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1.  ESICM LIVES 2016: part one 
Bos, L. | Schouten, L. | van Vught, L. | Wiewel, M. | Ong, D. | Cremer, O. | Artigas, A. | Martin-Loeches, I. | Hoogendijk, A. | van der Poll, T. | Horn, J. | Juffermans, N. | Schultz, M. | de Prost, N. | Pham, T. | Carteaux, G. | Dessap, A. Mekontso | Brun-Buisson, C. | Fan, E. | Bellani, G. | Laffey, J. | Mercat, A. | Brochard, L. | Maitre, B. | Howells, P. A. | Thickett, D. R. | Knox, C. | Park, D. P. | Gao, F. | Tucker, O. | Whitehouse, T. | McAuley, D. F. | Perkins, G. D. | Pham, T. | Laffey, J. | Bellani, G. | Fan, E. | Pisani, L. | Roozeman, J. P. | Simonis, F. D. | Giangregorio, A. | Schouten, L. R. | Van der Hoeven, S. M. | Horn, J. | Neto, A. Serpa | Festic, E. | Dondorp, A. M. | Grasso, S. | Bos, L. D. | Schultz, M. J. | Koster-Brouwer, M. | Verboom, D. | Scicluna, B. | van de Groep, K. | Frencken, J. | Schultz, M. | van der Poll, T. | Bonten, M. | Cremer, O. | Ko, J. I. | Kim, K. S. | Suh, G. J. | Kwon, W. Y. | Kim, K. | Shin, J. H. | Ranzani, O. T. | Prina, E. | Menendez, R. | Ceccato, A. | Mendez, R. | Cilloniz, C. | Gabarrus, A. | Ferrer, M. | Torres, A. | Urbano, A. | Zhang, L. A. | Swigon, D. | Pike, F. | Parker, R. S. | Clermont, G. | Scheer, C. | Kuhn, S. O. | Modler, A. | Vollmer, M. | Fuchs, C. | Hahnenkamp, K. | Rehberg, S. | Gründling, M. | Taggu, A. | Darang, N. | Öveges, N. | László, I. | Tánczos, K. | Németh, M. | Lebák, G. | Tudor, B. | Érces, D. | Kaszaki, J. | Huber, W. | Trásy, D. | Molnár, Z. | Ferrara, G. | Edul, V. S. Kanoore | Canales, H. S. | Martins, E. | Canullán, C. | Murias, G. | Pozo, M. O. | Eguillor, J. F. Caminos | Buscetti, M. G. | Ince, C. | Dubin, A. | Aya, H. D. | Rhodes, A. | Fletcher, N. | Grounds, R. M. | Cecconi, M. | Jacquet-Lagrèze, M. | Riche, M. | Schweizer, R. | Portran, P. | Fornier, W. | Lilot, M. | Neidecker, J. | Fellahi, J. L. | Escoresca-Ortega, A. | Gutiérrez-Pizarraya, A. | Charris-Castro, L. | Corcia-Palomo, Y. | Fernandez-Delgado, E. | Garnacho-Montero, J. | Roger, C. | Muller, L. | Elotmani, L. | Lipman, J. | Lefrant, J. Y. | Roberts, J. A. | Muñoz-Bermúdez, R. | Samper, M. | Climent, C. | Vasco, F. | Sara, V. | Luque, S. | Campillo, N. | Cerrato, S. Grau | Masclans, J. R. | Alvarez-Lerma, F. | Brugger, S. Carvalho | Jimenez, G. Jimenez | Torner, M. Miralbés | Cabello, J. Trujillano | Garrido, B. Balsera | Casals, X. Nuvials | Gaite, F. Barcenilla | Vidal, M. Vallverdú | Martínez, M. Palomar | Gusarov, V. | Shilkin, D. | Dementienko, M. | Nesterova, E. | Lashenkova, N. | Kuzovlev, A. | Zamyatin, M. | Demoule, A. | Carreira, S. | Lavault, S. | Palancca, O. | Morawiec, E. | Mayaux, J. | Arnulf, I. | Similowski, T. | Rasmussen, B. S. | Maltesen, R. G. | Hanifa, M. | Pedersen, S. | Kristensen, S. R. | Wimmer, R. | Panigada, M. | Bassi, G. Li | Ranzani, O. T. | Kolobow, T. | Zanella, A. | Cressoni, M. | Berra, L. | Parrini, V. | Kandil, H. | Salati, G. | Livigni, S. | Amatu, A. | Andreotti, A. | Tagliaferri, F. | Moise, G. | Mercurio, G. | Costa, A. | Vezzani, A. | Lindau, S. | Babel, J. | Cavana, M. | Consonni, D. | Pesenti, A. | Gattinoni, L. | Torres, A. | Mansouri, P. | Zand, F. | Zahed, L. | Dehghanrad, F. | Bahrani, M. | Ghorbani, M. | Cambiaghi, B. | Moerer, O. | Mauri, T. | Kunze-Szikszay, N. | Ritter, C. | Pesenti, A. | Quintel, M. | Vilander, L. M. | Kaunisto, M. A. | Vaara, S. T. | Pettilä, V. | Mulier, J. L. G. Haitsma | Rozemeijer, S. | Spoelstra-de Man, A. M. E. | Elbers, P. E. | Tuinman, P. R. | de Waard, M. C. | Oudemans-van Straaten, H. M. | Liberatore, A. M. A. | Souza, R. B. | Martins, A. M. C. R. P. F. | Vieira, J. C. F. | Koh, I. H. J. | Martínez, M. Galindo | Sánchez, R. Jiménez | Gascón, L. Martínez | Mulero, M. D. Rodríguez | Freire, A. Ortín | Muñoz, A. Ojados | Acebes, S. Rebollo | Martínez, Á. Fernández | Aliaga, S. Moreno | Para, L. Herrera | Payá, J. Murcia | Mulero, F. Rodríguez | Guerci, P. | Ince, Y. | Heeman, P. | Ergin, B. | Ince, C. | Uz, Z. | Massey, M. | Ince, Y. | Papatella, R. | Bulent, E. | Guerci, P. | Toraman, F. | Ince, C. | Longbottom, E. R. | Torrance, H. D. | Owen, H. C. | Hinds, C. J. | Pearse, R. M. | O’Dywer, M. J. | Trogrlic, Z. | van der Jagt, M. | Lingsma, H. | Ponssen, H. H. | Schoonderbeek, J. F. | Schreiner, F. | Verbrugge, S. J. | Duran, S. | van