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Reactive Oxygen Species Impair the Function of CD90+ Hematopoietic Progenitors Generated from Human Pluripotent Stem Cells

Cell stressors, such as elevated levels of reactive oxygen species (ROS), adversely affect hematopoietic stem cell (HSC) reconstituting ability. However, the effects of ROS have not been evaluated in the context of hematopoietic development from human pluripotent stem cells (hPSCs). Using our previously described in vitro system for efficient derivation of hematopoietic cells from hPSCs, we show t

Modelling Human Developmental Hematopoiesis. Towards in vitro Generation of Human Hematopoietic Stem Cells

The possibility to manufacture hematopoietic stem cells (HSCs) in the laboratory would provide an indefinite source of cells for patients requiring bone marrow transplantation. Moreover, combined with the progress in gene editing techniques, it would provide a novel platform for gene and cell replacement therapies for a range of currently incurable congenic and acquired disorders. During my PhD, I

The effect of mindfulness group therapy on a broad range of psychiatric symptoms : A randomised controlled trial in primary health care

Background The need for psychotherapy in primary health care is on the increase but individual-based treatment is costly. The main aim of this randomised controlled trial (RCT) was to compare the effect of mindfulness-based group therapy (MGT) with treatment as usual (TAU), mainly individual-based cognitive behavioural therapy (CBT), on a broad range of psychiatric symptoms in primary care patient

School achievement, IQ, and risk of alcohol use disorder : A prospective, Co-relative analysis in a Swedish national cohort

Objective: Most studies suggest that poor cognitive functioning in adolescence increases risk of alcohol use disorders (AUDs). We seek to clarify the causes of this association. Method: In Swedish individuals born from 1972 to 1990 in whom cognitive functioning was assessed by school achievement at age 16 years (males and females, N = 1,796,048) and by IQ at ages 18–20 (males, N = 554,644), we exa

Signaling via Smad2 and Smad3 is dispensable for adult murine hematopoietic stem cell function in vivo

Transforming growth factor-β (TGFβ) is a member of a large family of polypeptide growth factors. TGFβ signals mainly through the intracellular proteins Smad2 and Smad3, which are highly similar in amino acid sequence identity. A number of studies have shown that these proteins, dependent on context, have distinct roles in the TGFβ signaling pathway. TGFβ is one of the most potent inhibitors of hem

Prevalence and incidence of doctor-diagnosed Dupuytren's disease : A population-based study

The prevalence and incidence of doctor-diagnosed Dupuytren's disease in the general population is unknown. From the healthcare register for Skåne region (population 1.3 million) in southern Sweden, we identified all residents aged 3/420 years (on 31 December 2013), who 1998 to 2013 had consulted a doctor and received the diagnosis Dupuytren's disease (International Classification of Diseases 10th

Genomic correlates of glatiramer acetate adverse cardiovascular effects lead to a novel locus mediating coronary risk

Glatiramer acetate is used therapeutically in multiple sclerosis but also known for adverse effects including elevated coronary artery disease (CAD) risk. The mechanisms underlying the cardiovascular side effects of the medication are unclear. Here, we made use of the chromosomal variation in the genes that are known to be affected by glatiramer treatment. Focusing on genes and gene products repor

Supported fluid lipid bilayer as a scaffold to direct assembly of RNA nanostructures

RNA architectonics offers the possibility to design and assemble RNA into specific shapes, such as nanoscale 3D solids or nanogrids. Combining the minute size of these programmable shapes with precise positioning on a surface further enhances their potential as building blocks in nanotechnology and nanomedicine. Here we describe a bottom-up approach to direct the arrangement of nucleic acid nanost

Early- versus late-onset Alzheimer's disease in clinical practice : Cognitive and global outcomes over 3 years

Background: Whether age at onset influences Alzheimer's disease (AD) progression and the effectiveness of cholinesterase inhibitor (ChEI) therapy is not clear. We aimed to compare longitudinal cognitive and global outcomes in ChEI-treated patients with early-onset Alzheimer's disease (EOAD) versus late-onset Alzheimer's disease (LOAD) in clinical practice. Methods: This 3-year, prospective, observ

