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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

The role of parent and offspring sex on risk for externalizing psychopathology in offspring with parental alcohol use disorder : a national Swedish study

Purpose: The substantial literature showing that offspring of parents with alcohol use disorder (AUD) is at increased risk for externalizing psychopathology rarely examines the differential effects of parental and offspring sex. This literature also has other important limitations, such as modest sample sizes and use of unrepresentative samples. Using a large, nationwide Swedish sample, we aim to

The properties of α-synuclein secondary nuclei are dominated by the solution conditions rather than the seed fibril strain

Amyloid fibrils of α-synuclein (α-syn) are a component of Lewy bodies, the characteristic hallmark of Parkinson's disease. Amyloid fibrils arise through primary nucleation from monomers, which in the case of α-syn is often heterogeneous, followed by the growth of the nuclei by monomer addition. Secondary nucleation corresponds to the formation of new fibrils facilitated by pre-existing fibrils. Wh

Red Cell Distribution Width is Associated with Future Incidence of Abdominal Aortic Aneurysm in a Population-Based Cohort Study

Red cell distribution width (RDW) has been suggested to have a predictive potential for several cardiovascular diseases, but its association with abdominal aortic aneurysm (AAA) is unknown. We examined whether RDW is associated with the risk of AAA among 27,260 individuals from the population-based Malmö Diet and Cancer Study cohort. Data of baseline characteristics were collected during 1991–1996

Secondary Nucleation in Amyloid Formation

Research into Alzheimer's disease is still hampered by a lack of fundamental understanding of the underlying mechanisms. While the aggregation of the amyloid β peptide (Aβ) into amyloid fibrils is highly implicated as a key factor in the disease, the molecular nature of its involvement has proven complex and elusive. This thesis and the work herein is part of an ongoing effort to map out the aggre

Dynamics of oligomer populations formed during the aggregation of Alzheimer’s Aβ42 peptide

Oligomeric species populated during the aggregation of the Aβ42 peptide have been identified as potent cytotoxins linked to Alzheimer’s disease, but the fundamental molecular pathways that control their dynamics have yet to be elucidated. By developing a general approach that combines theory, experiment and simulation, we reveal, in molecular detail, the mechanisms of Aβ42 oligomer dynamics during

Improvement of Autism Symptoms After Comprehensive Intensive Early Interventions in Community Settings

BACKGROUND: Preschool children with autism in southern Sweden participated in a comprehensive Naturalistic Developmental Behavioral Intervention (NDBI) program. AIMS: To evaluate the ongoing NDBI program by comparing the pre- and postintervention outcomes in terms of improved autism symptom severity. METHOD: The improvement of Autism Diagnostic Observation Schedule (ADOS-R) test results between ba

Silver nanoparticles alter cell viability ex vivo and in vitro and induce proinflammatory effects in human lung fibroblasts

Silver nanoparticles (AgNPs) are commonly used in commercial and medical applications. However, AgNPs may induce toxicity, extracellular matrix (ECM) changes and inflammatory responses. Fibroblasts are key players in remodeling processes and major producers of the ECM. The aims of this study were to explore the effect of AgNPs on cell viability, both ex vivo in murine precision cut lung slices (PC