa, B., Castro, M., Catastini, A., Cauz, P., Cavaliere, D., Cavalli, Sforza, Cerri, M., Cerrito, A., Chen, L., Y. C., Chertok, Chiarelli, M., Chlachidze, G., Chlebana, G., Cho, F., Chokheli, K., Chung, D., W. H., Chung, Y. S., Ciocci, M. A., Clark, Clarke, A., Compostella, C., Convery, G., M. E., Conway, Corbo, J., Cordelli, M., Cox, M., C. A., Cox, D. J., Crescioli, Cuevas, F., Culbertson, J., Dagenhart, R., D'Ascenzo, D., Datta, N., Barbaro, De, Dell'Orso, Mauro, Demortier, M., Deninno, L., Devoto, M., D'Errico, F., Canto, Di, Ruzza, Di, Dittmann, B., J. R., D'Onofrio, Donati, Simone, Dong, P., Dorigo, M., Dorigo, T., Ebina, K., Elagin, A., Eppig, A., Erbacher, R., Errede, S., Ershaidat, N., Eusebi, R., Farrington, S., Feindt, M., Fernandez, J. P., Field, R., Flanagan, G., Forrest, R., Frank, M. J., Franklin, M., Freeman, J. C., Funakoshi, Y., Furic, I., Gallinaro, M., Garcia, J. E., Garfinkel, A. F., Garosi, P., Gerberich, H., Gerchtein, E., Giagu, S., Giakoumopoulou, V., Giannetti, P., Gibson, K., Ginsburg, C. M., Giokaris, N., Giromini, P., Giurgiu, G., Glagolev, V., Glenzinski, D., Gold, M., Goldin, D., Goldschmidt, N., Golossanov, A., Gomez, G., Gomez, Ceballos, Goncharov, G., González, M., Gorelov, O., Goshaw, I., A. T., Goulianos, Grillo, K., Grinstein, L., Grosso, Pilcher, Group, C., R. C., Guimaraes Da Costa, Hahn, J., S. R., Halkiadakis, Hamaguchi, E., Han, A., J. Y., Happacher, Hara, F., Hare, K., Hare, D., Harr, M., R. F., Hatakeyama, Hays, K., Heck, C., Heinrich, M., Herndon, J., Hewamanage, M., Hocker, S., Hopkins, A., Horn, W., Hou, D., Hughes, S., R. E., Hurwitz, Husemann, M., Hussain, U., Hussein, N., Huston, M., Introzzi, J., Iori, G., Ivanov, M., James, A., Jang, E., Jayatilaka, D., Jeon, B., E. J., Jindariani, Jones, S., Joo, M., K. K., Jun, S. Y., Junk, T. R., Kamon, Karchin, T., P. E., Kasmi, Kato, A., Ketchum, Y., Keung, W., Khotilovich, J., Kilminster, V., Kim, B., D. H., Kim, H. S., Kim, J. E., Kim, M. J., Kim, S. B., Kim, S. H., Kim, Y. K., Kim, Y. J., Kimura, Kirby, N., Klimenko, M., Knoepfel, S., Kondo, K., Kong, K., D. J., Konigsberg, Kotwal, J., A. V., Kreps, Kroll, M., Krop, J., Kruse, D., Krutelyov, M., Kuhr, V., Kurata, T., Kwang, M., Laasanen, S., A. T., Lami, Lammel, S., Lancaster, S., Lander, M., R. L., Lannon, Lath, K., Latino, A., Lecompte, G., Lee, T., Lee, E., H. S., Lee, J. S., Lee, S. W., Leo, Leone, S., Lewis, S., J. D., Limosani, Lin, A., C. J., Lindgren, Lipeles, M., Lister, E., Litvintsev, A., D. O., Liu, Liu, C., Liu, H., Liu, Q., Lockwitz, T., Loginov, S., Lucchesi, A., Lueck, D., Lujan, J., Lukens, P., Lungu, P., Lys, G., Lysak, J., Madrak, R., Maeshima, R., Maestro, K., Malik, P., Manca, S., Manousakis, Katsikakis, Margaroli, A., Marino, F., Martínez, C., Mastrandrea, M., Matera, P., Mattson, K., M. E., Mazzacane, Mazzanti, A., Mcfarland, P., K. S., Mcintyre, Mcnulty, P., Mehta, R., Mehtala, A., Mesropian, P., Miao, C., Mietlicki, T., Mitra, D., Miyake, A., Moed, H., Moggi, S., Mondragon, N., M. N., Moon, C. S., Moore, Morello, R., M. J., Morlock, Movilla, Fernandez, Mukherjee, P., Muller, A., Murat, T., Mussini, P., Nachtman, M., Nagai, J., Naganoma, Y., Nakano, J., Napier, I., Nett, A., Neu, J., Neubauer, C., M. S., Nielsen, Nodulman, J., Noh, L., S. Y., Norniella, Oakes, O., Oh, L., S. H., Oh, Y. D., Oksuzian, Okusawa, I., Orava, T., Ortolan, R., Pagan, Griso, Pagliarone, S., Palencia, C., Papadimitriou, E., Paramonov, V., A. A., Patrick, Pauletta, J., Paulini, G., Paus, M., Pellett, C., D. E., Penzo, Phillips, A., T. J., Piacentino, Pianori, G., Pilot, E., Pitts, J., Plager, K., Pondrom, C., Poprocki, L., Potamianos, S., Prokoshin, K., Pranko, F., Ptohos, A., Punzi, Giovanni, Rahaman, G., Ramakrishnan, A., Ranjan, V., Redondo, N., Renton, I., Rescigno, P., Riddick, M., Rimondi, T., Ristori, F., Robson, L., Rodrigo, A., Rodriguez, T., Rogers, T., Rolli, E., Roser, S., Ruffini, R., Ruiz, F., Russ, A., Rusu, J., Safonov, V., Sakumoto, A., W. K., Sakurai, Santi, Y., Sato, L., Saveliev, K., Savoy, Navarro, Schlabach, A., Schmidt, P., Schmidt, A., E. E., Schwarz, Scodellaro, T., Scribano, L., Scuri, A., Seidel, F., Seiya, S., Semenov, Y., Sforza, A., Shalhout, F., S. Z., Shears, Shepard, T., P. F., Shimojima, Shochet, M., Shreyber, Tecker, Simonenko, I., Sinervo, A., Sliwa, P., Smith, K., J. R., Snider, F. D., Soha, Sorin, A., Song, V., Squillacioti, H., Stancari, P., Denis, S. t., Stelzer, R., Stelzer, Chilton, Stentz, O., Strologas, D., Strycker, J., G. L., Sudo, Sukhanov, Y., Suslov, A., Takemasa, I., Takeuchi, K., Tang, Y., Tecchio, J., Teng, M., P. K., Thom, Thome, J., Thompson, J., G. A., Thomson, Toback, E., Tokar, D., Tollefson, S., Tomura, K., Tonelli, T., Torre, D., Torretta, S., Totaro, D., Trovato, P., Ukegawa, M., Uozumi, F., Varganov, S., Vázquez, A., Velev, F., Vellidis, G., Vidal, C., Vila, M., Vilar, I., Vizán, R., Vogel, J., Volpi, M., Wagner, G., Wagner, P., R. L., Wakisaka, Wallny, T., Wang, R., S. M., Warburton, Waters, A., Wester, D., W. C., Whiteson, Wicklund, D., A. B., Wicklund, Wilbur, E., Wick, S., Williams, F., H. H., Wilson, J. S., Wilson, Winer, P., B. L., Wittich, Wolbers, P., Wolfe, S., Wright, H., Wu, T., Wu, X., Yamamoto, Z., Yamato, K., Yang, D., Yang, T., U. K., Yang, Y. C., Yao, W. M., Yeh, G. P., Yi, Yoh, K., Yorita, J., Yoshida, K., Yu, T., G. B., Yu, Yu, I., S. S., Yun, J. C., Zanetti, Zeng, A., Zhou, Y., Zucchelli, C., Jy, S., Koh, Yh, Koike, M, Komatsu, M, Kominami, E, Kong, Hj, Kong, Wj, Korolchuk, Vi, Kotake, Y, Koukourakis, Mi, Kouri Flores JB, Kovács, Al, Kraft, C, Krainc, D, Krämer, H, Kretz Remy, C, Krichevsky, Am, Kroemer, G, Krüger, R, Krut, O, Ktistakis, Nt, Kuan, Cy, Kucharczyk, R, Kumar, A, Kumar, R, Kumar, S, Kundu, M, Kung, Hj, Kurz, T, Kwon, Hj, La Spada AR, Lafont, F, Lamark, T, Landry, J, Lane, Jd, Lapaquette, P, Laporte, Jf, László, L, Lavandero, S, Lavoie, Jn, Layfield, R, Lazo, Pa, Le, W, Le Cam, L, Ledbetter, Dj, Lee, Aj, Lee, Bw, Lee, Gm, Lee, J, Lee, Jh, Lee, M, Lee, Ms, Lee, Sh, Leeuwenburgh, C, Legembre, P, Legouis, R, Lehmann, M, Lei, Hy, Lei, Qy, Leib, Da, Leiro, J, Lemasters, Jj, Lemoine, A, Lesniak, Ms, Lev, D, Levenson, Vv, Levine, B, Levy, E, Li, F, Li, Jl, Li, L, Li, S, Li, W, Li, Xj, Li, Yb, Li, Yp, Liang, C, Liang, Q, Liao, Yf, Liberski, Pp, Lieberman, A, Lim, Hj, Lim, Kl, Lim, K, Lin, Cf, Lin, Fc, Lin, J, Lin, Jd, Lin, 