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Regulatory Roles of FACIT Collagens XII and XIV in Cornea Stromal and Endothelial Development and FunctionHemmavanh, Chinda 10 April 2014 (has links)
Purpose:
Corneal transparency depends upon the precise organization of corneal stromal extracellular matrix and corneal endothelial function. Stromal structure and extracellular matrix organization is responsible for proper refraction of light into the eye. The corneal endothelium is responsible for pumping excess fluid out of the cornea, effectively maintaining corneal hydration and thickness. Corneal transplantation is the current form of treatment for corneal endothelial and stromal dystrophies. The mechanisms controlling stromal collagen fibril packing and organization into orthogonal layers as well as maturation of the endothelium into a fully functioning cellular layer are unknown. Collagens XII and XIV, fibril associated collagens with interrupted triple helices (FACIT), have been implicated in matrix-matrix interactions regulating structure, cell behavior, and cell-matrix interactions. The overall aim is to determine the role of collagens XII and XIV in fibril assembly, fibril packing, lamellar assembly, stromal organization, corneal thickness, and endothelial maturation. The general hypothesis is that collagens XII and XIV regulate cornea stromal matrix development and structure, endothelial development, and corneal function. This dissertation assesses three specific hypotheses: 1) Collagen XIV regulates lateral fibril growth and fibril packing through fibrillar surface interactions; 2) Collagen XII regulates fibril packing, lamellar assembly, stromal organization, corneal thickness, and therefore, corneal function; and 3) FACIT collagens in the specialized posterior stroma regulate the acquisition of function in the corneal endothelium.
Materials and Methods: The temporal and spatial expression patterns of collagens XII and XIV were determined in the murine cornea using quantitative PCR, semi-quantitative immuno-blots and immuno-localization approaches. To determine the regulatory roles of collagens XII and XIV in stromal and endothelial development, mouse models null for collagens XII or XIV were. This was coupled with ultrastructural and morphometric analyses of fibril assembly, fibril packing, lamellar organization, and endothelial maturation. The roles of collagens XII and XIV in corneal structure were determined using measurements of corneal thickness at postnatal day (P) 30 and P60.
Results:
Collagen XIV had a dynamic expression pattern in wild type (WT) corneal development. Corneas at P4 expressed the highest amount of collagen XIV with a sharp reduction by P10. Collagen XIV localized in the full thickness of the stroma at P4 and P14. At P30 and P90 there was less immuno-reactivity for collagen XIV in the WT stroma. The collagen XIV null stromas contained larger diameter fibrils when compared to P30 WT stromas. The null stromas also exhibited irregular spacing of fibrils. In the absence of collagen XIV there was an abnormal increase in corneal thickness. Unlike collagen XIV, collagen XII localized homogenously throughout the WT corneal stroma from P4 to P90. Collagen XII content was relatively constant in the cornea from P4 to P90. The collagen XII P30 null stromas contained areas of increased fibril density and disruption of lamellar organization. Corneal thickness increased in the absence of collagen XII at P60. Corneas deficient in Col12a1-/- and/or Col14a1-/- exhibited a delay in maturation. The null corneal endothelia retained vacuoles seen only in the immature WT P4 cornea. The P30 Col12a1-/- and Col14a1-/- endothelia had patchy localization of ZO-1 similar to that of an immature endothelium. There was an abnormal increase in thickness at P30 in the absence of collagens XII and XIV suggesting an increase in stromal hydration.
Conclusions: Collagen XIV regulates fibril assembly, and regular fibril packing in early stromal development. Collagen XII regulates fibril packing, lamellar assembly, stromal organization, and influences the keratocyte network. Both collagens XII and XIV regulate endothelial maturation and acquisition of function through interactions between the stroma and underlying endothelium. Understanding the mechanisms behind stromal organization and endothelial maturation will improve treatment of stromal and endothelial dystrophies, as well as other diseases that involve extracellular matrix-cell interactions mediated by FACIT collagens.
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"Jag ser inte riktigt poängen med det..." : En studie om gymnasieelevers relation till ett digitalt matematikläromedels poängsystem utifrån ett motivationsperspektiv. / ”I don’t really see the point with it...” : A study on pupils from upper secondary school and their relation to one digital study material’s scoring system in mathematics education based on an motivational perspectiveGraae-Nielsen, Jan January 2018 (has links)
Spelfierade inslag i undervisningen blir allt vanligare, där bland annat poängsystem införs i digitala läroböcker för att motivera elever att studera. Inom ämnet matematik finns idag bland annat den digitala läroboken NOKflex, som används bland gymnasieskolor i Sverige. Syftet med detta arbete är att undersöka om eleverna upplever några motiverande effekter med den digitala lärobokens poängsystem, samt om deras användande av facit i den digitala läroboken skiljer sig gentemot deras användande av facit i en tryckt lärobok. Detta arbete har en kvalitativ ansats, där intervjumetoden fokusgrupper använts. Resultatet från fokusgruppsintervjuerna visar att poängsystemet bidrar till både positiva och negativa effekter för elevernas motivation, där den avgörande faktorn är vilken legitimitet läraren gett poängsystemet i undervisningen. Studien visar även att poängsystemet har en positiv inverkan på elevernas användande av facit, men synliggör samtidigt svagheter i systemet som gör att eleverna kan erhålla en stor mängd poäng utan att behöva genomföra några beräkningar eller ha rätt svar på specifika uppgifter.
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Women receiving notification of an abnormal Pap smear result : - experiences and impact on health-related quality of lifeRask, Marie January 2017 (has links)
Aim: The aim of this thesis was to investigate experiences of receiving notification of an abnormal Pap smear result and its impact on women’s health-related quality of life as well as to investigate women’s awareness of human papillomavirus. Methods: In total, 176 women and 20 healthcare professionals participated. Data were collected through individual interviews (I, II) and a questionnaire (IV) including the instrument Functional Assessment of Chronic Illness Therapy – Cervical Dysplasia (FACIT-CD) and Hospital Anxiety and Depression Scale (HADS). For the translation and cross-cultural adaptation of the FACIT-CD, and for evaluation of its linguistic validity and reliability, cognitive debriefing interviews and a questionnaire consisting of the Swedish instrument FACIT-CD was used. Data were analysed by content analysis (I, II) and by using statistical analysis (III, IV), while one part (III) was analysed according to FACIT translation methodology. Results: Women receiving notification of an abnormal Pap smear result have good overall HRQoL; they become anxious but not depressed. Reasons for anxiety were mainly that women misinterpreted the result as cancer, which could lead to lower attendance for further investigation, treatment and follow-up. To cope with the anxiety, women sought emotional support and information. They primarily used the Internet for information but also turned to healthcare professionals for information needs. Moreover, women had low awareness of HPV, its sexually transmitted nature, and its relationship to abnormal Pap smear results and cervical cancer. An awareness of HPV as a sexually transmitted infection did not lead to higher level of anxiety or more depression symptoms or worse HRQoL, compared to not being aware. Finally, the Swedish FACIT-CD is equivalent to the English version and linguistically valid and exhibited good internal consistency reliability. Conclusion: Women have low awareness of HPV and abnormal Pap smear results, whereupon they misinterpret their test result as cancer. It is of importance that women understand their test result, in order to minimise anxiety as well as to maintain high attendance for investigation, treatment and follow-up of abnormalities.
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