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1.  World Congress Integrative Medicine & Health 2017: Part one 
Brinkhaus, Benno | Falkenberg, Torkel | Haramati, Aviad | Willich, Stefan N. | Briggs, Josephine P. | Willcox, Merlin | Linde, Klaus | Theorell, Töres | Wong, Lisa M. | Dusek, Jeffrey | Wu, Darong | Eisenberg, David | Haramati, Aviad | Berger, Bettina | Kemper, Kathi | Stock-Schröer, Beate | Sützl-Klein, Hedda | Ferreri, Rosaria | Kaplan, Gary | Matthes, Harald | Rotter, Gabriele | Schiff, Elad | Arnon, Zahi | Hahn, Eckhard | Luberto, Christina M. | Martin, David | Schwarz, Silke | Tauschel, Diethard | Flower, Andrew | Gramminger, Harsha | Gupta, Hedwig H. | Gupta, S. N. | Kerckhoff, Annette | Kessler, Christian S. | Michalsen, Andreas | Kessler, Christian S. | Kim, Eun S. | Jang, Eun H. | Kim, Rana | Jan, Sae B. | Mittwede, Martin | Mohme, Wiebke | Ben-Arye, Eran | Bonucci, Massimo | Saad, Bashar | Breitkreuz, Thomas | Rossi, Elio | Kebudi, Rejin | Daher, Michel | Razaq, Samaher | Gafer, Nahla | Nimri, Omar | Hablas, Mohamed | Kienle, Gunver Sophia | Samuels, Noah | Silbermann, Michael | Bandelin, Lena | Lang, Anna-Lena | Wartner, Eva | Holtermann, Christoph | Binstock, Maxwell | Riebau, Robert | Mujkanovic, Edin | Cramer, Holger | Lauche, Romy | Michalsen, Andres | Ward, Lesley | Cramer, Holger | Irnich, Dominik | Stör, Wolfram | Burnstock, Geoffrey | Schaible, Hans-Georg | Ots, Thomas | Langhorst, Jost | Lauche, Romy | Sundberg, Tobias | Falkenberg, Torkel | Amarell, Catherina | Amarell, Catherina | Anheyer, Melanie | Eckert, Marion | Eckert, Marion | Ogal, Mercedes | Eckert, Marion | Amarell, Catherina | Schönauer, Annette | Reisenberger, Birgit | Brand, Bernhard | Anheyer, Dennis | Dobos, Gustav | Kroez, Matthias | Martin, David | Matthes, Harald | Ammendola, Aldo | Mao, Jun J. | Witt, Claudia | Yang, Yufei | Dobos, Gustav | Oritz, Miriam | Horneber, Markus | Voiß, Petra | Reisenberger, Birgit | von Rosenstiel, Alexandra | Eckert, Marion | Ogal, Mercedes | Amarell, Catharina | Anheyer, Melanie | Schad, Friedemann | Schläppi, Marc | Kröz, Matthias | Büssing, Arndt | Bar-Sela, Gil | Matthes, Harald | Schiff, Elad | Ben-Arye, Eran | Arnon, Zahi | Avshalomov, David | Attias, Samuel | Schönauer, Annette | Haramati, Aviad | Witt, Claudia | Brinkhaus, Benno | Cotton, Sian | Jong, Miek | Jong, Mats | Scheffer, Christian | Haramati, Aviad | Tauschel, Diethard | Edelhäuser, Friedrich | AlBedah, Abdullah | Lee, Myeong Soo | Khalil, Mohamed | Ogawa, Keiko | Motoo, Yoshiharu | Arimitsu, Junsuke | Ogawa, Masao | Shimizu, Genki | Stange, Rainer | Kraft, Karin | Kuchta, Kenny | Watanabe, Kenji | Bonin, D | Büssing, Arndt | Gruber, Harald | Koch, Sabine | Gruber, Harald | Pohlmann, Urs | Caldwell, Christine | Krantz, Barbara | Kortum, Ria | Martin, Lily | Wieland, Lisa S. | Kligler, Ben | Gould-Fogerite, Susan | Zhang, Yuqing | Wieland, Lisa S. | Riva, John J. | Lumpkin, Michael | Ratner, Emily | Ping, Liu | Jian, Pei | Hamme, Gesa-Meyer | Mao, Xiaosong | Chouping, Han | Schröder, Sven | Hummelsberger, Josef | Wullinger, Michael | Brodzky, Marc | Zalpour, Christoff | Langley, Julia | Weber, Wendy | Mudd, Lanay M. | Wayne, Peter | Witt, Clauda | Weidenhammer, Wolfgang | Fønnebø, Vinjar | Boon, Heather | Steel, Amie | Bugarcic, Andrea | Rangitakatu, Melisa | Steel, Amie | Adams, Jon | Sibbritt, David | Wardle, Jon | Leach, Matthew | Schloss, Janet | Dieze, Helene | Boon, Heather | Ijaz, Nadine | Willcox, Merlin | Heinrich, Michael | Lewith, George | Flower, Andrew | Graz, Bertrand | Adam, Daniela | Grabenhenrich, Linus | Ortiz, Miriam | Binting, Sylvia | Reinhold, Thomas | Brinkhaus, Benno | Andermo, Susanne | Sundberg, Tobias | Falkenberg, Torkel | Nordberg, Johanna Hök | Arman, Maria | Bhasin, Manoj | Fan, Xueyi | Libermann, Towia | Fricchione, Gregory | Denninger, John | Benson, Herbert | Berger, Bettina | Stange, Rainer | Michalsen, Andreas | Martin, David D. | Boers, Inge | Vlieger, Arine | Jong, Miek | Brinkhaus, Benno | Teut, Michael | Ullmann, Alexander | Ortiz, Miriam | Rotter, Gabriele | Binting, Sylvia | Lotz, Fabian | Roll, Stephanie | Canella, Claudia | Mikolasek, Michael | Rostock, Matthias | Beyer, Jörg | Guckenberger, Matthias | Jenewein, Josef | Linka, Esther | Six, Claudia | Stoll, Sarah | Stupp, Roger | Witt, Claudia M. | Chuang, Elisabeth | Kligler, Ben | McKee, Melissa D. | Cramer, Holger | Lauche, Romy | Klose, Petra | Lange, Silke | Langhorst, Jost | Dobos, Gustav | Chung, Vincent C. H. | Wong, Hoi L. C. | Wu, Xin Y. | Wen, Grace Y. G. | Ho, Robin S. T. | Ching, Jessica Y. L. | Wu, Justin C. Y. | Coakley, Amanda | Flanagan, Jane | Annese, Christine | Empoliti, Joanne | Gao, Zishan | Liu, Xugang | Yu, Shuguang | Yan, Xianzhong | Liang, Fanrong | Hohmann, Christoph D. | Steckhan, Nico | Ostermann, Thomas | Paetow, Arion | Hoff, Evelyn | Michalsen, Andreas | Hu, Xiao-Yang | Wu, Ruo-Han | Logue, Martin | Blonde, Clara | Lai, Lily Y. | Stuart, Beth | Flower, Andrew | Fei, Yu-Tong | Moore, Michael | Liu, Jian-Ping | Lewith, George | Hu, Xiao-Yang | Wu, Ruo-Han | Logue, Martin | Blonde, Clara | Lai, Lily Y. | Stuart, Beth | Flower, Andrew | Fei, Yu-Tong | Moore, Michael | Liu, Jian-Ping | Lewith, George | Jeitler, Michael | Zillgen, Hannah | Högl, Manuel | Steckhan, Nico | Stöckigt, Barbara | Seifert, Georg | Michalsen, Andreas | Kessler, Christian | Khadivzadeh, Talat | Bashtian, Maryam Hassanzadeh | Aval, Shapour Badiee | Esmaily, Habibollah | Kim, Jihye | Kim, Keun H. | Klocke, Carina | Joos, Stefanie | Koshak, Abdulrahman | Wie, Li | Koshak, Emad | Wali, Siraj | Alamoudi, Omer | Demerdash, Abdulrahman | Qutub, Majdy | Pushparaj, Peter | Heinrich, Michael | Kruse, Sigrid | Fischer, Isabell | Tremel, Nadine | Rosenecker, Joseph | Leung, Brenda | Takeda, Wendy | Liang, Ning | Feng, Xue | Liu, Jian-ping | Cao, Hui-juan | Luberto, Christina M. | Shinday, Nina | Philpotts, Lisa | Park, Elyse | Fricchione, Gregory L. | Yeh, Gloria | Munk, Niki | Zakeresfahani, Arash | Foote, Trevor R. | Ralston, Rick | Boulanger, Karen | Özbe, Dominik | Gräßel, Elmar | Luttenberger, Katharina | Pendergrass, Anna | Pach, Daniel | Bellmann-Strobl, Judit | Chang, Yinhui | Pasura, Laura | Liu, Bin | Jäger, Sven F. | Loerch, Ronny | Jin, Li | Brinkhaus, Benno | Ortiz, Miriam | Reinhold, Thomas | Roll, Stephanie | Binting, Sylvia | Icke, Katja | Shi, Xuemin | Paul, Friedemann | Witt, Claudia M. | Rütz, Michaela | Lynen, Andreas | Schömitz, Meike | Vahle, Maik | Salomon, Nir | Lang, Alon | Lahat, Adi | Kopylov, Uri | Ben-Horin, Shomron | Har-Noi, Ofir | Avidan, Benjamin | Elyakim, Rami | Gamus, Dorit | NG, Siew | Chang, Jessica | Wu, Justin | Kaimiklotis, John | Schumann, Dania | Buttó, Ludovica | Langhorst, Jost | Dobos, Gustav | Haller, Dirk | Cramer, Holger | Smith, Caroline | de Lacey, Sheryl | Chapman, Michael | Ratcliffe, Julie | Johnson, Neil | Lyttleton, Jane | Boothroyd, Clare | Fahey, Paul | Tjaden, Bram | van Vliet, Marja | van Wietmarschen, Herman | Jong, Miek | Tröger, Wilfried | Vuolanto, Pia | Aarva, Paulina | Sorsa, Minna | Helin, Kaija | Wenzel, Claudia | Zoderer, Iris | Pammer, Patricia | Simon, Patrick | Tucek, Gerhard | Wode, Kathrin | Henriksson, Roger | Sharp, Lena | Stoltenberg, Anna | Nordberg, Johanna Hök | Xiao-ying, Yang | Wang, Li-qiong | Li, Jin-gen | Liang, Ning | Wang, Ying | Liu, Jian-ping | Balneaves, Lynda | Capler, Rielle | Bocci, Chiara | Guffi, Marta | Paolini, Marina | Meaglia, Ilaria | Porcu, Patrizia | Ivaldi, Giovanni B. | Dragan, Simona | Bucuras, Petru | Pah, Ana M. | Badalica-Petrescu, Marius | Buleu, Florina | Hogea-Stoichescu, Gheorghe | Christodorescu, Ruxandra | Kao, Lan | Cho, Yumin | Klafke, Nadja | Mahler, Cornelia | von Hagens, Cornelia | Uhlmann, Lorenz | Bentner, Martina | Schneeweiss, Andreas | Mueller, Andreas | Szecsenyi, Joachim | Joos, Stefanie | Neri, Isabella | Ortiz, Miriam | Schnabel, Katharina | Teut, Michael | Rotter, Gabriele | Binting, Sylvia | Cree, Margit | Lotz, Fabian | Suhr, Ralf | Brinkhaus, Benno | Rossi, Elio | Baccetti, Sonia | Firenzuoli, Fabio | Monechi, Maria V. | Di Stefano, Mariella | Amunni, Gianni | Wong, Wendy | Chen, Bingzhong | Wu, Justin | Amri, Hakima | Haramati, Aviad | Kotlyanskaya, Lucy | Anderson, Belinda | Evans, Roni | Kligler, Ben | Marantz, Paul | Bradley, Ryan | Booth-LaForce, Cathryn | Zwickey, Heather | Kligler, Benjamin | Brooks, Audrey | Kreitzer, Mary J. | Lebensohn, Patricia | Goldblatt, Elisabeth | Esmel-Esmel, Neus | Jiménez-Herrera, Maria | Ijaz, Nadine | Boon, Heather | Jocham, Alexandra | Stock-Schröer, Beate | Berberat, Pascal O. | Schneider, Antonius | Linde, Klaus | Masetti, Morgana | Murakozy, Henriette | Van Vliet, Marja | Jong, Mats | Jong, Miek | Agdal, Rita | Atarzadeh, Fatemeh | Jaladat, Amir M. | Hoseini, Leila | Amini, Fatemeh | Bai, Chen | Liu, Tiegang | Zheng, Zian | Wan, Yuxiang | Xu, Jingnan | Wang, Xuan | Yu, He | Gu, Xiaohong | Daneshfard, Babak | Nimrouzi, Majid | Tafazoli, Vahid | Alorizi, Seyed M. Emami | Saghebi, Seyed A. | Fattahi, Mohammad R. | Salehi, Alireza | Rezaeizadeh, Hossein | Zarshenas, Mohammad M. | Nimrouzi, Majid | Fox, Kealoha | Hughes, John | Kostanjsek, Nenad | Espinosa, Stéphane | Lewith, George | Fisher, Peter | Latif, Abdul | Lefeber, Donald | Paske, William | Öztürk, Ali Ö. | Öztürk, Gizemnur | Boers, Inge | Tissing, Wim | Naafs, Marianne | Busch, Martine | Jong, Miek | Daneshfard, Babak | Sanaye, Mohammad R. | Dräger, Kilian | Fisher, Peter | Kreitzer, Mary J. | Evans, Roni | Leininger, Brent | Shafto, Kate | Breen, Jenny | Sanaye, Mohammad R. | Daneshfard, Babak | Simões-Wüst, Ana P. | Moltó-Puigmartí, Carolina | van Dongen, Martien | Dagnelie, Pieter | Thijs, Carel | White, Shelley | Wiesener, Solveig | Salamonsen, Anita | Stub, Trine | Fønnebø, Vinjar | Abanades, Sergio | Blanco, Mar | Masllorens, Laia | Sala, Roser | Al-Ahnoumy, Shafekah | Han, Dongwoon | He, Luzhu | Kim, Ha Yun | In Choi, Da | Alræk, Terje | Stub, Trine | Kristoffersen, Agnete | von Sceidt, Christel | Michalsen, Andreas | Bruset, Stig | Musial, Frauke | Anheyer, Dennis | Cramer, Holger | Lauche, Romy | Saha, Felix J. | Dobos, Gustav | Anheyer, Dennis | Haller, Heidemarie | Lauche, Romy | Dobos, Gustav | Cramer, Holger | Azizi, Hoda | Khadem, Nayereh | Hassanzadeh, Malihe | Estiri, Nazanin | Azizi, Hamideh | Tavassoli, Fatemeh | Lotfalizadeh, Marzieh | Zabihi, Reza | Esmaily, Habibollah | Azizi, Hoda | Shabestari, Mahmoud Mohammadzadeh | Paeizi, Reza | Azari, Masoumeh Alvandi | Bahrami-Taghanaki, Hamidreza | Zabihi, Reza | Azizi, Hamideh | Esmaily, Habibollah | Baars, Erik | De Bruin, Anja | Ponstein, Anne | Baccetti, Sonia | Di Stefano, Mariella | Rossi, Elio | Firenzuoli, Fabio | Segantini, Sergio | Monechi, Maria Valeria | Voller, Fabio | Barth, Jürgen | Kern, Alexandra | Lüthi, Sebastian | Witt, Claudia | Barth, Jürgen | Zieger, Anja | Otto, Fabius | Witt, Claudia | Beccia, Ariel | Dunlap, Corina | Courneene, Brendan | Bedregal, Paula | Passi, Alvaro | Rodríguez, Alfredo | Chang, Mayling | Gutiérrez, Soledad | Beissner, Florian | Beissner, Florian | Preibisch, Christine | Schweizer-Arau, Annemarie | Popovici, Roxana | Meissner, Karin | Beljanski, Sylvie | Belland, Laura | Rivera-Reyes, Laura | Hwang, Ula | Berger, Bettina | Sethe, Dominik | Hilgard, Dörte | Heusser, Peter | Bishop, Felicity | Al-Abbadey, Miznah | Bradbury, Katherine | Carnes, Dawn | Dimitrov, Borislav | Fawkes, Carol | Foster, Jo | MacPherson, Hugh | Roberts, Lisa | Yardley, Lucy | Lewith, George | Bishop, Felicity | Al-Abbadey, Miznah | Bradbury, Katherine | Carnes, Dawn | Dimitrov, Borislav | Fawkes, Carol | Foster, Jo | MacPherson, Hugh | Roberts, Lisa | Yardley, Lucy | Lewith, George | Bishop, Felicity | Holmes, Michelle | Lewith, George | Yardley, Lucy | Little, Paul | Cooper, Cyrus | Bogani, Patrizia | Maggini, Valentina | Gallo, Eugenia | Miceli, Elisangela | Biffi, Sauro | Mengoni, Alessio | Fani, Renato | Firenzuoli, Fabio | Brands-Guendling, Nadine | Guendling, Peter W. | Bronfort, Gert | Evans, Roni | Haas, Mitch | Leininger, Brent | Schulz, Craig | Bu, Xiangwei | Wang, J. | Fang, T. | Shen, Z. | He, Y. | Zhang, X. | Zhang, Zhengju | Wang, Dali | Meng, Fengxian | Büssing, Arndt | Baumann, Klaus | Frick, Eckhard | Jacobs, Christoph | Büssing, Arndt | Grünther, Ralph-Achim | Lötzke, Désirée | Büssing, Arndt | Jung, Sonny | Lötzke, Désirée | Recchia, Daniela R. | Robens, Sibylle | Ostermann, Thomas | Berger, Bettina | Stankewitz, Josephin | Kröz, Matthias | Jeitler, Mika | Kessler, Christian | Michalsen, Andreas | Cheon, Chunhoo | Jang, Bo H. | Ko, Seong G. | Huang, Ching W. | Sasaki, Yui | Ko, Youme | Cheshire, Anna | Ridge, Damien | Hughes, John | Peters, David | Panagioti, Maria | Simon, Chantal | Lewith, George | Cho, Hyun J. | Han, Dongwoon | Choi, Soo J. | Jung, Young S. | Im, Hyea B | Cooley, Kieran | Tummon-Simmons, Laura | Cotton, Sian | Luberto, Christina M. | Wasson, Rachel | Kraemer, Kristen | Sears, Richard | Hueber, Carly | Derk, Gwendolyn | Lill, JR | An, Ruopeng | Steinberg, Lois | Rodriguez, Lourdes Diaz | la Fuente, Francisca García-de | De la Vega, Miguel | Vargas-Román, Keyla | Fernández-Ruiz, Jonatan | Cantarero-Villanueva, Irene | Rodriguez, Lourdes Diaz | García-De la Fuente, Francisca | Jiménez-Guerrero, Fanny | Vargas-Román, Keyla | Fernández-Ruiz, Jonatan | Galiano-Castillo, Noelia | Diaz-Saez, Gualberto | Torres-Jimenez, José I. | Garcia-Gomez, Olga | Hortal-Muñoz, Luis | Diaz-Diez, Camino | Dicen, Demijon | Diezel, Helene | Adams, Jon | Steel, Amie | Wardle, Jon | Diezel, Helene | Steel, Amie | Frawley, Jane | Wardle, Jon | Broom, Alex | Adams, Jon | Dong, Fei | Yu, He | Liu, Tiegang | Ma, Xueyan | Yan, Liyi | Wan, Yuxiang | Zheng, Zian | Gu, Xiaohong | Dong, Fei | Yu, He | Wu, Liqun | Liu, Tiegang | Ma, Xueyan | Ma, Jiaju | Yan, Liyi | Wan, Yuxiang | Zheng, Zian | Zhen, Jianhua | Gu, Xiaohong | Dubois, Julie | Rodondi, Pierre-Yves | Edelhäuser, Friedrich | Schwartze, Sophia | Trapp, Barbara | Cysarz, Dirk