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Lujan, P. Luken, G. Lungu, J. Ly, R. Lysak, R. Madrak, K. Maeshima, P. Maestro, S. Malik, G. Manca, A. Manousakis-Katsikaki, F. Margaroli, C. Marino, M. Martínez, P. Mastrandrea, K. Matera, M. Mattson, A. Mazzacane, P. Mazzanti, K. McFarland, P. McIntyre, R. McNulty, A. Mehta, P. Mehtala, C. Mesropian, T. Miao, D. Mietlicki, A. Mitra, H. Miyake, S. Moed, N. Moggi, M. Mondragon, C. Moon, R. Moore, M. Morello, J. Morlock, P. Movilla Fernandez, A. Mukherjee, Th. Muller, P. Murat, M. Mussini, J. Nachtman, Y. Nagai, J. Naganoma, I. Nakano, A. Napier, J. Nett, C. Neu, M. Neubauer, J. Nielsen, L. Nodulman, S. Noh, O. Norniella, L. Oake, S. Oh, Y. Oh, I. Oksuzian, T. Okusawa, R. Orava, L. Ortolan, S. Pagan Griso, C. Pagliarone, E. Palencia, V. Papadimitriou, A. Paramonov, J. Patrick, G. Pauletta, M. Paulini, C. Pau, D. Pellett, A. Penzo, T. Phillip, G. Piacentino, E. Pianori, J. Pilot, K. Pitt, C. Plager, L. Pondrom, S. Poprocki, K. Potamiano, F. Prokoshin, A. Pranko, F. Ptoho, G. Punzi, A. Rahaman, V. Ramakrishnan, N. Ranjan, I. Redondo, P. Renton, M. Rescigno, T. Riddick, F. Rimondi, L. Ristori, A. Robson, T. Rodrigo, T. Rodriguez, E. Roger, S. Rolli, R. Roser, F. Ruffini, A. Ruiz, J. Ru, V. Rusu, A. Safonov, W. Sakumoto, Y. Sakurai, L. Santi, K. Sato, V. Saveliev, A. Savoy-Navarro, P. Schlabach, A. Schmidt, E. Schmidt, T. Schwarz, L. Scodellaro, A. Scribano, F. Scuri, S. Seidel, Y. Seiya, A. Semenov, F. Sforza, S. Shalhout, T. Shear, P. Shepard, M. Shimojima, M. Shochet, I. Shreyber-Tecker, A. Simonenko, P. Sinervo, K. Sliwa, J. Smith, F. Snider, A. Soha, V. Sorin, H. Song, P. Squillacioti, M. Stancari, R. St. Deni, B. Stelzer, O. Stelzer-Chilton, D. Stentz, J. Strologa, G. Strycker, Y. Sudo, A. Sukhanov, I. Suslov, K. Takemasa, Y. Takeuchi, J. Tang, M. Tecchio, P. Teng, J. Thom, J. Thome, G. Thompson, E. Thomson, D. Toback, S. Tokar, K. Tollefson, T. Tomura, D. Tonelli, S. Torre, D. Torretta, P. Totaro, M. Trovato, F. Ukegawa, S. Uozumi, A. Varganov, F. Vázquez, G. Velev, C. Vellidi, M. Vidal, I. Vila, R. Vilar, J. Vizán, M. Vogel, G. Volpi, P. Wagner, R. Wagner, T. Wakisaka, R. Wallny, S. Wang, A. Warburton, D. Water, W. Wester, D. Whiteson, A. Wicklund, E. Wicklund, S. Wilbur, F. Wick, H. William, J. Wilson, P. Wilson, B. Winer, P. Wittich, S. Wolber, H. Wolfe, T. Wright, X. Wu, Z. Wu, K. Yamamoto, D. Yamato, T. Yang, U. Yang, Y. Yang, W.-M. Yao, G. Yeh, K. Yi, J. Yoh, K. Yorita, T. Yoshida, G. Yu, I. Yu, S. Yu, J. Yun, A. Zanetti, Y. Zeng, C. Zhou, S. Zucchelli, and Universidad de Cantabria
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FERMILAB TEVATRON COLLIDER ,Particle physics ,CP-violating asymmetries ,Meson ,B physic ,General Physics and Astronomy ,FOS: Physical sciences ,B physics ,Angle distribution, Branching ratio, CDF experiments, CP violations, CP-violating asymmetries, Data sample, Fermilab Tevatron collider, Integrated luminosity, Longitudinal polarization, Vector meson ,Longitudinal polarization ,7. Clean energy ,01 natural sciences ,High Energy Physics - Experiment ,Vector meson ,Physics and Astronomy (all) ,High Energy Physics - Experiment (hep-ex) ,High Energy Physics - Phenomenology (hep-ph) ,Mixing (mathematics) ,Strange b mesons ,Phase (matter) ,0103 physical sciences ,STRANGE QUARK ,mixing ,Bottom-Strange Meson Mixing Phase ,proton antiproton collisions ,010306 general physics ,TEVATRON ,Nuclear Experiment ,BOTTOM QUARK ,Physics ,Integrated luminosity ,010308 nuclear & particles physics ,Branching ratio ,High Energy Physics - Phenomenology ,CDF experiments ,CP violations ,Full data ,Content (measure theory) ,Angle distribution ,CDF ,Production (computer science) ,High Energy Physics::Experiment ,Data sample - Abstract
We report a measurement of the bottom-strange meson mixing phase βs using the time evolution of Bs0→J/ψ(→μ+μ-)ϕ(→K+K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at s=1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of βs and the Bs0 decay-width difference ΔΓs and measure βs∈[-π/2,-1.51]∪[-0.06,0.30]∪[1.26,π/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of βs, we also determine ΔΓs=0.068±0.026(stat)±0.009(syst) ps-1 and the mean Bs0 lifetime τs=1.528±0.019(stat)±0.009(syst) ps, which are consistent and competitive with determinations by other experiments., This work was supported by the U.S. Department of Energy and National Science Foundation; the Italian Istituto Nazionale di Fisica Nucleare; the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Natural Sciences and Engineering Research Council of Canada; the National Science Council of the Republic of China; the Swiss National Science Foundation; the A. P. Sloan Foundation; the Bundesministerium für Bildung und Forschung, Germany; the Korean World Class University Program, the National Research Foundation of Korea; the Science and Technology Facilities Council and the Royal Society, UK; the Russian Foundation for Basic Research; the Ministerio de Ciencia e Innovación, and Programa Consolider-Ingenio 2010, Spain; the Slovak R&D Agency; the Academy of Finland; and the Australian Research Council (ARC).
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- 2012
25. Guidelines for the use and interpretation of assays for monitoring autophagy
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- Abstract
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field. © 2012 Landes Bioscience.
- Published
- 2012
26. Alpha-Synuclein affects neurite morphology, autophagy, vesicle transport and axonal degeneration in CNS neurons
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Koch, J C, primary, Bitow, F, additional, Haack, J, additional, d'Hedouville, Z, additional, Zhang, J-N, additional, Tönges, L, additional, Michel, U, additional, Oliveira, L M A, additional, Jovin, T M, additional, Liman, J, additional, Tatenhorst, L, additional, Bähr, M, additional, and Lingor, P, additional
- Published
- 2015
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27. ROCK2 is a major regulator of axonal degeneration, neuronal death and axonal regeneration in the CNS
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Koch, J C, primary, Tönges, L, additional, Barski, E, additional, Michel, U, additional, Bähr, M, additional, and Lingor, P, additional
