Radiation induced bystander signals are independent of DNA damage and DNA repair capacity of the irradiated cells.

Evidence is accumulating that irradiated cells produce signals, which interact with non-exposed cells in the same population. Here, we analysed the mechanism for bystander signal arising in wild-type CHO cells and repair deficient varients, focussing on the relationship between DNA repair capacity and bystander signal arising in irradiated cells. In order to investigate the bystander effect, we carried out medium transfer experiments after X-irradiation where micronuclei were scored in non-targeted DSB repair deficient xrs5 cells. When conditioned medium from irradiated cells was transferred to unirradiated xrs5 cells, the level of induction was independent of whether the medium came from irradiated wild-type, ssb or dsb repair deficient cells. This result suggests that the activation of a bystander signal is independent of the DNA repair capacity of the irradiated cells. Also, pre-treatment of the irradiated cells with 0.5% DMSO, which suppresses micronuclei induction in CHO but not in xrs5 cells, suppressed bystander effects completely in both conditioned media, suggesting that DMSO is effective for suppression of bystander signal arising independently of DNA damage in irradiated cells. Overall the work presented here adds to the understanding that it is the repair phenotype of the cells receiving bystander signals, which determines overall response rather than that of the cell producing the bystander signal.

Artificial Intelligence Model for Flowable Concrete Mixtures Used in Underwater Construction and Repair

This study explores using artificial neural networks to predict the rheological and mechanical properties of underwater concrete (UWC) mixtures and to evaluate the sensitivity of such properties to variations in mixture ingredients. Artificial neural networks (ANN) mimic the structure and operation of biological neurons and have the unique ability of self-learning, mapping, and functional approximation. Details of the development of the proposed neural network model, its architecture, training, and validation are presented in this study. A database incorporating 175 UWC mixtures from nine different studies was developed to train and test the ANN model. The data are arranged in a patterned format. Each pattern contains an input vector that includes quantity values of the mixture variables influencing the behavior of UWC mixtures (that is, cement, silica fume, fly ash, slag, water, coarse and fine aggregates, and chemical admixtures) and a corresponding output vector that includes the rheological or mechanical property to be modeled. Results show that the ANN model thus developed is not only capable of accurately predicting the slump, slump-flow, washout resistance, and compressive strength of underwater concrete mixtures used in the training process, but it can also effectively predict the aforementioned properties for new mixtures designed within the practical range of the input parameters used in the training process with an absolute error of 4.6, 10.6, 10.6, and 4.4%, respectively.

Comparative analysis of synovial fluid and plasma proteomes in juvenile arthritis - Proteomic patterns of joint inflammation in early stage disease

Synovial fluid is a potential source of novel biomarkers for many arthritic disorders involving joint inflammation, including juvenile idiopathic arthritis. We first compared the distinctive protein ‘fingerprints’ of local inflammation in synovial fluid with systemic profiles within matched plasma samples. The synovial fluid proteome at the time of joint inflammation was then evaluated across clinical subgroups to identify early disease associated proteins. We measured the synovial fluid and plasma proteomes using the two-dimensional fluorescence difference gel electrophoresis approach. Image analysis software was used to highlight the expression levels of joint and subgroup associated proteins across the study cohort (n = 32). A defined subset of 30 proteins had statistically significant differences (p < 0.05) between sample types such that synovial fluid could be differentiated from plasma. Furthermore distinctive synovial proteome expression patterns segregate patient subgroups. Protein expression patterns localized in the chronically inflamed joint therefore have the potential to identify patients more likely to suffer disease which will spread from a single joint to multiple joints. The proteins identified could act as criteria to prevent disease extension by more aggressive therapeutic intervention directed at an earlier stage than is currently possible.

Delayed post-surgical development of dural arteriovenous fistula after cervical meningocele repair

A 34-year-old female patient presented with an intracranial subarachnoid hemorrhage and was found to have a dural arteriovenous fistula at the site of previous cervical meningocele repair. Subsequent occlusion was achieved with endovascular embolization. To our knowledge, the phenomenon of the development of a spinal dural fistula at the site of a meningocele repair has not been recorded before.

