132 results match your criteria: "Centre for Individualized Medicine[Affiliation]"

The Nonsyndromic Ascending Thoracic Aorta in a Population-Based Setting: A 5-Year Prospective Cohort Study.

J Am Coll Cardiol

November 2024

Elite Centre for Individualized Medicine in Arterial Disease, Odense University Hospital, Odense, Denmark; Department of Cardiothoracic and Vascular Surgery, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

Background: Prospective data on the clinical course of the ascending thoracic aorta are lacking.

Objectives: This study sought to estimate growth rates of the ascending aorta and to evaluate occurrences of adverse aortic events (AAEs)-that is, thoracic aortic ruptures, type A aortic dissections, and thoracic aortic-related deaths.

Methods: In this prospective cohort study from the population-based, multicenter, randomized DANCAVAS (Danish Cardiovascular Screening trials) I and II, participants underwent cardiovascular risk assessments including electrocardiogram-gated, noncontrast computed tomography (CT) scans.

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Article Synopsis
  • The study compares the effectiveness of the CAC-score and 19 biomarkers in predicting cardiovascular disease (CVD) risk, suggesting the CAC-score adds value beyond traditional risk factors.
  • Researchers collected data from 1211 participants and tracked cardiovascular events over 10 years, finding a significant association between higher CAC-scores and increased risk of CVD events.
  • While the CAC-score improved risk prediction significantly, the selected biomarkers (like cholesterol and inflammatory markers) did not enhance the predictive capacity for cardiovascular events.
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Background: Pregnancy-associated plasma protein-A (PAPP-A) regulates bioavailability of insulin-like growth factor 1 (IGF1) in various tissues by proteolytic cleavage of a subset of IGF-binding proteins (IGFBPs). Pre-clinical studies have established a role of PAPP-A in atherosclerosis and proposed that targeting the proteolytic activity of PAPP-A has therapeutic value.This study aimed to investigate whether human atherosclerotic plaques contain proteolytically active PAPP-A, a prerequisite for further considering PAPP-A as a therapeutic target in patients.

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Aims: Cellular communication network factor 2 (CCN2) is a matricellular protein implicated in fibrotic diseases, with ongoing clinical trials evaluating anti-CCN2-based therapies. By uncovering CCN2 as abundantly expressed in non-diseased artery tissue, this study aimed to investigate the hypothesis that CCN2 plays a pivotal role in maintaining smooth muscle cell (SMC) phenotype and protection against atherosclerosis.

Methods And Results: Global- and SMC-specific Ccn2 knockout mouse models were employed to demonstrate that Ccn2 deficiency leads to SMC de-differentiation, medial thickening, and aorta elongation under normolipidaemic conditions.

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Retinoblastoma (RB) is a rare ocular cancer seen in children that counts for approximately 3% of all childhood cancers. It is found that mutation in RB1, a tumour Suppressor Gene on chromosome 13 as the cause of malignancy. Retinoblastoma protein is the target for ceramide to cause apoptosis.

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Multi-OMICs landscape of SARS-CoV-2-induced host responses in human lung epithelial cells.

iScience

January 2023

Centre of Molecular Inflammation Research (CEMIR), and Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7491 Trondheim, Norway.

Article Synopsis
  • The COVID-19 pandemic remains a health issue due to new variants, leading to extensive multi-Omics research on how the virus interacts with hosts and possible therapeutic targets.
  • Our research on a lung-derived human cell line reveals that the SARS-CoV-2 Norway/Trondheim-S15 strain causes significant changes in immune responses and cellular processes over time.
  • We discovered that the dynamics of protein modifications, like phosphorylation and acetylation, impact the release of metabolites, indicating potential new directions for developing targeted treatments against SARS-CoV-2.
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14-fold increased prevalence of rare glucokinase gene variant carriers in unselected Danish patients with newly diagnosed type 2 diabetes.