- Published
- 2014
- Full Text
- View/download PDF
28. Guidelines for the use and interpretation of assays for monitoring autophagy.
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Harris, J, Harris, Sd, Hashimoto, M, Haspel, Ja, Hayashi, S, Hazelhurst, La, He, C, He, Yw, Hébert, Mj, Heidenreich, Ka, Helfrich, Mh, Helgason, Gv, Henske, Ep, Herman, B, Herman, Pk, Hetz, C, Hilfiker, S, Hill, Ja, Hocking, Lj, Hofman, P, Hofmann, Tg, Höhfeld, J, Holyoake, Tl, Hong, Mh, Hood, Da, Hotamisligil, G, Houwerzijl, Ej, Høyer-Hansen, M, Hu, B, Hu, Ca, Hu, Hm, Hua, Y, Huang, C, Huang, J, Huang, S, Huang, Wp, Huber, Tb, Huh, Wk, Hung, Th, Hupp, Tr, Hur, Gm, Hurley, Jb, Hussain, Sn, Hussey, Pj, Hwang, Jj, Hwang, S, Ichihara, A, Ilkhanizadeh, S, Inoki, K, Into, T, Iovane, V, Iovanna, Jl, Ip, Ny, Isaka, Y, Ishida, H, Isidoro, C, Isobe, K, Iwasaki, A, Izquierdo, M, Izumi, Y, Jaakkola, Pm, Jäättelä, M, Jackson, Gr, Jackson, Wt, Janji, B, Jendrach, M, Jeon, Jh, Jeung, Eb, Jiang, H, Jiang, Jx, Jiang, M, Jiang, Q, Jiang, X, Jiménez, A, Jin, M, Jin, S, Joe, Co, Johansen, T, Johnson, De, Johnson, Gv, Jones, Nl, Joseph, B, Joseph, Sk, Joubert, Am, Juhász, G, Juillerat-Jeanneret, L, Jung, Ch, Jung, Yk, Kaarniranta, K, Kaasik, A, Kabuta, T, Kadowaki, M, Kagedal, K, Kamada, Y, Kaminskyy, Vo, Kampinga, Hh, Kanamori, H, Kang, C, Kang, Kb, Kang, Ki, Kang, R, Kang, Ya, Kanki, T, Kanneganti, Td, Kanno, H, Kanthasamy, Ag, Kanthasamy, A, Karantza, V, Kaushal, Gp, Kaushik, S, Kawazoe, Y, Ke, Py, Kehrl, Jh, Kelekar, A, Kerkhoff, C, Kessel, Dh, Khalil, H, Kiel, Ja, Kiger, Aa, Kihara, A, Kim, Dr, Kim, Dh, Kim, Ek, Kim, Hr, Kim, J, Kim, Jh, Kim, Jc, Kim, Jk, Kim, Pk, Kim, Sw, Kim, Y, Kimchi, A, Kimmelman, Ac, King, J, Kinsella, Tj, Kirkin, V, Kirshenbaum, La, Kitamoto, K, Kitazato, K, Klein, L, Klimecki, Wt, Klucken, J, Knecht, E, Ko, Bc, Koch, Jc, Koga, H, Koh, Jy, Koh, Yh, Koike, M, Komatsu, M, Kominami, E, Kong, Hj, Kong, Wj, Korolchuk, Vi, Kotake, Y, Koukourakis, Mi, Kouri Flores, Jb, Kovács, Al, Kraft, C, Krainc, D, Krämer, H, Kretz-Remy, C, Krichevsky, Am, Kroemer, G, Krüger, R, Krut, O, Ktistakis, Nt, Kuan, Cy, Kucharczyk, R, Kumar, A, Kumar, R, Kumar, S, Kundu, M, Kung, Hj, Kurz, T, Kwon, Hj, La Spada, Ar, Lafont, F, Lamark, T, Landry, J, Lane, Jd, Lapaquette, P, Laporte, Jf, László, L, Lavandero, S, Lavoie, Jn, Layfield, R, Lazo, Pa, Le, W, Le Cam, L, Ledbetter, Dj, Lee, Aj, Lee, Bw, Lee, Gm, Lee, J, Lee, Jh, Lee, M, Lee, Sh, Leeuwenburgh, C, Legembre, P, Legouis, R, Lehmann, M, Lei, Hy, Lei, Qy, Leib, Da, Leiro, J, Lemasters, Jj, Lemoine, A, Lesniak, M, Lev, D, Levenson, Vv, Levine, B, Levy, E, Li, F, Li, Jl, Li, L, Li, S, Li, W, Li, Xj, Li, Yb, Li, Yp, Liang, C, Liang, Q, Liao, Yf, Liberski, Pp, Lieberman, A, Lim, Hj, Lim, Kl, Lim, K, Lin, Cf, Lin, Fc, Lin, J, Lin, Jd, Lin, K, Lin, Ww, Lin, Wc, Lin, Yl, Linden, R, Lingor, P, Lippincott-Schwartz, J, Lisanti, Mp, Liton, Pb, Liu, B, Liu, Cf, Liu, K, Liu, L, Liu, Qa, Liu, W, Liu, Yc, Liu, Y, Lockshin, Ra, Lok, Cn, Lonial, S, Loos, B, Lopez-Berestein, G, López-Otín, C, Lossi, L, Lotze, Mt, Lőw, P, Lu, B, Lu, Z, Luciano, F, Lukacs, Nw, Lund, Ah, Lynch-Day, Ma, Ma, Y, Macian, F, Mackeigan, Jp, Macleod, Kf, Madeo, F, Maiuri, L, Maiuri, Mc, Malagoli, D, Malicdan, Mc, Malorni, W, Man, N, Mandelkow, Em, Manon, S, Manov, I, Mao, K, Mao, X, Mao, Z, Marambaud, P, Marazziti, D, Marcel, Yl, Marchbank, K, Marchetti, P, Marciniak, Sj, Marcondes, M, Mardi, M, Marfe, G, Mariño, G, Markaki, M, Marten, Mr, Martin, Sj, Martinand-Mari, C, Martinet, W, Martinez-Vicente, M, Masini, M, Matarrese, P, Matsuo, S, Matteoni, R, Mayer, A, Mazure, Nm, Mcconkey, Dj, Mcconnell, Mj, Mcdermott, C, Mcdonald, C, Mcinerney, Gm, Mckenna, Sl, Mclaughlin, B, Mclean, Pj, Mcmaster, Cr, Mcquibban, Ga, Meijer, Aj, Meisler, Mh, Meléndez, A, Melia, Tj, Melino, G, Mena, Ma, Menendez, Ja, Menna-Barreto, Rf, Menon, Mb, Menzies, Fm, Mercer, Ca, Merighi, A, Merry, De, Meschini, S, Meyer, Cg, Meyer, Tf, Miao, Cy, Miao, Jy, Michels, Pa, Michiels, C, Mijaljica, D, Milojkovic, A, Minucci, S, Miracco, C, Miranti, Ck, Mitroulis, I, Miyazawa, K, Mizushima, N, Mograbi, B, Mohseni, S, Molero, X, Mollereau, B, Mollinedo, F, Momoi, T, Monastyrska, I, Monick, Mm, Monteiro, Mj, Moore, Mn, Mora, R, Moreau, K, Moreira, Pi, Moriyasu, Y, Moscat, J, Mostowy, S, Mottram, Jc, Motyl, T, Moussa, Ce, Müller, S, Muller, S, Münger, K, Münz, C, Murphy, Lo, Murphy, Me, Musarò, A, Mysorekar, I, Nagata, E, Nagata, K, Nahimana, A, Nair, U, Nakagawa, T, Nakahira, K, Nakano, H, Nakatogawa, H, Nanjundan, M, Naqvi, Ni, Narendra, Dp, Narita, M, Navarro, M, Nawrocki, St, Nazarko, Ty, Nemchenko, A, Netea, Mg, Neufeld, Tp, Ney, Pa, Nezis, Ip, Nguyen, Hp, Nie, D, Nishino, I, Nislow, C, Nixon, Ra, Noda, T, Noegel, Aa, Nogalska, A, Noguchi, S, Notterpek, L, Novak, I, Nozaki, T, Nukina, N, Nürnberger, T, Nyfeler, B, Obara, K, Oberley, Td, Oddo, S, Ogawa, M, Ohashi, T, Okamoto, K, Oleinick, Nl, Oliver, Fj, Olsen, Lj, Olsson, S, Opota, O, Osborne, Tf, Ostrander, Gk, Otsu, K, Ou, Jh, Ouimet, M, Overholtzer, M, Ozpolat, B, Paganetti, P, Pagnini, U, Pallet, N, Palmer, Ge, Palumbo, C, Pan, T, Panaretakis, T, Pandey, Ub, Papackova, Z, Papassideri, I, Paris, I, Park, J, Park, Ok, Parys, Jb, Parzych, Kr, Patschan, S, Patterson, C, Pattingre, S, Pawelek, Jm, Peng, J, Perlmutter, Dh, Perrotta, I, Perry, G, Pervaiz, S, Peter, M, Peters, Gj, Petersen, M, Petrovski, G, Phang, Jm, Piacentini, M, Pierre, P, Pierrefite-Carle, V, Pierron, G, Pinkas-Kramarski, R, Piras, A, Piri, N, Platanias, Lc, Pöggeler, S, Poirot, M, Poletti, A, Poüs, C, Pozuelo-Rubio, M, Prætorius-Ibba, M, Prasad, A, Prescott, M, Priault, M, Produit-Zengaffinen, N, Progulske-Fox, A, Proikas-Cezanne, T, Przedborski, S, Przyklenk, K, Puertollano, R, Puyal, J, Qian, Sb, Qin, L, Qin, Zh, Quaggin, Se, Raben, N, Rabinowich, H, Rabkin, Sw, Rahman, I, Rami, A, Ramm, G, Randall, G, Randow, F, Rao, Va, Rathmell, Jc, Ravikumar, B, Ray, Sk, Reed, Bh, Reed, Jc, Reggiori, F, Régnier-Vigouroux, A, Reichert, A, Reiners JJ, Jr, Reiter, Rj, Ren, J, Revuelta, Jl, Rhodes, Cj, Ritis, K, Rizzo, E, Robbins, J, Roberge, M, Roca, H, Roccheri, Mc, Rocchi, S, Rodemann, Hp, Rodríguez de Córdoba, S, Rohrer, B, Roninson, Ib, Rosen, K, Rost-Roszkowska, Mm, Rouis, M, Rouschop, Km, Rovetta, F, Rubin, Bp, Rubinsztein, Dc, Ruckdeschel, K, Rucker EB, 3rd, Rudich, A, Rudolf, E, Ruiz-Opazo, N, Russo, R, Rusten, Te, Ryan, Km, Ryter, Sw, Sabatini, Dm, Sadoshima, J, Saha, T, Saitoh, T, Sakagami, H, Sakai, Y, Salekdeh, Gh, Salomoni, P, Salvaterra, Pm, Salvesen, G, Salvioli, R, Sanchez, Am, Sánchez-Alcázar, Ja, Sánchez-Prieto, R, Sandri, M, Sankar, U, Sansanwal, P, Santambrogio, L, Saran, S, Sarkar, S, Sarwal, M, Sasakawa, C, Sasnauskiene, A, Sass, M, Sato, K, Sato, M, Schapira, Ah, Scharl, M, Schätzl, Hm, Scheper, W, Schiaffino, S, Schneider, C, Schneider, Me, Schneider-Stock, R, Schoenlein, Pv, Schorderet, Df, Schüller, C, Schwartz, Gk, Scorrano, L, Sealy, L, Seglen, Po, Segura-Aguilar, J, Seiliez, I, Seleverstov, O, Sell, C, Seo, Jb, Separovic, D, Setaluri, V, Setoguchi, T, Settembre, C, Shacka, Jj, Shanmugam, M, Shapiro, Im, Shaulian, E, Shaw, Rj, Shelhamer, Jh, Shen, Hm, Shen, Wc, Sheng, Zh, Shi, Y, Shibuya, K, Shidoji, Y, Shieh, Jj, Shih, Cm, Shimada, Y, Shimizu, S, Shintani, T, Shirihai, O, Shore, Gc, Sibirny, Aa, Sidhu, Sb, Sikorska, B, Silva-Zacarin, Ec, Simmons, A, Simon, Ak, Simon, Hu, Simone, C, Simonsen, A, Sinclair, Da, Singh, R, Sinha, D, Sinicrope, Fa, Sirko, A, Siu, Pm, Sivridis, E, Skop, V, Skulachev, Vp, Slack, R, Smaili, S, Smith, Dr, Soengas, M, Soldati, T, Song, X, Sood, Ak, Soong, Tw, Sotgia, F, Spector, Sa, Spies, Cd, Springer, W, Srinivasula, Sm, Stefanis, L, Steffan, J, Stendel, R, Stenmark, H, Stephanou, A, Stern, St, Sternberg, C, Stork, B, Strålfors, P, Subauste, C, Sui, X, Sulzer, D, Sun, J, Sun, Sy, Sun, Zj, Sung, Jj, Suzuki, K, Suzuki, T, Swanson, M, Swanton, C, Sweeney, St, Sy, Lk, Szabadkai, G, Tabas, I, Taegtmeyer, H, Tafani, M, Takács-Vellai, K, Takano, Y, Takegawa, K, Takemura, G, Takeshita, F, Talbot, Nj, Tan, K, Tanaka, K, Tang, D, Tanida, I, Tannous, Ba, Tavernarakis, N, Taylor, G, Taylor, Ga, Taylor, Jp, Terada, L, Terman, A, Tettamanti, G, Thevissen, K, Thompson, Cb, Thorburn, A, Thumm, M, Tian, F, Tian, Y, Tocchini-Valentini, G, Tolkovsky, Am, Tomino, Y, Tönges, L, Tooze, Sa, Tournier, C, Tower, J, Towns, R, Trajkovic, V, Travassos, Lh, Tsai, Tf, Tschan, Mp, Tsubata, T, Tsung, A, Turk, B, Turner, L, Tyagi, Sc, Uchiyama, Y, Ueno, T, Umekawa, M, Umemiya-Shirafuji, R, Unni, Vk, Vaccaro, Mi, Valente, Em, Van