doi:10.1186/s12906-017-1782-4
PMCID: PMC5498855
2.  Effect of Oral Dexamethasone Without Immediate Antibiotics vs Placebo on Acute Sore Throat in Adults 
JAMA  2017;317(15):1535-1543.
Key Points
Question
Does a single dose of dexamethasone in the absence of antibiotics provide symptom relief for acute sore throat in adults presenting to primary care?
Findings
In this randomized clinical trial including 565 adults, the proportion of participants in the dexamethasone group achieving complete symptom resolution at 24 hours was not significantly different from those taking placebo. But at 48 hours significantly more in the dexamethasone group experienced complete resolution than did those in the placebo group.
Meaning
Among adults presenting to primary care practices with acute sore throat, a single dose of oral dexamethasone did not increase the likelihood of symptom resolution at 24 hours but did increase the likelihood at 48 hours.
This randomized controlled trial compared the effects of a single dose of dexamethasone vs placebo on sore throat symptoms among adults with acute sore throat not requiring immediate antibiotics.
Importance
Acute sore throat poses a significant burden on primary care and is a source of inappropriate antibiotic prescribing. Corticosteroids could be an alternative symptomatic treatment.
Objective
To assess the clinical effectiveness of oral corticosteroids for acute sore throat in the absence of antibiotics.
Design, Setting, and Participants
Double-blind, placebo-controlled randomized trial (April 2013-February 2015; 28-day follow-up completed April 2015) conducted in 42 family practices in South and West England, enrolled 576 adults recruited on the day of presentation to primary care with acute sore throat not requiring immediate antibiotic therapy.
Interventions
Single oral dose of 10 mg of dexamethasone (n = 293) or identical placebo (n = 283).
Main Outcomes and Measures
Primary: proportion of participants experiencing complete resolution of symptoms at 24 hours. Secondary: complete resolution at 48 hours, duration of moderately bad symptoms (based on a Likert scale, 0, normal; 6, as bad as it could be), visual analog symptom scales (0-100 mm; 0, no symptom to 100, worst imaginable), health care attendance, days missed from work or education, consumption of delayed antibiotics or other medications, adverse events.
Results
Among 565 eligible participants who were randomized (median age, 34 years [interquartile range, 26.0-45.5 year]; 75.2% women; 100% completed the intervention), 288 received dexamethasone; 277, placebo. At 24 hours, 65 participants (22.6%) in the dexamethasone group and 49 (17.7%) in the placebo group achieved complete resolution of symptoms, for a risk difference of 4.7% (95% CI, −1.8% to 11.2%) and a relative risk of 1.28 (95% CI; 0.92 to 1.78; P = .14). At 24 hours, participants receiving dexamethasone were not more likely than those receiving placebo to have complete symptom resolution. At 48 hours, 102 participants (35.4%) in the dexamethasone group vs 75 (27.1%) in the placebo group achieved complete resolution of symptoms, for a risk difference of 8.7% (95% CI, 1.2% to 16.2%) and a relative risk of 1.31 (95% CI, 1.02 to 1.68; P = .03). This difference also was observed in participants not offered delayed antibiotic prescription, for a risk difference of 10.3% (95% CI, 0.6% to 20.1%) and a relative risk of 1.37 (95% CI, 1.01 to 1.87; P = .046). There were no significant differences in any other secondary outcomes.
Results
Of 565 eligible randomized participants (median age, 34 years [interquartile range, 26.0-45.5 years]; 75.2% women; 100% completed the intervention), 288 received dexamethasone and 277, placebo. At 24 hours, participants receiving dexamethasone were not more likely than those receiving placebo to have complete symptom resolution. Results were similar among those who were not offered an antibiotic prescription and those who were offered a delayed antibiotic prescription. At 48 hours, more participants receiving dexamethasone than placebo had complete symptom resolution. This difference also was observed in patients not offered delayed antibiotics. There were no significant differences in any other secondary outcomes.
Conclusions and Relevance
Among adults presenting to primary care with acute sore throat, a single dose of oral dexamethasone compared with placebo did not increase the proportion of patients with resolution of symptoms at 24 hours. However, there was a significant difference at 48 hours.
Trial Registration
isrctn.org Identifier: ISRCTN17435450
doi:10.1001/jama.2017.3417
PMCID: PMC5470351  PMID: 28418482
3.  Extensive Core Microbiome in Drone-Captured Whale Blow Supports a Framework for Health Monitoring 
mSystems  2017;2(5):e00119-17.
The conservation and management of large whales rely in part upon health monitoring of individuals and populations, and methods generally necessitate invasive sampling. Here, we used a small, unmanned hexacopter drone to noninvasively fly above humpback whales from two populations, capture their exhaled breath (blow), and examine the associated microbiome. In the first extensive examination of the large-whale blow microbiome, we present surprising results about the discovery of a large core microbiome that was shared across individual whales from geographically separated populations in two ocean basins. We suggest that this core microbiome, in addition to other microbiome characteristics, could be a useful feature for health monitoring of large whales worldwide.
