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https://www.readbyqxmd.com/read/28890317/mitoneod-a-mitochondria-targeted-superoxide-probe
#1
Maria M Shchepinova, Andrew G Cairns, Tracy A Prime, Angela Logan, Andrew M James, Andrew R Hall, Sara Vidoni, Sabine Arndt, Stuart T Caldwell, Hiran A Prag, Victoria R Pell, Thomas Krieg, John F Mulvey, Pooja Yadav, James N Cobley, Thomas P Bright, Hans M Senn, Robert F Anderson, Michael P Murphy, Richard C Hartley
Mitochondrial superoxide (O2(⋅-)) underlies much oxidative damage and redox signaling. Fluorescent probes can detect O2(⋅-), but are of limited applicability in vivo, while in cells their usefulness is constrained by side reactions and DNA intercalation. To overcome these limitations, we developed a dual-purpose mitochondrial O2(⋅-) probe, MitoNeoD, which can assess O2(⋅-) changes in vivo by mass spectrometry and in vitro by fluorescence. MitoNeoD comprises a O2(⋅-)-sensitive reduced phenanthridinium moiety modified to prevent DNA intercalation, as well as a carbon-deuterium bond to enhance its selectivity for O2(⋅-) over non-specific oxidation, and a triphenylphosphonium lipophilic cation moiety leading to the rapid accumulation within mitochondria...
August 24, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28777774/symptom-guided-emergency-department-discharge-instructions-for-children-with-concussion
#2
Talia M Brooks, Marissa M Smith, Renee M Silvis, Trudy Lerer, Christine Henry Mulvey, Ralynne Maitland, Amy L Dunn, Kelsey Logan, Sharon R Smith
OBJECTIVES: The objective was to evaluate the use and utility of a novel set of emergency department discharge instructions (DIs) for concussion based on a child's ongoing symptoms: symptom-guided DIs (symptom DIs). Differences in clinical outcomes were also assessed. METHODS: A convenience sample of 114 children aged 7 to 17 years presenting to an urban pediatric emergency department with a complaint of concussion was assembled. Children were randomized to standard DIs or symptom DIs...
August 2017: Pediatric Emergency Care
https://www.readbyqxmd.com/read/28662314/litmp-trans-metal-trapping-of-fluorinated-aromatic-molecules-a-comparative-study-of-aluminum-and-gallium-carbanion-traps
#3
Ross McLellan, Marina Uzelac, Alan R Kennedy, Eva Hevia, Robert E Mulvey
Fluoroaromatic scaffolds pose a challenge to lithiation due to low stability of lithiated intermediates. Here we apply trans-metal-trapping (TMT) to a series of key fluorinated aromatics. In TMT, LiTMP performs the metalation, while an organometallic trap intercepts the emergent carbanion. This study contrasts the trapping abilities of iBu2 AlTMP and Ga(CH2 SiMe3 )3 , structurally mapping their TMT reactions and probing relative stabilities of metalated fluoroaromatic intermediates by NMR studies. Results show the installed Al-C(aryl) bonds are more prone to decomposition by benzyne formation and Li-F liberation, than the Ga-C(aryl) species...
August 1, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28648630/resolution-of-a-steroid-resistant-hypereosinophilic-immune-diathesis-with-mepolizumab-and-concomitant-amelioration-of-a-mixed-thrombotic-microangiopathy
#4
J Justin Mulvey, Cynthia Magro, Amy Chadburn
The anaphylatoxins produced by an unbridled complement cascade in atypical hemolytic uremic syndrome (aHUS) can alter the leukocyte environment in tissues and peripheral blood, causing clinically significant eosinophilia. While the membrane attack complex and C5a anaphlatoxin can be suppressed with anti-C5 biologics, the production of C3a is still capable of driving a destructive hypereosinophilic syndrome in spite of anticomplement therapy. The side-effects of glucocorticoids in treating hypereosinophilic syndrome limit their therapeutic index in long-term treatment and this behooves the use of alternative strategies...
