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https://www.readbyqxmd.com/read/29783694/adaptive-mutations-in-influenza-a-california-07-2009-enhance-polymerase-activity-and-infectious-virion-production
#1
Patrick D Slaine, Cara MacRae, Mariel Kleer, Emily Lamoureux, Sarah McAlpine, Michelle Warhuus, André M Comeau, Craig McCormick, Todd Hatchette, Denys A Khaperskyy
Mice are not natural hosts for influenza A viruses (IAVs), but they are useful models for studying antiviral immune responses and pathogenesis. Serial passage of IAV in mice invariably causes the emergence of adaptive mutations and increased virulence. Here, we report the adaptation of IAV reference strain A/California/07/2009(H1N1) (also known as CA/07) in outbred Swiss Webster mice. Serial passage led to increased virulence and lung titers, and dissemination of the virus to brains. We adapted a deep-sequencing protocol to identify and enumerate adaptive mutations across all genome segments...
May 18, 2018: Viruses
https://www.readbyqxmd.com/read/29771816/imitating-incidents-how-simulation-can-improve-safety-investigation-and-learning-from-adverse-events
#2
Carl Macrae
One of the most fundamental principles of patient safety is to investigate and learn from the past in order to improve the future. However, healthcare organizations can find it challenging to develop the robust organizational processes and work practices that are needed to rigorously investigate and learn from safety incidents. Key challenges include difficulties developing specialist knowledge and expertise, understanding complex incidents, coordinating collaborative action, and positively changing practice...
May 15, 2018: Simulation in Healthcare: Journal of the Society for Simulation in Healthcare
https://www.readbyqxmd.com/read/29748816/epicatechin-s-cardiovascular-protective-effects-are-mediated-via-opioid-receptors-and-nitric-oxide
#3
Kirsty MacRae, Kylie Connolly, Rebecca Vella, Andrew Fenning
PURPOSE: Cardiovascular disease is the leading cause of mortality globally. Epicatechin has previously been shown to improve vascular responses and possess cardioprotective properties. However, the mechanisms underpinning these cardiotropic outcomes remain unknown. The aim of this study was to further identify epicatechin's mechanism of action in the cardiovasculature. METHODS: The effects of epicatechin on isolated rat conduit arteries, resistance vessels and cardiac electrophysiology were investigated on resting tension and precontracted vessels and cardiac action potential parameters, both in the presence and in the absence of various antagonists...
May 10, 2018: European Journal of Nutrition
https://www.readbyqxmd.com/read/29736681/early-and-late-cortical-responses-to-directly-gazing-faces-are-task-dependent
#4
Nicolas Burra, David Framorando, Alan J Pegna
Gender categorisation of human faces is facilitated when gaze is directed toward the observer (i.e., a direct gaze), compared with situations where gaze is averted or the eyes are closed (Macrae, Hood, Milne, Rowe, & Mason, Psychological Science, 13(5), 460-464, 2002). However, the temporal dynamics underlying this phenomenon remain to some extent unknown. Here, we used electroencephalography (EEG) to assess the neural correlates of this effect, focusing on the event-related potential (ERP) components known to be sensitive to gaze perception (i...
May 7, 2018: Cognitive, Affective & Behavioral Neuroscience
https://www.readbyqxmd.com/read/29723163/a-fibrin-biofilm-covers-the-blood-clot-and-protects-from-microbial-invasion
#5
Fraser L Macrae, Cédric Duval, Praveen Papareddy, Stephen R Baker, Nadira Yuldasheva, Katherine J Kearney, Helen R McPherson, Nathan Asquith, Joke Konings, Alessandro Casini, Jay L Degen, Simon D Connell, Helen Philippou, Alisa S Wolberg, Heiko Herwald, Robert As Ariëns
Haemostasis requires conversion of fibrinogen to fibrin fibres that generate a characteristic network, interact with blood cells, and initiate tissue repair. The fibrin network is porous and highly permeable, but the spatial arrangement of the external clot face is unknown. Here we show that fibrin transitioned to the blood-air interface through Langmuir film formation, producing a protective film confining the clot. We demonstrated that only fibrin is required to form the film, and that it occurred in vitro and in vivo...
