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https://www.readbyqxmd.com/read/28924025/the-challenges-of-identifying-an-oxygenation-index-threshold-for-increased-mortality-in-pediatric-acute-respiratory-failure
#1
EDITORIAL
Samantha H Dallefeld, Tracy G Spears, Kanecia O Zimmerman
No abstract text is available yet for this article.
October 2017: Respiratory Care
https://www.readbyqxmd.com/read/28916340/identification-of-potent-nonabsorbable-agonists-of-the-calcium-sensing-receptor-for-gi-specific-administration
#2
Steven M Sparks, Paul K Spearing, Caroline J Diaz, David J Cowan, Channa Jayawickreme, Grace Chen, Thomas J Rimele, Claudia Generaux, Lindsey T Harston, Shane G Roller
Modulation of gastrointestinal nutrient sensing pathways provides a promising a new approach for the treatment of metabolic diseases including diabetes and obesity. The calcium-sensing receptor has been identified as a key receptor involved in mineral and amino acid nutrient sensing and thus is an attractive target for modulation in the intestine. Herein we describe the optimization of gastrointestinally restricted calcium-sensing receptor agonists starting from a 3-aminopyrrolidine-containing template leading to the identification of GI-restricted agonist 19 (GSK3004774)...
September 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28891437/investigation-of-ocular-bioactivation-potential-and-the-role-of-cytochrome-p450-2d-enzymes-in-rat
#3
Jennifer L Dumouchel, Upendra A Argikar, Jaimie Spear, Ann Brown, Christine E Dunne, Valerie M Kramlinger, Amanda L Cirello, Mithat Gunduz
BACKGROUND: Timolol is clinically administered topically (ocular) to reduce intraocular pressure and treat open-angle glaucoma. Ocular administration of timolol in low doses (0.5% w/v in the form of eye drops) has led to challenges for in vivo metabolite identification. An understanding of drug metabolism in the eye is important for clinical ocular therapeutics and potential drug candidates. METHODS: We aimed to investigate the metabolism of timolol in rat ocular and liver S9 fractions, as well as rat ocular tissue and plasma following a 0...
September 11, 2017: Drug Metabolism Letters
https://www.readbyqxmd.com/read/28873453/satellite-tagging-of-rehabilitated-green-sea-turtles-chelonia-mydas-from-the-united-arab-emirates-including-the-longest-tracked-journey-for-the-species
#4
David P Robinson, Rima W Jabado, Christoph A Rohner, Simon J Pierce, Kevin P Hyland, Warren R Baverstock
We collected movement data for eight rehabilitated and satellite-tagged green sea turtles Chelonia mydas released off the United Arab Emirates between 2005 and 2013. Rehabilitation periods ranged from 96 to 1353 days (mean = 437 ± 399 days). Seven of the eight tagged turtles survived after release; one turtle was killed by what is thought to be a post-release spear gun wound. The majority of turtles (63%) used shallow-water core habitats and established home ranges between Dubai and Abu Dhabi, the same area in which they had originally washed ashore prior to rescue...
2017: PloS One
https://www.readbyqxmd.com/read/28866269/discovery-of-a-novel-cns-penetrant-m4-pam-chemotype-based-on-a-6-fluoro-4-piperidin-1-yl-quinoline-3-carbonitrile-core
#5
Blake R Bewley, Paul K Spearing, Rebecca L Weiner, Vincent B Luscombe, Xiaoyan Zhan, Sichen Chang, Hyekyung P Cho, Alice L Rodriguez, Colleen M Niswender, P Jeffrey Conn, Thomas M Bridges, Darren W Engers, Craig W Lindsley
This Letter details the discovery and subsequent optimization of a novel M4 PAM scaffold based on an 6-fluoro-4-(piperidin-1-yl)quinoline-3-carbonitrile core, which represents a distinct departure from the classical M4 PAM chemotypes. Optimized compounds in this series demonstrated improved M4 PAM potency on both human and rat M4 (4 to 5-fold relative to HTS hit), and displayed attractive physicochemical and DMPK profiles, including good CNS penetration (rat brain:plasma Kp=5.3, Kp,uu=2.4; MDCK-MDR1 (P-gp) ER=1...
