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https://www.readbyqxmd.com/read/29053717/gpr40-partial-agonists-and-agopams-differentiating-effects-on-glucose-and-hormonal-secretions-in-the-rodent
#1
Michele J Pachanski, Melissa E Kirkland, Daniel T Kosinski, Joel Mane, Boonlert Cheewatrakoolpong, Jiyan Xue, Daphne Szeto, Gail Forrest, Corin Miller, Michelle Bunzel, Christopher W Plummer, Harry R Chobanian, Michael W Miller, Sarah Souza, Brande S Thomas-Fowlkes, Aimie M Ogawa, Adam B Weinglass, Jerry Di Salvo, Xiaoyan Li, Yue Feng, Daniel A Tatosian, Andrew D Howard, Steven L Colletti, Maria E Trujillo
GPR40 agonists are effective antidiabetic agents believed to lower glucose through direct effects on the beta cell to increase glucose stimulated insulin secretion. However, not all GPR40 agonists are the same. Partial agonists lower glucose through direct effects on the pancreas, whereas GPR40 AgoPAMs may incorporate additional therapeutic effects through increases in insulinotrophic incretins secreted by the gut. Here we describe how GPR40 AgoPAMs stimulate both insulin and incretin secretion in vivo over time in diabetic GK rats...
2017: PloS One
https://www.readbyqxmd.com/read/29050764/pharmacokinetic-studies-of-a-three-component-complex-that-repurposes-the-front-line-antibiotic-isoniazid-against-mycobacterium-tuberculosis
#2
Thomas J Manning, Kyle Wilkerson, Taylor Holder, Andrew Carson Bartley, Chelsea Jackson, Sydney Plummer, Dennis Phillips, Logan Krajewski, Greg Wylie
The frontline tuberculosis (Tb) antibiotic isoniazid has been repurposed using a three component complex aimed at increasing the delivery efficiency and adding new avenues to its mechanism of action. This study focuses on pharmacokinetic studies of the isoniazid-sucrose-copper (II)-PEG-3350 complex. The assays include the Plasma Protein Binding Assay (85.8%), Caco-2 Permeability Assay (B→APapp, 0.13 × 10(-6) cm/s), Cytochrome P450 Inhibition Assay (i.e. CYP2B6, IC50 = 7.26 μM), In vitro microsomal Stability Assay (t1/2 NADPH-Dependent > 240 min), and HepG2 Cytotoxicity (no toxicity)...
December 2017: Tuberculosis
https://www.readbyqxmd.com/read/29034829/the-impact-of-obesity-on-brain-iron-levels-and-%C3%AE-synuclein-expression-is-regionally-dependent
#3
Jian Han, Justin Plummer, Lumei Liu, Aria Byrd, Michael Aschner, Keith M Erikson
BACKGROUND: The importance of iron homeostasis is particularly apparent in the brain, where iron deficiency results in impaired cognition and iron accumulation is associated with neurodegenerative diseases. Obesity is linked to iron deficiency systemically, but the effects of obesity on brain iron and its associated consequences, including neurodegenerative processes remain unexplored. This preliminary study examined the effect of dietary-induced obesity on brain regional iron, α-synuclein expression, and F2-isoprostane (oxidative stress marker) concentrations in selected brain regions...
October 16, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/29028005/microbiome-and-infectivity-studies-reveal-complex-polyspecies-tree-disease-in-acute-oak-decline
#4
Sandra Denman, James Doonan, Emma Ransom-Jones, Martin Broberg, Sarah Plummer, Susan Kirk, Kelly Scarlett, Andrew R Griffiths, Maciej Kaczmarek, Jack Forster, Andrew Peace, Peter N Golyshin, Francis Hassard, Nathan Brown, John G Kenny, James E McDonald
Decline-diseases are complex and becoming increasingly problematic to tree health globally. Acute Oak Decline (AOD) is characterized by necrotic stem lesions and galleries of the bark-boring beetle, Agrilus biguttatus, and represents a serious threat to oak. Although multiple novel bacterial species and Agrilus galleries are associated with AOD lesions, the causative agent(s) are unknown. The AOD pathosystem therefore provides an ideal model for a systems-based research approach to address our hypothesis that AOD lesions are caused by a polymicrobial complex...