May 3, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29712883/small-vessels-dementia-and-chronic-diseases-molecular-mechanisms-and-pathophysiology
#6
REVIEW
Karen Horsburgh, Joanna M Wardlaw, Tom van Agtmael, Stuart M Allan, Mike L J Ashford, Philip M Bath, Rosalind Brown, Jason Berwick, M Zameel Cader, Roxana O Carare, John B Davis, Jessica Duncombe, Tracy D Farr, Jill H Fowler, Jozien Goense, Alessandra Granata, Catherine N Hall, Atticus H Hainsworth, Adam Harvey, Cheryl A Hawkes, Anne Joutel, Rajesh N Kalaria, Patrick G Kehoe, Catherine B Lawrence, Andy Lockhart, Seth Love, Malcolm R Macleod, I Mhairi Macrae, Hugh S Markus, Chris McCabe, Barry W McColl, Paul J Meakin, Alyson Miller, Maiken Nedergaard, Michael O'Sullivan, Terry J Quinn, Rikesh Rajani, Lisa M Saksida, Colin Smith, Kenneth J Smith, Rhian M Touyz, Rebecca C Trueman, Tao Wang, Anna Williams, Steven C R Williams, Lorraine M Work
Cerebral small vessel disease (SVD) is a major contributor to stroke, cognitive impairment and dementia with limited therapeutic interventions. There is a critical need to provide mechanistic insight and improve translation between pre-clinical research and the clinic. A 2-day workshop was held which brought together experts from several disciplines in cerebrovascular disease, dementia and cardiovascular biology, to highlight current advances in these fields, explore synergies and scope for development. These proceedings provide a summary of key talks at the workshop with a particular focus on animal models of cerebral vascular disease and dementia, mechanisms and approaches to improve translation...
April 30, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29712723/modification-by-isolevuglandins-highly-reactive-%C3%AE-ketoaldehydes-deleteriously-alters-hdl-structure-and-function
#7
Linda S May-Zhang, Valery Yermalitsky, Jiansheng Huang, Tiffany Pleasent, Mark S Borja, Michael N Oda, W Gray Jerome, Patricia G Yancey, MacRae F Linton, Sean S Davies
Cardiovascular disease (CVD) risk depends on HDL function, not HDL-cholesterol (HDL-C). Isolevuglandins (IsoLGs) are lipid dicarbonyls that react with lysine residues of proteins and phosphatidylethanolamine. IsoLG adducts are elevated in atherosclerosis. The consequences of IsoLG modification of HDL have not been studied. We hypothesized that IsoLG modification of apoA-I deleteriously alters HDL function. We determined the effect of IsoLG on HDL structure-function, and whether pentylpyridoxamine (PPM), a dicarbonyl scavenger, can preserve HDL function...
April 30, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29702294/worldwide-practice-patterns-in-lynch-syndrome-diagnosis-and-management-based-on-data-from-the-international-mismatch-repair-consortium
#8
Jennifer Y Pan, Robert W Haile, Allyson Templeton, Finlay Macrae, FeiFei Qin, Vandana Sundaram, Uri Ladabaum
BACKGROUND AND AIMS: Families with a history of Lynch syndrome often do not adhere to guidelines for genetic testing and screening. We investigated practice patterns related to Lynch syndrome worldwide, to ascertain potential targets for research and public policy efforts METHODS: We collected data from the International Mismatch Repair Consortium [IMRC], which comprises major research and clinical groups engaged in the care of families with Lynch syndrome worldwide. IMRC institutions were invited to complete a questionnaire to characterize diagnoses of Lynch syndrome and management practice patterns...
April 24, 2018: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29700065/a-new-approach-to-an-old-problem-one-brave-idea
#9
James Cranley, Calum A MacRae
No abstract text is available yet for this article.
April 27, 2018: Circulation Research
https://www.readbyqxmd.com/read/29697522/living-with-dementia-in-correctional-settings-a-case-report
#10
Shelley Peacock, Alexandra Hodson, Rhoda MacRae, Cindy Peternelj-Taylor
The prison population is aging at an alarming rate and many older persons have the potential to develop dementia while in prison. This case report aims to explore the needs of older people living with dementia in prison and discusses the interventions that exist to address these needs. As the condition progresses, persons with dementia become increasingly reliant on the support of others for their health and well-being because of the increasing complexity of physical healthcare and psychosocial needs. Very few interventions are cited in the research literature regarding the use, acceptability, and/or effectiveness of programming for people living with dementia in prison...
April 24, 2018: Journal of Forensic Nursing
https://www.readbyqxmd.com/read/29696980/enantioselective-synthesis-of-thailanstatin-a-methyl-ester-and-evaluation-of-in-vitro-splicing-inhibition
#11
Arun K Ghosh, Anne M Veitschegger, Shenyou Nie, Nicola Relitti, Andrew J MacRae, Melissa S Jurica
Thailanstatin A has been isolated recently from the fermentation broth of B. thailandensis MSMB43. We describe here an enantioselective convergent synthesis of thailanstatin A methyl ester and evaluation of its splicing activity. Synthesis of both highly functionalized tetrahydropyran rings were carried out from commercially available tri- O-acetyl-d-glucal as the key starting material. Our convergent synthesis involved the synthesis of both tetrahydropyran fragments in a highly stereoselective manner. The fragments were then coupled using cross-metathesis as the key step...
