Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Spray-Drying Microencapsulation of Bauhinia ungulata L. var. obtusifolia Aqueous Extract Containing Phenolic Compounds: A Comparative Study Using Different Wall Materials

: Species belonging to the Bauhinia genus, usually known as "pata-de-vaca", are popularly used to treat diabetes. Bauhinia ungulata var. obtusifolia (Ducke) Vaz is among them, of which the leaves are used as a tea for medicinal purposes in the Amazon region. A microencapsulation study of lyophilized aqueous extract from Bauhinia ungulata leaves, which contain phenolic compounds, using five different wall materials (maltodextrin DE 4-7, maltodextrin DE 11-14; β-cyclodextrin; pectin and sodium carboxymethylcellulose) is described in this paper. The microstructure, particle size distribution, thermal behavior, yield, and encapsulation efficiency were investigated and compared using different techniques. Using high-performance liquid chromatography, phenolics, and flavonoids were detected and quantified in the microparticles. The microparticles obtained with a yield and phenolics encapsulation efficiency ranging within 60-83% and 35-57%, respectively, showed a particle size distribution between 1.15 and 5.54 μm, spherical morphology, and a wrinkled surface. Among them, those prepared with sodium carboxymethylcellulose or pectin proved to be the most thermally stable. They had the highest flavonoid content (23.07 and 21.73 mg RUTE/g Extract) and total antioxidant activity by both the DPPH (376.55 and 367.86 μM TEq/g Extract) and ABTS (1085.72 and 1062.32 μM TEq/g Extract) assays. The chromatographic analyses allowed for quantification of the following substances retained by the microparticles, chlorogenic acid (1.74-1.98 mg/g Extract), p-coumaric acid (0.06-0.08 mg/g Extract), rutin (11.2-12.9 mg/g Extract), and isoquercitrin (0.49-0.53 mg/g Extract), compounds which considered to responsible for the antidiabetic property attributed to the species

Structural and Functional Characterization of an Ancient Bacterial Transglutaminase Sheds Light on the Minimal Requirements for Protein Cross-Linking

Transglutaminases are best known for their ability to catalyze protein cross-linking reactions that impart chemical and physical resilience to cellular structures. Here, we report the crystal structure and characterization of Tgl, a transglutaminase from the bacterium <i>Bacillus subtilis.</i> Tgl is produced during sporulation and cross-links the surface of the highly resilient spore. Tgl-like proteins are found only in spore-forming bacteria of the <i>Bacillus</i> and <i>Clostridia</i> classes, indicating an ancient origin. Tgl is a single-domain protein, produced in active form, and the smallest transglutaminase characterized to date. We show that Tgl is structurally similar to bacterial cell wall endopeptidases and has an NlpC/P60 catalytic core, thought to represent the ancestral unit of the cysteine protease fold. We show that Tgl functions through a unique partially redundant catalytic dyad formed by Cys116 and Glu187 or Glu115. Strikingly, the catalytic Cys is insulated within a hydrophobic tunnel that traverses the molecule from side to side. The lack of similarity of Tgl to other transglutaminases together with its small size suggests that an NlpC/P60 catalytic core and insulation of the active site during catalysis may be essential requirements for protein cross-linking

Novel Antitubercular 6‑Dialkylaminopyrimidine Carboxamides from Phenotypic Whole-Cell High Throughput Screening of a SoftFocus Library: Structure–Activity Relationship and Target Identification Studies

A BioFocus DPI SoftFocus library of ∼35 000 compounds was screened against <i>Mycobacterium tuberculosis</i> (Mtb) in order to identify novel hits with antitubercular activity. The hits were evaluated in biology triage assays to exclude compounds suggested to function via frequently encountered promiscuous mechanisms of action including inhibition of the QcrB subunit of the cytochrome <i>bc</i>₁ complex, disruption of cell–wall homeostasis, and DNA damage. Among the hits that passed this screening cascade, a 6-dialkylamino­pyrimidine carboxamide series was prioritized for hit to lead optimization. Compounds from this series were active against clinical Mtb strains, while no cross-resistance to conventional antituberculosis drugs was observed. This suggested a novel mechanism of action, which was confirmed by chemoproteomic analysis leading to the identification of BCG_3193 and BCG_3827 as putative targets of the series with unknown function. Initial structure–activity relationship studies have resulted in compounds with moderate to potent antitubercular activity and improved physicochemical properties

Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

Rationale &amp; Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting &amp; Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (&lt;60, 60-69, and &gt;_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 &amp; PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages &lt;60, 60-69, and &gt;_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Search for supersymmetry in hadronic final states with missing transverse energy using the variables αT and b-quark multiplicity in pp collisions at √s = 8 TeV

