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Circulating fibrosis biomarkers and risk of atrial fibrillation : The Cardiovascular Health Study (CHS)

Background Cardiac fibrosis is thought to play a central role in the pathogenesis of atrial fibrillation (AF). Retrospective studies have suggested that circulating fibrosis biomarkers are associated with AF, but prospective studies are limited. Methods We measured circulating levels of 2 fibrosis biomarkers, procollagen type III, N-terminal propeptide (PIIINP) and transforming growth factor β1 am

Plasma fatty acid binding protein 4 and risk of sudden cardiac death in older adults

Although fatty acid binding protein 4 (FABP4) may increase risk of diabetes and exert negative cardiac inotropy, it is unknown whether plasma concentrations of FABP4 are associated with incidence of sudden cardiac death (SCD). We prospectively analyzed data on 4,560 participants of the Cardiovascular Health Study. FABP4 was measured at baseline using ELISA, and SCD events were adjudicated through

Activation of enteroendocrine membrane progesterone receptors promotes incretin secretion and improves glucose tolerance in mice

Glucagon-like peptide-1 (GLP-1) secretion is classically regulated by ingested nutrients. To identify novel molecular targets controlling incretin secretion, we analyzed enteroendocrine cell pathways important for hormone biosynthesis and secretion. We demonstrate that progesterone increases GLP-1 secretion and extracellular signal-related kinase 1/2 (ERK1/2) phosphorylation in enteroendocrine GLU

Anti-idiotypic antibody specific to GAD65 autoantibody prevents type 1 diabetes in the NOD mouse

Overt autoantibodies to the smaller isoform of glutamate decarboxylase (GAD65Ab) are a characteristic in patients with Type 1 diabetes (T1D). Anti-idiotypic antibodies (anti-Id) directed to GAD65Ab effectively prevent the binding of GAD65 to GAD65Ab in healthy individuals. Levels of GAD65Ab-specific anti-Id are significantly lower in patients with T1D, leading to overt GAD65Ab in these patients. T

Effects of vasoactive agents on blood loss and transfusion requirements during pre-reperfusion stages of the orthotopic liver transplantation

Objective: To evaluate the effects of vasoactive drugs, specifically low-dose vasopressin and phenylephrine infusions, on blood loss / transfusion requirements during dissection and anhepatic (pre-reperfusion) stages of orthotopic liver transplantations. Methods: A retrospective analysis of 110 orthotopic liver transplantation (OLT) cases was performed. The variables studied were: blood loss befor

ErbB Signaling Is Required for the Proliferative Actions of GLP-2 in the Murine Gut

Background & Aims: Glucagon-like peptide-2 (GLP-2) is a 33-amino acid peptide hormone secreted by enteroendocrine cells in response to nutrient ingestion. GLP-2 stimulates crypt cell proliferation leading to expansion of the mucosal epithelium; however, the mechanisms transducing the trophic effects of GLP-2 are incompletely understood. Methods: We examined the gene expression profiles and gro

The Glucagon Receptor Is Required for the Adaptive Metabolic Response to Fasting

Glucagon receptor (Gcgr) signaling maintains hepatic glucose production during the fasting state; however, the importance of the Gcgr for lipid metabolism is unclear. We show here that fasted Gcgr-/- mice exhibit a significant increase in hepatic triglyceride secretion and fasting increases fatty acid oxidation (FAO) in wild-type (WT) but not in Gcgr-/- mice. Moreover fasting upregulated the expre

Modulation of diabetes in NOD mice by GAD65-specific monoclonal antibodies is epitope specific and accompanied by anti-idiotypic antibodies

Type 1 diabetes is caused by the autoimmune destruction of pancreatic beta cells. Here we show that administration of a human monoclonal antibody (b96.11) specific to the 65-kDa isoform of glutamate decarboxylase (GAD65) to prediabetic non-obese diabetic (NOD) mice significantly delays the onset of autoimmune diabetes. We found this effect to be epitope-specific, as only b96.11 showed this therape

Integrating global proteomic and genomic expression profiles generated from islet α cells : Opportunities and challenges to deriving reliable biological inferences

