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Alan Brown

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https://www.readbyqxmd.com/read/29045152/discovery-of-potent-and-orally-bioavailable-macrocyclic-peptide-peptoid-hybrid-cxcr7-modulators
#1
Markus Boehm, Kevin Beaumont, Rhys M Jones, Amit S Kalgutkar, Liying Zhang, Karen Atkinson, Guoyun Bai, Janice A Brown, Heather Eng, Gilles H Goetz, Brian R Holder, Bhagyashree Khunte, Sarah Lazzaro, Chris Limberakis, Sangwoo Ryu, Michael J Shapiro, Laurie Tylaska, Jiangli Yan, Rushia Turner, Siegfried S F Leung, Mahesh Ramaseshan, David A Price, Spiros Liras, Matthew P Jacobson, David J Earp, R Scott Lokey, Alan M Mathiowetz, Elnaz Menhaji-Klotz
The chemokine receptor CXCR7 is an attractive target for a variety of diseases. While several small molecule modulators of CXCR7 have been reported, peptidic macrocycles may provide advantages in terms of potency, selectivity, and reduced off-target activity. We produced a series of peptidic macrocycles that incorporate an N-linked peptoid functionality where the peptoid group enabled us to explore side chain diversity well beyond that of natural amino acids. At the same time, computational calculations and experimental assays were used to track and reduce polarity while closely monitoring physicochemical properties...
October 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29038277/dilution-factor-of-quantitative-bacterial-cultures-obtained-by-bronchoalveolar-lavage-in-patients-with-ventilator-associated-bacterial-pneumonia-implications-for-optimal-antimicrobial-therapy-ventilator-associated-bacterial-pneumonia-study-group
#2
George L Drusano, Michael L Corrado, Gino Girardi, Evelyn J Ellis-Grosse, Richard G Wunderink, Helen Donnelly, Kenneth V Leeper, Mona Brown, Tasnova Malek, Robert Duncan Hite, Michelle Ferrari, Danijela Djureinovic, Marin H Kollef, Lisa Mayfield, Ann Doyle, Jean Chastre, Alain Combes, Thomas J Walsh, Krisztina Dorizas, Hassan Alnuaimat, Brooks Edward Morgan, Jordi Rello, Cristopher Alan Mazo Torre, Ronald N Jones, Robert K Flamm, Leah Woosley, Paul G Ambrose, Sujata Bhavnani, Christopher M Rubino, Catharine C Bulik, Arnold Louie, Michael Vicchiarelli, Colleen Berman
Ventilator-Associated Bacterial Pneumonia (VABP) is a difficult therapeutic problem. Considerable controversy exists regarding the optimal chemotherapy for this entity. The recent IDSA/ATS guidelines recommended a 7-day therapeutic course for VABP based on the balance of no negative impact on all-cause mortality, less resistance emergence and fewer antibiotic days counterbalanced with a higher relapse rate for patients whose pathogen is a non-fermenter. The bacterial burden causing an infection will have a substantial impact on treatment outcome and resistance selection...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29035063/religious-anti-gay-prejudice-as-a-predictor-of-mental-health-abuse-and-substance-use
#3
Babucarr J Sowe, Alan J Taylor, Jac Brown
Anti-gay, or homonegative, prejudice is generally considered harmful to the wellbeing of sexual minority individuals. However, the origins or nature of such prejudice may vary. Despite a sizable body of literature suggesting homonegative prejudice is frequently religious-based, the psychological impact of exposure to religious anti-gay prejudice remains largely undetermined. Addressing this research gap, the authors examined whether opposition to same-sex sexuality on religious grounds predicted detrimental outcomes among same- and both-sex attracted individuals, as well as their heterosexual counterparts...
