Showing papers by "University of Naples Federico II published in 2013"
Katholieke Universiteit Leuven1, Gdańsk Medical University2, University of Valencia3, Zamorano4, Ghent University5, Charles University in Prague6, University of Glasgow7, University of Naples Federico II8, University Medical Center Utrecht9, Linköping University10, University of Birmingham11, University of Oslo12, Lund University13, Complutense University of Madrid14, University of Erlangen-Nuremberg15, John Radcliffe Hospital16, Tallinn University of Technology17, University of Lausanne18
TL;DR: 2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the management of Arterspertension of the European Society ofhypertension (ESH) and of theEuropean Society of Cardiology (ESC).
Abstract: Because of new evidence on several diagnostic and therapeutic aspects of hypertension, the present guidelines differ in many respects from the previous ones. Some of the most important differences are listed below:
1. Epidemiological data on hypertension and BP control in Europe.
2. Strengthening of the prognostic value of home blood pressure monitoring (HBPM) and of its role for diagnosis and management of hypertension, next to ambulatory blood pressure monitoring (ABPM).
3. Update of the prognostic significance of night-time BP, white-coat hypertension and masked hypertension.
4. Re-emphasis on integration of BP, cardiovascular (CV) risk factors, asymptomatic organ damage (OD) and clinical complications for total CV risk assessment.
5. Update of the prognostic significance of asymptomatic OD, including heart, blood vessels, kidney, eye and brain.
6. Reconsideration of the risk of overweight and target body mass index (BMI) in hypertension.
7. Hypertension in young people.
8. Initiation of antihypertensive treatment. More evidence-based criteria and no drug treatment of high normal BP.
9. Target BP for treatment. More evidence-based criteria and unified target systolic blood pressure (SBP) (<140 mmHg) in both higher and lower CV risk patients.
10. Liberal approach to initial monotherapy, without any all-ranking purpose.
11. Revised schema for priorital two-drug combinations.
12. New therapeutic algorithms for achieving target BP.
13. Extended section on therapeutic strategies in special conditions.
14. Revised recommendations on treatment of hypertension in the elderly.
15. Drug treatment of octogenarians.
16. Special attention to resistant hypertension and new treatment approaches.
17. Increased attention to OD-guided therapy.
18. New approaches to chronic management of hypertensive disease
7,018 citations
TL;DR: Mononuclear phagocyte plasticity includes the expression of functions related to the resolution of inflammation, tissue repair and remodelling, particularly when these cells are set in an M1 or an M2‐like activation mode.
Abstract: Mononuclear phagocyte plasticity includes the expression of functions related to the resolution of inflammation, tissue repair and remodelling, particularly when these cells are set in an M2 or an M2-like activation mode. Macrophages are credited with an essential role in remodelling during ontogenesis. In extraembryonic life, under homeostatic conditions, the macrophage trophic and remodelling functions are recapitulated in tissues such as bone, mammary gland, decidua and placenta. In pathology, macrophages are key components of tissue repair and remodelling that occur during wound healing, allergy, parasite infection and cancer. Interaction with cells bearing stem or progenitor cell properties is likely an important component of the role of macrophages in repair and remodelling. These properties of cells of the monocyte-macrophage lineage may represent a tool and a target for therapeutic exploitation.
1,884 citations
University of Bologna1, University of Utah2, University of Jena3, Imperial College London4, University of Barcelona5, Royal Liverpool and Broadgreen University Hospital NHS Trust6, University of Texas MD Anderson Cancer Center7, University of Poitiers8, Norwegian University of Science and Technology9, University of Adelaide10, Catholic University of Korea11, University of Chicago12, University of Toronto13, University of Bordeaux14, Masaryk University15, Heidelberg University16, Leipzig University17, University of Naples Federico II18, Fred Hutchinson Cancer Research Center19, University of Turin20, Wayne State University21, Cornell University22, Uppsala University23
TL;DR: Optimal responders to chronic myeloid leukemia treatment should continue therapy indefinitely, with careful surveillance, or they can be enrolled in controlled studies of treatment discontinuation once a deeper molecular response is achieved.
1,679 citations
Beth Israel Deaconess Medical Center1, Harvard University2, University of Pavia3, University of Maryland, Baltimore4, Columbia University5, Royal Hallamshire Hospital6, University of Tampere7, Imperial College London8, University of Oslo9, Mayo Clinic10, University of Naples Federico II11, University of Salerno12
TL;DR: A multidisciplinary task force of 16 physicians from seven countries used the electronic database PubMed to review the literature for CD-related terms and suggested a definition for each term, followed by feedback through a web survey on definitions and discussions during a meeting in Oslo.
