275 research outputs found

    Chronic pancreatitis of the pancreatic remnant is an independent risk factor for pancreatic fistula after distal pancreatectomy

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    Background: There is an ongoing debate about the best closure technique after distal pancreatectomy (DP). The aim of the closure is to prevent the formation of a clinically relevant post-operative pancreatic fistula (POPF). Stapler technique seems to be equal compared with hand-sewn closure of the remnant. For both techniques, a fistula rate of approximately 30% has been reported. Methods: We retrospectively analyzed our DPs between 01/2000 and 12/2010. In all cases, the pancreatic duct was over sewn with a separately stitched ligation of the pancreatic duct (5*0 PDS) followed by a single-stitched hand-sewn closure of the residual pancreatic gland. The POPF was classified according to the criteria of the International Study Group for Pancreatic Fistula (ISGPF). Univariate and multivariate analyses of potential risk factors for the formation of POPF were performed. Indications for operations included cystic tumors (n = 53), neuroendocrine tumors (n = 27), adenocarcinoma (n = 22), chronic pancreatitis (n = 9), metastasis (n = 6), and others (n = 7). Results: During the period, we performed 124 DPs (♀ = 74, ♂ = 50). The mean age was 57.5 years (18–82). The POPF rates according to the ISGPF criteria were: no fistula, 54.8% (n = 68); grade A, 24.2% (n = 30); grade B, 19.3% (n = 24); and grade C, 1.7% (n = 2). Therefore, in 21.0% (n = 26) of the cases, a clinically relevant pancreatic fistula occurred. The mean postoperative stay was significantly higher after grade B/C fistula (26.3 days) compared with no fistula/grade A fistula (13.7 days) (p < 0.05). The uni- and multivariate analyses showed chronic pancreatitis of the pancreatic remnant to be an independent risk factor for the development of POPF (p = 0.004 OR 7.09). Conclusion: By using a standardized hand-sewn closure technique of the pancreatic remnant after DP with separately stitched ligation of the pancreatic duct, a comparably low fistula rate can be achieved. Signs of chronic pancreatitis of the pancreatic remnant may represent a risk factor for the development of a pancreatic fistula after DP and therefore an anastomosis of the remnant to the intestine should be considered

    Discovery and saturation analysis of cancer genes across 21 tumour types

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    Although a few cancer genes are mutated in a high proportion of tumours of a given type (>20%), most are mutated at intermediate frequencies (2–20%). To explore the feasibility of creating a comprehensive catalogue of cancer genes, we analysed somatic point mutations in exome sequences from 4,742 human cancers and their matched normal-tissue samples across 21 cancer types. We found that large-scale genomic analysis can identify nearly all known cancer genes in these tumour types. Our analysis also identified 33 genes that were not previously known to be significantly mutated in cancer, including genes related to proliferation, apoptosis, genome stability, chromatin regulation, immune evasion, RNA processing and protein homeostasis. Down-sampling analysis indicates that larger sample sizes will reveal many more genes mutated at clinically important frequencies. We estimate that near-saturation may be achieved with 600–5,000 samples per tumour type, depending on background mutation frequency. The results may help to guide the next stage of cancer genomics

    Ecological Adaptation of Diverse Honey Bee (Apis mellifera) Populations

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    BACKGROUND: Honey bees are complex eusocial insects that provide a critical contribution to human agricultural food production. Their natural migration has selected for traits that increase fitness within geographical areas, but in parallel their domestication has selected for traits that enhance productivity and survival under local conditions. Elucidating the biochemical mechanisms of these local adaptive processes is a key goal of evolutionary biology. Proteomics provides tools unique among the major 'omics disciplines for identifying the mechanisms employed by an organism in adapting to environmental challenges. RESULTS: Through proteome profiling of adult honey bee midgut from geographically dispersed, domesticated populations combined with multiple parallel statistical treatments, the data presented here suggest some of the major cellular processes involved in adapting to different climates. These findings provide insight into the molecular underpinnings that may confer an advantage to honey bee populations. Significantly, the major energy-producing pathways of the mitochondria, the organelle most closely involved in heat production, were consistently higher in bees that had adapted to colder climates. In opposition, up-regulation of protein metabolism capacity, from biosynthesis to degradation, had been selected for in bees from warmer climates. CONCLUSIONS: Overall, our results present a proteomic interpretation of expression polymorphisms between honey bee ecotypes and provide insight into molecular aspects of local adaptation or selection with consequences for honey bee management and breeding. The implications of our findings extend beyond apiculture as they underscore the need to consider the interdependence of animal populations and their agro-ecological context

