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https://www.readbyqxmd.com/read/28922338/does-the-%C3%AE-receptor-antagonist-esmolol-have-analgesic-effects-a-randomised-placebo-controlled-cross-over-study-on-healthy-volunteers-undergoing-the-cold-pressor-test
#1
Fredrik Ander, Anders Magnuson, Alex de Leon, Rebecca Ahlstrand
BACKGROUND: Esmolol may attenuate the sympathetic response to pain and reduce postoperative opioid consumption. It is not clear whether esmolol has an analgesic effect per se. OBJECTIVES: The aim of this study was to evaluate the analgesic effect of esmolol in the absence of anaesthetics and opioids. We tested the hypothesis that esmolol would reduce the maximum pain intensity perceived during the cold pressor test (CPT) by 2 points on a 0 to 10 numeric pain rating scale (NRS) compared to placebo...
September 15, 2017: European Journal of Anaesthesiology
https://www.readbyqxmd.com/read/28914366/geriatric-assessment-with-management-intervention-in-older-adults-with-cancer-a-randomized-pilot-study
#2
Allison Magnuson, Tatyana Lemelman, Chintan Pandya, Molly Goodman, Marcus Noel, Mohammed Tejani, David Doughtery, William Dale, Arti Hurria, Michelle Janelsins, Feng Vankee Lin, Charles Heckler, Supriya Mohile
BACKGROUND: Older adults receiving cancer therapy have heightened risk for treatment-related toxicity. Geriatric assessment (GA) can identify impairments, which may contribute to vulnerability and adverse outcomes. GA management interventions can address these impairments and have the potential to improve outcomes when implemented. METHODS: We conducted a randomized pilot study comparing GA with management interventions versus usual care in patients with stage III/IV solid tumor malignancies (N = 71)...
September 15, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28892380/gne-781-a-highly-advanced-potent-and-selective-bromodomain-inhibitor-of-cyclic-adenosine-monophosphate-response-element-binding-protein-binding-protein-cbp
#3
F Anthony Romero, Jeremy M Murray, Kwong Wah Lai, Vickie Tsui, Brian K Albrecht, Le An, Maureen H Beresini, Gladys de Leon Boenig, Sarah M Bronner, Emily W Chan, Kevin X Chen, Zhongguo Chen, Edna F Choo, Kyle Clagg, Kevin Clark, Terry D Crawford, Patrick Cyr, Denise De Almeida Nagata, Karen E Gascoigne, Jane L Grogan, Georgia Hatzivassiliou, Wei Huang, Thomas L Hunsaker, Susan Kaufman, Stefan G Koenig, Ruina Li, Yingjie Li, Xiaorong Liang, Jiangpeng Liao, Wenfeng Liu, Justin Q Ly, Jonathan Maher, Colin Masui, Mark Merchant, Yingqing Ran, Alexander M Taylor, John S Wai, Fei Wang, Xiaocang Wei, Dong Yu, Bing-Yan Zhu, Xiaoyu Zhu, Steven R Magnuson
Inhibition of the bromodomain of the transcriptional regulator CBP/P300 is an especially interesting new therapeutic approach in oncology. We recently disclosed in vivo chemical tool 1 (GNE-272) for the bromodomain of CBP that was moderately potent and selective over BRD4(1). In pursuit of a more potent and selective CBP inhibitor we used structure-based design. Constraining the aniline of 1 into a tetrahydroquinoline motif maintained potency and increased selectivity 2-fold. Structure-activity relationship studies coupled with further structure-based design targeting the LPF shelf, BC loop and KAc regions allowed us to significantly increase potency and selectivity, resulting in the identification of non-CNS penetrant 19 (GNE-781; TR-FRET IC50 = 0...
