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2262: The impact of alcohol dysbiosis on host defense against pneumonia
- Derrick Richard Samuelson, Vincent Maffei, Eugene Blanchard, Meng Luo, Christopher Taylor, Judd Shellito, Martin Ronis, Patricia Molina, David Welsh
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- Journal:
- Journal of Clinical and Translational Science / Volume 1 / Issue S1 / September 2017
- Published online by Cambridge University Press:
- 10 May 2018, pp. 4-5
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OBJECTIVES/SPECIFIC AIMS: Alcohol consumption perturbs the normal intestinal microbial communities (alcohol dysbiosis). To begin to investigate the relationship between alcohol-mediated dysbiosis and host defense we developed an alcohol dysbiosis fecal adoptive transfer model, which allows us to isolate the host immune response to a pathogenic challenge at a distal organ (ie, the lung). This model system allowed us to determine whether the host immune responses to Klebsiella pneumoniae are altered by ethanol-associated dysbiosis, independent of alcohol use. We hypothesized that alcohol-induced changes in intestinal microbial communities would impair pulmonary host defenses against K. pneumoniae. METHODS/STUDY POPULATION: Mice were treated with a cocktail of antibiotics daily for 2 weeks. Microbiota-depleted mice were then recolonized by gavage for 3-days with intestinal microbiota from ethanol-fed or pair-fed animals. Following recolonization groups of mice were sacrificed prior to and 48 hours post respiratory infection with K. pneumoniae. We then assessed susceptibility to Klebsiella infection by determining colony counts for pathogen burden in the lungs. We also determined lung and intestinal immunology, intestinal permeability, as well as, liver damage and inflammation. RESULTS/ANTICIPATED RESULTS: We found that increased susceptibility to K. pneumoniae is, in part, mediated by the intestinal microbiota, as animals recolonized with an alcohol-induced dysbiotic intestinal microbial community have significantly higher lung burdens of K. pneumoniae (5×104 CFU vs. 1×103 CFU) independent of EtOH. We also found that increased susceptibility in alcohol-dysbiosis recolonized animals was associated with a decrease in the recruitment and/or proliferation of CD4+ and CD8+ T-cells (1.5×109 cells vs. 2.5×109 cells) in the lung following Klebsiella infection. However, there were increased numbers of T-cells in the intestinal tract following Klebsiella infection, which may suggest that T cells are being sequestered in the intestinal tract to the detriment of host defense in the lung. Interestingly, mice recolonized with an alcohol-dysbiotic microbiota had increased intestinal permeability as measured by increased levels of serum intestinal fatty acid binding protein (55 vs. 30 ng/mL). Alcohol-dysbiotic microbiota also increased liver steatosis (Oil Red-O staining) and liver inflammation (>2-fold expression of IL-17 and IL-23). DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings suggest that the commensal intestinal microbiota support mucosal host defenses against infectious agents by facilitating normal immune responses to pulmonary pathogens. Our data also suggest that increased intestinal permeability coupled with increased liver inflammation may impair the recruitment/proliferation of immune cells in the respiratory tract following infection. The role of the microbiota during host defense will be important areas of future research directed at understanding the effects of microbial dysbiosis in patients with AUDs.
Contributors
