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https://www.readbyqxmd.com/read/27911963/teaching-evidence-based-physical-diagnosis-six-bedside-lessons
#1
Steven McGee
Evidence-based physical diagnosis is an essential part of the bedside curriculum. By using the likelihood ratio, a simple measure of diagnostic accuracy, teachers can quickly adapt this approach to their bedside teaching. Six recurring themes in evidence-based physical diagnosis are fully reviewed, with examples, in this article.
December 2016: Southern Medical Journal
https://www.readbyqxmd.com/read/27814245/effects-of-periconception-cadmium-and-mercury-co-administration-to-mice-on-indices-of-chronic-disease-in-male-offspring-at-maturity
#2
Cagri Camsari, Joseph K Folger, Devin McGee, Steven J Bursian, Hongbing Wang, Jason G Knott, George W Smith
BACKGROUND: Long-term exposure to the heavy metals cadmium (Cd) and mercury (Hg) is known to increase risk of chronic diseases. However, to our knowledge, exposure to Cd and Hg beginning at the periconception period has not been studied to date. OBJECTIVE: The effect of co-administration of Cd and Hg during early development on indices of chronic diseases at adulthood was examined. METHODS: Adult female CD1 mice were subcutaneously administered a combination of cadmium chloride (CdCl2) and methylmercury (II) chloride (CH3HgCl; 0, 0...
November 4, 2016: Environmental Health Perspectives
https://www.readbyqxmd.com/read/27784800/consolidation-of-visuomotor-adaptation-memory-with-consistent-and-noisy-environments
#3
Rodrigo S Maeda, Steven E McGee, Daniel S Marigold
Our understanding of how we learn and retain motor behaviors is still limited. For instance, there is conflicting evidence as to whether the memory of a learned visuomotor perturbation consolidates; that is, the motor memory becomes resistant to interference from learning a competing perturbation over time. Here, we sought to determine the factors that influence consolidation during visually guided walking. Subjects learned a novel mapping relationship, created by prism lenses, between the perceived location of two targets and the motor commands necessary to direct the feet to their positions...
October 26, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27554445/characterization-of-3-3-dimethyl-substituted-n-aryl-piperidines-as-potent-microsomal-prostaglandin-e-synthase-1-inhibitors
#4
Steven L Kuklish, Stephen Antonysamy, Shobha N Bhattachar, Srinivasan Chandrasekhar, Matthew J Fisher, Adrian J Fretland, Karen Gooding, Anita Harvey, Norman E Hughes, John G Luz, Peter R Manninen, James E McGee, Antonio Navarro, Bryan H Norman, Katherine M Partridge, Steven J Quimby, Matthew A Schiffler, Ashley V Sloan, Alan M Warshawsky, Jeremy S York, Xiao-Peng Yu
Here we report on novel, potent 3,3-dimethyl substituted N-aryl piperidine inhibitors of microsomal prostaglandin E synthases-1(mPGES-1). Example 14 potently inhibited PGE2 synthesis in an ex vivo human whole blood (HWB) assay with an IC50 of 7nM. In addition, 14 had no activity in human COX-1 or COX-2 assays at 30μM, and failed to inhibit human mPGES-2 at 62.5μM in a microsomal prep assay. These data are consistent with selective mPGES-1-mediated reduction of PGE2. In dog, 14 had oral bioavailability (74%), clearance (3...
October 1, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27248295/possible-zika-virus-infection-among-pregnant-women-united-states-and-territories-may-2016
#5
Regina M Simeone, Carrie K Shapiro-Mendoza, Dana Meaney-Delman, Emily E Petersen, Romeo R Galang, Titilope Oduyebo, Brenda Rivera-Garcia, Miguel Valencia-Prado, Kimberly B Newsome, Janice Pérez-Padilla, Tonya R Williams, Matthew Biggerstaff, Denise J Jamieson, Margaret A Honein
Zika virus is a cause of microcephaly and brain abnormalities (1), and it is the first known mosquito-borne infection to cause congenital anomalies in humans. The establishment of a comprehensive surveillance system to monitor pregnant women with Zika virus infection will provide data to further elucidate the full range of potential outcomes for fetuses and infants of mothers with asymptomatic and symptomatic Zika virus infection during pregnancy. In February 2016, Zika virus disease and congenital Zika virus infections became nationally notifiable conditions in the United States (2)...
