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Clonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate

Ageing associates with significant alterations in somatic/adult stem cells and therapies to counteract these might have profound benefits for health. In the blood, haematopoietic stem cell (HSC) ageing is linked to several functional shortcomings. However, besides the recent realization that individual HSCs might be preset differentially already from young age, HSCs might also age asynchronously.

Socio-demographic factors and long-term use of benzodiazepines in patients with depression, anxiety or insomnia

Former studies that have attempted to characterize individual socio-demographic factors associated with long-term benzodiazepine use were based on relatively small sample sizes and/or self-reported data. Our aim was to clarify this using large-scale primary health care data from Sweden. The present study covered 71 primary health care centres containing individual-level data from a total of 919, 9

Antimicrobial combination treatment including ciprofloxacin decreased the mortality rate of Pseudomonas aeruginosa bacteraemia : a retrospective cohort study

Ineffective antimicrobial therapy of Pseudomonas aeruginosa bacteraemia increases mortality. Recent studies have proposed the use of antimicrobial combination therapy composed of a beta-lactam with either ciprofloxacin or tobramycin. To determine if combination therapy correlates to lower mortality and is superior compared to monotherapy, we investigated the effect of antimicrobial treatment regim

Strengthening the Reporting of Observational Studies in Epidemiology—Nutritional Epidemiology (STROBE-nut) : An Extension of the STROBE Statement

Background: Concerns have been raised about the quality of reporting in nutritional epidemiology. Research reporting guidelines such as the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement can improve quality of reporting in observational studies. Herein, we propose recommendations for reporting nutritional epidemiology and dietary assessment research by exte

Molecular mechanisms underlying lineage bias in aging hematopoiesis

Although hematopoietic stem cells (HSCs) have traditionally been thought to possess the ability to give rise to all the mature cell types in the hematopoietic system, this conception of hematopoiesis was based on evaluation of hematopoietic output from large numbers of HSCs using transplantation models. More recent studies evaluating HSCs at the clonal or near-clonal level, both in transplantation

The Incidence of Senile Cataract and Glaucoma is Increased in Patients with Plasma Cell Dyscrasias : Etiologic Implications

Plasma cell dyscrasias, including monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), Waldenström macroglobulinemia (WM) and light chain AL amyloidosis, are characterized by clonal expansion of plasma cells which produce a vast amount of an immunoglobulin-derived M-protein. We noted that MGUS diagnosis often coincided with diagnoses of senile cataract and glaucoma and

Snus use and risk of schizophrenia and non-affective psychosis

Background: Recent studies suggest a possible causal role for smoking in schizophrenia and psychosis. Most studies have focused on cigarette smoking, the most common form of tobacco use, but other forms of tobacco exist, including smokeless products such as Swedish snuff (or "snus"). Methods: We explored whether snus use is associated with schizophrenia and non-affective psychotic illness in a lar

Dietary polyphenol intake in europe : The european prospective investigation into cancer and nutrition (EPIC) study

Background/Objectives Polyphenols are plant secondary metabolites with a large variability in their chemical structure and dietary occurrence that have been associated with some protective effects against several chronic diseases. To date, limited data exist on intake of polyphenols in populations. The current cross-sectional analysis aimed at estimating dietary intakes of all currently known indi

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

Higher risk of revision for infection using systemic clindamycin prophylaxis than with cloxacillin : A report from the Swedish Knee Arthroplasty Register on 78,000 primary total knee arthroplasties for osteoarthritis

Background and purpose — Clindamycin has not been compared with other antibiotics for prophylaxis in arthroplasty. Since 2009, the Swedish Knee Arthroplasty Register (SKAR) has been collecting information on the prophylactic antibiotic regime used at every individual operation. In Sweden, when there is allergy to penicillin, clindamycin has been the recommended alternative. We examined whether the

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

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