Abstract: Objective The literature suggests a lack of consensus on the use of terms related to coeliac disease (CD) and gluten. Design A multidisciplinary task force of 16 physicians from seven countries used the electronic database PubMed to review the literature for CD-related terms up to January 2011. Teams of physicians then suggested a definition for each term, followed by feedback of these definitions through a web survey on definitions, discussions during a meeting in Oslo and phone conferences. In addition to ‘CD’, the following descriptors of CD were evaluated (in alphabetical order): asymptomatic, atypical, classical, latent, non-classical, overt, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, dermatitis herpetiformis, gluten, gluten ataxia, gluten intolerance, gluten sensitivity and gliadin-specific antibodies. Results CD was defined as ‘a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals’. Classical CD was defined as ‘CD presenting with signs and symptoms of malabsorption. Diarrhoea, steatorrhoea, weight loss or growth failure is required.’ ‘Gluten-related disorders’ is the suggested umbrella term for all diseases triggered by gluten and the term gluten intolerance should not to be used. Other definitions are presented in the paper. Conclusion This paper presents the Oslo definitions for CD-related terms.
1,324 citations
Katholieke Universiteit Leuven1, Gdańsk Medical University2, University of Valencia3, Ghent University4, Charles University in Prague5, University of Glasgow6, University of Naples Federico II7, Utrecht University8, Linköping University9, University of Münster10, University of Oslo11, Complutense University of Madrid12, University of Erlangen-Nuremberg13, John Radcliffe Hospital14, Tallinn University of Technology15, University of Lausanne16
TL;DR: The 2013 European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines continue to adhere to some fundamental principles that inspired the 2003 and 2007 guidelines, namely to base recommendations on properly conducted studies identified from an ext
Abstract: 1. INTRODUCTION1.1 PrinciplesThe 2013 European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines continue to adhere to some fundamental principles that inspired the 2003 and 2007 guidelines, namely to base recommendations on properly conducted studies identified from an ext
1,139 citations
Tel Aviv University1, Ludwig Maximilian University of Munich2, Hebrew University of Jerusalem3, Erasmus University Rotterdam4, Sapienza University of Rome5, University of Helsinki6, Semmelweis University7, Boston Children's Hospital8, University of Copenhagen9, University of Toronto10, University of Florence11, Jagiellonian University12, University of Barcelona13, University of Naples Federico II14, University of Paris15, University of Edinburgh16
TL;DR: These revised Porto criteria for the diagnosis of P IBD have been developed to meet present challenges and developments in PIBD and provide up-to-date guidelines for the definition and diagnosis of the IBD spectrum.
Abstract: Background: The diagnosis of pediatric-onset inflammatory bowel disease (PIBD) can be challenging in choosing the most informative diagnostic tests and correctly classifying PIBD into its different subtypes. Recent advances in our understanding of the natural history and phenotype of PIBD, increasing availability of serological and fecal biomarkers, and the emergence of novel endoscopic and imaging technologies taken together have made the previous Porto criteria for the diagnosis of PIBD obsolete. Methods: We aimed to revise the original Porto criteria using an evidencebased approach and consensus process to yield specific practice recommendations for the diagnosis of PIBD. These revised criteria are based on the Paris classification of PIBD and the original Porto criteria while incorporating novel data, such as for serum and fecal biomarkers. A consensus of at least 80% of participants was achieved for all recommendations and the summary algorithm. Results: The revised criteria depart from existing criteria by defining 2 categories of ulcerative colitis (UC, typical and atypical); atypical phenotypes of UC should be treated as UC. A novel approach based on multiple criteria for diagnosing IBD-unclassified (IBD-U) is proposed. Specifically, these revised criteria recommend upper gastrointestinal endoscopy and ileocolonscopy for all suspected patients with PIBD, with small bowel imaging (unless typical UC after endoscopy and histology) by magnetic resonance enterography or wireless capsule endoscopy.
929 citations
University of Copenhagen1, Centre Hospitalier Universitaire de Grenoble2, University of Valladolid3, University of Naples Federico II4, Innsbruck Medical University5, Ludwig Maximilian University of Munich6, Maastricht University7, University of Valencia8, Royal Lancaster Infirmary9, University of Salzburg10
TL;DR: These guidelines are intended to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthetists throughout Europe to integrate this knowledge into daily patient care wherever possible.
