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C. Ronald Kahn

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https://www.readbyqxmd.com/read/27801676/complementary-roles-of-irs-1-and-irs-2-in-the-hepatic-regulation-of-metabolism
#1
Cullen M Taniguchi, Kohjiro Ueki, C Ronald Kahn
No abstract text is available yet for this article.
November 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27775551/antibiotic-effects-on-gut-microbiota-and-metabolism-are-host-dependent
#2
Shiho Fujisaka, Siegfried Ussar, Clary Clish, Suzanne Devkota, Jonathan M Dreyfuss, Masaji Sakaguchi, Marion Soto, Masahiro Konishi, Samir Softic, Emrah Altindis, Ning Li, Georg Gerber, Lynn Bry, C Ronald Kahn
Interactions of diet, gut microbiota, and host genetics play important roles in the development of obesity and insulin resistance. Here, we have investigated the molecular links between gut microbiota, insulin resistance, and glucose metabolism in 3 inbred mouse strains with differing susceptibilities to metabolic syndrome using diet and antibiotic treatment. Antibiotic treatment altered intestinal microbiota, decreased tissue inflammation, improved insulin signaling in basal and stimulated states, and improved glucose metabolism in obesity- and diabetes-prone C57BL/6J mice on a high-fat diet (HFD)...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27742877/differential-roles-of-the-insulin-and-insulin-like-growth-factor-i-igf-i-receptors-in-response-to-insulin-and-igf-i
#3
Amelia Entingh-Pearsall, C Ronald Kahn
No abstract text is available yet for this article.
October 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27694991/novel-genetic-loci-underlying-human-intracranial-volume-identified-through-genome-wide-association
#4
Hieab H H Adams, Derrek P Hibar, Vincent Chouraki, Jason L Stein, Paul A Nyquist, Miguel E Rentería, Stella Trompet, Alejandro Arias-Vasquez, Sudha Seshadri, Sylvane Desrivières, Ashley H Beecham, Neda Jahanshad, Katharina Wittfeld, Sven J Van der Lee, Lucija Abramovic, Saud Alhusaini, Najaf Amin, Micael Andersson, Konstantinos Arfanakis, Benjamin S Aribisala, Nicola J Armstrong, Lavinia Athanasiu, Tomas Axelsson, Alexa Beiser, Manon Bernard, Joshua C Bis, Laura M E Blanken, Susan H Blanton, Marc M Bohlken, Marco P Boks, Janita Bralten, Adam M Brickman, Owen Carmichael, M Mallar Chakravarty, Ganesh Chauhan, Qiang Chen, Christopher R K Ching, Gabriel Cuellar-Partida, Anouk Den Braber, Nhat Trung Doan, Stefan Ehrlich, Irina Filippi, Tian Ge, Sudheer Giddaluru, Aaron L Goldman, Rebecca F Gottesman, Corina U Greven, Oliver Grimm, Michael E Griswold, Tulio Guadalupe, Johanna Hass, Unn K Haukvik, Saima Hilal, Edith Hofer, David Hoehn, Avram J Holmes, Martine Hoogman, Deborah Janowitz, Tianye Jia, Dalia Kasperaviciute, Sungeun Kim, Marieke Klein, Bernd Kraemer, Phil H Lee, Jiemin Liao, David C M Liewald, Lorna M Lopez, Michelle Luciano, Christine Macare, Andre Marquand, Mar Matarin, Karen A Mather, Manuel Mattheisen, Bernard Mazoyer, David R McKay, Rebekah McWhirter, Yuri Milaneschi, Nazanin Mirza-Schreiber, Ryan L Muetzel, Susana Muñoz Maniega, Kwangsik Nho, Allison C Nugent, Loes M Olde Loohuis, Jaap Oosterlaan, Martina