Achterberg, T. | Bakker, J. | Gommers, D. A. M. P. J. | Ista, E. | Krajčová, A. | Waldauf, P. | Duška, F. | Shah, A. | Roy, N. | McKechnie, S. | Doree, C. | Fisher, S. | Stanworth, S. J. | Jensen, J. F. | Overgaard, D. | Bestle, M. H. | Christensen, D. F. | Egerod, I. | Pivkina, A. | Gusarov, V. | Zhivotneva, I. | Pasko, N. | Zamyatin, M. | Jensen, J. F. | Egerod, I. | Bestle, M. H. | Christensen, D. F. | Alklit, A. | Hansen, R. L. | Knudsen, H. | Grode, L. B. | Overgaard, D. | Hravnak, M. | Chen, L. | Dubrawski, A. | Clermont, G. | Pinsky, M. R. | Parry, S. M. | Knight, L. D. | Connolly, B. C. | Baldwin, C. E. | Puthucheary, Z. A. | Denehy, L. | Hart, N. | Morris, P. E. | Mortimore, J. | Granger, C. L. | Jensen, H. I. | Piers, R. | Van den Bulcke, B. | Malmgren, J. | Metaxa, V. | Reyners, A. K. | Darmon, M. | Rusinova, K. | Talmor, D. | Meert, A. P. | Cancelliere, L. | Zubek, L. | Maia, P. | Michalsen, A. | Decruyenaere, J. | Kompanje, E. | Vanheule, S. | Azoulay, E. | Vansteelandt, S. | Benoit, D. | Van den Bulcke, B. | Piers, R. | Jensen, H. I. | Malmgren, J. | Metaxa, V. | Reyners, A. K. | Darmon, M. | Rusinova, K. | Talmor, D. | Meert, A. P. | Cancelliere, L. | Zubek, L. | Maia, P. | Michalsen, A. | Decruyenaere, J. | Kompanje, E. | Vanheule, S. | Azoulay, E. | Vansteelandt, S. | Benoit, D. | Ryan, C. | Dawson, D. | Ball, J. | Noone, K. | Aisling, B. | Prudden, S. | Ntantana, A. | Matamis, D. | Savvidou, S. | Giannakou, M. | Gouva, M. | Nakos, G. | Koulouras, V. | Aron, J. | Lumley, G. | Milliken, D. | Dhadwal, K. | McGrath, B. A. | Lynch, S. J. | Bovento, B. | Sharpe, G. | Grainger, E. | Pieri-Davies, S. | Wallace, S. | McGrath, B. | Lynch, S. J. | Bovento, B. | Grainger, E. | Pieri-Davies, S. | Sharpe, G. | Wallace, S. | Jung, M. | Cho, J. | Park, H. | Suh, G. | Kousha, O. | Paddle, J. | Gripenberg, L. Gamrin | Rehal, M. Sundström | Wernerman, J. | Rooyackers, O. | de Grooth, H. J. | Choo, W. P. | Spoelstra-de Man, A. M. | Swart, E. L. | Oudemans-van Straaten, H. M. | Talan, L. | Güven, G. | Altıntas, N. D. | Padar, M. | Uusvel, G. | Starkopf, L. | Starkopf, J. | Blaser, A. Reintam | Kalaiselvan, M. S. | Arunkumar, A. S. | Renuka, M. K. | Shivkumar, R. L. | Volbeda, M. | ten Kate, D. | Hoekstra, M. | van der Maaten, J. M. | Nijsten, M. W. | Komaromi, A. | Rooyackers, O. | Wernerman, J. | Norberg, Å. | Smedberg, M. | Mori, M. | Pettersson, L. | Norberg, Å. | Rooyackers, O. | Wernerman, J. | Theodorakopoulou, M. | Christodoulopoulou, T. | Diamantakis, A. | Frantzeskaki, F. | Kontogiorgi, M. | Chrysanthopoulou, E. | Lygnos, M. | Diakaki, C. | Armaganidis, A. | Gundogan, K. | Dogan, E. | Coskun, R. | Muhtaroglu, S. | Sungur, M. | Ziegler, T. | Guven, M. | Kleyman, A. | Khaliq, W. | Andreas, D. | Singer, M. | Meierhans, R. | Schuepbach, R. | De Brito-Ashurst, I. | Zand, F. | Sabetian, G. | Nikandish, R. | Hagar, F. | Masjedi, M. | Maghsudi, B. | Vazin, A. | Ghorbani, M. | Asadpour, E. | Kao, K. C. | Chiu, L. C. | Hung, C. Y. | Chang, C. H. | Li, S. H. | Hu, H. C. | El Maraghi, S. | Ali, M. | Rageb, D. | Helmy, M. | Marin-Corral, J. | Vilà, C. | Masclans, J. R. | Vàzquez, A. | Martín-Loeches, I. | Díaz, E. | Yébenes, J. C. | Rodriguez, A. | Álvarez-Lerma, F. | Varga, N. | Cortina-Gutiérrez, A. | Dono, L. | Martínez-Martínez, M. | Maldonado, C. | Papiol, E. | Pérez-Carrasco, M. | Ferrer, R. | Nweze, K. | Morton, B. | Welters, I. | Houard, M. | Voisin, B. | Ledoux, G. | Six, S. | Jaillette, E. | Nseir, S. | Romdhani, S. | Bouneb, R. | Loghmari, D. | Aicha, N. Ben | Ayachi, J. | Meddeb, K. | Chouchène, I. | Khedher, A. | Boussarsar, M. | Chan, K. S. | Yu, W. L. | Marin-Corral, J. | Vilà, C. | Masclans, J. R. | Nolla, J. | Vidaur, L. | Bonastre, J. | Suberbiola, B. | Guerrero, J. E. | Rodriguez, A. | Coll, N. Ramon | Jiménez, G. Jiménez | Brugger, S. Carvalho | Calero, J. Codina | Garrido, B. Balsera | García, M. | Martínez, M. Palomar | Vidal, M. Vallverdú | de la Torre, M. C. | Vendrell, E. | Palomera, E. | Güell, E. | Yébenes, J. C. | Serra-Prat, M. | Bermejo-Martín, J. F. | Almirall, J. | Tomas, E. | Escoval, A. | Froe, F. | Pereira, M. H. Vitoria | Velez, N. | Viegas, E. | Filipe, E. | Groves, C. | Reay, M. | Chiu, L. C. | Hu, H. C. | Hung, C. Y. | Chang, C. H. | Li, S. H. | Kao, K. C. | Ballin, A. | Facchin, F. | Sartori, G. | Zarantonello, F. | Campello, E. | Radu, C. M. | Rossi, S. | Ori, C. | Simioni, P. | Umei, N. | Shingo, I. | Santos, A. C. | Candeias, C. | Moniz, I. | Marçal, R. | e Silva, Z. Costa | Ribeiro, J. M. | Georger, J. F. | Ponthus, J. P. | Tchir, M. | Amilien, V. | Ayoub, M. | Barsam, E. | Martucci, G. | Panarello, G. | Tuzzolino, F. | Capitanio, G. | Ferrazza, V. | Carollo, T. | Giovanni, L. | Arcadipane, A. | Sánchez, M. López | González-Gay, M. A. | Díaz, F. J. Llorca | López, M. I. Rubio | Zogheib, E. | Villeret, L. | Nader, J. | Bernasinski, M. | Besserve, P. | Caus, T. | Dupont, H. | Morimont, P. | Habran, S. | Hubert, R. | Desaive, T. | Blaffart, F. | Janssen, N. | Guiot, J. | Pironet, A. | Dauby, P. | Lambermont, B. | Zarantonello, F. | Ballin, A. | Facchin, F. | Sartori, G. | Campello, E. | Pettenuzzo, T. | Citton, G. | Rossi, S. | Simioni, P. | Ori, C. | Kirakli, C. | Ediboglu, O. | Ataman, S. | Yarici, M. | Tuksavul, F. | Keating, S. | Gibson, A. | Gilles, M. | Dunn, M. | Price, G. | Young, N. | Remeta, P. | Bishop, P. | Zamora, M. D. Fernández | Muñoz-Bono, J. | Curiel-Balsera, E. | Aguilar-Alonso, E. | Hinojosa, R. | Gordillo-Brenes, A. | Arboleda-Sánchez, J. A. | Skorniakov, I. | Vikulova, D. | Whiteley, C. | Shaikh, O. | Jones, A. | Ostermann, M. | Forni, L. | Scott, M. | Sahatjian, J. | Linde-Zwirble, W. | Hansell, D. | Laoveeravat, P. | Srisawat, N. | Kongwibulwut, M. | Peerapornrattana, S. | Suwachittanont, N. | Wirotwan, T. O. | Chatkaew, P. | Saeyub, P. | Latthaprecha, K. | Tiranathanagul, K. | Eiam-ong, S. | Kellum, J. A. | Berthelsen, R. E. | Perner, A. | Jensen, A. E. K. | Jensen, J. U. | Bestle, M. H. | Gebhard, D. J. | Price, J. | Kennedy, C. E. | Akcan-Arikan, A. | Liberatore, A. M. A. | Souza, R. B. | Martins, A. M. C. R. P. F. | Vieira, J. C. F. | Kang, Y. R. | Nakamae, M. N. | Koh, I. H. J. | Hamed, K. | Khaled, M. M. | Soliman, R. Aly | Mokhtar, M. Sherif | Seller-Pérez, G. | Arias-Verdú, D. | Llopar-Valdor, E. | De-Diós-Chacón, I. | Quesada-García, G. | Herrera-Gutierrez, M. E. | Hafes, R. | Carroll, G. | Doherty, P. | Wright, C. | Vera, I. G. Guerra | Ralston, M. | Gemmell, M. L. | MacKay, A. | Black, E. | Wright, C. | Docking, R. I. | Appleton, R. | Ralston, M. R. | Gemmell, L. | Appleton, R. | Wright, C. | Docking, R. I. | Black, E. | Mackay, A. | Rozemeijer, S. | Mulier, J. L. G. Haitsma | Röttgering, J. G. | Elbers, P. W. G. | Spoelstra-de Man, A. M. E. | Tuinman, P. R. | de Waard, M. C. | Oudemans-van Straaten, H. M. | Mejeni, N. | Nsiala, J. | Kilembe, A. | Akilimali, P. | Thomas, G. | Egerod, I. | Andersson, A. E. | Fagerdahl, A. M. | Knudsen, V. | Meddeb, K. | Cheikh, A. Ben | Hamdaoui, Y. | Ayachi, J. | Guiga, A. | Fraj, N. | Romdhani, S. | Sma, N. | Bouneb, R. | Chouchene, I. | Khedher, A. | Bouafia, N. | Boussarsar, M. | Amirian, A. | Ziaian, B. | Masjedi, M. | Fleischmann, C. | Thomas-Rueddel, D. O. | Schettler, A. | Schwarzkopf, D. | Stacke, A. | Reinhart, K. | Filipe, E. | Escoval, A. | Martins, A. | Sousa, P. | Velez, N. | Viegas, E. | Tomas, E. | Snell, G. | Matsa, R. | Paary, T. T. S. | Kalaiselvan, M. S. | Cavalheiro, A. M. | Rocha, L. L. | Vallone, C. S. | Tonilo, A. | Lobato, M. D. S. | Malheiro, D. T. | Sussumo, G. | Lucino, N. M. | Zand, F. | Rosenthal, V. D. | Masjedi, M. | Sabetian, G. | Maghsudi, B. | Ghorbani, M. | Dashti, A. Sanaei | Yousefipour, A. | Goodall, J. R. | Williamson, M. | Tant, E. | Thomas, N. | Balci, C. | Gonen, C. | Haftacı, E. | Gurarda, H. | Karaca, E. | Paldusová, B. | Zýková, I. | Šímová, D. | Houston, S. | D’Antona, L. | Lloyd, J. | Garnelo-Rey, V. | Sosic, M. | Sotosek-Tokmazic, V. | Kuharic, J. | Antoncic, I. | Dunatov, S. | Sustic, A. | Chong, C. T. | Sim, M. | Lyovarin, T. | Díaz, F. M. Acosta | Galdó, S. Narbona | Garach, M. Muñoz | Romero, O. Moreno | Bailón, A. M. Pérez | Pinel, A. Carranza | Colmenero, M. | Gritsan, A. | Gazenkampf, A. | Korchagin, E. | Dovbish, N. | Lee, R. M. | Lim, M. P. P. | Chong, C. T. | Lim, B. C. L. | See, J. J. | Assis, R. | Filipe, F. | Lopes, N. | Pessoa, L. | Pereira, T. | Catorze, N. | Aydogan, M. S. | Aldasoro, C. | Marchio, P. | Jorda, A. | Mauricio, M. D. | Guerra-Ojeda, S. | Gimeno-Raga, M. | Colque-Cano, M. | Bertomeu-Artecero, A. | Aldasoro, M. | Valles, S. L. | Tonon, D. | Triglia, T. | Martin, J. C. | Alessi, M. 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Y. | Na, S. | Kim, J. | Chang, Y. F. | Chao, A. | Shih, P. Y. | Lee, C. T. | Yeh, Y. C. | Chen, L. W. | Adriaanse, M. | Trogrlic, Z. | Ista, E. | Lingsma, H. | Rietdijk, W. | Ponssen, H. H. | Schoonderbeek, J. F. | Schreiner, F. | Verbrugge, S. J. | Duran, S. | Gommers, D. A. M. P. J. | van der Jagt, M. | Funcke, S. | Sauerlaender, S. | Saugel, B. | Pinnschmidt, H. | Reuter, D. A. | Nitzschke, R. | Perbet, S. | Biboulet, C. | Lenoire, A. | Bourdeaux, D. | Pereira, B. | Plaud, B. | Bazin, J. E. | Sautou, V. | Mebazaa, A. | Constantin, J. M. | Legrand, M. | Boyko, Y. | Jennum, P. | Nikolic, M. | Oerding, H. | Holst, R.
doi:10.1186/s40635-016-0098-x
PMCID: PMC5042924
2.  Non-Market Values in a Cost-Benefit World: Evidence from a Choice Experiment 
PLoS ONE  2016;11(10):e0165365.
