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1. Factors Affecting Patient Compliance during Orthodontic Treatment with Aligners: Motivational Protocol and Psychological Well-Being

Author

Letizia Perillo, Fabrizia d'Apuzzo, Franca De Gregorio, Vincenzo Grassia, Manuel Barbetti, Giovanni Cugliari, Ludovica Nucci, and Tommaso Castroflorio

Subjects
clear aligners, compliance, patient adherence, psychological well-being, motivational techniques, quality of life, Dentistry, RK1-715
Abstract

Objective:Compliance is critical for successful outcomes in orthodontics, and personality traits may play a role in determining patient adherence. This study aimed to monitor compliance during treatment with removable clear aligners (CA) [Align Technology Inc, San José, Calif ], and evaluate the influence of motivational techniques and the patient’s profiles assessed through the psychological wellbeing (PWB) questionnaire on clinical outcomes.Methods:Thirty-nine consecutive patients in permanent dentition seeking treatment with CA were recruited from two universities. Casts were obtained before treatment and after 3, 6, and 12 months and the corresponding digital Clincheck©.STL files were used to calculate the discrepancy index to check for differences between virtual and real treatment stages. Patients were divided into two groups: the Case group, which received motivational techniques at each appointment, and the control group which received instructions only at the beginning. Psychological profiles were evaluated before treatment (T0) and after 3 (T1), 6 (T2), and 12 (T3) months.Results:There were no differences between the Case and Control groups regarding the use of motivational reminders. The analysis of the PWB showed that almost all values increased, and there was a strong correlation between dental casts and correspondent. STL files at every time point. The PWB showed increased values from T0 to T3 in the sample.Conclusion:Motivational techniques did not affect patient compliance, and treatment outcomes were achieved as planned. The PWB of all patients improved throughout the treatment with CA.

Published
2023
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2. Melanoma Brain Metastases: Immunotherapy or Targeted Therapy? A Systematic Review and Meta-Analyses

Author

Livia Onofrio, Aurora Gaeta, Oriana D’Ecclesiis, Giovanni Cugliari, Sara Gandini, and Paola Queirolo

Subjects
melanoma, brain metastases, immunotherapy, targeted therapy, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract

Background. Brain metastases are one of the leading causes of death in melanoma patients. This systematic review and meta-analysis aimed to look at the variables that affect melanoma patients’ intracranial treatment responses to immunotherapy and targeted therapy. Methods. A systematic search of PubMed and Scopus up to December 2023 was conducted to identify trials investigating treatment response of melanoma brain metastasis. This meta-analysis presents summary estimates (SEs) of treatment response and odd ratios (ORs) for the comparison between symptomatic and asymptomatic metastases. Generalised linear mixed models were used for the SE of the proportion of clinical responses and 95% CIs are reported. We investigated between-study heterogeneity using meta-regression. Results. We included 19 independent clinical trials for a total of 1074 patients with brain metastases. The SE of the overall response was 36% 95%CI [27%; 47%], I2 = 84%, similar to the SE for symptomatic metastases: SE = 29% 95%CI [16%; 47%], I2 = 80%. A significantly higher response of symptomatic metastases was observed between patients who had previously received immunotherapy compared to those who had not (47% vs. 9%, p-value = 0.001). The SE was greater for asymptomatic metastases (38% 95%CI [29%; 49%], I2 = 80%), and among these, patients that received the combo-immunotherapy importantly responded more than those who had received monotherapy (45% vs. 26.1%, p-value = 0.002). The major limit of our analysis is the absence of data about the specific intracranial response separately in asymptomatic and symptomatic patients in seven studies. Conclusions. This study shows the importance of starting immunotherapy as early as possible in asymptomatic patients. Randomised trials with greater statistical power are needed to find the best strategies for symptomatic and asymptomatic brain metastases.

Published
2024
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3. Periodontal Outcomes and Digital Data Integration of Orthodontic Treatment with Clear Aligners: A Prospective Pilot Study

Author

Serena Ravera, Tommaso Castroflorio, Edoardo Mantovani, Ambra Sedran, Giovanni Cugliari, and Andrea Deregibus

Subjects
clear aligners, periodontal index, occlusal contacts, tooth movement, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract

Pathologic tooth migration (PTM) is a complication of Stage III and IV periodontitis. This pilot study aims to analyze the periodontal response to orthodontic aligner therapy in stage IV periodontitis patients, by perio charting and digital orthodontic data obtained from intraoral scans. Following periodontal treatment of 21 recruited patients, 11 underwent clear aligner treatment. Periodontal data (Probing Pocket Depth—PPD, Recession Index—REC, Clinical Attachment Loss—CAL) were collected at baseline (T0), after periodontal treatment (T1), and at the end of the orthodontic treatment (T2). Digital data obtained at T1 and T2 were processed with the 3D software Geomagic® Control X™. Occlusograms obtained by the proximity sensors of the scans were converted into differently colored pixelated areas. These results were compared to highlight changes in clinical crown length or occlusal contact areas. The results showed a slight increase in the REC index and a statistically significant reduction of PPD and CAL at T1 and T2. Digital data showed a statistically significant decrease in terms of gingival recessions and clinical crowns at the end of orthodontic treatment. Hard occlusal contacts showed a statistically significant decrease by the end of the orthodontic treatment. The results are comparable to those reported in the scientific literature for fixed orthodontic treatment. Clear aligner treatment could be considered an option in patients with severe periodontitis, promoting final light occlusal contacts.

