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  • 1. Abat, F
    et al.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine. Alfredson Tendon Clinic Inc, Umeå, Sweden; Pure Sports Medicine Clinic, ISEH, UCLH, London, UK.
    Cucchiarini, M
    Madry, H
    Marmotti, A
    Mouton, C
    Oliveira, J M
    Pereira, H
    Peretti, G M
    Spang, Christoph
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Stephen, J
    van Bergen, C J A
    de Girolamo, L
    Current trends in tendinopathy: consensus of the ESSKA basic science committee. Part II2018In: Journal of experimental orthopaedics, ISSN 2197-1153, Vol. 5, no 38Article in journal (Refereed)
    Abstract [en]

    The treatment of painful chronic tendinopathy is challenging. Multiple non-invasive and tendon-invasive methods are used. When traditional non-invasive treatments fail, the injections of platelet-rich plasma autologous blood or cortisone have become increasingly favored. However, there is little scientific evidence from human studies supporting injection treatment. As the last resort, intra- or peritendinous open or endoscopic surgery are employed even though these also show varying results. This ESSKA basic science committee current concepts review follows the first part on the biology, biomechanics and anatomy of tendinopathies, to provide a comprehensive overview of the latest treatment options for tendinopathy as reported in the literature.

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  • 2.
    Abat, F.
    et al.
    Department of Orthopaedic Sports Medicine, ReSport Clinic, Passeig Fabra i Puig 47, Barcelona, Spain.
    Alfredson, Håkan
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports Medicine. Alfredson Tendon Clinic Inc, Umeå, Sweden; Pure Sports Medicine Clinic, ISEH, UCLH, London, United Kingdom.
    Cucchiarini, M.
    Molecular Biology, Center of Experimental Orthopaedics, Saarland University Medical Center, Kirrbergerstr Bldg 37, Homburg/Saar, Germany.
    Madry, H.
    Lehrstuhl für Experimentelle Orthopädie und Arthroseforschung, Universität des Saarlandes, Gebäude 37, Kirrbergerstr 1, Homburg, Germany.
    Marmotti, A.
    Department of Orthopaedics and Traumatology, San Luigi Gonzaga Hospital, Orbassano, University of Turin, Turin, Italy.
    Mouton, C.
    Department of Orthopedic Surgery, Clinique d’Eich-Centre Hospitalier de Luxembourg, 76, rue d’Eich, Luxembourg, Luxembourg.
    Oliveira, J.M.
    3B’s Research Group – Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Zona Industrial da Gandra, GMR, Barco, Portugal; ICVS/3B’s - PT Government Associate Laboratory, Braga, Guimarães, Portugal.
    Pereira, H.
    3B’s Research Group University of Minho, ICVS/3B’s–PT Government Associate Laboratory, Braga, Guimarães, Portugal; Orthopedic Department Centro Hospitalar Póvoa de Varzim, Vila do Conde, Portugal; Ripoll y De Prado Sports Clinic – FIFA Medical Centre of Excellence, Madrid, Murcia, Spain.
    Peretti, G.M.
    IRCCS Istituto Ortopedico Galeazzi, Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
    Romero-Rodriguez, D.
    Department of Physical Therapy and Sports Rehabilitation, ReSport Clinic Barcelona, Barcelona, Spain; EUSES Sports Science, University of Girona, Girona, Spain.
    Spang, Christoph
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Stephen, J.
    Fortius Clinic, 17 Fitzhardinge St, London, United Kingdom; The Biomechanics Group, Department of Mechanical Engineering, Imperial College, London, United Kingdom.
    van Bergen, C.J.A.
    Department of Orthopedic Surgery, Amphia Hospital Breda, Breda, Netherlands.
    de Girolamo, L.
    Orthopaedic Biotechnology Laboratory, Galeazzi Orthopaedic Institute, Milan, Italy.
    Current trends in tendinopathy: consensus of the ESSKA basic science committee. Part I: biology, biomechanics, anatomy and anexercise-based approach2017In: Journal of Experimental Orthopaedics, E-ISSN 2197-1153, Vol. 4, no 1, article id 18Article, review/survey (Refereed)
    Abstract [en]

    Chronic tendinopathies represent a major problem in the clinical practice of sports orthopaedic surgeons, sports doctors and other health professionals involved in the treatment of athletes and patients that perform repetitive actions. The lack of consensus relative to the diagnostic tools and treatment modalities represents a management dilemma for these professionals. With this review, the purpose of the ESSKA Basic Science Committee is to establish guidelines for understanding, diagnosing and treating this complex pathology.

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  • 3.
    Abbood, Maab Mohammed Abbood
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Bildning av ett elektroaktivt lipiddubbelskikt för studie av membranfördelningsbeteendet hos joniska läkemedel_ En laborativ studie2023Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
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  • 4.
    Abdelmalek, George
    et al.
    Rutgers New Jersey Medical School, NJ, Newark, United States.
    Mina, George Ehab
    Rutgers New Jersey Medical School, NJ, Newark, United States.
    Pant, Krittika
    Rutgers New Jersey Medical School, NJ, Newark, United States.
    Zheng, Zheshi
    Department of Statistics, Rutgers University, NJ, Piscataway, United States.
    Mahajan, Jasmine
    Rutgers New Jersey Medical School, NJ, Newark, United States.
    Srinivasan, Nivetha
    Rutgers New Jersey Medical School, NJ, Newark, United States.
    Gupta, Shivani
    Rutgers New Jersey Medical School, NJ, Newark, United States.
    Shafei, Jasmine
    Rutgers New Jersey Medical School, NJ, Newark, United States.
    Levidy, Michael F.
    Rutgers New Jersey Medical School, NJ, Newark, United States.
    McGrath, Aleksandra M
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Department of Hand Surgery, Norrland’s University Hospital, Umeå, Sweden.
    Chu, Alice
    Division of Pediatric Orthopedics, Department of Orthopedic Surgery, Rutgers New Jersey Medical School, NJ, Newark, United States.
    Intercostal nerve transfer for biceps reinnervation in obstetrical brachial plexus palsy: a preferred reporting items for systematic reviews and meta-analysis for individual patient data systematic review using individualized fusion and comparison to supraclavicular exploration and nerve grafting2024In: Journal of Children's Orthopaedics, ISSN 1863-2521, E-ISSN 1863-2548, Vol. 18, no 1, p. 54-63Article, review/survey (Refereed)
    Abstract [en]

    Introduction: The objective of this study was to search existing literature on nerve reconstruction surgery in patients with obstetric brachial plexus palsy to determine whether treatment with supraclavicular exploration and nerve grafting produced better elbow flexion outcomes compared to intercostal nerve transfer.

    Methods: This study was a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Individual Patient Data guidelines. A systematic search was conducted using multiple databases. An ordinal regression model was used to analyze the effect of using supraclavicular exploration and nerve grafting or intercostal nerve on elbow flexion with the two scores measured: elbow flexion Medical Research Council scores and Toronto active movements scale scores for elbow flexion.

    Results: A final patient database from 6 published articles consisted of 83 supraclavicular exploration and nerve grafting patients (73 patients with Medical Research Council and 10 patients with Toronto score) and 7 published articles which consisted of 131 intercostal nerve patients (84 patients with Medical Research Council and 47 patients with Toronto scores). Patients who underwent supraclavicular exploration and nerve grafting presented with an average Medical Research Council score of 3.9 ± 0.72 and an average Toronto score of 6.2 ± 2.2. Patients who underwent intercostal nerve transfer presented with an average Medical Research Council score of 3.9 ± 0.71 and an average Toronto score of 6.4 ± 1.2. There was no statistical difference between supraclavicular exploration and nerve grafting and intercostal nerve transfer when utilizing Medical Research Council elbow flexion scores (ordinal regression: 0.3821, standard error: 0.4590, p = 0.2551) or Toronto Active Movement Scale score for elbow flexion (ordinal regression: 0.7154, standard error: 0.8487, p = 0.2188).

    Conclusion: Regardless of surgical intervention utilized (supraclavicular exploration and nerve grafting or intercostal nerve transfers), patients had excellent outcomes for elbow flexion following obstetric brachial plexus palsy when utilizing Medical Research Council or Toronto scores for elbow flexion. The difference between these scores was not statistically significant.

    Type of study/Level of evidence: Therapeutic Study: Investigating the Result of Treatment/level III.