October 16, 2017: American Journal of Orthopsychiatry
https://www.readbyqxmd.com/read/29029933/highly-potent-and-selective-nav1-7-inhibitors-for-use-as-intravenous-agents-and-chemical-probes
#4
R Ian Storer, Andy Pike, Nigel A Swain, Aristos J Alexandrou, Bruce M Bechle, David C Blakemore, Alan D Brown, Neil A Castle, Matthew S Corbett, Neil J Flanagan, David Fengas, M Scott Johnson, Lyn H Jones, Brian E Marron, C Elizabeth Payne, David Printzenhoff, David J Rawson, Colin R Rose, Thomas Ryckmans, Jianmin Sun, Jonathan W Theile, Rubben Torella, Elaine Tseng, Joseph S Warmus
The discovery and selection of a highly potent and selective NaV1.7 inhibitor PF-06456384, designed specifically for intravenous infusion, is disclosed. Extensive in vitro pharmacology and ADME profiling followed by in vivo preclinical PK and efficacy model data are discussed. A proposed protein-ligand binding mode for this compound is also provided to rationalise the high levels of potency and selectivity over inhibition of related sodium channels. To further support the proposed binding mode, potent conjugates are described which illustrate the potential for development of chemical probes to enable further target evaluation...
November 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29026655/sharing-of-carbapenemase-encoding-plasmids-between-enterobacteriaceae-in-uk-sewage-uncovered-by-minion-sequencing
#5
Catherine Ludden, Sandra Reuter, Kim Judge, Theodore Gouliouris, Beth Blane, Francesc Coll, Plamena Naydenova, Martin Hunt, Alan Tracey, Katie L Hopkins, Nicholas M Brown, Neil Woodford, Julian Parkhill, Sharon J Peacock
Dissemination of carbapenem resistance among pathogenic Gram-negative bacteria is a looming medical emergency. Efficient spread of resistance within and between bacterial species is facilitated by mobile genetic elements. We hypothesized that wastewater contributes to the dissemination of carbapenemase-producing Enterobacteriaceae (CPE), and studied this through a cross-sectional observational study of wastewater in the East of England. We isolated clinically relevant species of CPE in untreated and treated wastewater, confirming that waste treatment does not prevent release of CPE into the environment...
July 2017: Microbial Genomics
https://www.readbyqxmd.com/read/29025127/are-participants-concerned-about-privacy-and-security-when-using-short-message-service-to-report-product-adherence-in-a-rectal-microbicide-trial
#6
Rebecca Giguere, William Brown Iii, Ivan C Balán, Curtis Dolezal, Titcha Ho, Alan Sheinfil, Mobolaji Ibitoye, Javier R Lama, Ian McGowan, Ross D Cranston, Alex Carballo-Diéguez
Objective: During a Phase 2 rectal microbicide trial, men who have sex with men and transgender women (n = 187) in 4 countries (Peru, South Africa, Thailand, United States) reported product use daily via short message service (SMS). To prevent disclosure of study participation, the SMS system program included privacy and security features. We evaluated participants' perceptions of privacy while using the system and acceptability of privacy/security features. Materials and Methods: To protect privacy, the SMS system: (1) confirmed participant availability before sending the study questions, (2) required a password, and (3) did not reveal product name or study participation...
August 24, 2017: Journal of the American Medical Informatics Association: JAMIA
https://www.readbyqxmd.com/read/29018178/attitudes-of-paediatric-and-obstetric-specialists-towards-prenatal-surgery-for-lethal-and-non-lethal-conditions
#7
Ryan M Antiel, Farr A Curlin, John D Lantos, Christopher A Collura, Alan W Flake, Mark P Johnson, Natalie E Rintoul, Stephen D Brown, Chris Feudtner
BACKGROUND: While prenatal surgery historically was performed exclusively for lethal conditions, today intrauterine surgery is also performed to decrease postnatal disabilities for non-lethal conditions. We sought to describe physicians' attitudes about prenatal surgery for lethal and non-lethal conditions and to elucidate characteristics associated with these attitudes. METHODS: Survey of 1200 paediatric surgeons, neonatologists and maternal-fetal medicine specialists (MFMs)...