Abstract: The aims of severe perioperative bleeding management are three-fold. First, preoperative identification by anamesis and laboratory testing of those patients for whom the perioperative bleeding risk may be increased. Second, implementation of strategies for correcting preoperative anaemia and stabilisation of the macro- and microcirculations in order to optimise the patient’s tolerance to bleeding. Third, targeted procoagulant interventions to reduce the amount of bleeding, morbidity, mortality and costs. The purpose of these guidelines is to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthetists throughout Europe to integrate this knowledge into daily patient care wherever possible. The Guidelines Committee of the European Society of Anaesthesiology (ESA) formed a task force with members of scientific subcommittees and individual expert members of the ESA. Electronic databases were searched without language restrictions from the year 2000 until 2012. These searches produced 20 664 abstracts. Relevant systematic reviews with meta-analyses, randomised controlled trials, cohort studies, case-control studies and cross-sectional surveys were selected. At the suggestion of the ESA Guideline Committee, the Scottish Intercollegiate Guidelines Network (SIGN) grading system was initially used to assess the level of evidence and to grade recommendations. During the process of guideline development, the official position of the ESA changed to favour the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. This report includes general recommendations as well as specific recommendations in various fields of surgical interventions. The final draft guideline was posted on the ESA website for four weeks and the link was sent to all ESA members. Comments were collated and the guidelines amended as appropriate. When the final draft was complete, the Guidelines Committee and ESA Board ratified the guidelines.
883 citations
TL;DR: Viral delivery of TFEB to the liver prevented weight gain and metabolic syndrome in both diet-induced and genetic mouse models of obesity, suggesting a new therapeutic strategy for disorders of lipid metabolism.
Abstract: The lysosomal-autophagic pathway is activated by starvation and plays an important role in both cellular clearance and lipid catabolism. However, the transcriptional regulation of this pathway in response to metabolic cues is uncharacterized. Here we show that the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is induced by starvation through an autoregulatory feedback loop and exerts a global transcriptional control on lipid catabolism via Ppargc1α and Ppar1α. Thus, during starvation a transcriptional mechanism links the autophagic pathway to cellular energy metabolism. The conservation of this mechanism in Caenorhabditis elegans suggests a fundamental role for TFEB in the evolution of the adaptive response to food deprivation. Viral delivery of TFEB to the liver prevented weight gain and metabolic syndrome in both diet-induced and genetic mouse models of obesity, suggesting a new therapeutic strategy for disorders of lipid metabolism.
737 citations
TL;DR: In this article, a detailed description of the analysis used by the CMS Collaboration in the search for the standard model Higgs boson in pp collisions at the LHC, which led to the observation of a new boson.
Abstract: A detailed description is reported of the analysis used by the CMS Collaboration in the search for the standard model Higgs boson in pp collisions at the LHC, which led to the observation of a new boson. The data sample corresponds to integrated luminosities up to 5.1 inverse femtobarns at sqrt(s) = 7 TeV, and up to 5.3 inverse femtobarns at sqrt(s) = 8 TeV. The results for five Higgs boson decay modes gamma gamma, ZZ, WW, tau tau, and bb, which show a combined local significance of 5 standard deviations near 125 GeV, are reviewed. A fit to the invariant mass of the two high resolution channels, gamma gamma and ZZ to 4 ell, gives a mass estimate of 125.3 +/- 0.4 (stat) +/- 0.5 (syst) GeV. The measurements are interpreted in the context of the standard model Lagrangian for the scalar Higgs field interacting with fermions and vector bosons. The measured values of the corresponding couplings are compared to the standard model predictions. The hypothesis of custodial symmetry is tested through the measurement of the ratio of the couplings to the W and Z bosons. All the results are consistent, within their uncertainties, with the expectations for a standard model Higgs boson.
643 citations
TL;DR: In this paper, the spin and parity quantum numbers of the Higgs boson were studied based on the collision data collected by the ATLAS experiment at the LHC, and the results showed that the standard model spin-parity J(...
608 citations
TL;DR: The concept for this analysis is to a large degree based on earlier BABAR work and we acknowledge the guidance provided by M. Mazur as discussed by the authors, who consulted with theorists A. Datta, S. Westhoff,S. Fajfer, J. Kamenik, and I. Nisandzic on the calculations of the charged Higgs contributions to the decay rates.
