Iodinated contrast for patients with chronic kidney disease-writing on the wall or free for all?

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A detailed genome-wide reconstruction of mouse metabolism based on human Recon 1

<p>Abstract</p> <p>Background</p> <p>Well-curated and validated network reconstructions are extremely valuable tools in systems biology. Detailed metabolic reconstructions of mammals have recently emerged, including human reconstructions. They raise the question if the various successful applications of microbial reconstructions can be replicated in complex organisms.</p> <p>Results</p> <p>We mapped the published, detailed reconstruction of human metabolism (Recon 1) to other mammals. By searching for genes homologous to Recon 1 genes within mammalian genomes, we were able to create draft metabolic reconstructions of five mammals, including the mouse. Each draft reconstruction was created in compartmentalized and non-compartmentalized version via two different approaches. Using gap-filling algorithms, we were able to produce all cellular components with three out of four versions of the mouse metabolic reconstruction. We finalized a functional model by iterative testing until it passed a predefined set of 260 validation tests. The reconstruction is the largest, most comprehensive mouse reconstruction to-date, accounting for 1,415 genes coding for 2,212 gene-associated reactions and 1,514 non-gene-associated reactions.</p> <p>We tested the mouse model for phenotype prediction capabilities. The majority of predicted essential genes were also essential in vivo. However, our non-tissue specific model was unable to predict gene essentiality for many of the metabolic genes shown to be essential in vivo. Our knockout simulation of the lipoprotein lipase gene correlated well with experimental results, suggesting that softer phenotypes can also be simulated.</p> <p>Conclusions</p> <p>We have created a high-quality mouse genome-scale metabolic reconstruction, iMM1415 (<it>Mus Musculus</it>, 1415 genes). We demonstrate that the mouse model can be used to perform phenotype simulations, similar to models of microbe metabolism. Since the mouse is an important experimental organism, this model should become an essential tool for studying metabolic phenotypes in mice, including outcomes from drug screening.</p

The distribution of a germline methylation marker suggests a regional mechanism of LINE-1 silencing by the piRNA-PIWI system

<p>Abstract</p> <p>Background</p> <p>A defense system against transposon activity in the human germline based on PIWI proteins and piRNA has recently been discovered. It represses the activity of LINE-1 elements via DNA methylation by a largely unknown mechanism. Based on the dispersed distribution of clusters of piRNA genes in a strand-specific manner on all human chromosomes, we hypothesized that this system might work preferentially on local and proximal sequences. We tested this hypothesis with a methylation-associated SNP (mSNP) marker which is based on the density of C-T transitions in CpG dinucleotides as a surrogate marker for germline methylation.</p> <p>Results</p> <p>We found significantly higher density of mSNPs flanking piRNA clusters in the human genome for flank sizes of 1-16 Mb. A dose-response relationship between number of piRNA genes and mSNP density was found for up to 16 Mb of flanking sequences. The chromosomal density of hypermethylated LINE-1 elements had a significant positive correlation with the chromosomal density of piRNA genes (<it>r </it>= 0.41, <it>P </it>= 0.05<it>)</it>. Genome windows of 1-16 Mb containing piRNA clusters had significantly more hypermethylated LINE-1 elements than windows not containing piRNA clusters. Finally, the minimum distance to the next piRNA cluster was significantly shorter for hypermethylated LINE-1 compared to normally methylated elements (14.4 Mb vs 16.1 Mb).</p> <p>Conclusions</p> <p>Our observations support our hypothesis that the piRNA-PIWI system preferentially methylates sequences in close proximity to the piRNA clusters and perhaps physically adjacent sequences on other chromosomes. Furthermore they suggest that this proximity effect extends up to 16 Mb. This could be due to an unknown localization signal, transcription of piRNA genes near the nuclear membrane or the presence of an unknown RNA molecule that spreads across the chromosome and targets the methylation directed by the piRNA-PIWI complex. Our data suggest a region specific molecular mechanism which can be sought experimentally.</p

Incidental detection by computed tomography is an independent prognostic factor for survival in patients operated for nonsmall cell lung carcinoma.

Efst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinnWe studied the rate of incidental detection of lung carcinomas and its effect on long-term survival in a nationwide cohort of patients operated for nonsmall cell lung cancer (NSCLC). All patients operated for NSCLC in Iceland during 1991-2010 were included. Demographic and clinicopathological features were compared in patients diagnosed incidentally using chest radiography or computed tomography (CT), and in those with symptomatic presentation. Multivariate analysis was used to evaluate prognostic factors. Out of 508 patients, 174 (34%) were diagnosed incidentally; in 26% of cases by chest radiography and in 8% by CT. The CT-detected tumours were significantly smaller than symptomatic tumours, diagnosed at earlier TNM (tumour, node and metastasis) stages and more often of adenocarcinoma histology. 5-year cancer-specific survival for symptomatic versus incidentally diagnosed patients detected by chest radiography and CT was 41%, 57% and 68%, respectively (p=0.003). After adjusting for stage, the hazard ratio (HR) for NSCLC mortality was significantly lower for incidental diagnosis by CT (HR 0.55, 95% CI 0.31‒0.98; p=0.04) compared to incidental diagnosis by chest radiography (HR 0.95, 95% CI 0.70‒1.27; p=0.71) or symptomatic diagnosis (HR 1.0). One-third of surgically treated NSCLCs were detected incidentally, with an increasing rate of incidental CT diagnosis. NSCLC patients diagnosed incidentally by CT appear to have better survival than those diagnosed incidentally by chest radiography, and particularly those who present with symptoms