September 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28862934/impact-of-spontaneous-extracranial-bleeding-events-on-health-state-utility-in-patients-with-atrial-fibrillation-results-from-the-engage-af-timi-48-trial
#4
Kaijun Wang, Haiyan Li, Winghan J Kwong, Elliott M Antman, Christian T Ruff, Robert P Giugliano, David J Cohen, Elizabeth A Magnuson
BACKGROUND: The impact of different types of extracranial bleeding events on health-related quality of life and health-state utility among patients with atrial fibrillation is not well understood. METHODS AND RESULTS: The ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) Trial compared edoxaban with warfarin with respect to the prevention of stroke or systemic embolism in atrial fibrillation...
August 11, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28856511/local-infiltration-analgesia-a-2-year-follow-up-of-patients-undergoing-total-hip-arthroplasty
#5
Ján Kuchálik, Anders Magnuson, Anders Lundin, Anil Gupta
PURPOSE: Local infiltration analgesia (LIA) is commonly used for postoperative pain management following total hip arthroplasty (THA). However, the long-term effects of the component drugs are unclear. The aim of our study was to investigate functional outcome, quality of life, chronic post-surgical pain, and adverse events in patients within 2 years of undergoing THA. METHODS: The study was a secondary analysis of data from a previous larger study. Eighty patients were randomized to receive either intrathecal morphine (Group ITM) or local infiltration analgesia (Group LIA) for pain management in a double-blind study...
August 30, 2017: Journal of Anesthesia
https://www.readbyqxmd.com/read/28844575/weight-regain-in-patients-with-symptoms-of-post-bariatric-surgery-hypoglycemia
#6
Sanskriti Varma, Jeanne M Clark, Michael Schweitzer, Thomas Magnuson, Todd T Brown, Clare J Lee
BACKGROUND: Weight regain (WR) and symptoms of post-bariatric surgery hypoglycemia (PBSH) are metabolic complications observed in a subset of postbariatric patients. Whether hypoglycemic symptoms are an important driver of increased caloric intake and WR after bariatric surgery is unknown. OBJECTIVE: This study aims to determine whether patients with PBSH symptoms have greater odds for WR. SETTING: Tertiary academic hospital. METHODS: Patients who underwent Roux-en-Y gastric bypass or sleeve gastrectomy at our tertiary academic hospital from August 2008 to August 2012 were mailed a survey, from which weight trajectory and PBSH symptoms were assessed...
June 23, 2017: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/28841233/patients-without-comorbidities-at-the-time-of-diagnosis-of-atrial-fibrillation-causes-of-death-during-long-term-follow-up-compared-to-matched-controls
#7
Tommy Andersson, Anders Magnuson, Ing-Liss Bryngelsson, Ole Frøbert, Karin M Henriksson, Nils Edvardsson, Dritan Poçi
BACKGROUND: Little is known about the long-term, cause-specific mortality risk in patients without comorbidities at the time of diagnosis of atrial fibrillation (AF). METHODS: From a nation-wide registry of patients hospitalized with incident AF between 1995 and 2008 we identified 9 519 patients with a first diagnosed AF and no comorbidities at the time of AF diagnosis. They were matched with 12 468 controls. The follow-up continued until December 2008. Causes of death were classified according to the ICD-10 codes...
August 25, 2017: Clinical Cardiology
https://www.readbyqxmd.com/read/28836289/illuminating-seizures-optogenetic-approaches-to-studying-networks-in-epilepsy
#8
Esther Krook-Magnuson
No abstract text is available yet for this article.
August 24, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28831381/draft-genome-sequence-of-a-monokaryotic-model-brown-rot-fungus-postia-rhodonia-placenta-sb12
#9
Jill Gaskell, Phil Kersten, Luis F Larrondo, Paulo Canessa, Diego Martinez, David Hibbett, Monika Schmoll, Christian P Kubicek, Angel T Martinez, Jagjit Yadav, Emma Master, Jon Karl Magnuson, Debbie Yaver, Randy Berka, Kathleen Lail, Cindy Chen, Kurt LaButti, Matt Nolan, Anna Lipzen, Andrea Aerts, Robert Riley, Kerrie Barry, Bernard Henrissat, Robert Blanchette, Igor V Grigoriev, Dan Cullen
No abstract text is available yet for this article.