October 10, 2017: Journal of Medical Ethics
https://www.readbyqxmd.com/read/28959120/examining-the-unique-characteristics-of-a-non-probability-sample-of-undocumented-female-sex-workers-with-dependent-children-the-case-of-haitians-in-the-dominican-republic
#8
Christine Tagliaferri Rael, Alan Sheinfil, Karen Hampanda, Alex Carballo-Diéguez, Andrea Norcini Pala, William Brown
No abstract text is available yet for this article.
September 2017: Sexuality & Culture
https://www.readbyqxmd.com/read/28952914/tenecteplase-versus-alteplase-before-endovascular-thrombectomy-extend-ia-tnk-a-multicenter-randomized-controlled-study
#9
Bruce Cv Campbell, Peter J Mitchell, Leonid Churilov, Nawaf Yassi, Timothy J Kleinig, Bernard Yan, Richard J Dowling, Steven J Bush, Helen M Dewey, Vincent Thijs, Marion Simpson, Mark Brooks, Hamed Asadi, Teddy Y Wu, Darshan G Shah, Tissa Wijeratne, Timothy Ang, Ferdinand Miteff, Christopher Levi, Martin Krause, Timothy J Harrington, Kenneth C Faulder, Brendan S Steinfort, Peter Bailey, Henry Rice, Laetitia de Villiers, Rebecca Scroop, Wayne Collecutt, Andrew A Wong, Alan Coulthard, P A Barber, Ben McGuinness, Deborah Field, Henry Ma, Winston Chong, Ronil V Chandra, Christopher F Bladin, Helen Brown, Kendal Redmond, David Leggett, Geoffrey Cloud, Anoop Madan, Neil Mahant, Bill O'Brien, John Worthington, Geoffrey Parker, Patricia M Desmond, Mark W Parsons, Geoffrey A Donnan, Stephen M Davis
Background and hypothesis Intravenous thrombolysis with alteplase remains standard care prior to thrombectomy for eligible patients within 4.5 h of ischemic stroke onset. However, alteplase only succeeds in reperfusing large vessel arterial occlusion prior to thrombectomy in a minority of patients. We hypothesized that tenecteplase is non-inferior to alteplase in achieving reperfusion at initial angiogram, when administered within 4.5 h of ischemic stroke onset, in patients planned to undergo endovascular therapy...
January 1, 2017: International Journal of Stroke: Official Journal of the International Stroke Society
https://www.readbyqxmd.com/read/28943825/can-a-short-video-improve-inhaler-use-in-urban-youth
#10
Sara Brown, Victoria Tutag Lehr, Nathan French, Christopher Alan Giuliano
OBJECTIVE: The primary aim was to determine whether watching a short video in the inpatient setting could produce an immediate improvement in pediatric patients' asthma knowledge and inhaler technique. METHODS: This prospective, quasi-experimental, pre-post study was conducted in a single center, in Detroit, Michigan, which primarily serves an urban, African-American population. Patients were eligible if they were between 8- and 16-years-old, had asthma, and would be discharged with an albuterol metered-dose inhaler...
July 2017: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/28943038/genetic-effects-on-efficacy-of-lipid-lowering-drugs
#11
REVIEW
William Virgil Brown, Alan S Brown, Brian A Ference, Peter P Toth, James A Underberg
No abstract text is available yet for this article.