Abstract: The concept for this analysis is to a large degree based on earlier BABAR work and we acknowledge the guidance provided by M. Mazur. The authors consulted with theorists A. Datta, S. Westhoff, S. Fajfer, J. Kamenik, and I. Nisandzic on the calculations of the charged Higgs contributions to the decay rates. We are grateful for the extraordinary contributions of our PEP-II colleagues in achieving the excellent luminosity and machine conditions that have made this work possible. The success of this project also relied critically on the expertise and dedication of the computing organizations that support BABAR. The collaborating institutions wish to thank SLAC for its support and the kind hospitality extended to them. This work is supported by the U.S. Department of Energy and National Science Foundation, the Natural Sciences and Engineering Research Council (Canada), the Commissariat a l'Energie Atomique and Institut National de Physique Nucleaire et de Physique des Particules (France), the Bundesministerium fur Bildung und Forschung and Deutsche Forschungsgemeinschaft (Germany), the Istituto Nazionale di Fisica Nucleare (Italy), the Foundation for Fundamental Research on Matter (Netherlands), the Research Council of Norway, the Ministry of Education and Science of the Russian Federation, Ministerio de Economia y Competitividad (Spain), and the Science and Technology Facilities Council (United Kingdom). Individuals have received support from the Marie-Curie IEF program (European Union) and the A. P. Sloan Foundation (USA).
TL;DR: In this paper, two-particle angular correlations for charged particles emitted in pPb collisions at a nucleon-nucleon center-of-mass energy of 5.02 TeV are presented.
TL;DR: The molecular mechanism through which clothianidin adversely affects the insect immune response and promotes replication of a viral pathogen in honey bees bearing covert infections is described and shed light on a further level of regulation of the immune response in insects and has implications for bee conservation.
Abstract: Large-scale losses of honey bee colonies represent a poorly understood problem of global importance. Both biotic and abiotic factors are involved in this phenomenon that is often associated with high loads of parasites and pathogens. A stronger impact of pathogens in honey bees exposed to neonicotinoid insecticides has been reported, but the causal link between insecticide exposure and the possible immune alteration of honey bees remains elusive. Here, we demonstrate that the neonicotinoid insecticide clothianidin negatively modulates NF-κB immune signaling in insects and adversely affects honey bee antiviral defenses controlled by this transcription factor. We have identified in insects a negative modulator of NF-κB activation, which is a leucine-rich repeat protein. Exposure to clothianidin, by enhancing the transcription of the gene encoding this inhibitor, reduces immune defenses and promotes the replication of the deformed wing virus in honey bees bearing covert infections. This honey bee immunosuppression is similarly induced by a different neonicotinoid, imidacloprid, but not by the organophosphate chlorpyriphos, which does not affect NF-κB signaling. The occurrence at sublethal doses of this insecticide-induced viral proliferation suggests that the studied neonicotinoids might have a negative effect at the field level. Our experiments uncover a further level of regulation of the immune response in insects and set the stage for studies on neural modulation of immunity in animals. Furthermore, this study has implications for the conservation of bees, as it will contribute to the definition of more appropriate guidelines for testing chronic or sublethal effects of pesticides used in agriculture.
TL;DR: Advances in water chemistry in the last decade have improved knowledge about the genesis, composition, and structure of dissolved organic matter, and its effect on the environment, and improved purification methods have enabled facile desalting and concentration of freshly collected DOM samples, thereby complementing the analytical process.
Abstract: Advances in water chemistry in the last decade have improved our knowledge about the genesis, com- position, and structure of dissolved organic matter, and its effect on the environment. Improvements in analyti- cal technology, for example Fourier-transform ion cyclo- tron (FT-ICR) mass spectrometry (MS), homo and hetero-correlated multidimensional nuclear magnetic res- onance (NMR) spectroscopy, and excitation emission matrix fluorimetry (EEMF) with parallel factor (PARAFAC) analysis for UV-fluorescence spectroscopy have resulted in these advances. Improved purification methods, for example ultrafiltration and reverse osmosis, have enabled facile desalting and concentration of fresh- ly collected DOM samples, thereby complementing the analytical process. Although its molecular weight (MW) remains undefined, DOM is described as a complex mixture of low-MW substances and larger-MW biomo- lecules, for example proteins, polysaccharides, and exo- cellular macromolecules. There is a general consensus that marine DOM originates from terrestrial and marine sources. A combination of diagenetic and microbial processes contributes to its origin, resulting in refractory organic matter which acts as carbon sink in the ocean. Ocean DOM is derived partially from humified products of plants decay dissolved in fresh water and transported to the ocean, and partially from proteinaceous and poly- saccharide material from phytoplankton metabolism, which undergoes in-situ microbial processes, becoming refractory. Some of the DOM interacts with radiation and is, therefore, defined as chromophoric DOM (CDOM). CDOM is classified as terrestrial, marine, anthropogenic, or mixed, depending on its origin. Ter- restrial CDOM reaches the oceans via estuaries, whereas autochthonous CDOM is formed in sea water by micro- bial activity; anthropogenic CDOM is a result of human activity. CDOM also affects the quality of water, by shielding it from solar radiation, and constitutes a car- bon sink pool. Evidence in support of the hypothesis that part of marine DOM is of terrestrial origin, being the result of a long-term carbon sedimentation, has been obtained from several studies discussed herein.
