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Michael O'Brien

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https://www.readbyqxmd.com/read/28103426/analytical-characterization-and-pharmacological-evaluation-of-the-new-psychoactive-substance-4-fluoromethylphenidate-4%C3%A2-f-mph-and-differentiation-between-the-%C3%A2-threo-and-%C3%A2-erythro-diastereomers
#1
Gavin McLaughlin, Noreen Morris, Pierce V Kavanagh, John D Power, Geraldine Dowling, Brendan Twamley, John O'Brien, Gary Hessman, Brian Murphy, Donna Walther, John S Partilla, Michael H Baumann, Simon D Brandt
Misuse of (±)-threo-methylphenidate (methyl-2-phenyl-2-(piperidin-2-yl)acetate; Ritalin®, MPH) has long been acknowledged, but the appearance of MPH analogs in the form of 'research chemicals' has only emerged in more recent years. 4-Fluoromethylphenidate (4 F-MPH) is one of these recent examples and this study presents the identification and analytical characterization of two powdered 4 F-MPH products that were obtained from an online vendor in 2015. Interestingly, the products appeared to have originated from two distinct batches given that one product consisted of (±)-threo-4 F-MPH isomers whereas the second sample consisted of a mixture of (±)-threo and (±)-erythro 4 F-MPH...
January 19, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28096418/multi-institute-analysis-of-carbapenem-resistance-reveals-remarkable-diversity-unexplained-mechanisms-and-limited-clonal-outbreaks
#2
Gustavo C Cerqueira, Ashlee M Earl, Christoph M Ernst, Yonatan H Grad, John P Dekker, Michael Feldgarden, Sinéad B Chapman, João L Reis-Cunha, Terrance P Shea, Sarah Young, Qiandong Zeng, Mary L Delaney, Diane Kim, Ellena M Peterson, Thomas F O'Brien, Mary Jane Ferraro, David C Hooper, Susan S Huang, James E Kirby, Andrew B Onderdonk, Bruce W Birren, Deborah T Hung, Lisa A Cosimi, Jennifer R Wortman, Cheryl I Murphy, William P Hanage
Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to the antibiotic era. Multiple different species can exhibit resistance due to many different mechanisms, and many different mobile elements are capable of transferring resistance between lineages. We prospectively sampled CRE from hospitalized patients from three Boston-area hospitals, together with a collection of CRE from a single California hospital, to define the frequency and characteristics of outbreaks and determine whether there is evidence for transfer of strains within and between hospitals and the frequency with which resistance is transferred between lineages or species...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28092665/antibody-10-1074-suppresses-viremia-in-hiv-1-infected-individuals
#3
Marina Caskey, Till Schoofs, Henning Gruell, Allison Settler, Theodora Karagounis, Edward F Kreider, Ben Murrell, Nico Pfeifer, Lilian Nogueira, Thiago Y Oliveira, Gerald H Learn, Yehuda Z Cohen, Clara Lehmann, Daniel Gillor, Irina Shimeliovich, Cecilia Unson-O'Brien, Daniela Weiland, Alexander Robles, Tim Kümmerle, Christoph Wyen, Rebeka Levin, Maggi Witmer-Pack, Kemal Eren, Caroline Ignacio, Szilard Kiss, Anthony P West, Hugo Mouquet, Barry S Zingman, Roy M Gulick, Tibor Keler, Pamela J Bjorkman, Michael S Seaman, Beatrice H Hahn, Gerd Fätkenheuer, Sarah J Schlesinger, Michel C Nussenzweig, Florian Klein
Monoclonal antibody 10-1074 targets the V3 glycan supersite on the HIV-1 envelope (Env) protein. It is among the most potent anti-HIV-1 neutralizing antibodies isolated so far. Here we report on its safety and activity in 33 individuals who received a single intravenous infusion of the antibody. 10-1074 was well tolerated and had a half-life of 24.0 d in participants without HIV-1 infection and 12.8 d in individuals with HIV-1 infection. Thirteen individuals with viremia received the highest dose of 30 mg/kg 10-1074...
