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  • 1.
    Jayaweera, Sanduni Wasana
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Surano, Solmaz
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Pettersson, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Oskarsson, Elvira
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Lettius, Lovisa
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Gharibyan, Anna L.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Anan, Intissar
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Olofsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Mechanisms of Transthyretin Inhibition of IAPP Amyloid Formation2021Ingår i: Biomolecules, E-ISSN 2218-273X, Vol. 11, nr 3, artikel-id 411Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Amyloid-formation by the islet amyloid polypeptide (IAPP), produced by the β-cells in the human pancreas, has been associated with the development of type II diabetes mellitus (T2DM). The human plasma-protein transthyretin (TTR), a well-known amyloid-inhibiting protein, is interestingly also expressed within the IAPP producing β-cells. In the present study, we have characterized the ability of TTR to interfere with IAPP amyloid-formation, both in terms of its intrinsic stability as well as with regard to the effect of TTR-stabilizing drugs. The results show that TTR can prolong the lag-phase as well as impair elongation in the course of IAPP-amyloid formation. We also show that the interfering ability correlates inversely with the thermodynamic stability of TTR, while no such correlation was observed as a function of kinetic stability. Furthermore, we demonstrate that the ability of TTR to interfere is maintained also at the low pH environment within the IAPP-containing granules of the pancreatic β-cells. However, at both neutral and low pH, the addition of TTR-stabilizing drugs partly impaired its efficacy. Taken together, these results expose mechanisms of TTR-mediated inhibition of IAPP amyloid-formation and highlights a potential therapeutic target to prevent the onset of T2DM.

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  • 2.
    Surano, Solmaz
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Grip, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Öhberg, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Karlsson, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Faergemann, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper. Sundsvall Regional Hospital, Sundsvall, Sweden.
    Bjurman, Maria
    Sollefteå Hospital, Region Västernorrland, Sollefteå, Sweden.
    Davidsson, Hugo
    Department of Otorhinolaryngology, Head and Neck Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Otorhinolaryngology, Head and Neck Surgery, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Ledin, Torbjörn
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Lindell, Ellen
    Department of Otorhinolaryngology, Head and Neck Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Otorhinolaryngology, Region Västra Götaland, Södra Älvsborg Hospital, Borås, Sweden.
    Mathé, Jan
    Department of Clinical Neuroscience, Karolinska Institutet and Capio S:t Görans Hospital, Stockholm, Sweden.
    Tjernström, Fredrik
    Department of Clinical Sciences, Othorhinolaryngology, Lund University, Lund, Sweden.
    Tomanovic, Tatjana
    Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Granåsen, Gabriel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Salzer, Jonatan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Internet-based vestibular rehabilitation versus standard care after acute onset vertigo: a study protocol for a randomized controlled trial2022Ingår i: Trials, E-ISSN 1745-6215, Vol. 23, nr 1, artikel-id 496Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Dizziness and vertigo affect around 15% of adults annually and represent common reasons for contacting health services, accounting for around 3% of all emergency department visits worldwide. Vertigo is also associated with excessive use of diagnostic imaging and emergency care and decreased productivity, primarily because of work absenteeism. Vestibular rehabilitation is an evidence-based treatment for chronic dizziness and supervised group exercise therapy has recently been shown to be effective after vestibular neuritis, a common cause of acute onset vertigo. However, such interventions are not readily available and there is a need for more easily accessible tools. The purpose of this study is to investigate the effects on vestibular symptoms of a 6-week online vestibular rehabilitation tool after acute onset vertigo, with the aim of aiding vestibular rehabilitation by presenting a more accessible tool that can help to reduce recovery time. Methods: Three hundred twenty individuals diagnosed with acute vestibular syndrome (AVS) will be recruited from multiple hospitals in Sweden and the effects of an online vestibular rehabilitation tool, YrselTräning, on vestibular symptoms after acute onset vertigo will be compared to standard care (written instructions leaflet) in a two-armed, evaluator-blinded, multicenter randomized controlled trial. The primary outcome will be the Vertigo Symptom Scale Short Form (VSS-SF) score at 6 weeks after symptom onset. Secondary outcomes include effects of the intervention on activities of daily living, mood and anxiety, vestibular function recovery, mobility measures, health economic effects, and the reliability of the Swedish VSS-SF translation. Discussion: Participants using the online vestibular rehabilitation tool are expected to recover earlier and to a greater extent from their symptoms as compared to standard care. Since up to 50% of people with AVS without treatment develop persistent symptoms, effective treatment of AVS will likely lead to a higher quality of life and help reduce the societal costs associated with dizziness and vertigo. Trial registration: Clinicaltrials.gov NCT05056324. Registered on September 24, 2021.

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