TL;DR: In this article, the production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs were measured using the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of 7 TeV and 8 TeV, corresponding to an integrated luminosity of about 25/fb.
TL;DR: This review focuses on the emerging complexity of the SOS signaling and SOS protein functions, and highlights recent understanding on how the SOS proteins contribute to different responses to salt stress besides ion homeostasis.
TL;DR: This review provides a comprehensive appraisal of several VS approaches currently available and special emphasis will be given to in silico chemogenomics approaches which utilize annotated ligand-target as well as protein-ligand interaction databases and which could predict or reveal promiscuous binding and polypharmacology.
Abstract: Virtual screening (VS) is a powerful technique for identifying hit molecules as starting points for medicinal chemistry. The number of methods and softwares which use the ligand and target-based VS approaches is increasing at a rapid pace. What, however, are the real advantages and disadvantages of the VS technology and how applicable is it to drug discovery projects? This review provides a comprehensive appraisal of several VS approaches currently available. In the first part of this work, an overview of the recent progress and advances in both ligand-based VS (LBVS) and structure-based VS (SBVS) strategies highlighting current problems and limitations will be provided. Special emphasis will be given to in silico chemogenomics approaches which utilize annotated ligand-target as well as protein-ligand interaction databases and which could predict or reveal promiscuous binding and polypharmacology, the knowledge of which would help medicinal chemists to design more potent clinical candidates with fewer side effects. In the second part, recent case studies (all published in the last two years) will be discussed where the VS technology has been applied successfully. A critical analysis of these case studies provides a good platform in order to estimate the applicability of various VS strategies in the new lead identification and optimization.
TL;DR: The proper selection of substrate concentration and buffer is proposed as a practical means of tailoring polydopamine functionality via control of competing pathways downstream of dopamine quinone.
Abstract: Rational approaches to engineering polydopamine films with tailored properties for surface coating and functionalization are currently challenged by the lack of detailed information about the polymer structure and the mechanism of buildup. Using an integrated chemical and spectroscopic approach enables the demonstration of: a) a three-component structure of polydopamine, comprising uncyclized (catecholamine) and cyclized (indole) units, as well as novel pyrrolecarboxylic acid moieties; b) remarkable variations in the relative proportions of the cyclized and uncyclized units with starting dopamine concentration; c) the occurrence of oligomer components up to the tetramer level; d) the covalent incorporation of Tris buffer; and e) the role of dopamine quinone as a crucial control point for directing the buildup pathways and tuning the properties. The importance of the uncyclized amine-containing units in polydopamine adhesion is also highlighted. The proper selection of substrate concentration and buffer is thus proposed as a practical means of tailoring polydopamine functionality via control of competing pathways downstream of dopamine quinone.
TL;DR: Two-particle correlations in relative azimuthal angle and pseudorapidity are measured using the ATLAS detector at the LHC and the resultant Δø correlation is approximately symmetric about π/2, and is consistent with a dominant cos2Δø modulation for all ΣE(T)(Pb) ranges and particle p(T).
Abstract: Two-particle correlations in relative azimuthal angle (Delta phi) and pseudorapidity (Delta eta) are measured in root S-NN = 5.02 TeV p + Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1 mu b(-1) of data as a function of transverse momentum (p(T)) and the transverse energy (Sigma E-T(Pb)) summed over 3.1 < eta < 4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2 < vertical bar Delta eta vertical bar < 5) "near-side" (Delta phi similar to 0) correlation that grows rapidly with increasing Sigma E-T(Pb). A long-range "away-side" (Delta phi similar to pi) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small Sigma E-T(Pb), is found to match the near-side correlation in magnitude, shape (in Delta eta and Delta phi) and Sigma E-T(Pb) dependence. The resultant Delta phi correlation is approximately symmetric about pi/2, and is consistent with a dominant cos2 Delta phi modulation for all Sigma E-T(Pb) ranges and particle p(T).
TL;DR: In this article, an intertemporal consumption model of investment in financial literacy is presented, where consumers benefit from such investment because financial literacy allows them to increase the returns on wealth.