May 27, 2016: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/27001799/multistate-outbreak-of-respiratory-infections-among-unaccompanied-children-june-2014-july-2014
#6
Sara Tomczyk, Carmen S Arriola, Bernard Beall, Alvaro Benitez, Stephen R Benoit, LaShondra Berman, Joseph Bresee, Maria da Gloria Carvalho, Amanda Cohn, Kristen Cross, Maureen H Diaz, Louise K Francois Watkins, Ryan Gierke, Jose E Hagan, Aaron M Harris, Seema Jain, Lindsay Kim, Miwako Kobayashi, Stephen Lindstrom, Lesley McGee, Meredith McMorrow, Benjamin L Metcalf, Matthew R Moore, Iaci Moura, W Allan Nix, Edith Nyangoma, M Steven Oberste, Sonja J Olsen, Fabiana Pimenta, Christina Socias, Kathleen Thurman, Jessica Waller, Stephen H Waterman, Matthew Westercamp, Melinda Wharton, Cynthia G Whitney, Jonas M Winchell, Bernard Wolff, Curi Kim
BACKGROUND: From January 2014-July 2014, more than 46 000 unaccompanied children (UC) from Central America crossed the US-Mexico border. In June-July, UC aged 9-17 years in 4 shelters and 1 processing center in 4 states were hospitalized with acute respiratory illness. We conducted a multistate investigation to interrupt disease transmission. METHODS: Medical charts were abstracted for hospitalized UC. Nonhospitalized UC with influenza-like illness were interviewed, and nasopharyngeal and oropharyngeal swabs were collected to detect respiratory pathogens...
July 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/26607905/the-anthropometric-definition-of-the-rectum-is-highly-variable
#7
Molly A Wasserman, Michael F McGee, Irene B Helenowski, Amy L Halverson, Anne-Marie Boller, Steven J Stryker
PURPOSE: The precise definition of the rectum is essential for localizing colorectal pathology, yet current definitions are nebulous. The objective of this study is to determine the anthropometric definition of common pelvic landmarks in relation to patient characteristics. METHODS: Seventy-one patients underwent open proctectomy with intra-operative measurements from the anal verge to various pelvic landmarks, and patient characteristics were evaluated. Analyses were performed using Spearman correlation and Wilcoxon rank sum...
February 2016: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/26169885/bedside-diagnosis-of-the-red-eye-a-systematic-review
#8
REVIEW
Sirisha Narayana, Steven McGee
BACKGROUND: In patients with red eye, traditional teachings suggest that photophobia, visual blurring, and eye pain indicate serious eye disease; in patients with presumed conjunctivitis, the finding of purulent drainage traditionally indicates a bacterial cause. The accuracy of these teachings is unknown. METHODS: A MEDLINE search was performed to retrieve articles published between 1966 and April 2014 relevant to the bedside diagnosis of serious eye disease and bacterial conjunctivitis...
November 2015: American Journal of Medicine
https://www.readbyqxmd.com/read/25813372/an-examination-of-survival-by-sex-and-race-in-the-heartware-ventricular-assist-device-for-the-treatment-of-advanced-heart-failure-advance-bridge-to-transplant-btt-and-continued-access-protocol-trials
#9
MULTICENTER STUDY
Emma J Birks, Edwin C McGee, Keith D Aaronson, Steven Boyce, William G Cotts, Samer S Najjar, Francis D Pagani, David R Hathaway, Kevin Najarian, Mary V Jacoski, Mark S Slaughter
BACKGROUND: The Ventricular Assist Device for the Treatment of Advanced Heart Failure (ADVANCE) Bridge to Transplant (BTT) trial was a multicenter, prospective trial of the HeartWare Ventricular Assist Device (HVAD). The performance of the HVAD in various demographic sub-groups was evaluated. METHODS: Baseline characteristics, adverse events, and survival were compared for men vs. women and whites vs. non-whites in the combined ADVANCE BTT and continued access protocol trial...
