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Objectives: low vitamin D during pregnancy is common and could adversely affect health outcomes. This study evaluated vitamin D status during pregnancy and early in life, and its association with glucose metabolism. Methods: maternal serum 25(OH)D, glucose, and insulin levels were measured longitudinally during pregnancy in Hispanic women with overweight/ obesity (n = 31) and their infants at birt

Inhibition of iduronic acid biosynthesis by ebselen reduces glycosaminoglycan accumulation in mucopolysaccharidosis type I fibroblasts

Mucopolysaccharidosis type I (MPS-I) is a rare lysosomal storage disorder caused by deficiency of the enzyme alpha-L-iduronidase, which removes iduronic acid in both chondroitin/dermatan sulfate (CS/DS) and heparan sulfate (HS) and thereby contributes to the catabolism of glycosaminoglycans (GAGs). To ameliorate this genetic defect, the patients are currently treated by enzyme replacement and bone

Ageing in the right place – the development of a web-based housing counselling intervention

Introduction: Despite a strong wish of most seniors to age in place, no services exist to support seniors in their residential reasoning, i.e., to plan and prepare for future housing needs. The aim of this study was to describe the first steps of development of a web-based housing counseling intervention aiming to promote active ageing.Material & Methods: A user-centered design process was app

Predicting sensitivity and resilience to modifiable risk factors for cardiometabolic morbidity and mortality

Background Lifestyle exposures play a major role in the development of disease, yet people vary in their susceptibility. A critical step towards precision medicine is identifying individuals who are resilient or sensitive to the environment, and, assess whether the allocation to these predicted groups are more or less likely to develop cardiometabolic disease.Methods We have used repeated data fro

Environment-wide association study (EWAS) on cardiometabolic traits: A systematic assessment of the association of lifestyle variables on a longitudinal setting

The present study aims to assess the over-time association of ∼300 lifestyle exposures with nine cardiometabolic traits with the ultimate aim of identifying exposures/exposure groups that could inform lifestyle interventions aiming at controlling cardiometabolic diseases. The analyses were undertaken in a longitudinal sample comprising >31000 adults living in northern Sweden. Linear mixed models w

CRISPR editing of the PPARGC1A Gly482ser (rs8192678) polymorphism in human white adipose cells shows differential effects on mitochondrial function and adipogenesis.

Background and aims: PPARGC1A encodes PGC-1α (peroxisome proliferator-activated receptor γ coactivator 1-α), a central regulator of energy metabolism and mitochondrial function. A common polymorphism in PPARGC1A (rs8192678, C/T, Gly482Ser) has been associated with obesity and related metabolic disorders, but no published functional studies have investigated direct allele-specific effects in adipoc

Diet and lifestyle behaviour disruption related to the pandemic was varied and bidirectional among US and UK adults participating in the ZOE COVID Study

Evidence of the impact of the COVID-19 pandemic on health behaviours in the general population is limited. In this retrospective longitudinal study including UK and US participants, we collected diet and lifestyle data pre-pandemic (896,286) and peri-pandemic (291,871) using a mobile health app, and we computed a bidirectional health behaviour disruption index. Disruption of health behaviour was h

Quantitative proteomic characterization of the lung extracellular matrix in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis

Remodeling of the extracellular matrix (ECM) is a common feature in lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Here, we applied a sequential tissue extraction strategy to describe disease-specific remodeling of human lung tissue in disease, using end-stages of COPD and IPF. Our strategy was based on quantitative comparison of the dis

A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions i

Temporal trend and regional disparity in osteoarthritis hospitalisations in Sweden 1998-2015

AIM: This study investigated time trend and regional disparities in hospitalisations due to osteoarthritis (OA) among people aged ≥20 years in Sweden from 1998 through 2015.METHODS: National and regional data on hospital admissions with a primary diagnosis of OA were collected from the National Patient Register. The absolute and relative regional disparities were assessed using the absolute weight

Sick Leave After Surgery for Thumb Carpometacarpal Osteoarthritis : A Population-Based Study

Purpose: Patients undergoing surgery for thumb carpometacarpal (CMC1) osteoarthritis often require sick leave owing to postoperative immobilization, pain, and decreased function. Our goal was to evaluate the amount of sick leave after surgery for 2 common CMC1 arthroplasty procedures. Methods: Using registry data from the Skåne region of southern Sweden, cross-linked with employment data showing p

Understanding the wicked problem of providing accessible housing for the ageing population in Sweden

While accessible housing is known as important to promote healthy ageing, the societal issue of providing accessible housing for the ageing population bears the characteristics of a “wicked problem”. The aim of this study was to gain a better understanding of crucial variables for decision-making about the provision of accessible housing for the ageing population in Sweden. Materials used for a de

The black box of regional growth

Regional growth models leave a large share of variation unexplained. While we should continuously aim to improve these models, the unique combination of conditions and human agency in each region will also invariably lead to region-specific growth trajectories. Theoretically, we should thus expect systematic deviations from growth predictions. We propose an approach to explore these unexplained de

Processes Underlying Glycemic Deterioration in Type 2 Diabetes : An IMI DIRECT Study

OBJECTIVE: We investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: A total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), β-cell glucose sensiti

Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals

The gut microbiome is shaped by diet and influences host metabolism; however, these links are complex and can be unique to each individual. We performed deep metagenomic sequencing of 1,203 gut microbiomes from 1,098 individuals enrolled in the Personalised Responses to Dietary Composition Trial (PREDICT 1) study, whose detailed long-term diet information, as well as hundreds of fasting and same-m

Multi-ancestry genome-wide gene–smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids

The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene–smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci assoc

Educational inequalities in all-cause and cause-specific mortality among people with gout : a register-based matched cohort study in southern Sweden

BACKGROUND: Gout is the most common inflammatory arthritis with a rising prevalence around the globe. While educational inequalities in incidence and prevalence of gout have been reported, no previous study investigated educational inequality in mortality among people with gout. The aim of this study was to assess absolute and relative educational inequalities in all-cause and cause-specific morta

Matrix metalloproteinase landscape in the imiquimod-induced skin inflammation mouse model

Inflammation and autoimmunity are known as central processes in many skin diseases, including psoriasis. It is therefore important to develop pre-clinical models that describe disease-related aspects to enable testing of pharmaceutical drug candidates and formulations. A widely accepted pre-clinical model of psoriasis is the imiquimod (IMQ)-induced skin inflammation mouse model, where topically ap

PDE5 inhibition mitigates heart failure in hyperlipidemia

PDE5 inhibitors was reported to play a protective role in both regulating lipid metabolism and reducing heart failure (HF). This study aimed to clarify the effectiveness of PDE5 inhibitors against hyperlipidemia-related HF by combining evidence from population-based study and animal models. The nationwide cohort study found that post-diagnostic use of PDE5 inhibitors was associated with a signific