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- By James Ahn, Eric L. Anderson, Annette L. Beautrais, Dennis Beedle, Jon S. Berlin, Benjamin L. Bregman, Peter Brown, Suzie Bruch, Jonathan Busko, Stuart Buttlaire, Laurie Byrne, Gerald Carroll, Valerie A. Carroll, Margaret Cashman, Joseph R. Check, Lara G. Chepenik, Robert N. Cuyler, Preeti Dalawari, Suzanne Dooley-Hash, William R. Dubin, Mila L. Felder, Avrim B. Fishkind, Reginald I. Gaylord, Rachel Lipson Glick, Travis Grace, Clare Gray, Anita Hart, Ross A. Heller, Amanda E. Horn, David S. Howes, David C. Hsu, Andy Jagoda, Margaret Judd, John Kahler, Daryl Knox, Gregory Luke Larkin, Patricia Lee, Jerrold B. Leikin, Eddie Markul, Marc L. Martel, J. D. McCourt, MaryLynn McGuire Clarke, Mark Newman, Anthony T. Ng, Barbara Nightengale, Kimberly Nordstrom, Jagoda Pasic, Jennifer Peltzer-Jones, Marcia A. Perry, Larry Phillips, Paul Porter, Seth Powsner, Michael S. Pulia, Erin Rapp, Divy Ravindranath, Janet S. Richmond, Silvana Riggio, Harvey L. Ruben, Derek J. Robinson, Douglas A. Rund, Omeed Saghafi, Alicia N. Sanders, Jeffrey Sankoff, Lorin M. Scher, Louis Scrattish, Richard D. Shih, Maureen Slade, Susan Stefan, Victor G. Stiebel, Deborah Taber, Vaishal Tolia, Gary M. Vilke, Alvin Wang, Michael A. Ward, Joseph Weber, Michael P. Wilson, James L. Young, Scott L. Zeller
- Edited by Leslie S. Zun
- Edited in association with Lara G. Chepenik, Mary Nan S. Mallory
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- Book:
- Behavioral Emergencies for the Emergency Physician
- Published online:
- 05 April 2013
- Print publication:
- 21 March 2013, pp viii-xii
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- By Rose Teteki Abbey, K. C. Abraham, David Tuesday Adamo, LeRoy H. Aden, Efrain Agosto, Victor Aguilan, Gillian T. W. Ahlgren, Charanjit Kaur AjitSingh, Dorothy B E A Akoto, Giuseppe Alberigo, Daniel E. Albrecht, Ruth Albrecht, Daniel O. Aleshire, Urs Altermatt, Anand Amaladass, Michael Amaladoss, James N. Amanze, Lesley G. Anderson, Thomas C. Anderson, Victor Anderson, Hope S. Antone, María Pilar Aquino, Paula Arai, Victorio Araya Guillén, S. Wesley Ariarajah, Ellen T. Armour, Brett Gregory Armstrong, Atsuhiro Asano, Naim Stifan Ateek, Mahmoud Ayoub, John Alembillah Azumah, Mercedes L. García Bachmann, Irena Backus, J. Wayne Baker, Mieke Bal, Lewis V. Baldwin, William Barbieri, António Barbosa da Silva, David Basinger, Bolaji Olukemi Bateye, Oswald Bayer, Daniel H. Bays, Rosalie Beck, Nancy Elizabeth Bedford, Guy-Thomas Bedouelle, Chorbishop Seely Beggiani, Wolfgang Behringer, Christopher M. Bellitto, Byard Bennett, Harold V. Bennett, Teresa Berger, Miguel A. Bernad, Henley Bernard, Alan E. Bernstein, Jon L. Berquist, Johannes Beutler, Ana María Bidegain, Matthew P. Binkewicz, Jennifer Bird, Joseph Blenkinsopp, Dmytro Bondarenko, Paulo Bonfatti, Riet en Pim Bons-Storm, Jessica A. Boon, Marcus J. Borg, Mark Bosco, Peter C. Bouteneff, François Bovon, William D. Bowman, Paul S. Boyer, David Brakke, Richard E. Brantley, Marcus Braybrooke, Ian Breward, Ênio José da Costa Brito, Jewel Spears Brooker, Johannes Brosseder, Nicholas Canfield Read Brown, Robert F. Brown, Pamela K. Brubaker, Walter Brueggemann, Bishop Colin O. Buchanan, Stanley M. Burgess, Amy Nelson Burnett, J. Patout Burns, David B. Burrell, David Buttrick, James P. Byrd, Lavinia Byrne, Gerado Caetano, Marcos Caldas, Alkiviadis Calivas, William J. Callahan, Salvatore Calomino, Euan K. Cameron, William S. Campbell, Marcelo Ayres Camurça, Daniel F. Caner, Paul E. Capetz, Carlos F. Cardoza-Orlandi, Patrick W. Carey, Barbara Carvill, Hal Cauthron, Subhadra Mitra Channa, Mark D. Chapman, James H. Charlesworth, Kenneth R. Chase, Chen Zemin, Luciano Chianeque, Philip Chia Phin Yin, Francisca H. Chimhanda, Daniel Chiquete, John T. Chirban, Soobin Choi, Robert Choquette, Mita Choudhury, Gerald Christianson, John Chryssavgis, Sejong Chun, Esther Chung-Kim, Charles M. A. Clark, Elizabeth A. Clark, Sathianathan Clarke, Fred Cloud, John B. Cobb, W. Owen Cole, John A Coleman, John J. Collins, Sylvia Collins-Mayo, Paul K. Conkin, Beth A. Conklin, Sean Connolly, Demetrios J. Constantelos, Michael A. Conway, Paula M. Cooey, Austin Cooper, Michael L. Cooper-White, Pamela Cooper-White, L. William Countryman, Sérgio Coutinho, Pamela Couture, Shannon Craigo-Snell, James L. Crenshaw, David Crowner, Humberto Horacio Cucchetti, Lawrence S. Cunningham, Elizabeth Mason Currier, Emmanuel Cutrone, Mary L. Daniel, David D. Daniels, Robert Darden, Rolf Darge, Isaiah Dau, Jeffry C. Davis, Jane Dawson, Valentin Dedji, John W. de Gruchy, Paul DeHart, Wendy J. Deichmann Edwards, Miguel