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  • 5.
    Abdul Rahim, Esra
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    EFFEKT OCH SÄKERHET AV CENOBAMAT_Med fokus på behandling vid fokal epilepsi2023Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 6.
    Abdulsalam Muhammednouri, Hevi
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Kvalitetsindikatorer på apotek. Patienters syn på apotekstjänster - ett enkätutvärderingsprojekt2021Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
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  • 7.
    Abo Allneaj, Razan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Antidepressiva läkemedelsförskrivning för barn och ungdomar: Effektivitet och säkerhet av fluoxetin och sertralin2021Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 8.
    Abramsson, Linnea
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Backman, Annica C.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lövheim, Hugo
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Edvardsson, David
    School of Nursing and Midwifery, La Trobe University, VIC, Bundoora, Australia.
    Gustafsson, Maria
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Use of heart failure medications in older individuals and associations with cognitive impairment2023In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 23, no 1, article id 524Article in journal (Refereed)
    Abstract [en]

    Background: To achieve the best treatment of heart failure, it is important to use all recommended drugs at their target doses. Given that underuse of medications can occur in individuals with cognitive impairment, we investigated the filled prescriptions and target doses of heart failure medication for older individuals with and without cognitive impairment as well as associated factors.

    Methods: The study was based on two separate datasets. The first dataset, which was based on data from questionnaires sent to nursing homes in Sweden, included 405 individuals with heart failure. The data were linked with the Swedish Prescribed Drug Register and the National Patient Register to obtain information regarding filled prescriptions of heart failure medications and heart failure diagnoses among the population. In the second dataset, medical records of individuals aged 75 years or older admitted to a hospital in northern Sweden were reviewed and individuals with heart failure were identified. Target doses of heart failure medications were evaluated in 66 individuals who lived at home.

    Results: Filled prescriptions of mineralocorticoid receptor antagonists and loop diuretics were significantly more common in individuals without cognitive impairment (OR 1.087; 95% CI 1.026–1.152, p < 0.05) and (OR 1.057; 95% CI 1.017–1.098, p < 0.05), respectively. There were no significant differences between individuals with and without cognitive impairment in terms of achieving target doses for any of the drug classes. A higher age was associated with fewer filled prescriptions and less ability to reach the target doses of beta blockers (OR 0.950; 95% CI 0.918–0.984, p < 0.05) and (OR 0.781; 95% CI 0.645–0.946, p < 0.05), respectively.

    Conclusions: Our results suggest that individuals with cognitive impairment are partly undertreated for heart failure in that they had fewer filled prescriptions of important heart medications. Separately, the relatively low proportion of older individuals reaching target doses is an important observation and indicates that treatment of heart failure could be further optimised among older individuals.

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  • 9.
    Abrudan, Teresa
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Psykiska biverkningar av hormonella preventivmedel: En litteraturstudie om samband och riskfaktorer2021Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 10.
    Achour, Cyrinne
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Bhattarai, Devi Prasad
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Esteva-Socias, Margalida
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Rodriguez-Barrueco, Ruth
    Malla, Sandhya
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Seier, Kerstin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Marchand, Virginie
    Motorine, Yuri
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Gilthorpe, Jonathan D.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Marzese, Diego Matias
    Bally, Marta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Roman, Angel-Carlos
    Pich, Andreas
    Aguilo, Francesca
    Reshaping the role of METTL3 in breast tumorigenesisManuscript (preprint) (Other academic)
  • 11.
    Adam, Iris
    et al.
    Department of Biology, University of Southern Denmark, Odense, Denmark.
    Riebel, Katharina
    Institute of Biology, Animal Sciences & Health, Leiden University, Leiden, Netherlands.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Wood, Neil
    Department of Molecular Physiology and Biophysics, Larner College of Medicine, University of Vermont, NJ, Burlington, United States.
    Previs, Michael J.
    Department of Molecular Physiology and Biophysics, Larner College of Medicine, University of Vermont, NJ, Burlington, United States.
    Elemans, Coen P. H.
    Department of Biology, University of Southern Denmark, Odense, Denmark.
    Daily vocal exercise is necessary for peak performance singing in a songbird2023In: Nature Communications, E-ISSN 2041-1723, Vol. 14, no 1, article id 7787Article in journal (Refereed)
    Abstract [en]

    Vocal signals, including human speech and birdsong, are produced by complicated, precisely coordinated body movements, whose execution is fitness-determining in resource competition and mate choice. While the acquisition and maintenance of motor skills generally requires practice to develop and maintain both motor circuitry and muscle performance, it is unknown whether vocal muscles, like limb muscles, exhibit exercise-induced plasticity. Here, we show that juvenile and adult zebra finches (Taeniopygia castanotis) require daily vocal exercise to first gain and subsequently maintain peak vocal muscle performance. Experimentally preventing male birds from singing alters both vocal muscle physiology and vocal performance within days. Furthermore, we find females prefer song of vocally exercised males in choice experiments. Vocal output thus contains information on recent exercise status, and acts as an honest indicator of past exercise investment in songbirds, and possibly in all vocalising vertebrates.

