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dsRNA-induced expression of thymic stromal lymphopoietin (TSLP) in asthmatic epithelial cells is inhibited by a small airway relaxant.

RATIONALE: Thymic Stromal Lymphopoietin (TSLP) is considered a hub cytokine that activates dendritic cells and T-cells producing asthma-like Th(2)-inflammation. Viral stimuli, a major cause of asthma exacerbations, have been shown to induce overexpression of TSLP in asthmatic epithelium. Capsazepine has multiple effects and is of interest because it relaxes human small airways. Here we have explor

Orthostatic Hypotension Predicts Incidence of Heart Failure: The Malmö Preventive Project.

BackgroundThe presence of orthostatic hypotension (OH) predicts all-cause mortality and incident cardiovascular disease. Whether or not OH is associated with the development of heart failure (HF) remains unknown.MethodsIn this Swedish population-based prospective study (the Malmö Preventive Project), the incidence of HF in relation to baseline OH, defined as decrease in systolic (SBP) >/=20 mm Hg

Glomerular filtration rate in patients with atrial fibrillation on warfarin treatment: A subgroup analysis from the AURICULA registry in Sweden.

INTRODUCTION: Numerous associations between chronic kidney disease (CKD) and atrial fibrillation (AF) have been reported and patients with CKD on anticoagulation therapy have an increased risk of bleeding. Currently, new anticoagulant agents are emerging in clinical practice, some of which are excreted by the kidneys. The proportion of AF patients on anticoagulant treatment with reduced renal func

Incidence of Coronary Events and Case Fatality Rate in Relation to Blood Lymphocyte and Neutrophil Counts.

OBJECTIVE: Elevated levels of blood leukocytes have been associated with acute coronary events (CEs), but data on leukocyte subclasses are limited. This study aimed to explore whether blood lymphocyte and neutrophil counts are associated with incidence of CEs and with fatal outcome in subjects who subsequently experienced a first CE. METHODS AND RESULTS: Neutrophil and lymphocyte counts were measu

Risk predictions for individual patients from logistic regression were visualized with bar-line charts.

OBJECTIVE: The interface of a computerized decision support system is crucial for its acceptance among end users. We demonstrate how combined bar-line charts can be used to visualize predictions for individual patients from logistic regression models. STUDY DESIGN AND SETTING: Data from a previous diagnostic study aiming at predicting the immediate risk of acute coronary syndrome (ACS) among 634 p

Mice with ribosomal protein S19 deficiency develop bone marrow failure and symptoms like patients with Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by a functional haploinsufficiency of genes encoding for ribosomal proteins. Among these genes, ribosomal protein S19 (RPS19) is mutated most frequently. Generation of animal models for diseases like DBA is challenging since the phenotype is highly dependent on the level of RPS19 downregulation. We report the generation of m

A network including TGFβ/Smad4, Gata2 and p57 regulates proliferation of mouse hematopoietic progenitor cells.

Transforming growth factor-β (TGFβ) is a potent inhibitor of hematopoietic stem and progenitor cell proliferation. However, the precise mechanism for this effect is unknown. Here, we have identified the transcription factor Gata2, previously described as an important regulator of hematopoietic stem cell (HSC) function, as an early and direct target gene for TGFβ-induced Smad signaling in hematopoi

Transcriptional regulation of the miR-212/miR-132 cluster in insulin-secreting β-cells by cAMP-regulated transcriptional co-activator 1 and salt-inducible kinases.

MicroRNAs are central players in the control of insulin secretion, but their transcriptional regulation is poorly understood. Our aim was to investigate cAMP-mediated transcriptional regulation of the miR-212/miR-132 cluster and involvement of further upstream proteins in insulin secreting β-cells. cAMP induced by forskolin+IBMX or GLP-1 caused increased expression of miR-212/miR-132, and elevated

Tumour markers in prostate cancer II: diagnostic and prognostic cellular biomarkers.