A. De La Torre, George E. Demacopoulos, Thomas de Mayo, Leah DeVun, Beatriz de Vasconcellos Dias, Dennis C. Dickerson, John M. Dillon, Luis Miguel Donatello, Igor Dorfmann-Lazarev, Susanna Drake, Jonathan A. Draper, N. Dreher Martin, Otto Dreydoppel, Angelyn Dries, A. J. Droge, Francis X. D'Sa, Marilyn Dunn, Nicole Wilkinson Duran, Rifaat Ebied, Mark J. Edwards, William H. Edwards, Leonard H. Ehrlich, Nancy L. Eiesland, Martin Elbel, J. Harold Ellens, Stephen Ellingson, Marvin M. Ellison, Robert Ellsberg, Jean Bethke Elshtain, Eldon Jay Epp, Peter C. Erb, Tassilo Erhardt, Maria Erling, Noel Leo Erskine, Gillian R. Evans, Virginia Fabella, Michael A. Fahey, Edward Farley, Margaret A. Farley, Wendy Farley, Robert Fastiggi, Seena Fazel, Duncan S. Ferguson, Helwar Figueroa, Paul Corby Finney, Kyriaki Karidoyanes FitzGerald, Thomas E. FitzGerald, John R. Fitzmier, Marie Therese Flanagan, Sabina Flanagan, Claude Flipo, Ronald B. Flowers, Carole Fontaine, David Ford, Mary Ford, Stephanie A. Ford, Jim Forest, William Franke, Robert M. Franklin, Ruth Franzén, Edward H. Friedman, Samuel Frouisou, Lorelei F. Fuchs, Jojo M. Fung, Inger Furseth, Richard R. Gaillardetz, Brandon Gallaher, China Galland, Mark Galli, Ismael García, Tharscisse Gatwa, Jean-Marie Gaudeul, Luis María Gavilanes del Castillo, Pavel L. Gavrilyuk, Volney P. Gay, Metropolitan Athanasios Geevargis, Kondothra M. George, Mary Gerhart, Simon Gikandi, Maurice Gilbert, Michael J. Gillgannon, Verónica Giménez Beliveau, Terryl Givens, Beth Glazier-McDonald, Philip Gleason, Menghun Goh, Brian Golding, Bishop Hilario M. Gomez, Michelle A. Gonzalez, Donald K. Gorrell, Roy Gottfried, Tamara Grdzelidze, Joel B. Green, Niels Henrik Gregersen, Cristina Grenholm, Herbert Griffiths, Eric W. Gritsch, Erich S. Gruen, Christoffer H. Grundmann, Paul H. Gundani, Jon P. Gunnemann, Petre Guran, Vidar L. Haanes, Jeremiah M. Hackett, Getatchew Haile, Douglas John Hall, Nicholas Hammond, Daphne Hampson, Jehu J. Hanciles, Barry Hankins, Jennifer Haraguchi, Stanley S. Harakas, Anthony John Harding, Conrad L. Harkins, J. William Harmless, Marjory Harper, Amir Harrak, Joel F. Harrington, Mark W. Harris, Susan Ashbrook Harvey, Van A. Harvey, R. Chris Hassel, Jione Havea, Daniel Hawk, Diana L. Hayes, Leslie Hayes, Priscilla Hayner, S. Mark Heim, Simo Heininen, Richard P. Heitzenrater, Eila Helander, David Hempton, Scott H. Hendrix, Jan-Olav Henriksen, Gina Hens-Piazza, Carter Heyward, Nicholas J. Higham, David Hilliard, Norman A. Hjelm, Peter C. Hodgson, Arthur Holder, M. Jan Holton, Dwight N. Hopkins, Ronnie Po-chia Hsia, Po-Ho Huang, James Hudnut-Beumler, Jennifer S. Hughes, Leonard M. Hummel, Mary E. Hunt, Laennec Hurbon, Mark Hutchinson, Susan E. Hylen, Mary Beth Ingham, H. Larry Ingle, Dale T. Irvin, Jon Isaak, Paul John Isaak, Ada María Isasi-Díaz, Hans Raun Iversen, Margaret C. Jacob, Arthur James, Maria Jansdotter-Samuelsson, David Jasper, Werner G. Jeanrond, Renée Jeffery, David Lyle Jeffrey, Theodore W. Jennings, David H. Jensen, Robin Margaret Jensen, David Jobling, Dale A. Johnson, Elizabeth A. Johnson, Maxwell E. Johnson, Sarah Johnson, Mark D. Johnston, F. Stanley Jones, James William Jones, John R. Jones, Alissa Jones Nelson, Inge Jonsson, Jan Joosten, Elizabeth Judd, Mulambya Peggy Kabonde, Robert Kaggwa, Sylvester Kahakwa, Isaac Kalimi, Ogbu U. Kalu, Eunice Kamaara, Wayne C. Kannaday, Musimbi Kanyoro, Veli-Matti Kärkkäinen, Frank Kaufmann, Léon Nguapitshi Kayongo, Richard Kearney, Alice A. Keefe, Ralph Keen, Catherine Keller, Anthony J. Kelly, Karen Kennelly, Kathi Lynn Kern, Fergus Kerr, Edward Kessler, George Kilcourse, Heup Young Kim, Kim Sung-Hae, Kim Yong-Bock, Kim Yung Suk, Richard King, Thomas M. King, Robert M. Kingdon, Ross Kinsler, Hans G. Kippenberg, Cheryl A. Kirk-Duggan, Clifton Kirkpatrick, Leonid Kishkovsky, Nadieszda Kizenko, Jeffrey Klaiber, Hans-Josef Klauck, Sidney Knight, Samuel Kobia, Robert Kolb, Karla Ann Koll, Heikki Kotila, Donald Kraybill, Philip D. W. Krey, Yves Krumenacker, Jeffrey Kah-Jin Kuan, Simanga R. Kumalo, Peter Kuzmic, Simon Shui-Man Kwan, Kwok Pui-lan, André LaCocque, Stephen E. Lahey, John