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Biological, clinical and population relevance of 95 loci for blood lipids

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 signi

Noncardiac Surgery in Patients With Aortic Stenosis: A Contemporary Study on Outcomes in a Matched Sample From the Danish Health Care System

BackgroundPast research has identified aortic stenosis (AS) as a major risk factor for adverse outcomes in noncardiac surgery; however, more contemporary studies have questioned the grave prognosis. To further our understanding of this, the risks of a 30-day major adverse cardiovascular event (MACE) and all-cause mortality were investigated in a contemporary Danish cohort. HypothesisAS is not an i

Grading obstructive lung disease using tomographic pulmonary scintigraphy in patients with chronic obstructive pulmonary disease (COPD) and long-term smokers.

The severity of chronic obstructive lung disease (COPD) is defined by the degree of flow limitation measured as forced expiratory volume in 1 s, which mainly reflects impairment of large and intermediate airways. However, COPD is primarily a small airways disease. Therefore, better diagnostic tools are needed. Ventilation-Perfusion (V/P) SPECT is a sensitive method to detect obstructive lung chang

Effect of the GLP-1 Receptor Agonist Lixisenatide on Counter-Regulatory Responses to Hypoglycemia in Subjects With Insulin-Treated Type 2 Diabetes.

Counter-regulatory responses are critical to prevent hypoglycemia in subjects with type 2 diabetes. This is particularly important in insulin-treated patients. This study explored the effect of the glucagon-like peptide 1 receptor agonist lixisenatide on the hormonal counter-regulatory responses to insulin-induced hypoglycemia when added to basal insulin therapy in subjects with type 2 diabetes.

Intranasal Immunization With an Apolipoprotein B-100 Fusion Protein Induces Antigen-Specific Regulatory T Cells and Reduces Atherosclerosis

Objective-Atherosclerosis is an inflammatory disease. Autoimmune responses to low-density lipoproteins (LDL) contribute to its progression, whereas immunization with LDL may induce atheroprotective or proatherogenic responses. The objective of this study was to develop an atheroprotective vaccine by targeting a peptide of the LDL protein constituent apolipoprotein B-100 (apoB-100) to the nasal muc

Tapasin discriminates peptide-human leukocyte antigen-A*02:01 complexes fromed with natural ligands

A plethora of peptides are generated intracellularly, and most peptide-human leukocyte antigen (HLA)-I interactions are of a transient, unproductive nature. Without a quality control mechanism, the HLA-I system would be stressed by futile attempts to present peptides not sufficient for the stable peptide-HLA-I complex formation required for long term presentation. Tapasin is thought to be central

The growth hormone receptor exon 3 deleted/full-length polymorphism is associated with central adiposity in the general population.

Objective: To test the hypothesis that the growth hormone (GH) receptor (GHR) d3/fl polymorphism influences anthropometry and body composition in the general population. Design and Setting: The Swedish Obese Subjects (SOS) reference study is a cross-sectional population-based study, randomly selected from a population registry. A sub-group of the population-based Malmö Diet and Cancer Study (MDC-C

Differences in physical activity patterns in patients with spondyloarthritis.

OBJECTIVE: To study patient reported physical activity in patients with spondyloarthritis (SpA) and possible differences in physical activity patterns between the SpA subtypes and genders. METHODS: In 2009 a questionnaire including questions concerning physical activity was sent to patients with a SpA diagnosis (n=3711). The WHO "Global recommendations of physical activity for health" requirin

Exercise and Diabetes-Related Cardiovascular Disease: Systematic Review of Published Evidence from Observational Studies and Clinical Trials.

The cost of treating cardiovascular disease (CVD) and diabetes is enormous and is set to rise in the coming years. Physical inactivity and sedentary behaviors are major risk factors for these diseases and are estimated to account for several million global deaths annually. Lifestyle interventions, particularly those aimed at enhancing physical activity levels, have a substantial favorable impact o

Ingestion of gallium phosphide nanowires has no adverse effect on Drosophila tissue function.

Engineered nanoparticles have been under increasing scrutiny in recent years. High aspect ratio nanoparticles such as carbon nanotubes and nanowires have raised safety concerns due to their geometrical similarity to asbestos fibers. III-V epitaxial semiconductor nanowires are expected to be utilized in devices such as LEDs and solar cells and will thus be available to the public. In addition, clea

From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus

Recent genome-wide association studies (GWASs) have identified a locus on chromosome 1p13 strongly associated with both plasma low-density lipoprotein cholesterol (LDL-C) and myocardial infarction (MI) in humans. Here we show through a series of studies in human cohorts and human-derived hepatocytes that a common noncoding polymorphism at the 1p13 locus, rs12740374, creates a C/EBP (CCAAT/enhancer

Midkine is part of the antibacterial activity released at the surface of differentiated bronchial epithelial cells

To resist infections, robust defense mechanisms of the airways are essential. Retinoic acid promotes differentiation and maintains the phenotypic characteristics of bronchial epithelium. In addition, it induces the expression of the antibacterial growth factor midkine (MK). In the present study, we explored the expression and antibacterial activity of MK in an airway context. MK was detected in br

Lymphomyeloid Contribution of an Immune-Restricted Progenitor Emerging Prior to Definitive Hematopoietic Stem Cells.

In jawed vertebrates, development of an adaptive immune-system is essential for protection of the born organism against otherwise life-threatening pathogens. Myeloid cells of the innate immune system are formed early in development, whereas lymphopoiesis has been suggested to initiate much later, following emergence of definitive hematopoietic stem cells (HSCs). Herein, we demonstrate that the emb

Mutations in genes encoding complement inhibitors CD46 and CFH affect the age at nephritis onset in patients with systemic lupus erythematosus

Introduction: Inherited deficiencies of several complement components strongly predispose to systemic lupus erythematosus (SLE) while deficiencies of complement inhibitors are found in kidney diseases such as atypical hemolytic uremic syndrome (aHUS). Methods: The exons of complement inhibitor genes CD46 and CFH (factor H) were fully sequenced using the Sanger method in SLE patients with nephritis