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  • 12. Adams, Hieab H. H.
    et al.
    Hibar, Derrek P.
    Chouraki, Vincent
    Stein, Jason L.
    Nyquist, Paul A.
    Renteria, Miguel E.
    Trompet, Stella
    Arias-Vasquez, Alejandro
    Seshadri, Sudha
    Desrivieres, Sylvane
    Beecham, Ashley H.
    Jahanshad, Neda
    Wittfeld, Katharine
    Van der Lee, Sven J.
    Abramovic, Lucija
    Alhusaini, Saud
    Amin, Najaf
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Arfanakis, Konstantinos
    Aribisala, Benjamin S.
    Armstrong, Nicola J.
    Athanasiu, Lavinia
    Axelsson, Tomas
    Beiser, Alexa
    Bernard, Manon
    Bis, Joshua C.
    Blanken, Laura M. E.
    Blanton, Susan H.
    Bohlken, Marc M.
    Boks, Marco P.
    Bralten, Janita
    Brickman, Adam M.
    Carmichael, Owen
    Chakravarty, M. Mallar
    Chauhan, Ganesh
    Chen, Qiang
    Ching, Christopher R. K.
    Cuellar-Partida, Gabriel
    Den Braber, Anouk
    Doan, Nhat Trung
    Ehrlich, Stefan
    Filippi, Irina
    Ge, Tian
    Giddaluru, Sudheer
    Goldman, Aaron L.
    Gottesman, Rebecca F.
    Greven, Corina U.
    Grimm, Oliver
    Griswold, Michael E.
    Guadalupe, Tulio
    Hass, Johanna
    Haukvik, Unn K.
    Hilal, Saima
    Hofer, Edith
    Hoehn, David
    Holmes, Avram J.
    Hoogman, Martine
    Janowitz, Deborah
    Jia, Tianye
    Kasperaviciute, Dalia
    Kim, Sungeun
    Klein, Marieke
    Kraemer, Bernd
    Lee, Phil H.
    Liao, Jiemin
    Liewald, David C. M.
    Lopez, Lorna M.
    Luciano, Michelle
    Macare, Christine
    Marquand, Andre
    Matarin, Mar
    Mather, Karen A.
    Mattheisen, Manuel
    Mazoyer, Bernard
    Mckay, David R.
    McWhirter, Rebekah
    Milaneschi, Yuri
    Mirza-Schreiber, Nazanin
    Muetzel, Ryan L.
    Maniega, Susana Munoz
    Nho, Kwangsik
    Nugent, Allison C.
    Loohuis, Loes M. Olde
    Oosterlaan, Jaap
    Papmeyer, Martina
    Pappa, Irene
    Pirpamer, Lukas
    Pudas, Sara
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Puetz, Benno
    Rajan, Kumar B.
    Ramasamy, Adaikalavan
    Richards, Jennifer S.
    Risacher, Shannon L.
    Roiz-Santianez, Roberto
    Rommelse, Nanda
    Rose, Emma J.
    Royle, Natalie A.
    Rundek, Tatjana
    Saemann, Philipp G.
    Satizabal, Claudia L.
    Schmaal, Lianne
    Schork, Andrew J.
    Shen, Li
    Shin, Jean
    Shumskaya, Elena
    Smith, Albert V.
    Sprooten, Emma
    Strike, Lachlan T.
    Teumer, Alexander
    Thomson, Russell
    Tordesillas-Gutierrez, Diana
    Toro, Roberto
    Trabzuni, Daniah
    Vaidya, Dhananjay
    Van der Grond, Jeroen
    Van der Meer, Dennis
    Van Donkelaar, Marjolein M. J.
    Van Eijk, Kristel R.
    Van Erp, Theo G. M.
    Van Rooij, Daan
    Walton, Esther
    Westlye, Lars T.
    Whelan, Christopher D.
    Windham, Beverly G.
    Winkler, Anderson M.
    Woldehawariat, Girma
    Wolf, Christiane
    Wolfers, Thomas
    Xu, Bing
    Yanek, Lisa R.
    Yang, Jingyun
    Zijdenbos, Alex
    Zwiers, Marcel P.
    Agartz, Ingrid
    Aggarwal, Neelum T.
    Almasy, Laura
    Ames, David
    Amouyel, Philippe
    Andreassen, Ole A.
    Arepalli, Sampath
    Assareh, Amelia A.
    Barral, Sandra
    Bastin, Mark E.
    Becker, Diane M.
    Becker, James T.
    Bennett, David A.
    Blangero, John
    van Bokhoven, Hans
    Boomsma, Dorret I.
    Brodaty, Henry
    Brouwer, Rachel M.
    Brunner, Han G.
    Buckner, Randy L.
    Buitelaar, Jan K.
    Bulayeva, Kazima B.
    Cahn, Wiepke
    Calhoun, Vince D.
    Cannon, Dara M.
    Cavalleri, Gianpiero L.
    Chen, Christopher
    Cheng, Ching -Yu
    Cichon, Sven
    Cookson, Mark R.
    Corvin, Aiden
    Crespo-Facorro, Benedicto
    Curran, Joanne E.
    Czisch, Michael
    Dale, Anders M.
    Davies, Gareth E.
    De Geus, Eco J. C.
    De Jager, Philip L.
    de Zubicaray, Greig I.
    Delanty, Norman
    Depondt, Chantal
    DeStefano, Anita L.
    Dillman, Allissa
    Djurovic, Srdjan
    Donohoe, Gary
    Drevets, Wayne C.
    Duggirala, Ravi
    Dyer, Thomas D.
    Erk, Susanne
    Espeseth, Thomas
    Evans, Denis A.
    Fedko, Iryna
    Fernandez, Guillen
    Ferrucci, Luigi
    Fisher, Simon E.
    Fleischman, Debra A.
    Ford, Ian
    Foroud, Tatiana M.
    Fox, Peter T.
    Francks, Clyde
    Fukunaga, Masaki
    Gibbs, J. Raphael
    Glahn, David C.
    Gollub, Randy L.
    Goring, Harald H. H.
    Grabe, Hans J.
    Green, Robert C.
    Gruber, Oliver
    Gudnason, Vilmundur
    Guelfi, Sebastian
    Hansell, Narelle K.
    Hardy, John
    Hartman, Catharina A.
    Hashimoto, Ryota
    Hegenscheid, Katrin
    Heinz, Andreas
    Le Hellard, Stephanie
    Hernandez, Dena G.
    Heslenfeld, Dirk J.
    Ho, Beng-Choon
    Hoekstra, Pieter J.
    Hoffmann, Wolfgang
    Hofman, Albert
    Holsboer, Florian
    Homuth, Georg
    Hosten, Norbert
    Hottenga, Jouke-Jan
    Pol, Hilleke E. Hulshoff
    Ikeda, Masashi
    Ikram, M. Kamran
    Jack, Clifford R., Jr.
    Jenldnson, Mark
    Johnson, Robert
    Jonsson, Erik G.
    Jukema, J. Wouter
    Kahn, Rene S.
    Kanai, Ryota
    Kloszewska, Iwona
    Knopman, David S.
    Kochunov, Peter
    Kwok, John B.
    Lawrie, Stephen M.
    Lemaitre, Herve
    Liu, Xinmin
    Longo, Dan L.
    Longstreth, W. T., Jr.
    Lopez, Oscar L.
    Lovestone, Simon
    Martinez, Oliver
    Martinot, Jean-Luc
    Mattay, Venkata S.
    McDonald, Colm
    McIntosh, Andrew M.
    McMahon, Katie L.
    McMahon, Francis J.
    Mecocci, Patrizia
    Melle, Ingrid
    Meyer-Lindenberg, Andreas
    Mohnke, Sebastian
    Montgomery, Grant W.
    Morris, Derek W.
    Mosley, Thomas H.
    Muhleisen, Thomas W.
    Mueller-Myhsok, Bertram
    Nalls, Michael A.
    Nauck, Matthias
    Nichols, Thomas E.
    Niessen, Wiro J.
    Noethen, Markus M.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Ohi, Kazutaka
    Olvera, Rene L.
    Ophoff, Roel A.
    Pandolfo, Massimo
    Paus, Tomas
    Pausova, Zdenka
    Penninx, Brenda W. J. H.
    Pike, G. Bruce
    Potkin, Steven G.
    Psaty, Bruce M.
    Reppermund, Simone
    Rietschel, Marcella
    Roffman, Joshua L.
    Romanczuk-Seiferth, Nina
    Rotter, Jerome I.
    Ryten, Mina
    Sacco, Ralph L.
    Sachdev, Perminder S.
    Saykin, Andrew J.
    Schmidt, Reinhold
    Schofield, Peter R.
    Sigurdsson, Sigurdur
    Simmons, Andy
    Singleton, Andrew
    Sisodiya, Sanjay M.
    Smith, Colin
    Smoller, Jordan W.
    Soininen, Hindu.
    Srikanth, Velandai
    Steen, Vidar M.
    Stott, David J.
    Sussmann, Jessika E.
    Thalamuthu, Anbupalam
    Tiemeier, Henning
    Toga, Arthur W.
    Traynor, Bryan J.
    Troncoso, Juan
    Turner, Jessica A.
    Tzourio, Christophe
    Uitterlinden, Andre G.
    Hernandez, Maria C. Valdes
    Van der Brug, Marcel
    Van der Lugt, Aad
    Van der Wee, Nic J. A.
    Van Duijn, Cornelia M.
    Van Haren, Neeltje E. M.
    Van't Ent, Dennis
    Van Tol, Marie Jose
    Vardarajan, Badri N.
    Veltman, Dick J.
    Vernooij, Meike W.
    Voelzke, Henry
    Walter, Henrik
    Wardlaw, Joanna M.
    Wassink, Thomas H.
    Weale, Michael E.
    Weinberger, Daniel R.
    Weiner, Michael W.
    Wen, Wei
    Westman, Eric
    White, Tonya
    Wong, Tien Y.
    Wright, Clinton B.
    Zielke, H. Ronald
    Zonderman, Alan B.
    Deary, Ian J.
    DeCarli, Charles
    Schmidt, Helena
    Martin, Nicholas G.
    De Craen, Anton J. M.
    Wright, Margaret J.
    Launer, Lenore J.
    Schumann, Gunter
    Fornage, Myriam
    Franke, Barbara
    Debette, Stephanie
    Medland, Sarah E.
    Ikram, M. Arfan
    Thompson, Paul M.
    Novel genetic loci underlying human intracranial volume identified through genome-wide association2016In: Nature Neuroscience, ISSN 1097-6256, E-ISSN 1546-1726, Vol. 19, no 12, p. 1569-1582Article in journal (Refereed)
    Abstract [en]

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

  • 13.
    af Bjerkén, Sara
    Umeå University, Faculty of Medicine, Integrative Medical Biology.
    On dopamine neurons: nerve fiber outgrowth and L-DOPA effects2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Parkinson’s disease is a disorder mainly characterized by progressive degeneration of dopamine producing neurons in the substantia nigra of the midbrain. The most commonly used treatment strategy is to pharmacologically restore the lost function by the administration of the dopaminergic precursor L-DOPA. Another treatment strategy is to replace the degenerated neurons with immature fetal ventral mesencephalic tissue, or ultimately stem cell-derived tissue. Grafting trials have, however, revealed poor reinnervation capacity of the grafts, leaving much of the striata dopamine-denervated. An additional drawback is the upcoming of dyskinesia (involuntary movements), a phenomenon also observed during L-DOPA treatment of Parkinson’s disease patients. Attempts to characterize nerve fiber formation from dopamine neurons have demonstrated that the nerve fibers are formed in two morphologically diverse outgrowth patterns, one early outgrowth seen in the absence of astrocytes and one later appearing outgrowth seen in co-existence with astrocytes.

    The overall objective of this thesis has been to study the dopaminergic outgrowth including guidance of nerve fiber formation, and to look into the mechanisms of L-DOPA-induced dyskinesia. The first paper in this thesis characterizes the different outgrowth patterns described above and their relation to different glial cells. The study demonstrated the two different outgrowth patterns to be a general phenomenon, applying not only to dopamine neurons. Attempts of characterization revealed no difference of origin in terms of dopaminergic subpopulations, i.e. A9 or A10, between the outgrowth patterns. Furthermore, the “roller-drum” technique was found optimal for studying the dual outgrowth sequences.

