Bloodstream infections following different types of surgery in a Finnish tertiary care hospital, 2009-2014

The risk and outcome of bloodstream infections (BSIs) were evaluated following surgery. BSIs were identified in Helsinki University Hospital during 2009-2014 as part of the national surveillance. Of 711 BSIs identified, 51% were secondary and 49% primary. The rate was highest after cardiovascular surgery (8.7 per 1000 procedures) and lowest after gynaecologic (1.0 per 1000). Surgical site infection was the most frequent source of secondary BSIs (34%) and 45% of primary BSIs were central-line-associated. The 28-day case fatality ranged from zero in gynaecology/obstetrics to 21% in cardiovascular surgery. Besides BSIs related to surgical site infections, half of BSIs were primary, providing additional foci for prevention. (C) 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Endoplasmic reticulum stress increases AT1R mRNA expression via TIA-1-dependent mechanism

As the formation of ribonucleoprotein complexes is a major mechanism of angiotensin II type 1 receptor (AT1R) regulation, we sought to identify novel AT1R mRNA binding proteins. By affinity purification and mass spectroscopy, we identified TIA-1. This interaction was confirmed by colocalization of AT1R mRNA and TIA-1 by FISH and immunofluorescence microscopy. In immunoprecipitates of endogenous TIA-1, reverse transcription-PCR amplified AT1R mRNA. TIA-1 has two binding sites within AT1R 3'-UTR. The binding site proximal to the coding region is glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-dependent whereas the distal binding site is not. TIA-1 functions as a part of endoplasmic reticulum (ER) stress response leading to stress granule (SG) formation and translational silencing. We and others have shown that AT1R expression is increased by ER stress-inducing factors. In unstressed cells, TIA-1 binds to AT1R mRNA and decreases AT1R protein expression. Fluorescence microscopy shows that ER stress induced by thapsigargin leads to the transfer of TIA-1 to SGs. In FISH analysis AT1R mRNA remains in the cytoplasm and no longer colocalizes with TIA-1. Thus, release of TIA-1-mediated suppression by ER stress increases AT1R protein expression. In conclusion, AT1R mRNA is regulated by TIA-1 in a ER stress-dependent manner.Peer reviewe

Predictive simulations of NBI ion power load to the ICRH antenna in Wendelstein 7-X

In Wendelstein 7-X (W7-X), a new ion cyclotron resonance heating (ICRH) antenna will be commissioned during the operational campaign OP2.1. The antenna will have to sustain power loads not only from thermal plasma and radiation but also fast ions. Predictive simulations of fast-ion power loads to the antenna components are therefore important to establish safe operational limits. In this work, the fast-ion power loads from the W7-X neutral beam injection (NBI) system to the ICRH antenna was simulated using the ASCOT suite of codes. Five reference magnetic configurations and five antenna positions were considered to provide an overview of power load behavior under various operating conditions. The NBI power load was found to have an exponential dependence on the antenna insertion depth. Differences between magnetic configurations were significant, with the antenna limiter power load varying between 380 W and 100 kW depending on the configuration. Qualitative differences in power load patterns between configurations were also observed, with the low mirror and low iota configurations exhibiting higher loads to the sensitive antenna straps. The local fast-ion power flux to the antenna limiter was also considered and found to exceed the 2.0 MW m−2 steady-state safety limit only in specific cases. The NBI system might thus pose a safety concern to the ICRH antenna during concurrent NBI-ICRH operation, but additional heat propagation simulations of antenna components are needed to establish more realistic operational time limits