December 2017: Genomics Data
https://www.readbyqxmd.com/read/28830649/identification-of-an-imidazopyridine-scaffold-to-generate-potent-and-selective-tyk2-inhibitors-that-demonstrate-activity-in-an-in-vivo-psoriasis-model
#10
Jun Liang, Anne Van Abbema, Mercedesz Balazs, Kathy Barrett, Leo Berezhkovsky, Wade S Blair, Christine Chang, Donnie Delarosa, Jason DeVoss, Jim Driscoll, Charles Eigenbrot, Simon Goodacre, Nico Ghilardi, Calum MacLeod, Adam Johnson, Pawan Bir Kohli, Yingjie Lai, Zhonghua Lin, Priscilla Mantik, Kapil Menghrajani, Hieu Nguyen, Ivan Peng, Amy Sambrone, Steven Shia, Jan Smith, Sue Sohn, Vickie Tsui, Mark Ultsch, Karen Williams, Lawren C Wu, Wenqian Yang, Birong Zhang, Steven Magnuson
Herein we report identification of an imidazopyridine class of potent and selective TYK2 inhibitors, exemplified by prototype 6, through constraint of the rotatable amide bond connecting the pyridine and aryl rings of compound 1. Further optimization led to generation of compound 30 that potently inhibits the TYK2 enzyme and the IL-23 pathway in cells, exhibits selectivity against cellular JAK2 activity, and has good pharmacokinetic properties. In mice, compound 30 demonstrated dose-dependent reduction of IL-17 production in a PK/PD model as well as in an imiquimod-induced psoriasis model...
September 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28819026/therapeutic-targeting-of-the-cbp-p300-bromodomain-blocks%C3%A2-the-growth-of-castration-resistant-prostate-cancer
#11
Lingyan Jin, Jesse Garcia, Emily Chan, Cecile de la Cruz, Ehud Segal, Mark Merchant, Samir Kharbanda, Ryan Raisner, Peter M Haverty, Zora Modrusan, Justin Ly, Edna Choo, Susan Kaufman, Maureen H Beresini, F Anthony Romero, Steven Magnuson, Karen E Gascoigne
Resistance invariably develops to anti-androgen therapies used to treat newly diagnosed prostate cancers, but effective treatments for castration-resistant disease remain elusive. Here we report that the transcriptional co-activator CBP/p300 is required to maintain the growth of castration-resistant prostate cancer. To exploit this vulnerability, we developed a novel small-molecule inhibitor of the CBP/p300 bromodomain that blocks prostate cancer growth in vitro and in vivo. Molecular dissection of the consequences of drug treatment revealed a critical role for CBP/p300 in histone acetylation required for the transcriptional activity of the androgen receptor and its target gene expression...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28768411/larval-red-drum-sciaenops-ocellatus-sublethal-exposure-to-weathered-deepwater-horizon-crude-oil-developmental-and-transcriptomic-consequences
#12
Elvis Genbo Xu, Alex J Khursigara, Jason Magnuson, E Starr Hazard, Gary Hardiman, Andrew J Esbaugh, Aaron P Roberts, Daniel Schlenk
The Deepwater Horizon (DWH) incident resulted in extensive oiling of the pelagic zone and shoreline habitats of many commercially important fish species. Exposure to the water-accommodated fraction (WAF) of oil from the spill causes developmental toxicity through cardiac defects in pelagic fish species. However, few studies have evaluated the effects of the oil on near-shore estuarine fish species such as red drum (Sciaenops ocellatus). Following exposure to a certified weathered slick oil (4.74 μg/L ∑PAH50) from the DWH event, significant sublethal impacts were observed ranging from impaired nervous system development [average 17 and 22% reductions in brain and eye area at 48 h postfertilization (hpf), respectively] to abnormal cardiac morphology (100% incidence at 24, 48, and 72 hpf) in red drum larvae...