ABSTRACT
The pulmonary system is a common site for bacterial infections in cetaceans, but very little is known about their respiratory microbiome. We used a small, unmanned hexacopter to collect exhaled breath condensate (blow) from two geographically distinct populations of apparently healthy humpback whales (Megaptera novaeangliae), sampled in the Massachusetts coastal waters off Cape Cod (n = 17) and coastal waters around Vancouver Island (n = 9). Bacterial and archaeal small-subunit rRNA genes were amplified and sequenced from blow samples, including many of sparse volume, as well as seawater and other controls, to characterize the associated microbial community. The blow microbiomes were distinct from the seawater microbiomes and included 25 phylogenetically diverse bacteria common to all sampled whales. This core assemblage comprised on average 36% of the microbiome, making it one of the more consistent animal microbiomes studied to date. The closest phylogenetic relatives of 20 of these core microbes were previously detected in marine mammals, suggesting that this core microbiome assemblage is specialized for marine mammals and may indicate a healthy, noninfected pulmonary system. Pathogen screening was conducted on the microbiomes at the genus level, which showed that all blow and few seawater microbiomes contained relatives of bacterial pathogens; no known cetacean respiratory pathogens were detected in the blow. Overall, the discovery of a shared large core microbiome in humpback whales is an important advancement for health and disease monitoring of this species and of other large whales.
IMPORTANCE The conservation and management of large whales rely in part upon health monitoring of individuals and populations, and methods generally necessitate invasive sampling. Here, we used a small, unmanned hexacopter drone to noninvasively fly above humpback whales from two populations, capture their exhaled breath (blow), and examine the associated microbiome. In the first extensive examination of the large-whale blow microbiome, we present surprising results about the discovery of a large core microbiome that was shared across individual whales from geographically separated populations in two ocean basins. We suggest that this core microbiome, in addition to other microbiome characteristics, could be a useful feature for health monitoring of large whales worldwide.
doi:10.1128/mSystems.00119-17
PMCID: PMC5634792
SSU rRNA gene; bacteria; drone; humpback whale; microbiome
4.  Vitamin D deficiency was common among nursing home residents and associated with dementia: a cross sectional study of 545 Swedish nursing home residents 
BMC Geriatrics  2017;17:229.
Background
Residents of nursing homes may have low 25-hydroxyvitamin D (25OHD) concentrations. Associations between vitamin D and cognitive performance, dementia and susceptibility to infections are not clearly established. The aim of this study was to investigate the prevalence of vitamin D deficiency and to identify associated factors among residents of nursing homes for elderly.
Methods
In this cross-sectional study blood samples for analysis of 25OHD were collected from all participating residents of Swedish nursing homes for the elderly from January to March 2012.
Exclusion criteria: dementia too severe to collect a blood test, terminally ill or refusing participation. Outcome Measures: Serum 25OHD concentrations. Logistic regression to evaluate factors associated with vitamin D deficiency (25OHD < 25 nmol/L).
Results
Blood samples were obtained from 545 of 901 residents of 22 nursing homes. Mean age 86 years (SD 6.9), 68% were women. Prevalence of vitamin D supplementation 17%, dementia 55%, lack of appetite ≥3 months 45% and any antibiotic treatment during the last 6 months 30%. Serum 25OHD concentrations: mean 34 nmol/L (SD 21, median 27, range 4–125), 82% (448/545) had 25OHD < 50 nmol/L and 41% (224/545) had 25OHD < 25 nmol/L. Adjusted OR (95% CI; p-value) for possible predictors of vitamin D deficiency (25OHD < 25 nmol/L): vitamin D supplementation 0.075 (0.031–0.18; p < 0.001), lack of appetite ≥3 months 0.75 (0.50–1.1; p = 0.15), hours outdoors/week 0.99 (0.96–1.0; p = 0.62), Fitzpatrick skin phototype (4–6) 0.69 (0.44–1.1; p = 0.12); dementia 2.3 (1.5–3.4; p < 0.001) and antibiotics last 6 months 1.6 (1.1–2.6; p < 0.029), adjusted for age and gender.
Conclusions
Vitamin D deficiency was common among nursing home residents and strongly associated with dementia. Regardless of causality or not, it is important to be alert for vitamin D deficiency in nursing homes residents with dementia. As expected vitamin D supplementation was associated with less vitamin D deficiency, however lack of appetite, staying outdoors and skin phototype were not significant predictors. Antibiotic treatments during the last 6 months were associated with vitamin D deficiency, potentially supporting the hypothesis that vitamin D deficiency is associated with infections.
doi:10.1186/s12877-017-0622-1
PMCID: PMC5634897  PMID: 29017462
Vitamin D; Homes for the aged; Nursing homes; Frail elderly; Dementia; Infectious disease; Antibiotics
5.  Antibiotic Prescription Patterns for Acute Diarrhea in a Hospital in Shanghai in 2016: A Cross-sectional Study 
Open Forum Infectious Diseases  2017;4(Suppl 1):S326.
Abstract
Background
Unnecessary antibiotic use increases the risk for antibiotic resistance. The rates of antibiotic use for upper respiratory infections are high in hospitals in China. Although most guidelines advise against the use of antibiotics for acute diarrhea, little is known about antibiotic use practices for acute diarrhea in China.
Methods
A retrospective prescription review from a Shanghai hospital outpatient electronic health records system was conducted from 1 January 2016 to 30 December 2016. Records were included for adult patients. The microbial resistance seasonal data in 2016 were extracted. Chi-squared and multivariable logistic regression and adjusted odd ratio (aOR) were used to assess the relationships between demographic characteristics and antibiotic prescribing.
Results
In total, there were 16,565 prescriptions, 16,060 prescriptions were included in the final analysis after excluding the follow up visits. There were 12,131 (76%) prescriptions with antibiotics prescribed. 5505 (45%) of the antibiotics prescribed were injectable. Of the antibiotics prescribed, levofloxacin was the most frequent (85%), followed by various cephalosporins (14%). Of the cephalosporin prescriptions, third-generation products were the most common (97%). Treatment with oral rehydration salts (ORS) was prescribed 34 (0.2%) times, probiotics were prescribed 3414 (21%) times and smectite was prescribed 2209 (14%) times. Multivariable regression analysis showed that those more likely to receive antibiotics were age 31–50 aOR 1.3 (1.1–1.4), P < 0.001, evaluated in the late evening (11pm to 7am) aOR 2.6 (2.2–2.9) P < 0.001, in the early evening (6pm-11pm) aOR 2.0 (1.8–2.2) P < 0.001, in the summer (June-August) aOR 1.7 (1.5–1.9) P < 0.001. At the same time, the Gram-positive and Gram-negative resistance rates to levofloxacin exceeded 40%, including 50% of E. coliisolates.
Conclusion
High rates of antibiotic use were observed for acute diarrhea in this hospital. Given the inappropriateness of antibiotics for acute diarrhea and the nonsensical high rates of of intravenous levofloxacin use and the concurrent high rates of the levofloxacin resistance, a more effective antibiotic stewardship program is needed to improve patient outcomes, reduce costs, reinforce policy and address the underlying causes of antibiotic abuse.
Disclosures
All authors: No reported disclosures.
doi:10.1093/ofid/ofx163.770
PMCID: PMC5632036
6.  Antibiotic Use Among Future Health Professionals: A Multicentre Cross-Sectional Study of Chinese Medical Student 
Open Forum Infectious Diseases  2017;4(Suppl 1):S257.
Abstract
Background
Antibiotic use leads to antibiotic resistance and antibiotic misuse is high in China and other developing countries. This may arise from beliefs and behaviours of doctors and the pressure they receive from patients. This study aims to understand antibiotic use behaviour for self-limited illness among medical students - the future healthcare professionals.
Methods
This is part of a large cross-sectional study of Chinese university students of science, social science and humanities, and medicine. An electronic survey health belief model (HBM) questionnaire was distributed at six universities in China from September to November 2015. The score assessment was based on the constructs of HBM theory. Chi-squared and multivariable logistic regression and adjusted odd ratios (aOR) were used to assess the relationship between demographic characteristics, antibiotic use knowledge and behavior.
Results
In total, 11455 students were asked to participate and 11192 (97.5%) completed the questionnaires. 1819 medical students completed the survey. In the past month 529 (29%) medical students reported at least one self-limited illness. Of those, 285 (54%) self-medicated and 77 (27%) of them used antibiotics. 111 (21%) saw a doctor among whom 64 (58%) received antibiotics. 133 (25%) did nothing. In the past year, 279 (15%) of students used antibiotics for prophylaxis, 273 (15%) ever demanded an antibiotic from a doctor, 1166 (64%) kept a personal stock of antibiotics, 1034 (57%) bought antibiotics at a pharmacy, 97% of these without a prescription. Students with high HBM scores about antibiotics were significantly less likely to self-medicate with antibiotics (aOR 0.37, 95% CI 0.15-0.91, P = 0.031), to use antibiotics for prophylaxis (aOR 0.35, 95% CI 0.21–0.60, P < 0.0001) or demand an antibiotic (aOR 0.46, 95% CI 0.26-0.81, P = 0.007). Students whose father has a higher education level, whose mother is a doctor or who are from urban areas were more likely to stock antibiotics and self-medicate.