Tsz Pang Lai, Emiel Lamberts, Armando Lampe, Craig Lampe, Beverly J. Lanzetta, Eve LaPlante, Lizette Larson-Miller, Ariel Bybee Laughton, Leonard Lawlor, Bentley Layton, Robin A. Leaver, Karen Lebacqz, Archie Chi Chung Lee, Marilyn J. Legge, Hervé LeGrand, D. L. LeMahieu, Raymond Lemieux, Bill J. Leonard, Ellen M. Leonard, Outi Leppä, Jean Lesaulnier, Nantawan Boonprasat Lewis, Henrietta Leyser, Alexei Lidov, Bernard Lightman, Paul Chang-Ha Lim, Carter Lindberg, Mark R. Lindsay, James R. Linville, James C. Livingston, Ann Loades, David Loades, Jean-Claude Loba-Mkole, Lo Lung Kwong, Wati Longchar, Eleazar López, David W. Lotz, Andrew Louth, Robin W. Lovin, William Luis, Frank D. Macchia, Diarmaid N. J. MacCulloch, Kirk R. MacGregor, Marjory A. MacLean, Donald MacLeod, Tomas S. Maddela, Inge Mager, Laurenti Magesa, David G. Maillu, Fortunato Mallimaci, Philip Mamalakis, Kä Mana, Ukachukwu Chris Manus, Herbert Robinson Marbury, Reuel Norman Marigza, Jacqueline Mariña, Antti Marjanen, Luiz C. L. Marques, Madipoane Masenya (ngwan'a Mphahlele), Caleb J. D. Maskell, Steve Mason, Thomas Massaro, Fernando Matamoros Ponce, András Máté-Tóth, Odair Pedroso Mateus, Dinis Matsolo, Fumitaka Matsuoka, John D'Arcy May, Yelena Mazour-Matusevich, Theodore Mbazumutima, John S. McClure, Christian McConnell, Lee Martin McDonald, Gary B. McGee, Thomas McGowan, Alister E. McGrath, Richard J. McGregor, John A. McGuckin, Maud Burnett McInerney, Elsie Anne McKee, Mary B. McKinley, James F. McMillan, Ernan McMullin, Kathleen E. McVey, M. Douglas Meeks, Monica Jyotsna Melanchthon, Ilie Melniciuc-Puica, Everett Mendoza, Raymond A. Mentzer, William W. Menzies, Ina Merdjanova, Franziska Metzger, Constant J. Mews, Marvin Meyer, Carol Meyers, Vasile Mihoc, Gunner Bjerg Mikkelsen, Maria Inêz de Castro Millen, Clyde Lee Miller, Bonnie J. Miller-McLemore, Alexander Mirkovic, Paul Misner, Nozomu Miyahira, R. W. L. Moberly, Gerald Moede, Aloo Osotsi Mojola, Sunanda Mongia, Rebeca Montemayor, James Moore, Roger E. Moore, Craig E. Morrison O.Carm, Jeffry H. Morrison, Keith Morrison, Wilson J. Moses, Tefetso Henry Mothibe, Mokgethi Motlhabi, Fulata Moyo, Henry Mugabe, Jesse Ndwiga Kanyua Mugambi, Peggy Mulambya-Kabonde, Robert Bruce Mullin, Pamela Mullins Reaves, Saskia Murk Jansen, Heleen L. Murre-Van den Berg, Augustine Musopole, Isaac M. T. Mwase, Philomena Mwaura, Cecilia Nahnfeldt, Anne Nasimiyu Wasike, Carmiña Navia Velasco, Thulani Ndlazi, Alexander Negrov, James B. Nelson, David G. Newcombe, Carol Newsom, Helen J. Nicholson, George W. E. Nickelsburg, Tatyana Nikolskaya, Damayanthi M. A. Niles, Bertil Nilsson, Nyambura Njoroge, Fidelis Nkomazana, Mary Beth Norton, Christian Nottmeier, Sonene Nyawo, Anthère Nzabatsinda, Edward T. Oakes, Gerald O'Collins, Daniel O'Connell, David W. Odell-Scott, Mercy Amba Oduyoye, Kathleen O'Grady, Oyeronke Olajubu, Thomas O'Loughlin, Dennis T. Olson, J. Steven O'Malley, Cephas N. Omenyo, Muriel Orevillo-Montenegro, César Augusto Ornellas Ramos, Agbonkhianmeghe E. Orobator, Kenan B. Osborne, Carolyn Osiek, Javier Otaola Montagne, Douglas F. Ottati, Anna May Say Pa, Irina Paert, Jerry G. Pankhurst, Aristotle Papanikolaou, Samuele F. Pardini, Stefano Parenti, Peter Paris, Sung Bae Park, Cristián G. Parker, Raquel Pastor, Joseph Pathrapankal, Daniel Patte, W. Brown Patterson, Clive Pearson, Keith F. Pecklers, Nancy Cardoso Pereira, David Horace Perkins, Pheme Perkins, Edward N. Peters, Rebecca Todd Peters, Bishop Yeznik Petrossian, Raymond Pfister, Peter C. Phan, Isabel Apawo Phiri, William S. F. Pickering, Derrick G. Pitard, William Elvis Plata, Zlatko Plese, John Plummer, James Newton Poling, Ronald Popivchak, Andrew Porter, Ute Possekel, James M. Powell, Enos Das Pradhan, Devadasan Premnath, Jaime Adrían Prieto Valladares, Anne Primavesi, Randall Prior, María Alicia Puente Lutteroth, Eduardo Guzmão Quadros, Albert Rabil, Laurent William Ramambason, Apolonio M. Ranche, Vololona Randriamanantena Andriamitandrina, Lawrence R. Rast, Paul L. Redditt, Adele Reinhartz, Rolf Rendtorff, Pål Repstad, James N. Rhodes, John K. Riches, Joerg Rieger, Sharon H. Ringe, Sandra Rios, Tyler