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Preeclampsia and high blood pressure in early pregnancy as risk factors of severe maternal cardiovascular disease during 50-years of follow-up

Objectives: Studies suggest preeclampsia as a risk factor for long term cardiovascular diseases (CVD), while evidence is limited regarding the risk of high blood pressures (BP) in early pregnancy. Study design: A register-based follow-up of 2434 mothers in the Helsingborg Birth Cohort. Associations of high BP in early pregnancy (>95th percentile systolic [SBP], diastolic [BDP], or mean arterial BP

Is There Any Role for Opioids in the Management of Knee and Hip Osteoarthritis? A Systematic Review and Meta-Analysis

Objective: Opioids have long been prescribed for chronic pain conditions, including osteoarthritis (OA). However, there is little information about their temporal efficacy, or differences in efficacy and safety between opioids with strong versus weak/intermediate μ opioid receptor–binding affinity. To explore these research questions, we conducted a systematic review and meta-analyses of randomize

Short-term effect of induced alterations in testosterone levels on fasting plasma amino acid levels in healthy young men

Long term effect of testosterone (T) deficiency impairs metabolism and is associated with muscle degradation and metabolic disease. The association seems to have a bidirectional nature and is not well understood. The present study aims to investigate the early and unidirectional metabolic effect of induced T changes by measuring fasting amino acid (AA) levels in a human model, in which short-term

KRAS signaling in malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos-exposed individuals and rapidly leads to death. MPM harbors loss-of-function mutations in BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point muta

Plasma Vitamin C and type 2 diabetes : Genome-wide association study and mendelian randomization analysis in European populations

OBJECTIVE Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to disc

Engineering human hematopoietic environments through ossicle and bioreactor technologies exploitation

The bone marrow microenvironment contains cellular niches that maintain the pool of hematopoietic stem and progenitor cells and support hematopoietic maturation. Malignant hematopoietic cells also co-opt normal cellular interactions to promote their own growth and evade therapy. In vivo systems used to study human hematopoiesis have been developed through transplantation into immunodeficient mouse

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glyc

Safety, Pharmacokinetics, and Pharmacodynamics of the ADAMTS-5 Inhibitor GLPG1972/S201086 in Healthy Volunteers and Participants With Osteoarthritis of the Knee or Hip

GLPG1972/S201086 is a disintegrin and metalloproteinase with thrombospondin motif-5 (ADAMTS-5) inhibitor in development as an osteoarthritis disease-modifying therapy. We report the safety, tolerability, pharmacokinetics, and pharmacodynamics (turnover of plasma/serum ARGS-aggrecan neoepitope fragments [ARGS]) of GLPG1972 in 3 randomized, double-blind, placebo-controlled phase 1 trials. Study A, a

Phenotypic drug screening in a human fibrosis model identified a novel class of antifibrotic therapeutics

Fibrogenic processes instigate fatal chronic diseases leading to organ failure and death. Underlying biological processes involve induced massive deposition of extracellular matrix (ECM) by aberrant fibroblasts. We subjected diseased primary human lung fibroblasts to an advanced three-dimensional phenotypic high-content assay and screened a repurposing drug library of small molecules for inhibitin

A prospective study of the relationships between movement and glycemic control during day and night in pregnancy

Both disturbed sleep and lack of exercise can disrupt metabolism in pregnancy. Accelerometery was used to objectively assess movement during waking (physical activity) and movement during sleeping (sleep disturbance) periods and evaluated relationships with continuous blood glucose variation during pregnancy. Data was analysed prospectively. 15-women without pre-existing diabetes mellitus wore con

Proteomics profiling of human synovial fluid suggests increased protein interplay in early-osteoarthritis (OA) that is lost in late-stage OA

The underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear) and from deceased controls without knee OA.Synovial fluid samples were analyzed using state-of-the-art

Once after a full moon : acute type A aortic dissection and lunar phases

OBJECTIVES: Acute type A aortic dissection (ATAAD) is a rare but severe condition, routinely treated with emergent cardiac surgery. Many surgeons have the notion that patients with ATAAD tend to come in clusters, but no studies have examined these observations. This investigation was undertaken to study the potential association between the lunar cycle and the incidence of ATAAD. METHODS: We colle

Enhancing teachers’ classroom communication skills – Measuring the effect of a continued professional development programme for mainstream school teachers

Continued professional development (CPD), tailored to teachers’ needs and expectations, is required for updated skills and knowledge. In this study, twenty-five teachers working with first and second grade students participated in an 11-week programme focusing on enhancing classroom communication. The participating teachers were randomly assigned to either a direct intervention track (intervention

Falls After Stroke : A Follow-up after Ten Years in Lund Stroke Register

OBJECTIVES: To evaluate incidence of self-reported falls and associated factors in a ten-year perspective after stroke.METHODS: From a population-based cohort of first-ever stroke patients (n = 416) included in the Lund Stroke Register between March 1, 2001, and February 28, 2002, we performed a follow up of all 145 survivors ten years after stroke. We collected data on age, gender, main stroke ty

Bone marrow transplantation without myeloablative conditioning in a mouse model for Diamond-Blackfan anemia corrects the disease phenotype

Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by a functional haploinsufficiency of genes coding for ribosomal proteins. Among these genes, the ribosomal protein S19 (RPS19) gene is the most frequently mutated. Previously, a mouse model deficient in RPS19 was developed by our laboratory, which recapitulates the hematopoietic disease phenotype by manifesting pathologic f

Novel Reclassification of Adult Diabetes Is Useful to Distinguish Stages of β-Cell Function Linked to the Risk of Vascular Complications : The DOLCE Study From Northern Ukraine

Background: Presently, persons with diabetes are classified as having type 1 (T1D) or type 2 diabetes (T2D) based on clinical diagnosis. However, adult patients exhibit diverse clinical representations and this makes treatment approaches challenging to personalize. A recent Scandinavian study proposed a novel classification of adult diabetes into five clusters based on disease pathophysiology and

Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes : The EPIC-InterAct Case-Cohort Study

Background: Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations. Methods and Findings: Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Canc

Association between low-density lipoprotein cholesterol-lowering genetic variants and risk of type 2 diabetes : A meta-analysis

IMPORTANCE Low-density lipoprotein cholesterol (LDL-C)-lowering alleles in or near NPC1L1 or HMGCR, encoding the respective molecular targets of ezetimibe and statins, have previously been used as proxies to study the efficacy of these lipid-lowering drugs. Alleles near HMGCR are associated with a higher risk of type 2 diabetes, similar to the increased incidence of new-onset diabetes associated w