September 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28859518/socioeconomic-indicators-as-predictors-of-smoking-cessation-among-spanish-speaking-mexican-americans
#6
Christine Vinci, Lin Guo, Claire A Spears, Liang Li, Virmarie Correa-Fernández, Paul E Etcheverry, Cho Y Lam, Diana S Hoover, David W Wetter
OBJECTIVE: Smoking-related illnesses are the leading cause of death among Latinos, and within this ethnic group, Mexican Americans are the largest subgroup in the U.S. Understanding the factors associated with successful smoking cessation could inform interventions for this population. Although socioeconomic status (SES) is a powerful predictor of cessation outcomes in the general U.S. population, it has generally been a poor predictor of quitting smoking among Latinos. Within a sample of Spanish-speaking Mexican Americans (n = 199), this study examined a broad array of objective and subjective indicators of SES (i...
September 1, 2017: Ethnicity & Health
https://www.readbyqxmd.com/read/28830236/testing-many-treatments-within-a-single-protocol-over-10%C3%A2-years-at-mrc-clinical-trials-unit-at-ucl-multi-arm-multi-stage-platform-umbrella-and-basket-protocols
#7
Mahesh Kb Parmar, Fay H Cafferty, Matthew R Sydes, Babak Choodari-Oskooei, Ruth E Langley, Louise Brown, Patrick Pj Phillips, Melissa R Spears, Sam Rowley, Richard Kaplan, Nicholas D James, Timothy Maughan, Nicholas Paton, Patrick J Royston
BACKGROUND: There is real need to change how we do some of our clinical trials, as currently the testing and development process is too slow, too costly and too failure-prone - often we find that a new treatment is no better than the current standard. PURPOSE AND METHODS: Much of the focus on the development and testing pathway has been in improving the design of phase I and II trials. In this paper we present examples of new methods for improving the design of phase III trials (and the necessary lead up to them) as they are the most time-consuming and expensive part of the pathway...
August 1, 2017: Clinical Trials: Journal of the Society for Clinical Trials
https://www.readbyqxmd.com/read/28828473/informed-consent-to-study-purpose-in-randomized-clinical-trials-of-antibiotics-1991-through-2011
#8
Peter Doshi, Peter Hur, Mark Jones, Husam Albarmawi, Tom Jefferson, Daniel J Morgan, Patricia A Spears, John H Powers
Importance: Potential research participants may assume that randomized trials comparing new interventions with older interventions always hypothesize greater efficacy for the new intervention, as in superiority trials. However, antibiotic trials frequently use "noninferiority" hypotheses allowing a degree of inferior efficacy deemed "clinically acceptable" compared with an older effective drug, in exchange for nonefficacy benefits (eg, decreased adverse effects). Considering these different benefit-harm trade-offs, proper informed consent necessitates supplying different information on the purposes of superiority and noninferiority trials...
August 21, 2017: JAMA Internal Medicine
https://www.readbyqxmd.com/read/28815746/matthew-baillie-s-specimens-and-engravings
#9
Caitlin Spear, Maggie Reilly, Stuart W McDonald
In 1799, Matthew Baillie, William Hunter's nephew, published his famous atlas of pathology. It was entitled A Series of Engravings Accompanied with Explanations which are Intended to Illustrate the Morbid Anatomy of Some of the Most Important Parts of the Human Body. The present study aims to match the illustrations to extant specimens in the collections of William and John Hunter, preserved at the University of Glasgow and at the Royal College of Surgeons of England respectively. Baillie's book contains 10 fasciculi, consisting of 73 plates and 206 figures...
