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Coming theses from other universities

  • Assessment of everyday functioning for adults with hearing loss : The development of Hearing and Functioning in Everyday life Questionnaire (HFEQ) Author: Elin Karlsson Link: Publication date: 2022-01-18 14:46
  • A pharmacokinetic approach to intra-brain distribution with a focus on cyclic peptides Author: Erik Melander Link: Publication date: 2022-01-18 09:18

    When designing treatments for disorders of the central nervous system (CNS) reaching the site of action is a major hurdle in the development process. Regardless if the target is extra- or intracellular, precise measurements to understand the distribution within the CNS are required. There is however a lack of understanding of differences in blood-brain barrier transport and intra-brain distribution of both small and large molecules. In this thesis the regional Blood-Brain Barrier transport of antipsychotic agents, along with their brain tissue binding and regional cellular accumulation was quantified. Furthermore, a novel LC-MS/MS method was developed for the quantitative analysis of the cyclic peptide kalata B1 was developed for analysis of brain tissue and plasma samples. The Blood-Brain Barrier transport, permeability, intra-brain distribution and cellular accumulation were assessed for two cyclic peptides, SFTI-1 and kalata B1. 

    The antipsychotics exhibited clear differences in their regional BBB transport as well as their brain tissue binding, with the most dramatic spatial differences in BBB transport being observed for the p-glycoprotein substrates risperidone and paliperidone. The highest level of transporter mediated protection was observed in the cerebellum, with pronounced efflux for several of the antipsychotics. The development of a quantitative method for the cyclic peptide kalata B1 was successfully validated and applied to measure low concentration of the peptide in biological matrices. The BBB transport of SFTI-1 was markedly higher than that of kalata B1 whereas both peptides exhibited similar permeability across an in vitro BBB model. It was also shown that SFTI-1 resides mainly within the interstitial fluid within the brain, but that kalata B1 readily enters the cells of the brain parenchyma. The cellular accumulation of kalata B1 was abolished under cold conditions, and was not observable in lung tissue, suggesting an active process that is tissue specific. It was also shown that both peptides are taken up into cell cultures of neurons and astrocytes.

    In conclusion this thesis and the studies herein contribute to a better understanding of distribution patterns of both antipsychotics and cyclic peptides and provides valuable lessons in terms of what types of studies should be prioritized for the development of such molecules into therapeutic agents.

  • Using Mobile Health Technology to Support Health-related Quality of Life : From the Perspective of Older Adults with Cognitive Impairment Author: Line Christiansen Link: Publication date: 2022-01-12 10:42

    The prevalence of cognitive impairment and illness increases with age. For older adults, maintaining or improving health-related quality of life (HRQoL) in the early stages of cognitive impairment is important to prevent consequences related to the progression of the condition. This thesis aims to identify factors affecting HRQoL and describe how mHealth technology can support HRQoL in older adults with cognitive impairment.

    Four studies were conducted using quantitative and qualitative approaches. A cross-sectional design was used to identify factors affecting older adults’ HRQoL (Study I) and investigate the relationship between mHealth technology use and self-rated quality of life (QoL) (Study III). A phenomenographical design was used to describe variations in older adults’ perceptions of mHealth technology and its impact on HRQoL (Study II). A prospective longitudinal design was used to examine older adults’ HRQoL changes over time (Study IV).Participants were selected from two longitudinal population studies using a purposive sampling strategy to include those aged 55 years and above with mild cognitive impairment or mild dementia. Data were obtained from questionnaires and semi-structured interviews. Data from the quantitative studies were analysed using statistical analysis, including descriptive and comparative analysis and regression analysis, while data from the qualitative study were examined using phenomenographical analysis in consecutive steps.

    The results showed that most older adults experienced good HRQoL with regard to both physical and mental health. The likelihood of having good-to-excellent QoL increased with age and was higher among males and those with higher education levels. Those diagnosed with dementia reported poorer HRQoL. Factors associated with low HRQoL included dependency in activities of daily living, receiving informal care and feelings of loneliness and pain. The use of mHealth technology was perceived as supportive in maintaining social interactions and facilitating independent living. The technology literacy levels among the study sample varied significantly. Those who reported having moderate-to-high technical skills and using the internet regularly via mHealth technology had higher odds of experiencing good-to-excellent QoL. No significant changes were observed in the older adults’ HRQoL over time in relation to the non-use and use of a customized mHealth application.

    The indicators of HRQoL are clinically relevant for the secondary prevention of dementia to help maintain good HRQoL in older adults with incipient cognitive impairment. The technology-related differences reflect the risk of digital exclusion. To improve preconditions for being digitally involved in society, societal initiatives that aim to empower the technology literacy level of older adults are needed.