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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

Dietary Intakes of Individual Flavanols and Flavonols Are Inversely Associated with Incident Type 2 Diabetes in European Populations

Dietary flavanols and flavonols, flavonoid subclasses, have been recently associated with a lower risk of type 2 diabetes (T2D) in Europe. Even within the same subclass, flavonoids may differ considerably in bioavailability and bioactivity. We aimed to examine the association between individual flavanol and flavonol intakes and risk of developing T2D across European countries. The European Prospec

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.

Inducible nitric oxide synthase expression is increased in the alveolar compartment of asthmatic patients

Introduction: Increased exhaled nitric oxide (NO) levels in asthma are suggested to be through inducible NO synthase (iNOS). The aim of this study was to investigate the expression of iNOS in bronchoalveolar lavage (BAL) cells and tissue from central and peripheral airways and compare it with the exhaled bronchial and alveolar NO levels in patients with asthma vs a control group. Methods: Thirty-t

Cellular Barcoding Links B-1a B Cell Potential to a Fetal Hematopoietic Stem Cell State at the Single-Cell Level

Hematopoietic stem cells (HSCs) undergo a functional switch in neonatal mice hallmarked by a decrease in self-renewing divisions and entry into quiescence. Here, we investigated whether the developmental attenuation of B-1a cell output is a consequence of a shift in stem cell state during ontogeny. Using cellular barcoding for in vivo single-cell fate analyses, we found that fetal liver definitive

Direct Conversion of Fibroblasts to Megakaryocyte Progenitors

Current sources of platelets for transfusion are insufficient and associated with risk of alloimmunization and blood-borne infection. These limitations could be addressed by the generation of autologous megakaryocytes (MKs) derived in vitro from somatic cells with the ability to engraft and differentiate in vivo. Here, we show that overexpression of a defined set of six transcription factors effic

Accuracy diagrams : a novel way to illustrate uncertainty of estimated GFR

Most studies that validate GFR equations present accuracy results stratified by measured GFR (mGFR; diagnostic correctness) or by estimated GFR (eGFR; diagnostic predictiveness) only, without a clear distinction in interpretation. The accuracy of a GFR equation is normally reported in percent (e.g. P30), but is often misinterpreted when stratified by eGFR. The aim of the study was to develop new a

Risk of ocular manifestations in patients with giant cell arteritis : a nationwide study in Sweden

Objective: No large-scale nationwide study has determined the risk of ocular manifestations in patients with giant cell arteritis (GCA). The aim was to study the incidence and risk factors of ocular manifestations in patients with GCA in Sweden. Method: A national cohort was created by linking Swedish nationwide registers. GCA patients were identified from the Swedish Hospital Inpatient and Outpat

Reporting on methods to generate and purify rodent and human oligodendrocytes from different sources

Oligodendrocytes are part of the glial cells located in the central nervous system, capable of providing trophic support to neurons and ensheathing their axons. These cells can become dysfunctional under pathologic condition. Rodent and human pluripotent stem cells are inexhaustible sources for producing oligodendrocytes that can be used for disease modeling and cell replacement therapy studies. T

Impaired hepatic lipid synthesis from polyunsaturated fatty acids in TM6SF2 E167K variant carriers with NAFLD

Background: Carriers of the transmembrane 6 superfamily member 2 E167K gene variant (TM6SF2EK/KK) have decreased expression of the TM6SF2 gene and increased risk of NAFLD and NASH. Unlike common 'obese/metabolic' NAFLD, these subjects lack hypertriglyceridemia and have lower risk of cardiovascular disease. In animals, phosphatidylcholine (PC) deficiency results in a similar phenotype. PCs surround

SF-36 Shows Increased Quality of Life Following Complete Reduction of Postmastectomy Lymphedema with Liposuction

Background: Arm lymphedema after breast cancer surgery affects women both from physical and psychological points of view. Lymphedema leads to adipose tissue deposition. Liposuction and controlled compression therapy (CCT) reduces the lymphedema completely. Methods and Results: Sixty female patients with arm lymphedema were followed for a 1-year period after surgery. The 36-item short-form health s

Genetic variation at 16q24.2 is associated with small vessel stroke

Objective: Genome-wide association studies (GWAS) have been successful at identifying associations with stroke and stroke subtypes, but have not yet identified any associations solely with small vessel stroke (SVS). SVS comprises one quarter of all ischemic stroke and is a major manifestation of cerebral small vessel disease, the primary cause of vascular cognitive impairment. Studies across neuro

Analysing the vulnerability of electric distribution systems: A step towards incorporating the societal consequences of disruptions

Reliable electrical power supply is a prerequisite for the modern society, and if it fails it can cause severe consequences in terms of economic losses and even fatalities. It is thus important to analyse the vulnerability of the electric power system. Network analysis has previously been used to analyse the vulnerability of electric transmission systems, however recent events in Sweden have shown

Identifying critical components in technical infrastructure networks

A new method for identifying and ranking critical components and sets of components in technical infrastructures is presented. The criticality of a component or a set of components is defined as the vulnerability of the system to failure in a specific component, or set of components. The identification of critical components is increasingly difficult when considering multiple simultaneous failures

Fetal hemoglobin in umbilical cord blood in preeclamptic and normotensive pregnancies : A cross-sectional comparative study

Preeclampsia (PE) is associated with increased fetal hemoglobin (HbF) in the maternal circulation but its source is unknown. To investigate whether excessive HbF is produced in the placenta or the fetus, the concentration of HbF (cHbF) in the arterial and venous umbilical cord blood (UCB) was compared in 15825 normotensive and 444 PE pregnancies. The effect of fetal gender on cHbF was also evaluat

Human Primary Bone Marrow Mesenchymal Stromal Cells and Their in vitro Progenies Display Distinct Transcriptional Profile Signatures

Bone marrow mesenchymal stromal cells (BM-MSCs) are a rare population of cells that gives rise to skeletal tissues and the hematopoietic stroma in vivo. Recently, we have demonstrated that BM-MSCs fulfill stringent in vivo stem cell criteria when propagated as non-adherent mesenspheres but not as adherent-cultured cells. Motivated by these profound functional differences, the current study aimed t

Prognostic factors for change in self-reported anxiety and depression in spondyloarthritis patients : data from the population-based SpAScania cohort from southern Sweden

Objectives: Anxiety and depression symptoms are more common in patients with spondyloarthritis (SpA) than in the general population. This study describes prognostic factors for change in self-reported anxiety and depression over 2 years in a well-defined SpA cohort. Method: In 2009, 3716 adult patients from the SpAScania cohort received a postal questionnaire to assess quality of life (QoL) and ph