May 2, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28632788/high-throughput-identification-and-rational-design-of-synergistic-small-molecule-pairs-for-combating-and-bypassing-antibiotic-resistance
#5
Morgan A Wambaugh, Viplendra P S Shakya, Adam J Lewis, Matthew A Mulvey, Jessica C S Brown
Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28628457/clonal-clusters-and-virulence-factors-of-group-c-and-g-streptococcus-causing-severe-infections-manitoba-canada-2012-2014
#6
Sylvain A Lother, Walter Demczuk, Irene Martin, Michael Mulvey, Brenden Dufault, Philippe Lagacé-Wiens, Yoav Keynan
The incidence of group C and G Streptococcus (GCGS) bacteremia, which is associated with severe disease and death, is increasing. We characterized clinical features, outcomes, and genetic determinants of GCGS bacteremia for 89 patients in Winnipeg, Manitoba, Canada, who had GCGS bacteremia during 2012-2014. Of the 89 patients, 51% had bacteremia from skin and soft tissue, 70% had severe disease features, and 20% died. Whole-genome sequencing analysis was performed on isolates derived from 89 blood samples and 33 respiratory sample controls: 5 closely related genetic lineages were identified as being more likely to cause invasive disease than non-clade isolates (83% vs...
July 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28606370/factors-influencing-pediatrician-retirement-a-survey-of-american-academy-of-pediatrics-chapter-members
#7
Mary E Rimsza, Holly Ruch-Ross, Harold K Simon, Thomas W Pendergass, Holly J Mulvey
OBJECTIVE: To assess the factors that may influence physicians' desire to retire through an analysis of data collected through the American Academy of Pediatrics (AAP) State Pediatrician Workforce Survey. STUDY DESIGN: An electronic survey was sent to retired and nonretired US pediatricians who held AAP membership. The respondents were asked about the importance of 12 factors that would influence or had influenced their decision to retire. The physicians who were not yet retired also were asked: "If you could afford to today, would you retire from medicine?" RESULTS: The survey was completed by 8867 pediatricians...
September 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/28604172/opioids-combined-with-antidepressants-or-antiepileptic-drugs-for-cancer-pain-systematic-review-and-meta-analysis
#8
Chris M Kane, Matthew R Mulvey, Sophie Wright, Cheryl Craigs, Judy M Wright, Michael I Bennett
BACKGROUND: Combining antidepressant or antiepileptic drugs with opioids has resulted in increased pain relief when used for neuropathic pain in non-cancer conditions. However, evidence to support their effectiveness in cancer pain is lacking. AIM: To determine if there is additional benefit when opioids are combined with antidepressant or antiepileptic drugs for cancer pain. DESIGN: Systematic review and meta-analysis. Randomised control trials comparing opioid analgesia in combination with antidepressant or antiepileptic drugs versus opioid monotherapy were sought...
June 1, 2017: Palliative Medicine
https://www.readbyqxmd.com/read/28577489/european-contribution-to-the-study-of-ros-a-summary-of-the-findings-and-prospects-for-the-future-from-the-cost-action-bm1203-eu-ros
#9
REVIEW
Javier Egea, Isabel Fabregat, Yves M Frapart, Pietro Ghezzi, Agnes Görlach, Thomas Kietzmann, Kateryna Kubaichuk, Ulla G Knaus, Manuela G Lopez, Gloria Olaso-Gonzalez, Andreas Petry, Rainer Schulz, Jose Vina, Paul Winyard, Kahina Abbas, Opeyemi S Ademowo, Catarina B Afonso, Ioanna Andreadou, Haike Antelmann, Fernando Antunes, Mutay Aslan, Markus M Bachschmid, Rui M Barbosa, Vsevolod Belousov, Carsten Berndt, David Bernlohr, Esther Bertrán, Alberto Bindoli, Serge P Bottari, Paula M Brito, Guia Carrara, Ana I Casas, Afroditi Chatzi, Niki Chondrogianni, Marcus Conrad, Marcus S Cooke, João G Costa, Antonio Cuadrado, Pham My-Chan Dang, Barbara De Smet, Bilge Debelec-Butuner, Irundika H K Dias, Joe Dan Dunn, Amanda J