August 18, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28763358/effects-of-esmolol-on-the-esophagogastric-junction-a-double-blind-randomized-crossover-study-on-14-healthy-volunteers
#13
Fredrik Ander, Anders Magnuson, Lars Berggren, Rebecca Ahlstrand, Alex de Leon
BACKGROUND: Passive regurgitation may occur throughout the perioperative period, increasing the risk for pulmonary aspiration and postoperative pulmonary complications. Hypnotics and opioids, especially remifentanil, that are used during anesthesia have been shown to decrease the pressure in the esophagogastric junction (EGJ), that otherwise acts as a barrier against passive regurgitation of gastric contents. Esmolol, usually used to counteract tachycardia and hypertension, has been shown to possess properties useful during general anesthesia...
October 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28762561/diet-induced-obesity-causes-visceral-but-not-subcutaneous-lymph-node-hyperplasia-via-increases-in-specific-immune-cell-populations
#14
A M Magnuson, D P Regan, J K Fouts, A D Booth, S W Dow, M T Foster
OBJECTIVES: The spatial proximity of adipose depots to secondary lymph nodes allows a unique relation between the two systems. Obesity, predominately visceral adiposity, links to numerous diseases; hence, we postulate that secondary lymphatics within this region contributes to disease risk. MATERIAL AND METHODS: Male C57BL/6 mice were fed standard CHOW (18% kcal fat) or Western diet (45% kcal fat) for 7 weeks. Visceral and subcutaneous lymph nodes and associated adipose depots they occupy were excised...
October 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28750695/cost-effectiveness-of-long-term%C3%A2-ticagrelor-in-patients-with-prior-myocardial-infarction-results-from-the-pegasus-timi-54-trial
#15
RANDOMIZED CONTROLLED TRIAL
Elizabeth A Magnuson, Haiyan Li, Kaijun Wang, Katherine Vilain, Ali Shafiq, Marc P Bonaca, Deepak L Bhatt, Marc Cohen, Philippe Gabriel Steg, Robert F Storey, Eugene Braunwald, Marc S Sabatine, David J Cohen
BACKGROUND: In patients with a myocardial infarction (MI) 1 to 3 years earlier, treatment with ticagrelor + low-dose aspirin (ASA) reduces the risk of cardiovascular (CV) death, MI, or stroke compared with low-dose aspirin alone, but at an increased risk of major bleeding. OBJECTIVES: The authors evaluated cost-effectiveness of ticagrelor + low-dose ASA in patients with prior MI within the prior 3 years. METHODS: The authors performed a prospective economic substudy alongside the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54) trial, which randomized 21,162 patients to ASA alone, ticagrelor 60 mg twice daily + low-dose ASA, or ticagrelor 90 mg twice daily + low-dose ASA...
August 1, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28740608/gne-886-a-potent-and-selective-inhibitor-of-the-cat-eye-syndrome-chromosome-region-candidate-2-bromodomain-cecr2
#16
Terry D Crawford, James E Audia, Steve Bellon, Daniel J Burdick, Archana Bommi-Reddy, Alexandre Côté, Richard T Cummings, Martin Duplessis, E Megan Flynn, Michael Hewitt, Hon-Ren Huang, Hariharan Jayaram, Ying Jiang, Shivangi Joshi, James R Kiefer, Jeremy Murray, Christopher G Nasveschuk, Arianne Neiss, Eneida Pardo, F Anthony Romero, Peter Sandy, Robert J Sims, Yong Tang, Alexander M Taylor, Vickie Tsui, Jian Wang, Shumei Wang, Yongyun Wang, Zhaowu Xu, Laura Zawadzke, Xiaoqin Zhu, Brian K Albrecht, Steven R Magnuson, Andrea G Cochran
The biological function of bromodomains, epigenetic readers of acetylated lysine residues, remains largely unknown. Herein we report our efforts to discover a potent and selective inhibitor of the bromodomain of cat eye syndrome chromosome region candidate 2 (CECR2). Screening of our internal medicinal chemistry collection led to the identification of a pyrrolopyridone chemical lead, and subsequent structure-based drug design led to a potent and selective CECR2 bromodomain inhibitor (GNE-886) suitable for use as an in vitro tool compound...