In support of natural resource and ecosystem service policy, monetary value estimates are often presented to decision makers along with other types of information. There is some evidence that, presented with such ‘mixed’ information, people prioritise monetary over non-monetary information. We conduct a discrete choice experiment among New Zealand decision makers in which we manipulate the information presented to participants. We find that providing explicit monetary information strengthens the pursuit of economic benefits as well as the avoidance of environmental damage. Cultural impacts, of which we provided only qualitative descriptions, did not affect respondents’ choices. Our study provides further evidence that concerns regarding the use of monetary information in decisions with complex, multi-value impacts are valid. Further research is needed to validate our results and find ways to reduce any bias in monetary and non-market information.
doi:10.1371/journal.pone.0165365
PMCID: PMC5082611  PMID: 27783657
3.  ESICM LIVES 2016: part two 
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C. | Mittal, S. | Rao, B. K. | Ayachi, J. | Fraj, N. | Romdhani, S. | Khedher, A. | Meddeb, K. | Sma, N. | Azouzi, A. | Bouneb, R. | Chouchene, I. | El Ghardallou, M. | Boussarsar, M. | Jennings, R. | Walter, E. | Ribeiro, J. M. | Moniz, I. | Marçal, R. | Santos, A. C. | Candeias, C. | e Silva, Z. Costa | Gomez, S. E. Zamora | Nieto, O. R. Perez | Gonzalez, J. A. Castanon | Cuellar, A. I. Vasquez | Mildh, H. | Pettilä, V. | Korhonen, A. M. | Karlsson, S. | Ala-Kokko, T. | Reinikainen, M. | Vaara, S. T. | Zaleska-Kociecka, M. | Grabowski, M. | Dąbrowski, M. | Wozniak, S. | Piotrowska, K. | Banaszewski, M. | Imiela, J. | Stepinska, J. | Pérez, A. González
doi:10.1186/s40635-016-0099-9
PMCID: PMC5042923
4.  Study protocol for an evaluation of the effectiveness of ‘care bundles’ as a means of improving hospital care and reducing hospital readmission for patients with chronic obstructive pulmonary disease (COPD) 
Background
Chronic Obstructive Pulmonary Disease is one of the commonest respiratory diseases in the United Kingdom, accounting for 10 % of unplanned hospital admissions each year. Nearly a third of these admitted patients are re-admitted to hospital within 28 days of discharge. Whilst there is a move within the NHS to ensure that people with long-term conditions receive more co-ordinated care, there is little research evidence to support an optimum approach to this in COPD. This study aims to evaluate the effectiveness of introducing standardised packages of care i.e. care bundles, for patients with acute exacerbations of COPD as a means of improving hospital care and reducing re-admissions.
Methods / Design
This mixed-methods evaluation will use a controlled before-and-after design to examine the effect of, and costs associated with, implementing care bundles for patients admitted to hospital with an acute exacerbation of COPD, compared with usual care. It will quantitatively measure a range of patient and organisational outcomes for two groups of hospitals - those who deliver care using COPD care bundles, and those who deliver care without the use of COPD care bundles. These care bundles may be provided for patients with COPD following admission, prior to discharge or at both points in the care pathway. The primary outcome will be re-admission to hospital within 28 days of discharge, although the study will additionally investigate a number of secondary outcomes including length of stay, total bed days, in-hospital mortality, costs of care and patient / carer experience. A series of nested qualitative case studies will explore in detail the context and process of care as well as the impact of COPD bundles on staff, patients and carers.
Discussion
The results of the study will provide information about the effectiveness of care bundles as a way of managing in-hospital care for patients with an acute exacerbation of COPD. Given the number of unplanned hospital admissions for this patient group and their rate of subsequent re-admission, it is hoped that this evaluation will make a timely contribution to the evidence on care provision, to the benefit of patients, clinicians, managers and policy-makers.
Trial registration
International Standard Randomised Controlled Trials – ISRCTN13022442 - 11 February 2015
doi:10.1186/s12890-016-0197-1
PMCID: PMC4766609  PMID: 26916196
COPD; Care bundles; Delivery of care; Quality improvement; Admission avoidance
5.  Polymorphisms in MIR137HG and microRNA-137-regulated genes influence gray matter structure in schizophrenia 
Translational Psychiatry  2016;6(2):e724-.
Evidence suggests that microRNA-137 (miR-137) is involved in the genetic basis of schizophrenia. Risk variants within the miR-137 host gene (MIR137HG) influence structural and functional brain-imaging measures, and miR-137 itself is predicted to regulate hundreds of genes. We evaluated the influence of a MIR137HG risk variant (rs1625579) in combination with variants in miR-137-regulated genes TCF4, PTGS2, MAPK1 and MAPK3 on gray matter concentration (GMC). These genes were selected based on our previous work assessing schizophrenia risk within possible miR-137-regulated gene sets using the same cohort of subjects. A genetic risk score (GRS) was determined based on genotypes of these four schizophrenia risk-associated genes in 221 Caucasian subjects (89 schizophrenia patients and 132 controls). The effects of the rs1625579 genotype with the GRS of miR-137-regulated genes in a three-way interaction with diagnosis on GMC patterns were assessed using a multivariate analysis. We found that schizophrenia subjects homozygous for the MIR137HG risk allele show significant decreases in occipital, parietal and temporal lobe GMC with increasing miR-137-regulated GRS, whereas those carrying the protective minor allele show significant increases in GMC with GRS. No correlations of GMC and GRS were found in control subjects. Variants within or upstream of genes regulated by miR-137 in combination with the MIR137HG risk variant may influence GMC in schizophrenia-related regions in patients. Given that the genes evaluated here are involved in protein kinase A signaling, dysregulation of this pathway through alterations in miR-137 biogenesis may underlie the gray matter loss seen in the disease.