January 16, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28089755/biodistribution-and-retention-of-locally-administered-human-mesenchymal-stromal-cells-quantitative-polymerase-chain-reaction-based-detection-of-human-dna-in-murine-organs
#4
Michael Creane, Linda Howard, Timothy O'Brien, Cynthia M Coleman
BACKGROUND: Determining the distributive fate and retention of a cell therapy product after administration is an essential part of characterizing it's biosafety profile. Therefore, regulatory guidelines stipulate that biodistribution assays are a requirement prior to advancing a cell therapy to the clinic. Here the development of a highly sensitive quantitative polymerase chain reaction (qPCR)-based method of tracking the biodistribution and retention of human mesenchymal stromal cells (hMSCs) in mice, rats or rabbits is described...
January 12, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28089238/ruxolitinib-for-symptom-control-in-patients-with-chronic-lymphocytic-leukaemia-a-single-group-phase-2-trial
#5
Preetesh Jain, Michael Keating, Sarah Renner, Charles Cleeland, Huang Xuelin, Graciela Nogueras Gonzalez, David Harris, Ping Li, Zhiming Liu, Ivo Veletic, Uri Rozovski, Nitin Jain, Phillip Thompson, Prithviraj Bose, Courtney DiNardo, Alessandra Ferrajoli, Susan O'Brien, Jan Burger, William Wierda, Srdan Verstovsek, Hagop Kantarjian, Zeev Estrov
BACKGROUND: Disease-related symptoms impair the quality of life of patients with chronic lymphocytic leukaemia (CLL) who do not require systemic therapy. Available therapies are not specifically aimed at symptom control. Because stimulation of the B-cell receptor activates JAK2 in CLL cells and the JAK2 inhibitor ruxolitinib improves symptoms in patients with myelofibrosis, we postulated that ruxolitinib would improve disease-related symptoms in patients with CLL. We did a phase 2 trial of ruxolitinib to test this hypothesis...
January 11, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28081302/education-and-support-needs-in-patients-with-head-and-neck-cancer-a-multi-institutional-survey
#6
Joe Jabbour, Chris Milross, Puma Sundaresan, Ardalan Ebrahimi, Heather L Shepherd, Haryana M Dhillon, Gary Morgan, Bruce Ashford, Muzib Abdul-Razak, Eva Wong, Michael Veness, Carsten E Palme, Cate Froggatt, Ruben Cohen, Rafael Ekmejian, Jessica Tay, David Roshan, Jonathan R Clark
BACKGROUND: Head and neck cancer (HNC) encompasses a diverse group of tumors, and thus providing appropriate and tailored information to patients before, during, and after treatment is a challenge. The objective of the current study was to characterize the experience and unmet needs of patients with HNC with regard to information and support provision. METHODS: A 28-question, cross-sectional survey was completed by patients treated for HNC at 1 of 4 institutions in New South Wales, Australia (Chris O'Brien Lifehouse and Liverpool, Westmead, and Wollongong hospitals)...
January 12, 2017: Cancer
https://www.readbyqxmd.com/read/28077600/ibrutinib-therapy-increases-t-cell-repertoire-diversity-in-patients-with-chronic-lymphocytic-leukemia
#7
Qingsong Yin, Mariela Sivina, Harlan Robins, Erik Yusko, Marissa Vignali, Susan O'Brien, Michael J Keating, Alessandra Ferrajoli, Zeev Estrov, Nitin Jain, William G Wierda, Jan A Burger
The Bruton's tyrosine kinase inhibitor ibrutinib is a highly effective, new targeted therapy for chronic lymphocytic leukemia (CLL) that thwarts leukemia cell survival, growth, and tissue homing. The effects of ibrutinib treatment on the T cell compartment, which is clonally expanded and thought to support the growth of malignant B cells in CLL, are not fully characterized. Using next-generation sequencing technology, we characterized the diversity of TCRβ-chains in peripheral blood T cells from 15 CLL patients before and after 1 y of ibrutinib therapy...
January 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28061919/myasthenia-gravis-and-its-aeromedical-implications
#8
Tania Jagathesan, Michael D O'Brien
BACKGROUND: Myasthenia gravis is an autoimmune condition where antibodies form against the acetylcholine receptors at the neuromuscular junction, eventually causing damage to the motor end plate. The clinical features include muscle fatigability as well as ocular, bulbar, and limb weakness, which can have implications on the role of a pilot or air traffic controller. This retrospective study reviewed the United Kingdom Civil Aviation Authority (UK CAA) experience of myasthenia gravis...
