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Genetics of coronary heart disease: towards causal mechanisms, novel drug targets and more personalized prevention.

Coronary heart disease (CHD) is an archetypical multifactorial disorder that is influenced by genetic susceptibility as well as both modifiable and nonmodifiable risk factors, and their interactions. Advances during recent years in the field of multifactorial genetics, in particular genomewide association studies (GWASs) and their meta-analyses, have provided the statistical power to identify and

International Development of the Patient-Reported Outcome Indices for Multiple Sclerosis (PRIMUS)

Background: The Patient-Reported Indices for Multiple Sclerosis (PRIMUS) comprises a suite of three scales for assessing symptoms, activity limitations, and quality of life in multiple sclerosis (MS). It was developed in the UK and has been shown to have excellent psychometric properties. This study describes the adaptation of eight language versions for Canadian English, Canadian French, French,

Pharmacokinetics, phenotype and product choice in haemophilia B: how to strike a balance?

At the 7th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD) held in Brussels, Belgium, in February 2014, Pfizer sponsored a satellite symposium entitled: "Pharmacokinetics, phenotype and product choice in haemophilia B: How to strike a balance?" Co-chaired by Cedric Hermans (Cliniques Universitaires Saint Luc, Brussels, Belgium) and Mike Laffan (Imperial Col

Altered serotonin (5-HT) 1D and 2A receptor expression may contribute to defective insulin and glucagon secretion in human type 2 diabetes.

Islet produced 5-hydroxy tryptamine (5-HT) is suggested to regulate islet hormone secretion in a paracrine and autocrine manner in rodents. Hitherto, no studies demonstrate a role for this amine in human islet function, nor is it known if 5-HT signaling is involved in the development of beta cell dysfunction in type 2 diabetes (T2D). To clarify this, we performed a complete transcriptional mapping

Postmortem heart weight modelled using piecewise linear regression in 27,645 medicolegal autopsy cases.

The interpretation of postmortem heart weight is often difficult, and references for normal heart weight are important. However, to assess the cause of death at a medicolegal autopsy it is also important to have references based on an unselected population of medicolegal autopsy cases with non-natural causes of death (not due directly to disease). We aimed at studying and deriving references for a

Increased carotid plaque burden in men with the fibrillin-1 2/3 genotype

Fibrillin-1 (FBN1) is an important constituent of the vascular wall and earlier studies have indicated an effect of the FBN1 2/3 genotype on blood pressure as well as aortic stiffness in men. The aim of the present study was to determine whether the FBN1 2/3 genotype was associated with the presence of carotid plaque and incident cardiovascular morbidity and mortality in middle-aged subjects. The

Comparison of grey scale median (GSM) measurement in ultrasound images of human carotid plaques using two different softwares.

Grey scale median (GSM) measured on ultrasound images of carotid plaques has been used for several years now in research to find the vulnerable plaque. Centres have used different software and also different methods for GSM measurement. This has resulted in a wide range of GSM values and cut-off values for the detection of the vulnerable plaque. The aim of this study was to compare the values obta

Cord blood insulinoma-associated protein 2 autoantibodies are associated with increased risk of type 1 diabetes in the population-based Diabetes Prediction in Skane study

Aims/hypothesis The aim of this study was to examine the effect of cord blood autoantibodies on the risk for type 1 diabetes in children followed prospectively from birth. Methods The Diabetes Prediction in Skane (DiPiS) study consists of 35,853 children from the general population born during 2000-2004. Samples were collected at birth and analysed for HLA genotypes and autoantibodies to glutamate

Methanol production from steel-work off-gases and biomass based synthesis gas

Off-gases generated during steelmaking are to a large extent used as fuels in process units within the plant. The surplus gases are commonly supplied to a plant for combined heat and power production. The main objective of this study has been to techno-economically investigate the feasibility of an innovative way of producing methanol from these off-gases, thereby upgrading the economic value of t

A gene score of nine LDL and HDL regulating genes is associated with fluvastatin induced cholesterol changes in women.

While conventional pharmacogenetic studies have considered single gene effects, we tested if a genetic score of nine LDL- and HDL-associated SNPs, previously shown to predict cardiovascular disease, is related to fluvastatin induced lipid change. In patients with asymptomatic plaque in the right carotid artery, thus candidates for statin therapy, we related Score LDL (APOB(rs693), APOE(rs4420638),

Decline of C-peptide during the first year after diagnosis of Type 1 diabetes in children and adolescents

Aims/hypothesis: We studied the decline of C-peptide during the first year after diagnosis of Type 1 diabetes (T1D), and its relation to various factors. Methods: 3824/4017 newly diagnosed patients (95%) were classified as T1D in a national study. In a non-selected subgroup of 1669 T1D patients we determined non-fasting C-peptide both at diagnosis and after 1 year, and analyzed decline in relation

Epigenetic regulation of glucose-stimulated osteopontin (OPN) expression in diabetic kidney.

Diabetes nephropathy (DN) is the leading cause of end stage renal disease and it affects up to 40% of diabetic patients. In addition to hyperglycemia, genetic factors are thought to contribute to the development of DN, but few if any genetic factors have been convincingly linked to DN. Other possible mechanisms may involve epigenetic regulation of glucose-stimulated gene activity which was suggest

Factors Influencing Occupational Engagement in Day Centers for People with Psychiatric Disabilities.

Occupational engagement is a vital factor in people's lives since it has been shown to be important for health and well-being. Community-based day centers (DCs), both meeting place-oriented and work-oriented ones, are common service alternatives in many western countries for enabling engagement in productive and leisure occupations among people with psychiatric disabilities. Little is, however, kn