Papmeyer, Irene Pappa, Lukas Pirpamer, Sara Pudas, Benno Pütz, Kumar B Rajan, Adaikalavan Ramasamy, Jennifer S Richards, Shannon L Risacher, Roberto Roiz-Santiañez, Nanda Rommelse, Emma J Rose, Natalie A Royle, Tatjana Rundek, Philipp G Sämann, Claudia L Satizabal, Lianne Schmaal, Andrew J Schork, Li Shen, Jean Shin, Elena Shumskaya, Albert V Smith, Emma Sprooten, Lachlan T Strike, Alexander Teumer, Russell Thomson, Diana Tordesillas-Gutierrez, Roberto Toro, Daniah Trabzuni, Dhananjay Vaidya, Jeroen Van der Grond, Dennis Van der Meer, Marjolein M J Van Donkelaar, Kristel R Van Eijk, Theo G M Van Erp, Daan Van Rooij, Esther Walton, Lars T Westlye, Christopher D Whelan, Beverly G Windham, Anderson M Winkler, Girma Woldehawariat, Christiane Wolf, Thomas Wolfers, Bing Xu, Lisa R Yanek, Jingyun Yang, Alex Zijdenbos, Marcel P Zwiers, Ingrid Agartz, Neelum T Aggarwal, Laura Almasy, David Ames, Philippe Amouyel, Ole A Andreassen, Sampath Arepalli, Amelia A Assareh, Sandra Barral, Mark E Bastin, Diane M Becker, James T Becker, David A Bennett, John Blangero, Hans van Bokhoven, Dorret I Boomsma, Henry Brodaty, Rachel M Brouwer, Han G Brunner, Randy L Buckner, Jan K Buitelaar, Kazima B Bulayeva, Wiepke Cahn, Vince D Calhoun, Dara M Cannon, Gianpiero L Cavalleri, Christopher Chen, Ching-Yu Cheng, Sven Cichon, Mark R Cookson, Aiden Corvin, Benedicto Crespo-Facorro, Joanne E Curran, Michael Czisch, Anders M Dale, Gareth E Davies, Eco J C De Geus, Philip L De Jager, Greig I de Zubicaray, Norman Delanty, Chantal Depondt, Anita L DeStefano, Allissa Dillman, Srdjan Djurovic, Gary Donohoe, Wayne C Drevets, Ravi Duggirala, Thomas D Dyer, Susanne Erk, Thomas Espeseth, Denis A Evans, Iryna O Fedko, Guillén Fernández, Luigi Ferrucci, Simon E Fisher, Debra A Fleischman, Ian Ford, Tatiana M Foroud, Peter T Fox, Clyde Francks, Masaki Fukunaga, J Raphael Gibbs, David C Glahn, Randy L Gollub, Harald H H Göring, Hans J Grabe, Robert C Green, Oliver Gruber, Vilmundur Gudnason, Sebastian Guelfi, Narelle K Hansell, John Hardy, Catharina A Hartman, Ryota Hashimoto, Katrin Hegenscheid, Andreas Heinz, Stephanie Le Hellard, Dena G Hernandez, Dirk J Heslenfeld, Beng-Choon Ho, Pieter J Hoekstra, Wolfgang Hoffmann, Albert Hofman, Florian Holsboer, Georg Homuth, Norbert Hosten, Jouke-Jan Hottenga, Hilleke E Hulshoff Pol, Masashi Ikeda, M Kamran Ikram, Clifford R Jack, Mark Jenkinson, Robert Johnson, Erik G Jönsson, J Wouter Jukema, René S Kahn, Ryota Kanai, Iwona Kloszewska, David S Knopman, Peter Kochunov, John B Kwok, Stephen M Lawrie, Hervé Lemaître, Xinmin Liu, Dan L Longo, W T Longstreth, Oscar L Lopez, Simon Lovestone, Oliver Martinez, Jean-Luc Martinot, Venkata S Mattay, Colm McDonald, Andrew M McIntosh, Katie L McMahon, Francis J McMahon, Patrizia Mecocci, Ingrid Melle, Andreas Meyer-Lindenberg, Sebastian Mohnke, Grant W Montgomery, Derek W Morris, Thomas H Mosley, Thomas W Mühleisen, Bertram Müller-Myhsok, Michael A Nalls, Matthias Nauck, Thomas E Nichols, Wiro J Niessen, Markus M Nöthen, Lars Nyberg, Kazutaka Ohi, Rene L Olvera, Roel A Ophoff, Massimo Pandolfo, Tomas Paus, Zdenka Pausova, Brenda W J H Penninx, G Bruce Pike, Steven G Potkin, Bruce M