Abstract: We present an intertemporal consumption model of investment in financial literacy. Consumers benefit from such investment because financial literacy allows them to increase the returns on wealth. Since literacy depreciates over time and has a cost in terms of current consumption, the model delivers an optimal investment in literacy. Furthermore, literacy and wealth are determined jointly, and are positively correlated over the life-cycle. The model drives our empirical approach to the analysis of the effect of financial literacy on wealth and saving and indicates that the stock of financial literacy early in life is a valid instrument in the regression of wealth on financial literacy. Using microeconomic and aggregate data, we find strong support for the model’s predictions.
TL;DR: In this paper, measurements of two-and four-particle angular correlations for charged particles emitted in pPb collisions are presented over a wide range in pseudorapidity and full azimuth.
TL;DR: Genomic and genetic studies have elucidated the role of mobile genetic elements in the transfer of antibiotic resistance genes and substantiate the rate of genetic alterations associated with acquisition in A. baumannii of various resistance genes, including OXA- and metallo-β-lactamase-type carbapenemase genes.
Dalhousie University1, Charité2, National Institutes of Health3, University of Geneva4, Karolinska Institutet5, State University of Campinas6, University of Adelaide7, University of Paris8, Medical University of Graz9, Mayo Clinic10, Academia Sinica11, University of Bonn12, University of Cagliari13, Johns Hopkins University14, French Institute of Health and Medical Research15, Ludwig Maximilian University of Munich16, Neuroscience Research Australia17, University of Toronto18, University of Göttingen19, Osaka University20, University of California, San Diego21, United States Department of Veterans Affairs22, University of Würzburg23, National Taiwan University24, Hokkaido University25, University of Antioquia26, University of Naples Federico II27, University of New South Wales28, Fujita Health University29, Nagoya University30, Harvard University31, Dresden University of Technology32, University of Iowa33, Université de Montréal34, University of Queensland35, Heidelberg University36
TL;DR: The key phenotypic measures of the “Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder” scale currently used in the Consortium on lithium Genetics (ConLiGen) study are reported.
Abstract: OBJECTIVE: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. MATERIALS AND METHODS: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (κ)] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. RESULTS: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (κ = 0.66 and κ = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (ICC1 = 0.71 and ICC2 = 0.75, respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). CONCLUSIONS: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.
TL;DR: The workflow of applying culture-independent HTS to food matrices is described, the current scenario and future perspectives of HTS uses to study food microbiota are presented, and the decision-making process leading to the best choice of working conditions to fulfill the specific needs of food research is described.
Abstract: Following recent trends in environmental microbiology, food microbiology has benefited from the advances in molecular biology and adopted novel strategies to detect, identify, and monitor microbes in food. An in-depth study of the microbial diversity in food can now be achieved by using high-throughput sequencing (HTS) approaches after direct nucleic acid extraction from the sample to be studied. In this review, the workflow of applying culture-independent HTS to food matrices is described. The current scenario and future perspectives of HTS uses to study food microbiota are presented, and the decision-making process leading to the best choice of working conditions to fulfill the specific needs of food research is described.
TL;DR: Current observational worldwide data on non-valvular atrial fibrillation, collected at the end of the vitamin K antagonist-only era, indicate that these drugs are frequently not being used according to stroke risk scores and guidelines, with overuse in patients at low risk and underuse in those at high risk of stroke.
Abstract: Background: Limited data are available on the characteristics, clinical management, and outcomes of patients with atrial fibrillation at risk of stroke, from a worldwide perspective. The aim of this study was to describe the baseline characteristics and initial therapeutic management of patients with non-valvular atrial fibrillation across the spectrum of sites at which these patients are treated. Methods and Findings: The Global Anticoagulant Registry in the FIELD (GARFIELD) is an observational study of patients newly diagnosed with non-valvular atrial fibrillation. Enrollment into Cohort 1 (of 5) took place between December 2009 and October 2011 at 540 sites in 19 countries in Europe, Asia-Pacific, Central/South America, and Canada. Investigator sites are representative of the distribution of atrial fibrillation care settings in each country. Cohort 1 comprised 10,614 adults ($18 years) diagnosed with non-valvular atrial fibrillation within the previous 6 weeks, with $1 investigator-defined stroke risk factor (not limited to those in existing risk-stratification schemes), and regardless of therapy. Data collected at baseline included demographics, medical history, care setting, nature of atrial fibrillation, and treatments initiated at diagnosis. The mean (SD) age of the population was 70.2 (11.2) years; 43.2% were women. Mean6SD CHADS2 score was 1.961.2, and 57.2% had a score $2. Mean CHA2DS2-VASc score was 3.261.6, and 8,957 (84.4%) had a score $2. Overall, 38.0% of patients with a CHADS2 score $2 did not receive anticoagulant therapy, whereas 42.5% of those at low risk (score 0) received anticoagulant therapy. Conclusions: These contemporary observational worldwide data on non-valvular atrial fibrillation, collected at the end of the vitamin K antagonist-only era, indicate that these drugs are frequently not being used according to stroke risk scores and guidelines, with overuse in patients at low risk and underuse in those at high risk of stroke.