Diabetes Res Clin Pract

December 2022

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address:

Aims: Rare variants in the glucokinase gene (GCK) cause Maturity-Onset Diabetes of the Young (MODY2/GCK-MODY). We investigated the prevalence of GCK variants, phenotypic characteristics, micro- and macrovascular disease at baseline and follow-up, and treatment among individuals with and without pathogenic GCK variants.

Methods: This is a cross-sectional study in a population-based cohort of 5,433 individuals without diabetes (Inter99 cohort) and in 2,855 patients with a new clinical diagnosis of type 2 diabetes (DD2 cohort) with sequencing of GCK.

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Tongue squamous cell carcinoma is an aggressive oral cancer with a high incidence of metastasis and poor prognosis. Most of the oral cavity cancer patients present in clinics with locally advanced unresectable tumors. Neoadjuvant treatment is beneficial for these individuals as it reduces the tumor size aiding complete resection.

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Background: Tumor necrosis factor (TNF) is pathologically elevated in human abdominal aortic aneurysms (AAA). Non-selective TNF inhibition-based therapeutics are approved for human use but have been linked to several side effects. Compounds that target the proinflammatory soluble form of TNF (solTNF) but preserve the immunomodulatory capabilities of the transmembrane form of TNF (tmTNF) may prevent these side effects.

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Objectives: Although ascending aortic diameter changes acutely after dissection, recommendation for prophylactic surgery of thoracic aortic aneurysms rely on data from dissected aortas. In this case-control study we aim to identify risk markers for acute and chronic aortic syndromes of the ascending aorta (ACAS-AA). Furthermore, to develop a predictive model for ACAS-AA.

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Atherosclerotic cardiovascular disease is the leading cause of death worldwide. For decades, mouse modeling of atherosclerosis has been the mainstay for preclinical testing of genetic and pharmacological intervention. Mouse models of atherosclerosis depend on supraphysiological levels of circulating cholesterol carried in lipoprotein particles.

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Background The aim of this study was to prospectively evaluate the effects of renal artery stenting in consecutive patients with severe atherosclerotic renal artery stenosis and high-risk clinical presentations as defined in a national protocol developed in 2015. Methods and Results Since the protocol was initiated, 102 patients have been referred for revascularization according to the following high-risk criteria: severe renal artery stenosis (≥70%) with true resistant hypertension, rapidly declining kidney function, or recurrent heart failure/sudden pulmonary edema. At baseline, the mean 24-hour ambulatory systolic blood pressure was 166.

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A recent study found that only 23.8% of blood pressure (BP) devices available for purchase from Australian pharmacies were validated for accuracy. The extent to which pharmacists are aware of this, and other issues related to the accuracy of BP devices, is not known and gathering this information was the aim of this study.

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The pathogenesis of abdominal aortic aneurysm involves vascular inflammation and elastin degradation. contains cycloastragenol, which is known to be anti-inflammatory and to protect against elastin degradation. We hypothesized that cycloastragenol supplementation inhibits abdominal aortic aneurysm progression.

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Epithelial-mesenchymal transition (EMT) is a dynamic and complex cellular process that is known to be hijacked by cancer cells to facilitate invasion, metastasis and therapeutic resistance. Several quantitative measures to assess the interplay between EMT and cancer progression are available, based on large scale genome and transcriptome data. However, these large scale multi-omics studies have repeatedly illustrated a lack of correlation in mRNA and protein abundances that may be influenced by diverse post-translational regulation.

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Suboptimal medication adherence is a major barrier to hypertension control in Kenya, especially among informal urban settlement areas (sometimes referred to as "slums"). The few studies that have specifically explored medication adherence among this population have received discordant results, implying that additional factors which influence medication adherence merit further investigation. This study explores the relationship between family support and medication adherence among people with hypertension in informal settlements in Nairobi, Kenya.

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Aim: To investigate the efficacy and safety of a non-calorie-restricted low-carbohydrate diet (LCD) on glycaemic control, body composition, and cardiovascular risk factors in patients with type 2 diabetes (T2D) instructed to maintain their non-insulin antidiabetic medication and physical activity.