doi:10.1038/tp.2015.211
PMCID: PMC4872419  PMID: 26836412
6.  Critical role of NKT Cells in Posttransplant Alloantibody Production 
We previously reported that posttransplant alloantibody production in CD8-deficient hosts is IL-4+CD4+ T cell-dependent and IgG1 isotype-dominant. The current studies investigated the hypothesis that IL-4-producing NKT cells contribute to maximal alloantibody production. To investigate this, alloantibody levels were examined in CD8-deficient wild-type, CD1d KO and Jα18 KO transplant recipients. We found that the magnitude of IgG1 alloantibody production was critically dependent on the presence of type I NKT cells, which are activated by day 1 posttransplant. Unexpectedly, type I NKT cell contribution to enhanced IgG1 alloantibody levels was IFN-γ-dependent and IL-4-independent. Cognate interactions between Type I NKT and B cells alone do not stimulate alloantibody production. Instead, NKT cells appear to enhance maturation of IL-4+CD4+ T cells. To our knowledge, this is the first report to substantiate a critical role for type I NKT cells in enhancing in vivo antibody production in response to endogenous antigenic stimuli.
doi:10.1111/ajt.12922
PMCID: PMC4207222  PMID: 25220596
7.  A cluster randomised controlled trial to investigate the effectiveness and cost effectiveness of the ‘Girls Active’ intervention: a study protocol 
BMC Public Health  2015;15:526.
Background
Despite the health benefits of physical activity, data from the UK suggest that a large proportion of adolescents do not meet the recommended levels of moderate-to-vigorous physical activity (MVPA). This is particularly evident in girls, who are less active than boys across all ages and may display a faster rate of decline in physical activity throughout adolescence. The ‘Girls Active’ intervention has been designed by the Youth Sport Trust to target the lower participation rates observed in adolescent girls. ‘Girls Active’ uses peer leadership and marketing to empower girls to influence decision making in their school, develop as role models and promote physical activity to other girls. Schools are provided with training and resources to review their physical activity, sport and PE provision, culture and practices to ensure they are relevant and attractive to adolescent girls.
Methods/Design
This study is a two-arm cluster randomised controlled trial (RCT) aiming to recruit 20 secondary schools. Clusters will be randomised at the school level (stratified by school size and proportion of Black and Minority Ethnic (BME) pupils) to receive either the ‘Girls Active’ intervention or carry on with usual practice (1:1). The 20 secondary schools will be recruited from state secondary schools within the Midlands area. We aim to recruit 80 girls aged 11–14 years in each school. Data will be collected at three time points; baseline and seven and 14 months after baseline. Our primary aim is to investigate whether ‘Girls Active’ leads to higher objectively measured (GENEActiv) moderate-to-vigorous physical activity in adolescent girls at 14 months after baseline assessment compared to the control group. Secondary outcomes include other objectively measured physical activity variables, adiposity, physical activity-related psychological factors and the cost-effectiveness of the ‘Girls Active’ intervention. A thorough process evaluation will be conducted during the course of the intervention delivery.
Discussion
The findings of this study will provide valuable information on whether this type of school-based approach to increasing physical activity in adolescent girls is both effective and cost-effective in the UK.
Trial registration
ISRCTN10688342. Registered 12 January 2015.
doi:10.1186/s12889-015-1886-z
PMCID: PMC4453020  PMID: 26036965
Physical activity; Peers; Accelerometer; Adolescent; Girls; Intervention; Cost-effectiveness
8.  Comparison of Ordinal vs. Agatston Coronary Calcification Scoring for Cardiovascular Disease Mortality in Community-Living Individuals 
Objective
Coronary artery calcification (CAC) by the Agatston method predicts cardiovascular disease (CVD), but requires cardiac gated computed tomography (CT) scans, a procedure not covered by most insurance providers. An ordinal CAC score (scored 0-12 based on artery number and extent of calcification involvement) can be measured on standard chest CTs. However, the correlation of ordinal and Agatston CAC scores and the relative association with CVD mortality is uncertain, which we sought to determine.
Design
Nested case-control study
Setting
Community-living individuals undergoing “whole body” CT scans for preventive medicine.
Patients
4,544 consecutive patients with CT scans, were followed from 2000-2009. We selected cases who died of CVD (n=57) and age, sex, and CT slice-thickness matched each to 3 controls (N=171).
Interventions
Cardiac gated 3mm chest CTs and non-gated 6mm standard chest CTs.
Main outcome
CVD death over 9 years follow-up.
Results
The intra- and inter-reader kappa for the ordinal CAC score was 0.90 and 0.76 respectively. The correlation of Agatston and ordinal CAC scores was 0.72 (p< 0.001). In models adjusted for traditional CVD risk factors, the odds of CVD death per 1 SD greater CAC was 1.66 (1.03-2.68) using the ordinal CAC score and 1.57 (1.00-2.46) using the Agatston score.
Conclusions
A simple ordinal CAC score is reproducible, strongly correlated with Agatston CAC scores, and provides similar prediction for CVD death in predominantly Caucasian community-living individuals.
doi:10.1007/s10554-014-0392-1
PMCID: PMC4009350  PMID: 24610090
calcium; cardiovascular diseases; circulation; imaging; epidemiology
9.  Perivascular Spaces Are Associated with Atherosclerosis: An Insight from the Northern Manhattan Study 
Background and Purpose
Perivascular spaces are potential spaces found between brain blood vessels and surrounding leptomeninges that have been associated with cardiovascular risk factors and dementia, but less is known about their relationship to atherosclerosis. We tested the hypothesis that perivascular spaces are associated with atherosclerosis.
Materials and Methods
Participants from the Northern Manhattan Study who remained stroke-free were invited to participate in an MR imaging substudy. Parenchymal hypointensities of <3 mm identified on brain axial T1-weighted MR imaging were scored as perivascular spaces. A semiquantitative score was created to express the degree of brain involvement. Generalized linear models were used to assess statistical associations with carotid plaque as a surrogate marker of atherosclerosis.
Results
The studied sample included 706 participants (mean age, 72.6 ±8.0 years; 60% women, 61% Hispanic, 68% with hypertension, 19% with diabetes, and 57% with high cholesterol). The perivascular spaces score ranged from 0 to 19 with 52% of the sample having a perivascular spaces score of ≤4. In unadjusted analysis, perivascular spaces were associated with age (β = 0.01 per year, P = <.001), non-Hispanic black race-ethnicity (β = 0.16, P = .02), hypertension (β = 0.24, P = <.001), and carotid plaque (β = 0.22, P < .001). In multivariable analysis, only age (β = 0.01, P = .02), hypertension (β = 0.17, P = .01), and carotid plaque (β = 0.22, P = < .001) remained independently associated with perivascular spaces.