August 17, 2017: Clinical Anatomy
https://www.readbyqxmd.com/read/28812208/genetic-testing-in-inherited-heart-diseases-practical-considerations-for-clinicians
#10
REVIEW
Melanie Care, Vijay Chauhan, Danna Spears
PURPOSE OF REVIEW: Genetic testing has become an important element in the care of patients with inherited cardiac conditions (ICCs). The purpose of this review is to provide clinicians with insights into the utility of genetic testing as well as challenges associated with interpreting results. RECENT FINDINGS: Genetic testing may be indicated for individuals who are affected with or who have family histories of various ICCs. Various testing options are available and determining the most appropriate test for any given clinical scenario is key when interpreting results...
August 16, 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28801752/biosimilar-g-csf-versus-filgrastim-and-lenograstim-in-healthy-unrelated-volunteer-hematopoietic-stem-cell-donors
#11
Roiya Farhan, Elżbieta Urbanowska, Hanna Zborowska, Małgorzata Król, Maria Król, Tigran Torosian, Iwona Piotrowska, Krzysztof Bogusz, Kamila Skwierawska, Wiesław Wiktor-Jędrzejczak, Emilian Snarski
The World Marrow Donor Organization recommends original granulocyte-colony stimulating factor (G-CSF) for the mobilization of stem cells in healthy unrelated hematopoietic stem cell donors. We report the comparison of a biosimilar G-CSF (Zarzio) with two original G-CSFs (filgrastim and lenograstim) in mobilization in unrelated donors. We included data of 313 consecutive donors who were mobilized during the period from October 2014 to March 2016 at the Medical University of Warsaw. The primary endpoints of this study were the efficiency of CD34+ cell mobilization to the circulation and results of the first apheresis...
August 11, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28800492/adding-abiraterone-to-androgen-deprivation-therapy-in-men-with-metastatic-hormone-sensitive-prostate-cancer-a%C3%A2-systematic-review-and-meta-analysis
#12
Larysa H M Rydzewska, Sarah Burdett, Claire L Vale, Noel W Clarke, Karim Fizazi, Thian Kheoh, Malcolm D Mason, Branko Miladinovic, Nicholas D James, Mahesh K B Parmar, Melissa R Spears, Christopher J Sweeney, Matthew R Sydes, NamPhuong Tran, Jayne F Tierney
BACKGROUND: There is a need to synthesise the results of numerous randomised controlled trials evaluating the addition of therapies to androgen deprivation therapy (ADT) for men with metastatic hormone-sensitive prostate cancer (mHSPC). This systematic review aims to assess the effects of adding abiraterone acetate plus prednisone/prednisolone (AAP) to ADT. METHODS: Using our framework for adaptive meta-analysis (FAME), we started the review process before trials had been reported and worked collaboratively with trial investigators to anticipate when eligible trial results would emerge...
August 8, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28750615/implications-of-male-circumcision-for-women-in-papua-new-guinea-a-transformational-grounded-theory-study
#13
Michelle Redman-MacLaren, Jane Mills, Rachael Tommbe, David MacLaren, Rick Speare, William J H McBride
BACKGROUND: Male circumcision reduces the risk of female-to-male transmission of human immunodeficiency virus (HIV) and is being explored for HIV prevention in Papua New Guinea (PNG). PNG has a concentrated HIV epidemic which is largely heterosexually transmitted. There are a diverse range of male circumcision and penile modification practices across PNG. Exploring the implications of male circumcision for women in PNG is important to inform evidence-based health policy that will result in positive, intended consequences...
July 27, 2017: BMC Women's Health
https://www.readbyqxmd.com/read/28747493/role-of-viral-hemorrhagic-septicemia-virus-matrix-m-protein-in-suppressing-host-transcription
#14
Qi Ke, Wade Weaver, Adam Pore, Bartolomeo Gorgoglione, Julia Halo Wildschutte, Peng Xiao, Brian S Shepherd, Allyn Spear, Krishnamurthy Malathi, Carol A Stepien, Vikram N Vakharia, Douglas W Leaman
Viral hemorrhagic septicemia virus (VHSV) is a pathogenic fish rhabdovirus found in discrete locales throughout the Northern Hemisphere. VHSV infection of fish cells leads to upregulation of the host's virus detection response, but the virus quickly suppresses interferon (IFN) production and antiviral gene expression. By systematically screening each of the six VHSV structural and nonstructural genes, we identified matrix protein (M) as the virus' most potent antihost protein. Only M of VHSV genotype IV sublineage b (VHSV-IVb) suppressed mitochondrial antiviral signaling protein (MAVS) and type I IFN-induced gene expression in a dose-dependent manner...