    The second and the third paper also utilized the “roller-drum” technique in order to promote both patterns of neuronal fiber formation. The effects of glial cell line-derived neurotrophic factor (GDNF) on the formation of dopamine nerve fibers, was investigated. Cultures prepared from gdnf knockout mice revealed that dopaminergic neurons survive and form nerve fiber outgrowth in the absence of GDNF. The dopaminergic nerve fibers exhibited an outgrowth pattern consistent with that previous observed in rat. GDNF was found to exert effect on the glial-associated outgrowth whereas the non-glial-associated was not affected. Astrocytic proliferation was inhibited using cytosine β-D-arabinofuranoside, resulting in reduced glial-associated outgrowth. The non-glial-associated dopaminergic outgrowth was on the other hand promoted, and was retained over longer time in culture. Furthermore, the non-glial-associated nerve fibers were found to target the fetal frontal cortex. Different developmental stages were shown to promote and affect the outgrowths differently. Taken together, these data indicate and state the importance of astrocytes and growth factors for neuronal nerve fiber formation and guidance. It also stresses the importance of fetal donor age at the time for transplantation.

    The fourth and fifth studies focus on L-DOPA dynamics and utilize in vivo chronoamperometry. In study four, 6-OHDA dopamine-depleted rats were exposed to chronic L-DOPA treatment and then rated as dyskinetic or non-dyskinetic. The electrochemical recordings demonstrated reduced KCl-evoked release in the intact striatum after chronic L-DOPA treatment. Time for maximal dopamine concentration after L-DOPA administration was found to be shorter in dyskinetic animals than in non-dyskinetic animals. The serotonergic nerve fiber content in the striatum was evaluated and brains from dyskinetic animals were found to exhibit significantly higher nerve fiber density compared to non-dyskinetic animals. Furthermore, the mechanisms behind the conversion of L-DOPA to dopamine in 6-OHDA dopamine-depleted rats were studied. Local administration of L-DOPA in the striatum increased the KCl-evoked dopamine release in the intact striatum. Acute application of L-DOPA resulted sometimes in a rapid conversion to dopamine, probably without vesicle packaging. This type of direct conversion is presumably occurring in non-neuronal tissue. Furthermore, KCl-evoked dopamine releases were present upon local application of L-DOPA in the dopamine-depleted striatum, suggesting that the conversion to dopamine took place elsewhere, than in dopaminergic nerve fibers. In conclusion, these studies state the importance of astrocytes for neuronal nerve fiber formation and elucidate the complexity of L-DOPA conversion in the brain.

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  • 14.
    af Bjerkén, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Flygare, Carolina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Remes, Jussi
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Strandberg, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Eriksson, Linda
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Bäckström, David C.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Jakobson Mo, Susanna
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Reliability and validity of visual analysis of [18F]FE-PE2I PET/CT in early Parkinsonian disease2023In: Nuclear medicine communications, ISSN 0143-3636, E-ISSN 1473-5628, Vol. 44, no 5, p. 397-406Article in journal (Refereed)
    Abstract [en]

    Objective: [18F]FE-PE2I (FE-PE2I) is a new radiotracer for dopamine transporter (DAT) imaging with PET. The aim of this study was to evaluate the visual interpretation of FE-PE2I images for the diagnosis of idiopathic Parkinsonian syndrome (IPS). The inter-rater variability, sensitivity, specificity, and diagnostic accuracy for visual interpretation of striatal FE-PE2I compared to [123I]FP-CIT (FP-CIT) single-photon emission computed tomography (SPECT) was evaluated.

    Methods: Thirty patients with newly onset parkinsonism and 32 healthy controls with both an FE-PE2I and FP-CIT were included in the study. Four patients had normal DAT imaging, of which three did not fulfil the IPS criteria at the clinical reassessment after 2 years. Six raters evaluated the DAT images blinded to the clinical diagnosis, interpreting the image as being ‘normal’ or ‘pathological’, and assessed the degree of DAT-reduction in the caudate and putamen. The inter-rater agreement was assessed with intra-class correlation and Cronbach’s α. For calculation of sensitivity and specificity, DAT images were defined as correctly classified if categorized as normal or pathological by ≥4/6 raters.

    Results: The overall agreement in visual evaluation of the FE-PE2I- and FP-CIT images was high for the IPS patients (α = 0.960 and 0.898, respectively), but lower in healthy controls (FE-PE2I: α = 0.693, FP-CIT: α = 0.657). Visual interpretation gave high sensitivity (both 0.96) but lower specificity (FE-PE2I: 0.86, FP-CIT: 0.63) with an accuracy of 90% for FE-PE2I and 77% for FP-CIT.

    Conclusion: Visual evaluation of FE-PE2I PET imaging demonstrates high reliability and diagnostic accuracy for IPS.

  • 15.
    af Bjerkén, Sara
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Histology and Cell Biology.
    Boger, Heather A
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Histology and Cell Biology.
    Nelson, Matthew
    Hoffer, Barry J
    Granholm, Ann-Charlotte
    Strömberg, Ingrid
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Histology and Cell Biology.
    Effects of glial cell line-derived neurotrophic factor deletion on ventral mesencephalic organotypic tissue cultures.2007In: Brain Research, ISSN 0006-8993, Vol. 1133, no 1, p. 10-9Article in journal (Refereed)
    Abstract [en]

    Glial cell line-derived neurotrophic factor (GDNF) is potent for survival and promotion of nerve fibers from midbrain dopamine neurons. It is also known to exert different effects on specific subpopulations of dopamine neurons. In organotypic tissue cultures, dopamine neurons form two diverse nerve fiber growth patterns, targeting the striatum differently. The aim of this study was to investigate the effect of GDNF on the formation of dopamine nerve fibers. Organotypic tissue cultures of ventral mesencephalon of gdnf gene-deleted mice were studied. The results revealed that dopamine neurons survive in the absence of GDNF. Tyrosine hydroxylase immunoreactivity demonstrated, in gdnf knockout and wildtype cultures, nerve fiber formation with two separate morphologies occurring either in the absence or the presence of astrocytes. The outgrowth that occurred in the absence of astrocytes was unaffected by gdnf deletion, whereas nerve fibers guided by the presence of astrocytes were affected in that they reached significantly shorter distances from the gdnf gene-deleted tissue slice, compared to those measured in wildtype cultures. Treatment with GDNF reversed this effect and increased nerve fiber density independent of genotype. Furthermore, migration of astrocytes reached significantly shorter distances from the tissue slice in GDNF knockout compared to wildtype cultures. Exogenous GDNF increased astrocytic migration in gdnf gene-deleted tissue cultures, comparable to lengths observed in wildtype tissue cultures. In conclusion, cultured midbrain dopamine neurons survive in the absence of GDNF, and the addition of GDNF improved dopamine nerve fiber formation - possibly as an indirect effect of astrocytic stimulation.

  • 16.
    af Bjerkén, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Marschinke, Franziska
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Strömberg, Ingrid
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Inhibition of astrocytes promotes long-distance growing nerve fibers in ventral mesencephalic cultures2008In: International Journal of Developmental Neuroscience, ISSN 0736-5748, E-ISSN 1873-474X, Vol. 26, no 7, p. 683-691Article in journal (Refereed)
    Abstract [en]

    Tyrosine hydroxylase-positive nerve fiber formation occurs in two diverse morphological patterns in rat fetal ventral mesencephalic slice cultures; one is non-glial-associated and the other is glial-associated. The aim of this study was to characterize the non-glial-associated nerve fibers and its relation to migration of astrocytes. Organotypic slice cultures were prepared from embryonic days 12, 14, and 18 rat fetuses and maintained for 5, 7 or 14 days in vitro. Inhibition of cell proliferation using cytosine beta-D-arabinofuranoside was conducted in embryonic day 14 ventral mesencephalic cultures. The treatment impaired astrocytic migration at 7 and 14 days in vitro. The reduced migration of astrocytes exerted a negative effect on the glial-associated tyrosine hydroxylase-positive nerve fibers, reducing the outgrowth from the tissue slice. The non-glial-associated outgrowth was, however, positively affected by reduced astrocytic migration, reaching distances around 3mm in 2 weeks, and remained for longer time in culture. Co-cultures of fetal ventral mesencephalon and frontal cortex revealed the cortex as a target for the non-glial-associated tyrosine hydroxylase-positive outgrowth. The age of the fetal tissue at plating affected the astrocytes such that older tissue increased the length of astrocyte migration. Younger tissue at plating promoted the presence of non-glial-associated outgrowth and long radial-glia-like processes, while older tissue promoted migration of neurons instead of formation of nerve fiber network. In conclusion, inhibition of astrocytic proliferation promotes the persistence of long-distance growing tyrosine hydroxylase-positive nerve fibers in ventral mesencephalic slices cultures. Furthermore, the long-distance growing nerve fibers target the frontal cortex and are absent in cultures derived from older tissue.

