Recommendations from the United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis

In collaboration with United European Gastroenterology, the working group on 'Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed European guidelines for the management of chronic pancreatitis using an evidence-based approach.Recommendations of multidisciplinary review groups based on systematic literature reviews to answer predefined clinical questions are summarised. Recommendations are graded using the Grading of Recommendations Assessment, Development and Evaluation system.Recommendations covered topics related to the clinical management of chronic pancreatitis: aetiology, diagnosis of chronic pancreatitis with imaging, diagnosis of pancreatic exocrine insufficiency, surgical therapy, medical therapy, endoscopic therapy, treatment of pancreatic pseudocysts, pancreatic pain, nutrition and malnutrition, diabetes mellitus and the natural course of the disease and quality of life.The HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research. This article summarises the HaPanEU recommendations and statements

Potential conservation of circadian clock proteins in the phylum Nematoda as revealed by bioinformatic searches

Although several circadian rhythms have been described in C. elegans, its molecular clock remains elusive. In this work we employed a novel bioinformatic approach, applying probabilistic methodologies, to search for circadian clock proteins of several of the best studied circadian model organisms of different taxa (Mus musculus, Drosophila melanogaster, Neurospora crassa, Arabidopsis thaliana and Synechoccocus elongatus) in the proteomes of C. elegans and other members of the phylum Nematoda. With this approach we found that the Nematoda contain proteins most related to the core and accessory proteins of the insect and mammalian clocks, which provide new insights into the nematode clock and the evolution of the circadian system.Fil: Romanowski, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Garavaglia, Matías Javier. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goya, María Eugenia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ghiringhelli, Pablo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Ing.genética y Biolog.molecular y Celular. Area Virus de Insectos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Golombek, Diego Andres. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Moonlighting Proteins Hal3 and Vhs3 Form a Heteromeric PPCDC with Ykl088w in Yeast CoA Biosynthesis

Premi a l'excel·lència investigadora. 2010Unlike most other organisms, the essential five-step Coenzyme A biosynthetic pathway has not been fully resolved in yeast. Specifically, the gene(s) encoding the phosphopantothenoylcysteine decarboxylase (PPCDC) activity still remains unidentified. Sequence homology analyses suggest three candidates, namely Ykl088w, Hal3 and Vhs3, as putative PPCDC enzymes in Saccharomyces cerevisiae. Interestingly, Hal3 and Vhs3 have been characterized as negative regulatory subunits of the Ppz1 protein phosphatase. Here we show that YKL088w does not encode a third Ppz1 regulatory subunit, and that the essential roles of Ykl088w and the Hal3/Vhs3 pair are complementary, cannot be interchanged and can be attributed to PPCDC-related functions. We demonstrate that while known eukaryotic PPCDCs are homotrimers, the active yeast enzyme is a heterotrimer which consists of Ykl088w and Hal3/Vhs3 monomers that separately provides two essential catalytic residues. Our results unveil Hal3/Vhs3 as moonlighting proteins, involved in both CoA biosynthesis and protein phosphatase regulation

High-Luminosity Large Hadron Collider (HL-LHC): Technical Design Report

The Large Hadron Collider (LHC) is one of the largest scientific instruments ever built. Since opening up a new energy frontier for exploration in 2010, it has gathered a global user community of about 9000 scientists working in fundamental particle physics and the physics of hadronic matter at extreme temperature and density. To sustain and extend its discovery potential, the LHC will need a major upgrade in the 2020s. This will increase its instantaneous luminosity (rate of collisions) by a factor of five beyond the original design value and the integrated luminosity (total number of collisions) by a factor ten. The LHC is already a highly complex and exquisitely optimised machine so this upgrade must be carefully conceived and will require new infrastructures (underground and on surface) and over a decade to implement. The new configuration, known as High Luminosity LHC (HL-LHC), relies on a number of key innovations that push accelerator technology beyond its present limits. Among these are cutting-edge 11–12 Tesla superconducting magnets, compact superconducting cavities for beam rotation with ultra-precise phase control, new technology and physical processes for beam collimation and 100 metre-long high-power superconducting links with negligible energy dissipation, all of which required several years of dedicated R&D effort on a global international level. The present document describes the technologies and components that will be used to realise the project and is intended to serve as the basis for the detailed engineering design of the HL-LHC

Human Papillomaviruses and genital co-infections in gynaecological outpatients

<p>Abstract</p> <p>Background</p> <p>High grade HPV infections and persistence are the strongest risk factors for cervical cancer. Nevertheless other genital microorganisms may be involved in the progression of HPV associated lesions.</p> <p>Methods</p> <p>Cervical samples were collected to search for human Papillomavirus (HPV), bacteria and yeast infections in gynaecologic outpatients. HPV typing was carried out by PCR and sequencing on cervical brush specimens. <it>Chlamydia trachomatis </it>was identified by strand displacement amplification (SDA) and the other microorganisms were detected by conventional methods.</p> <p>Results</p> <p>In this cross-sectional study on 857 enrolled outpatients, statistical analyses revealed a significant association of HPV with <it>C. trachomatis </it>and <it>Ureaplasma urealyticum (</it>at high density) detection, whereas no correlation was found between HPV infection and bacterial vaginosis, <it>Streptococcus agalactiae</it>, yeasts, <it>Trichomonas vaginalis </it>and <it>U. urealyticum</it>. <it>Mycoplasma hominis </it>was isolated only in a few cases both in HPV positive and negative women and no patient was infected with <it>Neisseria gonorrhoeae</it>.</p> <p>Conclusion</p> <p>Although bacterial vaginosis was not significantly associated with HPV, it was more common among the HPV positive women. A significant association between HPV and <it>C. trachomatis </it>was found and interestingly also with <it>U. urealyticum </it>but only at a high colonization rate. These data suggest that it may be important to screen for the simultaneous presence of different microorganisms which may have synergistic pathological effects.</p