The impact of tumour size on the probability of synchronous metastasis and survival in renal cell carcinoma patients: a population-based study.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.The observed low metastatic potential and favorable survival of small incidentally detected renal cell carcinomas (RCCs) have been a part of the rationale for recommending partial nephrectomy as a first treatment option and active surveillance in selected patients. We examined the relationship between tumor size and the odds of synchronous metastases (SMs) (primary outcome) and disease specific survival (secondary outcome) in a nationwide RCC registry.Retrospective study of the 794 RCC patients diagnosed in Iceland between 1971 and 2005. Histological material and TNM staging were reviewed centrally. The presence of SM and survival were recorded. Cubic spline analysis was used to assess relationship between tumor size and probability of SM. Univariate and multivariate statistics were used to estimate prognostic factors for SM and survival.The probability of SM increased in a non-linear fashion with increasing tumor size (11, 25, 35, and 50%) for patients with tumors of ≤4, 4.1-7.0, 7.1-10.0, and >10 cm, respectively. On multivariate analysis, tumor size was an independent prognostic factor for disease-specific survival (HR = 1.05, 95% CI 1.02-1.09, p < 0.001), but not for SM.Tumor size affected the probability of disease-specific mortality but not SM, after correcting for TNM staging in multivariate analysis. This confirms the prognostic ability of the 2010 TNM staging system for renal cell cancer in the Icelandic population.Landspitali University Hospital Scientific Foundation Memorial Foundation of Bergthora Magnusdottir and Jakob J. Bjarnaso

Erratum: The impact of tumour size on the probability of synchronous metastasis and survival in renal cell carcinoma patients: a population-based study.

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Therapeutics and COVID-19-A living WHO guideline : Endorsement by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine

The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the Living WHO guideline on therapeutics and COVID-19. This trustworthy continuously updated guideline serves as a highly useful decision aid for Nordic anaesthesiologists caring for patients with COVID-19.Non peer reviewe

Temperature responses in a subarctic springtail from two geothermally warmed habitats

Common-garden experiments with populations sampled along natural thermal gradients help to reveal local adaptation, disentangle environmental and genetic effects, and ultimately predict, by analogy, future biotic responses to climate change. In this regard, geothermal habitats are useful model systems as they exhibit dramatic changes in soil temperature. The springtail Protaphorura pseudovanderdrifti has apparently coped with such local geothermal warming in Iceland, as this species occurs along a more than half-century-old geothermal gradient in a grassland and persists along a newly emerged temperature gradient in a previously non-geothermal planted spruce forest. We measured thermal reaction norms for development and walking speed and acute cold shock tolerance of P. pseudovanderdrifti originating from the grassland and forest geothermal gradients. Temperature-dependent juvenile development showed little variation among subpopulations from the recently warmed forest, probably due to insufficient evolutionary time, but springtails from the warmed grassland plots had significantly steeper reaction norms than their counterparts from the corresponding unwarmed plot. In contrast, cold tolerance and locomotory activity showed no conclusive clinal pattern despite significant within-habitat variation. There appeared to be significant differences between habitats, as springtails from the forest had more temperature-sensitive developmental rate and locomotory activity, walked faster, and exhibited more variable cold tolerance than grassland springtails did. The planting of a forest, therefore, seems to have exerted a stronger effect on the thermal phenotype of P. pseudovanderdrifti than the emergence of a geothermal gradient. Thus, habitat properties may be no less important in shaping thermal reaction norms than the mean temperature. These local-scale findings suggest that, in addition to warming per se, global transformation of communities may drive the evolution of thermal phenotypes to an extent comparable with the effect of rising environmental temperature

A descriptive study of the surge response and outcomes of ICU patients with COVID-19 during first wave in Nordic countries

Abstract Background We sought to provide a description of surge response strategies and characteristics, clinical management and outcomes of patients with severe COVID-19 in the intensive care unit (ICU) during the first wave of the pandemic in Denmark, Finland, Iceland, Norway and Sweden. Methods Representatives from the national ICU registries for each of the five countries provided clinical data and a description of the strategies to allocate ICU resources and increase the ICU capacity during the pandemic. All adult patients admitted to the ICU for COVID-19 disease during the first wave of COVID-19 were included. The clinical characteristics, ICU management and outcomes of individual countries were described with descriptive statistics. Results Most countries more than doubled their ICU capacity during the pandemic. For patients positive for SARS-CoV-2, the ratio of requiring ICU admission for COVID-19 varied substantially (1.6-6.7%). Apart from age (proportion of patients aged 65 years or over between 29-62%), baseline characteristics, chronic comorbidity burden and acute presentations of COVID-19 disease were similar among the five countries. While utilization of invasive mechanical ventilation was high (59-85%) in all countries, the proportion of patients receiving renal replacement therapy (7-26%) and various experimental therapies for COVID-19 disease varied substantially (e.g. use of hydroxychloroquine 0-85%). Crude ICU mortality ranged from 11% to 33%. Conclusion There was substantial variability in the critical care response in Nordic ICUs to the first wave of COVID-19 pandemic, including usage of experimental medications. While ICU mortality was low in all countries, the observed variability warrants further attention.Peer reviewe