  • 17.
    af Bjerkén, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Nevalainen, Nina
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Lundblad, Martin
    Pomerleau, Francois
    Gerhardt, Greg A.
    Strömberg, Ingrid
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    L-DOPA conversion to dopamine in the rat dopamine-depleted striatumManuscript (Other academic)
  • 18.
    af Bjerkén, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stenmark Persson, Rasmus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Barkander, Anna
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Karalija, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Pelegrina-Hidalgo, Noelia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Gerhardt, Greg A
    Virel, Ana
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Strömberg, Ingrid
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Noradrenaline is crucial for the substantia nigra dopaminergic cell maintenance2019In: Neurochemistry International, ISSN 0197-0186, E-ISSN 1872-9754, Vol. 131, article id 104551Article in journal (Refereed)
    Abstract [en]

    In Parkinson's disease, degeneration of substantia nigra dopaminergic neurons is accompanied by damage on other neuronal systems. A severe denervation is for example seen in the locus coerulean noradrenergic system. Little is known about the relation between noradrenergic and dopaminergic degeneration, and the effects of noradrenergic denervation on the function of the dopaminergic neurons of substantia nigra are not fully understood. In this study, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) was injected in rats, whereafter behavior, striatal KCl-evoked dopamine and glutamate releases, and immunohistochemistry were monitored at 3 days, 3 months, and 6 months. Quantification of dopamine-beta-hydroxylase-immunoreactive nerve fiber density in the cortex revealed a tendency towards nerve fiber regeneration at 6 months. To sustain a stable noradrenergic denervation throughout the experimental timeline, the animals in the 6-month time point received an additional DSP4 injection (2 months after the first injection). Behavioral examinations utilizing rotarod revealed that DSP4 reduced the time spent on the rotarod at 3 but not at 6 months. KCl-evoked dopamine release was significantly increased at 3 days and 3 months, while the concentrations were normalized at 6 months. DSP4 treatment prolonged both time for onset and reuptake of dopamine release over time. The dopamine degeneration was confirmed by unbiased stereology, demonstrating significant loss of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra. Furthermore, striatal glutamate release was decreased after DSP4. In regards of neuroinflammation, reactive microglia were found over the substantia nigra after DSP4 treatment. In conclusion, long-term noradrenergic denervation reduces the number of dopaminergic neurons in the substantia nigra and affects the functionality of the nigrostriatal system. Thus, locus coeruleus is important for maintenance of nigral dopaminergic neurons.

  • 19.
    Agarkova, Irina
    et al.
    ETH-Zurich Hoenggerberg.
    Schoenauer, Roman
    ETH-Zurich Hoenggerberg.
    Ehler, Elisabeth
    King×s College London,.
    Carlsson, Lena
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Carlsson, Eva
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Perriard, Jean-Claude
    ETH-Zurich Hoenggerberg.
    The molecular composition of the sarcomeric M-band correlates with muscle fiber type2004In: European Journal of Cell Biology, ISSN 0171-9335, Vol. 83, no 5, p. 193-204Article in journal (Refereed)
    Abstract [en]

    The M-band is the transverse structure that cross-links the thick filaments in the center and provides a perfect alignment of the A-band in the activated sarcomere. The molecular composition of the M-bands in adult mouse skeletal muscle is fiber-type dependent. All M-bands in fast fibers contain M-protein while M-bands in slow fibers contain a significant proportion of the EH-myomesin isoform, previously detected only in embryonic heart muscle. This fiber-type specificity develops during the first postnatal weeks. However, the ratio between the amounts of myosin and of myomesin, taken as sum of both isoforms, remains nearly constant in all studied muscles. Ultrastructural analysis demonstrates that some of the soleus fibers show a diffuse appearance of the M-band, resembling the situation in the embryonic heart. A model is proposed to explain the functional consequence of differential M-band composition for the physiological and morphological properties of sarcomeres in different muscle types.

  • 20.
    Ahlgren, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Waling, Kerstin
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Kadi, Fawzi
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Djupsjöbacka, Mats
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation. Centre for Musculoskeletal Research, National Institute for Working Life, Umeå , Sweden.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Sundelin, Gunnevi
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Effects on physical performance and pain from three dynamic training programs for women with work-related trapezius myalgia2001In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 33, no 4, p. 162-9Article in journal (Refereed)
    Abstract [en]

    To compare training programs for women with trapezius myalgia regarding physical performance and pain, 102 women were randomized to strength, endurance, co-ordination and non-training groups. Before and after the intervention, static strength and dynamic muscular endurance in shoulder muscles were measured on a Cybex II dynamometer. Muscle activity in shoulder muscles was monitored via surface EMG. The signal amplitude ratio between the active and passive phase of repeated contractions indicated the ability to relax. Pain at present, pain in general and pain at worst were measured on visual analogue scales. After training, within group comparisons showed that the training groups rated less pain, and in the strength training group ratings of pain at worst differed from the non-training group. Using the non-training group as a reference, static strength increased in the strength and endurance training groups and muscular endurance in all training groups. The study indicates that regular exercises with strength, endurance or co-ordination training of neck/shoulder muscles might alleviate pain for women with work-related trapezius myalgia.

  • 21.
    Ahmadi, Mahboobah
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Liu, Jing-Xia
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Andersen, Peter M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Pedrosa-Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Human extraocular muscles in ALS2010In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 51, no 7, p. 3494-3501Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To investigate the general morphology, fiber type content, and myosin heavy chain (MyHC) composition of extraocular muscles (EOMs) from postmortem donors with amyotrophic lateral sclerosis (ALS) and to evaluate whether EOMs are affected or truly spared in this disease. METHODS. EOM and limb muscle samples obtained at autopsy from ALS donors and EOM samples from four control donors were processed for immunohistochemistry with monoclonal antibodies against distinct MyHC isoforms and analyzed by SDS-PAGE. In addition, hematoxylin and eosin staining and nicotinamide tetrazolium reductase (NADH-TR) activity were studied. RESULTS. Wide heterogeneity was observed in the appearance of the different EOMs from each single donor and between donors, irrespective of ALS type or onset. Pathologic morphologic findings in ALS EOMs included presence of atrophic and hypertrophic fibers, either clustered in groups or scattered; increased amounts of connective tissue; and areas of fatty replacement. The population of fibers stained with anti-MyHCslow tonic was smaller than that of MyHCIpositive fibers and was mostly located in the orbital layer in most of the ALS EOM samples, whereas an identical staining pattern for both fiber populations was observed in the control specimens. MyHCembryonic was notably absent from the ALS EOMs. CONCLUSIONS. The EOMs showed signs of involvement with altered fiber type composition, contractile protein content, and cellular architecture. However, when compared to the limb muscles, the EOMs were remarkably preserved. EOMs are a useful model for the study of the pathophysiology of ALS.

  • 22.
    Ahmed, Amina Mohamed
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Effekter på placentans funktion i samband med Covid-19 infektion och vaccination_Placentaskador av covid-19 virus2023Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 23.
    Ait Gouraine, Ilham
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    M2 MAKROFAGERS ROLL I BRÖSTTUMÖR2023Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 24.
    Akcan, Martina
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Genetic causes of interindividual differences in CYP2D6 dependent metabolism2023Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
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  • 25.
    Akram Jamil, Perjin
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Är biverkningar orsaken till att vissa patienter avbryter sin antipsykotiska läkemedelsbehandling?2020Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 26.
    Al Abed, Haidar
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Hur säkrar vi tillgången till essentiella läkemedel vid krissituationer?: En komparativ analys av läkemedelsberedskapen i historiskt perspektiv2022Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
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  • 27.
    Al Abed, Haidar
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Interprofessionell utbildning inom VFU med fokus på krisinformation runt läkemedel: En enkätundersökning i pandemitider2020Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 28.
    Al Attar, Asraa
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Kunskapsnivån hos nyutbildad och erfaren apotekspersonal i Sverige om riskerna vid långtidsanvändning av protonpumphämmare.2021Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
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  • 29.
    Al Dammad, Noura
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Effekt och säkerhet av januskinas-hämmare hos patienter med reumatoid artrit – En jämförelse mellan tofacitinib och metotrexat i singel- och kombinationsterapi2023Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 30.
    Alaa, Almasri
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Inverkan av hydrolyserat kollagen på ledvärk - En litteraturstudie2022Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 31.
    Alahmad, Alaa Daham
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Effekter av koffein på Parkinsons sjukdom2023Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 32.
    Alakpa, Enateri V.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Bahrd, Anton
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Wiklund, Krister
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Andersson, Magnus
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Novikov, Lev N.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Ljungberg, Christina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Kelk, Peyman
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Bioprinted schwann and mesenchymal stem cell co-cultures for enhanced spatial control of neurite outgrowth2023In: Gels, E-ISSN 2310-2861, Vol. 9, no 3, article id 172Article in journal (Refereed)
    Abstract [en]