October 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28742741/an-unusual-case-of-acute-parotitis-in-a-young-adult
#15
Azra Sehic, Caitlin Haenig, Francis Spear
Acute bacterial parotitis is uncommon in young adults. Infection with Serratia marcescens is even rarer and usually found in hospitalized patients. This case report focuses on a young woman with acute bacterial parotitis caused by S. marcescens that required a longer-than-normal course of antibiotics.
August 2017: JAAPA: Official Journal of the American Academy of Physician Assistants
https://www.readbyqxmd.com/read/28731824/evolutionary-scenarios-and-primate-natural-history
#16
Harry W Greene
Scenarios summarize evolutionary patterns and processes by interpreting organismal traits and their natural history correlates in a phylogenetic context. They are constructed by (1) describing phenotypes (including physiology and behavior), ideally with attention to formative roles of development, experience, and culture; (2) inferring homologies, homoplasies, ancestral character states, and their transformations with phylogenetic analyses; and (3) integrating those components with ecological and other ancillary data...
August 2017: American Naturalist
https://www.readbyqxmd.com/read/28726478/the-association-of-positive-emotion-and-first-smoking-lapse-an-ecological-momentary-assessment-study
#17
Christine Vinci, Liang Li, Cai Wu, Cho Y Lam, Lin Guo, Virmarie Correa-Fernández, Claire A Spears, Diana S Hoover, Paul E Etcheverry, David W Wetter
OBJECTIVE: Individuals attempting to quit smoking typically have poor success rates, and the majority fail to maintain long-term abstinence. Although a large body of evidence documents the impact of negative affect on reducing abstinence, there is a much smaller body of research on positive emotions, which could be an important mechanism that is associated with successful cessation. As such, this study examined positive emotions in real-time via ecological momentary assessment (EMA) to determine whether discrete positive emotions were uniquely related to 2 cessation milestones: quit day lapse and first lapse...
July 20, 2017: Health Psychology: Official Journal of the Division of Health Psychology, American Psychological Association
https://www.readbyqxmd.com/read/28718946/evidence-for-plical-support-of-the-patella
#18
Robert M Geraghty, Michelle Spear
There is a consensus that there is no overt anterior joint capsule in the knee. However, other anterior structures act in lieu of a joint capsule: the quadriceps tendon and patellar retinacular fibres. In the absence of a capsule, the synovium forms the suprapatellar pouch. Other synovial structures, the plicae, are more controversial. They are often described as embryonic remnants with no function, despite surrounding the patella. We aimed to identify plical anatomy and histology on cadaveric dissection and to examine their embryology using the human virtual embryo website...
July 18, 2017: Journal of Anatomy
https://www.readbyqxmd.com/read/28717166/targeting-cellular-calcium-homeostasis-to-prevent-cytokine-mediated-beta-cell-death
#19
Amy L Clark, Kohsuke Kanekura, Zeno Lavagnino, Larry D Spears, Damien Abreu, Jana Mahadevan, Takuya Yagi, Clay F Semenkovich, David W Piston, Fumihiko Urano
Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715752/switching-to-sanitation-understanding-latrine-adoption-in-a-representative-panel-of-rural-indian-households
#20
Diane Coffey, Dean Spears, Sangita Vyas
Open defecation, which is still practiced by about a billion people worldwide, is one of the most compelling examples of how place influences health in developing countries. Efforts by governments and development organizations to address the world's remaining open defecation would be greatly supported by a better understanding of why some people adopt latrines and others do not. We analyze the 2005 and 2012 rounds of the India Human Development Survey (IHDS), a nationally representative panel of households in India, the country which is home to 60% of the people worldwide who defecate in the open...
July 6, 2017: Social Science & Medicine
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