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Epigenetic markers associated with metformin response and intolerance in drug-naïve patients with type 2 diabetes

Metformin is the first-line pharmacotherapy for managing type 2 diabetes (T2D). However, many patients with T2D do not respond to or tolerate metformin well. Currently, there are no phenotypes that successfully predict glycemic response to, or tolerance of, metformin. We explored whether blood-based epigenetic markers could discriminate metformin response and tolerance by analyzing genome-wide DNA

Novel Methods for the Quantification of Dipeptidyl Peptidase 3 (DPP3) Concentration and Activity in Human Blood Samples

BACKGROUND: The ubiquitously expressed dipeptidyl peptidase 3 (DPP3) is involved in protein metabolism, blood pressure regulation, and pain modulation. These diverse functions of DPP3 are attributed to the degradation of bioactive peptides like angiotensin II. However, because of limitations in currently available assays for determination of active DPP3 in plasma, the exact physiological function

Antibodies against apoB100 peptide 210 inhibit atherosclerosis in apoE-/- mice

Atherosclerotic plaques are characterized by an accumulation and subsequent oxidation of LDL, resulting in adaptive immune responses against formed or exposed neoepitopes of the LDL particle. Autoantibodies against native p210, the 3136–3155 amino acid sequence of the LDL protein apolipoprotein B-100 (apoB100) are common in humans and have been associated with less severe atherosclerosis and decre

Effect of AMY1 copy number variation and various doses of starch intake on glucose homeostasis : data from a cross-sectional observational study and a crossover meal study

BACKGROUND: Copy number (CN) variation (CNV) of the salivary amylase gene (AMY1) influences the ability to digest starch and may influence glucose homeostasis, obesity and gut microbiota composition. Hence, the aim was to examine the association of AMY1 CNV with fasting glucose, BMI, and gut microbiota composition considering habitual starch intake and to investigate the effect of AMY1 CNV on the

Contrast-Associated Acute Kidney Injury in Patients with and without Diabetes Mellitus Undergoing Computed Tomography Angiography and Local Thrombolysis for Acute Lower Limb Ischemia

Repetitive iodinated contrast media exposure may be harmful for the kidneys. The aim of the present study was to evaluate if patients with diabetes mellitus (DM) undergoing CT angiography (CTA) and local continuous thrombolysis for acute lower limb ischemia (ALI) had an increased risk of developing contrast-associated acute kidney injury (CA-AKI) compared to patients without DM. Methods: This is a

Soft Drink and Juice Consumption and Renal Cell Carcinoma Incidence and Mortality in the European Prospective Investigation into Cancer and Nutrition

BACKGROUND: Renal cell carcinoma (RCC) accounts for more than 80% of kidney cancers in adults, and obesity is a known risk factor. Regular consumption of sweetened beverages has been linked to obesity and several chronic diseases, including some types of cancer. It is uncertain whether soft drink and juice consumption is associated with risk of RCC. We investigated the associations of soft drink a

Association between sugar intake and intima media thickness as a marker for atherosclerosis : A cross-sectional study in the Malmö diet and cancer study (Sweden)

It has been suggested that sugar intake may play a role in the development of atherosclero-sis. However, studies on this matter are lacking. Intima media thickness (IMT) is a well-established measurement of subclinical atherosclerosis. This study aimed to investigate the cross-sectional association between sugar intake (i.e., added, free and total sugar and sugar-rich foods and beverages) and IMT.

Bioactive adrenomedullin a prognostic biomarker in patients with mild to moderate dyspnea at the emergency department : an observational study

Acute dyspnea with underlying congestion is a leading cause of emergency department (ED) visits with high rates of hospitalization. Adrenomedullin is a vasoactive neuropeptide hormone secreted by the endothelium that mediates vasodilation and maintains vascular integrity. Plasma levels of biologically active adrenomedullin (bio-ADM) predict septic shock and vasopressor need in critically ill patie

Associations between biomarkers of multimorbidity burden and mortality risk among patients with acute dyspnea

The patients’ burden of comorbidities is a cornerstone in risk assessment, clinical management and follow-up. The aim of this study was to evaluate if biomarkers associated with comorbidity burden can predict outcome in acute dyspnea patients. We included 774 patients with dyspnea admitted to an emergency department and measured 80 cardiovascular protein biomarkers in serum collected at admission.

Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline

Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to

Power Dynamics in Barnahus Collaboration

Barnahus collaboration spans different regulatory fields and brings together conflicting logics, creating an institutional tension between justice and welfare. In this chapter, collaboration in Swedish Barnahus is analysed in a critical manner, drawing on institutional theory and a three-dimensional concept of power. The complex institutional power dynamics evolving in Barnahus collaboration are iBarnahus collaboration spans different regulatory fields and brings together conflicting logics, creating an institutional tension between justice and welfare. In this chapter, collaboration in Swedish Barnahus is analysed in a critical manner, drawing on institutional theory and a three-dimensional concept of power. The complex institutional power dynamics evolving in Barnahus collaboration are i

Treatment with the WNT5A-mimicking peptide Foxy-5 effectively reduces the metastatic spread of WNT5A-low prostate cancer cells in an orthotopic mouse model

Prostate cancer patients with high WNT5A expression in their tumors have been shown to have more favorable prognosis than those with low WNT5A expression. This suggests that reconstitution of Wnt5a in low WNT5A-expressing tumors might be an attractive therapeutic approach. To explore this idea, we have in the present study used Foxy-5, a WNT5A mimicking peptide, to investigate its impact on primar

Association analysis identifies 65 new breast cancer risk loci

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of

Incident diabetes mellitus may explain the association between sleep duration and incident coronary heart disease

Aims/hypothesis: Sleep duration is a risk factor for incident diabetes mellitus and CHD. The primary aim of the present study was to investigate, in sex-specific analyses, the role of incident diabetes as the possible biological mechanism for the reported association between short/long sleep duration and incident CHD. Considering that diabetes is a major risk factor for CHD, we hypothesised that a

Obesity, metabolic factors and risk of different histological types of lung cancer : A Mendelian randomization study

BACKGROUND: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer.METHODS AND FINDINGS: We identified genetic instruments for potential metabolic risk factors and eval

Midlife risk factor exposure and incidence of cardiac arrest depending on cardiac or non-cardiac origin

Objective: Little is known about midlife risk factors of future cardiac arrest. Our objective was to evaluate cardiovascular risk factors in midlife in relation to the risk of cardiac arrest (CA) of cardiac and non-cardiac origin later in life. Methods: We cross-matched individuals of the population based Malmö Diet and Cancer study (n = 30,447) with the local CA registry of the city of Malmö. Bas

Association between fat intake, physical activity and mortality depending on genetic variation in FTO.

Objective:We wanted to explore if FTO genotype interacts with fat intake, or leisure-time physical activity, on fat mass, lean mass and mortality.Subjects and methods:Among 22 799 individuals (44-74 years) in the population-based Malmö diet and cancer cohort that were genotyped for rs9939609 in FTO and had information on dietary intake (from a modified diet history method) and no history of diabet