September 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28938451/antibody-mediated-targeting-of-the-fgfr1c-isoform-increases-glucose-uptake-in-white-and-brown-adipose-tissue-in-male-mice
#12
Jo E Lewis, Ricardo J Samms, Scott Cooper, Jeni C Luckett, Alan C Perkins, James D Dunbar, Dennis P Smith, Paul J Emmerson, Andrew C Adams, Francis J P Ebling, Kostas Tsintzas
The increased prevalence of obesity and its cardiometabolic implications demonstrates the imperative to identify novel therapeutic targets able to effect meaningful metabolic changes in this population. Antibody-mediated targeting of fibroblast growth factor receptor 1c isoform (FGFR1c) has been shown to ameliorate hyperglycemia and protect from diet- and genetically-induced obesity in rodents and nonhuman primates. However, it is currently unknown which tissue(s) contribute to this glucose-lowering effect...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28935285/is-the-pelvic-examination-still-crucial-in-patients-presenting-to-the-emergency-department-with%C3%A2-vaginal-bleeding-or-abdominal-pain-when-an-intrauterine-pregnancy-is-identified-on-ultrasonography-a-randomized-controlled-trial
#13
Judith A Linden, Benjamin Grimmnitz, Laura Hagopian, Alan H Breaud, Breanne K Langlois, Kerrie P Nelson, Lauren L Hart, James A Feldman, Jeremy Brown, Marc Reid, Elise Desormeau, Patricia M Mitchell
STUDY OBJECTIVE: We determine whether omitting the pelvic examination in emergency department (ED) evaluation of vaginal bleeding or lower abdominal pain in ultrasonographically confirmed early intrauterine pregnancy is equivalent to performing the examination. METHODS: We conducted a prospective, open-label, randomized, equivalence trial in pregnant patients presenting to the ED from February 2011 to November 2015. Patients were randomized to no pelvic examination versus pelvic examination...
September 19, 2017: Annals of Emergency Medicine
https://www.readbyqxmd.com/read/28933922/alan-gregg-the-diary-of-a-thoughtful-eye-witness
#14
Susan Ladwig, Theodore Brown
No abstract text is available yet for this article.
November 2017: American Journal of Public Health
https://www.readbyqxmd.com/read/28916570/dietary-poly-phenols-brown-adipose-tissue-activation-and-energy-expenditure-a-narrative-review
#15
REVIEW
Laura Mele, Guillaume Bidault, Pedro Mena, Alan Crozier, Furio Brighenti, Antonio Vidal-Puig, Daniele Del Rio
The incidence of overweight and obesity has reached epidemic proportions, making the control of body weight and its complications a primary health problem. Diet has long played a first-line role in preventing and managing obesity. However, beyond the obvious strategy of restricting caloric intake, growing evidence supports the specific antiobesity effects of some food-derived components, particularly (poly)phenolic compounds. The relatively new rediscovery of active brown adipose tissue in adult humans has generated interest in this tissue as a novel and viable target for stimulating energy expenditure and controlling body weight by promoting energy dissipation...
September 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28913575/day-to-day-fasting-glycaemic-variability-in-devote-associations-with-severe-hypoglycaemia-and-cardiovascular-outcomes-devote-2
#16
Bernard Zinman, Steven P Marso, Neil R Poulter, Scott S Emerson, Thomas R Pieber, Richard E Pratley, Martin Lange, Kirstine Brown-Frandsen, Alan Moses, Ann Marie Ocampo Francisco, Jesper Barner Lekdorf, Kajsa Kvist, John B Buse
AIMS/HYPOTHESIS: The Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) was a double-blind, randomised, event-driven, treat-to-target prospective trial comparing the cardiovascular safety of insulin degludec with that of insulin glargine U100 (100 units/ml) in patients with type 2 diabetes at high risk of cardiovascular events. This paper reports a secondary analysis investigating associations of day-to-day fasting glycaemic variability (pre-breakfast self-measured blood glucose [SMBG]) with severe hypoglycaemia and cardiovascular outcomes...