Conclusion
High rates of antibiotic self-medication (54%) and stocking (64%) were found among medical students. Along with the high rates of unnecessarily prescribed antibiotics by doctors (58%), there is clearly a need for effective antibiotic stewardship and training programs in Chinese healthcare institutions and medical schools.
Disclosures
All authors: No reported disclosures.
doi:10.1093/ofid/ofx163.559
PMCID: PMC5632178
7.  Uva-ursi extract and ibuprofen as alternative treatments of adult female urinary tract infection (ATAFUTI): study protocol for a randomised controlled trial 
Trials  2017;18:421.
Background
Women with acute uncomplicated urine infection are usually treated with antibiotics. One trial has demonstrated that delayed antibiotic treatment offered without symptom relief results in a modest reduction in antibiotic use. There is some evidence that ibuprofen provides symptom relief and reduces antibiotic use. Uva-ursi, a herbal product, has a traditional use for urinary infection symptom relief. We set out to test: in adult women with suspected UTI who accept the delayed prescription strategy: Do NSAIDs or uva-ursi (a herbal product) provide relief from urinary symptoms and reduce antibiotic use.
Methods/design
Adult women with suspected urinary tract infection presenting to primary care will be randomised using a factorial trial design in which patients will be randomised to one of two interventions as below:Group 1 – Uva-ursi + advice to take ibuprofenGroup 2 – Placebo + advice to take ibuprofenGroup 3 – Uva-ursi + no advice to take ibuprofenGroup 4 – Placebo + no advice to take ibuprofen
Patients and physicians will be blinded to the randomised group for the herb.
The main outcome is symptom severity at days 2–4 recorded in a validated, self-report diary used in previous studies.
Secondary outcomes include antibiotic use and symptom duration.
In total the trial will require 328 patients in order to achieve at least 90% power for the primary endpoint and 80% for the secondary endpoint.
In accordance with CONSORT guidelines all comparative analyses will be conducted on an intention-to-treat basis using SPSS or similar package.
Discussion
The outcomes from this trial have the potential to modify the current approach to the management of acute urinary symptoms with less dependence on the use of antibiotics.
Trial registration
ISRCTN registry, ID: ISRCTN43397016. Registered on 11 February 2015.
Electronic supplementary material
The online version of this article (doi:10.1186/s13063-017-2145-7) contains supplementary material, which is available to authorized users.
doi:10.1186/s13063-017-2145-7
PMCID: PMC5591533  PMID: 28886751
Antibiotic resistance; Urinary tract infection; Uva-ursi; NSAID; Ibuprofen
8.  Cost effectiveness of amoxicillin for lower respiratory tract infections in primary care: an economic evaluation accounting for the cost of antimicrobial resistance 
The British Journal of General Practice  2016;66(650):e633-e639.
Background
Lower respiratory tract infections (LRTIs) are a major disease burden and are often treated with antibiotics. Typically, studies evaluating the use of antibiotics focus on immediate costs of care, and do not account for the wider implications of antimicrobial resistance.
Aim
This study sought to establish whether antibiotics (principally amoxicillin) are cost effective in patients with LRTIs, and to explore the implications of taking into account costs associated with resistance.
Design and setting
Multinational randomised double-blinded trial in 2060 patients with acute cough/LRTIs recruited in 12 European countries.
Method
A cost-utility analysis from a health system perspective with a time horizon of 28 days was conducted. The primary outcome measure was the quality-adjusted life year (QALY). Hierarchical modelling was used to estimate incremental cost-effectiveness ratios (ICERs).
Results
Amoxicillin was associated with an ICER of €8216 (£6540) per QALY gained when the cost of resistance was excluded. If the cost of resistance is greater than €11 (£9) per patient, then amoxicillin treatment is no longer cost effective. Including possible estimates of the cost of resistance resulted in ICERs ranging from €14 730 (£11 949) per QALY gained — when only multidrug resistance costs and health care costs are included — to €727 135 (£589 856) per QALY gained when broader societal costs are also included.
Conclusion
Economic evaluation of antibiotic prescribing strategies that do not include the cost of resistance may provide misleading results that could be of questionable use to policymakers. However, further work is required to estimate robust costs of resistance.
doi:10.3399/bjgp16X686533
PMCID: PMC5198702  PMID: 27402969
amoxicillin; antibiotic resistance; cost-effectiveness; economic costs; lower respiratory tract infection; quality-adjusted life years
9.  Self-Assessment of Antimicrobial Stewardship in Primary Care: Self-Reported Practice Using the TARGET Primary Care Self-Assessment Tool 
Antibiotics  2017;6(3):16.
Multifaceted antimicrobial stewardship (AMS) interventions including: antibiotic guidance, reviews of antibiotic use using audits, education, patient facing materials, and self-assessment, are successful in improving antimicrobial use. We aimed to measure the self-reported AMS activity of staff completing a self-assessment tool (SAT). The Royal College of General Practitioners (RCGP)/Public Health England (PHE) SAT enables participants considering an AMS eLearning course to answer 12 short questions about their AMS activities. Questions cover guidance, audit, and reflection about antibiotic use, patient facing materials, and education. Responses are recorded digitally. Data were collated, anonymised, and exported into Microsoft Excel. Between November 2014 and June 2016, 1415 users completed the SAT. Ninety eight percent reported that they used antibiotic guidance for treating common infections and 63% knew this was available to all prescribers. Ninety four percent of GP respondents reported having used delayed prescribing when appropriate, 25% were not using Read codes, and 62% reported undertaking a practice-wide antibiotic audit in the last two years, of which, 77% developed an audit action plan. Twenty nine percent had undertaken other antibiotic-related clinical courses. Fifty six percent reported sharing patient leaflets covering infection. Many prescribers reported undertaking a range of AMS activities. GP practice managers should ensure that all clinicians have access to prescribing guidance. Antibiotic audits should be encouraged to enable GP staff to understand their prescribing behaviour and address gaps in good practice. Prescribers are not making full use of antibiotic prescribing-related training opportunities. Read coding facilitates more accurate auditing and its use by all clinicians should be encouraged.
doi:10.3390/antibiotics6030016
PMCID: PMC5617980  PMID: 28813003
TARGET; antimicrobial resistance; antimicrobial stewardship; primary care; self-assessment; general practice
10.  Global mapping of miRNA-target interactions in cattle (Bos taurus) 
Scientific Reports  2017;7:8190.
With roles in development, cell proliferation and disease, micro-RNA (miRNA) biology is of great importance and a potential therapeutic target. Here we used cross-linking immunoprecipitation (CLIP) and ligation of miRNA-target chimeras on the Argonaute (AGO) protein to globally map miRNA interactions in the cow. The interactome is the deepest reported to date. miRNA targeting principles are consistent with observations in other species, but with expanded pairing rules. Experimental mapping robustly predicted functional miR-17 regulatory sites. From miRNA-specific targeting for >5000 mRNAs we determined gene ontologies (GO). This confirmed repression of genes important for embryonic development and cell cycle progress by the let-7 family, and repression of those involved in cell cycle arrest by the miR-17 family, but also suggested a number of unappreciated miRNA functions. Our results provide a significant resource for understanding of bovine and species-conserved miRNA regulation, and demonstrate the power of experimental methods for establishing comprehensive interaction maps.
doi:10.1038/s41598-017-07880-8
PMCID: PMC5557892  PMID: 28811507
11.  Complete plastome sequencing of both living species of Circaeasteraceae (Ranunculales) reveals unusual rearrangements and the loss of the ndh gene family 
BMC Genomics  2017;18:592.
Background
Among the 13 families of early-diverging eudicots, only Circaeasteraceae (Ranunculales), which consists of the two monotypic genera Circaeaster and Kingdonia, lacks a published complete plastome sequence. In addition, the phylogenetic position of Circaeasteraceae as sister to Lardizabalaceae has only been weakly or moderately supported in previous studies using smaller data sets. Moreover, previous plastome studies have documented a number of novel structural rearrangements among early-divergent eudicots. Hence it is important to sequence plastomes from Circaeasteraceae to better understand plastome evolution in early-diverging eudicots and to further investigate the phylogenetic position of Circaeasteraceae.
Results
Using an Illumina HiSeq 2000, complete plastomes were sequenced from both living members of Circaeasteraceae: Circaeaster agrestis and Kingdonia uniflora. Plastome structure and gene content were compared between these two plastomes, and with those of other early-diverging eudicot plastomes. Phylogenetic analysis of a 79-gene, 99-taxon data set including exemplars of all families of early-diverging eudicots was conducted to resolve the phylogenetic position of Circaeasteraceae.
