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Unravelling ATTR Cardiac Amyloidosis in Iceland : A Nationwide Epidemiological Study
(2025) Bergmann, Hekla María; Úlfarsson, Ævar Örn; Einarsson, Hafsteinn; Jóhannsdóttir, Helena Xiang; Gunnarsson, Gunnar Thór; Hrafnkelsdóttir, Þórdís Jóna; Andersen, Karl Konráð; Ingimarsdóttir, Inga Jóna; Faculty of Industrial Engineering, Mechanical Engineering and Computer Science; Faculty of Medicine
Introduction: Cardiac amyloidosis (CA) arises from the deposition of misfolded amyloid proteins in the heart's extracellular matrix, leading to significant cardiac disease. Recent data suggest that CA is under-recognised, and advances in treatment have increased focus on this condition with the intention of implementing treatment earlier to improve prognosis. There is limited knowledge regarding the prevalence of transthyretin CA (ATTR-CA) on a national level, particularly in Iceland. Therefore, this study represents the first nationwide effort to evaluate the baseline characteristics, diagnostics, and treatment of ATTR-CA in Iceland. Methods: A retrospective study of all patients diagnosed with ATTR-CA in Iceland from 6 May 2013 to 11 March 2024 was identified in the Icelandic Cardiac Amyloid Registry (ICE-CAR) created in 2023 by heart failure (HF) specialists at Landspitali University Hospital in Reykjavik, Iceland. Diagnosis was based on different combinations of transthoracic echocardiography, an elevated Perugini score on bone scintigraphy and heart biopsies, as well measurements of free light chains, M-component measurements in blood and urine. Patients were grouped according to the National Amyloidosis Centre (NAC) prognostic staging system for ATTR-CA. Results: In total, 65 patients with ATTR-CA were identified (males n = 60, females n = 5, median age 81.4 years [IQR 75.5-85.5 years]), all wild-type and no mutant variant. Diagnosis was made with myocardial biopsy in 7 cases. Upon diagnosis, 83% of the patients had an interventricular septum thickness of ≥15 mm and 92% showed a posterior wall thickness of ≥12 mm. Approximately 57% of patients belonged to New York Heart Association (NYHA) functional class I-II. The HF phenotypes according to left ventricular ejection fraction (LVEF) were distributed as follows: reduced (HFrEF) n = 24 (37%), mildly reduced (HFmrEF) n = 9 (14%), preserved (HFpEF) n = 29 (44.5%), and unknown LVEF n = 3 (4.5%). A total of 54 patients had reported NAC stage: stage I 23 (35.4%), stage II 20 (30.8%), stage III 11 (16.9%). Around 32% received disease-modifying treatment. Conclusion: Despite the low NYHA class observed in the study population, our findings in Iceland's nationwide assessment of ATTR-CA indicate more advanced age and lower LVEF at diagnosis compared to other studies. This highlights the critical need for early detection and appropriate therapeutic interventions in managing ATTR-CA.
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Þemahefti um námsmat í leikskólum
(Menntamálaráðuneytið, 2013-12-20) Hreinsdóttir, Anna Magnea; Deild kennslu- og menntunarfræði
Mat á námi og velferð barna er mikilvægur þáttur í leikskólastarfi. Í aðalnámskrá leikskóla 2011 var sú stefna mörkuð að námsmat eigi að taka mið af áhuga barna, getu þeirra og hæfni. Mennta- og menningarmálaráðuneytið fékk Önnu Magneu Hreinsdóttur leikskólafulltrúa í Garðabæ til taka saman þemahefti um námsmat í leikskólum, sem ætlað er að styðja kennara og starfsfólk leikskóla við innleiðingu nýrrar aðalnámskrár um mat á námi barna. Rétt er að undirstrika að samkvæmt aðalnámskrá leikskóla er leikur ein helsta námsleið barna og fléttast grunnþættir menntunar og námssvið leikskólans inn í leik þegar starfsfólk tengir á markvissan hátt markmiðin við leik barnanna. Umhverfið er jafnframt mikilvægur áhrifaþáttur í námi barna sem hafa ber í huga þegar nám þeirra og velferð er metin. Fjallað er um hugmyndafræði námsmats og tengsl þess við skipulag námsumhverfis og stuðning leikskólakennara við leik og nám barnanna. Gerð er grein fyrir hvernig ólíkar námshneigðir barna byggja á þekkingarleit þeirra, leikni og siðferðislegum viðhorfum. Einnig er gerð grein fyrir markmiðum leikskólastarfs og hvernig þau tengjast lykilhæfni og hæfniviðmiðum aðalnámskrá leikskóla. Gefin eru dæmi um fjölbreyttar aðferðir í mati án fyrirfram gefna hugmynda og viðmiða og rætt um einstaklingsnámskrár, próf og önnur mælitæki. Rætt er um upplýsingar sem fylgja börnum úr leikskóla í grunnskóla sem eru til þess fallnar að koma í veg fyrir endurtekningu í námi. Að lokum er minnt á mikilvægi þess að í leikskólum skapist menning lærdómssamfélags þar sem kennarar og annað starfsfólk lærir með börnum og fjölskyldum þeirra. Því ætti efni þetta að nýtast sem grunnur í samræðum kennara um nám, kennslu og námsmat og við þróunarvinnu leikskóla í að efla einstaklingsmiðað mat.