Roberts, David M. Robinson, James M. Robinson, Joanne Maguire Robinson, Richard A. H. Robinson, Roy R. Robson, Jack B. Rogers, Maria Roginska, Sidney Rooy, Rev. Garnett Roper, Maria José Fontelas Rosado-Nunes, Andrew C. Ross, Stefan Rossbach, François Rossier, John D. Roth, John K. Roth, Phillip Rothwell, Richard E. Rubenstein, Rosemary Radford Ruether, Markku Ruotsila, John E. Rybolt, Risto Saarinen, John Saillant, Juan Sanchez, Wagner Lopes Sanchez, Hugo N. Santos, Gerhard Sauter, Gloria L. Schaab, Sandra M. Schneiders, Quentin J. Schultze, Fernando F. Segovia, Turid Karlsen Seim, Carsten Selch Jensen, Alan P. F. Sell, Frank C. Senn, Kent Davis Sensenig, Damían Setton, Bal Krishna Sharma, Carolyn J. Sharp, Thomas Sheehan, N. Gerald Shenk, Christian Sheppard, Charles Sherlock, Tabona Shoko, Walter B. Shurden, Marguerite Shuster, B. Mark Sietsema, Batara Sihombing, Neil Silberman, Clodomiro Siller, Samuel Silva-Gotay, Heikki Silvet, John K. Simmons, Hagith Sivan, James C. Skedros, Abraham Smith, Ashley A. Smith, Ted A. Smith, Daud Soesilo, Pia Søltoft, Choan-Seng (C. S.) Song, Kathryn Spink, Bryan Spinks, Eric O. Springsted, Nicolas Standaert, Brian Stanley, Glen H. Stassen, Karel Steenbrink, Stephen J. Stein, Andrea Sterk, Gregory E. Sterling, Columba Stewart, Jacques Stewart, Robert B. Stewart, Cynthia Stokes Brown, Ken Stone, Anne Stott, Elizabeth Stuart, Monya Stubbs, Marjorie Hewitt Suchocki, David Kwang-sun Suh, Scott W. Sunquist, Keith Suter, Douglas Sweeney, Charles H. Talbert, Shawqi N. Talia, Elsa Tamez, Joseph B. Tamney, Jonathan Y. Tan, Yak-Hwee Tan, Kathryn Tanner, Feiya Tao, Elizabeth S. Tapia, Aquiline Tarimo, Claire Taylor, Mark Lewis Taylor, Bishop Abba Samuel Wolde Tekestebirhan, Eugene TeSelle, M. Thomas Thangaraj, David R. Thomas, Andrew Thornley, Scott Thumma, Marcelo Timotheo da Costa, George E. “Tink” Tinker, Ola Tjørhom, Karen Jo Torjesen, Iain R. Torrance, Fernando Torres-Londoño, Archbishop Demetrios [Trakatellis], Marit Trelstad, Christine Trevett, Phyllis Trible, Johannes Tromp, Paul Turner, Robert G. Tuttle, Archbishop Desmond Tutu, Peter Tyler, Anders Tyrberg, Justin Ukpong, Javier Ulloa, Camillus Umoh, Kristi Upson-Saia, Martina Urban, Monica Uribe, Elochukwu Eugene Uzukwu, Richard Vaggione, Gabriel Vahanian, Paul Valliere, T. J. Van Bavel, Steven Vanderputten, Peter Van der Veer, Huub Van de Sandt, Louis Van Tongeren, Luke A. Veronis, Noel Villalba, Ramón Vinke, Tim Vivian, David Voas, Elena Volkova, Katharina von Kellenbach, Elina Vuola, Timothy Wadkins, Elaine M. Wainwright, Randi Jones Walker, Dewey D. Wallace, Jerry Walls, Michael J. Walsh, Philip Walters, Janet Walton, Jonathan L. Walton, Wang Xiaochao, Patricia A. Ward, David Harrington Watt, Herold D. Weiss, Laurence L. Welborn, Sharon D. Welch, Timothy Wengert, Traci C. West, Merold Westphal, David Wetherell, Barbara Wheeler, Carolinne White, Jean-Paul Wiest, Frans Wijsen, Terry L. Wilder, Felix Wilfred, Rebecca Wilkin, Daniel H. Williams, D. Newell Williams, Michael A. Williams, Vincent L. Wimbush, Gabriele Winkler, Anders Winroth, Lauri Emílio Wirth, James A. Wiseman, Ebba Witt-Brattström, Teofil Wojciechowski, John Wolffe, Kenman L. Wong, Wong Wai Ching, Linda Woodhead, Wendy M. Wright, Rose Wu, Keith E. Yandell, Gale A. Yee, Viktor Yelensky, Yeo Khiok-Khng, Gustav K. K. Yeung, Angela Yiu, Amos Yong, Yong Ting Jin, You Bin, Youhanna Nessim Youssef, Eliana Yunes, Robert Michael Zaller, Valarie H. Ziegler, Barbara Brown Zikmund, Joyce Ann Zimmerman, Aurora Zlotnik, Zhuo Xinping
- Edited by Daniel Patte, Vanderbilt University, Tennessee
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- The Cambridge Dictionary of Christianity
- Published online:
- 05 August 2012
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- 20 September 2010, pp xi-xliv
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Association between Faecalibacterium prausnitzii and dietary fibre in colonic fermentation in healthy human subjects
- Robin F. J. Benus, Tjip S. van der Werf, Gjalt W. Welling, Patricia A. Judd, Moira A. Taylor, Hermie J. M. Harmsen, Kevin Whelan
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- Journal:
