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BACKGROUND: The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS: Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequ
Background: The time spent in nursing homes (NHs) by patients with Alzheimer’s disease (AD) might be influenced by many factors, e.g., sociodemographic and clinical characteristics, rate of disease progression, and concomitant disorders. Whether different aspects of cholinesterase inhibitor (ChEI) therapy (drug agent, dose, and duration) affect time spent in NHs has not been investigated. We studi
Background: Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations. Methods and Findings: Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Canc
Burkitt lymphoma (BL) is a rare, aggressive disorder constituting 1% of all non-Hodgkin lymphoma. Diffuse large B-cell lymphoma (DLBCL) is more common, accounting for 30% of malignant lymphoma. Standard treatment for adult BL and for certain subgroups of patients with DLBCL remains to be defined due to paucity of randomised trials performed. The focus in this thesis lies on the effect of prognosti
The reactor containment is one of the most important buildings at a nuclear power plant. In case of an accident the containment wall is the final protection against radioactive leakage to the surrounding environment. A reactor containment contains different types of concrete structures. They can be grouped as external structures constituting a barrier between the inside of the containment and the
Glucagon secreted by pancreatic α-cells plays an important role in the regulation of blood glucose. In this thesis, different techniques such as electrophysiology, immunohistochemistry and hormone secretion assay were combined to explore the mechanisms by which glucagon secretion is regulated. Like pancreatic β-cells, which produce insulin, α-cells are electrically excitable and equipped with dif
Popular Abstract in English Sugar is the main source of energy in our bodies. If your blood sugar drops below a certain level, it can cause serious damage to your brain. On the other hand, having a very high blood sugar level for a long time can cause diabetes. For this reason, blood sugar levels in our bodies are maintained within a certain range by a group of hormones that work together. These hIslet dysfunction is central to the development and progression of type 2 diabetes (T2D). Epigenetic modifications are essential for establishing and maintaining cell identity and function in normal circumstances. Exposure to adverse environmental factors may alter the epigenome, and result in changes of gene expression and the resulting phenotype. The aim of this thesis was to analyze DNA methyla
Medications are of considerable help if healthcare providers are able to administer them to patients safely and appropriately. The medication use process is complex and a team of professionals – doctors, nurses, and pharmacists – work together with the patient for optimal treatment effect. The process involves many sub-processes and in every step there is a possibility for an error. Cytotoxic drug
Background: Inflammatory cytokines are linked to obesity-related insulin resistance and may predict type 2 diabetes independently of obesity. We previously reported that a majority of a cohort of 73 non-diabetic women with normal plasma (p-) glucose with Amerindian heritage in Lima, Peru, during a 5-year period increased both body weight and p-glucose levels, yet p-insulin was unaltered. A high pr
Abstract Treatment of chronic inflammatory arthritis has undergone major changes over the past years following introduction of targeted biological therapies. Tumour necrosis factor (TNF) blocking therapy has been the most important biological treatment of chronic arthritis to date. The overall objective of this thesis was to develop a new assessment method of efficacy of biological therapy in clin
Increased risk of Hodgkin lymphoma (HL) associated with personal history of several autoimmune diseases (ADs), such as rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, and immune thrombocytopenic purpura, are known. Whether there are other HL-related ADs and whether the increased risk of HL after ADs holds across sex, age, year of diagnosis, or HL histological subtype is unclear. W
A method for the quantitative determination of non-steroidal anti-inflammatory drugs (NSAIDs) in sewage sludge was developed and validated. The target compounds were extracted using pressurized hot water extraction (PHWE) and then purified and preconcentrated by three-phase hollow fiber liquid phase microextraction (HF-LPME) followed by LC-ESI-MS analysis. The PHWE was optimized with regard to the
In the US and most European countries, testicular cancer is the most common malignancy in young men aged 20-40 years. Since the introduction of cisplatin-based treatment in the 1970s, more than 95% of the patients are cured. The increasing incidence of testicular cancer and high survival rates, has led to a growing number of testicular cancer survivors (TCSs). As they have a long life expectancy i
Detailed understanding of biological systems governing specific mechanisms and pathways is essential in the development of novel disease therapies. Stimulus-secretion coupling in hormone secreting cells is a complex system of pathways that link activation of cellular processes by i.e. nutrients to the release of hormone. Stimulus-secretion coupling in the insulin secreting beta-cell is intensely r
Low bone mineral density (BMD) is a risk factor for fractures and much of the fracture preventive effort today is devoted to preventing low BMD. Physical activity (PA) has been described as one of the best strategies to optimize skeletal development in the growing child. However, most exercise intervention studies in children have involved the use of volunteers and specifically designed high impac
The energy efficiency and thermal performance of highly glazed office buildings are often questioned. However, nowadays glazed buildings are increasingly being built around the world, mainly due to an architectural trend, followed by the preference of companies to a distinctive image that a glazed office building can provide. Due to insufficient knowledge concerning the performance as to energy us
