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In vivo inhibition of nuclear factor of activated T-cells leads to atherosclerotic plaque regression in IGF-II/LDLR -/-ApoB100/100 mice

AIMS: Despite vast clinical experience linking diabetes and atherosclerosis, the molecular mechanisms leading to accelerated vascular damage are still unclear. Here, we investigated the effects of nuclear factor of activated T-cells inhibition on plaque burden in a novel mouse model of type 2 diabetes that better replicates human disease.METHODS & RESULTS: IGF-II/LDLR-/-ApoB100/100mice were ge

The genomic grade index predicts postoperative clinical outcome in patients with soft-tissue sarcoma

Background: Soft-tissue sarcomas (STSs) are a group of rare, heterogeneous, and aggressive tumors, with high metastatic risk and relatively few efficient systemic therapies. We hypothesized that the Genomic Grade Index (GGI), a 108-gene signature previously developed in early-stage breast cancer, might improve the prognostic assessment of patients with early-stage STS. Patients and methods: We col

Adiposity and genetic factors in relation to triglycerides and triglyceride-rich lipoproteins in the women's genome health study

BACKGROUND: Previous results from Scandinavian cohorts have shown that obesity accentuates the effects of common genetic susceptibility variants on increased triglycerides (TG). Whether such interactions are present in the US population and further selective for particular TG-rich lipoprotein subfractions is unknown. METHODS: We examined these questions using body mass index (BMI) and waist circum

Interaction of dietary and genetic factors influencing body iron status and risk of type 2 diabetes within the EPIC-InterAct study

OBJECTIVE Meat intake has been consistently shown to be positively associated with incident type 2 diabetes. Part of that association may be mediated by body iron status, which is influenced by genetic factors. We aimed to test for interactions of genetic and dietary factors influencing body iron status in relation to the risk of incident type 2 diabetes. RESEARCH DESIGN AND METHODS The case-cohor

Social constraints and psychological well-being after prostate cancer : A follow-up at 12 and 24 months after surgery

Objective: Studies indicate that social constraints (barriers to emotional expression) may be a risk factor for psychological morbidity. We aimed to investigate the association between prostate cancer–related social constraints and psychological well-being following prostate cancer surgery. Methods: In a group of 3478 partnered patients, participating in the Laparoscopic Prostatectomy Robot Open t

Probing the Virtual Proteome to Identify Novel Disease Biomarkers

BACKGROUND: Proteomic approaches allow measurement of thousands of proteins in a single specimen, which can accelerate biomarker discovery. However, applying these technologies to massive biobanks is not currently feasible because of the practical barriers and costs of implementing such assays at scale. To overcome these challenges, we used a "virtual proteomic" approach, linking genetically predi

Repairing the brain : Cell replacement using stem cell-based technologies

Current approaches to cell replacement therapy in Parkinson's disease are strongly focused on the dopamine system, with the view that restoring dopaminergic inputs in a localized and physiologic manner will provide superior benefits in terms of effect and longevity compared with oral medication. Experience using transplants of fetal tissue containing dopaminergic cell precursors has provided valua

Risk of Synchronous and Metachronous Colorectal Cancer : Population-Based Estimates in Denmark with Focus on Non-Hereditary Cases Diagnosed After Age 50

Background and Aims: The risk of synchronous and metachronous colorectal cancer is influenced by heritable and environmental factors. As a basis for comparative studies, we provide population-based estimates of synchronous and metachronous colorectal cancer with a focus on non-heritable cases. Material and Methods: Based on data from national Danish cancer registers, we estimated the proportion of

Prostate cancer risk-associated single-nucleotide polymorphism affects prostate-specific antigen glycosylation and its function

BACKGROUND: Genetic association studies have reported single-nucleotide polymorphisms (SNPs) at chromosome 19q13.3 to be associated with prostate cancer (PCa) risk. Recently, the rs61752561 SNP (Asp84Asn substitution) in exon 3 of the kallikrein-related peptidase 3 (KLK3) gene encoding prostate-specific antigen (PSA) was reported to be strongly associated with PCa risk (P 2.3 108). However, the bi

Long non-coding RNA in stem cell pluripotency and lineage commitment : functions and evolutionary conservation

LncRNAs have recently emerged as new and fundamental transcriptional and post-transcriptional regulators acting at multiple levels of gene expression. Indeed, lncRNAs participate in a wide variety of stem cell and developmental processes, acting in cis and/or in trans in the nuclear and/or in the cytoplasmic compartments, and generating an intricate network of interactions with RNAs, enhancers, an

Proteogenomic characterization of patient-derived xenografts highlights the role of REST in neuroendocrine differentiation of castration-resistant prostate cancer

Purpose: An increasing number of castration-resistant prostate cancer (CRPC) tumors exhibit neuroendocrine (NE) features. NE prostate cancer (NEPC) has poor prognosis, and its development is poorly understood. Experimental Design: We applied mass spectrometry–based proteomics to a unique set of 17 prostate cancer patient–derived xenografts (PDX) to characterize the effects of castration in vivo, a

Effects on the glucagon response to hypoglycaemia during DPP-4 inhibition in elderly subjects with type 2 diabetes : A randomized, placebo-controlled study

Aims: Maintainance of glucagon response to hypoglycaemia is important as a safeguard against hypoglycaemia during glucose-lowering therapy in type 2 diabetes. During recent years, DPP-4 (dipeptidyl peptidase-4) inhibition has become more commonly used in elderly patients. However, whether DPP-4 inhibition affects the glucagon response to hypoglycaemia in the elderly is not known and was the aim of

Value of Intact Prostate Specific Antigen and Human Kallikrein 2 in the 4 Kallikrein Predictive Model : An Individual Patient Data Meta-Analysis

Purpose: The 4 kallikrein panel, commercially available as the 4Kscore®, is a statistical model that has been shown to accurately predict Gleason Grade Group 2 or greater (high grade) cancer on biopsy and the long-term risk of distant prostate cancer metastases. The panel includes 2 novel markers, namely intact prostate specific antigen and hK2. It has been questioned whether these 2 additional ma

Abdominal obesity in type 1 diabetes associated with gender, cardiovascular risk factors and complications, and difficulties achieving treatment targets : A cross sectional study at a secondary care diabetes clinic

Background: Abdominal obesity is linked to cardiovascular diseases in type 1 diabetes (T1D). The primary aim was to explore associations between abdominal obesity and cardiovascular complications, metabolic and inflammatory factors. The secondary aim was to explore whether achieved recommended treatment targets differed between the obese and non-obese participants. Methods: Cross sectional study o

90-Day readmission after radical prostatectomy—a prospective comparison between robot-assisted and open surgery

Purpose: All types of surgery are associated with complications. The debate is ongoing whether robot-assisted radical prostatectomy can lower this risk compared to open surgery. The objective of the present study was to evaluate post-operative adverse events leading to readmissions, using clinical records to classify these adverse events systematically. Materials and methods: A prospective control

The association between weight at birth and breast cancer risk revisited using Mendelian randomisation

Observational studies suggest that higher birth weight (BW) is associated with increased risk of breast cancer in adult life. We conducted a two-sample Mendelian randomisation (MR) study to assess whether this association is causal. Sixty independent single nucleotide polymorphisms (SNPs) known to be associated at P < 5 × 10 −8 with BW were used to construct (1) a 41-SNP instrumental variable (IV