Submitted by Vitor Silverio Rodrigues ([email protected]) on 2014-05-27T11:30:34Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:48:49Z : No. of bitstreams: 1 2-s2.0-84883824987.pdf: 1540579 bytes, checksum: be6bbff5192436d9fcdbc367ffd1650e (MD5) Made available in DSpace on 2014-05-27T11:30:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-09-01 An inclusive search for supersymmetric processes that produce final states with jets and missing transverse energy is performed in pp collisions at a centre-of-mass energy of 8 TeV. The data sample corresponds to an integrated luminosity of 11.7 fb-1 collected by the CMS experiment at the LHC. In this search, a dimensionless kinematic variable, αT, is used to discriminate between events with genuine and misreconstructed missing transverse energy. The search is based on an examination of the number of reconstructed jets per event, the scalar sum of transverse energies of these jets, and the number of these jets identified as originating from bottom quarks. No significant excess of events over the standard model expectation is found. Exclusion limits are set in the parameter space of simplified models, with a special emphasis on both compressed-spectrum scenarios and direct or gluino-induced production of third-generation squarks. For the case of gluino-mediated squark production, gluino masses up to 950-1125 GeV are excluded depending on the assumed model. For the direct pair-production of squarks, masses up to 450 GeV are excluded for a single light first- or second-generation squark, increasing to 600 GeV for bottom squarks. © 2013 CERN for the benefit of the CMS collaboration. CERN, Geneva Yerevan Physics Institute, Yerevan Institut für Hochenergiephysik der OeAW, Wien National Centre for Particle and High Energy Physics, Minsk Universiteit Antwerpen, Antwerpen Vrije Universiteit Brussel, Brussel Université Libre de Bruxelles, Bruxelles Ghent University, Ghent Université Catholique de Louvain, Louvain-la-Neuve Université de Mons, Mons Centro Brasileiro de Pesquisas Fisicas, Rio de Janeiro Universidade do Estado do Rio de Janeiro, Rio de Janeiro Universidade Estadual Paulista, São Paulo Universidade Federal do ABC, São Paulo Institute for Nuclear Research and Nuclear Energy, Sofia University of Sofia, Sofia Institute of High Energy Physics, Beijing State Key Laboratory of Nuclear Physics and Technology Peking University, Beijing Universidad de Los Andes, Bogota Technical University of Split, Split University of Split, Split Institute Rudjer Boskovic, Zagreb University of Cyprus, Nicosia Charles University, Prague Academy of Scientific Research and Technology of the Arab Republic of Egypt Egyptian Network of High Energy Physics, Cairo National Institute of Chemical Physics and Biophysics, Tallinn Department of Physics University of Helsinki, Helsinki Helsinki Institute of Physics, Helsinki Lappeenranta University of Technology, Lappeenranta DSM/IRFU CEA/Saclay, Gif-sur-Yvette Laboratoire Leprince-Ringuet, Ecole Polytechnique IN2P3-CNRS, Palaiseau Institut Pluridisciplinaire Hubert Curien, Universite de Strasbourg, Universite de Haute Alsace Mulh CNRS/IN2P3, Strasbourg CNRS-IN2P3, Institut de Physique Nucléaire de Lyon Université de Lyon, Université Claude Bernard Lyon 1, Villeurbanne Institute of High Energy Physics and Informatization Tbilisi State University, Tbilisi I. Physikalisches Institut RWTH Aachen University, Aachen III. Physikalisches Institut A RWTH Aachen University, Aachen III. Physikalisches Institut B RWTH Aachen University, Aachen Deutsches Elektronen-Synchrotron, Hamburg University of Hamburg, Hamburg Institut für Experimentelle Kernphysik, Karlsruhe Institute of Nuclear and Particle Physics (INPP) NCSR Demokritos, Aghia Paraskevi University of Athens, Athens University of Ioánnina, Ioánnina KFKI Research Institute for Particle and Nuclear Physics, Budapest Institute of Nuclear Research ATOMKI, Debrecen University of Debrecen, Debrecen Panjab University, Chandigarh University of Delhi, Delhi Saha Institute of Nuclear Physics, Kolkata Bhabha Atomic Research Centre, Mumbai Tata Institute of Fundamental Research - EHEP, Mumbai Tata Institute of Fundamental Research - HECR, Mumbai Institute for Research in Fundamental Sciences (IPM), Tehran INFN Sezione di Bari, Bari Università di Bari, Bari Politecnico di Bari, Bari INFN Sezione di Bologna, Bologna Università di Bologna, Bologna INFN Sezione di Catania, Catania Università di Catania, Catania INFN Sezione di Firenze, Firenze Università di Firenze, Firenze INFN Laboratori Nazionali di Frascati, Frascati INFN Sezione di Genova, Genova Università di Genova, Genova INFN Sezione di Milano-Bicocca, Milano Università di Milano-Bicocca, Milano INFN Sezione di Napoli, Napoli Università di