Both plastomes possess the typical quadripartite structure of land plant plastomes. However, a large ~49 kb inversion and a small ~3.5 kb inversion were found in the large single-copy regions of both plastomes, while Circaeaster possesses a number of other rearrangements, particularly in the Inverted Repeat. In addition, infA was found to be a pseudogene and accD was found to be absent within Circaeaster, whereas all ndh genes, except for ndhE and ndhJ, were found to be either pseudogenized (ΨndhA, ΨndhB, ΨndhD, ΨndhH and ΨndhK) or absent (ndhC, ndhF, ndhI and ndhG) in Kingdonia. Circaeasteraceae was strongly supported as sister to Lardizabalaceae in phylogenetic analyses.
Conclusion
The first plastome sequencing of Circaeasteraceae resulted in the discovery of several unusual rearrangements and the loss of ndh genes, and confirms the sister relationship between Circaeasteraceae and Lardizabalaceae. This research provides new insight to characterize plastome structural evolution in early-diverging eudicots and to better understand relationships within Ranunculales.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-017-3956-3) contains supplementary material, which is available to authorized users.
doi:10.1186/s12864-017-3956-3
PMCID: PMC5551029  PMID: 28793854
Early-diverging eudicots; Circaeasteraceae; Plastome; Rearrangements; Gene loss; Phylogenetic analyses
12.  Andrographis paniculata (Chuān Xīn Lián) for symptomatic relief of acute respiratory tract infections in adults and children: A systematic review and meta-analysis 
PLoS ONE  2017;12(8):e0181780.
Introduction
Antimicrobial resistance (AMR) is a substantial threat to public health. Safe and effective alternatives are required to reduce unnecessary antibiotic prescribing. Andrographis Paniculata (A. Paniculata, Chuān Xīn Lián) has traditionally been used in Indian and Chinese herbal medicine for cough, cold and influenza, suggesting a role in respiratory tract infections (RTIs). This systematic review aimed to evaluate the clinical effectiveness and safety of A. Paniculata for symptoms of acute RTIs (ARTIs).
Materials and methods
English and Chinese databases were searched from their inception to March 2016 for randomised controlled trials (RCTs) evaluating oral A. Paniculata without language barriers (Protocol ID: CRD42016035679). The primary outcomes were improvement in ARTI symptoms and adverse events (AEs). A random effects model was used to pool the mean differences and risk ratio with 95% CI reported. Methodological quality was evaluated using the Cochrane risk of bias tool; two reviewers independently screened eligibility and extracted data.
Results
Thirty-three RCTs (7175 patients) were included. Most trials evaluated A. Paniculata (as a monotherapy and as a herbal mixture) provided commercially but seldom reported manufacturing or quality control details. A. Paniculata improved cough (n = 596, standardised mean difference SMD: -0.39, 95% confidence interval CI [-0.67, -0.10]) and sore throat (n = 314, SMD: -1.13, 95% CI [-1.37, -0.89]) when compared with placebo. A. Paniculata (alone or plus usual care) has a statistically significant effect in improving overall symptoms of ARTIs when compared to placebo, usual care, and other herbal therapies. Evidence also suggested that A. Paniculata (alone or plus usual care) shortened the duration of cough, sore throat and sick leave/time to resolution when compared versus usual care. No major AEs were reported and minor AEs were mainly gastrointestinal. The methodological quality of included trials was overall poor.
Conclusions
A. Paniculata appears beneficial and safe for relieving ARTI symptoms and shortening time to symptom resolution. However, these findings should be interpreted cautiously owing to poor study quality and heterogeneity. Well-designed trials evaluating the effectiveness and potential to reduce antibiotic use of A. Paniculata are warranted.
doi:10.1371/journal.pone.0181780
PMCID: PMC5544222  PMID: 28783743
13.  Assessing the impact of Benzo[a]pyrene on Marine Mussels: Application of a novel targeted low density microarray complementing classical biomarker responses 
PLoS ONE  2017;12(6):e0178460.
Despite the increasing use of mussels in environmental monitoring and ecotoxicological studies, their genomes and gene functions have not been thoroughly explored. Several cDNA microarrays were recently proposed for Mytilus spp., but putatively identified partial transcripts have rendered the generation of robust transcriptional responses difficult in terms of pathway identification. We developed a new low density oligonucleotide microarray with 465 probes covering the same number of genes. Target genes were selected to cover most of the well-known biological processes in the stress response documented over the last decade in bivalve species at the cellular and tissue levels. Our new ‘STressREsponse Microarray’ (STREM) platform consists of eight sub-arrays with three replicates for each target in each sub-array. To assess the potential use of the new array, we tested the effect of the ubiquitous environmental pollutant benzo[a]pyrene (B[a]P) at 5, 50, and 100 μg/L on two target tissues, the gills and digestive gland, of Mytilus galloprovincialis exposed invivo for three days. Bioaccumulation of B[a]P was also determined demonstrating exposure in both tissues. In addition to the well-known effects of B[a]P on DNA metabolism and oxidative stress, the new array data provided clues about the implication of other biological processes, such as cytoskeleton, immune response, adhesion to substrate, and mitochondrial activities. Transcriptional data were confirmed using qRT-PCR. We further investigated cellular functions and possible alterations related to biological processes highlighted by the microarray data using oxidative stress biomarkers (Lipofuscin content) and the assessment of genotoxicity. DNA damage, as measured by the alkaline comet assay, increased as a function of dose.DNA adducts measurements using 32P-postlabeling method also showed the presence of bulky DNA adducts (i.e. dG-N2-BPDE). Lipofiscin content increased significantly in B[a]P exposed mussels. Immunohistochemical analysis of tubulin and actin showed changes in cytoskeleton organisation. Our results adopting an integrated approach confirmed that the combination of newly developed transcriptomic approcah, classical biomarkers along with chemical analysis of water and tissue samples should be considered for environmental bioimonitoring and ecotoxicological studies to obtain holistic information to assess the impact of contaminants on the biota.
doi:10.1371/journal.pone.0178460
PMCID: PMC5484464  PMID: 28651000
14.  The Amyloid Precursor Protein Is a Conserved Receptor for Slit to Mediate Axon Guidance 
eNeuro  2017;4(3):ENEURO.0185-17.2017.
Abstract
The amyloid precursor protein (APP) is a receptor-like membrane protein. Although APP processing and β-amyloid production play a central role in Alzheimer’s disease (AD) pathogenesis, the physiological function of APP remains elusive. Here, we identify APP as a novel receptor for Slit that mediates axon guidance and neural circuit formation. APP deficiency abolishes the Slit repulsive effect in a 3D olfactory explant culture, consistent with its callosal projection deficit in vivo and reminiscent of Slit loss. Inactivation of APP ortholog APL-1 in Caenorhabditis elegans results in pioneer axon mistargeting and genetic analysis places APL-1 in the SLT-1 (Slit)/SAX-3 (Robo) repulsive pathway. Slit binds to APP through the E1 domain, which triggers APP ectodomain shedding and recruitment of the intracellular FE65 and Pak1 complex and associated Rac1 GTPase activation. Our study establishes APP as a novel receptor for Slit ligand mediating axon guidance and neural circuit formation.
doi:10.1523/ENEURO.0185-17.2017
PMCID: PMC5534435
amyloid precursor protein; axon guidance; receptor; Slit; corpus callosum; mice; Caenorhabditis elegans; explant culture; Alzheimer’s disease
15.  Victims or vectors: a survey of marine vertebrate zoonoses from coastal waters of the Northwest Atlantic 
Diseases of aquatic organisms  2008;81(1):13-38.
Surveillance of zoonotic pathogens in marine birds and mammals in the Northwest Atlantic revealed a diversity of zoonotic agents. We found amplicons to sequences from Brucella spp., Leptospira spp., Giardia spp. and Cryptosporidium spp. in both marine mammals and birds. Avian influenza was detected in a harp seal and a herring gull. Routine aerobic and anaerobic culture showed a broad range of bacteria resistant to multiple antibiotics. Of 1460 isolates, 797 were tested for resistance, and 468 were resistant to one or more anti-microbials. 73% (341/468) were resistant to 1–4 drugs and 27% (128/468) resistant to 5–13 drugs. The high prevalence of resistance suggests that many of these isolates could have been acquired from medical and agricultural sources and inter-microbial gene transfer. Combining birds and mammals, 45% (63/141) of stranded and 8% (2/26) of by-caught animals in this study exhibited histopathological and/or gross pathological findings associated with the presence of these pathogens. Our findings indicate that marine mammals and birds in the Northwest Atlantic are reservoirs for potentially zoonotic pathogens, which they may transmit to beach goers, fishermen and wildlife health personnel. Conversely, zoonotic pathogens found in marine vertebrates may have been acquired via contamination of coastal waters by sewage, run-off and agricultural and medical waste. In either case these animals are not limited by political boundaries and are therefore important indicators of regional and global ocean health.
doi:10.3354/dao01936
PMCID: PMC5452619  PMID: 18828560
Zoonosis; Vertebrate; Northwest Atlantic; Pinniped; Cetacean; Bird
16.  Occurrence and patterns of antibiotic resistance in vertebrates off the Northeastern United States coast 
FEMS microbiology ecology  2009;67(3):421-431.