October 13, 2017: ISME Journal
https://www.readbyqxmd.com/read/29026685/pharmacokinetics-of-carfilzomib-in-patients-with-advanced-malignancies-and-varying-degrees-of-hepatic-impairment-an-open-label-single-arm-phase-1-study
#5
Jennifer Brown, Ruth Plummer, Todd M Bauer, Stephen Anthony, John Sarantopoulos, Filip De Vos, Mike White, Marco Schupp, Ying Ou, Ulka Vaishampayan
BACKGROUND: Carfilzomib is approved in the United States and Europe for treatment of relapsed or refractory multiple myeloma (MM). This study evaluated pharmacokinetics (PK) and safety of carfilzomib in patients with relapsed or progressive advanced malignancies and varying degrees of impaired hepatic function. METHODS: Patients with normal hepatic function (normal) or hepatic impairment (mild, moderate, or severe) received carfilzomib infusion in 28-day cycles...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29023576/overexpression-of-tissue-nonspecific-alkaline-phosphatase-tnap-in-endothelial-cells-accelerates-coronary-artery-disease-in-a-mouse-model-of-familial-hypercholesterolemia
#6
Filippo Romanelli, AnthonyMarco Corbo, Maryam Salehi, Manisha C Yadav, Soha Salman, David Petrosian, Omid J Rashidbaigi, Jesse Chait, Jes Kuruvilla, Maria Plummer, Ilian Radichev, Kenneth B Margulies, A Martin Gerdes, Anthony B Pinkerton, José Luis Millán, Alexei Y Savinov, Olga V Savinova
OBJECTIVE: Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelium leads to arterial calcification in mice. The purpose of this study was to examine the effect of elevated endothelial TNAP on coronary atherosclerosis. In addition, we aimed to examine endogenous TNAP activity in human myocardium. APPROACH AND RESULTS: A vascular pattern of TNAP activity was observed in human non-failing, ischemic, and idiopathic dilated hearts (5 per group); no differences were noted between groups in this study...
2017: PloS One
https://www.readbyqxmd.com/read/29020037/a-conserved-fungal-glycosyltransferase-facilitates-pathogenesis-of-plants-by-enabling-hyphal-growth-on-solid-surfaces
#7
Robert King, Martin Urban, Rebecca P Lauder, Nichola Hawkins, Matthew Evans, Amy Plummer, Kirstie Halsey, Alison Lovegrove, Kim Hammond-Kosack, Jason J Rudd
Pathogenic fungi must extend filamentous hyphae across solid surfaces to cause diseases of plants. However, the full inventory of genes which support this is incomplete and many may be currently concealed due to their essentiality for the hyphal growth form. During a random T-DNA mutagenesis screen performed on the pleomorphic wheat (Triticum aestivum) pathogen Zymoseptoria tritici, we acquired a mutant unable to extend hyphae specifically when on solid surfaces. In contrast "yeast-like" growth, and all other growth forms, were unaffected...
October 11, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28993802/glycemia-is-related-to-impaired-cerebrovascular-autoregulation-after-severe-pediatric-traumatic-brain-injury-a-retrospective-observational-study
#8
Adam M H Young, Hadie Adams, Joseph Donnelly, Mathew R Guilfoyle, Helen Fernandes, Mathew R Garnett, Marek Czosnyka, Peter Smielewski, Mark Plummer, Shruti Agrawal, Peter J Hutchinson
INTRODUCTION: A strong association exists between hyperglycemia and outcome in pediatric traumatic brain injury (TBI). Herein, we describe observations of serum markers of glucose metabolism in a cohort of pediatric TBI patients and how these variables are related to parameters of intracranial pathophysiology. METHODS: A retrospective analysis was performed on pediatric severe TBI patients admitted to Addenbrookes Hospital Paediatric Intensive Care Unit (PICU) between January 2001 and December 2013...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28985985/corneal-response-to-injury-and-infection-in-the-horse
#9
REVIEW
Caryn E Plummer
This article describes the natural responses of the immune system and the cornea to injury and infection. The process of reepithelialization and reformation of stromal collagen is discussed, as are the clinical signs and manifestations of the effects of the healing response when it is routine and when it is pathologic. Excessive inflammatory or immune responses by host tissues can cause further damage that may be present from the antecedent injury or the effect of a pathogen. The clinical signs and manifestations of wound healing as well as potential therapeutic interventions are described...