Psaty, Simone Reppermund, Marcella Rietschel, Joshua L Roffman, Nina Romanczuk-Seiferth, Jerome I Rotter, Mina Ryten, Ralph L Sacco, Perminder S Sachdev, Andrew J Saykin, Reinhold Schmidt, Peter R Schofield, Sigurdur Sigurdsson, Andy Simmons, Andrew Singleton, Sanjay M Sisodiya, Colin Smith, Jordan W Smoller, Hilkka Soininen, Velandai Srikanth, Vidar M Steen, David J Stott, Jessika E Sussmann, Anbupalam Thalamuthu, Henning Tiemeier, Arthur W Toga, Bryan J Traynor, Juan Troncoso, Jessica A Turner, Christophe Tzourio, Andre G Uitterlinden, Maria C Valdés Hernández, Marcel Van der Brug, Aad Van der Lugt, Nic J A Van der Wee, Cornelia M Van Duijn, Neeltje E M Van Haren, Dennis Van T Ent, Marie-Jose Van Tol, Badri N Vardarajan, Dick J Veltman, Meike W Vernooij, Henry Völzke, Henrik Walter, Joanna M Wardlaw, Thomas H Wassink, Michael E Weale, Daniel R Weinberger, Michael W Weiner, Wei Wen, Eric Westman, Tonya White, Tien Y Wong, Clinton B Wright, H Ronald Zielke, Alan B Zonderman, Ian J Deary, Charles DeCarli, Helena Schmidt, Nicholas G Martin, Anton J M De Craen, Margaret J Wright, Lenore J Launer, Gunter Schumann, Myriam Fornage, Barbara Franke, Stéphanie Debette, Sarah E Medland, M Arfan Ikram, Paul M Thompson
Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height...
December 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/27617202/interactions-between-host-genetics-and-gut-microbiome-in-diabetes-and-metabolic-syndrome
#5
REVIEW
Siegfried Ussar, Shiho Fujisaka, C Ronald Kahn
BACKGROUND: Diabetes, obesity, and the metabolic syndrome are multifactorial diseases dependent on a complex interaction of host genetics, diet, and other environmental factors. Increasing evidence places gut microbiota as important modulators of the crosstalk between diet and development of obesity and metabolic dysfunction. In addition, host genetics can have important impact on the composition and function of gut microbiota. Indeed, depending on the genetic background of the host, diet and other environmental factors may produce different changes in gut microbiota, have different impacts on host metabolism, and create different interactions between the microbiome and the host...
September 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27602389/in-vivo-r-11-c-pk11195-pet-imaging-of-18kda-translocator-protein-in-recent-onset-psychosis
#6
Thalia F van der Doef, Lot D de Witte, Arjen L Sutterland, Ellen Jobse, Maqsood Yaqub, Ronald Boellaard, Lieuwe de Haan, Jonas Eriksson, Adriaan A Lammertsma, René S Kahn, Bart N M van Berckel
Evidence is accumulating that immune dysfunction is involved in the pathophysiology of schizophrenia. It has been hypothesized that microglia activation is present in patients with schizophrenia. Various in vivo and post-mortem studies have investigated this hypothesis, but as yet with inconclusive results. Microglia activation is associated with elevations in 18 kDa translocator protein (TSPO) levels, which can be measured with the positron emission tomography (PET) tracer (R)-[(11)C]PK11195. The purpose of the present study was to investigate microglia activation in psychosis in vivo at an early stage of the disease...