den Berghe, G, van der Klei, Ij, van Doorn, W, van Dyk, Lf, van Egmond, M, van Grunsven, La, Vandenabeele, P, Vandenberghe, Wp, Vanhorebeek, I, Vaquero, Ec, Velasco, G, Vellai, T, Vicencio, Jm, Vierstra, Rd, Vila, M, Vindis, C, Viola, G, Viscomi, Maria Teresa, Voitsekhovskaja, Ov, von Haefen, C, Votruba, M, Wada, K, Wade-Martins, R, Walker, Cl, Walsh, Cm, Walter, J, Wan, Xb, Wang, A, Wang, C, Wang, D, Wang, F, Wang, G, Wang, H, Wang, Hg, Wang, Hd, Wang, J, Wang, K, Wang, M, Wang, Rc, Wang, X, Wang, Yj, Wang, Y, Wang, Z, Wang, Zc, Wansink, Dg, Ward, Dm, Watada, H, Waters, Sl, Webster, P, Wei, L, Weihl, Cc, Weiss, Wa, Welford, Sm, Wen, Lp, Whitehouse, Ca, Whitton, Jl, Whitworth, Aj, Wileman, T, Wiley, Jw, Wilkinson, S, Willbold, D, Williams, Rl, Williamson, Pr, Wouters, Bg, Wu, C, Wu, Dc, Wu, Wk, Wyttenbach, A, Xavier, Rj, Xi, Z, Xia, P, Xiao, G, Xie, Z, Xu, Dz, Xu, J, Xu, L, Xu, X, Yamamoto, A, Yamashina, S, Yamashita, M, Yan, X, Yanagida, M, Yang, D, Yang, E, Yang, Jm, Yang, Sy, Yang, W, Yang, Wy, Yang, Z, Yao, Mc, Yao, Tp, Yeganeh, B, Yen, Wl, Yin, Jj, Yin, Xm, Yoo, Oj, Yoon, G, Yoon, Sy, Yorimitsu, T, Yoshikawa, Y, Yoshimori, T, Yoshimoto, K, You, Hj, Youle, Rj, Younes, A, Yu, L, Yu, Sw, Yu, Wh, Yuan, Zm, Yue, Z, Yun, Ch, Yuzaki, M, Zabirnyk, O, Silva-Zacarin, E, Zacks, D, Zacksenhaus, E, Zaffaroni, N, Zakeri, Z, Zeh HJ, 3rd, Zeitlin, So, Zhang, H, Zhang, Hl, Zhang, J, Zhang, Jp, Zhang, L, Zhang, My, Zhang, Xd, Zhao, M, Zhao, Yf, Zhao, Y, Zhao, Zj, Zheng, X, Zhivotovsky, B, Zhong, Q, Zhou, Cz, Zhu, C, Zhu, Wg, Zhu, Xf, Zhu, X, Zhu, Y, Zoladek, T, Zong, Wx, Zorzano, A, Zschocke, J, Zuckerbraun, B., and Viscomi M. T. (ORCID:0000-0002-9096-4967)
- Abstract
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused o
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- 2012
29. Galectin-1-expression and effect on proliferation and migration of glioma cells
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Strik, H.M., primary, Schmidt, K., additional, Lingor, P., additional, Tönges, L., additional, Wischhusen, J., additional, Weller, M., additional, and Bähr, M., additional
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- 2006
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30. Inhibition of rho kinase enhances survival of dopaminergic neurons and attenuates axonal loss in a mouse model of Parkinson's disease.
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Tönges L, Frank T, Tatenhorst L, Saal KA, Koch JC, Szego EM, Bähr M, Weishaupt JH, Lingor P, Tönges, Lars, Frank, Tobias, Tatenhorst, Lars, Saal, Kim A, Koch, Jan C, Szego, Éva M, Bähr, Mathias, Weishaupt, Jochen H, and Lingor, Paul
- Abstract
Axonal degeneration is one of the earliest features of Parkinson's disease pathology, which is followed by neuronal death in the substantia nigra and other parts of the brain. Inhibition of axonal degeneration combined with cellular neuroprotection therefore seem key to targeting an early stage in Parkinson's disease progression. Based on our previous studies in traumatic and neurodegenerative disease models, we have identified rho kinase as a molecular target that can be manipulated to disinhibit axonal regeneration and improve survival of lesioned central nervous system neurons. In this study, we examined the neuroprotective potential of pharmacological rho kinase inhibition mediated by fasudil in the in vitro 1-methyl-4-phenylpyridinium cell culture model and in the subchronic in vivo 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. Application of fasudil resulted in a significant attenuation of dopaminergic cell loss in both paradigms. Furthermore, dopaminergic terminals were preserved as demonstrated by analysis of neurite network in vitro, striatal fibre density and by neurochemical analysis of the levels of dopamine and its metabolites in the striatum. Behavioural tests demonstrated a clear improvement in motor performance after fasudil treatment. The Akt survival pathway was identified as an important molecular mediator for neuroprotective effects of rho kinase inhibition in our paradigm. We conclude that inhibition of rho kinase using the clinically approved small molecule inhibitor fasudil may be a promising new therapeutic strategy for Parkinson's disease. [ABSTRACT FROM AUTHOR]
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- 2012
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31. Large-fiber neuropathy in Parkinson's disease: a narrative review.
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Kwon EH, Steininger J, Scherbaum R, Gold R, Pitarokoili K, and Tönges L
- Abstract
Background: Numerous studies reported a higher prevalence of polyneuropathy (PNP) in patients with Parkinson's disease (PD) compared to the general population. Importantly, PNP symptoms can aggravate both motor and sensory disturbances in PD patients and negatively impact the disease course. Recent analyses indicate distinct PNP patterns in PD., Main Text: This review aims to provide an overview of the current insights into etiological factors, diagnostic methods, and management strategies of large fiber neuropathy in PD. Despite the higher prevalence, the causes of PNP in PD are still not fully understood. A genetic predisposition can underlie PNP onset in PD. Main research attention is focused on long-term levodopa exposure which is suggested to increase PNP risk by depletion of methylation cofactors such as vitamin B12 and accumulation of homocysteine that altogether can alter peripheral nerve homeostasis. Beyond a potential "iatrogenic" cause, alpha-synuclein deposition has been detected in sural nerve fibers that could contribute to peripheral neuronal degeneration as part of the systemic manifestation of PD. Whereas mild axonal sensory PNP predominates in PD, a considerable proportion of patients also show motor and upper limb nerve involvement. Intriguingly, a correlation between PNP severity and PD severity has been demonstrated. Therefore, PNP screening involving clinical and instrument-based assessments should be implemented in the clinical routine for early detection and monitoring. Given the etiological uncertainty, therapeutic or preventive options remain limited. Vitamin supplementation and use of catechol-O-methyltransferase-inhibitors can be taken into consideration., Conclusion: PNP is increasingly recognized as a complicating comorbidity of PD patients. Long-term, large-scale prospective studies are required to elucidate the causative factors for the development and progression of PD-associated PNP to optimize treatment approaches. The overall systemic role of "idiopathic" PNP in PD and a putative association with the progression of neurodegeneration should also be investigated further., (© 2024. The Author(s).)
