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A hypothesis for insulin resistance in primary human adipocytes involving MRTF-A and suppression of PPARγ

Obesity is the main risk factor behind insulin resistance and type 2 diabetes. Still, the mechanism behind adipocyte dysfunction is not yet resolved. Recently, we reported that rapid actin remodeling correlates with adipose cell size changes after short-term overfeeding. Therefore, we hypothesized that the actin-driven myocardin-related transcription factor (MRTF-A) contributes to impaired mature

Protective functions of ZO-2/Tjp2 expressed in hepatocytes and cholangiocytes against liver injury and cholestasis

BACKGROUND & AIMS: Liver tight junctions (TJs) establish tissue barriers that isolate bile from the blood circulation. TJP2/ZO-2-inactivating mutations cause progressive cholestatic liver disease in humans. Since the underlying mechanisms remain elusive, we characterized mice with liver-specific inactivation of Tjp2.METHODS: Tjp2 was deleted in hepatocytes, cholangiocytes, or both. Effects on

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

Vasoactive Biomarkers Associated With Long-Term Incidence of Symptomatic Peripheral Arterial Disease and Mortality

We evaluated if plasma biomarkers can predict incident peripheral arterial disease (PAD) and mortality in a longitudinal cohort study. Men (n = 3618) and women (n = 1542) were included in the Malmö Preventive Project and underwent analysis of: C-terminal endothelin-1 (CT-proET-1), N-Terminal prosomatostatin (NT-proSST), midregional proatrial natriuretic peptide (MR-proANP), procalcitonin (PCT), an

The bacterial microbiota in first-void urine from men with and without idiopathic urethritis

BACKGROUND: Non-gonococcal urethritis (NGU) is a common syndrome in men. NGU may have several causes, but many cases are caused by sexually transmitted infections that may also cause complications in their female partners. Chlamydia trachomatis and Mycoplasma genitalium are the most common causes of NGU, but in up to 35% of the cases, none of the known viral or bacterial causes are found. Traditio

Glucocorticoid-induced tumour necrosis factor receptor family-related protein (GITR) drives atherosclerosis in mice and is associated with an unstable plaque phenotype and cerebrovascular events in humans

AIMS: GITR-a co-stimulatory immune checkpoint protein-is known for both its activating and regulating effects on T-cells. As atherosclerosis bears features of chronic inflammation and autoimmunity, we investigated the relevance of GITR in cardiovascular disease (CVD). METHODS AND RESULTS: GITR expression was elevated in carotid endarterectomy specimens obtained from patients with cerebrovascular e

Calculating the Starting Age for Screening in Relatives of Patients With Colorectal Cancer Based on Data From Large Nationwide Data Sets

BACKGROUND & AIMS: Although colorectal cancer (CRC) screening guidelines acknowledge the need for earlier screening for high-risk individuals, such as those with family history of CRC, there is limited information on how many years earlier these high-risk individuals should be screened; current practice is based on weak evidence. We aimed to provide risk-adapted recommendations on the starting

Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and e

Replacement of Red and Processed Meat With Other Food Sources of Protein and the Risk of Type 2 Diabetes in European Populations : The EPIC-InterAct Study

OBJECTIVE: There is sparse evidence for the association of suitable food substitutions for red and processed meat on the risk of type 2 diabetes. We modeled the association between replacing red and processed meat with other protein sources and the risk of type 2 diabetes and estimated its population impact.RESEARCH DESIGN AND METHODS: The European Prospective Investigation into Cancer (EPIC)-Inte

Farmland birds occupying forest clear-cuts respond to both local and landscape features

Agricultural landscapes have changed fast in Europe, which has led to steep declines in farmland biodiversity. While this has differentially impacted “farmland species”, some of these seem to be able to use alternative man-made open habitats in forests, such as forest clear-cuts and powerline rights-of-way. We investigated the use of clear-cuts by two historically declining farmland birds, the Yel

Management of oxytocin for labour augmentation in relation to mode of birth in Robson group 1

Objective: To compare mode of birth in Robson group 1 according to administration of oxytocin for labour augmentation. Design and participants: A retrospective review of 724 medical records from women in Robson group 1 was performed. The outcome measurements were: mode of birth in relation to presence of labour dystocia when initiating augmentation with oxytocin, duration of augmentation with oxyt

Validation of the Skåne University Hospital nomogram for the preoperative prediction of a disease-free axilla in patients with breast cancer

BACKGROUND: Axillary staging via sentinel lymph node biopsy (SLNB) is performed for clinically node-negative (N0) breast cancer patients. The Skåne University Hospital (SUS) nomogram was developed to assess the possibility of omitting SLNB for patients with a low risk of nodal metastasis. Area under the receiver operating characteristic curve (AUC) was 0.74. The aim was to validate the SUS nomogra

Factors associated with serum ferritin levels and iron excess : results from the EPIC-EurGast study

Purpose: Excess iron is involved in the development of non-communicable diseases such as cancer, type 2 diabetes and cardiovascular conditions. We aimed to describe the prevalence of excess iron and its determinants in healthy European adults. Methods: Sociodemographic, lifestyle, iron status, dietary information, and HFE genotyping were obtained from controls from the nested case–control study EP

Rare coding variants in 35 genes associate with circulating lipid levels—A multi-ancestry analysis of 170,000 exomes

Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African,

Investigating the causal relationships between excess adiposity and cardiometabolic health in men and women

AIMS/HYPOTHESIS: Excess adiposity is differentially associated with increased risk of cardiometabolic disease in men and women, according to observational studies. Causal inference studies largely assume a linear relationship between BMI and cardiometabolic outcomes, which may not be the case. In this study, we investigated the shapes of the causal relationships between BMI and cardiometabolic dis

Dietary Intake of 91 Individual Polyphenols and 5-Year Body Weight Change in the EPIC-PANACEA Cohort

Polyphenols are bioactive compounds from plants with antioxidant properties that may have a protective role against body weight gain, with adipose tissue and systemic oxidative stress as potential targets. We aimed to investigate the dietary intake of individual polyphenols and their association with 5-year body weight change in a sub-cohort of the European Prospective Investigation into Cancer an