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Coordinate changes in histone modifications, mRNA levels and metabolite profiles in clonal INS-1 832/13 β-cells accompany functional adaptations to lipotoxicity.

Lipotoxicity is a presumed pathogenetic process whereby elevated circulating and stored lipids in Type 2 Diabetes cause pancreatic β-cell failure. To resolve the underlying molecular mechanisms, we exposed clonal INS-1 832/13 β-cells to palmitate for 48 h. We observed elevated basal insulin secretion but impaired glucose-stimulated insulin secretion in palmitate-exposed cells. Glucose utilization

Age-Related Clonal Hematopoiesis Associated with Adverse Outcomes.

Background The incidence of hematologic cancers increases with age. These cancers are associated with recurrent somatic mutations in specific genes. We hypothesized that such mutations would be detectable in the blood of some persons who are not known to have hematologic disorders. Methods We analyzed whole-exome sequencing data from DNA in the peripheral-blood cells of 17,182 persons who were uns

Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies

Background Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. Methods In a collaborative met

Low back pain - epidemiology of consultations.

OBJECTIVES: Low back pain (LBP) affects most people at some stage in life. However, the burden on the health care system is unclear. We studied: 1) the one-year consultation prevalence 2) the rate of first-time consultation for LBP and related the frequency to other musculoskeletal conditions and 3) the health care utilization of LBP patients compared to the general population. METHODS: Using th

Association of the Charlson Comorbidity Index With Mortality in Systemic Lupus Erythematosus

Objective. To investigate whether comorbidity as assessed by the Charlson Comorbidity Index (CCI) is associated with mortality in a long-term followup of systemic lupus erythematosus (SLE) patients. Methods. Data were collected from 499 SLE patients attending the Lupus Clinic at the McGill University Health Center, Montreal, Quebec, Canada, and 170 SLE patients from the Department of Rheumatology

Evidence that BMI and type 2 diabetes share only a minor fraction of genetic variance: a follow-up study of 23,585 monozygotic and dizygotic twins from the Finnish Twin Cohort Study

We investigated whether BMI predicts type 2 diabetes in twins and to what extent that is explained by common genetic factors. This was a population-based twin cohort study. Monozygotic (n = 4,076) and dizygotic (n = 9,109) non-diabetic twin pairs born before 1958 answered a questionnaire in 1975, from which BMI was obtained. Information on incident cases of diabetes was obtained by linkage to nati

Probiotic therapy to men with incipient arteriosclerosis initiates increased bacterial diversity in colon: A randomized controlled trial.

OBJECTIVE: This study aimed to clarify the microbial change in the intestinal microbiota in patients, with cardiovascular disease, consuming a drink with high numbers of live Lactobacillus plantarum. METHODS: Sixteen males, with atherosclerotic plaque on the carotid wall, were randomly selected from a larger cohort and included in this double blind, placebo controlled study. Colonic biopsies, take

Women pioneers in basal ganglia surgery

Background: Stereotactic functional neurosurgery on basal ganglia has a long history and the pioneers are mostly men. We aimed at finding out if there were women who have contributed pioneering work in this field. Methods: The literature was searched to identify women who have been first to publish innovative papers related to human basal ganglia surgery. Results: Six women fulfilling our criteria

Methods, quality control and specimen management in an international multicentre investigation of type 1 diabetes: TEDDY

BackgroundThe vast array and quantity of longitudinal samples collected in The Environmental Determinants of Diabetes in the Young study present a series of challenges in terms of quality control procedures and data validity. To address this, pilot studies have been conducted to standardize and enhance both biospecimen collection and sample obtainment in terms of autoantibody collection, stool sam

Synergism by individual macronutrients explains the marked early GLP-1 and islet hormone responses to mixed meal challenge in mice.

Apart from glucose, proteins and lipids also stimulate incretin and islet hormone secretion. However, the glucoregulatory effect of macronutrients in combination is poorly understood. We therefore developed an oral mixed meal model in mice to 1) explore the glucagon-like peptide-1 (GLP-1) and islet hormone responses to mixed meal versus isocaloric glucose, and 2) characterize the relative contribu

Association of cigarette smoking with organ damage in primary systemic vasculitis.

Objectives: To study the association between late organ damage in patients with primary systemic vasculitis (PSV) and cigarette smoking. PSV included Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS), and polyarteritis nodosa (PAN). Methods: The pattern and extent of organ damage according to the Vasculitis Damage Index (VDI) were analysed for 86 prevalent

Synapsins I and II Are Not Required for Insulin Secretion from Mouse Pancreatic beta-cells

Synapsins are a family of phosphoproteins that modulate the release of neurotransmitters from synaptic vesicles. The release of insulin from pancreatic beta-cells has also been suggested to be regulated by synapsins. In this study, we have utilized a knock out mouse model with general disruptions of the synapsin I and II genes [synapsin double knockout (DKO)]. Stimulation with 20 mM glucose increa

Alterations in bile acid synthesis in carriers of HNF1α mutations.

OBJECTIVES: Heterozygous mutations in hepatocyte nuclear factor 1α (HNF1α) cause maturity onset diabetes of the young 3 (MODY3), an autosomal dominant form of diabetes. Deficiency of HNF1α in mice results in diabetes, hypercholesterolaemia and increased bile acid (BA) and cholesterol synthesis. Little is known about alterations in lipid metabolism in patients with MODY3. The aim of this study was

Physical Activity and Mortality in Individuals With Diabetes Mellitus A Prospective Study and Meta-analysis

Background: Physical activity (PA) is considered a cornerstone of diabetes mellitus management to prevent complications, but conclusive evidence is lacking. Methods: This prospective cohort study and meta-analysis of existing studies investigated the association between PA and mortality in individuals with diabetes. In the EPIC study (European Prospective Investigation Into Cancer and Nutrition),

Intrapartum cardiotocography (CTG) and ST-analysis of labor in diabetic patients

Aim: To determine the prevalence and types of intrapartum cardiotocography (CTG) patterns and investigate their relationship to moderate acidemia in term fetuses of diabetic mothers. Also, to assess if the combination of fetal electrocardiogram (FECG) and those CTG patterns strengthens the association with moderate acidemia. Material and methods: The material for this study is obtained from the Sw

Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency.

Objective: The objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency. Design: Randomized, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university c

Challenges in estimating the validity of dietary acrylamide measurements

Acrylamide is a chemical compound present in tobacco smoke and food, classified as a probable human carcinogen and a known human neurotoxin. Acrylamide is formed in foods, typically carbohydrate-rich and protein-poor plant foods, during high-temperature cooking or other thermal processing. The objectives of this study were to compare dietary estimates of acrylamide from questionnaires (DQ) and 24-