Napoli 'Federico II', Napoli Università della Basilicata (Potenza), Napoli Università G. Marconi (Roma), Napoli INFN Sezione di Padova, Padova Università di Padova, Padova Università di Trento (Trento), Padova INFN Sezione di Pavia, Pavia Università di Pavia, Pavia INFN Sezione di Perugia, Perugia Università di Perugia, Perugia INFN Sezione di Pisa, Pisa Università di Pisa, Pisa Scuola Normale Superiore di Pisa, Pisa INFN Sezione di Roma, Roma Università di Roma, Roma INFN Sezione di Torino, Torino Università di Torino, Torino Università del Piemonte Orientale (Novara), Torino INFN Sezione di Trieste, Trieste Università di Trieste, Trieste Kangwon National University, Chunchon Kyungpook National University, Daegu Institute for Universe and Elementary Particles Chonnam National University, Kwangju Korea University, Seoul University of Seoul, Seoul Sungkyunkwan University, Suwon Vilnius University, Vilnius Centro de Investigacion y de Estudios Avanzados del IPN, Mexico City Universidad Iberoamericana, Mexico City Benemerita Universidad Autonoma de Puebla, Puebla Universidad Autónoma de San Luis Potosí, San Luis Potosí University of Auckland, Auckland University of Canterbury, Christchurch National Centre for Physics Quaid-I-Azam University, Islamabad National Centre for Nuclear Research, Swierk Institute of Experimental Physics, Faculty of Physics University of Warsaw, Warsaw Laboratório de Instrumentação e Física Experimental de Partículas, Lisboa Joint Institute for Nuclear Research, Dubna Petersburg Nuclear Physics Institute, Gatchina (St. Petersburg) Institute for Nuclear Research, Moscow Institute for Theoretical and Experimental Physics, Moscow P.N. Lebedev Physical Institute, Moscow Skobeltsyn Institute of Nuclear Physics Lomonosov Moscow State University, Moscow State Research Center of Russian Federation Institute for High Energy Physics, Protvino Faculty of Physics and Vinca Institute of Nuclear Sciences University of Belgrade, Belgrade Centro de Investigaciones Energéticas Medioambientales y Tecnológicas (CIEMAT), Madrid Universidad Autónoma de Madrid, Madrid Universidad de Oviedo, Oviedo Instituto de Física de Cantabria (IFCA) CSIC-Universidad de Cantabria, Santander European Organization for Nuclear Research CERN, Geneva Paul Scherrer Institut, Villigen Institute for Particle Physics ETH Zurich, Zurich Universität Zürich, Zurich National Central University, Chung-Li National Taiwan University (NTU), Taipei Chulalongkorn University, Bangkok Cukurova University, Adana Physics Department Middle East Technical University, Ankara Bogazici University, Istanbul Istanbul Technical University, Istanbul National Scientific Center Kharkov Institute of Physics and Technology, Kharkov University of Bristol, Bristol Rutherford Appleton Laboratory, Didcot Imperial College, London Brunel University, Uxbridge Baylor University, Waco The University of Alabama, Tuscaloosa Boston University, Boston Brown University, Providence University of California, Davis, Davis University of California, Los Angeles University of California, Riverside, Riverside University of California, San Diego, La Jolla University of California, Santa Barbara, Santa Barbara California Institute of Technology, Pasadena Carnegie Mellon University, Pittsburgh University of Colorado at Boulder, Boulder Cornell University, Ithaca Fairfield University, Fairfield Fermi National Accelerator Laboratory, Batavia University of Florida, Gainesville Florida International University, Miami Florida State University, Tallahassee Florida Institute of Technology, Melbourne University of Illinois at Chicago (UIC), Chicago The University of Iowa, Iowa City Johns Hopkins University, Baltimore The University of Kansas, Lawrence Kansas State University, Manhattan Lawrence Livermore National Laboratory, Livermore University of Maryland, College Park Massachusetts Institute of Technology, Cambridge University of Minnesota, Minneapolis University of Mississippi, Oxford University of Nebraska-Lincoln, Lincoln State University of New York at Buffalo, Buffalo Northeastern University, Boston Northwestern University, Evanston University of Notre Dame, Notre Dame The Ohio State University, Columbus Princeton University, Princeton University of Puerto Rico, Mayaguez Purdue University, West Lafayette Purdue University Calumet, Hammond Rice University, Houston University of Rochester, Rochester The Rockefeller University, New York Rutgers The State University of New Jersey, Piscataway University of Tennessee, Knoxville Texas A and M University, College Station Texas Tech University, Lubbock Vanderbilt University, Nashville University of Virginia, Charlottesville Wayne State University, Detroit University of Wisconsin, Madison Universidade Estadual Paulista, São Paul