The Impact of Admissions for the Management of End-stage renal disease on hospital bed occupancy

BACKGROUND:

End-stage renal disease (ESRD) is increasingly prevalent but the inpatient costs associated with this condition are poorly defined due to limitations with data extraction and failure to differentiate between hospitalisation for renal and non-renal disease reasons. The impact of admissions primarily for the management of ESRD on hospital bed utilisation was assessed over a 5-year period in a large teaching hospital.

METHODS:

All admission episodes were reviewed and the ESRD group was identified by a primary International Classification of Diseases code for ESRD or a non-specific primary renal failure code with a secondary code for ESRD. The frequency and duration of hospitalisation and contribution to bed day occupancy of this group with ESRD was determined.

RESULTS:

There were 70,808 patients responsible for a total of 116,915 admissions and 919,212 bed days over the study period. Of these, 988 (1.4%) patients were admitted for the management of ESRD, accounting for 2,387 (2.0%) of admissions and utilisation of 23,011 (2.5%) bed days. After adjustment for age and gender, those admitted for ESRD management were significantly more likely to have a prolonged admission exceeding 30 days (odds ratio 1.46, 95% confidence interval 1.23-1.72, p < 0.001). When the admission was an emergency rather than an elective event, the patient was 4.6 times more likely to be hospitalised for over 30 days.

CONCLUSIONS:

Persons admitted for ESRD management are hospitalised more frequently and for longer than the overall inpatient population, occupying a substantial number of bed days.

Hypercapnic acidosis attenuates pulmonary epithelial wound repair by an NF-kappa B dependent mechanism

Background: Hypercapnic acidosis exerts protective effects in acute lung injury but may also slow cellular repair. These effects may be mediated via inhibition of nuclear factor-kappa B (NF-kappa B), a pivotal transcriptional regulator in inflammation and repair.

Preliminary Results of a Prospective Randomized Trial of Restrictive Versus Standard Fluid Regime in Elective Open Abdominal Aortic Aneurysm Repair

Background: Open abdominal aortic aneurysm (AAA) repair is associated with a significant morbidity (primarily respiratory and cardiac complications) and an overall mortality rate of 4% to 10%. We tested the hypothesis that perioperative fluid restriction would reduce complications and improve outcome after elective open AAA repair.

Soluble endostatin is a novel inhibitor of epithelial repair in idiopathic pulmonary fibrosis

Background and aim: Aberrant angiogenesis and defective epithelial repair are key features of idiopathic pulmonary fibrosis (IPF). Endostatin is an antiangiogenic peptide with known effects on endothelial cells. This study aimed to establish the levels of endostatin in the bronchoalveolar lavage fluid (BALF) in IPF and to investigate its actions on distal lung epithelial cells (DLEC) and primary type II cells.

Short interfering RNA-mediated gene silencing in Globodera pallida and Meloidogyne incognita infective stage juveniles

The analysis of gene function through RNA interference (RNAi)-based reverse genetics in plant parasitic nematodes (PPNs) remains inexplicably reliant on the use of long double-stranded RNA (dsRNA) silencing triggers; a practice inherently disadvantageous due to the introduction of superfluous dsRNA sequence. increasing chances of aberrant or off-target gene silencing through interactions between nascent short interfering RNAs (siRNAs) and non-cognate mRNA targets. Recently, we have shown that non-nematode, long dsRNAs have a propensity to elicit profound impacts on the phenotype and migrational abilities of both root knot and cyst nematodes. This study presents, to our knowledge for the first time, gene-specific knockdown of FMRFamide-like peptide (flp) transcripts, using discrete 21 bp siRNAs in potato cyst nematode Globodera pallida, and root knot nematode Meloidogyne incognita infective (J2) stage juveniles. Both knockdown at the transcript level through quantitative (q)PCR analysis and functional data derived from migration assay, indicate that siRNAs targeting certain areas of the FMRFamide-like peptide (FLP) transcripts are potent and specific in the silencing of gene function. In addition, we present a method of manipulating siRNA activity through the management of strand thermodynamics. Initial evaluation of strand thermodynamics as a determinant of RNA-induced Silencing Complex (RISC) strand selection (inferred from knockdown efficacy) in the siRNAs presented here suggested that the purported influence of 5' stand stability on guide incorporation may be somewhat promiscuous. However, we have found that on strategically incorporating base mismatches in the sense strand of a G. pallida-specific siRNA we could specifically increase or decrease the knockdown of its target (specific to the antisense strand), presumably through creating more favourable thermodynamic profiles for incorporation of either the sense (non-target-specific) or antisense (target-specific) strand into a cleavage-competent RISC. Whilst the efficacy of similar approaches to siRNA modification has been demonstrated in the context of Drosophila whole-cell lysate preparations and in mammalian cell cultures, it remained to be seen how these sense strand mismatches may impact on gene silencing in vivo, in relation to different targets and in different sequence contexts. This work presents the first application of such an approach in a whole organism; initial results show promise. (C) 2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