Conclusions
Perivascular spaces were more frequently found in older participants, in those with hypertension, and in the presence of carotid plaque. These results suggest that mechanisms leading to atherosclerosis might also lead to an increased number of perivascular spaces. These results need confirmation in prospective studies.
doi:10.3174/ajnr.A3498
PMCID: PMC4380264  PMID: 23557952
10.  Evidence-based development of a post-surgical lumbar discectomy leaflet intervention: a Delphi consensus study 
BMJ Open  2015;5(3):e006069.
Objective
To produce free, expert-informed postoperative information for lumbar discectomy patients, satisfying UK National Health Service Information Standards.
Design
A mixed methods approach utilising the Delphi technique and focus groups.
Setting
Five spinal centres across the UK.
Participants
Panel members included 23 physiotherapists, 11 patients and 17 spinal surgeons.
Intervention
Three rounds of questionnaires including open and closed questions and attendance at a clinician/patient focus group.
Results
Response rates of 85%, 26% and 35% were achieved for the Delphi rounds. Ten clinicians and six patients participated in the focus groups. Consensus for leaflet sections was achieved in round 1 and content in round 3. The focus groups informed further revisions.
Conclusions
A consensually agreed, Information Standard compliant, patient lumbar discectomy leaflet was produced containing: (1) normal spine anatomy; (2) anatomy disc herniation and surgery; (3) back protection strategies and (4) frequently asked questions. Illustrations of exercises enable tailoring to the individual patient.
doi:10.1136/bmjopen-2014-006069
PMCID: PMC4360785  PMID: 25762227
REHABILITATION MEDICINE
11.  Pre-B cell colony enhancing factor (PBEF/NAMPT/Visfatin) and vascular endothelial growth factor (VEGF) cooperate to increase the permeability of the human placental amnion 
Placenta  2012;34(1):42-49.
Fluid efflux across the region of the amnion overlying the placenta is an essential component of the intramembranous absorption pathway that maintains amniotic fluid volume homeostasis. Dysregulation of this pathway may result in adverse pregnancy outcomes, however the factors controlling amnion permeability are unknown. Here, we report a novel mechanism that increases placental amnion permeability. Pre-B Cell Colony Enhancing Factor (PBEF) is a stress-responsive cytokine expressed by the human amnion, and is known to induce Vascular Endothelial Growth Factor (VEGF) production by other cell types. Interestingly, VEGF is up-regulated in the ovine amnion when intramembranous absorption is augmented. In this study, we show that PBEF induced VEGF secretion by primary human amniotic epithelial cells (AEC) derived from the placental amnion, as well as from the reflected amnion that lines the remainder of the gestational sac. Further, PBEF treatment led to the increased expression of VEGFR2 in placental AEC, but not reflected AEC. To test the hypothesis that PBEF and VEGF increase placental amnion permeability, we monitored the transfer of 2′,7′-dichlorofluorescein (DCF) from the fetal to the maternal side of human amnion explants. A treatment regimen including both PBEF and VEGF increased the rate of DCF transfer across the placental amnion, but not the reflected amnion. In summary, our results suggest that by augmenting VEGFR2 expression in the placental amnion, PBEF primes the tissue for a VEGF-mediated increase in permeability. This mechanism may have important implications in amniotic fluid volume control throughout gestation.
doi:10.1016/j.placenta.2012.10.008
PMCID: PMC3541826  PMID: 23151382
Pre-B cell colony enhancing factor (PBEF); Visfatin; Nicotinamide phosphoribosyltransferase (NAMPT); Vascular endothelial growth factor (VEGF); Amnion; Permeability
12.  Observation of T2-like coherent optical phonons in epitaxial Ge2Sb2Te5/GaSb(001) films 
Scientific Reports  2013;3:2965.
The phonon spectrum of Ge2Sb2Te5 is a signature of its crystallographic structure and underlies the phase transition process used in memory applications. Epitaxial materials allow coherent optical phonons to be studied in femtosecond anisotropic reflectance measurements. A dominant phonon mode with frequency of 3.4 THz has been observed in epitaxial Ge2Sb2Te5 grown on GaSb(001). The dependence of signal strength upon pump and probe polarization is described by a theory of transient stimulated Raman scattering that accounts for the symmetry of the crystallographic structure through use of the Raman tensor. The 3.4 THz mode has the character of the 3 dimensional T2 mode expected for the Oh point group, confirming that the underlying crystallographic structure is cubic. New modes are observed in both Ge2Sb2Te5 and GaSb after application of large pump fluences, and are interpreted as 1 and 2 dimensional modes associated with segregation of Sb.
doi:10.1038/srep02965
PMCID: PMC3797426  PMID: 24129388
13.  Mirrored pyramidal wells for simultaneous multiple vantage point microscopy 
Journal of microscopy  2008;232(1):1-6.
Summary
We report a novel method for obtaining simultaneous images from multiple vantage points of a microscopic specimen using size-matched microscopic mirrors created from anisotropically etched silicon. The resulting pyramidal wells enable bright-field and fluorescent side-view images, and when combined with z-sectioning, provide additional information for 3D reconstructions of the specimen. We have demonstrated the 3D localization and tracking over time of the centrosome of a live Dictyostelium discoideum. The simultaneous acquisition of images from multiple perspectives also provides a five-fold increase in the theoretical collection efficiency of emitted photons, a property which may be useful for low-light imaging modalities such as bioluminescence, or low abundance surface-marker labelling.
doi:10.1111/j.1365-2818.2008.02110.x
PMCID: PMC3789065  PMID: 19017196
Confocal microscopy; fluorescence microscopy; PSF; tilted views; 3D microscopy; 3D reconstruction
14.  Influence of Patients’ Coronary Artery Calcium on Subsequent Medication Use Patterns 
Objectives
To determine whether information on the presence and extent of coronary artery calcium (CAC) is associated with the likelihood of physicians’ prescribing preventive therapies.
Method
In a longitudinal design, asymptomatic participants (N=510) were evaluated by computed tomography for CAC. Changes to medications were at the discretion of the patient’s primary care provider, who received the CT report.
Results
In multivariable analysis, the likelihood of patients reporting that their primary care physician prescribed preventive therapies was significantly associated with the presence and extent of CAC.