    Bioprinting nerve conduits supplemented with glial or stem cells is a promising approach to promote axonal regeneration in the injured nervous system. In this study, we examined the effects of different compositions of bioprinted fibrin hydrogels supplemented with Schwann cells and mesenchymal stem cells (MSCs) on cell viability, production of neurotrophic factors, and neurite outgrowth from adult sensory neurons. To reduce cell damage during bioprinting, we analyzed and optimized the shear stress magnitude and exposure time. The results demonstrated that fibrin hydrogel made from 9 mg/mL of fibrinogen and 50IE/mL of thrombin maintained the gel&rsquo;s highest stability and cell viability. Gene transcription levels for neurotrophic factors were significantly higher in cultures containing Schwann cells. However, the amount of the secreted neurotrophic factors was similar in all co-cultures with the different ratios of Schwann cells and MSCs. By testing various co-culture combinations, we found that the number of Schwann cells can feasibly be reduced by half and still stimulate guided neurite outgrowth in a 3D-printed fibrin matrix. This study demonstrates that bioprinting can be used to develop nerve conduits with optimized cell compositions to guide axonal regeneration.

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  • 33.
    Alakpa, Enateri V.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Jayawarna, Vineetha
    Burgess, Karl E. V.
    West, Christopher C.
    Peault, Bruno
    Ulijn, Rein V.
    Dalby, Matthew J.
    Improving cartilage phenotype from differentiated pericytes in tunable peptide hydrogels2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 6895Article in journal (Refereed)
    Abstract [en]

    Differentiation of stem cells to chondrocytes in vitro usually results in a heterogeneous phenotype. This is evident in the often detected over expression of type X collagen which, in hyaline cartilage structure is not characteristic of the mid-zone but of the deep-zone ossifying tissue. Methods to better match cartilage developed in vitro to characteristic in vivo features are therefore highly desirable in regenerative medicine. This study compares phenotype characteristics between pericytes, obtained from human adipose tissue, differentiated using diphenylalanine/serine (F2/S) peptide hydrogels with the more widely used chemical induced method for chondrogenesis. Significantly higher levels of type II collagen were noted when pericytes undergo chondrogenesis in the hydrogel in the absence of induction media. There is also a balanced expression of collagen relative to aggrecan production, a feature which was biased toward collagen production when cells were cultured with induction media. Lastly, metabolic profiles of each system show considerable overlap between both differentiation methods but subtle differences which potentially give rise to their resultant phenotype can be ascertained. The study highlights how material and chemical alterations in the cellular microenvironment have wide ranging effects on resultant tissue type.

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  • 34.
    Alakpa, Enateri V.
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Saeed, Anwer
    Chung, Peter
    Riehle, Mathis O.
    Gadegaard, Nikolaj
    Dalby, Matthew J.
    Cusack, Maggie
    The Prismatic Topography of Pinctada maxima Shell Retains Stem Cell Multipotency and Plasticity In Vitro2018In: Advanced Biosystems, ISSN 2366-7478, Vol. 2, no 6, article id 1800012Article in journal (Refereed)
    Abstract [en]

    The shell of the bivalve mollusc Pinctada maxima is composed of the calcium carbonate polymorphs calcite and aragonite (nacre). Mother-of-pearl, or nacre, induces vertebrate cells to undergo osteogenesis and has good osteointegrative qualities in vivo. The calcite counterpart, however, is less researched in terms of the response of vertebrate cells. This study shows that isolation of calcite surface topography from the inherent chemistry allows viable long-term culture of bone marrow derived mesenchymal stem cells (MSCs). Self-renewal is evident from the increased gene expression of the self-renewal markers CD63, CD166, and CD271 indicating that cells cultured on the calcite topography maintain their stem cell phenotype. MSCs also retain their multipotency and can undergo successful differentiation into osteoblasts and adipocytes. When directed to adipogenesis, MSCs cultured on prism replicas are more amenable to differentiation than MSCs cultured on tissue culture polystyrene indicating a higher degree of plasticity in MSCs growing on calcite P. maxima prismatic topography. The study highlights the potential of the calcite topography of P. maxima as a biomimetic design for supporting expansion of MSC populations in vitro, which is of fundamental importance if it meets the demands for autologous MSCs for therapeutic use.

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  • 35.
    Al-Ani, Yaseen
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Information om en pandemi riktat till skolelever: En studie gällande information om Covid-19 riktad till skolpersonal och elever med fokus på läkemedel och smittspridning2020Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 36.
    Alattar, Fatima Mahmood Hashim
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Effekt och säkerhet avduala orexinreceptorantagonisterna suvorexant och daridorexant vid behandling av insomni2023Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
  • 37.
    Alayadi, Iman
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Läkemedelstillförsel via lipidnanopartiklar - Doxorubicin och pacitaxel vid bröstcancer2022Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
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  • 38.
    Albiin, Nils
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Middle ear structure in relation to function: the rat in middle ear research1985Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The present study was undertaken to evaluate the rat as a model for middle ear re­search. The rat was chosen primarily because the gross structure of its middle ear shows several similarities to that of man. It was considered of great importance to make a thorough structural study of the rat middle ear and to compare the results with those reported for the human middle ear. The thesis therefore includes indepen­dent studies on various aspects of rat middle ear structure and function as well as a review of the literature. The most pertinent findings in the experimental part of this study were the following.

    The rat Eustachian tube consists of a nasopharyngeal, and a cartilaginous and bony portion. The orifice of the nasopharyngeal portion is composed of two soft tissue lips, which appear to be opened mainly by the action of the salpingopharyngeal mus­cle, but also by the levator and tensor veli palatini muscles. The cartilaginous por­tion appears to be opened solely by the tensor veli palatini muscle. The tensor tympani muscle seems to have no effect on the tube.

    A ciliated and secretory epithelium lines the inferomedial walls of the tube throughout its length. In the tympanic cavity these thelial cell types extend as two tracts - one anterior and the other inferoposterior to  the promontory - which communicate with the epitympanic/attic compartments. The remaining parts of the tube and the tympanic cavity are covered by a squamous/cuboidal, non-ciliated epithelium. The subepithelial loose connective tissue contains vessels, nerves, and connective tissue cells, among these mast cells. The mast cells are confined to areas covered by the ciliated epithelium, and in the floor of the bulla, in the pars flaccida, and along the manubrial vessels. Glands are restricted to the Eustachian tube.

    In the clearance/transport of serum-like material, from the epitympanum towards the tube, hydrostatic forces appear to be important.

    The tympanic membrane is vascularized from meatal and tympanal vessels. Meatal ves­sels branch in the pars flaccida and along the handle of the malleus, where they are localized directly beneath the outer, keratinizing, stratified, squamous epithelium. Furthermore, meatal vessels form a vascular network at the junction between the fi­brocartilaginous annulus and the tympanic sulcus. Tympanal vessels send branches to the periphery of the pars tensa, where they run immediately beneath the tympanal, simple, squamous epithelium. In the major portion of the pars tensa, no blood vessels were found.

    The rat stapedial artery is a thin-walled vessel with a wide lumen. Without branch­ing, it runs through the tympanic cavity to the extratympanal regions it supplies. In contrast to the corresponding artery in man, the rat stapedial artery persists throughout life. The artery does not seem to be affected by the fluid produced during experimentally induced otitis media with effusion.

    The middle ear structure in the rat and in man show both similarities and differ­ences. If the differences are kept in mind and considered, it would seem that the rat is indeed a suitable model for experimental middle ear research.