Edson, Mariam El Assar, Jamel El-Benna, Péter Ferdinandy, Ana S Fernandes, Kari E Fladmark, Ulrich Förstermann, Rashid Giniatullin, Zoltán Giricz, Anikó Görbe, Helen Griffiths, Vaclav Hampl, Alina Hanf, Jan Herget, Pablo Hernansanz-Agustín, Melanie Hillion, Jingjing Huang, Serap Ilikay, Pidder Jansen-Dürr, Vincent Jaquet, Jaap A Joles, Balaraman Kalyanaraman, Danylo Kaminskyy, Mahsa Karbaschi, Marina Kleanthous, Lars-Oliver Klotz, Bato Korac, Kemal Sami Korkmaz, Rafal Koziel, Damir Kračun, Karl-Heinz Krause, Vladimír Křen, Thomas Krieg, João Laranjinha, Antigone Lazou, Huige Li, Antonio Martínez-Ruiz, Reiko Matsui, Gethin J McBean, Stuart P Meredith, Joris Messens, Verónica Miguel, Yuliya Mikhed, Irina Milisav, Lidija Milković, Antonio Miranda-Vizuete, Miloš Mojović, María Monsalve, Pierre-Alexis Mouthuy, John Mulvey, Thomas Münzel, Vladimir Muzykantov, Isabel T N Nguyen, Matthias Oelze, Nuno G Oliveira, Carlos M Palmeira, Nikoletta Papaevgeniou, Aleksandra Pavićević, Brandán Pedre, Fabienne Peyrot, Marios Phylactides, Gratiela G Pircalabioru, Andrew R Pitt, Henrik E Poulsen, Ignacio Prieto, Maria Pia Rigobello, Natalia Robledinos-Antón, Leocadio Rodríguez-Mañas, Anabela P Rolo, Francis Rousset, Tatjana Ruskovska, Nuno Saraiva, Shlomo Sasson, Katrin Schröder, Khrystyna Semen, Tamara Seredenina, Anastasia Shakirzyanova, Geoffrey L Smith, Thierry Soldati, Bebiana C Sousa, Corinne M Spickett, Ana Stancic, Marie José Stasia, Holger Steinbrenner, Višnja Stepanić, Sebastian Steven, Kostas Tokatlidis, Erkan Tuncay, Belma Turan, Fulvio Ursini, Jan Vacek, Olga Vajnerova, Kateřina Valentová, Frank Van Breusegem, Lokman Varisli, Elizabeth A Veal, A Suha Yalçın, Olha Yelisyeyeva, Neven Žarković, Martina Zatloukalová, Jacek Zielonka, Rhian M Touyz, Andreas Papapetropoulos, Tilman Grune, Santiago Lamas, Harald H H W Schmidt, Fabio Di Lisa, Andreas Daiber
The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members...
May 18, 2017: Redox Biology
https://www.readbyqxmd.com/read/28531208/phylogenetic-analysis-of-emergent-streptococcus-pneumoniae-serotype-22f-causing-invasive-pneumococcal-disease-using-whole-genome-sequencing
#10
Walter H B Demczuk, Irene Martin, Linda Hoang, Paul Van Caeseele, Brigitte Lefebvre, Greg Horsman, David Haldane, Jonathan Gubbay, Sam Ratnam, Gregory German, Jennifer Daley Bernier, Lori Strudwick, Allison McGeer, George G Zhanel, Gary Van Domselaar, Morag Graham, Michael R Mulvey
Since implementation of the 13-valent polyvalent conjugate vaccine (PCV13) in Canada during 2010, the proportion of PCV13 serotypes causing invasive pneumococcal disease (IPD) has declined from 55% (n = 1492) in 2010 to 31% (n = 764) in 2014. A concurrent increase of non-PCV13 serotypes has occurred and 22F has become the most prevalent serotype in Canada increasing from 7% (n = 183) to 11% (n = 283). Core single nucleotide variant phylogenetic analysis was performed on 137 Streptococcus pneumoniae serotype 22F isolates collected across Canada from 2005-2015...
2017: PloS One
https://www.readbyqxmd.com/read/28505331/antimicrobial-susceptibility-of-clinical-isolates-of-neisseria-gonorrhoeae-to-alternative-antimicrobials-with-therapeutic-potential
#11
P R S Lagacé-Wiens, H J Adam, N M Laing, M R Baxter, I Martin, M R Mulvey, J A Karlowsky, D J Hoban, G G Zhanel
Background: The prevalence of MDR Neisseria gonorrhoeae is increasing globally and represents a public health emergency. Development and approval of new anti-gonococcal agents may take years. As a concurrent approach to developing new antimicrobials, the laboratory and clinical evaluation of currently licensed antimicrobials not widely used for the treatment of gonorrhoea may provide new options for the treatment of gonococcal infections. Objectives: To determine the in vitro activity of nine alternative, currently licensed and late-development antimicrobials with the potential to treat gonococcal infections against 112 clinical isolates of N...
