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High levels of cystatin C predict the metabolic syndrome: the prospective Malmö Diet and Cancer Study.

OBJECTIVE: Cystatin C is a novel marker of cardiovascular disease (CVD), however the underlying mechanisms remain unclear. Here, we prospectively investigated whether plasma levels of cystatin C predict new-onset metabolic syndrome (MetS) as well as long-term progression and incidence of the different components of the MetS. METHODS: Cystatin C was measured in 1502 individuals included in the Malm

Androgen receptor polymorphism dependent variation in prostate specific antigen concentrations of European men.

Background Androgens acting via the androgen receptor (AR) stimulate production of prostate specific antigen (PSA), which is a clinical marker of prostate cancer (PCa). Since genetic variants in the AR may have a significant impact on the risk of being diagnosed with PCa, the aim was to investigate if AR-variants were associated with the risk of having PSA above clinically used cut-off thresholds

Secreted frizzled-related protein 4 reduces insulin secretion and is overexpressed in type 2 diabetes.

A plethora of candidate genes have been identified for complex polygenic disorders, but the underlying disease mechanisms remain largely unknown. We explored the pathophysiology of type 2 diabetes (T2D) by analyzing global gene expression in human pancreatic islets. A group of coexpressed genes (module), enriched for interleukin-1-related genes, was associated with T2D and reduced insulin secretio

Cancer risk in patients with type 2 diabetes mellitus and their relatives.

Epidemiological studies indicate that risks of certain cancers are increased in individuals hospitalized for type 2 diabetes mellitus (T2DM), which may not be representative of the entire population of T2DM patients as most of them are treated in primary health cares. To examine the subsequent cancer risk in individuals with T2DM from hospitals and primary health cares, and in their siblings and s

Alcohol Consumption Has a Protective Effect against Hematological Malignancies: a Population-Based Study in Sweden Including 420,489 Individuals with Alcohol Use Disorders.

It has been suggested that alcohol consumption is associated with increased risk of a few solid cancers, although studies that examined the association with hematological malignancies have shown inconsistent results. In this study, we examined the risk of hematological malignancies among individuals who had alcohol use disorders (AUDs) in Sweden.

REST mediates androgen receptor actions on gene repression and predicts early recurrence of prostate cancer.

The androgen receptor (AR) is a key regulator of prostate tumorgenesis through actions that are not fully understood. We identified the repressor element (RE)-1 silencing transcription factor (REST) as a mediator of AR actions on gene repression. Chromatin immunoprecipitation showed that AR binds chromatin regions containing well-characterized cis-elements known to mediate REST transcriptional rep

Association of tamoxifen with meningioma: a population-based study in Sweden.

Previous studies suggest that hormone therapy may play an important role in the development of meningioma. However, it is unclear whether medication with tamoxifen can prevent meningioma. Our study cohort included all women who were diagnosed with breast cancer between 1961 and 2010, and a total of 227 535 women were identified with breast cancer with a median age at diagnosis of 63 years. Women d

Variability in the CIITA gene interacts with HLA in multiple sclerosis.

The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and typ

Risk of breast cancer among patients with bioprosthetic or mechanical valve replacement: a population-based study in Sweden.

The association between breast cancer and warfarin is inconclusive as most previous studies examined their association using patients with thromboembolism, whereas thromboembolism itself is a risk factor for cancer. We explored this issue using patients received mechanical heart valves replacement as a proxy for warfarin exposure as these patients need a lifelong warfarin treatment, and compared t

Prediction of Blood Pressure Changes Over Time and Incidence of Hypertension by a Genetic Risk Score in Swedes.

Recent Genome-Wide Association Studies (GWAS) have pinpointed different single nucleotide polymorphisms consistently associated with blood pressure (BP) and hypertension prevalence. However, little data exist regarding single nucleotide polymorphisms predicting BP variation over time and hypertension incidence. The aim of this study was to confirm the association of a genetic risk score (GRS), bas

Outcome of Ischemic Foot Ulcer in Diabetic Patients Who Had no Invasive Vascular Intervention.

OBJECTIVE/BACKGROUND: There is limited information regarding outcome in patients not available for revascularisation. Our aim was to identify factors related to ulcer healing in diabetic patients with severe peripheral arterial disease who were not available for revascularisation. METHODS: Diabetic patients with a foot ulcer, consecutively presenting at a multidisciplinary foot centre with systoli

High Plasma Levels of Heparin-Binding Epidermal Growth Factor Are Associated With a More Stable Plaque Phenotype and Reduced Incidence of Coronary Events.

Rupture of atherosclerotic plaques is the major cause of acute coronary events (CEs). Plaque destabilization is the consequence of an imbalance between inflammatory-driven degradation of fibrous tissue and smooth muscle cell-dependent tissue repair. Proinflammatory factors have been documented extensively as biomarkers of cardiovascular risk but factors that contribute to stabilization of atherosc

Lactose intolerance and risk of lung, breast and ovarian cancers: aetiological clues from a population-based study in Sweden.

Background:Individuals with lactose intolerance are recommended to avoid milk or dairy products, which may affect the development of cancer.Methods:We identified individuals with lactose intolerance from several Swedish Registers linked to the Swedish Cancer Registry to calculate standardised incidence ratios (SIRs) for cancers in the breast, lung, and ovary.Results:A total of 22 788 individuals w

Cancer risk and mortality in asthma patients: A Swedish national cohort study.

Background. Previous studies found an increased risk of cancer in hospitalized asthma patients, but it is not known whether patients from primary health care show a similar risk pattern. In addition, it is unclear whether the diagnosis of asthma can influence the prognosis of subsequent cancer. Methods. Asthma patients were identified from Swedish inpatient, outpatient, and primary health care reg

Analytical Validation of the Automated Bone Scan Index as an Imaging Biomarker to Standardize the Quantitative Changes in Bone Scans of Patients with Metastatic Prostate Cancer.

A reproducible and quantitative imaging biomarker to standardize the evaluation of changes in bone scans is an unmet need for prostate cancer patients with skeletal metastasis. Here we have performed a series of analytical validation studies to evaluate the performance of the automated Bone Scan Index (BSI) as an imaging biomarker in patients with metastatic prostate cancer (mPCa).

Stem cell-based therapy for malignant glioma.

Stem cells have been extensively investigated as tumour-tropic vectors for gene delivery to solid tumours. In this review, we discuss the potential for using stem cells as cellular vector systems in gene therapy for malignant gliomas, with a focus on neural stem cells, and multipotent mesenchymal stromal cells. Tumour cell-derived substances and factors associated with tumour-induced inflammation

Inhibition of Microglial Activation Protects Hippocampal Neurogenesis and Improves Cognitive Deficits in a Transgenic Mouse Model for Alzheimer's Disease

Background: Activated microglia with macrophage-like functions invade and surround beta-amyloid (A beta) plaques in Alzheimer's disease (AD), possibly contributing to the turnover of A beta, but they can also secrete proinflammatory factors that may be involved in the pathogenesis of AD. Microglia are known to modulate adult hippocampal neurogenesis. Objectives/Methods: To determine the role of mi