April 26, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29685887/cardiopulmonary-resuscitation-in-infants-and-children-with-cardiac-disease-a-scientific-statement-from-the-american-heart-association
#12
REVIEW
Bradley S Marino, Sarah Tabbutt, Graeme MacLaren, Mary Fran Hazinski, Ian Adatia, Dianne L Atkins, Paul A Checchia, Allan DeCaen, Ericka L Fink, George M Hoffman, John L Jefferies, Monica Kleinman, Catherine D Krawczeski, Daniel J Licht, Duncan Macrae, Chitra Ravishankar, Ricardo A Samson, Ravi R Thiagarajan, Rune Toms, James Tweddell, Peter C Laussen
Cardiac arrest occurs at a higher rate in children with heart disease than in healthy children. Pediatric basic life support and advanced life support guidelines focus on delivering high-quality resuscitation in children with normal hearts. The complexity and variability in pediatric heart disease pose unique challenges during resuscitation. A writing group appointed by the American Heart Association reviewed the literature addressing resuscitation in children with heart disease. MEDLINE and Google Scholar databases were searched from 1966 to 2015, cross-referencing pediatric heart disease with pertinent resuscitation search terms...
April 23, 2018: Circulation
https://www.readbyqxmd.com/read/29662311/the-95-rgd-97-sequence-on-the-a%C3%AE-chain-of-fibrinogen-is-essential-for-binding-to-its-erythrocyte-receptor
#13
Filomena A Carvalho, Ana Filipa Guedes, Cedric Duval, Fraser L Macrae, Luke Swithenbank, David H Farrell, Robert As Ariëns, Nuno C Santos
Background: Erythrocyte aggregation, a cardiovascular risk factor, is increased by high plasma fibrinogen levels. Here, the effect of different fibrinogen mutations on binding to its human erythrocyte receptor was assessed in order to identify the interaction sites. Methods: Three fibrinogen variants were tested, specifically mutated in their putative integrin recognition sites on the Aα chain (mutants D97E, D574E and D97E/D574E) and compared with wild-type fibrinogen...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29653304/a-review-of-the-pharmaceutical-exposome-in-aquatic-fauna
#14
REVIEW
Thomas H Miller, Nicolas R Bury, Stewart F Owen, James I MacRae, Leon P Barron
Pharmaceuticals have been considered 'contaminants of emerging concern' for more than 20 years. In that time, many laboratory studies have sought to identify hazard and assess risk in the aquatic environment, whilst field studies have searched for targeted candidates and occurrence trends using advanced analytical techniques. However, a lack of a systematic approach to the detection and quantification of pharmaceuticals has provided a fragmented literature of serendipitous approaches. Evaluation of the extent of the risk for the plethora of human and veterinary pharmaceuticals available requires the reliable measurement of trace levels of contaminants across different environmental compartments (water, sediment, biota - of which biota has been largely neglected)...
April 10, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29610263/cardiac-dysfunction-and-metabolic-inflexibility-in-a-mouse-model-of-diabetes-without-dyslipidaemia
#15
Maria Rohm, Dragana Savic, Vicky Ball, M Kate Curtis, Sarah Bonham, Roman Fischer, Nathalie Legrave, James I MacRae, Damian J Tyler, Frances M Ashcroft
Diabetes is a well-established risk factor for heart disease leading to impaired cardiac function and a metabolic switch towards fatty acid usage. Here, we investigated if hyperglycaemia/hypoinsulinaemia in the absence of dyslipidaemia is sufficient to drive these changes, and if they can be reversed by restoring euglycaemia. Using the βV59M mouse model, in which diabetes can be rapidly induced and reversed, we show that stroke volume and cardiac output were reduced within two weeks of diabetes induction. Flux through pyruvate dehydrogenase was decreased, as measured in vivo by hyperpolarized [1-13 C]pyruvate magnetic resonance spectroscopy...