August 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28495876/a-subcellular-map-of-the-human-proteome
#12
Peter J Thul, Lovisa Åkesson, Mikaela Wiking, Diana Mahdessian, Aikaterini Geladaki, Hammou Ait Blal, Tove Alm, Anna Asplund, Lars Björk, Lisa M Breckels, Anna Bäckström, Frida Danielsson, Linn Fagerberg, Jenny Fall, Laurent Gatto, Christian Gnann, Sophia Hober, Martin Hjelmare, Fredric Johansson, Sunjae Lee, Cecilia Lindskog, Jan Mulder, Claire M Mulvey, Peter Nilsson, Per Oksvold, Johan Rockberg, Rutger Schutten, Jochen M Schwenk, Åsa Sivertsson, Evelina Sjöstedt, Marie Skogs, Charlotte Stadler, Devin P Sullivan, Hanna Tegel, Casper Winsnes, Cheng Zhang, Martin Zwahlen, Adil Mardinoglu, Fredrik Pontén, Kalle von Feilitzen, Kathryn S Lilley, Mathias Uhlén, Emma Lundberg
Resolving the spatial distribution of the human proteome at a subcellular level can greatly increase our understanding of human biology and disease. Here we present a comprehensive image-based map of subcellular protein distribution, the Cell Atlas, built by integrating transcriptomics and antibody-based immunofluorescence microscopy with validation by mass spectrometry. Mapping the in situ localization of 12,003 human proteins at a single-cell level to 30 subcellular structures enabled the definition of the proteomes of 13 major organelles...
May 26, 2017: Science
https://www.readbyqxmd.com/read/28471460/using-hyperlopit-to-perform-high-resolution-mapping-of-the-spatial-proteome
#13
Claire M Mulvey, Lisa M Breckels, Aikaterini Geladaki, Nina Kočevar Britovšek, Daniel J H Nightingale, Andy Christoforou, Mohamed Elzek, Michael J Deery, Laurent Gatto, Kathryn S Lilley
The organization of eukaryotic cells into distinct subcompartments is vital for all functional processes, and aberrant protein localization is a hallmark of many diseases. Microscopy methods, although powerful, are usually low-throughput and dependent on the availability of fluorescent fusion proteins or highly specific and sensitive antibodies. One method that provides a global picture of the cell is localization of organelle proteins by isotope tagging (LOPIT), which combines biochemical cell fractionation using density gradient ultracentrifugation with multiplexed quantitative proteomics mass spectrometry, allowing simultaneous determination of the steady-state distribution of hundreds of proteins within organelles...
June 2017: Nature Protocols
https://www.readbyqxmd.com/read/28431734/gender-and-engineering-aptitude-is-the-color-of-science-technology-engineering-and-math-materials-related-to-children-s-performance
#14
Kelly Lynn Mulvey, Bridget Miller, Victoria Rizzardi
To investigate gender stereotypes, demonstrated engineering aptitude, and attitudes, children (N=105) solved an engineering problem using either pastel-colored or primary-colored materials. Participants also evaluated the acceptability of denial of access to engineering materials based on gender and counter-stereotypic preferences (i.e., a boy who prefers pastel-colored materials). Whereas material color was not related to differences in female participants' performance, younger boys assigned to pastel materials demonstrated lower engineering aptitude than did other participants...
August 2017: Journal of Experimental Child Psychology
https://www.readbyqxmd.com/read/28427966/ivig-for-treatment-of-severe-refractory-heparin-induced-thrombocytopenia
#15
Anand Padmanabhan, Curtis G Jones, Shannon M Pechauer, Brian R Curtis, Daniel W Bougie, Mehraboon S Irani, Barbara J Bryant, Jack B Alperin, Thomas G Deloughery, Kevin P Mulvey, Binod Dhakal, Renren Wen, Demin Wang, Richard H Aster
BACKGROUND: Heparin-induced thrombocytopenia (HIT) complicated by severe thrombocytopenia and thrombosis can pose significant treatment challenges. Use of alternative anticoagulants in this setting may increase bleeding risks, especially in patients who have a protracted disease course. Additional therapies are lacking in this severely affected patient population. METHODS: We describe three patients with HIT who had severe thromboembolism and prolonged thrombocytopenia refractory to standard treatment but who achieved an immediate and sustained response to IVIg therapy...