The main goal of prostate cancer tissue biomarkers is to improve diagnostic and prognostic accuracy. A particularly important question is whether the cancer needs immediate treatment or if treatment can be deferred. It is highly unlikely that a single biomarker that provides comprehensive prognostic information about a newly diagnosed prostate cancer will be forthcoming. Despite extensive research

The Proteome of Primary Prostate Cancer.

Clinical management of the prostate needs improved prognostic tests and treatment strategies. Because proteins are the ultimate effectors of most cellular reactions, are targets for drug actions and constitute potential biomarkers; a quantitative systemic overview of the proteome changes occurring during prostate cancer (PCa) initiation and progression can result in clinically relevant discoveries

Low β2-adrenergic receptor level may promote development of castration resistant prostate cancer and altered steroid metabolism.

The underlying mechanisms responsible for the development of castration-resistant prostate cancer (CRPC) in patients who have undergone androgen deprivation therapy are not fully understood. This is the first study to address whether β2-adrenergic receptor (ADRB2)- mediated signaling may affect CRPC progression in vivo. By immunohistochemical analyses, we observed that low levels of ADRB2 is assoc

Dopamine Neuron Diversity : Recent Advances and Current Challenges in Human Stem Cell Models and Single Cell Sequencing

Human midbrain dopamine (DA) neurons are a heterogeneous group of cells that share a common neurotransmitter phenotype and are in close anatomical proximity but display different functions, sensitivity to degeneration, and axonal innervation targets. The A9 DA neuron subtype controls motor function and is primarily degenerated in Parkinson's disease (PD), whereas A10 neurons are largely unaffected

Stem Derived Dopamine Neurons : Will They Replace DBS as the Leading Neurosurgical Treatment for Parkinson's Disease?

The use of stem cell derived dopamine neurons for treating patients with Parkinson's disease has now evolved to the first in human clinical trials. In this debate, we argue that assuming these trials give positive outcomes that this therapy will supercede DBS as the neurosurgical treatment of choice for PD patients in the future given it is a one-off therapy that repairs a critical pathway in the

GDNF Therapy : Can We Make It Work?

In two recent postmortem studies, Jeffrey Kordower and colleagues report new findings that open up for an interesting discussion on the status of GDNF/NRTN signaling in patients with Parkinson's disease (PD), adding an interesting perspective on the, admittedly very limited, signs of restorative effects previously seen in GDNF/NRTN-treated patients. Their new findings show that the level of the GD

Quantitative proteomic analysis of human peripheral nerves from subjects with type 2 diabetes

AIMS: Diabetic peripheral neuropathy (DPN) is a common and severe complication to type 2 diabetes (T2D). The pathogenesis of DPN is not fully known, but several pathways and gene polymorphisms contributing to DPN are described. DPN can be studied using nerve biopsies, but studies on the proteome of the nerve itself, and its surrounding tissue as a whole, are lacking. Studies on the posterior inter

Whose Relevance? : Web Search Engines as Multi-sided Relevance Machines

This opinion piece takes Google's response to the so-called COVID-19 infodemic, as a starting point to argue for the need to consider societal relevance as a complement to other types of relevance. The authors maintain that if information science wants to be a discipline at the forefront of research on relevance, search engines, and their use, then the information science research community needs

RUBIC (ReproUnion Biobank and Infertility Cohort) : A binational clinical foundation to study risk factors, life course, and treatment of infertility and infertility-related morbidity

Background: Infertility affects 15%–25% of all couples during their reproductive life span. It is a significant societal and public health problem with potential psychological, social, and economic consequences. Furthermore, infertility has been linked to adverse long-term health outcomes. Despite the advanced diagnostic and therapeutic techniques available, approximately 30% of infertile couples

Right ventricular stroke work index by echocardiography in adult patients with pulmonary arterial hypertension

BACKGROUND: In adult patients with pulmonary arterial hypertension (PAH), right ventricular (RV) failure may worsen rapidly, resulting in a poor prognosis. In this population, non-invasive assessment of RV function is challenging. RV stroke work index (RVSWI) measured by right heart catheterization (RHC) represents a promising index for RV function. The aim of the present study was to comprehensiv