    Cellular Communication through Light

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    Information transfer is a fundamental of life. A few studies have reported that cells use photons (from an endogenous source) as information carriers. This study finds that cells can have an influence on other cells even when separated with a glass barrier, thereby disabling molecule diffusion through the cell-containing medium. As there is still very little known about the potential of photons for intercellular communication this study is designed to test for non-molecule-based triggering of two fundamental properties of life: cell division and energy uptake. The study was performed with a cellular organism, the ciliate Paramecium caudatum. Mutual exposure of cell populations occurred under conditions of darkness and separation with cuvettes (vials) allowing photon but not molecule transfer. The cell populations were separated either with glass allowing photon transmission from 340 nm to longer waves, or quartz being transmittable from 150 nm, i.e. from UV-light to longer waves. Even through glass, the cells affected cell division and energy uptake in neighboring cell populations. Depending on the cuvette material and the number of cells involved, these effects were positive or negative. Also, while paired populations with lower growth rates grew uncorrelated, growth of the better growing populations was correlated. As there were significant differences when separating the populations with glass or quartz, it is suggested that the cell populations use two (or more) frequencies for cellular information transfer, which influences at least energy uptake, cell division rate and growth correlation. Altogether the study strongly supports a cellular communication system, which is different from a molecule-receptor-based system and hints that photon-triggering is a fine tuning principle in cell chemistry

    Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

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    The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

    Masked mRNA is stored with aggregated nuclear speckles and its asymmetric redistribution requires a homolog of mago nashi

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    <p>Abstract</p> <p>Background</p> <p>Many rapidly developing systems rely on the regulated translation of stored transcripts for the formation of new proteins essential for morphogenesis. The microspores of the water fern <it>Marsilea vestita </it>dehydrate as they mature. During this process both mRNA and proteins required for subsequent development are stored within the microspores as they become fully desiccated and enter into senescence. At this point microspores become transcriptionally silent and remain so upon rehydration and for the remainder of spermatogenesis. Transcriptional silencing coupled with the translation of preformed RNA makes the microspore of <it>M. vestita </it>a useful system in which to study post-transcriptional regulation of RNA.</p> <p>Results</p> <p>We have characterized the distribution of mRNA as well as several conserved markers of subnuclear bodies within the nuclei of desiccating spores. During this period, nuclear speckles containing RNA were seen to aggregate forming a single large coalescence. We found that aggregated speckles contain several masked mRNA species known to be essential for spermatogenesis. During spermatogenesis masked mRNA and associated speckle proteins were shown to fragment and asymmetrically localize to spermatogenous but not sterile cells. This asymmetric localization was disrupted by RNAi knockdown of the <it>Marsilea </it>homolog of the Exon Junction Complex core component Mago nashi.</p> <p>Conclusions</p> <p>A subset of masked mRNA is stored in association with nuclear speckles during the dormant phase of microspore development in <it>M. vestita</it>. The asymmetric distribution of specific mRNAs to spermatogenous but not sterile cells mirrors their translational activities and appears to require the EJC or EJC components. This suggests a novel role for nuclear speckles in the post-transcriptional regulation of transcripts.</p

    Family history of cancer and risk for esophageal and gastric cancer in Shanxi, China