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- 2024
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32. Clinical and device-based predictors of improved experience of activities of daily living after a multidisciplinary inpatient treatment for people with Parkinson's disease: a cohort study.
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Oppermann J, Tschentscher V, Welzel J, Geritz J, Hansen C, Gold R, Maetzler W, Scherbaum R, and Tönges L
- Abstract
Background: The inpatient Parkinson's Disease Multimodal Complex Treatment (PD-MCT) is an important therapeutical approach to improving gait and activities of daily living (ADL) of people with PD (PwP). Wearable device-based parameters (DBP) are new options for specific gait analyses toward individualized treatments., Objectives: We sought to identify predictors of perceived ADL benefit taking clinical scores and DBP into account. Additionally, we analyzed DBP and clinical scores before and after PD-MCT., Design: Exploratory observational cohort study., Methods: Clinical scores and DBP of 56 PwP (mean age: 66.3 years, median Hoehn and Yahr (H&Y) stage: 2.5) were examined at the start and the end of a 14-day inpatient PD-MCT in a German University Medical Center. Participants performed four straight walking tasks under single- and dual-task conditions for gait analyses. Additionally, clinical scores of motor and nonmotor functions and quality of life (QoL) were assessed. Using dichotomized data of change in Movement Disorders Society Unified Parkinson's Disease Rating Scale Part II (MDS-UPDRS II) as a dependent variable and clinical and DBP as independent variables, a binomial logistic regression model was implemented., Results: Young age, high perceived ADL impairment at baseline, high dexterity skills, and a steady gait were significant predictors of ADL benefit after PD-MCT. DBP like gait speed, number of steps, step time, stance time, and double limb support time were improved after PD-MCT. In addition, motor functions (e.g., MDS-UPDRS III and IV), QoL, perceived ADL (MDS-UPDRS II), and experience of nonmotor functions (MDS-UPDRS I) improved significantly., Conclusion: The logistic regression model identified a group of PwP who had the most probable perceived ADL benefit after PD-MCT. Additionally, gait improved toward a faster and more dynamic gait. Using wearable technology in context of PD-MCT is promising to offer more personalized therapeutical concepts., Trial Registration: German Clinical Trial Register, https://drks.de; DRKS00020948 number, 30 March 2020, retrospectively registered., Competing Interests: RG is the Editor-in-Chief of Therapeutic Advances in Neurological Disorders. Therefore, the peer review process was managed by alternative members of the Board and the Editor was not involved in the decision-making process. The authors declare that there is no conflict of interest., (© The Author(s), 2024.)
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- 2024
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33. Longitudinal evaluation of polyneuropathy in Parkinson's disease.
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Kwon EH, Bieber A, Schülken P, Müller K, Kühn E, Averdunk P, Kools S, Hilker L, Kirchgässler A, Ebner L, Ortmann L, Basner L, Steininger J, Kleinz T, Motte J, Fisse AL, Schneider-Gold C, Gold R, Scherbaum R, Muhlack S, Tönges L, and Pitarokoili K
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- Humans, Male, Female, Aged, Middle Aged, Longitudinal Studies, Severity of Illness Index, Parkinson Disease complications, Parkinson Disease physiopathology, Polyneuropathies physiopathology, Polyneuropathies diagnosis, Polyneuropathies etiology, Polyneuropathies epidemiology, Disease Progression, Neural Conduction physiology
- Abstract
Background: Increasing evidence indicates a higher prevalence of polyneuropathy (PNP) in Parkinson's disease (PD). However, the involvement of large fiber neuropathy in PD still remains poorly understood. Given the lack of longitudinal data, we investigated the course of PNP associated with PD., Methods: In total, 41 PD patients underwent comprehensive clinical evaluation including motor and non-motor assessments as well as nerve conduction studies at baseline and at 2 years of follow-up. The definition of PNP was based on electrophysiological standard criteria. Common causes of PNP were excluded., Results: At baseline, PNP was diagnosed in 65.85% of PD patients via electroneurography. Patients with PNP presented with higher age (p = 0.019) and PD motor symptom severity (UPDRS III; p < 0.001). Over the course of 2 years, PNP deteriorated in 21.95% of cases, and 26.83% remained without PNP. Deterioration of nerve amplitude was most prevalent in the median sensory nerve affecting 57.58% of all PD cases with an overall reduction of median sensory nerve amplitude of 45.0%. With regard to PD phenotype, PNP progression was observed in 33.33% of the tremor dominant and 23.81% of the postural instability/gait difficulties subtype. Decrease of sural nerve amplitude correlated with lower quality of life (PDQ-39, p = 0.037) and worse cognitive status at baseline (MoCA, p = 0.042)., Conclusion: The study confirms the high PNP rate in PD, and demonstrates a significant electrophysiological progression also involving nerves of the upper extremities. Longitudinal studies with larger cohorts are urgently needed and should elucidate the link between PD and PNP with the underlying pathomechanisms., (© 2024. The Author(s).)
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- 2024
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34. A Short Progressive Supranuclear Palsy Quality of Life Scale.
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Jensen I, Stiel S, Bebermeier S, Schrag A, Greten S, Doll-Lee J, Wegner F, Ye L, Heine J, Krey L, Höllerhage M, Süß P, Winkler J, Berg D, Paschen S, Tönges L, Gruber D, Gandor F, Jost WH, Kühn AA, Claus I, Warnecke T, Pedrosa DJ, Eggers C, Trenkwalder C, Classen J, Schwarz J, Pötter-Nerger M, Kassubek J, Schnitzler A, Höglinger GU, and Klietz M
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- Humans, Female, Male, Aged, Retrospective Studies, Middle Aged, Surveys and Questionnaires, Aged, 80 and over, Activities of Daily Living, Severity of Illness Index, Supranuclear Palsy, Progressive psychology, Quality of Life psychology
- Abstract
Objective: The Progressive Supranuclear Palsy quality of life scale (PSP-QoL) has been shown to be a useful tool for capturing health-related quality of life of patients in "everyday life" and in progressive supranuclear palsy (PSP) research. However, at 45 items in length, the questionnaire can take a long time, exhausting PSP patients, in particular if cognitive impaired, which can have a negative impact on the assessment. The aim of this study was to establish a condensed version of the PSP-QoL for research and routine clinical care., Methods: In this retrospective study, data originating from a German cohort of PSP patients was analyzed. Data from 245 PSP patients were included in this study. The short PSP-QoL questionnaire was created using a two-factor solution and item-total and inter-item correlations for mental and physical aspects of daily living of the PSP-QoL followed by confirmatory factor analysis., Results: The final scale included 12 items representing mental (five items) and physical symptoms (seven items). The specified two-factor model displayed an excellent fit in the confirmatory factor analysis. The short Progressive Supranuclear Palsy Quality of Life scale (PSP-ShoQoL) correlated moderately with the PSP Rating Scale (r [243] = 0.514, P < 0.001) and Geriatric depression scale (r [231] = 0.548, P < 0.001). Sensitivity to change confirmed a significant decrease in QoL after 12 months., Discussion: In this study, we created a 12-item PSP-ShoQoL designed to "facilitate" daily clinical work that correlated strongly with the PSP-QoL and was sensitive to change. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
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- 2024
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35. The association of vagal atrophy with parameters of autonomic function in multiple system atrophy and progressive supranuclear palsy.
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Kleinz T, Scholz L, Huckemann S, Rohmann R, Kühn E, Averdunk P, Kools S, Hilker L, Bieber A, Müller K, Motte J, Fisse AL, Schneider-Gold C, Gold R, Kwon EH, Tönges L, and Pitarokoili K
- Abstract
Background: Vagal atrophy is a hallmark of Parkinson's disease (PD) and has been found to be associated with autonomic dysfunction, while analyses of the vagus nerve (VN) in atypical Parkinsonian syndromes (APS) have not yet been performed. We here investigate the characteristics of the VN in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) and, in a second step, its potential as a possible biomarker for orthostatic dysregulation., Objectives: The aim was to compare the VN pathology in MSA and PSP with healthy individuals and patients with PD as a differentiating factor and to further analyse the correlation of the VN with clinical parameters and cardiovascular response., Design: We conducted a monocentric, cross-sectional cohort study in 41 APS patients and compared nerve ultrasound (NUS) parameters with 90 PD patients and 39 healthy controls., Methods: In addition to a detailed neurological history and examination, several clinical severity and motor scores were obtained. Autonomic symptoms were reported in the Scales for Outcomes in Parkinson's Disease - Autonomic questionnaire. Further scores were used to detect other non-motor symptoms, quality of life and cognition. Additionally, we performed a head up tilt test (HUTT) and NUS of the VN. We conducted correlation analyses of the VN cross-sectional area (CSA) with clinical scores and the heart rate and blood pressure variability parameters of the HUTT., Results: The examination demonstrated a high prevalence of abnormal autonomic response in both MSA (90%) and PSP (80%). The VN CSA correlated with spectral parameters of the HUTT, which are associated with sympatho-vagal imbalance. In addition, the CSA of the VN in patients with PD and PSP were significantly smaller than in healthy controls. In MSA, however, there was no marked vagal atrophy in comparison., Conclusion: The occurrence of autonomic dysfunction was high in MSA and PSP, which underlines its impact on these syndromes. Our findings indicate a connection between vagal pathology and autonomic dysfunction and might contribute to a better comprehension of APS. To further evaluate the clinical relevance and the VN as a possible marker of autonomic dysfunction in APS, prospective longitudinal observations are necessary., (© The Author(s), 2024.)