2016: NPJ Schizophrenia
https://www.readbyqxmd.com/read/27525440/insulin-and-igf-1-receptors-regulate-foxo-mediated-signaling-in-muscle-proteostasis
#7
Brian T O'Neill, Kevin Y Lee, Katherine Klaus, Samir Softic, Megan T Krumpoch, Joachim Fentz, Kristin I Stanford, Matthew M Robinson, Weikang Cai, Andre Kleinridders, Renata O Pereira, Michael F Hirshman, E Dale Abel, Domenico Accili, Laurie J Goodyear, K Sreekumaran Nair, C Ronald Kahn
Diabetes strongly impacts protein metabolism, particularly in skeletal muscle. Insulin and IGF-1 enhance muscle protein synthesis through their receptors, but the relative roles of each in muscle proteostasis have not been fully elucidated. Using mice with muscle-specific deletion of the insulin receptor (M-IR-/- mice), the IGF-1 receptor (M-IGF1R-/- mice), or both (MIGIRKO mice), we assessed the relative contributions of IR and IGF1R signaling to muscle proteostasis. In differentiated muscle, IR expression predominated over IGF1R expression, and correspondingly, M-IR-/- mice displayed a moderate reduction in muscle mass whereas M-IGF1R-/- mice did not...
September 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27518562/astrocytic-insulin-signaling-couples-brain-glucose-uptake-with-nutrient-availability
#8
Cristina García-Cáceres, Carmelo Quarta, Luis Varela, Yuanqing Gao, Tim Gruber, Beata Legutko, Martin Jastroch, Pia Johansson, Jovica Ninkovic, Chun-Xia Yi, Ophelia Le Thuc, Klara Szigeti-Buck, Weikang Cai, Carola W Meyer, Paul T Pfluger, Ana M Fernandez, Serge Luquet, Stephen C Woods, Ignacio Torres-Alemán, C Ronald Kahn, Magdalena Götz, Tamas L Horvath, Matthias H Tschöp
We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and circuit connectivity. Accordingly, astrocytic IR ablation reduces glucose-induced activation of hypothalamic pro-opio-melanocortin (POMC) neurons and impairs physiological responses to changes in glucose availability...
August 11, 2016: Cell
https://www.readbyqxmd.com/read/27496960/cross-talk-between-insulin-and-wnt-signaling-in-preadipocytes-role-of-wnt-co-receptor-ldl-receptor-related-protein-5-lrp5
#9
Jane Palsgaard, Brice Emanuelli, Jonathon N Winnay, Grzegorz Sumara, Gerard Karsenty, C Ronald Kahn
No abstract text is available yet for this article.
August 5, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27451432/effect-of-cholesterol-reduction-on-receptor-signaling-in-neurons
#10
Kenji Fukui, Heather A Ferris, C Ronald Kahn
No abstract text is available yet for this article.
July 22, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27303627/-white-paper-meeting-summary-and-catalyst-for-future-inquiry-%C3%A2-complex-mechanisms-linking-neurocognitive-dysfunction%C3%A2-to-insulin-resistance-and-other-metabolic-dysfunction
#11
REVIEW
Luke E Stoeckel, Zoe Arvanitakis, Sam Gandy, Dana Small, C Ronald Kahn, Alvaro Pascual-Leone, Aaron Pawlyk, Robert Sherwin, Philip Smith
Scientific evidence has established several links between metabolic and neurocognitive dysfunction, and epidemiologic evidence has revealed an increased risk of Alzheimer's disease and vascular dementia in patients with diabetes. In July 2015, the National Institute of Diabetes, Digestive, and Kidney Diseases gathered experts from multiple clinical and scientific disciplines, in a workshop entitled "The Intersection of Metabolic and Neurocognitive Dysfunction", to clarify the state-of-the-science on the mechanisms linking metabolic dysfunction, and insulin resistance and diabetes in particular, to neurocognitive impairment and dementia...