Abscess of adrenal gland caused by disseminated subacute Nocardia farcinica pneumonia. A case report and mini-review of the literature

<p>Abstract</p> <p>Background</p> <p>Infections caused by <it>Nocardia farcinica </it>are uncommon and show a great variety of clinical manifestations in immunocompetent and immunocompromised patients. Because of its unspecific symptoms and tendency to disseminate it may mimic the clinical symptoms and radiologic findings of a tumour disease and the diagnosis of nocardiosis can easily be missed, because there are no characteristic symptoms.</p> <p>Case presentation</p> <p>We present a case of an adrenal gland abscess caused by subacute disseminated <it>N. farcinica </it>pneumonia.</p> <p>Conclusion</p> <p>An infection with <it>N. farcinica </it>is potentially lethal because of its tendency to disseminate -particularly in the brain- and its high resistance to antibiotics. Awareness of this differential diagnosis allows early and appropriate treatment to be administered.</p

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Mining expressed sequence tags identifies cancer markers of clinical interest

BACKGROUND: Gene expression data are a rich source of information about the transcriptional dis-regulation of genes in cancer. Genes that display differential regulation in cancer are a subtype of cancer biomarkers. RESULTS: We present an approach to mine expressed sequence tags to discover cancer biomarkers. A false discovery rate analysis suggests that the approach generates less than 22% false discoveries when applied to combined human and mouse whole genome screens. With this approach, we identify the 200 genes most consistently differentially expressed in cancer (called HM200) and proceed to characterize these genes. When used for prediction in a variety of cancer classification tasks (in 24 independent cancer microarray datasets, 59 classifications total), we show that HM200 and the shorter gene list HM100 are very competitive cancer biomarker sets. Indeed, when compared to 13 published cancer marker gene lists, HM200 achieves the best or second best classification performance in 79% of the classifications considered. CONCLUSION: These results indicate the existence of at least one general cancer marker set whose predictive value spans several tumor types and classification types. Our comparison with other marker gene lists shows that HM200 markers are mostly novel cancer markers. We also identify the previously published Pomeroy-400 list as another general cancer marker set. Strikingly, Pomeroy-400 has 27 genes in common with HM200. Our data suggest that a core set of genes are responsive to the deregulation of pathways involved in tumorigenesis in a variety of tumor types and that these genes could serve as transcriptional cancer markers in applications of clinical interest. Finally, our study suggests new strategies to select and evaluate cancer biomarkers in microarray studies

Evolution of H3N2 Influenza Virus in a Guinea Pig Model

Studies of influenza virus evolution under controlled experimental conditions can provide a better understanding of the consequences of evolutionary processes with and without immunological pressure. Characterization of evolved strains assists in the development of predictive algorithms for both the selection of subtypes represented in the seasonal influenza vaccine and the design of novel immune refocused vaccines. To obtain data on the evolution of influenza in a controlled setting, naïve and immunized Guinea pigs were infected with influenza A/Wyoming/2003 (H3N2). Virus progeny from nasal wash samples were assessed for variation in the dominant and other epitopes by sequencing the hemagglutinin (HA) gene to quantify evolutionary changes. Viral RNA from the nasal washes from infection of naïve and immune animals contained 6% and 24.5% HA variant sequences, respectively. Analysis of mutations relative to antigenic epitopes indicated that adaptive immunity played a key role in virus evolution. HA mutations in immunized animals were associated with loss of glycosylation and changes in charge and hydrophobicity in and near residues within known epitopes. Four regions of HA-1 (75–85, 125–135, 165–170, 225–230) contained residues of highest variability. These sites are adjacent to or within known epitopes and appear to play an important role in antigenic variation. Recognition of the role of these sites during evolution will lead to a better understanding of the nature of evolution which help in the prediction of future strains for selection of seasonal vaccines and the design of novel vaccines intended to stimulated broadened cross-reactive protection to conserved sites outside of dominant epitopes

EST Analysis of Ostreococcus lucimarinus, the Most Compact Eukaryotic Genome, Shows an Excess of Introns in Highly Expressed Genes

Background: The genome of the pico-eukaryotic (bacterial-sized) prasinophyte green alga Ostreococcus lucimarinus has one of the highest gene densities known in eukaryotes, yet it contains many introns. Phylogenetic studies suggest this unusually compact genome (13.2 Mb) is an evolutionarily derived state among prasinophytes. The presence of introns in the highly reduced O. lucimarinus genome appears to be in opposition to simple explanations of genome evolution based on unidirectional tendencies, either neutral or selective. Therefore, patterns of intron retention in this species can potentially provide insights into the forces governing intron evolution. Methodology/Principal Findings: Here we studied intron features and levels of expression in O. lucimarinus using expressed sequence tags (ESTs) to annotate the current genome assembly. ESTs were assembled into unigene clusters that were mapped back to the O. lucimarinus Build 2.0 assembly using BLAST and the level of gene expression was inferred from the number of ESTs in each cluster. We find a positive correlation between expression levels and both intron number (R = +0.0893, p =,0.0005) and intron density (number of introns/kb of CDS; R = +0.0753, p =,0.005). Conclusions/Significance: In a species with a genome that has been recently subjected to a great reduction of non-coding DNA, these results imply the existence of selective/functional roles for introns that are principally detectable in highly expressed genes. In these cases, introns are likely maintained by balancing the selective forces favoring their maintenanc