TL;DR: Recent pre-clinical evidence indicating that targeting the intracellular environment surrounding the misfolded mutant CFTR instead of protein itself could constitute an attractive therapeutic option to sensitize patients carrying the F508del-CFTR mutation to the beneficial action of CFTR potentiators on lung inflammation is reviewed.
Abstract: Cystic fibrosis (CF) patients harboring the most common deletion mutation of the cystic fibrosis transmembrane conductance regulator (CFTR), F508del, are poor responders to potentiators of CFTR channel activity which can be used to treat a small subset of CF patients who genetically carry plasma membrane-resident CFTR mutants. The misfolded F508del-CFTR protein is unstable in the plasma membrane even if rescued by pharmacological agents that prevent its intracellular retention and degradation. CF is a conformational disease in which defective CFTR induces an impressive derangement of general proteostasis resulting from disabled autophagy. In this review, we discuss how rescuing Beclin 1 (BECN1), a major player of autophagosome formation, either by means of direct gene transfer or indirectly by administration of proteostasis regulators, could stabilize F508del-CFTR at the plasma membrane. We focus on the relationship between the improvement of peripheral proteostasis and CFTR plasma membrane stability in F508del-CFTR homozygous bronchial epithelia or mouse lungs. Moreover, this article reviews recent preclinical evidence indicating that targeting the intracellular environment surrounding the misfolded mutant CFTR instead of protein itself could constitute an attractive therapeutic option to sensitize patients carrying the F508del-CFTR mutation to the beneficial action of CFTR potentiators on lung inflammation.
TL;DR: In this article, the authors used quantitative phosphoproteomics to compare the global changes in phosphopeptides in WT and snrk2.2.3/2.6 triple mutant seedlings.
Abstract: Sucrose nonfermenting 1 (SNF1)-related protein kinase 2s (SnRK2s) are central components of abscisic acid (ABA) signaling pathways. The snrk2.2/2.3/2.6 triple-mutant plants are nearly completely insensitive to ABA, suggesting that most of the molecular actions of ABA are triggered by the SnRK2s-mediated phosphorylation of substrate proteins. Only a few substrate proteins of the SnRK2s are known. To identify additional substrate proteins of the SnRK2s and provide insight into the molecular actions of ABA, we used quantitative phosphoproteomics to compare the global changes in phosphopeptides in WT and snrk2.2/2.3/2.6 triple mutant seedlings in response to ABA treatment. Among the 5,386 unique phosphorylated peptides identified in this study, we found that ABA can increase the phosphorylation of 166 peptides and decrease the phosphorylation of 117 peptides in WT seedlings. In the snrk2.2/2.3/2.6 triple mutant, 84 of the 166 peptides, representing 58 proteins, could not be phosphorylated, or phosphorylation was not increased under ABA treatment. In vitro kinase assays suggest that most of the 58 proteins can serve as substrates of the SnRK2s. The SnRK2 substrates include proteins involved in flowering time regulation, RNA and DNA binding, miRNA and epigenetic regulation, signal transduction, chloroplast function, and many other cellular processes. Consistent with the SnRK2 phosphorylation of flowering time regulators, the snrk2.2/2.3/2.6 triple mutant flowered significantly earlier than WT. These results shed new light on the role of the SnRK2 protein kinases and on the downstream effectors of ABA action, and improve our understanding of plant responses to adverse environments.
TL;DR: Results suggest that Metformin might be associated with a significant reduction in the risk of cancer and cancer-related mortality, and randomized trials specifically designed to evaluate the efficacy of metformin as an anticancer agent are warranted.
Abstract: Aims/Hypothesis
Diabetes treatments were related with either an increased or reduced risk of cancer. There is ongoing debate about a potential protective action of metformin. To summarize evidence on the association between metformin and risk of cancer and cancer mortality in patients with diabetes.