Evidence-based prioritisation and enrichment of genes interacting with metformin in type 2 diabetes

Aims/hypothesis: There is an extensive body of literature suggesting the involvement of multiple loci in regulating the action of metformin; most findings lack replication, without which distinguishing true-positive from false-positive findings is difficult. To address this, we undertook evidence-based, multiple data integration to determine the validity of published evidence. Methods: We (1) buil

Body Height and Incident Risk of Venous Thromboembolism : A Cosibling Design

BACKGROUND: Body height has been associated with an increased risk of venous thromboembolism (VTE), but the association can be confounded with shared familial factors (genetic/environmental). A cosibling design is useful for deeper understanding about the relationship between VTE and height.METHODS AND RESULTS: From Swedish national registry databases, we used a corelative design with full sibling

High Risk of Venous Thromboembolism in Klinefelter Syndrome

BACKGROUND: Klinefelter syndrome (KS) is the most common sex chromosome disorder. The genetic background is the extra X chromosome. Venous thromboembolism (VTE) has been observed among KS patients. The aim of the present study was to examine whether KS is associated with VTE.METHODS AND RESULTS: We followed up all hospital in- and outpatients (N=1085) in Sweden with a diagnosis of KS between Janua

Autoimmune diseases and venous thromboembolism : a review of the literature

Venous thromboembolism (VTE) is major health problem and is sometimes complicated by lethal pulmonary embolism (PE). Disturbances of the coagulation and anticoagulation systems are important risk factors for VTE. Comparative studies suggest that coagulation and innate immunity have a shared evolutionary origin. It is therefore unsurprising that the immune and coagulation systems are linked, with m

Risk of second primary cancers in women diagnosed with endometrial cancer in German and Swedish cancer registries

Along with the increasing incidence and favorable prognosis, more women diagnosed with endometrial cancer may develop second primary cancers (SPCs). We aimed at investigating risk of SPCs after endometrial cancer in Germany and Sweden to provide insight into prevention strategies for SPCs. Endometrial cancer patients diagnosed at age ≥15 years in Germany during 1997–2011 and in Sweden nationwide d

Impact of a Tertiary Eligibility Threshold on Tertiary Education and Earnings : A Discontinuity Approach

This study evaluates the impact of achieving tertiary eligibility in upper-secondary education on tertiary education and earnings in Sweden. Using a regression discontinuity design, we estimate the impact of tertiary eligibility and show that it has a substantial impact on the probability of enrolling in tertiary education. For students who achieve tertiary eligibility, the probability of enrollin

Aggregation and Fibril Structure of AβM01-42 and Aβ1-42

A mechanistic understanding of Aβ aggregation and high-resolution structures of Aβ fibrils and oligomers are vital to elucidating relevant details of neurodegeneration in Alzheimer's disease, which will facilitate the rational design of diagnostic and therapeutic protocols. The most detailed and reproducible insights into structure and kinetics have been achieved using Aβ peptides produced by reco

Comparison of Mortality and Nonfatal Cardiovascular Events in Adults With Atrial Fibrillation With Versus Without Levothyroxine Treatment

Levothyroxine has been suggested to be cardiotoxic, but previous studies on the risk of cardiovascular events associated with levothyroxine treatment have been inconclusive. We aimed to study the association between levothyroxine treatment and all-cause mortality as well as cardiovascular events. Study population included all adults (n = 12,283) ≥ 45 years diagnosed with atrial fibrillation (AF) a

Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis

Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with

The prevalence, incidence, and progression of hand osteoarthritis in relation to body mass index, smoking, and alcohol consumption

Objective. To estimate the extent that overweight/obesity, smoking, and alcohol are associated with prevalence and longitudinal changes of radiographic hand osteoarthritis (OA). Methods. Participants from the Osteoarthritis Initiative (n = 1232) were included, of whom 994 had 4-year followup data. In analyses on incident hand OA, only persons without hand OA at baseline were included (n = 406). Ou