Conclusions
This study suggests that physicians’ prescribing practices are influenced by patients’ CAC scores obtained via CT.
doi:10.5993/AJHB.36.5.5
PMCID: PMC3753401  PMID: 22584090
coronary calcium; computed tomography; physician prescribing practices; preventive therapies
15.  Cajachalcone: An Antimalarial Compound from Cajanus cajan Leaf Extract 
Cajanus cajan L, a member of the family Fabaceae, was identified from the Nigerian antimalarial ethnobotany as possessing antimalarial properties. The bioassay-guided fractionation of the crude methanol extract of C. cajan leaves was done in vitro using the multiresistant strain of Plasmodium falciparum (K1) in the parasite lactate dehydrogenase assay. Isolation of compound was achieved by a combination of chromatographic techniques, while the structure of the compound was elucidated by spectroscopy. This led to the identification of a cajachalcone, 2′,6′-dihydroxy-4-methoxy chalcone, as the biologically active constituent from the ethyl acetate fraction. Cajachalcone had an IC50 value of 2.0 μg/mL (7.4 μM) and could be a lead for anti-malarial drug discovery.
doi:10.1155/2013/703781
PMCID: PMC3732606  PMID: 23970954
16.  DNA Sequencing Research Group (DSRG): Evaluation of RNA Amplification Kits at Subnanogram Input Amounts of Total RNA for RNA-Seq 
Multiple recent publications on RNA-Seq have demonstrated the power of next generation sequencing technologies in whole transcriptome analysis. The vendor specific protocols used for RNA library construction typically require at least 100ng of total RNA. However, under certain conditions such as single cells, stem cells, difficult to isolate cell types, or fractionated cancer cells, only a small amount of material is available. In these cases, effective transcriptome profiling requires amplification of subnanogram amounts of RNA. Several RNA amplification kits are available for amplification prior to library construction and next generation sequencing but these kits have not been comprehensively field evaluated for accuracy and performance of RNA-Seq for picogram amounts of RNA.
This study conducted by the DNA Sequencing Research Group (DSRG) focuses on the evaluation of amplification kits for RNA-Seq. Four commercial amplification kits were chosen: Ovation v2 (NuGEN Technologies), SMARTer (Clontech), Seqplex (Sigma Aldrich), and Super-AMP (Miltenyi Biotech). Starting material was 5ng, 500pg and 50pg of human total reference RNA (Clontech) spiked with Ambion ERCC control mix (Life Technologies) following the manufacturer's protocol. Each kit was tested at 3 different sites to assess reproducibility. Total RNA and ERCC RNA spike-in control mixes from the same lots were sent to 12 ABRF lab sites for amplification and cDNA generation. Ideally, this would have resulted in 36 different amplified samples, 3 from each input RNA. Libraries were constructed at one site from the amplified cDNAs using the TruSeq RNA library preparation kit on the Tecan Freedom EVO Liquid Handling Robot. As an unamplified control, ribosomal depletion and PolyA selection were performed separately using 5ng, 100ng and 1ug of total RNA prior to library construction. All libraries were pooled and sequenced using the Illumina HiSeq platform. An overview of the study and the results will be presented.
PMCID: PMC3635359
17.  Comparing the performance of six human papillomavirus tests in a screening population 
British Journal of Cancer  2013;108(4):908-913.
Background:
Several new assays have been developed for high-risk HPV testing of cervical samples; we compare six HPV tests in a screening population.
Methods:
Residual material from liquid-based PreservCyt samples was assayed. Four tests (Hybrid Capture 2, Cobas, Abbott and Becton-Dickinson (BD)) measured HPV DNA while two used RNA (APTIMA and NorChip).
Results:
Positivity rates ranged from 13.4 to 16.3% for the DNA-based tests with a significantly lower positivity rate for the Abbott assay. The Gen-Probe APTIMA assay was positive in 10.3% of women, which was significantly lower than all the DNA tests; the NorChip PreTect HPV-Proofer test was much lower at 5.2%. 40 CIN2+ cases were identified, of which 19 were CIN3+. All CIN3+ cases were HPV positive by all tests except for one, which was negative by the Abbott assay and five which were negative by the NorChip test.
Conclusion:
All HPV tests except NorChip showed high sensitivity for high-grade lesions positive by cytology, suggesting co-testing is unnecessary when using HPV tests. Positivity rates in cytology-negative specimens were similar for the DNA-based tests, but lower for the APTIMA test suggesting this maintains the high sensitivity of DNA tests, but with better specificity.
doi:10.1038/bjc.2013.22
PMCID: PMC3590662  PMID: 23370211
biomarkers; cervix; HPV
18.  Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice 
Annals of Oncology  2011;22(12):2616-2624.
Background: Personalizing non-small-cell lung cancer (NSCLC) therapy toward oncogene addicted pathway inhibition is effective. Hence, the ability to determine a more comprehensive genotype for each case is becoming essential to optimal cancer care.
Methods: We developed a multiplexed PCR-based assay (SNaPshot) to simultaneously identify >50 mutations in several key NSCLC genes. SNaPshot and FISH for ALK translocations were integrated into routine practice as Clinical Laboratory Improvement Amendments-certified tests. Here, we present analyses of the first 589 patients referred for genotyping.
Results: Pathologic prescreening identified 552 (95%) tumors with sufficient tissue for SNaPshot; 51% had ≥1 mutation identified, most commonly in KRAS (24%), EGFR (13%), PIK3CA (4%) and translocations involving ALK (5%). Unanticipated mutations were observed at lower frequencies in IDH and β-catenin. We observed several associations between genotypes and clinical characteristics, including increased PIK3CA mutations in squamous cell cancers. Genotyping distinguished multiple primary cancers from metastatic disease and steered 78 (22%) of the 353 patients with advanced disease toward a genotype-directed targeted therapy.
Conclusions: Broad genotyping can be efficiently incorporated into an NSCLC clinic and has great utility in influencing treatment decisions and directing patients toward relevant clinical trials. As more targeted therapies are developed, such multiplexed molecular testing will become a standard part of practice.
doi:10.1093/annonc/mdr489
PMCID: PMC3493130  PMID: 22071650
carcinoma; non-small cell; genotype; molecular targeted therapy
19.  Lower prevalence of silent brain infarcts in the physically active 
Neurology  2011;76(24):2112-2118.
Objective:
To examine the independent association between physical activity and subclinical cerebrovascular disease as measured by silent brain infarcts (SBI) and white matter hyperintensity volume (WMHV).
Methods:
The Northern Manhattan Study (NOMAS) is a population-based prospective cohort examining risk factors for incident vascular disease, and a subsample underwent brain MRI. Our primary outcomes were SBI and WMHV. Baseline measures of leisure-time physical activity were collected in person. Physical activity was categorized by quartiles of the metabolic equivalent (MET) score. We used logistic regression models to examine the associations between physical activity and SBI, and linear regression to examine the association with WMHV.
Results:
There were 1,238 clinically stroke-free participants (mean age 70 ± 9 years) of whom 60% were women, 65% were Hispanic, and 43% reported no physical activity. A total of 197 (16%) participants had SBI. In fully adjusted models, compared to those who did not engage in physical activity, those in the upper quartile of MET scores were almost half as likely to have SBI (adjusted odds ratio 0.6, 95% confidence interval 0.4–0.9). Physical activity was not associated with WMHV.