Materials And Methods: In an open-label randomized controlled trial, patients with T2D were randomized 2:1 to either a LCD with a maximum of 20 E% (percentage of total energy intake) from carbohydrates (n = 49) or a control diet with 50-60 E% from carbohydrates (n = 22) for 6 months. Examinations at enrolment and after 3 and 6 months included blood sample analyses, anthropometrics, blood pressure, accelerometer-based assessment of physical activity, and food diaries.

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CD4 T-cell DNA methylation changes during pregnancy significantly correlate with disease-associated methylation changes in autoimmune diseases.

Epigenetics

September 2022

Department of Clinical Immunology and Transfusion Medicine and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Epigenetics may play a central, yet unexplored, role in the profound changes that the maternal immune system undergoes during pregnancy and could be involved in the pregnancy-induced modulation of several autoimmune diseases. We investigated changes in the methylome in isolated circulating CD4 T-cells in non-pregnant and pregnant women, during the 1 and 2 trimester, using the Illumina Infinium Human Methylation 450K array, and explored how these changes were related to autoimmune diseases that are known to be affected during pregnancy. Pregnancy was associated with several hundreds of methylation differences, particularly during the 2 trimester.

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Background: Basement membrane (BM) accumulation is a hallmark of micro-vessel disease in diabetes mellitus (DM). We previously reported marked upregulation of BM components in internal thoracic arteries (ITAs) from type 2 DM (T2DM) patients by mass spectrometry. Here, we first sought to determine if BM accumulation is a common feature of different arteries in T2DM, and second, to identify other effects of T2DM on the arterial proteome.

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Basement membrane collagen IV deficiency promotes abdominal aortic aneurysm formation.

Sci Rep

June 2021

Centre for Individualized Medicine in Artery Diseases, Odense University Hospital, J. B. Winsløws Vej 4, 5000, Odense C, Denmark.

Abdominal aortic aneurysm (AAA) is a complex disease which is incompletely accounted for. Basement membrane (BM) Collagen IV (COL4A1/A2) is abundant in the artery wall, and several lines of evidence indicate a protective role of baseline COL4A1/A2 in AAA development. Using Col4a1/a2 hemizygous knockout mice (Col4a1/a2, 129Svj background) we show that partial Col4a1/a2 deficiency augmented AAA formation.

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A crucial mutational mechanism in malignancy is structural variation, in which chromosomal rearrangements alter gene functions that drive cancer progression. Herein, the presence and pattern of structural variations were investigated in twelve prospectively acquired treatment-naïve pancreatic cancers specimens obtained via endoscopic ultrasound (EUS). In many patients, this diagnostic biopsy procedure and specimen is the only opportunity to identify somatic clinically relevant actionable alterations that may impact their care and outcome.

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Why and when to screen for cardiovascular disease in healthy individuals.

Heart

May 2021

Department of Cardiothoracic and Vascular Surgery, Odense University Hospital, Elitary Research Centre for Individualized Medicine in Arterial Disease (CIMA), University of Southern Denmark, Odense, Denmark.

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Introduction: As the only part of the human vasculature, the retina is available for direct, noninvasive inspection. Retinal vascular fractal dimension (DF) is a method to measure the structure of the retinal vascular tree, with higher noninteger values between 1 and 2 representing a more complex and dense retinal vasculature. Retinal vascular structure has been associated with a variety of systemic diseases, and this study examined the association of DF and macrovascular cardiac disease in a case-control design.

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Current guidelines recommend angiotensin receptor blocker neprilysin inhibitors (ARNI) (sacubitril/valsartan) as a replacement for angiotensin-converting-enzymeinhibitor (ACE-I) in heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal medical therapy. The effects of ARNIs have not previously been assessed in a systematic review. We searched for relevant trials until October 2019 in CENTRAL, MEDLINE, Embase, LILACS, BIOSIS, CNKI, VIP, WanFang and CBM.

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