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  • 39. Al-Bishri, Awwad
    et al.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Al-Thobaiti, Yasser
    Sunzel, Bo
    Rosenquist, Jan
    Effect of betamethasone on the degree of macrophage recruitment and nerve growth factor receptor p75 immunoreaction during recovery of the sciatic nerve after injury: an experimental study in rats.2008In: British Journal of Oral & Maxillofacial Surgery, ISSN 0266-4356, E-ISSN 1532-1940, Vol. 46, no 6, p. 455-9Article in journal (Refereed)
    Abstract [en]

    PURPOSE: This study was designed to explain our previous findings of beneficial effects of betamethasone given perioperatively on decreasing the incidence of neurosensory disturbance after sagittal split osteotomy and improving functional recovery after crush injury to rat sciatic nerves. We analysed the pattern of macrophage recruitment and expression of nerve growth factor p75. MATERIAL AND METHODS: The sciatic nerve was crushed in each of 42 animals by tying the nerve against a glass rod for 30s. Half the rats were given betamethasone and half were not. The effect of betamethasone was evaluated immunohistochemically in a double blind manner after 2, 7 and 17 days using antibodies against macrophage marker (ED1) and p75. RESULTS: We found an initial and significant decrease in the number of macrophages recruited after two days in the group treated with betamethasone compared with controls (p=0.001). By 7 days there were significantly more macrophages in the steroid group than in the control group (p=0.001). There was however, a tendency for the number of p75R to be higher in the in the steroid group but the difference was not significant. At 17 days, there were significantly fewer macrophages in the steroid group (p=0.008) than in the control. CONCLUSION: We conclude that the beneficial effect of a moderate perioperative dose of betamethasone on recovery of a nerve is reflected in the recruitment of macrophages but to only a small extent in expression of p75.

  • 40.
    Alfredson, H.
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Öhberg, L.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Is vasculo-neural ingrowth the cause of pain in chronic Achilles tendinosis?: An investigation using US and colour Doppler, immunohistochemistry, and diagnostic injections2003In: Knee Surgery, Sports Traumatology, Arthroscopy, ISSN 0942-2056, Vol. 11, no 5, p. 334-338Article in journal (Refereed)
  • 41.
    Alfredson, Hakan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). ISEH, UCLH, London, UK.
    Persistent pain in the Achilles midportion?: Consider the plantaris tendon as a possible culprit!2017In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 51, no 10, p. 833-834Article, review/survey (Refereed)
  • 42.
    Alfredson, Håkan
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Anatomy.
    Thorsen, Kim
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Sports Medicine.
    Fahlström, Martin
    Umeå University, Faculty of Medicine, Community Medicine and Rehabilitation, Rehabilitation Medicine. Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Sports Medicine.
    Johansson, Håkan
    Lorentzon, Ronny
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Sports Medicine.
    Glutamate NMDAR1 receptors localised to nerves in human Achilles tendons. Implications for treatment?2001In: Knee Surgery, Sports Traumatology, Arthroscopy, ISSN 0942-2056, E-ISSN 1433-7347, Vol. 9, no 2, p. 123-126Article in journal (Refereed)
    Abstract [en]

    In this investigation, we show the presence of both free glutamate (microdialysis) and glutamate NMDAR1 receptors (immunohistochemical analyses of tendon biopsies), in tendons from patients with chronic Achilles tendon pain (Achilles tendinosis) and in controls (pain-free tendons). The NMDAR1 immunoreaction was usually confined to acetylcholinesterase-positive structures, implying that the reaction is present in nerves. Glutamate is a potent pain mediator in the human central nervous system, and in animals it has been shown that peripherally administered glutamate NMDA receptor antagonists diminish the response to formalin-induced nociception. Our present finding of glutamate NMDA receptors in human Achilles tendons might have implications for pain treatment.

  • 43.
    Alfredson, Håkan
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Sports Medicine.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Anatomy.
    Thorsen, Kim
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Sports Medicine.
    Lorentzon, Ronny
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Sports Medicine.
    In vivo microdialysis and immunohistochemical analyses of tendon tissue demonstrated high amounts of free glutamate and glutamate NMDAR1 receptors, but no signs of inflammation, in Jumper's knee.2001In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 19, no 5, p. 881-886Article in journal (Refereed)
    Abstract [en]

    This investigation describes, to our knowledge, the first experiment where the microdialysis technique was used to study certain metabolic events in human patellar tendons in combination with immunohistochemical analyses of tendon biopsies. In five patients (four men and one woman) with a long duration (range 12-36 months) of pain symptoms from Jumper's knee (localized tenderness in the patellar tendon verified as tendon changes with ultrasonography or MRI), and in five controls (four men and one woman) with normal patellar tendons, a standard microdialysis catheter was inserted into the patellar tendon under local anestesia. The local concentrations of glutamate (excitatory neurotransmitter) and prostaglandin E2 (PGE2) were registered under resting conditions. Samplings were done every 15 min during a 2 h period. In all individuals (patients and controls) biopsies were taken for immunohistochemical analyses. The results showed that it was possible to detect and measure the concentrations of glutamate and PGE2 in the patellar tendon with the use of microdialysis technique. There were significantly higher concentrations of free glutamate, but not PGE2, in tendons with tendinosis compared to normal tendons. In the biopsies, there were no inflammatory cell infiltrates, but, for the first time, it was shown that there was immunoreaction for the glutamate receptor NMDAR1 in association with nerve structures in human patellar tendons. These findings altogether indicate that glutamate might be involved in painful Jumper's knee, and further emphasizes that there is no chemical inflammation (normal PGE2 levels) in this chronic condition.

  • 44.
    Alfredson, Håkan
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Sports Medicine.
    Masci, Lorenzo
    Institute of Sports Exercise and Health, University College Hospital London, London, United Kingdom; Sports & Exercise Medicine, Queen Mary University of London, London, United Kingdom.
    Spang, Christoph
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Private Orthopaedic Spine Center, Würzburg, Germany.
    Is There a Relationship Between Quadriceps Tendinopathy and Suprapatellar Plica? An Observational Case Series2022In: International Medical Case Reports Journal, E-ISSN 1179-142X, Vol. 15, p. 81-84Article in journal (Refereed)
    Abstract [en]

    Purpose: Chronic painful quadriceps tendinopathy is a relatively rare condition known to be difficult to manage. Conservative management is first-line treatment and if that fails open intra-tendinous revision surgery followed by a long rehabilitation period is used. There is sparse research on etiology and new treatment methods. This observational study aimed to evaluate the intra-articular findings in patients with chronic painful quadriceps tendinopathy resistant to conservative management.

    Patients and Methods: Seven male athletes (mean age 33 years, range 22–40) suffering from chronic painful quadriceps tendinopathy in altogether 10 tendons, not responding to conservative management including heavy strength training, were included. Clinical examination and ultrasound scanning were used for diagnosis. Arthroscopy was used for evaluation of the inside of the knee.

    Results: In all 10 knees, there were obliterating major plica formations in the suprapatellar pouch.

    Conclusion: Obliterating plica formations in the suprapatellar pouch may be involved in the aetiology and pathology in quadriceps tendinopathy.

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  • 45.
    Alfredson, Håkan
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Sports Medicine. Institute of Sports Exercise and Health, University College Hospital London, London, United Kingdom.
    Masci, Lorenzo
    Institute of Sports Exercise and Health, University College Hospital London, London, United Kingdom; Sports and Exercise Medicine, Queen Mary University of London, London, United Kingdom.
    Spang, Christoph
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Private Orthopaedic Spine Center Dr. Alfen, Würzburg, Germany.
    Sharp pain in a normal Achilles tendon of a professional female football player was related to a plantaris tendon in a rare position: a case report2021In: Journal of Medical Case Reports, E-ISSN 1752-1947, Vol. 15, no 1, article id 513Article in journal (Refereed)
    Abstract [en]

    Background: Plantaris tendinopathy and plantaris-associated Achilles tendinopathy can be responsible for chronic pain in the Achilles tendon midportion, often accompanied by medial tenderness. As conservative treatments are less successful for this patient group, proper diagnosis is important for decision making. This report presents a case with plantaris tendinopathy in a rare (superficial) location.

    Case presentation: This article describes a pain history and treatment timeline of a professional Swedish female soccer player (32 years old, Northern European ethnicity, white) who suffered from sharp pain in the Achilles tendon midportion and tenderness on the medial and superficial side for about 2 years. Conservative treatments, including eccentric exercises, were not successful and, to some extent, even caused additional irritation in that region. Ultrasound showed a wide and thick plantaris tendon located on the superficial side of the Achilles tendon midportion. The patient was surgically treated with local removal of the plantaris tendon. After surgery there was a relatively quick (4–6 weeks) rehabilitation, with immediate weight bearing, gradual increased loading, and return to running activities after 4 weeks. At follow-up at 8 weeks, the patient was running and had not experienced any further episodes of sharp pain during change of direction or sprinting.

    Conclusions: The plantaris tendon should be considered as a possible source of Achilles tendon pain. This case study demonstrates that the plantaris tendon can be found in unexpected (superficial) positions and needs to be carefully visualized during clinical and imaging examinations.