October 3, 2017: Veterinary Clinics of North America. Equine Practice
https://www.readbyqxmd.com/read/28982126/natural-and-cross-inducible-anti-siv-antibodies-in-mauritian-cynomolgus-macaques
#10
Hongzhao Li, Mikaela Nykoluk, Lin Li, Lewis R Liu, Robert W Omange, Geoff Soule, Lukas T Schroeder, Nikki Toledo, Mohammad Abul Kashem, Jorge F Correia-Pinto, Binhua Liang, Nancy Schultz-Darken, Maria J Alonso, James B Whitney, Francis A Plummer, Ma Luo
Cynomolgus macaques are an increasingly important nonhuman primate model for HIV vaccine research. SIV-free animals without pre-existing anti-SIV immune responses are generally needed to evaluate the effect of vaccine-induced immune responses against the vaccine epitopes. Here, in order to select such animals for vaccine studies, we screened 108 naïve female Mauritian cynomolgus macaques for natural (baseline) antibodies to SIV antigens using a Bio-Plex multiplex system. The antigens included twelve 20mer peptides overlapping the twelve SIV protease cleavage sites (-10/+10), respectively (PCS peptides), and three non-PCS Gag or Env peptides...
2017: PloS One
https://www.readbyqxmd.com/read/28973430/antecedent-hypoglycemia-does-not-attenuate-the-acceleration-of-gastric-emptying-by-hypoglycemia
#11
Palash Kar, Karen L Jones, Mark P Plummer, Yasmine Ali Abdelhamid, Emma J Giersch, Matthew J Summers, Seva Hatzinikolas, Simon Heller, Michael Horowitz, Adam M Deane
Context: Acute hypoglycemia accelerates gastric emptying and increases cardiac contractility. However, antecedent hypoglycemia attenuates counter-regulatory hormonal responses to subsequent hypoglycemia. Objective: To determine the effect of antecedent hypoglycemia on gastric and cardiac responses to subsequent hypoglycemia in health. Design: A prospective, single-blind, randomised, cross over study. Patients: Ten healthy young men aged 18-35 years of age were studied for 36 hours on two occasions...
July 26, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28971100/comparison-of-the-luminal-and-mucosa-associated-microbiota-in-the-colon-of-pigs-with-and-without-swine-dysentery
#12
Eric R Burrough, Bailey L Arruda, Paul J Plummer
Colonic contents and mucosal scrapings from pigs inoculated with Brachyspira hyodysenteriae or Brachyspira hampsonii were collected at necropsy and classified as either positive (n = 29) or negative (n = 7) for swine dysentery (SD) based upon lesions and positive culture from the source pig. The microbiota in each sample was analyzed by bacterial census taking (16S rRNA gene sequencing). Procrustes analysis revealed similar clustering by disease classification with a relatively high M2 value (0.44) suggesting differences in the microbiota between mucosal and luminal samples from the same pig...
2017: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/28967467/an-exploration-of-participants-experience-of-an-intensive-care-nursing-transition-to-specialty-practice-program
#13
Auxillia E Madhuvu, Virginia Plummer, Julia Morphet
BACKGROUND: Transition to specialty practice programs were developed to support, educate and facilitate recruitment and retention of nurses in specialised areas of practice. The intensive care nursing transition to specialty practice program in this study was implemented in 2000. To date, in Australia there are no published studies which focus on intensive care nursing transition to specialty practice programs. OBJECTIVES: The study aimed to explore the effects of an intensive care nursing transition to specialty practice program offered in two intensive care units in a single Australian health service...
September 26, 2017: Australian Critical Care: Official Journal of the Confederation of Australian Critical Care Nurses
https://www.readbyqxmd.com/read/28958663/improving-real-world-walking-habits-after-stroke-requires-behavioural-change-techniques-not-just-exercise-and-gait-training-synopsis
#14
Prudence Plummer
No abstract text is available yet for this article.