Systematic profiling of expressed gene products represents a promising research strategy for elucidating the molecular phenotypes of islet cells. To this end, we have combined complementary genomic and proteomic methods to better assess the molecular composition of murine pancreatic islet glucagon-producing αTC-1 cells as a model system, with the expectation of bypassing limitations inherent to ei

Characterization and functional role of voltage gated cation conductances in the glucagon-like peptide-1 secreting GLUTag cell line

Glucagon-like peptide-1 (GLP-1) is released from intestinal L-cells in response to nutrient ingestion. It is currently under therapeutic evaluation because it enhances insulin secretion in type 2 diabetes. Previous studies using the GLP-1 secreting cell line GLUTag have shown that the cells are electrically active, and that the action potential frequency is regulated by nutrients. In this study we

Binary tree-structured vector quantization approach to clustering and visualizing microarray data

Motivation: With the increasing number of gene expression databases, the need for more powerful analysis and visualization tools is growing. Many techniques have successfully been applied to unravel latent similarities among genes and/or experiments. Most of the current systems for microarray data analysis use statistical methods, hierarchical clustering, self-organizing maps, support vector machi

Diagnosis and management of individuals with Fetal Valproate Spectrum Disorder; A consensus statement from the European Reference Network for Congenital Malformations and Intellectual Disability

Background: A pattern of major and minor congenital anomalies, facial dysmorphic features, and neurodevelopmental difficulties, including cognitive and social impairments has been reported in some children exposed to sodium valproate (VPA) during pregnancy. Recognition of the increased risks of in utero exposure to VPA for congenital malformations, and for the neurodevelopmental effects in particu

Benchmarking subcellular localization and variant tolerance predictors on membrane proteins

Background: Membrane proteins constitute up to 30% of the human proteome. These proteins have special properties because the transmembrane segments are embedded into lipid bilayer while extramembranous parts are in different environments. Membrane proteins have several functions and are involved in numerous diseases. A large number of prediction methods have been introduced to predict protein subc

SMAC mimetics promote NIK-dependent inhibition of CD4+ TH17 cell differentiation

Second mitochondria-derived activator of caspase (SMAC) mimetics (SMs) are selective antagonists of the inhibitor of apoptosis proteins (IAPs), which activate noncanonical NF-B signaling and promote tumor cell death. Through gene expression analysis, we found that treatment of CD4+ T cells with SMs during T helper 17 (TH17) cell differentiation disrupted the balance between two antagonistic transc

6 av 10 ST-läkare på BUP funderar på att hoppa av - Upplevelse av brist på effektiv psykologisk behandling och låg autonomi på arbetsplatsen främsta orsaker

The Swedish Association for Child and Adolescent Psychiatry conducted a survey among their specialty trainees in 2018. Of the 48% response rate, around 48% admitted hesitancy to continue in their chosen specialty. A further 12% planned to depart from their field after completion of training. Factors associated with discontinuation in training were the perception of ineffective psychotherapeutic tr

Ab Initio Optical Potentials and Nucleon Scattering on Medium Mass Nuclei

We derive ab initio optical potentials from self-consistent Green's function theory and compute the elastic scattering of neutrons off oxygen and calcium isotopes. The comparison with scattering data is satisfactory at low scattering energies. The method is benchmarked against the no-core shell model with continuum calculations, showing that virtual excitations of the target are crucial to predict

Online sexual abuse of adolescents by a perpetrator met online : A cross-sectional study

Background: The current study aimed at exploring adolescents' experiences of online sexual contacts leading to online sexual abuse by a perpetrator whom the victim had first met online. Associations with socio demographic background, experience of abuse, relation to parents, health and risk behaviors were studied. Methods: The participants were a representative national sample of 5175 students in

Can We Use Satellite-Based FAPAR to Detect Drought?

Drought in Australia has widespread impacts on agriculture and ecosystems. Satellite-based Fraction of Absorbed Photosynthetically Active Radiation (FAPAR) has great potential to monitor and assess drought impacts on vegetation greenness and health. Various FAPAR products based on satellite observations have been generated and made available to the public. However, differences remain among these d