The prevalence of antibiotic-resistant bacteria in the marine environment is a growing concern, but the degree to which marine mammals, seabirds and fish harbor these organisms is not well documented. This project sought to identify the occurrence and patterns of antibiotic resistance in bacteria isolated from vertebrates of coastal waters in the northeastern United States. 472 isolates of clinical interest were tested for resistance to a suite of 16 antibiotics. Fifty-eight percent were resistant to at least one antibiotic, while 43% were resistant to multiple antibiotics. A multiple antibiotic resistance (MAR) index value greater than or equal to 0.2 was observed in 38% of the resistant pathogens, suggesting exposure of the animals to bacteria from significantly contaminated sites. Groups of antibiotics were identified for which bacterial resistance commonly co-occurred. Antibiotic resistance was more widespread in bacteria isolated from seabirds than marine mammals, and was more widespread in stranded or bycaught marine mammals than live marine mammals. Structuring of resistance patterns based on sample type (live/stranded/bycaught) but not animal group (mammal/bird/fish) was observed. These data indicate that antibiotic resistance is widespread in marine vertebrates, and they may be important reservoirs of antibiotic resistant bacteria in the marine environment.
doi:10.1111/j.1574-6941.2009.00648.x
PMCID: PMC5444207  PMID: 19187217
antibiotic resistance; marine; coastal; mammals; seabirds; vertebrates
17.  ‘You feel like your whole world is caving in’: A qualitative study of primary care patients’ conceptualisations of emotional distress 
Health (London, England : 1997)  2016;21(3):295-315.
General practitioners are tasked with determining the nature of patients’ emotional distress and providing appropriate care. For patients whose symptoms appear to fall near the ‘boundaries’ of psychiatric disorder, this can be difficult with important implications for treatment. There is a lack of qualitative research among patients with symptoms severe enough to warrant consultation, but where general practitioners have refrained from diagnosis. We aimed to explore how patients in this potentially large group conceptualise their symptoms and consequently investigate lay understandings of complex distinctions between emotional distress and psychiatric disorder. Interviews were conducted with 20 primary care patients whom general practitioners had identified as experiencing emotional distress, but had not diagnosed with major depressive disorder. Participants described severe emotional experiences with substantial impact on their lives. The term ‘depression’ was used in many different ways; however, despite severity, they often considered their emotional experience to be different to their perceived notions of ‘actual’ depression or mental illness. Where anxiety was mentioned, use appeared to refer to an underlying generalised state. Participants drew on complex, sometimes fluid and often theoretically coherent conceptualisations of their emotional distress, as related to, but distinct from, mental disorder. These conceptualisations differ from those frequently drawn on in research and treatment guidelines, compounding the difficulty for general practitioners. Developing models of psychological symptoms that draw on patient experience and integrate psychological/psychiatric theory may help patients understand the nature of their experience and, critically, provide the basis for a broader range of primary care interventions.
doi:10.1177/1363459316674786
PMCID: PMC5439536  PMID: 28177273
depression; emotional distress; mental disorder; primary care; qualitative
18.  A qualitative study of undergraduate clerkships in the intensive care unit: It’s a brand new world 
Introduction
While ICU clerkships are commonplace in undergraduate medical education, little is known about how students learn there. This study aimed to explore students’ perceptions of the ICU as a learning environment, the factors influencing their learning and any perceived differences between learning in the ICU and non-ICU settings.
Methods
We used interpretivist methodology, a social cognitive theoretical framework and a qualitative descriptive strategy. Ten medical students and four graduate doctors participated in four semi-structured focus group discussions. Data were analyzed by six-step thematic data analysis. Peer debriefing, audit trail and a reflexive diary were used.
Results
Social cognitive influences on learning were apparent in the discussions. Numerous differences emerged between ICU and non-ICU clinical clerkships, in particular an unfamiliarity with the environment and the complex illness, and difficulty preparing for the clerkship. A key emergent theme was the concept of three phases of student learning, termed pre-clerkship, early clerkship and learning throughout the clerkship. A social cognitive perspective identified changes in learner agency, self-regulatory activities and reciprocal determinism through these phases. The findings were used to construct a workplace model of undergraduate intensive care learning, providing a chronological perspective on the clerkship experience.
Conclusions
The ICU, a rich, social learning environment, is different in many respects to other hospital settings. Students navigate through three phases of an ICU clerkship, each with its own attendant emotional, educational and social challenges and with different dynamics between learner and environment. This chronological perspective may facilitate undergraduate educational design in the ICU.
doi:10.1007/s40037-017-0349-x
PMCID: PMC5466567  PMID: 28390032
Qualitative research; Clinical workplace learning; Undergraduate education; Intensive care medicine; Social cognitive theory
19.  Patient-reported outcome measures for monitoring primary care patients with depression: PROMDEP feasibility randomised trial 
BMJ Open  2017;7(3):e015266.
Objectives
To determine the feasibility of a trial of patient-reported outcome measures (PROMs) for monitoring primary care patients with depression.
Design
Partly individually randomised, partly cluster-randomised controlled trial.
Setting
Nine general practices in Southern England.
Participants
47 adults with new episodes of depression: 22 intervention, 25 control.
Randomisation
Remote computerised sequence generation and allocation.
Interventions
Patient Health Questionnaire, Distress Thermometer Analogue Scale and PSYCHLOPS problem profile for monitoring depression, following diagnosis and at 10–35 days later. Feedback of scores to patients was determined by practitioners.
Blinding
Non-blinded, using self-completed measures.
Primary outcome
Beck Depression Inventory (BDI-II).
Secondary outcome measures
Work and Social Adjustment Scale (WSAS), EuroQol Five-item, Five-level (EQ-5D-5L) Scale for quality of life, modified Client Service Receipt Inventory for costs, Medical Informant Satisfaction Scale (MISS), qualitative interviews with 14 patients and 13 practice staff about feasibility and acceptability of trial design.
Results
Three practices failed to recruit the target of six patients in 12 months. Follow-up rates were intervention patients: 18 (82%) at 12 weeks and 15 (68%) at 26 weeks; controls: 18 (72%) and 15 (60%), respectively. At 12 weeks, mean BDI-II score was lower among intervention group patients than controls by 5.8 points (95% CI −11.1 to −0.5), adjusted for baseline differences and clustering. WSAS scores were not significantly different. At 26 weeks, there were no significant differences in symptoms, social functioning, quality of life or costs, but mean satisfaction score was higher among controls by 22.0 points (95% CI −40.7 to −3.29). Intervention patients liked completing PROMs, but were disappointed when practitioners did not use the results to inform management.
Conclusions
PROMs may improve depression outcome in the short term, even if PROM scores do not inform practitioners' management. Challenges in recruiting and following up patients need addressing for a definitive trial of relatively brief measures which can potentially inform management. https://www.isrctn.com/search?q=97492541
Trial registration number
ISRCTN 97492541; Pre-results.
doi:10.1136/bmjopen-2016-015266
PMCID: PMC5387943  PMID: 28363932
depression; PRIMARY CARE; Patient reported outcome measures
20.  Pneumococcal conjugate vaccine implementation in middle-income countries 
Pneumonia  2017;9:6.
Background
Since 2000, the widespread adoption of pneumococcal conjugate vaccines (PCVs) has had a major impact in the prevention of pneumonia. Limited access to international financial support means some middle-income countries (MICs) are trailing in the widespread use of PCVs. We review the status of PCV implementation, and discuss any needs and gaps related to low levels of PCV implementation in MICs, with analysis of possible solutions to strengthen the PCV implementation process in MICs.