April 17, 2017: Chest
https://www.readbyqxmd.com/read/28417608/comparison-of-antithrombotic-agents-during-urgent-percutaneous-coronary-intervention-following-thrombolytic-therapy-a-retrospective-cohort-study
#16
Jaya R Mallidi, Peter Robinson, Paul F Visintainer, Amir S Lotfi, Scott Mulvey, Gregory R Giugliano
BACKGROUND: The optimal antithrombotic regimen for urgent percutaneous coronary interventions (PCI) following thrombolytic therapy for ST segment myocardial infarction (STEMI) is currently unknown. METHODS: We performed a retrospective analysis of all patients referred to our institution from January 2005 to July 2014 who underwent urgent PCI within 24 hr after receiving thrombolytic therapy. The patients were divided into three cohorts based on the anticoagulation strategy during PCI-bivalirudin, heparin alone or heparin plus Glycoprotein IIb/IIIa inhibitor (GPI)...
April 18, 2017: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/28389840/children-s-and-adolescents-expectations-about-challenging-unfair-group-norms
#17
Kelly Lynn Mulvey, Melanie Killen
Youth often hold group norms that perpetuate inequality. One way these norms can be changed is by challenging these norms by choosing to include new members into these groups who hold morally just norms. In the current study, children's and adolescents' inclusion decisions and social reasoning about challenging group norms through inclusion were investigated. The sample included 9-10 (children) and 13-14 year-olds (adolescents) (N = 673, 54.4% female). Participants supported including challengers into groups holding norms supporting relational aggression and unequal allocation of resources, but they were less likely to support including a challenger into a physically aggressive group...
April 7, 2017: Journal of Youth and Adolescence
https://www.readbyqxmd.com/read/28375722/the-link-between-mental-illness-and-firearm-violence-implications-for-social-policy-and-clinical-practice
#18
John S Rozel, Edward P Mulvey
The United States has substantially higher levels of firearm violence than most other developed countries. Firearm violence is a significant and preventable public health crisis. Mental illness is a weak risk factor for violence despite popular misconceptions reflected in the media and policy. That said, mental health professionals play a critical role in assessing their patients for violence risk, counseling about firearm safety, and guiding the creation of rational and evidence-based public policy that can be effective in mitigating violence risk without unnecessarily stigmatizing people with mental illness...
May 8, 2017: Annual Review of Clinical Psychology
https://www.readbyqxmd.com/read/28373355/the-rhomboid-protease-glpg-promotes-the-persistence-of-extraintestinal-pathogenic-escherichia-coli-within-the-gut
#19
Colin W Russell, Amanda C Richards, Alexander S Chang, Matthew A Mulvey
Extraintestinal pathogenic Escherichia coli (ExPEC) strains are typically benign within the mammalian gut but can disperse to extraintestinal sites to cause diseases like urinary tract infections and sepsis. As occupation of the intestinal tract is often a prerequisite for ExPEC-mediated pathogenesis, we set out to understand how ExPEC colonizes this niche. A screen using transposon sequencing (Tn-seq) was performed to search for genes within ExPEC isolate F11 that are important for growth in intestinal mucus, which is thought to be a major source of nutrients for E...
June 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28336136/antimicrobial-susceptibility-of-2906-pseudomonasaeruginosa-clinical-isolates-obtained-from-patients-in-canadian-hospitals-over-a-period-of-8-years-results-of-the-canadian-ward-surveillance-study-canward-2008-2015
#20
Andrew Walkty, Philippe Lagace-Wiens, Heather Adam, Melanie Baxter, James Karlowsky, Michael R Mulvey, Melissa McCracken, George G Zhanel
Pseudomonas aeruginosa is an important nosocomial pathogen. The purpose of this study was to evaluate the antimicrobial susceptibility profile of P. aeruginosa clinical isolates obtained from inpatients and outpatients at hospitals across Canada from January 2008 to December 2015 (CANWARD Study). Susceptibility testing was performed using broth microdilution, as described by the Clinical and Laboratory Standards Institute. In total, 2906 P. aeruginosa isolates were evaluated. The percentage of isolates susceptible to common antipseudomonal antimicrobials was: colistin 94...
January 2017: Diagnostic Microbiology and Infectious Disease
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