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Exploring the Gap Between Clinical Trials and Real World Practice in Psoriatic Arthritis
(University of Iceland, School of Health Sciences, Faculty of Medicine, 2026-02-13) Palsson, Olafur; Björn Guðbjörnsson, Meliha C Kapetanovic; Læknadeild (HÍ); Faculty of Medicine (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
Sóragigt er langvinnur, mögulega alvarlegur bólgusjúkdómur í liðum tengdur húðsjúkdómnum psoriasis. Hann getur haft djúpar og langvarandi afleiðingar, bæði fyrir sjúklinga sem þjást af honum og fyrir samfélagið. Eftirlit og meðferð sóragigtar er afar fjölþætt og getur þarfnast þverfaglegs samstarfs. Meðferðarleiðbeiningar við sóragigt byggja að miklu leyti á niðurstöðum slembiraðaðra tvíblindra rannsókna, en við vitum að einungis um þriðjungur sjúklinga uppfyllir inntökuskilyrðin í rannsóknirnar, oft vegna aldurs eða of lítillar sjúkdómsvirkni við inntöku. Í fyrstu greininni sýnum við fram á að sjúklingar með sóragigt sem uppfylla ekki inntökuskilyrði slembiraðaðra rannsókna á líftæknilyfjum fá jafn mikinn ávinning af slíkum lyfjum og halda áfram notkun þeirra í sama mæli eins og þeir sem uppfylla inntökuskilyrðin. Einn þáttur meðferðar við sóragigt er að stilla langvinna liðverki. Bólgueyðandi gigtarlyf eru hornsteinn verkjameðferðar sóragigtar en af þeim er hægt að fá aukaverkanir sem geta jafnvel verið alvarlegar. Í annarri greininni sýnum við fram á að við upphaf líftæknilyfjameðferðar með TNF hemlum minnkar notkunin á bólgueyðandi gigtarlyfjum um 40-50%. Þetta gefur til kynna óbeinan öryggisávinning af því að hefja slíka meðferð. Markmið meðferðar við sóragigt er að upphefja öll einkenni og teikn um sjúkdóminn ef það er hægt, með öðrum orðum að koma sjúklingum í sjúkdómshlé, helst án nokkurra aukaverkana meðferðar. Að ná og viðhalda sjúkdómshlé yfir lengri tíma, svo kallað viðvarandi sjúkdómshlé, hefur sýnt sig bæta langtímahorfur í iktsýki í gegnum aukið líkamlegt hreysti, betri lífsgæði og minni þróun liðskemmda. Áhrif viðvarandi sjúkdómshlés hefur hingað til ekki verið mikið rannsakað í sóragigt. Í þriðju og fjórðu greininni skoðum við tíðni viðvarandi sjúkdómshlés og forspárþætti fyrir því bæði í Svíþjóð og á Íslandi. Þrátt fyrir gott aðgengi að lyfjameðferðum upplifir helmingur sjúklinga aldrei sjúkdómshlé og færri en þriðjungur þeirra fá viðvarandi sjúkdómshlé. Karlkyn og minni þreyta við upphaf meðferðar spá fyrir betri líkum á að ná viðvarandi sjúkdómshlé.
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Exploration of microbial communities from Icelandic marine waters using metagenomics
(University of Iceland, School of Health Sciences, Faculty of Food Science and Nutrition, 2024-12-18) Jégousse, Clara; Viggó Þór Marteinsson, María Guðjónsdóttir; Matvæla- og næringarfræðideild (HÍ); Faculty of Food Science and Nutrition (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
Marine microorganisms are vital in maintaining ocean health by supporting food webs and regulating biogeochemical cycles. The ocean around Iceland, where warm Atlantic and cold Arctic currents meet, is a unique marine environment. While primary production in Icelandic waters has been monitored since the 1950s with microscopy and satellite imaging, molecular insights into microbial taxonomic and metabolic diversity remain limited. This thesis investigates the microbial communities in Icelandic marine waters using metagenomics. The main objectives were to find out what species can be detected in Icelandic marine waters? in what proportions? what is their potential function in the marine ecosystem? and how do environmental factors shape their distribution? The findings of this thesis offer insights into the relationships between microbial communities and their environments, establishing a foundation for future research. The publicly available datasets from this study serve as a baseline, supporting ecosystem modelling and sustainable management of Icelandic marine waters in a changing climate.