- British Journal of Nutrition / Volume 104 / Issue 5 / 14 September 2010
- Published online by Cambridge University Press:
- 29 March 2010, pp. 693-700
- Print publication:
- 14 September 2010
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The intestinal microbiota are a complex ecosystem influencing the immunoregulation of the human host, providing protection from colonising pathogens and producing SCFA as the main energy source of colonocytes. Our objective was to investigate the effect of dietary fibre exclusion and supplementation on the intestinal microbiota and SCFA concentrations. Faecal samples were obtained from healthy volunteers before and after two 14 d periods of consuming formulated diets devoid or supplemented with fibre (14 g/l). The faecal microbiota were analysed using fluorescent in situ hybridisation and SCFA were measured using GLC. There were large and statistically significant reductions in the numbers of the Faecalibacterium prausnitzii (P ≤ 0·01) and Roseburia spp. (P ≤ 0·01) groups during both the fibre-free and fibre-supplemented diets. Significant and strong positive correlations between the proportion of F. prausnitzii and the proportion of butyrate during both baseline normal diets were found (pre-fibre free r 0·881, P = 0·001; pre-fibre supplemented r 0·844, P = 0·002). A significant correlation was also found between the proportional reduction in F. prausnitzii and the proportional reduction in faecal butyrate during both the fibre-free (r 0·806; P = 0·005) and the fibre-supplemented diet (r 0·749; P = 0·013). These findings may contribute to the understanding of the association between fibre, microbiota and fermentation in health, during enteral nutrition and in disease states such as Crohn's disease.
Diagnostic accuracy of clinical prediction rules to exclude acute coronary syndrome in the emergency department setting: a systematic review
- Erik P. Hess, Venkatesh Thiruganasambandamoorthy, George A. Wells, Patricia Erwin, Allan S. Jaffe, Judd E. Hollander, Victor M. Montori, Ian G. Stiell
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- Journal:
- Canadian Journal of Emergency Medicine / Volume 10 / Issue 4 / July 2008
- Published online by Cambridge University Press:
- 21 May 2015, pp. 373-382
- Print publication:
- July 2008
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Objective:
We sought to determine the diagnostic accuracy of clinical prediction rules to exclude acute coronary syndrome (ACS) in the emergency department (ED) setting.
Methods:We searched MEDLINE, EMBASE, Web of Science and the Cochrane Database of Systematic Reviews. We contacted content experts to identify additional articles for review. Reference lists of included studies were hand searched. We selected articles for review based on the following criteria: 1) enrolled consecutive ED patients; 2) incorporated variables from the history or physical examination, electrocardiogram and cardiac biomarkers; 3) did not incorporate cardiac stress testing or coronary angiography into prediction rule; 4) based on original research; 5) prospectively derived or validated; 6) did not require use of a computer; and 7) reported sufficient data to construct a 2 ∞ 2 contingency table. We assessed study quality and extracted data independently and in duplicate using a standardized data extraction form.
Results:Eight studies met inclusion criteria, encompassing 7937 patients. None of the studies verified the prediction rule with a reference standard on all or a random sample of patients. Six studies did not report blinding prediction rule assessors to reference standard results, and vice versa. Three prediction rules were prospectively validated. Sensitivities and specificities ranged from 94% to 100% and 13% to 57%, and positive and negative likelihood ratios from 1.1 to 2.2 and 0.01 to 0.17, respectively.
Conclusion:Current prediction rules for ACS have substantial methodological limitations and have not been successfully implemented in the clinical setting. Future methodologically sound studies are needed to guide clinical practice.