April 2, 2018: Diabetes
https://www.readbyqxmd.com/read/29594215/age-not-charlson-co-morbidity-index-predicts-for-mortality-after-stereotactic-ablative-radiotherapy-for-medically-inoperable-stage-i-non-small-cell-lung-cancer
#16
Oliver Edwin Holmes, Robert MacRae, Graham Cook, Peter Cross, Vimoj Nair, Horia Marginean, Jason R Pantarotto
Purpose: In this single institution retrospective study of patients with stage I medically inoperable non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR) we attempt to model overall survival (OS) using initial prognostic variables with specific attention on the Charlson co-morbidity index (CCI). Methods: Between 2008 and 2013, 335 patients with medically inoperable stage I NSCLC were treated with SABR or hypofractionated radiotherapy (50-60 Gy in at least 5 Gy or 4 Gy fractions respectively) at our institution...
August 2017: Clinical and Translational Radiation Oncology
https://www.readbyqxmd.com/read/29576456/phase-transitions-in-the-assembly-and-function-of-human-mirisc
#17
Jessica Sheu-Gruttadauria, Ian J MacRae
miRISC is a multi-protein assembly that uses microRNAs (miRNAs) to identify mRNAs targeted for repression. Dozens of miRISC-associated proteins have been identified, and interactions between many factors have been examined in detail. However, the physical nature of the complex remains unknown. Here, we show that two core protein components of human miRISC, Argonaute2 (Ago2) and TNRC6B, condense into phase-separated droplets in vitro and in live cells. Phase separation is promoted by multivalent interactions between the glycine/tryptophan (GW)-rich domain of TNRC6B and three evenly spaced tryptophan-binding pockets in the Ago2 PIWI domain...
March 16, 2018: Cell
https://www.readbyqxmd.com/read/29571116/the-critically-ill-patient-with-tuberculosis-in-intensive-care-clinical-presentations-management-and-infection-control
#18
REVIEW
Akaninyene Otu, Madiha Hashmi, Ahmed M Mukhtar, Arthur Kwizera, Simon Tiberi, Bruce Macrae, Alimudin Zumla, Martin W Dünser, Mervyn Mer
Tuberculosis (TB) is one of the top ten causes of death worldwide. In 2016, there were 490,000 cases of multi-drug resistant TB globally. Over 2 billion people have asymptomatic latent Mycobacterium tuberculosis infection. TB represents an important, but neglected management issue in patients presenting to intensive care units. Tuberculosis in intensive care settings may present as the primary diagnosis (active drug sensitive or resistant TB disease). In other patients TB may be an incidental co-morbid finding as previously undiagnosed sub-clinical or latent TB which may re-activate under conditions of stress and immunosuppression...
June 2018: Journal of Critical Care
https://www.readbyqxmd.com/read/29556351/perfluorocarbon-enhanced-glasgow-oxygen-level-dependent-gold-magnetic-resonance-metabolic-imaging-identifies-the-penumbra-following-acute-ischemic-stroke
#19
Graeme A Deuchar, David Brennan, William M Holmes, Martin Shaw, I Mhairi Macrae, Celestine Santosh
The ability to identify metabolically active and potentially salvageable ischaemic penumbra is crucial for improving treatment decisions in acute stroke patients. Our solution involves two complementary novel MRI techniques (Glasgow Oxygen Level Dependant (GOLD) Metabolic Imaging), which when combined with a perfluorocarbon (PFC) based oxygen carrier and hyperoxia can identify penumbra due to dynamic changes related to continued metabolism within this tissue compartment. Our aims were (i) to investigate whether PFC offers similar enhancement of the second technique (Lactate Change) as previously demonstrated for the T2 *OC technique (ii) to demonstrate both GOLD metabolic imaging techniques working concurrently to identify penumbra, following administration of Oxycyte® (O-PFC) with hyperoxia...
2018: Theranostics
https://www.readbyqxmd.com/read/29550835/transcriptomic-landscape-of-acute-promyelocytic-leukemia-reveals-aberrant-surface-expression-of-the-platelet-aggregation-agonist-podoplanin
#20
Vincent-Philippe Lavallée, Jalila Chagraoui, Tara MacRae, Miriam Marquis, Arnaud Bonnefoy, Jana Krosl, Sébastien Lemieux, Anne Marinier, Caroline Pabst, Georges-Étienne Rivard, Josée Hébert, Guy Sauvageau
Acute promyelocytic leukemia (APL) is a medical emergency because of associated lethal early bleeding, a condition preventable by prompt diagnosis and therapeutic intervention. The mechanisms underlying the hemostatic anomalies of APL are not completely elucidated. RNA-sequencing-based characterization of APL (n = 30) was performed and compared to that of other acute myeloid leukemia (n = 400) samples and normal promyelocytes. Perturbations in the transcriptome of coagulation and fibrinolysis-related genes in APL extend beyond known culprits and now include Thrombin, Factor X and Urokinase Receptor...
February 23, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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