Conclusions:
Increased levels of physical activity were associated with a lower risk of SBI but not WMHV. Engaging in moderate to heavy physical activities may be an important component of prevention strategies aimed at reducing subclinical brain infarcts.
doi:10.1212/WNL.0b013e31821f4472
PMCID: PMC3111237  PMID: 21653889
21.  Intensity-modulated radiotherapy increases dose to the brachial plexus compared with conventional radiotherapy for head and neck cancer 
The British Journal of Radiology  2011;84(997):58-63.
Objective
The preferential use of intensity-modulated radiotherapy (IMRT) over conventional radiotherapy (CRT) in the treatment of head and neck cancer has raised concerns regarding dose to non-target tissue. The purpose of this study was to compare dose-volume characteristics with the brachial plexus between treatment plans generated by IMRT and CRT using several common treatment scenarios.
Method
The brachial plexus was delineated on radiation treatment planning CT scans from 10 patients undergoing IMRT for locally advanced head and neck cancer using a Radiation Therapy Oncology Group-endorsed atlas. No brachial plexus constraint was used. For each patient, a conventional three-g0ield shrinking-g0ield plan was generated and the dose-volume histogram (DVH) for the brachial plexus was compared with that of the IMRT plan.
Results
The mean irradiated volumes of the brachial plexus using the IMRT vs the CRT plan, respectively, were as follows: V50 (18±5 ml) vs (11±6 ml), p = 0.01; V60 (6±4 ml) vs (3±3 ml), p = 0.02; V66 (3±1 ml) vs (1±1 ml), p = 0.04, V70 (0±1 ml) vs (0±1 ml), p = 0.68. The maximum point dose to the brachial plexus was 68.9 Gy (range 62.3–78.7 Gy) and 66.1 Gy (range 60.2–75.6 Gy) for the IMRT and CRT plans, respectively (p = 0.01).
Conclusion
Dose to the brachial plexus is significantly increased among patients undergoing IMRT compared with CRT for head and neck cancer. Preliminary studies on brachial plexus-sparing IMRT are in progress.
doi:10.1259/bjr/62332495
PMCID: PMC3473798  PMID: 20858665
22.  A Methodology Study for Metagenomics Using Next Generation Sequencers 
Metagenomic studies have benefited immensely from next-generation sequencing. However, although much has been published, there are still many unanswered questions. In this DSRG study we aim to answer some of the larger questions by evaluating different DNA extraction methods and comparing two platforms, the Roche/454 and theIllumina next-generation systems. We are using differentanalysis methods to evaluate the sequence data off these platforms in order to determine how the method and/or platform performs comparatively, as well as to establish arecommended analysis pipeline for future users. The results should help establish preferred experimental and technical strategies for gene prediction and determination of biodiversity within microbial communities.
PMCID: PMC3630548
23.  DSRG Metagenomics Study: Next-Generation Techniques and Data Analysis 
Next-generation sequencing has vastly changed the processes associated with metagenomic research and there is a current rush of scientific studies in this field. However, although much has been published, there are still many unanswered questions. In this DSRG study we aim to answer some of the larger questions by evaluating different DNA extraction methods and comparing two platforms, the Roche/454 and the Illumina next-generation systems. Here, we present initial results from two community samples using one extraction method. We examined both 16S and whole genome DNA samples from each and sequenced all samples on the two next-generation platforms. We detail the different analysis methods used to evaluate the sequence data off these platforms and show how the platforms perform comparatively. Future goals of the study will also be highlighted with results helping to establish preferred experimental and technical strategies for metagenomic analysis studies.
PMCID: PMC3630662
24.  β-catenin Initiates Tooth Neogenesis in Adult Rodent Incisors 
Journal of Dental Research  2010;89(9):909-914.
β-catenin signaling is required for embryonic tooth morphogenesis and promotes continuous tooth development when activated in embryos. To determine whether activation of this pathway in the adult oral cavity could promote tooth development, we induced mutation of epithelial β-catenin to a stabilized form in adult mice. This caused increased proliferation of the incisor tooth cervical loop, outpouching of incisor epithelium, abnormal morphology of the epithelial-mesenchymal junction, and enhanced expression of genes associated with embryonic tooth development. Ectopic dental-like structures were formed from the incisor region following implantation into immunodeficient mice. Thus, forced activation of β-catenin signaling can initiate an embryonic-like program of tooth development in adult rodent incisor teeth.
doi:10.1177/0022034510370090
PMCID: PMC3148824  PMID: 20530729
tooth; development; β-catenin; Wnt; dental
25.  Periodontitis is associated with cognitive impairment among older adults: analysis of NHANES-III 
Background
Periodontitis is ubiquitous and associated with serological evidence of exposure to periodontal organisms, systemic inflammation and vascular disease. Dementia is a major public health problem likely related to a complex interaction between genetics and diseases associated with systemic inflammation, including diabetes, smoking and stroke.
Methods
To assess relationships between systemic exposure to periodontal pathogens and cognitive test outcomes, data were analysed from the Third National Health and Nutrition Examination Survey (NHANES-III), a nationally representative cross sectional observational study among older adults. We included 2355 participants ≥60 years who completed measures of cognition and Poryphyromonas gingivalis IgG. Using SUDAAN, logistic regression models examined the association of P gingivalis IgG with cognitive test performance.
Results
Poor immediate verbal memory (<5/9 points) was prevalent in 5.7% of patients, and 6.5% overall had impaired delayed recall (<4/9); 22.1% had difficulty with serial subtractions (<5/5 trials correct). Individuals with the highest P gingivalis IgG (>119 ELISA Units (EU)) were more likely to have poor delayed verbal recall (OR 2.89, 95% CI 1.14 to 7.29) and impaired subtraction (OR 1.95, 95% CI 1.22 to 3.11) than those with the lowest (≤57 EU), with dose–response relationships for both (p trend, delayed memory=0.045, subtraction=0.04). After adjusting for socioeconomic and vascular variables, these relationships remained robust for the highest P gingivalis IgG group (delayed verbal memory OR 3.01 (95% CI 1.06 to 8.53); subtraction OR 2.00 (95% CI 1.19 to 3.36)). In contrast, immediate verbal memory was not significantly associated with P gingivalis.
Conclusion
A serological marker of periodontitis is associated with impaired delayed memory and calculation. Further exploration of relationships between oral health and cognition is warranted.
doi:10.1136/jnnp.2009.174029
PMCID: PMC3073380  PMID: 19419981

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