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Pathways to Health and Well-being

Adverse early-life conditions have lasting effects on old-age health and mortality (Almond, 2006, Barker, 1992, Barker, 1994, Mazumder et al., 2010 and Roseboom et al., 2006). Some have even considered reductions in early life disease exposure to be a primary driver of historical mortality declines (Finch and Crimmins, 2004). Consequently, understanding the mechanisms through which early and later

Beta-cell function and metabolic control in Latent Autoimmune Diabetes in Adults with early insulin versus conventional treatment: a 3-year follow-up

Objectives: The optimal treatment of latent autoimmune diabetes in adults (LADA) is not established. We explored whether early insulin treatment, which has shown beneficial effects in rodents and in human pilot studies, would result in better preservation of beta-cell function or metabolic control, compared with conventional treatment. Subjects and methods: Glucagon-stimulated C-peptide and HbAlc

Plasma fibronectin deficiency impedes atherosclerosis progression and fibrous cap formation

Atherosclerotic lesions are asymmetric focal thickenings of the intima of arteries that consist of lipids, various cell types and extracellular matrix (ECM). These lesions lead to vascular occlusion representing the most common cause of death in the Western world. The main cause of vascular occlusion is rupture of atheromatous lesions followed by thrombus formation. Fibronectin (FN) is one of the

Immune responses against aldehyde-modified laminin accelerate atherosclerosis in Apoe(-/-) mice.

BACKGROUND: LDL oxidation in the vascular wall is associated with aldehyde modification of surrounding extracellular matrix proteins that may target autoimmune responses against vascular tissues. Here we investigated the possible influence of immunity against a malondialdehyde (MDA)-modified form of the basement membrane protein laminin on atherosclerosis. METHODS AND RESULTS: IgM and IgG autoanti

Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes

Aims/hypothesis Latent autoimmune diabetes in adults (LADA) is phenotypically a hybrid of type 1 and type 2 diabetes. Genetically LADA is poorly characterised but does share genetic predisposition with type 1 diabetes. We aimed to improve the genetic characterisation of LADA and hypothesised that type 2 diabetes-associated gene variants also predispose to LADA, and that the associations would be s

Modelling of OGTT curve identifies 1 h plasma glucose level as a strong predictor of incident type 2 diabetes: results from two prospective cohorts

Aims/hypothesis The relevance of the OGTT in predicting type 2 diabetes is unclear. We assessed the performance of 14 OGTT glucose traits in type 2 diabetes prediction. Methods We studied 2,603 and 2,386 Europeans from the Botnia study and Malmo Prevention Project (MPP) cohorts with baseline OGTT data. Over a follow-up period of 4.94 years and 23.5 years, 155 (5.95%) and 467 (19.57%) participants,

Dietary intakes and food sources of phenolic acids in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Phenolic acids are secondary plant metabolites that may have protective effects against oxidative stress, inflammation and cancer in experimental studies. To date, limited data exist on the quantitative intake of phenolic acids. We estimated the intake of phenolic acids and their food sources and associated lifestyle factors in the European Prospective Investigation into Cancer and Nutrition (EPIC

Vaccines against atherosclerosis.

Atherosclerosis is the primary cause of acute myocardial infarction and stroke. It is well established that arterial inflammation in response to accumulation and oxidation of lipoproteins in the vascular wall is the major factor responsible for the development of atherosclerosis. During recent years, it has become apparent that this vascular inflammation is modulated by a complex array of autoimmu

Cardiovascular risk with androgen deprivation therapy for prostate cancer: Potential mechanisms.

Androgen deprivation therapy (ADT) is frequently used for the treatment of advanced prostate cancer. ADT is associated with numerous side effects related to its mode of action, namely the suppression of testosterone to castrate levels. Recently, several large retrospective studies have also reported an increased risk of diabetes and cardiovascular disease in men receiving ADT, although these risks

Atherosclerotic plaques in the internal carotid artery and associations with lung function assessed by different methods.

Background: Previous studies on associations between reduced lung function and cardiovascular disease (CVD) have mainly been based on forced expiratory volume in 1-s (FEV(1) ) and vital capacity (VC). This study examined potential associations between five different lung function variables and plaques in the internal carotid artery (ICA). Methods: Subjects (n = 450) from a previous population-base

Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells.

Heritable epigenetic signatures are proposed to serve as an important regulatory mechanism in lineage fate determination. To investigate this, we profiled chromatin modifications in murine hematopoietic stem cells, lineage restricted progenitors and CD4(+) T cells using modified genome-scale miniChIP technology. We show that genes involved in mature hematopoietic cell function associate with disti

Design of recombinant antibody microarrays for urinary proteomics.

PURPOSE: Urinary proteomics has become a key discipline within clinical proteomics for noninvasive diagnosis and monitoring of disease, and biomarker discovery. In order to decipher complex proteomes, high demands will, however, be placed upon the methodology applied. The purpose of this study was to develop a recombinant antibody microarray platform for urinary proteomics. EXPERIMENTAL DESIGN: W

Fixed ratio or lower limit of normal for the FEV1 /VC ratio: relation to symptoms and extended lung function tests.

There is no general agreement on the spirometric definition of chronic obstructive pulmonary disease (COPD). The global initiative for obstructive lung disease recommends a fixed ratio between forced expiratory volume in one-second (FEV1 ) and forced vital capacity (FVC) of <0·7 (FR) for the diagnosis of COPD. European Respiratory Society and American Thoracic Society favour the use of the fifth p