2016: F1000Research
https://www.readbyqxmd.com/read/27241713/fat-specific-dicer-deficiency-accelerates-aging-and-mitigates-several-effects-of-dietary-restriction-in-mice
#12
Felipe C G Reis, Jéssica L O Branquinho, Bruna B Brandão, Beatriz A Guerra, Ismael D Silva, Andrea Frontini, Thomas Thomou, Loris Sartini, Saverio Cinti, C Ronald Kahn, William T Festuccia, Alicia J Kowaltowski, Marcelo A Mori
Aging increases the risk of type 2 diabetes, and this can be prevented by dietary restriction (DR). We have previously shown that DR inhibits the downregulation of miRNAs and their processing enzymes - mainly Dicer - that occurs with aging in mouse white adipose tissue (WAT). Here we used fat-specific Dicer knockout mice (AdicerKO) to understand the contributions of adipose tissue Dicer to the metabolic effects of aging and DR. Metabolomic data uncovered a clear distinction between the serum metabolite profiles of Lox control and AdicerKO mice, with a notable elevation of branched-chain amino acids (BCAA) in AdicerKO...
June 2016: Aging
https://www.readbyqxmd.com/read/27222392/unraveling-the-paradox-of-selective-insulin-resistance-in-the-liver-the-brain-liver-connection
#13
Heather A Ferris, C Ronald Kahn
No abstract text is available yet for this article.
June 2016: Diabetes
https://www.readbyqxmd.com/read/27207537/differential-roles-of-insulin-and-igf-1-receptors-in-adipose-tissue-development-and-function
#14
Jeremie Boucher, Samir Softic, Abdelfattah El Ouaamari, Megan T Krumpoch, Andre Kleinridders, Rohit N Kulkarni, Brian T O'Neill, C Ronald Kahn
To determine the roles of insulin and insulin-like growth factor 1 (IGF-1) action in adipose tissue, we created mice lacking the insulin receptor (IR), IGF-1 receptor (IGF1R), or both using Cre-recombinase driven by the adiponectin promoter. Mice lacking IGF1R only (F-IGFRKO) had a ∼25% reduction in white adipose tissue (WAT) and brown adipose tissue (BAT), whereas mice lacking both IR and IGF1R (F-IR/IGFRKO) showed an almost complete absence of WAT and BAT. Interestingly, mice lacking only the IR (F-IRKO) had a 95% reduction in WAT, but a paradoxical 50% increase in BAT with accumulation of large unilocular lipid droplets...
August 2016: Diabetes
https://www.readbyqxmd.com/read/27207510/lipodystrophy-due-to-adipose-tissue-specific-insulin-receptor-knockout-results-in-progressive-nafld
#15
Samir Softic, Jeremie Boucher, Marie H Solheim, Shiho Fujisaka, Max-Felix Haering, Erica P Homan, Jonathon Winnay, Antonio R Perez-Atayde, C Ronald Kahn
Ectopic lipid accumulation in the liver is an almost universal feature of human and rodent models of generalized lipodystrophy and is also a common feature of type 2 diabetes, obesity, and metabolic syndrome. Here we explore the progression of fatty liver disease using a mouse model of lipodystrophy created by a fat-specific knockout of the insulin receptor (F-IRKO) or both IR and insulin-like growth factor 1 receptor (F-IR/IGFRKO). These mice develop severe lipodystrophy, diabetes, hyperlipidemia, and fatty liver disease within the first weeks of life...
August 2016: Diabetes
https://www.readbyqxmd.com/read/26974159/pi3-kinase-mutation-linked-to-insulin-and-growth-factor-resistance-in-vivo
#16
Jonathon N Winnay, Marie H Solheim, Ercument Dirice, Masaji Sakaguchi, Hye-Lim Noh, Hee Joon Kang, Hirokazu Takahashi, Kishan K Chudasama, Jason K Kim, Anders Molven, C Ronald Kahn, Pål R Njølstad
The phosphatidylinositol 3-kinase (PI3K) signaling pathway is central to the action of insulin and many growth factors. Heterozygous mutations in the gene encoding the p85α regulatory subunit of PI3K (PIK3R1) have been identified in patients with SHORT syndrome - a disorder characterized by short stature, partial lipodystrophy, and insulin resistance. Here, we evaluated whether SHORT syndrome-associated PIK3R1 mutations account for the pathophysiology that underlies the abnormalities by generating knockin mice that are heterozygous for the Pik3r1Arg649Trp mutation, which is homologous to the mutation found in the majority of affected individuals...