January 1, 2017: Aerospace Medicine and Human Performance
https://www.readbyqxmd.com/read/28052967/official-american-thoracic-society-infectious-diseases-society-of-america-centers-for-disease-control-and-prevention-clinical-practice-guidelines-diagnosis-of-tuberculosis-in-adults-and-children
#9
David M Lewinsohn, Michael K Leonard, Philip A LoBue, David L Cohn, Charles L Daley, Ed Desmond, Joseph Keane, Deborah A Lewinsohn, Ann M Loeffler, Gerald H Mazurek, Richard J O'Brien, Madhukar Pai, Luca Richeldi, Max Salfinger, Thomas M Shinnick, Timothy R Sterling, David M Warshauer, Gail L Woods
BACKGROUND: Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain. METHODS: A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence...
January 15, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28043128/formulation-and-evaluation-of-anisamide-targeted-amphiphilic-cyclodextrin-nanoparticles-to-promote-therapeutic-gene-silencing-in-a-3d-prostate-cancer-bone-metastases-model
#10
James C Evans, Meenakshi Malhotra, Kathleen A Fitzgerald, Jianfeng Guo, Michael F Cronin, Caroline M Curtin, Fergal J O'Brien, Raphael Darcy, Caitriona M O'Driscoll
In recent years, RNA interference (RNAi) has emerged as a potential therapeutic offering the opportunity to treat a wide range of diseases, including prostate cancer. Modified cyclodextrins have emerged as effective gene delivery vectors in a range of disease models. The main objective of the current study was to formulate anisamide-targeted cyclodextrin nanoparticles to interact with the sigma receptor (overexpressed on the surface of prostate cancer cells). The inclusion of octaarginine in the nanoparticle optimized uptake and endosomal release of siRNA in two different prostate cancer cell lines (PC3 and DU145 cells)...
January 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28011389/extended-release-naltrexone-for-pre-release-prisoners-a-randomized-trial-of-medical-mobile-treatment
#11
Michael S Gordon, Frank J Vocci, Terrence T Fitzgerald, Kevin E O'Grady, Charles P O'Brien
BACKGROUND: Extended-release naltrexone (XR-NTX), is an effective treatment for opioid use disorder but is rarely initiated in US prisons or with criminal justice populations. Mobile treatment for chronic diseases has been implemented in a variety of settings. Mobile treatment may provide an opportunity to expand outreach to parolees to surmount barriers to traditional clinic treatment. METHODS: Male and female prisoners (240) with pre-incarceration histories of opioid use disorder who are within one month of release from prison will be enrolled in this randomized clinical trial...
December 20, 2016: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28010051/qmg-and-mg-adl-correlations-study-of-eculizumab-treatment-of-myasthenia-gravis
#12
James F Howard, Miriam Freimer, Fanny O'Brien, Jing Jing Wang, Stephen R Collins, John T Kissel, Laura Herbelin, April L McVey, Mazen M Dimachkie, Mamatha Pasnoor, Debbie Lu, Alexander Waltz, Vinay Chaudhry, Andrea Corse, Elizabeth Mosmiller, Caroline Klein, Manisha Chopra, Elizabeth Richardson, Janice M Massey, Lisa D Hobson-Webb, Jeffrey Guptill, Wendy King, Annabel K Wang, Kaveh Saremi, Patricia A Tully, Denise Davis, Veronica Martin, Robert M Pascuzzi, Sandy Guingrich, Angela Micheels, Michael Pulley, Kenneth Hentschel, Lisa Smith, Rhonda Calhoun, James Gilchrist, George Sachs, Brigid Crabtree, Elena Kim Perez, Kenneth Gorson, Elizabeth Harrahy Cobb, Elinita Rosseto, Zaeem Siddiqi, Syed Nizamuddin Ahmed, Derrick Blackmore, Shannon Butler-Tyler, Sarah Louise Miller, Caroline Carmichael, Ted Burns, William David, Peter Donofrio, Bashar Katirji, Richard Lewis, Shin Oh, David Richman, Mark Sivak, Rup Tandan, Gil Wolfe, Shawn Bird, David Hilton-Jones
INTRODUCTION: A phase 2 study of eculizumab for treating myasthenia gravis (MG) used the quantitative myasthenia gravis score (QMG) and myasthenia gravis activities of daily living profile (MG-ADL) to evaluate baseline disease severity and treatment response. Correlations were then analyzed between these assessments. METHODS: Patients were given eculizumab or placebo during the first 16-week treatment period of the crossover study, with treatment assignments reversed for the second treatment period following a 5-week washout...