September 15, 2017: Diabetologia
https://www.readbyqxmd.com/read/28913543/devote-3-temporal-relationships-between-severe-hypoglycaemia-cardiovascular-outcomes-and-mortality
#17
Thomas R Pieber, Steven P Marso, Darren K McGuire, Bernard Zinman, Neil R Poulter, Scott S Emerson, Richard E Pratley, Vincent Woo, Simon Heller, Martin Lange, Kirstine Brown-Frandsen, Alan Moses, Jesper Barner Lekdorf, Lucine Lehmann, Kajsa Kvist, John B Buse
AIMS/HYPOTHESIS: The double-blind Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) assessed the cardiovascular safety of insulin degludec. The incidence and rates of adjudicated severe hypoglycaemia, and all-cause mortality were also determined. This paper reports a secondary analysis investigating associations of severe hypoglycaemia with cardiovascular outcomes and mortality...
September 15, 2017: Diabetologia
https://www.readbyqxmd.com/read/28893315/heterogeneous-drug-penetrance-of-veliparib-and-carboplatin-measured-in-triple-negative-breast-tumors
#18
Imke H Bartelink, Brendan Prideaux, Gregor Krings, Lisa Wilmes, Pei Rong Evelyn Lee, Pan Bo, Byron Hann, Jean-Philippe Coppé, Diane Heditsian, Lamorna Swigart-Brown, Ella F Jones, Sergey Magnitsky, Ron J Keizer, Niels de Vries, Hilde Rosing, Nela Pawlowska, Scott Thomas, Mallika Dhawan, Rahul Aggarwal, Pamela N Munster, Laura J Esserman, Weiming Ruan, Alan H B Wu, Douglas Yee, Véronique Dartois, Radojka M Savic, Denise M Wolf, Laura van 't Veer
BACKGROUND: Poly(ADP-ribose) polymerase inhibitors (PARPi), coupled to a DNA damaging agent is a promising approach to treating triple negative breast cancer (TNBC). However, not all patients respond; we hypothesize that non-response in some patients may be due to insufficient drug penetration. As a first step to testing this hypothesis, we quantified and visualized veliparib and carboplatin penetration in mouse xenograft TNBCs and patient blood samples. METHODS: MDA-MB-231, HCC70 or MDA-MB-436 human TNBC cells were implanted in 41 beige SCID mice...
September 11, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28892042/structures-of-the-human-mitochondrial-ribosome-in-native-states-of-assembly
#19
Alan Brown, Sorbhi Rathore, Dari Kimanius, Shintaro Aibara, Xiao-Chen Bai, Joanna Rorbach, Alexey Amunts, V Ramakrishnan
Mammalian mitochondrial ribosomes (mitoribosomes) have less rRNA content and 36 additional proteins compared with the evolutionarily related bacterial ribosome. These differences make the assembly of mitoribosomes more complex than the assembly of bacterial ribosomes, but the molecular details of mitoribosomal biogenesis remain elusive. Here, we report the structures of two late-stage assembly intermediates of the human mitoribosomal large subunit (mt-LSU) isolated from a native pool within a human cell line and solved by cryo-EM to ∼3-Å resolution...
October 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28884768/the-composition-of-potentially-bioactive-triterpenoid-glycosides-in-red-raspberry-is-influenced-by-tissue-extraction-procedure-and-genotype
#20
Gordon J McDougall, J William Allwood, Gema Pereira-Caro, Emma M Brown, Cheryl Latimer, Gary Dobson, Derek Stewart, Nigel G Ternan, Roger Lawther, Gloria O'Connor, Ian Rowland, Alan Crozier, Chris I R Gill
The beneficial effects of consumption of berry fruits on a range of chronic diseases has been attributed (at least in part) to the presence of unique phytochemicals. Recently, we identified novel ursolic acid-based triterpenoid glycosides (TTPNs) in raspberry fruit and demonstrated their survival in human ileal fluids after feeding which confirmed their colon-availability in vivo. In this paper, in vitro digestion studies demonstrated that certain TTPNs were stable under gastrointestinal conditions and confirmed that these components may have been responsible for bioactivity noted in previous studies...
September 8, 2017: Food & Function
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