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- 2024
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36. Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson's disease study.
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Westenberger A, Skrahina V, Usnich T, Beetz C, Vollstedt EJ, Laabs BH, Paul JJ, Curado F, Skobalj S, Gaber H, Olmedillas M, Bogdanovic X, Ameziane N, Schell N, Aasly JO, Afshari M, Agarwal P, Aldred J, Alonso-Frech F, Anderson R, Araújo R, Arkadir D, Avenali M, Balal M, Benizri S, Bette S, Bhatia P, Bonello M, Braga-Neto P, Brauneis S, Cardoso FEC, Cavallieri F, Classen J, Cohen L, Coletta D, Crosiers D, Cullufi P, Dashtipour K, Demirkiran M, de Carvalho Aguiar P, De Rosa A, Djaldetti R, Dogu O, Dos Santos Ghilardi MG, Eggers C, Elibol B, Ellenbogen A, Ertan S, Fabiani G, Falkenburger BH, Farrow S, Fay-Karmon T, Ferencz GJ, Fonoff ET, Fragoso YD, Genç G, Gorospe A, Grandas F, Gruber D, Gudesblatt M, Gurevich T, Hagenah J, Hanagasi HA, Hassin-Baer S, Hauser RA, Hernández-Vara J, Herting B, Hinson VK, Hogg E, Hu MT, Hummelgen E, Hussey K, Infante J, Isaacson SH, Jauma S, Koleva-Alazeh N, Kuhlenbäumer G, Kühn A, Litvan I, López-Manzanares L, Luxmore M, Manandhar S, Marcaud V, Markopoulou K, Marras C, McKenzie M, Matarazzo M, Merello M, Mollenhauer B, Morgan JC, Mullin S, Musacchio T, Myers B, Negrotti A, Nieves A, Nitsan Z, Oskooilar N, Öztop-Çakmak Ö, Pal G, Pavese N, Percesepe A, Piccoli T, Pinto de Souza C, Prell T, Pulera M, Raw J, Reetz K, Reiner J, Rosenberg D, Ruiz-Lopez M, Ruiz Martinez J, Sammler E, Santos-Lobato BL, Saunders-Pullman R, Schlesinger I, Schofield CM, Schumacher-Schuh AF, Scott B, Sesar Á, Shafer SJ, Sheridan R, Silverdale M, Sophia R, Spitz M, Stathis P, Stocchi F, Tagliati M, Tai YF, Terwecoren A, Thonke S, Tönges L, Toschi G, Tumas V, Urban PP, Vacca L, Vandenberghe W, Valente EM, Valzania F, Vela-Desojo L, Weill C, Weise D, Wojcieszek J, Wolz M, Yahalom G, Yalcin-Cakmakli G, Zittel S, Zlotnik Y, Kandaswamy KK, Balck A, Hanssen H, Borsche M, Lange LM, Csoti I, Lohmann K, Kasten M, Brüggemann N, Rolfs A, Klein C, and Bauer P
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Glucosylceramidase genetics, alpha-Synuclein genetics, Genetic Predisposition to Disease, Ubiquitin-Protein Ligases genetics, Cohort Studies, Protein Kinases genetics, Mutation, Adult, Parkinson Disease genetics, Genetic Testing methods, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 genetics
- Abstract
Estimates of the spectrum and frequency of pathogenic variants in Parkinson's disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinson's disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (∼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 × 10-34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 × 10-35). Female patients were 22% more likely to have a positive PDGT (P = 3 × 10-4), and for individuals with FH+ this likelihood was 55% higher (P = 1 × 10-14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that ∼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)
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- 2024
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37. [Facets of neurodegeneration : The fine art of diagnostic workup and individualized treatment].
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Tönges L
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- Humans, Precision Medicine, Neurodegenerative Diseases diagnosis, Neurodegenerative Diseases therapy
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- 2024
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38. [Multidisciplinary Complex Treatment of Parkinson's disease : Cornerstone of an individualized treatment].
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Scherbaum R and Tönges L
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- Humans, Combined Modality Therapy, Germany, Evidence-Based Medicine, Quality of Life, Interdisciplinary Communication, Treatment Outcome, Intersectoral Collaboration, Activities of Daily Living, Parkinson Disease therapy, Precision Medicine, Patient Care Team
- Abstract
Background: The inpatient Parkinson's disease multimodal complex treatment (PD-MCT) was applied more than 15,000 times in 2022, in Germany. This number is increasing as is Parkinson's disease (PD), which affects more than 400,000 people in Germany and leads to 100,000 disability-adjusted life years. In recent years, several observational studies have been conducted on the effectiveness of this kind of multidisciplinary care., Objective: To summarize and discuss the evidence on the nature, benefits and potential of PD-MCT., Methods: A narrative review of selected empirical findings was carried out., Results: The PD-MCT frequently lasts for 2-3 weeks and aims to maintain the quality of life of people with PD. Disease symptoms and activities of daily living are jointly improved by pharmacological strategies and activating therapies (physiotherapy, occupational therapy, speech and language therapy, physical training, art therapy). The PD-MCT is a useful measure to avoid or mitigate crisis situations in the course of the disease. A total of eight observational studies (n = 1246) have shown good effectiveness with a total mean improvement of the International Parkinson and Movement Disorder Society unified Parkinson's disease rating scale III (MDS-UPDRS III) by 7.8 points. The transfer of effects into everyday life through intensive and specialized community-based care must be ensured in order to achieve sustained effects on the quality of life. Ideally, this transfer can be supported by integrated PD networks and digital technologies in the future., Conclusion: There is potential for development in the standardization, patient selection and quality assurance of PD-MCT as well as in the embedding in care structures such as PD networks. Open research questions include a precise definition of the target group and higher quality evidence of short-term and long-term effectiveness., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)
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- 2024
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39. Guideline "Parkinson's disease" of the German Society of Neurology (Deutsche Gesellschaft für Neurologie): concepts of care.
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Tönges L, Buhmann C, Eggers C, Lorenzl S, and Warnecke T
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Introduction: In 2023, the German Society of Neurology published a new guideline on Parkinson's disease. An important section dealt with PD care concepts, which represent a particularly dynamic field of PD research, including their implementation in clinical practice. Parkinson's disease is the second most common age-associated neurodegenerative disease. Current estimates of the number of cases in the population describe a significant increase in prevalence in Germany by 2030 with higher proportions in rural areas, which also have a lack of sufficient PD care resources., Recommendations: In comparison with other international guidelines, which have so far mentioned palliative care and Parkinson's nurses in particular, the German S2k guideline expands the recommended concepts of PD care to include PD day clinics, inpatient complex treatment, and PD networks., Conclusion: Concepts of PD care guidelines are necessary because of the complex and rapidly evolving field of PD care provision. If applied appropriately, the potential for optimized care can be exploited and both the patient burden and the economic burden can be reduced. Given that modern care concepts have so far only been applied in a few regions, it is often impossible to generate broad evidence-based data, so that the evaluation of PD care concepts is partly dependent on expert opinion., (© 2024. The Author(s).)
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- 2024
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40. [How the implementation of a school for people with Parkinson's disease can succeed-Results of a consensus study and a formative evaluation].
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Gerschel T, Prokop S, Schulze L, Feige T, Zschieschang A, Barbe MT, Bitterlich R, Caffier J, Csoti I, Eggers C, Gaßner H, Gülke E, Hähnel T, Herbst H, Jochim A, Kiparski A, Klietz M, von Liel A, Lingor P, Loewenbrück K, Maetzler W, Pürner D, van Riesen C, Schmitz-Pfeiffer H, Süß T, Tönges L, Weiß D, Wolz M, and Falkenburger B
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- Humans, Germany, Pilot Projects, Patient Participation, Consensus, Computer-Assisted Instruction methods, Curriculum, Focus Groups, Male, Decision Making, Shared, Parkinson Disease therapy, Patient Education as Topic methods
- Abstract
Background: As the most rapidly increasing neurodegenerative disease worldwide, Parkinson's disease is highly relevant to society. Successful treatment requires active patient participation. Patient education has been successfully implemented for many chronic diseases, such as diabetes and could also provide people with Parkinson's disease with skills to manage the disease better and to participate in shared decision making., Material and Methods: To prepare the implementation of a concept for patient education for people with Parkinson's disease, a structured consensus study was conducted and a pilot project formatively evaluated. The structured consensus study included experts from all over Germany. It consisted of two online surveys and an online consensus conference. The formative evaluation was conducted as three focus groups. Transcripts were evaluated using content-structuring qualitative content analysis., Results: From the consensus procedure 59 consented statements emerged, mainly regarding the contents of a patient school and a group size of 6-8 persons. Only two statements could not be consented. The formative evaluation detected a tendency towards a positive attitude for a digital training format and a very positive evaluation of the contents., Discussion: Overall, important recommendations for a patient school can be drawn from this study. The following subjects require further investigation: format, inclusion criteria, group composition and inclusion of caregivers., (© 2024. The Author(s).)