December 23, 2016: Muscle & Nerve
https://www.readbyqxmd.com/read/28003274/long-term-outcome-of-acute-promyelocytic-leukemia-treated-with-all-trans-retinoic-acid-arsenic-trioxide-and-gemtuzumab
#13
Yasmin Abaza, Hagop M Kantarjian, Guillermo Garcia-Manero, Elihu Estey, Gautam Borthakur, Elias Jabbour, Stefan Faderl, Susan O'Brien, William Wierda, Sherry Pierce, Mark Brandt, Deborah McCue, Rajyalakshmi Luthra, Keyur Patel, Steven Kornblau, Tapan Kadia, Naval Daver, Courtney DiNardo, Nitin Jain, Srdan Verstovsek, Alessandra Ferrajoli, Michael Andreeff, Marina Konopleva, Zeev Estrov, Maria Foudray, David McCue, Jorge Cortes, Farhad Ravandi
The combination of all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of standard risk newly diagnosed patients with acute promyelocytic leukemia (APL). A recent study demonstrated the efficacy of this regimen with added gemtuzumab ozogamycin (GO) in high-risk patients. We examined the long-term outcome of newly diagnosed APL patients treated at our institution on three consecutive prospective clinical trials using the combination of ATRA, ATO, with or without GO...
December 21, 2016: Blood
https://www.readbyqxmd.com/read/27998223/phase-i-phase-ii-study-of-blinatumomab-in-pediatric-patients-with-relapsed-refractory-acute-lymphoblastic-leukemia
#14
Arend von Stackelberg, Franco Locatelli, Gerhard Zugmaier, Rupert Handgretinger, Tanya M Trippett, Carmelo Rizzari, Peter Bader, Maureen M O'Brien, Benoît Brethon, Deepa Bhojwani, Paul Gerhardt Schlegel, Arndt Borkhardt, Susan R Rheingold, Todd Michael Cooper, Christian M Zwaan, Phillip Barnette, Chiara Messina, Gérard Michel, Steven G DuBois, Kuolung Hu, Min Zhu, James A Whitlock, Lia Gore
Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. We evaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children < 18 years old with relapsed/refractory BCP-ALL in a phase I dosage-escalation part and a phase II part, using 6-week treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II)...
December 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27995742/tracking-the-amphibian-pathogens-batrachochytrium-dendrobatidis-and-batrachochytrium-salamandrivorans-using-a-highly-specific-monoclonal-antibody-and-lateral-flow-technology
#15
Michael J Dillon, Andrew E Bowkett, Michael J Bungard, Katie M Beckman, Michelle F O'Brien, Kieran Bates, Matthew C Fisher, Jamie R Stevens, Christopher R Thornton
The fungus Batrachochytrium dendrobatidis (Bd) causes chytridiomycosis, a lethal epizootic disease of amphibians. Rapid identification of the pathogen and biosecurity is essential to prevent its spread, but current laboratory-based tests are time-consuming and require specialist equipment. Here, we describe the generation of an IgM monoclonal antibody (mAb), 5C4, specific to Bd as well as the related salamander and newt pathogen Batrachochytrium salamandrivorans (Bsal). The mAb, which binds to a glycoprotein antigen present on the surface of zoospores, sporangia and zoosporangia, was used to develop a lateral-flow assay (LFA) for rapid (15 min) detection of the pathogens...
December 19, 2016: Microbial Biotechnology
https://www.readbyqxmd.com/read/27978692/catalytic-dearomatization-approach-to-quinolizidine-alkaloids-five-step-total-synthesis-of-%C3%A2-lasubine-ii
#16
Michael J James, Niall D Grant, Peter O'Brien, Richard J K Taylor, William P Unsworth
A series of high-yielding silver(I)-catalyzed cyclization reactions of pyridine-, isoquinoline-, and pyrazine-ynones are described. The operationally simple and mild reaction conditions are a significant improvement over previously reported thermal cyclizations. The quinolizinone products were also used in a novel dearomatization strategy to prepare 0.53 g of the alkaloid lasubine II in five steps and 36% overall yield.