Main body
We searched PubMed, PubMed Central, Ovid MEDLINE, and SCOPUS databases using search terms related to pneumococcal immunization, governmental health policy or programmes, and MICs. Two authors independently reviewed the full text of the references, which were assessed for eligibility using pre-defined inclusion and exclusion criteria. The search terms identified 1,165 articles and the full texts of 21 were assessed for suitability, with eight articles included in the systematic review. MICs are implementing PCVs at a slower rate than donor-funded low-income countries and wealthier developed countries. A significant difference in the uptake of PCV in lower middle-income countries (LMICs) (71%) and upper middle-income countries (UMICs) (48%) is largely due to an unsuccessful process of “graduation” of MICs from GAVI assistance, an issue that arises as countries cross the income eligibility threshold and are no longer eligible to receive the same levels of financial assistance. A lack of country-specific data on disease burden, a lack of local expertise in economic evaluation, and the cost of PCV were identified as the leading causes of the slow uptake of PCVs in MICs. Potential solutions mentioned in the reviewed papers include the use of vaccine cost-effectiveness analysis and the provision of economic evidence to strengthen decision-making, the evaluation of the burden of disease, and post-introduction surveillance to monitor vaccine impact.
Conclusion
The global community needs to recognise the impediments to vaccine introduction into MICs. Improving PCV access could help decrease the incidence of pneumonia and reduce the selection pressure for pneumococcal antimicrobial resistance.
Electronic supplementary material
The online version of this article (doi:10.1186/s41479-017-0030-5) contains supplementary material, which is available to authorized users.
doi:10.1186/s41479-017-0030-5
PMCID: PMC5471880  PMID: 28702308
Immunization; Streptococcus pneumoniae; Pneumonia; Pneumococcal vaccines; Middle-income countries; GAVI; Health policy
21.  An efficient field and laboratory workflow for plant phylotranscriptomic projects1 
Applications in Plant Sciences  2017;5(3):apps.1600128.
Premise of the study:
We describe a field and laboratory workflow developed for plant phylotranscriptomic projects that involves cryogenic tissue collection in the field, RNA extraction and quality control, and library preparation. We also make recommendations for sample curation.
Methods and Results:
A total of 216 frozen tissue samples of Caryophyllales and other angiosperm taxa were collected from the field or botanical gardens. RNA was extracted, stranded mRNA libraries were prepared, and libraries were sequenced on Illumina HiSeq platforms. These included difficult mucilaginous tissues such as those of Cactaceae and Droseraceae.
Conclusions:
Our workflow is not only cost effective (ca. $270 per sample, as of August 2016, from tissue to reads) and time efficient (less than 50 h for 10–12 samples including all laboratory work and sample curation), but also has proven robust for extraction of difficult samples such as tissues containing high levels of secondary compounds.
doi:10.3732/apps.1600128
PMCID: PMC5357122
Caryophyllales; cryogenic field sampling; phylogenomics; phylotranscriptomics; RNA
22.  From the track to the ocean: Using flow control to improve marine bio-logging tags for cetaceans 
PLoS ONE  2017;12(2):e0170962.
Bio-logging tags are an important tool for the study of cetaceans, but superficial tags inevitably increase hydrodynamic loading. Substantial forces can be generated by tags on fast-swimming animals, potentially affecting behavior and energetics or promoting early tag removal. Streamlined forms have been used to reduce loading, but these designs can accelerate flow over the top of the tag. This non-axisymmetric flow results in large lift forces (normal to the animal) that become the dominant force component at high speeds. In order to reduce lift and minimize total hydrodynamic loading this work presents a new tag design (Model A) that incorporates a hydrodynamic body, a channel to reduce fluid speed differences above and below the housing and wing to redirect flow to counter lift. Additionally, three derivatives of the Model A design were used to examine the contribution of individual flow control features to overall performance. Hydrodynamic loadings of four models were compared using computational fluid dynamics (CFD). The Model A design eliminated all lift force and generated up to ~30 N of downward force in simulated 6 m/s aligned flow. The simulations were validated using particle image velocimetry (PIV) to experimentally characterize the flow around the tag design. The results of these experiments confirm the trends predicted by the simulations and demonstrate the potential benefit of flow control elements for the reduction of tag induced forces on the animal.
doi:10.1371/journal.pone.0170962
PMCID: PMC5308854  PMID: 28196148
23.  Standardised versus individualised multiherb Chinese herbal medicine for oligomenorrhoea and amenorrhoea in polycystic ovary syndrome: a randomised feasibility and pilot study in the UK 
BMJ Open  2017;7(2):e011709.
Objectives
To explore feasibility of a randomised study using standardised or individualised multiherb Chinese herbal medicine (CHM) for oligomenorrhoea and amenorrhoea in women with polycystic ovary syndrome (PCOS), to pilot study methods and to obtain clinical data to support sample size calculations.
Design
Prospective, pragmatic, randomised feasibility and pilot study with participant and practitioner blinding.
Setting
2 private herbal practices in the UK.
Participants
40 women diagnosed with PCOS and oligomenorrhoea or amenorrhoea following Rotterdam criteria.
Intervention
6 months of either standardised CHM or individualised CHM, 16 g daily taken orally as a tea.
Main outcome measures
Our primary objective was to determine whether oligomenorrhoea and amenorrhoea were appropriate as the primary outcome measures for the main study. Estimates of treatment effects were obtained for menstrual rate, body mass index (BMI), weight and hirsutism. Data were collected regarding safety, feasibility and acceptability.
Results
Of the 40 participants recruited, 29 (72.5%) completed the study. The most frequently cited symptoms of concern were hirsutism, weight and menstrual irregularity. Statistically significant improvements in menstrual rates were found at 6 months within group for both standardised CHM (mean difference (MD) 0.18±0.06, 95% CI 0.06 to 0.29; p=0.0027) and individualised CHM (MD 0.27±0.06, 95% CI 0.15 to 0.39; p<0.001), though not between group (p=0.26). No improvements were observed for BMI nor for weight in either group. Improvements in hirsutism scores found within group for both groups were not statistically significant between group (p=0.09). Liver and kidney function and adverse events data were largely normal. Participant feedback suggests changing to tablet administration could facilitate adherence.
Conclusions
A CHM randomised controlled trial for PCOS is feasible and preliminary data suggest that both individualised and standardised multiherb CHMs have similar safety profiles and clinical effects on promoting menstrual regularity. These data will inform the design of a study in primary care that will incorporate an appropriate control.
Trial registration number
ISRCTN 31072075; Results.
doi:10.1136/bmjopen-2016-011709
PMCID: PMC5293993  PMID: 28159846
Polycystic Ovary Syndrome; Chinese herbal medicine; Traditional Chinese Medicine; COMPLEMENTARY MEDICINE; PRIMARY CARE
24.  Sequence Type 631 Vibrio parahaemolyticus, an Emerging Foodborne Pathogen in North America 
Journal of Clinical Microbiology  2017;55(2):645-648.
doi:10.1128/JCM.02162-16
PMCID: PMC5277537  PMID: 27974540
Vibrio parahaemolyticus; core genome multilocus sequence type analysis; emerging pathogen; genomics; molecular epidemiology
25.  Human Induced Pluripotent Stem Cell-Derived Macrophages Share Ontogeny with MYB-Independent Tissue-Resident Macrophages 
Stem Cell Reports  2017;8(2):334-345.
Summary
Tissue-resident macrophages, such as microglia, Kupffer cells, and Langerhans cells, derive from Myb-independent yolk sac (YS) progenitors generated before the emergence of hematopoietic stem cells (HSCs). Myb-independent YS-derived resident macrophages self-renew locally, independently of circulating monocytes and HSCs. In contrast, adult blood monocytes, as well as infiltrating, gut, and dermal macrophages, derive from Myb-dependent HSCs. These findings are derived from the mouse, using gene knockouts and lineage tracing, but their applicability to human development has not been formally demonstrated. Here, we use human induced pluripotent stem cells (iPSCs) as a tool to model human hematopoietic development. By using a CRISPR-Cas9 knockout strategy, we show that human iPSC-derived monocytes/macrophages develop in an MYB-independent, RUNX1-, and SPI1 (PU.1)-dependent fashion. This result makes human iPSC-derived macrophages developmentally related to and a good model for MYB-independent tissue-resident macrophages, such as alveolar and kidney macrophages, microglia, Kupffer cells, and Langerhans cells.
Highlights
•Human iPSC-derived macrophages are MYB independent but RUNX1 and SPI1 dependent•Transcription factor dependence genetically uncovers ontogeny of hiPSC macrophages
Macrophages are highly plastic multifunctional immune cells that play an essential role in mammalian tissues and their dysregulation is implicated in many pathological conditions. In this article, Buchrieser and colleagues define that iPSC-derived macrophages are of the same ontogeny as mouse tissue-resident macrophages, and are MYB independent. This work lays the foundation for the generation of authentic tissue-specialized macrophage subtypes.
doi:10.1016/j.stemcr.2016.12.020
PMCID: PMC5312255  PMID: 28111278
human iPSC macrophages; MYB; RUNX1; SPI1; hematopoiesis

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