Regulation of AT1R expression through HuR by insulin

Peer reviewe

Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients

Background: Reduced nocturnal fall (non-dipping) of blood pressure (BP) is a predictor of cardiovascular target organ damage. No genome-wide association studies (GWAS) on BP dipping have been previously reported.Methods: To study genetic variation affecting BP dipping, we conducted a GWAS in Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (n = 204) using the mean night-to-day BP ratio from up to four ambulatory BP recordings conducted on placebo. Associations with P< 1 x 10(-5) were further tested in two independent cohorts: Haemodynamics in Primary and Secondary Hypertension (DYNAMIC) (n = 183) and Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic Syndrome (DILGOM) (n = 180). We also tested the genome-wide significant single nucleotide polymorphism (SNP) for association with left ventricular hypertrophy in GENRES.Results: In GENRES GWAS, rs4905794 near BCL11B achieved genome-wide significance (beta = - 4.8%, P = 9.6 x 10(-9) for systolic and beta = - 4.3%, P = 2.2 x 10(-6) for diastolic night-to-day BP ratio). Seven additional SNPs in five loci had P values < 1 x 10(-5). The association of rs4905794 did not significantly replicate, even though in DYNAMIC the effect was in the same direction (beta = - 0.8%, P = 0.4 for systolic and beta = - 1.6%, P = 0.13 for diastolic night-to-day BP ratio). In GENRES, the associations remained significant even during administration of four different antihypertensive drugs. In separate analysis in GENRES, rs4905794 was associated with echocardiographic left ventricular mass (beta = -7.6 g/m(2), P = 0.02).Conclusions: rs4905794 near BCL11B showed evidence for association with nocturnal BP dipping. It also associated with left ventricular mass in GENRES. Combined with earlier data, our results provide support to the idea that BCL11B could play a role in cardiovascular pathophysiology

Posttranscriptional regulation of angiotensin II type 1 receptor expression by glyceraldehyde 3-phosphate dehydrogenase

Regulation of angiotensin II type 1 receptor (AT1R) has a pathophysiological role in hypertension, atherosclerosis and heart failure. We started from an observation that the 3′-untranslated region (3′-UTR) of AT1R mRNA suppressed AT1R translation. Using affinity purification for the separation of 3′-UTR-binding proteins and mass spectrometry for their identification, we describe glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as an AT1R 3′-UTR-binding protein. RNA electrophoretic mobility shift analysis with purified GAPDH further demonstrated a direct interaction with the 3′-UTR while GAPDH immunoprecipitation confirmed this interaction with endogenous AT1R mRNA. GAPDH-binding site was mapped to 1–100 of 3′-UTR. GAPDH-bound target mRNAs were identified by expression array hybridization. Analysis of secondary structures shared among GAPDH targets led to the identification of a RNA motif rich in adenines and uracils. Silencing of GAPDH increased the expression of both endogenous and transfected AT1R. Similarly, a decrease in GAPDH expression by H2O2 led to an increased level of AT1R expression. Consistent with GAPDH having a central role in H2O2-mediated AT1R regulation, both the deletion of GAPDH-binding site and GAPDH overexpression attenuated the effect of H2O2 on AT1R mRNA. Taken together, GAPDH is a translational suppressor of AT1R and mediates the effect of H2O2 on AT1R mRNA

Employment status and differences in the one-year coverage of physician visits: different needs or unequal access to services?

BACKGROUND: The dichotomy employed vs. unemployed is still a relevant, but rather crude measure of status in current labour markets. Also, studies concerning the association of employment status with health have to specify the type of the employment as well as the characteristics of the unemployment. This study aims to reveal differences and potential inequalities in physician visits among seven groups in the core-periphery structures of the labour markets. METHODS: A total of 16 000 Finns responded to a postal survey in 2003. Their visits to physicians in public primary health care, occupational health care, private health services, hospital outpatient clinics and dental care services during previous year were measured as indicators of service utilisation. Participants were classified as employees having a permanent or fixed-term and full-time or part-time contract and as those experiencing short-term, prolonged or long-term unemployment. Differences in the one-year coverage of physician visits between these groups of employees were analysed using logistic regression analyses where differences in the need for services were controlled for by including demographics and self-rated health assessments in the models. RESULTS: Permanently employed respondents had visited a physician most often, and the need-adjusted regression models showed significantly lower odds ratios for a visit among fixed-term employees (OR 0.65, 95% CI 0.53–0.81) and in particular among the long-term unemployed (OR 0.21, 95% CI 0.14–0.31). A stratified analysis according to health care sector showed the lowest odds ratios in occupational health care and private physicians (ORs between 0.05 and 0.73) and also low odds ratios for dentists (ORs between 0.45 and 0.91), whereas visits to public primary health care were more common among non-permanent employees and the unemployed (ORs between 1.46 and 2.39). CONCLUSION: The use of physician services varies according to labour market status, being relatively low among the non-permanently employed and the unemployed. This underuse is emphasised when clinical need is taken into account. The main reasons for the variance evidently lie in the structures of the Finnish health service system. The result may indicate non-optimal health care of the population on the periphery of the labour market, but it may also reflect the importance of employment status as a context for need and the decision to visit a physician

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD