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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

Word definition skills in elementary school children - The contribution of bilingualism, cognitive factors, and social factors

Purpose: Vocabulary relates to overall language proficiency and is important for academic success. Word definition (WD) tasks can be used to assess vocabulary depth and definition skills. We investigate monolingual and bilingual children's performances on a WD task, and how bilingualism, level of parental education, school characteristics (proportion of students with Swedish as second language and

Reduced expression of OXPHOS and DNA damage genes is linked to protection from microvascular complications in long-term type 1 diabetes : the PROLONG study

Type 1 diabetes is a chronic autoimmune disease requiring insulin treatment for survival. Prolonged duration of type 1 diabetes is associated with increased risk of microvascular complications. Although chronic hyperglycemia and diabetes duration have been considered as the major risk factors for vascular complications, this is not universally seen among all patients. Persons with long-term type 1

Culturing patient-derived malignant hematopoietic stem cells in engineered and fully humanized 3D niches

Human malignant hematopoietic stem and progenitor cells (HSPCs) reside in bone marrow (BM) niches, which remain challenging to explore due to limited in vivo accessibility and constraints with humanized animal models. Several in vitro systems have been established to culture patient-derived HSPCs in specific microenvironments, but they do not fully recapitulate the complex features of native bone

Human Primary Bone Marrow Mesenchymal Stromal Cells and Their in vitro Progenies Display Distinct Transcriptional Profile Signatures

Bone marrow mesenchymal stromal cells (BM-MSCs) are a rare population of cells that gives rise to skeletal tissues and the hematopoietic stroma in vivo. Recently, we have demonstrated that BM-MSCs fulfill stringent in vivo stem cell criteria when propagated as non-adherent mesenspheres but not as adherent-cultured cells. Motivated by these profound functional differences, the current study aimed t

Prognostic factors for change in self-reported anxiety and depression in spondyloarthritis patients : data from the population-based SpAScania cohort from southern Sweden

Objectives: Anxiety and depression symptoms are more common in patients with spondyloarthritis (SpA) than in the general population. This study describes prognostic factors for change in self-reported anxiety and depression over 2 years in a well-defined SpA cohort. Method: In 2009, 3716 adult patients from the SpAScania cohort received a postal questionnaire to assess quality of life (QoL) and ph

No independent association between pulse wave velocity and dementia : a population-based, prospective study

OBJECTIVE:: Carotid–femoral pulse wave velocity (CFPWV), a marker of aortic stiffness, has been associated with cognitive test results and markers of cerebral small vessel disease, but its association with dementia has not been studied in detail. Our aim was to assess the association of CFPWV with prevalent and incident dementia in a large population-based study. METHODS:: In total, CFPWV was meas

Interaction between genes and macronutrient intake on the risk of developing type 2 diabetes : Systematic review and findings from European Prospective Investigation into Cancer (EPIC)-InterAct

Background: Gene-diet interactions have been reported to contribute to the development of type 2 diabetes (T2D). However, to our knowledge, few examples have been consistently replicated to date. Objective: We aimed to identify existing evidence for genemacronutrient interactions and T2D and to examine the reported interactions in a large-scale study. Design: We systematically reviewed studies rep

Comparison of citrated and fresh whole blood for viscoelastic coagulation testing during elective neurosurgery

Background Previous viscoelastic haemostatic tests studies have often indicated a hypercoagulative test signal with citrated blood, which could influence clinical decision makings. Purpose The aim of this study was to compare fresh and citrated whole blood using two non-automated viscoelastic ROTEM and Sonoclot tests. Our hypothesis was that citrated blood would demonstrate a hypercoagulative resp