University of Southern Denmark

About: University of Southern Denmark is a education organization based out in Odense, Syddanmark, Denmark. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 11928 authors who have published 37918 publications receiving 1258559 citations. The organization is also known as: SDU.

Evaluation of prenatal diagnosis of congenital heart diseases by ultrasound: experience from 20 European registries

Abstract: Objectives To evaluate prenatal diagnosis of congenital heart diseases by ultrasound investigation in well-defined European populations. Design Data from 20 registries of congenital malformations in 12 European countries were included. The prenatal ultrasound screening programs in the countries ranged from no routine screening to three ultrasound investigations per patient routinely performed. Results There were 2454 cases with congenital heart disease with an overall prenatal detection rate of 25%. Termination of pregnancy was performed in 293 cases (12%). There was considerable variation in prenatal detection rate between regions, with the lowest detection rates being in countries without ultrasound screening (11%) and in Eastern European countries (Croatia, Lithuania and Ukraine; 8%). In Western European countries with ultrasound screening, detection rate ranged from 19–48%. There was a significant difference in prenatal detection rate and proportion of induced abortions between isolated congenital heart disease and congenital heart disease associated with chromosome anomalies, multiple malformations and syndromes (P < 0.0001). There were 1694 cases with isolated congenital heart disease of which 16% were diagnosed prenatally. Malformations affecting the size of the ventricles were detected prenatally in half of the cases. Conclusions Prenatal detection rate of congenital heart disease varies significantly between countries even with the same screening recommendations. The presence of associated malformations significantly increases the prenatal detection rate. Copyright © 2001 International Society of Ultrasound in Obstetrics and Gynecology

RelE toxins from Bacteria and Archaea cleave mRNAs on translating ribosomes, which are rescued by tmRNA

Abstract: RelE of Escherichia coli is a global inhibitor of translation that is activated by nutritional stress. Activation of RelE depends on Lon-mediated degradation of RelB, the antagonist that neutralizes RelE. In vitro, RelE cleaves synthetic mRNAs positioned at the ribosomal A-site. We show here that in vivo overexpression of RelE confers cleavage of mRNA and tmRNA in their coding regions. RelE-mediated cleavage depended on translation of the RNAs and occurred at both sense and stop codons. RelE cleavage of mRNA and tmRNA was also induced by amino acid starvation. An ssrA deletion strain was hypersensitive to RelE, whereas overproduction of tmRNA counteracted RelE toxicity. After neutralization of RelE by RelB, rapid recovery of translation required tmRNA, indicating that tmRNA alleviated RelE toxicity by rescuing ribosomes stalled on damaged mRNAs. RelE proteins from Gram-positive Bacteria and Archaea cleaved tmRNA with a pattern similar to that of E. coli RelE, suggesting that the function and target of RelE may be conserved across the prokaryotic domains.

Effects of aging on human skeletal muscle after immobilization and retraining

Abstract: Inactivity is a recognized compounding factor in sarcopenia and muscle weakness in old age. However, while the negative effects of unloading on skeletal muscle in young individuals are well elucidated, only little is known about the consequence of immobilization and the regenerative capacity in elderly individuals. Thus the aim of this study was to examine the effect of aging on changes in muscle contractile properties, specific force, and muscle mass characteristics in 9 old (61-74 yr) and 11 young men (21-27 yr) after 2 wk of immobilization and 4 wk of retraining. Both young and old experienced decreases in maximal muscle strength, resting twitch peak torque and twitch rate of force development, quadriceps muscle volume, pennation angle, and specific force after 2 wk of immobilization (P < 0.05). The decline in quadriceps volume and pennation angle was smaller in old compared with young (P < 0.05). In contrast, only old men experienced a decrease in quadriceps activation. After retraining, both young and old regained their initial muscle strength, but old had smaller gains in quadriceps volume compared with young, and pennation angle increased in young only (P < 0.05). The present study is the first to demonstrate that aging alters the neuromuscular response to short-term disuse and recovery in humans. Notably, immobilization had a greater impact on neuronal motor function in old individuals, while young individuals were more affected at the muscle level. In addition, old individuals showed an attenuated response to retraining after immobilization compared with young individuals.