October 2017: Journal of Physiotherapy
https://www.readbyqxmd.com/read/28950288/select-3-a-phase-i-study-of-selumetinib-in-combination-with-platinum-doublet-chemotherapy-for-advanced-nsclc-in-the-first-line-setting
#15
MULTICENTER STUDY
Alastair Greystoke, Nicola Steele, Hendrik-Tobias Arkenau, Fiona Blackhall, Noor Md Haris, Colin R Lindsay, Raffaele Califano, Mark Voskoboynik, Yvonne Summers, Karen So, Dana Ghiorghiu, Angela W Dymond, Stuart Hossack, Ruth Plummer, Emma Dean
BACKGROUND: We investigated selumetinib (AZD6244, ARRY-142886), an oral, potent, and highly selective, allosteric MEK1/2 inhibitor, plus platinum-doublet chemotherapy for patients with advanced/metastatic non-small cell lung cancer. METHODS: In this Phase I, open-label study (NCT01809210), treatment-naïve patients received selumetinib (50, 75, 100 mg BID PO) plus standard doses of gemcitabine or pemetrexed plus cisplatin or carboplatin. Primary objectives were safety, tolerability, and determination of recommended Phase II doses...
September 26, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28945792/how-do-environmental-governance-processes-shape-evaluation-of-outcomes-by-stakeholders-a-causal-pathways-approach
#16
Ryan Plummer, Angela Dzyundzyak, Julia Baird, Örjan Bodin, Derek Armitage, Lisen Schultz
Multi-stakeholder environmental management and governance processes are essential to realize social and ecological outcomes. Participation, collaboration, and learning are emphasized in these processes; to gain insights into how they influence stakeholders' evaluations of outcomes in relation to management and governance interventions we use a path analysis approach to examine their relationships in individuals in four UNESCO Biosphere Reserves. We confirm a model showing that participation in more activities leads to greater ratings of process, and in turn, better evaluations of outcomes...
2017: PloS One
https://www.readbyqxmd.com/read/28943715/methods-for-eliciting-annotating-and-analyzing-databases-for-child-speech-development
#17
Mary E Beckman, Andrew R Plummer, Benjamin Munson, Patrick F Reidy
Methods from automatic speech recognition (ASR), such as segmentation and forced alignment, have facilitated the rapid annotation and analysis of very large adult speech databases and databases of caregiver-infant interaction, enabling advances in speech science that were unimaginable just a few decades ago. This paper centers on two main problems that must be addressed in order to have analogous resources for developing and exploiting databases of young children's speech. The first problem is to understand and appreciate the differences between adult and child speech that cause ASR models developed for adult speech to fail when applied to child speech...
September 2017: Computer Speech & Language
https://www.readbyqxmd.com/read/28941249/selective-pressure-for-rapid-membrane-integration-constrains-the-sequence-of-bacterial-outer-membrane-proteins
#18
Janine H Peterson, Ashlee M Plummer, Karen G Fleming, Harris D Bernstein
Almost all bacterial outer membrane proteins (OMPs) contain a β barrel domain that serves as a membrane anchor, but the assembly and quality control of these proteins are poorly understood. Here we show that the introduction of a single lipid-facing arginine residue near the middle of the β barrel of the E. coli OMPs OmpLA and EspP creates an energy barrier that impedes membrane insertion. Although several unintegrated OmpLA mutants remained insertion-competent, they were slowly degraded by the periplasmic protease DegP...
September 23, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28932606/plummer-vinson-syndrome-a-rare-syndrome-in-male-with-review-of-the-literature
#19
Priyadarshini Karthikeyan, Nalini Aswath, Ramesh Kumaresan
INTRODUCTION: Plummer Vinson syndrome also known as Paterson Brown-Kelly syndrome is a syndrome associated with the triad of symptoms comprising microcytic hypochromic anemia, oesophageal strictures, and dysphagia. PVS is commonly found in women of middle age especially in the fourth and fifth decade of life and is rarely reported in males. CASE REPORT: The authors report a case of 43-year-old male patient who presented with the classic symptoms of Plummer Vinson syndrome...
2017: Case Reports in Dentistry
https://www.readbyqxmd.com/read/28929557/survivors-perceptions-of-public-health-messages-during-an-ebola-crisis-in-liberia-and-sierra-leone-an-exploratory-study
#20
Patricia Schwerdtle, Veronique De Clerck, Virginia Plummer
The outbreak of Ebola virus disease in Guinea, Liberia, and Sierra Leone was the largest epidemic of Ebola ever recorded. The healthcare workforce was diminished and exhausted as the region emerged from civil war. Few qualitative, descriptive studies have been conducted to date that concentrate on the voices of Ebola survivors and their perceptions of health messages. In this study, we employed an interpretive, qualitative design to explore participant experiences. Twenty five survivors who had recovered from Ebola were recruited from three villages in Liberia and Sierra Leone in August 2015...
September 20, 2017: Nursing & Health Sciences
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