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  • 46.
    Alfredson, Håkan
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine. ISEH, UCLH, London, UK; Pure Sports Medicine Clinic, London, UK.
    Masci, Lorenzo
    Spang, Christoph
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Surgical plantaris tendon removal for patients with plantaris tendon-related pain only and a normal Achilles tendon: a case series2018In: BMJ Open Sport & Exercise Medicine, ISSN 2055-7647, Vol. 4, no 1, article id e000462Article in journal (Refereed)
    Abstract [en]

    Objectives: Surgical removal of the plantaris tendon can cure plantaris-associated Achilles tendinopathy, a condition in which Achilles and plantaris tendinopathy coexist. However, rare cases with plantaris tendinopathy alone are often misdiagnosed due to a normal Achilles tendon.

    Design and setting: Prospective case series study at one centre.

    Participants: Ten consecutive patients (9 men and one woman, mean age 35 years, range 19–67) with plantaris tendon-related pain alone in altogether 13 tendons were included. All had had a long duration (median 10 months, range 3 months to 10 years) of pain symptoms on the medial side of the Achilles tendon mid-portion. Preoperative ultrasound showed thickened plantaris tendon but a normal Achilles tendon.

    Interventions: Operative treatment consisting of ultrasound-guided excision of the plantaris tendon.

    Primary and secondary outcome measures: Scores from Victorian Institute of Sports Assessment-Achilles questionnaire (VISA-A)were taken preoperatively and postoperatively (median duration 10 months). Patient satisfaction and time until full return to sports activity level was asked by a questionnaire.

    Results: The VISA-A scores increased from 61 (range 45–81) preoperatively to 97 (range 94–100) postoperatively (p<0.01). Follow-up results at 10 months (range 7–72 months) on 9/10 patients showed full satisfaction and return to their preinjury sports or recreational activity

    Conclusion: The plantaris tendon should be kept in mind when evaluating painful conditions in the Achilles tendon region, especially when no Achilles tendinopathy is present. Excision of the plantaris tendon via a minor surgical procedure in local anaesthesia results in a good outcome.

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  • 47.
    Alfredson, Håkan
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Section of Sports Medicine. Institute of Sports, Exercise and Health, University College Hospital, London, UK.
    Masci, Lorenzo
    Department of Sports and Exercise Medicine, Queen Mary University, London, United Kingdom.
    Spang, Christoph
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Research Unit, Orthopaedic Spine Center, Dr. Alfen, Würzburg, Germany.
    Ultrasound and surgical inspection of plantaris tendon involvement in chronic painful insertional Achilles tendinopathy: A case series2021In: BMJ Open Sport and Exercise Medicine, ISSN 2055-7647, Vol. 7, no 1, article id e000979Article in journal (Refereed)
    Abstract [en]

    Objectives: Chronic painful insertional Achilles tendinopathy is known to be difficult to manage. The diagnosis is not always easy because multiple different tissues can be involved. The plantaris tendon has recently been described to frequently be involved in chronic painful mid-portion Achilles tendinopathy. This study aimed to evaluate possible plantaris tendon involvement in patients with chronic painful insertional Achilles tendinopathy.

    Methods: Ninety-nine consecutive patients (74 males, 25 females) with a mean age of 40 years (range 24-64) who were surgically treated for insertional Achilles tendinopathy, were included. Clinical examination, ultrasound (US)+Doppler examination, and surgical findings were used to evaluate plantaris tendon involvement.

    Results: In 48/99 patients, there were clinical symptoms of plantaris tendon involvement with pain and tenderness located medially at the Achilles tendon insertion. In all these cases, surgical findings showed a thick and wide plantaris tendon together with a richly vascularised fatty infiltration between the plantaris and Achilles tendon. US examination suspected plantaris involvement in 32/48 patients.

    Conclusion: Plantaris tendon involvement can potentially be part of the pathology in chronic painful insertional Achilles tendinopathy and should be considered for diagnosis and treatment when there is distinct and focal medial pain and tenderness.

    Level of evidence: IV case series.

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  • 48.
    Alfredson, Håkan
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Sports medicine. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine. ISEH, UCLH, London, UK; Pure Sports Medicine Clinic, London, UK.
    Spang, Christoph
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Dr Alfen, Orthopedic Spine Center, 97080 Würzburg, Germany.
    Clinical presentation and surgical management of chronic Achilles tendon disorders: a retrospective observation on a set of consecutive patients being operated by the same orthopedic surgeon2018In: Foot and Ankle Surgery, ISSN 1268-7731, E-ISSN 1460-9584, Vol. 24, no 6, p. 490-494Article in journal (Refereed)
    Abstract [en]

    Background: Non-invasive treatment is not always successful in patients with Achilles tendon disorders, and surgical treatment is instituted as the next step. There is sparse knowledge about the diagnoses, pain levels before surgery, surgically confirmed pathologies and postoperative complications in large patient groups.

    Aims: To study the diagnoses, pain scores before surgery, macroscopic surgical findings and postoperative complications in a series of patients treated for Achilles disorders.

    Material and methods: One surgeon operated on 771 Achilles tendons of 481 men and 290 women during a 10-year period. The clinically and ultrasound confirmed diagnoses, pre-operative pain and functional scores (Visual Analogue Scale, VAS, range 0-100; Victorian Institute Sports Tendon Assessment - Achilles questionnaire, VISA-A), macroscopic findings during surgery and postoperative complications, were retrospectively collected from a database.

    Results: Clinically, by ultrasound and during surgery midportion Achilles tendinopathy was confirmed in 519 (67%) patients, 41% of them had a thickened plantaris tendon located close the Achilles tendon. Partial midportion rupture was found in 31 (4%) patients, chronic midportion rupture in 12 (2%) patients and insertional Achilles tendinopathy, including superficial and retro-calcaneal bursitis, Haglund deformity, distal Achilles tendinopathy, plantaris tendon pathology, and bone spurs, in 209 (27%) patients. The mean pre-operative pain scores for midportion Achilles tendinopathy were 73 (VAS) and 45 (VISA-A), and for insertional Achilles tendinopathy 77 (VAS) and 39 (VISA-A). For midportion Achilles tendinopathy there were 14 (3%), and for insertional Achilles tendinopathy 10 (5%), postoperative complications.

    Conclusions: Patients presenting high pain scores from midportion Achilles tendinopathy were the most common. Plantaris tendon involvement is a frequent observation. For insertional Achilles tendinopathy the combination of pathology in the subcutaneous and retrocalcaneal bursa, a Haglund deformity and distal Achilles tendinopathy/tendinosis was most frequent. 

  • 49.
    Alfredson, Håkan
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Spang, Christoph
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Bilateral Achilles tendinosis: the similar morphological appearance and the benefit of unilateral treatment has benefits for the contralateral tendon2013In: International journal of experimental pathology (Print), ISSN 0959-9673, E-ISSN 1365-2613, Vol. 94, no 4, p. A18-A18Article in journal (Other academic)
  • 50.
    Alfredson, Håkan
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Spang, Christoph
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Unilateral surgical treatment for patients with midportion Achilles tendinopathy may result in bilateral recovery2014In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 48, no 19, p. 1421-1424Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Bilateral midportion Achilles tendinopathy/tendinosis is not unusual, and treatment of both sides is often carried out. Experiments in animals suggest of the potential involvement of central neuronal mechanisms in Achilles tendinosis. OBJECTIVES: To evaluate the outcome of surgery for Achilles tendinopathy. METHODS: This observational study included 13 patients (7 men and 6 women, mean age 53 years) with a long duration (6-120 months) of chronic painful bilateral midportion Achilles tendinopathy. The most painful side at the time for investigation was selected to be operated on first. Treatment was ultrasound-guided and Doppler-guided scraping procedure outside the ventral part of the tendon under local anaesthetic. The patients started walking on the first day after surgery. Follow-ups were conducted and the primary outcome was pain by visual analogue scale. In an additional part of the study, specimens from Achilles and plantaris tendons in three patients with bilateral Achilles tendinosis were examined. RESULTS: Short-term follow-ups showed postoperative improvement on the non-operated side as well as the operated side in 11 of 13 patients. Final follow-up after 37 (mean) months showed significant pain relief and patient satisfaction on both sides for these 11 patients. In 2 of 13 patients operation on the other, initially non-operated side, was instituted due to persisting pain. Morphologically, it was found that there were similar morphological effects, and immunohistochemical patterns of enzyme involved in signal substance production, bilaterally. CONCLUSION: Unilateral treatment with a scraping operation can have benefits contralaterally; the clinical implication is that unilateral surgery may be a logical first treatment in cases of bilateral Achilles tendinopathy.

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