Enteral feeding: the effect on faecal output, the faecal microflora and SCFA concentrations
- Kevin Whelan, Patricia A Judd, Victor R. Preedy, Moira A. Taylor
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- Journal:
- Proceedings of the Nutrition Society / Volume 63 / Issue 1 / February 2004
- Published online by Cambridge University Press:
- 07 March 2007, pp. 105-113
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Enteral tube feeding is common in both the hospital and community environment; however, patients can suffer alterations in faecal output that can have serious clinical sequelae. Problems associated with accurate characterisation of faecal output and definition of diarrhoea impede the comparison of research studies and prevent standardised assessment of therapeutic interventions in clinical practice. The colonic microflora may protect the patient against diarrhoea by preventing enteropathogenic infection and by producing SCFA that stimulate colonic water absorption. However, studies in healthy volunteers suggest that the composition of the enteral formula may have a negative impact on the microflora and SCFA concentrations. The addition of fructo-oligosaccharides to the enteral formula may partially prevent negative alterations to the microflora, although conclusive data from studies in patients are not yet available. Modification of the microflora with probiotics and prebiotics may hold potential in prophylaxis against diarrhoea during enteral tube feeding.
Appetite during consumption of enteral formula as a sole source of nutrition: the effect of supplementing pea-fibre and fructo-oligosaccharides
- Kevin Whelan, Loukia Efthymiou, Patricia A. Judd, Victor R. Preedy, Moira A. Taylor
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- Journal:
- British Journal of Nutrition / Volume 96 / Issue 2 / August 2006
- Published online by Cambridge University Press:
- 08 March 2007, pp. 350-356
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- August 2006
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Liquid enteral formulas are commonly used as a sole source of nutritional support of patients in hospital and community settings. Their effect on appetite has important consequences for dietary management of such patients and is likely to be affected by the formula composition. The aim of the present study was to compare appetite within healthy subjects consuming both a standard formula and one supplemented with pea-fibre (10g/l) and fructo-oligosaccharide (FOS; 5g/l) as a sole source of nutrition. Eleven healthy subjects consumed a standard formula or a pea-fibre/FOS formula as a sole source of nutrition for 14d in a double-blind, cross-over trial. Appetite was recorded using standard 100mm lines anchored at each end by a phrase denoting the most extreme appetite sensation. Consumption of the pea-fibre/FOS formula resulted in higher mean fullness (46 v.37mm, P=0·035), minimum fullness (13 v. 9mm, P=0·024) and minimum satiety (12 v. 8mm, P=0·012) compared to the standard formula. As there were no differences in macronutrient intake between formulas, these differences are likely to be due to supplementation with pea-fibre and FOS. The effect on appetite of the composition of an enteral formula, both with respect to nutrient content and functional components such as pea-fibre and FOS, may be an important aspect to consider in the dietary management of patients consuming enteral formula as a sole source of nutrition.
Neurocognitive impairment as a moderator in the development of borderline personality disorder
- PATRICIA HOFFMAN JUDD
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- Journal:
- Development and Psychopathology / Volume 17 / Issue 4 / December 2005
- Published online by Cambridge University Press:
- 12 December 2005, pp. 1173-1196
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Borderline personality disorder (BPD) is characterized by a pervasive instability of interpersonal relationships, affects, self-image, marked impulsivity, dissociation, and paranoia. The cognitive dimension of the disorder has received relatively little attention and is poorly understood. This paper proposes that neurocognitive impairment is a key moderator in the development of BPD and elaborates a possible pathway for the expression of the cognitive domain. Neurocognitive impairment is hypothesized to moderate the relationship between caretaking and insecure disorganized attachment and pathological dissociation in the formation of the disorder contributing to impaired metacognition and a range of cognitive difficulties. The empirical evidence from studies of cognitive processes, brain function, attachment, and dissociation that support this theory are reviewed and discussed. Areas for future research that might verify or refute this theory are suggested.
The author thanks Geralyn Windt for assistance in manuscript preparation, Dr. Jack Maser for early review of the manuscript, and Dr. Elizabeth Twamley for her invaluable consultation and expert review of the manuscript.
African plant foods rich in non-starch polysaccharides reduce postprandial blood glucose and insulin concentrations in healthy human subjects
- Uchenna A. Onyechi, Patricia A. Judd, Peter R. Ellis
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- Journal:
- British Journal of Nutrition / Volume 80 / Issue 5 / November 1998
- Published online by Cambridge University Press:
- 09 March 2007, pp. 419-428
- Print publication:
- November 1998
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The effects of two vegetable flours, prepared from the African plants Detarium senegalense Gmelin, a legume, and Cissus rotundifolia, a shrub, on postprandial blood glucose and insulin concentrations in human subjects, were investigated. Chemical analysis indicated that these flours contained significant amounts of NSP. The detarium in particular was found to be a rich source of water-soluble NSP (SNSP). The flours were incorporated into two types of breakfast meal, a stew meal and a wheat bread meal, containing 50 g and 70 g available carbohydrate respectively. Both meals also contained 10–12g NSP, the major fraction of which was SNSP. Control and fibre-rich meals were consumed on separate days in randomized order by two different groups of subjects (n 5, stew meals; n 10, bread meals). Venous blood samples were taken at fasting (0 min) and postprandially at 30 min intervals for 2·5 h and the plasma analysed for glucose and insulin. Compared with the controls, detarium and cissus meals elicited significant reductions (P < 0·006) in plasma glucose levels at most postprandial time points and for area-under-the-curve (AUC) values (AUC reductions 38–62%). Significant reductions (P < 0·002) in plasma insulin levels at various postprandial time points and for AUC values were also seen after detarium and cissus breads (AUC reductions 43 and 36% respectively), but not after the fibre-rich stew meals. SNSP and starch are possibly the main, but not the only, components responsible for the glucose- and insulin-lowering effects of cissus flour. The main SNSP fraction of detarium, identified as a high-molecular-weight xyloglucan, is likely to be a primary factor in determining the physiological activity of detarium flour.
