6,110 research outputs found

    Standardisation of Target Volume Delineation for Carotid-sparing Intensity-modulated Radiotherapy in Early Glottis Cancer.

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    Aims Recently, carotid-sparing intensity-modulated radiotherapy (IMRT) for early laryngeal glottis (T1/T2N0M0) cancer has generated interest in the hope of avoiding long-term carotid toxicity, as well as concerns relating to geographical misses and long-term normal tissue toxicity. The aim of this review was to summarise the current literature on carotid-sparing IMRT for early glottis cancer, with particular focus on definitions of target volumes and the carotid arteries as organs at risk. In addition, we make suggestions for standardisation of these structures, dose constraints and dose reporting.Materials and methods From 73 references, 16 articles met the criteria for inclusion in this systematic review. These papers described two case reports, 11 planning studies and three prospective studies.Results There was variation in all target volume definitions with no clear consensus. The greatest variability was in clinical target volume definition. Carotid artery and spinal cord delineation were not always defined and most studies did not use a carotid artery constraint. Of the eight studies that reported carotid artery delineation, no two studies delineated the same length of carotid artery, yet most studies reported mean doses. Most studies used IMRT with three to seven fields. Five studies used arc therapy and two studies used tomotherapy.Conclusion This review highlights a lack of consensus in target volume definitions in carotid-sparing IMRT. Ultimately, long-term prospective data are required to show the benefit of carotid-sparing IMRT. Pooled data will prove useful as most studies will report on small numbers of patients. Therefore, adopting a consensus now on target volume definition, dose constraints and dose reporting will be crucial

    Lack of association between the GRP78 polymorphisms in the promoter and 3' UTR and susceptibility to chronic HBV infection in a Chinese Han population

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    <p>Abstract</p> <p>Background</p> <p>Hepatitis B virus (HBV) infection causes large amount of unfolding or false-folding protein accumulation in the endoplasmic reticulum (ER), which in turn induces the expression of glucose-regulated protein 78 (GRP78). The aim in the present study was to analyse the potential association between GRP78 single-nucleotide polymorphisms (SNPs) and the risk of HBV infection.</p> <p>Methods</p> <p>The associations between seven common <it>GRP78 </it>polymorphisms in the promoter (rs391957, rs17840762, rs17840761, rs11355458) and in the 3' untranslated region (UTR) (rs16927997, rs1140763, rs12009) and possible risk of chronic HBV infection were assessed in a case-control study. 496 cases and 539 individually matched healthy controls were genotyped.</p> <p>Results</p> <p>Overall, no associations were observed in genotypic analyses. In addition, haplotypes and diplotypes combining those SNPs in the promoter or in the 3' UTR in high linkage disequilibrium (LD) were also not associated with HBV risk.</p> <p>Conclusion</p> <p>These observations do not support a role for <it>GRP78 </it>polymorphisms in HBV infection in a predominantly Chinese Han population.</p

    Analysis of Porcine Transcriptional Response to Salmonella enterica serovar Choleraesuis suggests novel targets of NFkappaB are activated in the Mesenteric Lymph Node

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    <p>Abstract</p> <p>Background</p> <p>Specific knowledge of the molecular pathways controlling host-pathogen interactions can increase our understanding of immune response biology as well as provide targets for drug development and genetic improvement of disease resistance. Toward this end, we have characterized the porcine transcriptional response to <it>Salmonella enterica </it>serovar Choleraesuis (<it>S</it>. Choleraesuis), a <it>Salmonella </it>serovar that predominately colonizes swine, yet can cause serious infections in human patients. Affymetrix technology was used to screen for differentially expressed genes in pig mesenteric lymph nodes (MLN) responding to infection with <it>S</it>. Choleraesuis at acute (8 hours (h), 24 h and 48 h post-inoculation (pi)) and chronic stages (21 days (d) pi).</p> <p>Results</p> <p>Analysis of variance with false discovery rate control identified 1,853 genes with significant changes in expression level (<it>p</it>-value < 0.01, <it>q</it>-value < 0.26, and fold change (FC) > 2) during infection as compared to un-inoculated control pigs. Down-regulation of translation-related genes at 8 hpi and 24 hpi implied that <it>S</it>. Choleraesuis repressed host protein translation. Genes involved in the Th1, innate immune/inflammation response and apoptosis pathways were induced significantly. However, antigen presentation/dendritic cell (DC) function pathways were not affected significantly during infection. A strong NF<it>κ</it>B-dependent response was observed, as 58 known NF<it>κ</it>B target genes were induced at 8, 24 and/or 48 hpi. Quantitative-PCR analyses confirmed the microarray data for 21 of 22 genes tested. Based on expression patterns, these target genes can be classified as an "Early" group (induced at either 8 or 24 hpi) and a "Late" group (induced only at 48 hpi). Cytokine activity or chemokine activity were enriched within the Early group genes GO annotations, while the Late group was predominantly composed of signal transduction and cell metabolism annotated genes. Regulatory motif analysis of the human orthologous promoters for both Early and Late genes revealed that 241 gene promoters were predicted to contain NF<it>κ</it>B binding sites, and that of these, 51 Early and 145 Late genes were previously not known to be NF<it>κ</it>B targets.</p> <p>Conclusion</p> <p>Our study provides novel genome-wide transcriptional profiling data on the porcine response to <it>S</it>. Choleraesuis and expands the understanding of NF<it>κ</it>B signaling in response to <it>Salmonella </it>infection. Comparison of the magnitude and timing of porcine MLN transcriptional response to different <it>Salmonella </it>serovars, <it>S</it>. Choleraesuis and <it>S</it>. Typhimurium, clearly showed a larger but later transcriptional response to <it>S</it>. Choleraesuis. Both microarray and QPCR data provided evidence of a strong NF<it>κ</it>B-dependent host transcriptional response during <it>S</it>. Choleraesuis infection. Our data indicate that a lack of strong DC-mediated antigen presentation in the MLN may cause <it>S</it>. Choleraesuis infected pigs to develop a systemic infection, and our analysis predicts nearly 200 novel NF<it>κ</it>B target genes which may be applicable across mammalian species.</p

    Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease

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    Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures
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