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Coming dissertations at MedFak

  • Tissue Factor regulation, signaling and functions beyond coagulation with a focus on diabetes Author: Desirée Edén Link: Publication date: 2020-01-30 09:49

    Background: Tissue factor (TF) is a 47 kDa transmembrane glycoprotein best known for initiating the coagulation cascade upon binding of its ligand FVIIa. Apart from its physiological role in coagulation, TF and TF/FVIIa signaling has proved to be involved in diseases such as diabetes, cancer and cardiovascular diseases. Biological functions coupled to TF/FVIIa signaling include diet-induced obesity, apoptosis, angiogenesis and migration.

    Aim: The aim of this thesis was to investigate the role of TF/FVIIa in cells of importance in diabetes, to further investigate the mechanism behind TF/FVIIa anti-apoptotic signaling in cancer cells and lastly to examine the regulation of TF expression in monocytes by micro RNAs (miRNA).

    Results: In paper I we found that TF/FVIIa signaling augments cytokine-induced beta cell death and impairs glucose stimulated insulin secretion from human pancreatic islets. In paper II the relevance of TF/FVIIa in isolated human primary adipocytes was investigated. Adipocytes are a target cell for insulin and diabetics typically have increased lipolysis and impaired glucose uptake. No evidence was found for a role of TF/FVIIa in lipolysis or glucose uptake in adipocytes. However, adipocytes were found to express TF and FVII. The FVII produced was sufficient to initiate coagulation in the adipocytes. In paper III an anti-apoptotic TF/FVIIa induced signaling pathway in prostate and breast cancer cells was investigated in depth. Previous research has shown that TF/FVIIa signaling results in transactivation of insulin-like growth factor 1 receptor (IGF-1R) leading to subsequent protection from apoptosis induced by TNF-related apoptosis inducing ligand (TRAIL). The current results propose a mechanism where IGF-1R transactivation by TF/FVIIa is dependent on integrin β1 (ITGβ1) signaling. TF/FVIIa/ ITGβ1 signaling was found to result in phosphorylation of src and subsequent phosphorylation of caveolin 1 (Cav1). Once phosphorylated, the inhibitory effect of Cav1 on IGF-1R is cancelled, resulting in IGF-1R activation. In paper IV the role of miRNA regulation of TF expression in monocytic cells was investigated. The miRNA miR-223-3p was identified to be differentially expressed in U937 cells undergoing differentiation to a more monocyte-like phenotype and an anti-parallel correlation between TF and miR-223-3p expression in monocytes was proved. Hence, miR-223-3p regulates the inducible expression of TF in monocytes.

    Conclusions: The work in this thesis furthers the knowledge of molecular mechanisms behind TF regulation and TF/FVIIa signaling and some functional consequences as well as their biological relevance in diabetes. 

  • In Vivo Accuracy and Precision in Prosthodontics Author: Robert Nedelcu Link: Publication date: 2020-01-24 13:49

    Background: There has been a dramatic increase in commercially available intraoral scanners (IOS) in the last decade, offering to replace indirect digitization of models (MOD) fabricated from impressions (IMPR). IOS has benefits of less patient discomfort and a faster workflow to fabricate fixed dental prosthesis (FDP), and implant-supported prostheses (IFD). However, in vivo evidence is lacking not only for IOS, but also for MOD, FDP and IFD fit.

    Aims: Paper I: to evaluate in vitro finish line distinction and accuracy in seven IOS and one MOD. To assess parameters of resolution, tessellation, topography, and color. Paper II: to evaluate a method of acquiring an in vivo reference measurement in dentate subjects and analyse accuracy and precision of IOS and MOD. Paper III: to evaluate an in vivo reference-measurement method in fully edentulous maxillae with full-arch implant treatments and to analyse accuracy of MOD and fit of existing IFD. Paper IV: to analyse precision and accuracy of IOS using different acquisition protocols compared to the reference-measurement in Paper III.

    Material and Methods: Paper I: A model with a crown preparation was reference-scanned with an industrial scanner, (ATOS), scanned with seven IOS and the MOD of an IMPR was digitized. Best-fit Alignment and 3D Compare Analysis was followed by descriptive analysis. Paper II: A reference-scan was acquired with ATOS. Subjects were scanned with IOS and one MOD of an IMPR was digitized. Accuracy and precision were evaluated after Best-Fit Alignment and 3D Compare Analysis. Paper III: A reference-measurement of implant positions was acquired with ATOS. MOD from IMPR was digitized and IFD scanned. Datum and Relative Point System Alignment was followed by accuracy and precision analysis. Paper IV: Subjects in Paper III were scanned with IOS using three different protocols, followed by accuracy and precision analysis.

    Results: Paper I: There were considerable differences between IOS depiction of finish line and finish line accuracy. Paper II: IOS presented varying results for impressions in up to ten units. No differences were found for MOD. Paper III: IFD was significantly less accurate than MOD. Paper IV: Differences were found between scanning protocols. Compared to Paper III, IFD was less accurate. No differences were found for MOD.

    Conclusion: There are relevant differences between IOS when scanning subgingival preparations. Some IOS are better suited for long-span scans. Some IOS can be used for full-arch impressions for IFD in the maxilla, however, adequate soft-tissue management is crucial.  

  • A pathway into the profession : The use, feasibility and outcomes of a peer learning intervention for nursing students and newly graduated nurses Author: Ylva Pålsson Link: Publication date: 2020-01-24 13:28

    The overall aim of present thesis was to study the use, feasibility and outcomes of a peer learning intervention for nursing students and new graduates, including studies using a quasi-experimental (Study I and III), descriptive (Study II) and mixed-methods (Study IV) design. Data were collected using questionnaires, observations, checklists for intervention fidelity, individual interviews and group interviews. When studying peer learning outcomes among nursing students, peer learning seems to have a significant interaction effect on self-efficacy, based on a comparison of changes over time between the intervention (n=42) and comparison (n=28) groups. Studying each group separately over time, significant improvements were found in the intervention group on thirteen of the twenty variables, whereas the comparison group improved on four (Study I). Observations of how nursing students (n=16) used peer learning revealed that the student pairs collaborated to different extents and in different ways. All students were observed practicing several competencies together (Study II). Testing the peer learning model in new graduates’ workplace introduction (n=10) revealed that new graduates’ descriptions of peer learning were consistent with the theoretical description (Study III). Feasibility was tested in relation to compliance and acceptability, and lessons were learned. In Study IV, fidelity to the intervention was generally good. When first-line managers (n=8) described their perception of using the peer learning intervention with new graduates, predominantly positive outcomes were expressed. When examining the effect of peer learning in workplace introduction for newly graduated nurses (n=35), it was difficult to draw any conclusions due to recruitment problems (Study IV). The conclusions is that peer learning is a useful model for nursing students’ that seems to improve self-efficacy more than traditional supervision does. The model gives nursing students opportunities to practice several competencies on each other, and these competencies, e.g., leadership and organizational skills are useful in their future profession. The students practice teaching and supervision skills on each other, which seems to be a natural part of the peer relationship. Peer learning in the context of new graduates’ workplace introduction describes in a way consistent with the theoretical description of peer learning outcomes thus, also here it seems as a useful model. When developing and testing new interventions such as peer learning, it is important to do so systematically to minimize problems when conducting an evaluation, where the MRC framework can be useful. First-line managers generally expressed a positive attitude toward the peer learning model.