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The immunomodulatory role of LL-37 in the pathogenesis of psoriasis
(University of Iceland, School of Health Science, Faculty of Medicine, 2025-03-14) Sigurgrimsdottir, Hildur; Björn Rúnar Lúðvíksson, Jóna Freysdóttir; Læknadeild (HÍ); Faculty of Medicine (UI); Heilbrigðisvísindasvið (HÍ); School of Health Sciences (UI)
Psoriasis is an autoimmune disease of the skin, and the most common form, plaque psoriasis, is characterized by raised, well-demarcated, erythematous plaques with adherent silvery scales. The immunopathogenesis has a mixed Th1 and Th17 inflammatory profile, and keratinocytes in the basal layer of the skin hyperproliferate and do not mature properly, causing elongated rete ridges and parakeratosis. Alterations in the immune biomarker microenvironment accompany the pathogenesis of psoriasis, both in skin and blood. LL-37 is an anti-microbial peptide of the innate immune system that has extensive immunomodulatory functions besides having an anti-microbial function. LL-37 takes part in the induction of psoriasis, with a potential role as an autoantigen. In this project, we wanted to further define the immunomodulatory effect of LL-37 upon various immune biomarker secretion by keratinocytes and white blood cells. Blood and skin samples were obtained from psoriasis patients undergoing phototherapy. When analysed, the results corroborated the role of T17 cells, both CD4+ and CD8+ T cells, in the pathogenesis of psoriasis, as the percentage of Th17 and Tc17 cells was reduced following phototherapy. In addition, the reduction of Th17 cells positively correlated with both PASI and the histological Trozak score. Within the skin, the number of T cells reduced with psoriasis treatment, and the intensity of immunofluorescent staining of IL-17 in the dermis correlated to the PASI score. There was also a reduction in the percentage of skin-homing CLA+ T cells, both in T17 cells and T22 cells, as well as in CD103+CLA+ skin-homing T cells. Further phenotypic analysis of these skin-homing T cells in psoriasis patients was performed by measuring the expression of the chemokine receptors CXCR3, CCR4, and CCR6. Two groups of CXCR3 expressing T cells were observed, expressing high or intermediate levels, and these two groups were subsequently analysed separately. Different chemokine receptor expression patterns emerged when T cells were subtyped based on the expression of CLA and CD103. When peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with two distinct stimulations mimicking the Th1 and Th17 microenvironment, various biomarker secretory patterns emerged, particularly in association with the presence of LL-37. Due to the differences in CXCR3hi expression of T cells between psoriasis patients and healthy controls (HC), their functional capacity was analysed further. CXCR3hiCD4+ T cells cultured using Th1 and Th17 stimulation, secreted lower levels of IL-10, CXCL8, and IL-1β than CXCR3negCD4+ T cells. The pathogenesis of psoriasis is in part driven by the secretion of immune biomarkers by keratinocytes. Thus, given the above findings, investigation of their inflammatory profile in the same immunomodulatory microenvironment as for the PBMC was performed, focusing on LL-37. The results demonstrate that primary keratinocytes secrete a wide array of chemokines, growth factors, and cytokines that can be significantly affected by Th1 and Th17-driven stimulation. Furthermore, their immune biomarker fingerprinting was frequently altered in the presence of LL-37. In many instances, LL-37 reduced the secretion of immune biomarkers when added to Th1 stimulation as compared to Th1 stimulation alone. Under Th1 and Th17 inflammatory stimulation, LL-37 modulated the secretion of keratinocytes towards a more inflammatory response by increasing secretion of CXCL8 and IL-1β and decreasing secretion of IL-10. In addition, LL-37 also affected the intracellular signalling pathways of keratinocytes by decreasing the phosphorylation of ERK1/2. When the expression of LL-37 in psoriatic skin was analysed, a change in expression pattern of psoriasis patients was observed following treatment, from being distributed all over the epidermis to being defined to the basal layer as also was found in HC skin biopsies. Taken together, this research details the changes in circulatory T cells and the microenvironment in psoriatic plaques, both at cellular and molecular levels, that occur concomitant to phototherapy. We document the secretory potential of PBMCs and keratinocytes of immune biomarkers after stimulation that mimics the psoriasis microenvironment. Furthermore, the immunomodulatory properties of LL-37 on secretion and intracellular signalling pathway activation are described, both in keratinocytes and PBMCs, as well as the biological expression of LL-37 in psoriatic skin. A more detailed understanding of the fundamental pathways that contribute to the pathogenesis of psoriasis is a driving force in more focused therapy. The effects of immunomodulatory agents such as LL-37 need to be mapped out in diverse biological mimicking situations, and we think that we have contributed to this field. This research adds to the basic knowledge regarding the pathogenesis of psoriasis, concerning cellular and molecular changes occurring following psoriasis treatment, and what effects different inflammatory microenvironments and LL-37 have thereon.

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