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Dynamical modelling of haematopoiesis: an integrated view over the system in homeostasis and under perturbation.

A very high number of different types of blood cells must be generated daily through a process called haematopoiesis in order to meet the physiological requirements of the organism. All blood cells originate from a population of relatively few haematopoietic stem cells residing in the bone marrow, which give rise to specific progenitors through different lineages. Steady-state dynamics are governe

One-hour glucose value as a long-term predictor of cardiovascular morbidity and mortality : the Malmö Preventive Project

OBJECTIVE: To examine the predictive capability of a 1-h vs 2-h postload glucose value for cardiovascular morbidity and mortality.DESIGN: Prospective, population-based cohort study (Malmö Preventive Project) with subject inclusion 1974-1992.RESULTS: Median age was 48 (25th-75th percentile: 48-49) years and mean FBG 4.6 ± 0.6 mmol/L. FBG and 2-h postload BG did not independently predict cardiovascu

Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and

Organ Specific Killing af a Dispensable Organ or a Cell Population in an Organ - a Successful Design for Cancer Therapy - a Hypothesis

Purpose: This article hypothesizes that designing cancer therapies based on the organ specific toxicity of the normal tissue of the organ from which the tumors originated could be worthwhile. A prerequisite for successful therapy is that the individual can recover from damage done to the organ or cells.Results: Therapeutic examples are given for lymphoma, kidney cancer, melanoma and leukemia.Concl

A novel rare CUBN variant and three additional genes identified in Europeans with and without diabetes : results from an exome-wide association study of albuminuria

Aims/hypothesis: Identifying rare coding variants associated with albuminuria may open new avenues for preventing chronic kidney disease and end-stage renal disease, which are highly prevalent in individuals with diabetes. Efforts to identify genetic susceptibility variants for albuminuria have so far been limited, with the majority of studies focusing on common variants. Methods: We performed an

Cell-based therapy for Parkinson's disease : A journey through decades toward the light side of the Force

This review describes the history, development, and evolution of cell-based replacement therapy for Parkinson's disease (PD), from the first pioneering trials with fetal ventral midbrain progenitors to future trials using stem cells as well as reprogrammed cells. In the spirit of Tom Isaacs, the review takes parallels to the storyline of Star Wars, including the temptations from the dark side and

Challenges in transdisciplinary research : Example from a study on people as part of energy and ventilation systems in residential buildings (PEIRE)

Energy efficiency measures in residential buildings typically include changes in ventilation and heating systems, and increased thermal insulation of the building envelope. The expected energy efficiency is not always reached, despite large knowledge and professional implementation of each separate measure. Thereis a lack in understanding of how technical systems interact, and how the ocupants are

Interleukin-25 reduces Th17 cells and inflammatory responses in human peripheral blood mononuclear cells

Background: The absence of interleukin-25 (IL-25) favors the induction of Th1 and Th17 immune responses in mice. Th1 immune responses have been associated with the pathology of atherosclerosis, a lipid and inflammation driven disease of the arterial wall. Purpose of research: To evaluate the effect of IL-25 on human peripheral blood mononuclear cells (hPBMCs) in the presence and absence of oxidize

Markers of basement membrane remodeling are associated with higher mortality in patients with known atherosclerosis

Background-Patients with atherosclerosis have a high risk of cardiovascular events and death. Atherosclerosis is characterized by accumulation of lipids, cells and extracellular matrix proteins in the intima. We hypothesized that dysregulated remodeling of the basement membrane proteins may be associated with clinical outcomes in patients with atherosclerosis. Methods and Results-Neoepitope fragme

Biogenic aerosol particles in the earth system model EC-earth

Treatments of emissions of primary biological aerosol particles (PBAP) were implemented in the global Earth System model EC-Earth. These emission schemes were improved to account for the strong peaks of PBAP concentrations in connection to precipitation events, which has been measured recently. The model is now able to treat the emission of bacteria, spores and pollen in dependency of precipitatio

Validation of standardized creatinine and cystatin C GFR estimating equations in a large multicentre European cohort of children

Background: Most validations of paediatric glomerular filtration rate (GFR) estimating equations using standardized creatinine (CR) and cystatin C (CYS) assays have comprised relatively small cohorts, which makes accuracy across subgroups of GFR, age, body mass index (BMI) and gender uncertain. To overcome this, a large cohort of children referred for GFR determination has been established from se

Glucocorticoid-induced tumour necrosis factor receptor family-related protein (GITR) drives atherosclerosis in mice and is associated with an unstable plaque phenotype and cerebrovascular events in humans

AIMS: GITR-a co-stimulatory immune checkpoint protein-is known for both its activating and regulating effects on T-cells. As atherosclerosis bears features of chronic inflammation and autoimmunity, we investigated the relevance of GITR in cardiovascular disease (CVD). METHODS AND RESULTS: GITR expression was elevated in carotid endarterectomy specimens obtained from patients with cerebrovascular e

A novel method for creatinine adjustment makes the revised Lund–Malmö GFR estimating equation applicable in children

The aim of this study was to establish creatinine growth curves separately for males and females that can be used to adjust childhood levels of serum creatinine to corresponding adult levels. Linear regression with fractional polynomials of age as independent variable was used to construct creatinine growth curves for a reference cohort (n = 83,157 samples from Belgium and Sweden, age 2–40 years).

Lipoprotein-associated phospholipase A2 activity, genetics and calcific aortic valve stenosis in humans

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity has been shown to predict calcific aortic valve stenosis (CAVS) outcomes. Our objective was to test the association between plasma Lp-PLA2 activity and genetically elevated Lp-PLA2 mass/activity with CAVS in humans. Methods and results: Lp-PLA2 activity was measured in 890 patients undergoing cardiac surgery, including 476 pati

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Incisional negative pressure wound therapy in the prevention of surgical site infection after vascular surgery with inguinal incisions: rational and design of a randomized controlled trial (INVIPS-Trial).

Background/Aims: Inguinal incisions are a common route of access in vascular surgery. Due to anatomical challenges and a diverse bacterial flora in this area, surgical site infections (SSI) represent a common, debilitating and sometimes life-threatening complication. The INVIPS-Trial evaluates the role of Negative Pressure Wound Therapy (NPWT) on closed inguinal incisions in elective vascular surg

Alpha-amylase 1A copy number variants and the association with memory performance and Alzheimer’s dementia

Background: Previous studies have shown that copy number variation (CNV) in the alpha (α)-amylase gene (AMY1A) is associated with body mass index, insulin resistance, and blood glucose levels, factors also shown to increase the risk of Alzheimer’s dementia (AD). We have previously demonstrated the presence of α-amylase in healthy neuronal dendritic spines and a reduction of the same in AD patients