July 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28734349/integrated-preservation-and-sample-clean-up-procedures-for-studying-water-ingestion-by-recreational-swimmers-via-urinary-biomarker-determination
#17
Ricardo Cantú, Jody A Shoemaker, Catherine A Kelty, Larry J Wymer, Thomas D Behymer, Alfred P Dufour, Matthew L Magnuson
The use of cyanuric acid as a biomarker for ingestion of swimming pool water may lead to quantitative knowledge of the volume of water ingested during swimming, contributing to a better understanding of disease resulting from ingestion of environmental contaminants. When swimming pool water containing chlorinated cyanurates is inadvertently ingested, cyanuric acid is excreted quantitatively within 24 h as a urinary biomarker of ingestion. Because the volume of water ingested can be quantitatively estimated by calculation from the concentration of cyanuric acid in 24 h urine samples, a procedure for preservation, cleanup, and analysis of cyanuric acid was developed to meet the logistical demands of large scale studies...
August 22, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28724744/ten-years-transmission-of-the-new-variant-of-chlamydia-trachomatis-in-sweden-prevalence-of-infections-and-associated-complications
#18
Jenny Dahlberg, Ronza Hadad, Karin Elfving, Inger Larsson, Jenny Isaksson, Anders Magnuson, Hans Fredlund, Magnus Unemo, Bjőrn Herrmann
OBJECTIVES: In 2006, a new variant of Chlamydia trachomatis (nvCT) was discovered in Sweden. It has a deletion in the plasmid resulting in failed detection by the single target systems from Abbott and Roche used at that time, whereas the third system used, from Becton Dickinson (BD), detects nvCT. The proportion of nvCT was initially up to 65% in counties using Abbott/Roche systems. This study analysed the proportion of nvCT from 2007 to 2015 in four selected counties and its impact on chlamydia-associated complications...
July 19, 2017: Sexually Transmitted Infections
https://www.readbyqxmd.com/read/28710067/a-comparison-of-passive-hind-limb-cycling-and-active-upper-limb-exercise-provides-new-insights-into-systolic-dysfunction-following-spinal-cord-injury
#19
Kathryn M DeVeau, Kathryn A Harman, Jordan W Squair, Andrei V Krassioukov, David Magnuson, Christopher R West
BACKGROUND: Active upper-limb and passive lower-limb exercise are two interventions used in the spinal cord injury (SCI) population. While the global cardiac responses have been previously studied, it is unclear how either exercise influences contractile cardiac function. Here, the cardiac contractile and volumetric responses to upper-limb (swim) and passive lower-limb exercise are investigated in rodents with a severe high-thoracic SCI. METHODS: Animals were divided into a control (CON), SCI no exercise (NO-EX), SCI passive hind-limb cycling (PHLC) or SCI swim (SWIM) group...
July 14, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28705881/defining-a-novel-role-for-the-pdx1-transcription-factor-in-islet-%C3%AE-cell-maturation-and-proliferation-during-weaning
#20
Jason M Spaeth, Manisha Gupte, Mark Perelis, Yu-Ping Yang, Holly Cyphert, Shuangli Guo, Jin-Hua Liu, Min Guo, Joseph Bass, Mark A Magnuson, Christopher Wright, Roland Stein
The transcription factor encoded by the Pancreas Duodenum Homeobox-1 (Pdx1) gene is a critical transcriptional regulator, as it has fundamental actions in the formation of all pancreatic cell types, islet β cell development, and adult islet β cell function. Transgenic- and cell line-based experiments have identified 5'-flanking conserved sequences that control pancreatic and β cell-type-specific transcription, which are found within Area I (base pairs (bp) -2694 to -2561), II (bp -2139 to -1958), III (bp -1879 to -1799), and IV (bp -6200 to -5670)...
July 13, 2017: Diabetes
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