The effect of moderately increased intakes of complex carbohydrates (cereals, vegetables and fruit) for 12 weeks on iron and zinc metabolism
- Pamela M. Manson, Patricia A. Judd, Susan J. Fairweather-Tait, John Eagles, Margret J. Minski
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- Journal:
- British Journal of Nutrition / Volume 63 / Issue 3 / May 1990
- Published online by Cambridge University Press:
- 09 March 2007, pp. 597-611
- Print publication:
- May 1990
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Fifteen adult women were given diets in which the intake of complex carbohydrates was increased from 20 to 30 g over a 12 week period. Metabolic balances were carried out, iron and zinc absorption tests performed using stable isotopes, and Fe and Zn status monitored. Although effects on bowel function were observed, the changed diet had no influence on any of the previously described variables. It was concluded that a moderate increase in cereals, fruit and vegetables did not have an adverse effect on Fe or Zn nutrition.
The hypocholesterolaemic effects of pectins in rats
- Patricia A. Judd, A. S. Truswell
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- Journal:
- British Journal of Nutrition / Volume 53 / Issue 3 / May 1985
- Published online by Cambridge University Press:
- 24 July 2007, pp. 409-425
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- May 1985
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1. The hypocholesterolaemic effects of pectins were studied in a series of five experiments in weanling Sprague-Dawley rats.
2. Expt A examined the effects of differing levels of dietary fat on plasma and liver lipids. Rats were given diets containing 100 g pectin, National Formulary (NF)/kg, and either 50,100, 150 or 200 g oil/kg. All diets contained 10 g cholesterol/kg. Plasma cholesterol levels were lower in all pectin-fed groups compared with rats given the control diet containing 100 g Solkafloc and 100 g oil/kg. Liver lipid and cholesterol levels increased with increasing fat content of the diet, reaching a plateau at 150 g fat/kg diet, but were still significantly lower in all pectin-fed groups compared with the control group.
3. Expt B. The effects of molecular weight and degree of methoxylation of pectins were studied in five groups of rats given either a control diet containing 100 g Solkafloc/kg or high molecular weight, high methoxyl pectin (HMW HMP); high molecular weight, low methoxyl pectin (HMW LMP); low molecular weight, high methoxyl pectin (LMW HMP); low molecular weight, low methoxyl pectin (LMW LMP). All diets in this and subsequent experiments contained 100 g fat and 10 g cholesterol/kg. Plasma cholesterol levels were significantly lower than control values only in the HMW HMP group. Compared with controls, animals given HMW pectins had lower levels of liver lipid and liver cholesterol; on the LMW HMP diet the liver cholesterol, but not the liver lipid, was lower.
4. Expt C. An attempt was made to clarify the possible effect of degree of methoxylation by feeding diets containing either 100 g Solkafloc/kg,100 g pectin NF/kg or 100 g very high methoxyl pectin/kg.Plasma cholesterol levels were significantly reduced by both pectins but there was no difference in effect between the two. Both had similar viscosities suggesting that this is a more important factor than methoxyl content.
5. Expts D and E. Effects of dose on hypocholesterolaemic effects of HMP and LMP were studied. Diets containing 50 or 100 g Solkafloc, HMP or LMP/kg were given in Expt D, and 25 g Solkafloc or HMP/kg, 50 g Solkafloc, HMP or LMP/kg and 100 g Solkafloc or LMP/kg in Expt E. Plasma cholesterol levels were significantly reduced in groups given 50 or 100 g HMP/kg and in groups given 100 g LMP/kg.
6.HMP were found to be more effective at lowering plasma cholesterol levels than LMP. LMW pectins were not effective. This suggests that the hypocholesterolaemic effects are at least partly due to viscosity.
7. Gut length and weight was increased in pectin-fed animals compared with controls despite their lower body-weight. The weight of small intestinal contents at death was also greater in pectin-fed rats (Expts A and B), particularly in the distal small intestine.
Comparison of the effects of high- and low-methoxyl pectins on blood and faecal lipids in man
- Patricia A. Judd, A. S. Truswell
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- Journal:
- British Journal of Nutrition / Volume 48 / Issue 3 / November 1982
- Published online by Cambridge University Press:
- 09 March 2007, pp. 451-458
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- November 1982
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1. The effects on blood and faecal lipids of the addition of 15 g of either high- or low-methoxyl pectin to the habitual diets of ten healthy young adults have been studied.
2. Serum total cholesterol levels were reduced by a mean of 16% during consumption of low-methoxyl pectin and 18% during consumption of high-methoxyl pectin. High density lipoprotein cholesterol levels and triglyceride levels were unchanged.
3. There was no difference in faecal fat and steroid excretion between the two pectins.
4. The results suggest that it is the gel-forming properties of the pectins which are important in the cholesterol-lowering effect rather than differences in bile acid bindingdue to different methoxyl contents.