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- 2024
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41. Care of Late-Stage Parkinsonism: Resource Utilization of the Disease in Five European Countries.
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Kruse C, Lipinski A, Verheyen M, Balzer-Geldsetzer M, Wittenberg M, Lorenzl S, Richinger C, Schmotz C, Tönges L, Woitalla D, Klebe S, Bloem BR, Hommel A, Meissner WG, Laurens B, Boraud T, Foubert-Samier A, Vergnet S, Tison F, Costa N, Odin P, Rosqvist K, Norlin JM, Hjalte F, Schrag A, and Dodel R
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- Humans, Europe epidemiology, Germany, Neurodegenerative Diseases, Parkinsonian Disorders epidemiology, Parkinsonian Disorders therapy, Parkinson Disease epidemiology, Parkinson Disease therapy
- Abstract
Background: Parkinson's disease (PD) is a neurodegenerative disease that leads to progressive disability. Cost studies have mainly explored the early stages of the disease, whereas late-stage patients are underrepresented., Objective: The aim is to evaluate the resource utilization and costs of PD management in people with late-stage disease., Methods: The Care of Late-Stage Parkinsonism (CLaSP) study collected economic data from patients with late-stage PD and their caregivers in five European countries (France, Germany, the Netherlands, UK, Sweden) in a range of different settings. Patients were eligible to be included if they were in Hoehn and Yahr stage >3 in the on state or Schwab and England stage at 50% or less. In total, 592 patients met the inclusion criteria and provided information on their resource utilization. Costs were calculated from a societal perspective for a 3-month period. A least absolute shrinkage and selection operator approach was utilized to identify the most influential independent variables for explaining and predicting costs., Results: During the 3-month period, the costs were €20,573 (France), €19,959 (Germany), €18,319 (the Netherlands), €25,649 (Sweden), and €12,156 (UK). The main contributors across sites were formal care, hospitalization, and informal care. Gender, age, duration of the disease, Unified Parkinson's Disease Rating Scale 2, the EQ-5D-3L, and the Schwab and England Scale were identified as predictors of costs., Conclusion: Costs in this cohort of individuals with late-stage PD were substantially higher compared to previously published data on individuals living in earlier stages of the disease. Resource utilization in the individual sites differed in part considerably among these three parameters mentioned. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
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- 2024
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42. The comorbidity and co-medication profile of patients with progressive supranuclear palsy.
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Greten S, Wegner F, Jensen I, Krey L, Rogozinski S, Fehring M, Heine J, Doll-Lee J, Pötter-Nerger M, Zeitzschel M, Hagena K, Pedrosa DJ, Eggers C, Bürk K, Trenkwalder C, Claus I, Warnecke T, Süß P, Winkler J, Gruber D, Gandor F, Berg D, Paschen S, Classen J, Pinkhardt EH, Kassubek J, Jost WH, Tönges L, Kühn AA, Schwarz J, Peters O, Dashti E, Priller J, Spruth EJ, Krause P, Spottke A, Schneider A, Beyle A, Kimmich O, Donix M, Haussmann R, Brandt M, Dinter E, Wiltfang J, Schott BH, Zerr I, Bähr M, Buerger K, Janowitz D, Perneczky R, Rauchmann BS, Weidinger E, Levin J, Katzdobler S, Düzel E, Glanz W, Teipel S, Kilimann I, Prudlo J, Gasser T, Brockmann K, Hoffmann DC, Klockgether T, Krause O, Heck J, Höglinger GU, and Klietz M
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- Humans, Aged, Cross-Sectional Studies, Comorbidity, Supranuclear Palsy, Progressive drug therapy, Supranuclear Palsy, Progressive epidemiology, Supranuclear Palsy, Progressive diagnosis, Neurodegenerative Diseases epidemiology
- Abstract
Background: Progressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients., Objectives: To explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease., Methods: Cross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were evaluated using AiDKlinik®., Results: In total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drug-drug interactions was higher in PSP patients, especially severe and moderate interactions., Conclusions: PSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients., (© 2023. The Author(s).)
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- 2024
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43. Inpatient care of neuromyelitis optica spectrum disorder in Germany: Nationwide analysis from 2010 to 2021.
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Richter D, Bartig D, Tönges L, Kümpfel T, Schwake C, Gold R, Krogias C, and Ayzenberg I
- Abstract
Background: Despite tremendous development in the treatment of neuromyelitis optica spectrum disorder (NMOSD), less is known about the characteristics of hospitalized patients and inpatient care utilization., Objective: To investigate the development of inpatient NMOSD case numbers and implemented immunotherapies in the last decade in Germany., Methods: We conducted a nationwide retrospective study using an administrative database of all hospitalized NMOSD patients between 2010 and 2021. We evaluated yearly data on case numbers, demographics, treatment regimens, and seasonal variations of apheresis therapy as a surrogate marker of severe relapse incidence., Results: During the observational period case number of inpatients substantially increased (2010: n = 463, 2021: n = 992). The mean age was 48.1 ± 2.5 years (74% females). The pooled yearly rate of plasmapheresis/immunoadsorption was 14% (95% CI [13-15%]), without seasonal variations. Its application peaked in 2013 (18%, 95% CI [15-21%]) with decreasing trend since. Predominant immunotherapy was rituximab (40%, 95% CI [34-45%]), followed by tocilizumab (4%, 95% CI [3-5%]) since 2013 and eculizumab (4%, 95% CI [3-5%]) since 2020. Inpatient mortality ranged between 0% and 1% per year., Conclusions: Inpatient case numbers of NMOSD substantially increased during the past decade, probably reflecting improving disease awareness. In parallel with the administration of highly effective therapies rate of apheresis therapies decreased. A stable apheresis rate over the year makes seasonal variations of the steroid-refractive relapses unlikely., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2023.)
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- 2023
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44. Data-driven subtyping of Parkinson's disease: comparison of current methodologies and application to the Bochum PNS cohort.
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Chen Q, Scherbaum R, Gold R, Pitarokoili K, Mosig A, Zella S, and Tönges L
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- Humans, Levodopa therapeutic use, Mental Status and Dementia Tests, Germany, Parkinson Disease diagnosis, Parkinson Disease drug therapy
- Abstract
Considerable efforts have been made to better describe and identify Parkinson's disease (PD) subtypes. Cluster analyses have been proposed as an unbiased development approach for PD subtypes that could facilitate their identification, tracking of progression, and evaluation of therapeutic responses. A data-driven clustering analysis was applied to a PD cohort of 114 subjects enrolled at St. Josef-Hospital of the Ruhr University in Bochum (Germany). A wide spectrum of motor and non-motor scores including polyneuropathy-related measures was included into the analysis. K-means and hierarchical agglomerative clustering were performed to identify PD subtypes. Silhouette and Calinski-Harabasz Score Elbow were then employed as supporting evaluation metrics for determining the optimal number of clusters. Principal Component Analysis (PCA), analysis of variance (ANOVA), and analysis of covariance (ANCOVA) were conducted to determine the relevance of each score for the clusters' definition. Three PD cluster subtypes were identified: early onset mild type, intermediate type, and late-onset severe type. The between-cluster analysis consistently showed highly significant differences (P < 0.01), except for one of the scores measuring polyneuropathy (Neuropathy Disability Score; P = 0.609) and Levodopa dosage (P = 0.226). Parkinson's Disease Questionnaire (PDQ-39), Non-motor Symptom Questionnaire (NMSQuest), and the MDS-UPDRS Part II were found to be crucial factors for PD subtype differentiation. The present analysis identifies a specific set of criteria for PD subtyping based on an extensive panel of clinical and paraclinical scores. This analysis provides a foundation for further development of PD subtyping, including k-means and hierarchical agglomerative clustering.Trial registration: DRKS00020752, February 7, 2020, retrospectively registered., (© 2023. The Author(s).)
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- 2023
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45. Significance of clinical symptoms and red flags in early differential diagnosis of Parkinson's disease and atypical Parkinsonian syndromes.
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Schröter N, van Eimeren T, Classen J, Levin J, Redecker C, Wolz M, and Tönges L
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- Humans, Diagnosis, Differential, Multiple System Atrophy diagnosis, Parkinson Disease diagnosis, Parkinsonian Disorders diagnosis, Supranuclear Palsy, Progressive diagnosis
- Abstract
The clinical presentation of Parkinson's disease and atypical Parkinsonian syndromes is often heterogeneous. Additional diagnostic procedures including brain imaging and biomarker analyses can help to appreciate the various syndromes, but a precise clinical evaluation and differentiation is always necessary. To better assess the relevance of distinct clinical symptoms that arose within 1 year of disease manifestation and evaluate their indicative potential for an atypical Parkinsonian syndrome, we conducted a modified Delphi panel with seven movement disorder specialists. Five different topics with several clinical symptom items were discussed and consensus criteria were tested. This resulted in distinct symptom patterns for each atypical Parkinsonian syndrome showing the multitude of clinical involvement in each neurodegenerative disease. Strongly discriminating clinical signs were few and levels of indication were variable. A prospective validation of the assessments made is needed. This demonstrates that both clinical evaluation and elaborate additional diagnostic procedures are needed to achieve a high diagnostic standard., (© 2023. The Author(s).)