June 2015: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/25384157/discovery-of-am-7209-a-potent-and-selective-4-amidobenzoic-acid-inhibitor-of-the-mdm2-p53-interaction
#10
Yosup Rew, Daqing Sun, Xuelei Yan, Hilary P Beck, Jude Canon, Ada Chen, Jason Duquette, John Eksterowicz, Brian M Fox, Jiasheng Fu, Ana Z Gonzalez, Jonathan Houze, Xin Huang, Min Jiang, Lixia Jin, Yihong Li, Zhihong Li, Yun Ling, Mei-Chu Lo, Alexander M Long, Lawrence R McGee, Joel McIntosh, Jonathan D Oliner, Tao Osgood, Anne Y Saiki, Paul Shaffer, Yu Chung Wang, Sarah Wortman, Peter Yakowec, Qiuping Ye, Dongyin Yu, Xiaoning Zhao, Jing Zhou, Julio C Medina, Steven H Olson
Structure-based rational design and extensive structure-activity relationship studies led to the discovery of AMG 232 (1), a potent piperidinone inhibitor of the MDM2-p53 association, which is currently being evaluated in human clinical trials for the treatment of cancer. Further modifications of 1, including replacing the carboxylic acid with a 4-amidobenzoic acid, afforded AM-7209 (25), featuring improved potency (KD from ITC competition was 38 pM, SJSA-1 EdU IC50 = 1.6 nM), remarkable pharmacokinetic properties, and in vivo antitumor activity in both the SJSA-1 osteosarcoma xenograft model (ED50 = 2...
December 26, 2014: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/25042256/optimization-beyond-amg-232-discovery-and-sar-of-sulfonamides-on-a-piperidinone-scaffold-as-potent-inhibitors-of-the-mdm2-p53-protein-protein-interaction
#11
Yingcai Wang, Jiang Zhu, Jiwen Jim Liu, Xiaoqi Chen, Jeff Mihalic, Jeffrey Deignan, Ming Yu, Daqing Sun, Frank Kayser, Lawrence R McGee, Mei-Chu Lo, Ada Chen, Jing Zhou, Qiuping Ye, Xin Huang, Alexander M Long, Peter Yakowec, Jonathan D Oliner, Steven H Olson, Julio C Medina
We recently reported on the discovery of AMG 232, a potent and selective piperidinone inhibitor of the MDM2-p53 interaction. AMG 232 is being evaluated in human clinical trials for cancer. Continued exploration of the N-alkyl substituent of this series, in an effort to optimize interactions with the MDM2 glycine-58 shelf region, led to the discovery of sulfonamides such as compounds 31 and 38 that have similar potency, hepatocyte stability and rat pharmacokinetic properties to AMG 232.
August 15, 2014: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/24916916/testing-demographic-differences-for-alcohol-use-initiation-among-adolescents-for-the-decisional-balance-and-situational-temptation-prevention-inventories
#12
Marie A Sillice, Andrea L Paiva, Steven F Babbin, Heather A McGee, Joseph S Rossi, Colleen A Redding, Kathryn S Meier, Karin Oatley, Wayne F Velicer
Alcohol use by middle school-aged students is a public health concern because of the numerous adverse social, health and psychological outcomes. Prevention programs attempt to intervene before alcohol use begins. A tailored, computer-delivered program for the prevention of alcohol use and a series of new transtheoretical model measures were developed, including decisional balance (Pros and Cons) of alcohol use and Situational Temptations to Try Alcohol. This study investigated if there were any demographic differences on these measures in a sample of 6th grade middle school students from 20 schools (N=4151) at baseline...