New molecular targets in radiotherapy: DNA damage signalling and repair in targeted and non-targeted cells

Ionising radiation plays a key role in therapy due to its ability to directly induce DNA damage, in particular DNA double-strand breaks leading to cell death. Cells have multiple repair pathways which attempt to maintain genomic stability. DNA repair proteins have become key targets for therapy, using small molecule inhibitors, in combination with radiation and or chemotherapeutic agents as a means of enhancing cell killing. Significant advances in our understanding of the response of cells to radiation exposures has come from the observation of non-targeted effects where cells respond via mechanisms other than those which are a direct consequence of energy-dependent DNA damage. Typical of these is bystander signalling where cells respond to the fact that their neighbours have been irradiated. Bystander cells show a DNA damage response which is distinct from directly irradiated cells. In bystander cells, ATM- and Rad3-related (ATR) protein kinase-dependent signalling in response to stalled replication forks is an early event in the DNA damage response. The ATM protein kinase is activated downstream of ATR in bystander cells. This offers the potential for differential approaches for the modulation of bystander and direct effects with repair inhibitors which may impact on the response of tumours and on the protection of normal tissues during radiotherapy. (C) 2009 Elsevier B.V. All rights reserved.

Evaluation of Five Interleukin Genes for Association with End-Stage Renal Disease in White Europeans

Background: Genetic variation within interleukin genes has been reported to be associated with end-stage renal disease (ESRD). These findings have not been consistently replicated. No study has yet reported the comprehensive investigation of IL1A, IL1B, IL1RN, IL6 and IL10 genes. Methods: 664 kidney transplant recipients (cases) and 577 kidney donors (controls) were genotyped to establish if common variants in interleukin genes are associated with ESRD. Single nucleotide polymorphism (SNP) genotype data for each gene were downloaded for a northern and western European population from the International HapMap Project. Haploview was used to visualize linkage disequilibrium and select tag SNPs. Thirty SNPs were genotyped using MassARRAY (R) iPLEX Gold technology and data were analyzed using the chi(2) test for trend. Independent replication was conducted in 1,269 individuals with similar phenotypic characteristics. Results: Investigating all common variants in IL1A, IL1B, IL1RN, IL6 and IL10 genes revealed a statistically significant association (rs452204 p(empirical) = 0.02) with one IL1RN variant and ESRD. This IL1RN SNP tags three other variants, none of which have previously been reported to be associated with renal disease. Independent replication in a separate transplant population of comparable size did not confirm the original observation. Conclusions: Common variants in these five candidate interleukin genes are not major risk factors for ESRD in white Europeans. Copyright (C) 2010 S. Karger AG, Basel

Retroperitoneal Approach to Abdominal Aortic Aneurysm Repair Preserves Splanchnic Perfusion as Measured by Gastric Tonometry

Background: We investigated if minimizing bowel manipulation and mesenteric traction using the retroperitoneal approach in open abdominal aortic aneurysm (AAA) repair preserves splanchnic perfusion, as measured by gastric tonometry, and reduces the systemic inflammatory response and dysfunction of the various organs.