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Coming theses from other universities

  • Internet-based treatment for vulvodynia Author: Andrea Hess Engström Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-482806 Publication date: 2022-09-29 12:53

    Localized provoked vulvodynia is the most common cause of sexual pain and most often affects women between 20 and 30 years old. The etiology of provoked vulvodynia remains unclear, but an interplay of biomedical and psychosocial mechanisms is believed to contribute to the onset. The choice of treatment for provoked vulvodynia depends on locally available resources. Internet interventions can reach patients in distant geographical areas and may thus promote equal access to healthcare services. A few studies have investigated the effects of cognitive behavioral therapy on provoked vulvodynia. However, there appear to be no studies of the effects of an internet intervention using an acceptance and commitment therapy approach, also called third-wave cognitive behavioral therapy, for women with provoked vulvodynia.

    The aim of this thesis was to investigate the effects and patient experiences of a guided internet-based intervention for women with provoked vulvodynia during the waiting period for clinical treatment. All four studies included in this thesis were tied to a multicenter randomized controlled study: the EMBLA study. Participants were randomized to a six-week guided internet intervention or a waiting list before treatment as usual. Pain during intercourse, other pain-related variables, and pain acceptance were variables used to assess the effects of the intervention. Later, interviews were carried out with participants to ascertain their experiences of this internet-based treatment. Lastly, health-related quality of life and healthcare utilization were assessed to obtain a health economic evaluation of the intervention. 

    Internet-based treatment had a positive effect on pain during intercourse and pain acceptance, but the results should be interpreted with caution due to the small sample size. This form of treatment was perceived as credible and helpful for managing provoked vulvodynia, but some difficulties related to the internet-based treatment were also reported. The intervention contributed to meaningful clinical effects at low costs per patient, indicating that internet-based treatment is not inferior to the standard of care. Internet-based treatment may serve as a complement to regular care, especially for patients living in geographical locations with low access to specialized care or where there are long waiting lists to initiate treatment.

  • Development of novel affinity enrichment strategies for clinical applications using selected reaction monitoring Author: Andreas Hober Link: http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-318308 Publication date: 2022-09-20 17:38

    Proteins are key components of any living organism and an essential part of life itself. They can provide cells with structure and perform life-sustaining intracellular reactions. As organisms grow more complex, this task expands even further. The proteins’ areas of responsibility suddenly also include communication and coordination between cells and throughout entire organisms, such as the human body. Everything that can be touched and felt on a living organism is composed of millions and millions of proteins tightly packed together. They are even the molecules responsible for propagating the signals that make up the sense of feeling. Understanding the role of proteins in the complex system of life is essential for understanding what makes up a healthy human and what causes disease. This knowledge makes up the foundation of modern medicine, and to further this knowledge, allowing for new treatments and preventative interventions, the study of proteins is crucial. The large-scale study of proteins, proteomics, is an extensive field of research where a vast toolbox of technologies has been implemented. The foundation for this toolbox is made up of mass spectrometry- and affinity-based technologies.

    In this thesis, both mass spectrometry-based proteomics and affinity-based proteomics will be explored. The first part, Paper I and Paper II, describe the use of selected reaction monitoring for measuring proteins of clinical relevance in human blood plasma. The second part, Paper III and Paper IV, highlight the importance of validating reagents used for affinity-based proteomics and how this can be achieved in a high throughput manner. Lastly, Paper V showcases how a combined strategy, relying on both affinity-based proteomics and mass spectrometry-based proteomics, can capitalize on the best properties of each technology and how this combined strategy can even be utilized for diagnostic purposes.

  • Ex‘PLA’ining the progression of pathological proteins in Alzheimer’s and Parkinson’s diseases : see(d)ing is believing Author: Anish Behere Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-482999 Publication date: 2022-09-20 13:48

    Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common forms of neurodegenerative disorders affecting approximately 50 million people worldwide. The underlying neuropathological processes leading to AD and PD share many similarities, i.e. aberrant protein aggregation of tau and alpha-synuclein (αSyn) in the brain. Monitoring tau and αSyn aggregation is challenging, due to morphological heterogeneity of the aggregating species and problems in preserving the antigen conformation ex vivo.

    In paper-I, we validated the usefulness of proximity ligation assay (PLA), a technique that enabled us to visualize previously undetected early αSyn pathology in the A30P-tg mouse model of PD. We observed an age-progressive increase in the levels of phosphorylated αSyn (pSynS129) and the compactness of aggregates in the brain. Although loss of dopaminergic neurons was not found, a subtle dysregulation of other catecholamines was recorded in the older mice.

    In paper-II, we revealed a wide distribution of pSynS129 aggregates in alpha-synucleinopathy-patient brains. By using a PLA setup with certain antibody pair combinations on brain sections, we observed unique staining patterns, which could not be visualized using regular immunohistochemistry (IHC). In A30P-tg mice, the morphological pattern of the PLA signals indicated an intracellular shift of pSynS129  from the periphery towards the neuronal soma.

    In Paper-III, we demonstrated that multiplex pTauS202,T205-pTauT231, singleplex pTauT231 and singleplex pSynS129 PLAs can recognize an extensive tau and αSyn pathology compared to regular IHC. We found that using our PLA approach we could differentiate between pTauS202,T205 and pTauT231 pathology in AD brains, whereas IHC could not. Similarly, in the PD brain, singleplex pSynS129 PLA detected novel structures, i.e. apparent thick intercellular tunnelling nanotubes and early aggregates; whereas pSynS129 IHC was limited to the detection of mature pathology. Lastly, we demonstrated that our multiplex PLA approach detected co-aggregates of pSynS129-pTau.

    In Paper-IV, in an αSyn seeding mouse model we observed pSynS129 immunoreactivity close to the striatal injection site one day post-injection (dpi). Intriguingly, this type of staining disappeared with the concurrent formation of peri-nuclear pSynS129 inclusions in specific brain regions after 14 dpi. In parallel, astrocytic activation prior to pSynS129 inclusion formation was observed.

    In conclusion, we have developed several novel PLAs that detect both tau and αSyn pathology with a higher ex vivo sensitivity and specificity than currently used immunostaining methods. This thesis work provides valuable insights that potentially could be used for the development of future biomarkers for tauopathies and synucleinopathies.

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