September 2014: Addictive Behaviors
https://www.readbyqxmd.com/read/24850761/a-von-willebrand-factor-fragment-containing-the-d-d3-domains-is-sufficient-to-stabilize-coagulation-factor-viii-in-mice
#13
Andrew Yee, Robert D Gildersleeve, Shufang Gu, Colin A Kretz, Beth M McGee, Keisha M Carr, Steven W Pipe, David Ginsburg
Plasma factor VIII (FVIII) and von Willebrand factor (VWF) circulate together as a complex. We identify VWF fragments sufficient for FVIII stabilization in vivo and show that hepatic expression of the VWF D'D3 domains (S764-P1247), either as a monomer or a dimer, is sufficient to raise FVIII levels in Vwf(-/-) mice from a baseline of ∼5% to 10%, to ∼50% to 100%. These results demonstrate that a fragment containing only ∼20% of the VWF sequence is sufficient to support FVIII stability in vivo. Expression of the VWF D'D3 fragment fused at its C terminus to the Fc segment of immunoglobulin G1 results in markedly enhanced survival in the circulation (t1/2 > 7 days), concomitant with elevated plasma FVIII levels (>25% at 7 days) in Vwf(-/-) mice...
July 17, 2014: Blood
https://www.readbyqxmd.com/read/24846031/a-piece-of-my-mind-bedside-teaching-rounds-reconsidered
#14
Steven McGee
No abstract text is available yet for this article.
May 21, 2014: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/24758962/diagnosing-and-treating-dizziness
#15
REVIEW
Alexandra Molnar, Steven McGee
Dizziness is a common presenting concern in primary care practice. The most useful diagnostic approach in distinguishing different types of dizziness is a thorough history and physical examination; additional tests are rarely necessary. Effective treatments exist for many causes of dizziness, and these treatments are often accomplished in the clinic or at home without the need for medication.
May 2014: Medical Clinics of North America
https://www.readbyqxmd.com/read/24601644/novel-inhibitors-of-the-mdm2-p53-interaction-featuring-hydrogen-bond-acceptors-as-carboxylic-acid-isosteres
#16
Ana Z Gonzalez, Zhihong Li, Hilary P Beck, Jude Canon, Ada Chen, David Chow, Jason Duquette, John Eksterowicz, Brian M Fox, Jiasheng Fu, Xin Huang, Jonathan Houze, Lixia Jin, Yihong Li, Yun Ling, Mei-Chu Lo, Alexander M Long, Lawrence R McGee, Joel McIntosh, Jonathan D Oliner, Tao Osgood, Yosup Rew, Anne Y Saiki, Paul Shaffer, Sarah Wortman, Peter Yakowec, Xuelei Yan, Qiuping Ye, Dongyin Yu, Xiaoning Zhao, Jing Zhou, Steven H Olson, Daqing Sun, Julio C Medina
We previously reported the discovery of potent and selective morpholinone and piperidinone inhibitors of the MDM2-p53 interaction. These inhibitors have in common a carboxylic acid moiety that engages in an electrostatic interaction with MDM2-His96. Our continued search for potent and diverse inhibitors led to the discovery of novel replacements for these acids uncovering new interactions with the MDM2 protein. In particular, using pyridine or thiazole as isosteres of the carboxylic acid moiety resulted in very potent analogues...
April 10, 2014: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/24548297/selective-and-potent-morpholinone-inhibitors-of-the-mdm2-p53-protein-protein-interaction
#17
Ana Z Gonzalez, John Eksterowicz, Michael D Bartberger, Hilary P Beck, Jude Canon, Ada Chen, David Chow, Jason Duquette, Brian M Fox, Jiasheng Fu, Xin Huang, Jonathan B Houze, Lixia Jin, Yihong Li, Zhihong Li, Yun Ling, Mei-Chu Lo, Alexander M Long, Lawrence R McGee, Joel McIntosh, Dustin L McMinn, Jonathan D Oliner, Tao Osgood, Yosup Rew, Anne Y Saiki, Paul Shaffer, Sarah Wortman, Peter Yakowec, Xuelei Yan, Qiuping Ye, Dongyin Yu, Xiaoning Zhao, Jing Zhou, Steven H Olson, Julio C Medina, Daqing Sun
We previously reported the discovery of AMG 232, a highly potent and selective piperidinone inhibitor of the MDM2-p53 interaction. Our continued search for potent and diverse analogues led to the discovery of novel morpholinone MDM2 inhibitors. This change to a morpholinone core has a significant impact on both potency and metabolic stability compared to the piperidinone series. Within this morpholinone series, AM-8735 emerged as an inhibitor with remarkable biochemical potency (HTRF IC50 = 0.4 nM) and cellular potency (SJSA-1 EdU IC50 = 25 nM), as well as pharmacokinetic properties...