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    <p>Abstract</p> <p>Background</p> <p>Family history (FH) by different relative types and risk of upper gastrointestinal (UGI) cancers has been only rarely reported; the data on UGI cancer survival are sparse.</p> <p>Methods</p> <p>600 esophageal squamous cell carcinoma (ESCC) cases, 598 gastric cardia adenocarcinoma cases, and 316 gastric non-cardia adenocarcinoma cases, and 1514 age-, gender-, and neighborhood-matched controls were asked for FH in first degree relatives and non-blood relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regressions, and hazard ratios (HRs) from Cox proportional hazard regressions were estimated.</p> <p>Results</p> <p>Increased ESCC risk was associated with FH of any cancer (OR = 1.72, 95% CI = 1.39–2.12), FH of any UGI cancer (OR = 2.28, 95%CI = 1.77–2.95) and FH of esophageal cancer (OR = 2.84, 95%CI = 2.09–3.86), but not FH of non-UGI cancer. Individuals with two or more affected first-degree relatives had 10-fold increased ESCC risk. FH of gastric cardia cancer was associated with an increased risk of all three cancers. Cancer in non-blood relatives was not associated with risk of any UGI cancer. FH of UGI cancer was associated with a poorer survival rate among younger ESCC cases (HR = 1.82, 95%CI = 1.01–3.29).</p> <p>Conclusion</p> <p>These data provide strong evidence that shared susceptibility is involved in esophageal carcinogenesis and also suggest a role in prognosis.</p

    The role of rewards and demands in burnout among surgical nurses

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    Job rewards have both, an intrinsic and an extrinsic motivational potential, and lead to employees’ development as well as help them to achieve work goals. Rewards can balance job demands and protect from burnout. Due to changes on the labour market, new studies are needed. The aim of our study was to examine the role of demands and individual rewards (and their absence) in burnout among surgical nurses. Materials and Methods: The study was conducted in 2009 and 2010 with 263 nurses who worked in surgical wards and clinics in hospitals in Southern Poland. The hypotheses were tested by the use of measures of demands and rewards (Effort-Reward Imbalance Questionnaire by Siegrist) and burnout syndrome (Maslach Burnout Inventory). A cross-sectional, correlational study design was applied. Results: Nurses experienced the largest deficiencies in salary and prestige. Exhaustion was explained by stronger demands and lack of respect (large effect). Depersonalization was explained by stronger demands, lack of respect and greater job security (medium effect). Reduced personal achievement was explained by more demands and greater job security (small effect). Conclusions: Excessive demands and lack of esteem are key reasons for burnout among surgical nurses. Job security can increase burnout when too many resources are invested and career opportunities do not appear. These results may help to improve human resource management in the healthcare sector

    Activation of Estrogen Receptor-α by E2 or EGF Induces Temporally Distinct Patterns of Large-Scale Chromatin Modification and mRNA Transcription

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    Estrogen receptor-α (ER) transcription function is regulated in a ligand-dependent (e.g., estradiol, E2) or ligand-independent (e.g., growth factors) manner. Our laboratory seeks to understand these two modes of action. Using a cell line that contains a visible prolactin enhancer/promoter array (PRL-HeLa) regulated by ER, we analyzed ER response to E2 and EGF by quantifying image-based results. Data show differential recruitment of GFP-ER to the array, with the AF1 domain playing a vital role in EGF-mediated responsiveness. Temporal analyses of large-scale chromatin dynamics, and accumulation of array-localized reporter mRNA over 24 hours showed that the EGF response consists of a single pulse of reporter mRNA accumulation concomitant with transient increase in array decondensation. Estradiol induced a novel cyclical pattern of mRNA accumulation with a sustained increase in array decondensation. Collectively, our work shows that there is a stimuli-specific pattern of large-scale chromatin modification and transcript levels by ER

    A Factor Graph Nested Effects Model To Identify Networks from Genetic Perturbations

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    Complex phenotypes such as the transformation of a normal population of cells into cancerous tissue result from a series of molecular triggers gone awry. We describe a method that searches for a genetic network consistent with expression changes observed under the knock-down of a set of genes that share a common role in the cell, such as a disease phenotype. The method extends the Nested Effects Model of Markowetz et al. (2005) by using a probabilistic factor graph to search for a network representing interactions among these silenced genes. The method also expands the network by attaching new genes at specific downstream points, providing candidates for subsequent perturbations to further characterize the pathway. We investigated an extension provided by the factor graph approach in which the model distinguishes between inhibitory and stimulatory interactions. We found that the extension yielded significant improvements in recovering the structure of simulated and Saccharomyces cerevisae networks. We applied the approach to discover a signaling network among genes involved in a human colon cancer cell invasiveness pathway. The method predicts several genes with new roles in the invasiveness process. We knocked down two genes identified by our approach and found that both knock-downs produce loss of invasive potential in a colon cancer cell line. Nested effects models may be a powerful tool for inferring regulatory connections and genes that operate in normal and disease-related processes
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