Fri0203 a single-center investigation on the prevalence of malignancies in patients with polymyalgia rheumatica and giant cell arteritis by way of 18f-fdg pet/ct: a prospective cohort study

Abstract: Background: Several chronic inflammatory diseases are associated with a higher risk of cancer.[1] Whether, this is the case in Polymyalgia Rheumatica (PMR) and Giant Cell Arteritis (GCA) is still a matter of debate. Objectives: To identify the prevalence of newly diagnosed cancers in patients with PMR and GCA by means of 18F-FDG PET/CT. Moreover, to compare the characteristics of the patients with and without cancer. Methods: Eighty consecutive patients with newly diagnosed PMR/GCA were studied. Diagnosis of PMR/GCA was confirmed by a 40-weeks follow up. A unilateral temporal artery biopsy (TAB) was also performed at the time of diagnosis. All included patients underwent an 18F-FDG PET/CT before, or in case of GCA, within 3 days of initiation of high dose oral glucocorticoid (40-75mg). All cancer-suspicious 18F-FDG-PET/CT findings were assessed thoroughly and malignant diseases were confirmed by histology. Total PMR and GCA scores were defined as the sum of a 4-point visual grading scale in each articular/periarticular site as well as arterial segment. Results: Of the 80 patients, 64 (83.1%) were diagnosed with pure PMR, 10 (13.0%) with concomitant GCA with PMR and 3 (3.9%) with pure GCA. Three patients were diagnosed with rheumatoid arthritis during follow up and excluded from the study. Five types of cancer in 4 (5.2%;95% CI:1.4-12.8%) patients were found. Two patients had breast cancer, one patient had adenocarcinoma of colon and one patient had adenocarcinoma of colon together with skin cancer. Besides, 4 (5.2%;95% CI:1.4-12.8%) patients had Monoclonal Gammopathy of Unknown Significance (MGUS). Age and C-reactive protein were significantly higher among those with solid cancers (p:0.049) and MGUS (p:0.017), respectively (Table1). Conclusion: The prevalence of cancers in this cohort was higher, compared to the 1-year prevalence of all cancer sites of 1.2% among age-, gender- and region-matched background population in 2016. Occult malignancies are important and relatively prevalent findings in newly diagnosed PMR/GCA patients. References: [1]Hemminki K, et al. Cancer risk in hospitalized rheumatoid arthritis patients. Rheumatology (Oxford) 2008;47:698-701. Disclosure of Interests: None declared

A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes

Abstract: An association mapping study of type-2-diabetes-related quantitative traits in the Greenlandic population identified a common variant in TBC1D4 that increases plasma glucose levels and serum insulin levels after an oral glucose load and type 2 diabetes risk, with effect sizes several times larger than any previous findings of large-scale genome-wide association studies for these traits. This systematic genetic association study of quantitative traits related to type 2 diabetes (T2D) has identified a nonsense variant in the gene TBC1D4 which is present in 17% of the Greenlandic population, known to be a small founder population with a high incidence of T2D. The gene variant increases the levels of plasma glucose, serum insulin, and dramatically increases T2D risk. It also modestly reduces the concentrations of fasting plasma and fasting serum insulin. This work illustrates the value of founder populations — or of small and historically isolated populations — in maximizing the effectiveness of genetic association studies of this type. The Greenlandic population, a small and historically isolated founder population comprising about 57,000 inhabitants, has experienced a dramatic increase in type 2 diabetes (T2D) prevalence during the past 25 years1. Motivated by this, we performed association mapping of T2D-related quantitative traits in up to 2,575 Greenlandic individuals without known diabetes. Using array-based genotyping and exome sequencing, we discovered a nonsense p.Arg684Ter variant (in which arginine is replaced by a termination codon) in the gene TBC1D4 with an allele frequency of 17%. Here we show that homozygous carriers of this variant have markedly higher concentrations of plasma glucose (β = 3.8 mmol l−1, P = 2.5 × 10−35) and serum insulin (β = 165 pmol l−1, P = 1.5 × 10−20) 2 hours after an oral glucose load compared with individuals with other genotypes (both non-carriers and heterozygous carriers). Furthermore, homozygous carriers have marginally lower concentrations of fasting plasma glucose (β = −0.18 mmol l−1, P = 1.1 × 10−6) and fasting serum insulin (β = −8.3 pmol l−1, P = 0.0014), and their T2D risk is markedly increased (odds ratio (OR) = 10.3, P = 1.6 × 10−24). Heterozygous carriers have a moderately higher plasma glucose concentration 2 hours after an oral glucose load than non-carriers (β = 0.43 mmol l−1, P = 5.3 × 10−5). Analyses of skeletal muscle biopsies showed lower messenger RNA and protein levels of the long isoform of TBC1D4, and lower muscle protein levels of the glucose transporter GLUT4, with increasing number of p.Arg684Ter alleles. These findings are concomitant with a severely decreased insulin-stimulated glucose uptake in muscle, leading to postprandial hyperglycaemia, impaired glucose tolerance and T2D. The observed effect sizes are several times larger than any previous findings in large-scale genome-wide association studies of these traits2,3,4 and constitute further proof of the value of conducting genetic association studies outside the traditional setting of large homogeneous populations.