March 27, 2014: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/24456472/discovery-of-amg-232-a-potent-selective-and-orally-bioavailable-mdm2-p53-inhibitor-in-clinical-development
#18
Daqing Sun, Zhihong Li, Yosup Rew, Michael Gribble, Michael D Bartberger, Hilary P Beck, Jude Canon, Ada Chen, Xiaoqi Chen, David Chow, Jeffrey Deignan, Jason Duquette, John Eksterowicz, Benjamin Fisher, Brian M Fox, Jiasheng Fu, Ana Z Gonzalez, Felix Gonzalez-Lopez De Turiso, Jonathan B Houze, Xin Huang, Min Jiang, Lixia Jin, Frank Kayser, Jiwen Jim Liu, Mei-Chu Lo, Alexander M Long, Brian Lucas, Lawrence R McGee, Joel McIntosh, Jeff Mihalic, Jonathan D Oliner, Tao Osgood, Matthew L Peterson, Philip Roveto, Anne Y Saiki, Paul Shaffer, Maria Toteva, Yingcai Wang, Yu Chung Wang, Sarah Wortman, Peter Yakowec, Xuelei Yan, Qiuping Ye, Dongyin Yu, Ming Yu, Xiaoning Zhao, Jing Zhou, Jiang Zhu, Steven H Olson, Julio C Medina
We recently reported the discovery of AM-8553 (1), a potent and selective piperidinone inhibitor of the MDM2-p53 interaction. Continued research investigation of the N-alkyl substituent of this series, focused in particular on a previously underutilized interaction in a shallow cleft on the MDM2 surface, led to the discovery of a one-carbon tethered sulfone which gave rise to substantial improvements in biochemical and cellular potency. Further investigation produced AMG 232 (2), which is currently being evaluated in human clinical trials for the treatment of cancer...
February 27, 2014: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/24418731/an-analysis-of-pump-thrombus-events-in-patients-in-the-heartware-advance-bridge-to-transplant-and-continued-access-protocol-trial
#19
Samer S Najjar, Mark S Slaughter, Francis D Pagani, Randall C Starling, Edwin C McGee, Peter Eckman, Antone J Tatooles, Nader Moazami, Robert L Kormos, David R Hathaway, Kevin B Najarian, Geetha Bhat, Keith D Aaronson, Steven W Boyce
BACKGROUND: The HeartWare left ventricular assist device (HVAD, HeartWare Inc, Framingham, MA) is the first implantable centrifugal continuous-flow pump approved for use as a bridge to transplantation. An infrequent but serious adverse event of LVAD support is thrombus ingestion or formation in the pump. In this study, we analyze the incidence of pump thrombus, evaluate the comparative effectiveness of various treatment strategies, and examine factors pre-disposing to the development of pump thrombus...
January 2014: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/24342231/csf-neurofilament-light-chain-is-elevated-in-oms-decreasing-with-immunotherapy-and-other-pediatric-neuroinflammatory-disorders
#20
Michael R Pranzatelli, Elizabeth D Tate, Nathan R McGee, Steven J Verhulst
Using a panel of seven brain cell-specific biomarkers in cerebrospinal fluid (CSF), pediatric opsoclonus-myoclonus syndrome (OMS) (n=234) was compared to pediatric non-inflammatory neurological controls (n=84) and other inflammatory neurological disorders (OIND) (n=44). Only CSF NFL was elevated in untreated OMS versus controls (+83%). It was 87% higher in OIND than in OMS. On combination treatment with front-loaded ACTH, IVIg, rituximab, median CSF NFL decreased by 60% to control levels. These biochemical data suggest neuronal/axonal injury in some children with OMS without indicators of astrogliosis, and reduction on sufficient immunotherapy...
January 15, 2014: Journal of Neuroimmunology
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