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- 2023
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46. Quality Control-A Stepchild in Quantitative Proteomics: A Case Study for the Human CSF Proteome.
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Rozanova S, Uszkoreit J, Schork K, Serschnitzki B, Eisenacher M, Tönges L, Barkovits-Boeddinghaus K, and Marcus K
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- Humans, Proteome analysis, Proteomics methods, Biomarkers analysis, Quality Control, Tandem Mass Spectrometry methods, Neurodegenerative Diseases
- Abstract
Proteomic studies using mass spectrometry (MS)-based quantification are a main approach to the discovery of new biomarkers. However, a number of analytical conditions in front and during MS data acquisition can affect the accuracy of the obtained outcome. Therefore, comprehensive quality assessment of the acquired data plays a central role in quantitative proteomics, though, due to the immense complexity of MS data, it is often neglected. Here, we address practically the quality assessment of quantitative MS data, describing key steps for the evaluation, including the levels of raw data, identification and quantification. With this, four independent datasets from cerebrospinal fluid, an important biofluid for neurodegenerative disease biomarker studies, were assessed, demonstrating that sample processing-based differences are already reflected at all three levels but with varying impacts on the quality of the quantitative data. Specifically, we provide guidance to critically interpret the quality of MS data for quantitative proteomics. Moreover, we provide the free and open source quality control tool MaCProQC , enabling systematic, rapid and uncomplicated data comparison of raw data, identification and feature detection levels through defined quality metrics and a step-by-step quality control workflow.
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- 2023
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47. Vagal cross-sectional area correlates with parasympathetic dysfunction in Parkinson's disease.
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Huckemann S, Mueller K, Averdunk P, Kühn E, Hilker L, Kools S, Scholz L, Bulut Y, Brünger J, Fiegert S, Grüter T, Fisse AL, Motte J, Yoon MS, Gold R, Schneider-Gold C, Tönges L, and Pitarokoili K
- Abstract
The aim of this prospective study was to investigate autonomic function in Parkinson's disease with a multidimensional approach including clinical evaluation tools, head-up tilt test and morphological studies of the vagus nerve. Head-up tilt test parameters including high frequency power of the heart frequency interval, the ratio of low frequency power of the distance between two consecutive R waves in electrocardiogram (RR interval) to the high frequency and low frequency power of systolic blood pressure were used to evaluate parasympathetic, cardiac sympathetic and vasomotor sympathetic functions, respectively, in 80 patients with Parkinson's disease. We examined the cross-sectional area of the vagus nerves bilaterally using nerve ultrasound and compared mean values with a control group of healthy subjects ( n = 40) as well as patients with chronic inflammatory demyelinating polyneuropathy ( n = 76). The cross-sectional area of right/left vagus nerve of Parkinson's patients was significantly lower compared to the right/left vagus nerve of the control group and of chronic demyelinating polyneuropathy patients. Furthermore, the cross-sectional area of the right vagus nerve was significantly larger from the one of the left vagus nerve for all groups. Based on tilt test, 43 patients (disease duration 7 ± 5, age at evaluation 71 ± 9, Hoehn and Yahr score 2.8 ± 8) were diagnosed with autonomic dysfunction (orthostatic hypertension n = 11, chronotropic incompetence n = 31, postural orthostatic tachycardia syndrome n = 1). Patients with orthostatic hypotension showed significantly higher Unified Parkinson's Disease Rating Scale-III values than those with chronotropic incompetence. The cross-sectional area of the vagus nerve correlated inversely with heart rate in rest and supine position and positively with tilt test parameters representing parasympathetic modulation through vagal activity [high frequency power of the distance between two consecutive R waves in electrocardiogram (RR interval)] at rest. We demonstrate for the first time that morphological characteristics of the vagus nerve correlate with parameters of parasympathetic function from the spectral analysis of cardiovascular parameters in tilt test for Parkinson's patients. This correlation reveals the impact of the atrophy of vagal atrophy for autonomic function in Parkinson's disease. Nerve ultrasound of the vagus nerve could potentially be used as an adjunct to tilt table examination to diagnose autonomic dysfunction., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)
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- 2023
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48. [Adenosine A2A Receptor Antagonists as a Treatment Option for Parkinson's Disease?]
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Jost WH and Tönges L
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- Humans, Antiparkinson Agents therapeutic use, Receptor, Adenosine A2A therapeutic use, Quality of Life, Dopamine, Adenosine A2 Receptor Antagonists therapeutic use, Parkinson Disease drug therapy
- Abstract
In Parkinson's disease, the focus has long been on motor symptoms and therapy with dopaminergic substances. In recent years, the importance of non-motor symptoms has been increasingly recognized, as they occur early in the course of the disease and restrict considerably the quality of life. However, this also made the need for treatment of non-dopaminergic deficits obvious. Adenosine A
2A receptor antagonists were identified as an additional therapy, since the adenosine A2A receptors are non-dopaminergic and selectively localized in the basal ganglia. This means that the striato-thalamo-cortical loops can be modulated. An adenosine A2A receptor antagonist was already approved in Japan in 2013 and in the USA in 2019 as an add-on to L-DOPA. Approval for this drug in Europe is expected in the near future. In this overview, we present the theoretical basis and current data on its efficacy and therapeutic use., Competing Interests: W. Jost ist oder war als Berater und Referent für folgende Firmen tätig: Abbvie, Bial, Desitin, Kyowa Kirin, Stada, UCB, Zambon L. Tönges erhielt Honorare als wissenschaftlicher Berater, für Vortrags- und Schulungstätigkeiten oder Autorenschaften von Abbvie, Bayer, Boehringer, Bial, Desitin, GE, Kyowa Kirin, Stadapharm, UCB Pharma und Zambon., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)- Published
- 2022
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49. Parkinson's disease multimodal complex treatment improves gait performance: an exploratory wearable digital device-supported study.
- Author
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Scherbaum R, Moewius A, Oppermann J, Geritz J, Hansen C, Gold R, Maetzler W, and Tönges L
- Subjects
- Aged, Fear, Gait, Humans, Walking physiology, Parkinson Disease drug therapy, Parkinson Disease therapy, Wearable Electronic Devices
- Abstract
Background: Wearable device-based parameters (DBP) objectively describe gait and balance impairment in Parkinson's disease (PD). We sought to investigate correlations between DBP of gait and balance and clinical scores, their respective changes throughout the inpatient multidisciplinary Parkinson's Disease Multimodal Complex Treatment (PD-MCT), and correlations between their changes., Methods: This exploratory observational study assessed 10 DBP and clinical scores at the start (T1) and end (T2) of a two-week PD-MCT of 25 PD in patients (mean age: 66.9 years, median HY stage: 2.5). Subjects performed four straight walking tasks under single- and dual-task conditions, and four balance tasks., Results: At T1, reduced gait velocity and larger sway area correlated with motor severity. Shorter strides during motor-motor dual-tasking correlated with motor complications. From T1 to T2, gait velocity improved, especially under dual-task conditions, stride length increased for motor-motor dual-tasking, and clinical scores measuring motor severity, balance, dexterity, executive functions, and motor complications changed favorably. Other gait parameters did not change significantly. Changes in motor complications, motor severity, and fear of falling correlated with changes in stride length, sway area, and measures of gait stability, respectively., Conclusion: DBP of gait and balance reflect clinical scores, e.g., those of motor severity. PD-MCT significantly improves gait velocity and stride length and favorably affects additional DBP. Motor complications and fear of falling are factors that may influence the response to PD-MCT. A DBP-based assessment on admission to PD inpatient treatment could allow for more individualized therapy that can improve outcomes., Trial Registration Number and Date: DRKS00020948 number, 30-Mar-2020, retrospectively registered., (© 2022. The Author(s).)
- Published
- 2022
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50. [Relevance of COMT inhibitors in the treatment of motor fluctuations].
- Author
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Jost WH, Buhmann C, Classen J, Eggert K, Kohl Z, Outeiro T, Tönges L, Woitalla D, and Reichmann H
- Subjects
- Antiparkinson Agents adverse effects, Catechol O-Methyltransferase therapeutic use, Humans, Levodopa adverse effects, Tolcapone therapeutic use, Catechol O-Methyltransferase Inhibitors therapeutic use, Parkinson Disease diagnosis, Parkinson Disease drug therapy
- Abstract
Catechol O‑methyltransferase (COMT) inhibitors have been established in the treatment of Parkinson's disease for more than 20 years. They are considered the medication of choice for treating motor fluctuations. The available COMT inhibitors, entacapone, opicapone and tolcapone, differ pharmacokinetically in terms of their half-lives with implications for the dose frequency, in their indication requirements and in their spectrum of side effects, including diarrhea and yellow discoloration of urine. Many patients with motor fluctuations are currently not treated with COMT inhibitors and are, therefore, unlikely to receive individually optimized drug treatment. This manuscript summarizes the results of a working group including several Parkinson's disease experts, in which the value of COMT inhibitors was critically discussed., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)
- Published
- 2022
- Full Text
- View/download PDF
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