April 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/26948272/insulin-resistance-in-human-ips-cells-reduces-mitochondrial-size-and-function
#17
Alison M Burkart, Kelly Tan, Laura Warren, Salvatore Iovino, Katelyn J Hughes, C Ronald Kahn, Mary-Elizabeth Patti
Insulin resistance, a critical component of type 2 diabetes (T2D), precedes and predicts T2D onset. T2D is also associated with mitochondrial dysfunction. To define the cause-effect relationship between insulin resistance and mitochondrial dysfunction, we compared mitochondrial metabolism in induced pluripotent stem cells (iPSC) from 5 healthy individuals and 4 patients with genetic insulin resistance due to insulin receptor mutations. Insulin-resistant iPSC had increased mitochondrial number and decreased mitochondrial size...
2016: Scientific Reports
https://www.readbyqxmd.com/read/26856717/role-of-dietary-fructose-and-hepatic-de-novo-lipogenesis-in-fatty-liver-disease
#18
REVIEW
Samir Softic, David E Cohen, C Ronald Kahn
Nonalcoholic fatty liver disease (NAFLD) is a liver manifestation of metabolic syndrome. Overconsumption of high-fat diet (HFD) and increased intake of sugar-sweetened beverages are major risk factors for development of NAFLD. Today the most commonly consumed sugar is high fructose corn syrup. Hepatic lipids may be derived from dietary intake, esterification of plasma free fatty acids (FFA) or hepatic de novo lipogenesis (DNL). A central abnormality in NAFLD is enhanced DNL. Hepatic DNL is increased in individuals with NAFLD, while the contribution of dietary fat and plasma FFA to hepatic lipids is not significantly altered...
May 2016: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/26831110/myotubes-derived-from-human-induced-pluripotent-stem-cells-mirror-in-vivo-insulin-resistance
#19
Salvatore Iovino, Alison M Burkart, Laura Warren, Mary Elizabeth Patti, C Ronald Kahn
Induced pluripotent stem cells (iPS cells) represent a unique tool for the study of the pathophysiology of human disease, because these cells can be differentiated into multiple cell types in vitro and used to generate patient- and tissue-specific disease models. Given the critical role for skeletal muscle insulin resistance in whole-body glucose metabolism and type 2 diabetes, we have created a novel cellular model of human muscle insulin resistance by differentiating iPS cells from individuals with mutations in the insulin receptor (IR-Mut) into functional myotubes and characterizing their response to insulin in comparison with controls...
February 16, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26657864/cdk4-is-an-essential-insulin-effector-in-adipocytes
#20
Sylviane Lagarrigue, Isabel C Lopez-Mejia, Pierre-Damien Denechaud, Xavier Escoté, Judit Castillo-Armengol, Veronica Jimenez, Carine Chavey, Albert Giralt, Qiuwen Lai, Lianjun Zhang, Laia Martinez-Carreres, Brigitte Delacuisine, Jean-Sébastien Annicotte, Emilie Blanchet, Sébastien Huré, Anna Abella, Francisco J Tinahones, Joan Vendrell, Pierre Dubus, Fatima Bosch, C Ronald Kahn, Lluis Fajas
Insulin resistance is a fundamental pathogenic factor that characterizes various metabolic disorders, including obesity and type 2 diabetes. Adipose tissue contributes to the development of obesity-related insulin resistance through increased release of fatty acids, altered adipokine secretion, and/or macrophage infiltration and cytokine release. Here, we aimed to analyze the participation of the cyclin-dependent kinase 4 (CDK4) in adipose tissue biology. We determined that white adipose tissue (WAT) from CDK4-deficient mice exhibits impaired lipogenesis and increased lipolysis...
January 2016: Journal of Clinical Investigation
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