Methods
Data source: MEDLINE and EMBASE (January 1966-April 2012). We selected randomized studies comparing metformin and other hypoglycaemic agents and observational studies exploring the association between exposure to metformin and cancer. Outcomes were cancer mortality, all malignancies and site-specific cancers.
Results
Of 25307 citations identified, 12 randomized controlled trials (21,595 patients) and 41 observational studies (1,029,389 patients) met the inclusion criteria. In observational studies there was a significant association of exposure to metformin with the risk of cancer death [6 studies, 24,410 patients, OR:0.65, 95%CI: 0.53-0.80], all malignancies [18 studies, 561,836 patients, OR:0.73, 95%CI: 0.61-0.88], liver [8 studies, 312,742 patients, OR:0.34; 95%CI: 0.19-0.60] colorectal [12 studies, 871,365 patients, OR:0.83, 95%CI: 0.74–0.92], pancreas [9 studies, 847,248 patients, OR:0.56, 95%CI: 0.36–0.86], stomach [2 studies, 100701 patients, OR:0.83, 95%CI: 0.76–0.91], and esophagus cancer [2 studies, 100694 patients, OR:0.90, 95%CI: 0.83–0.98]. No significant difference of risk was observed in randomized trials. Metformin was not associated with the risk of: breast cancer, lung cancer, ovarian cancer, uterus cancer, prostate cancer, bladder cancer, kidney cancer, and melanoma.
Conclusions/Interpretation
Results suggest that Metformin might be associated with a significant reduction in the risk of cancer and cancer-related mortality. Randomized trials specifically designed to evaluate the efficacy of metformin as an anticancer agent are warranted.
Seoul National University of Science and Technology1, Catholic University of Leuven2, Utrecht University3, Georgia State University4, Aarhus University5, University of Naples Federico II6, University of Georgia7, University of Savoy8, Cardiff University9, Shanghai Jiao Tong University10, Kaunas University of Technology11, Indiana University12, University of Bern13, University of Western Australia14
TL;DR: The authors revisited the conceptual and operational definitions of PSM to address weaknesses previously noted in the literature and took a more systematic and comprehensive approach by combining the efforts of international PSM scholars to develop and then test a revised measurement instrument for PSM in 12 countries.
Abstract: The growth in international research on public service motivation (PSM) raises a number of important questions about the degree to which the theory and research developed in one country can contribute to our understanding of PSM in other counties. To help address this issue, this study revisits the conceptual and operational definitions of PSM to address weaknesses previously noted in the literature. Although some important steps have been taken to both improve and internationalize the PSM scale, this work has been done incrementally. In contrast, this study takes a more systematic and comprehensive approach by combining the efforts of international PSM scholars to develop and then test a revised measurement instrument for PSM in 12 countries. Although the resulting four dimensional 16-item measure of PSM reported here provides a better theoretical and empirical foundation for the measurement of PSM, our results suggest that the exact meaning and scaling of PSM dimensions are likely to differ across cultures and languages. These results raise serious concerns regarding the ability to develop a single universal scale of PSM, or making direct comparisons of PSM across countries. Its earlier versions were delivered at the Annual Conference of the European Group for Public Administration, Toulouse, France, September 8–10, 2010, and at the 11th National Public Management Research Conference at Syracuse University, Syracuse, NY, June 2–4, 2011. Address correspondence to the author at smook@
TL;DR: Evidence is provided that also neutrophils can be driven towards distinct phenotypes in response to microenvironmental signals, and the identification of mechanisms and molecules associated with macrophage and neutrophil plasticity and polarized activation provides a basis for new diagnostic and therapeutic strategies.
Abstract: Tumor-associated macrophages (TAMs) are a key component of the tumor microenvironment and orchestrate various aspects of cancer. Diversity and plasticity are hallmarks of cells of the monocyte–macrophage lineage. In response to distinct signals macrophages undergo M1 (classical) or M2 (alternative) activation, which represent extremes of a continuum in a spectrum of activation states. Metabolic adaptation is a key component of macrophage plasticity and polarization, instrumental to their function in homeostasis, immunity and inflammation. Generally, TAMs acquire an M2-like phenotype that plays important roles in many aspects of tumor growth and progression. There is now evidence that also neutrophils can be driven towards distinct phenotypes in response to microenvironmental signals. The identification of mechanisms and molecules associated with macrophage and neutrophil plasticity and polarized activation provides a basis for new diagnostic and therapeutic strategies. J. Cell. Physiol. 228: 1404–1412, 2013. © 2012 Wiley Periodicals, Inc.