December 16, 2016: Organic Letters
https://www.readbyqxmd.com/read/27966066/effects-of-bariatric-surgery-on-liver-function-tests-in-patients-with-nonalcoholic-fatty-liver-disease
#17
Geraldine J Ooi, Paul R Burton, Lisa Doyle, John M Wentworth, Prithi S Bhathal, Ken Sikaris, Michael A Cowley, Stuart K Roberts, William Kemp, Arul Earnest, Paul E O'Brien, Wendy A Brown
OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) affects over 80% of obese patients and is fueled by the metabolic syndrome. Weight loss is strongly advocated as a central treatment for NAFLD and has been shown to induce histological improvement. We aimed to define the patterns of improvement in NAFLD with weight loss and determine target weight goals for NAFLD resolution. METHODS: A prospective study of 84 morbidly obese patients with NAFLD undergoing bariatric surgery was conducted...
December 13, 2016: Obesity Surgery
https://www.readbyqxmd.com/read/27935956/correction-chromosomal-level-assembly-of-the-asian-seabass-genome-using-long-sequence-reads-and-multi-layered-scaffolding
#18
Shubha Vij, Heiner Kuhl, Inna S Kuznetsova, Aleksey Komissarov, Andrey A Yurchenko, Peter Van Heusden, Siddharth Singh, Natascha M Thevasagayam, Sai Rama Sridatta Prakki, Kathiresan Purushothaman, Jolly M Saju, Junhui Jiang, Stanley Kimbung Mbandi, Mario Jonas, Amy Hin Yan Tong, Sarah Mwangi, Doreen Lau, Si Yan Ngoh, Woei Chang Liew, Xueyan Shen, Lawrence S Hon, James P Drake, Matthew Boitano, Richard Hall, Chen-Shan Chin, Ramkumar Lachumanan, Jonas Korlach, Vladimir Trifonov, Marsel Kabilov, Alexey Tupikin, Darrell Green, Simon Moxon, Tyler Garvin, Fritz J Sedlazeck, Gregory W Vurture, Gopikrishna Gopalapillai, Vinaya Kumar Katneni, Tansyn H Noble, Vinod Scaria, Sridhar Sivasubbu, Dean R Jerry, Stephen J O'Brien, Michael C Schatz, Tamás Dalmay, Stephen W Turner, Si Lok, Alan Christoffels, László Orbán
[This corrects the article DOI: 10.1371/journal.pgen.1005954.].
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27932390/official-american-thoracic-society-infectious-diseases-society-of-america-centers-for-disease-control-and-prevention-clinical-practice-guidelines-diagnosis-of-tuberculosis-in-adults-and-children
#19
David M Lewinsohn, Michael K Leonard, Philip A LoBue, David L Cohn, Charles L Daley, Ed Desmond, Joseph Keane, Deborah A Lewinsohn, Ann M Loeffler, Gerald H Mazurek, Richard J O'Brien, Madhukar Pai, Luca Richeldi, Max Salfinger, Thomas M Shinnick, Timothy R Sterling, David M Warshauer, Gail L Woods
BACKGROUND: Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain. METHODS: A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence...
December 8, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/27931134/constitutive-activation-of-alternative-nuclear-factor-kappa-b-pathway-in-canine-diffuse-large-b-cell-lymphoma-contributes-to-tumor-cell-survival-and-is-a-target-of-new-adjuvant-therapies
#20
Davis M Seelig, Daisuke Ito, Colleen L Forster, Una A Yoon, Matthew Breen, Linda J Burns, Veronika Bachanova, Kerstin Lindblad-Toh, Timothy D O'Brien, Stephen C Schmechel, Anthony E Rizzardi, Jaime F Modiano, Michael A Linden
Activation of the classical nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway is a common molecular event observed in both human and canine diffuse large B-cell lymphoma (DLBCL). Although the oncogenic potential of the alternative NFκB pathway (ANFκBP) has also been recently identified in DLBCL, its precise role in tumor pathogenesis and potential as a treatment target is understudied. We hypothesized that up-regulation of the ANFκBP plays an important role in the proliferation and survival of canine DLBCL cells, and we demonstrate that the ANFκBP is constitutively active in primary canine DLBCL samples and a cell line (CLBL1)...
December 8, 2016: Leukemia & Lymphoma
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