Published
2023
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4. The association between genetically elevated polyunsaturated fatty acids and risk of cancerResearch in context

Author

Philip C. Haycock, Maria Carolina Borges, Kimberley Burrows, Rozenn N. Lemaitre, Stephen Burgess, Nikhil K. Khankari, Konstantinos K. Tsilidis, Tom R. Gaunt, Gibran Hemani, Jie Zheng, Therese Truong, Brenda M. Birmann, Tracy OMara, Amanda B. Spurdle, Mark M. Iles, Matthew H. Law, Susan L. Slager, Fatemeh Saberi Hosnijeh, Daniela Mariosa, Michelle Cotterchio, James R. Cerhan, Ulrike Peters, Stefan Enroth, Puya Gharahkhani, Loic Le Marchand, Ann C. Williams, Robert C. Block, Christopher I. Amos, Rayjean J. Hung, Wei Zheng, Marc J. Gunter, George Davey Smith, Caroline Relton, Richard M. Martin, Nathan Tintle, Terri Rice, Iona Cheng, Mark Jenkins, Steve Gallinger, Alex J. Cornish, Amit Sud, Jayaram Vijayakrishnan, Margaret Wrensch, Mattias Johansson, Aaron D. Norman, Alison Klein, Alyssa Clay-Gilmour, Andre Franke, Andres V. Ardisson Korat, Bill Wheeler, Björn Nilsson, Caren Smith, Chew-Kiat Heng, Ci Song, David Riadi, Elizabeth B. Claus, Eva Ellinghaus, Evgenia Ostroumova, Hosnijeh, Florent de Vathaire, Giovanni Cugliari, Giuseppe Matullo, Irene Oi-Lin Ng, Jeanette E. Passow, Jia Nee Foo, Jiali Han, Jianjun Liu, Jill Barnholtz-Sloan, Joellen M. Schildkraut, John Maris, Joseph L. Wiemels, Kari Hemminki, Keming Yang, Lambertus A. Kiemeney, Lang Wu, Laufey Amundadottir, Marc-Henri Stern, Marie-Christine Boutron, Mark Martin Iles, Mark P. Purdue, Martin Stanulla, Melissa Bondy, Mia Gaudet, Lenha Mobuchon, Nicola J. Camp, Pak Chung Sham, Pascal Guénel, Paul Brennan, Philip R. Taylor, Quinn Ostrom, Rachael Stolzenberg-Solomon, Rajkumar Dorajoo, Richard Houlston, Robert B. Jenkins, Sharon Diskin, Sonja I. Berndt, Spiridon Tsavachidis, Stephen J. Channock, Tabitha Harrison, Tessel Galesloot, Ulf Gyllensten, Vijai Joseph, Y. Shi, Wenjian Yang, Yi Lin, and Stephen K. Van Den Eeden

Subjects
Mendelian randomization, Cancer risk, Polyunsaturated fatty acids, Omega 3, Omega 6, Delta-5 desaturase, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: The causal relevance of polyunsaturated fatty acids (PUFAs) for risk of site-specific cancers remains uncertain. Methods: Using a Mendelian randomization (MR) framework, we assessed the causal relevance of PUFAs for risk of cancer in European and East Asian ancestry individuals. We defined the primary exposure as PUFA desaturase activity, proxied by rs174546 at the FADS locus. Secondary exposures were defined as omega 3 and omega 6 PUFAs that could be proxied by genetic polymorphisms outside the FADS region. Our study used summary genetic data on 10 PUFAs and 67 cancers, corresponding to 562,871 cases and 1,619,465 controls, collected by the Fatty Acids in Cancer Mendelian Randomization Collaboration. We estimated odds ratios (ORs) for cancer per standard deviation increase in genetically proxied PUFA exposures. Findings: Genetically elevated PUFA desaturase activity was associated (P

Published
2023
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5. DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases

Author

Matthias Wielscher, Pooja R. Mandaviya, Brigitte Kuehnel, Roby Joehanes, Rima Mustafa, Oliver Robinson, Yan Zhang, Barbara Bodinier, Esther Walton, Pashupati P. Mishra, Pascal Schlosser, Rory Wilson, Pei-Chien Tsai, Saranya Palaniswamy, Riccardo E. Marioni, Giovanni Fiorito, Giovanni Cugliari, Ville Karhunen, Mohsen Ghanbari, Bruce M. Psaty, Marie Loh, Joshua C. Bis, Benjamin Lehne, Nona Sotoodehnia, Ian J. Deary, Marc Chadeau-Hyam, Jennifer A. Brody, Alexia Cardona, Elizabeth Selvin, Alicia K. Smith, Andrew H. Miller, Mylin A. Torres, Eirini Marouli, Xin Gào, Joyce B. J. van Meurs, Johanna Graf-Schindler, Wolfgang Rathmann, Wolfgang Koenig, Annette Peters, Wolfgang Weninger, Matthias Farlik, Tao Zhang, Wei Chen, Yujing Xia, Alexander Teumer, Matthias Nauck, Hans J. Grabe, Macus Doerr, Terho Lehtimäki, Weihua Guan, Lili Milani, Toshiko Tanaka, Krista Fisher, Lindsay L. Waite, Silva Kasela, Paolo Vineis, Niek Verweij, Pim van der Harst, Licia Iacoviello, Carlotta Sacerdote, Salvatore Panico, Vittorio Krogh, Rosario Tumino, Evangelia Tzala, Giuseppe Matullo, Mikko A. Hurme, Olli T. Raitakari, Elena Colicino, Andrea A. Baccarelli, Mika Kähönen, Karl-Heinz Herzig, Shengxu Li, BIOS consortium, Karen N. Conneely, Jaspal S. Kooner, Anna Köttgen, Bastiaan T. Heijmans, Panos Deloukas, Caroline Relton, Ken K. Ong, Jordana T. Bell, Eric Boerwinkle, Paul Elliott, Hermann Brenner, Marian Beekman, Daniel Levy, Melanie Waldenberger, John C. Chambers, Abbas Dehghan, and Marjo-Riitta Järvelin

Subjects
Science
Abstract

Chronic inflammation, marked by C-reactive protein, has been associated with changes in methylation, but the causal relationship is unclear. Here, the authors perform a Epigenome-wide association meta-analysis for C-reactive protein levels and find that these methylation changes are likely the consequence of inflammation and could contribute to disease.

Published
2022
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7. Effects of nutritional intake on performance in master athletes during an extreme ultra-trail

Author

Felicina Biorci, Giovanni Cugliari, Marcello Lucchese, and Marco Ivaldi

Subjects
nutrient intake, body composition, blood glucose, sleep, master athlete, ultra-trail, Sports medicine, RC1200-1245
Abstract

The purpose of our study was to monitor a well-trained master athlete who competed in the race, keeping under review his performance outcomes. TransPyrenea (La Grande Traversée des Pyrénées) is an Ultra Trail 13-16-d race, 866 km long, 53200 meters of elevation gain, performed for the first time in 2016, becoming the longest race in the world. At every checkpoint, a member of the team ascertained total macronutrients intake and body composition. A wearable device was used to monitor glycemia during all the race. The athlete completed the race with an average speed of 2.6 km/h, including 26 hours and 30 minutes of sleeping. Multiple regression analysis showed that the increase of the speed (β: 0.5 km/h, 95% CI: 0.07 | 1.02 km/h, p-value: .035 and β: 1.32 km/h, 95% CI: 0.53 | 2.11 km/h, p-value: .004) was related to the increase of one hour of sleep and one kg of weight respectively. This evidence could induce the use of specific nutritional supplements and the analysis of body composition on the management strategies of the race, with eventually the planning of a greater number of hours of sleep to acquire greater speed.

Published
2020
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9. Analysis of Class II Intermaxillary Elastics Applied Forces: An in-vitro Study

Author

Tommaso Castroflorio, Ambra Sedran, Francesca Spadaro, Gabriele Rossini, Giovanni Cugliari, Vincenzo Quinzi, and Andrea Deregibus

Subjects
class II, adult treatment, elastics, anchorage sites, forces, Dentistry, RK1-715
Abstract

ObjectivesThe aims of this study were: (1) to assess the average inter-arch distances characterizing Class II malocclusions, (2) to analyze the applied forces at those distances by different elastics, and (3) to compare measured forces with those declared by manufacturers, both in dry and wet environments.Materials and MethodsSettings and sample population: Class II models of 167 adult subjects (96 women and 71 men, age: 28 ± 3 years) referred to the Orthodontic Department of the University of Turin, Turin, Italy, between January 2018 and January 2020, were collected. Distances between facial axes (FA) points of upper canines and lower first molars (A), upper first premolar and lower first molar (B), upper second premolar and lower first molar (C), upper canine and lower first premolar (D), and upper canine and lower second premolar (E), were measured using 3Shape Ortho® Viewer program. Different elastics' diameters and forces were tested at those distances. The MTS Insight® Electromechanical Testing System was used to measure the tensile forces of elastics. The applied forces were measured in dry (T0) and wet conditions, after 1 (T1), 6 (T2), and 12 h (T3).ResultsAverage distances were calculated: A = 24.64 mm (SD 2.10), B = 16.3 mm (SD 1.94), C = 9.78 mm (SD 1.77), D = 9.8 mm (SD 1.88), and E = 15.99 mm (SD 2.06). Significant differences (p < 0.05) were highlighted between the measured force and the force declared by manufacturers, and all elastics had a significant force decay (p < 0.05).ConclusionThe results showed that 3/16" 4.5 oz are the most reliable elastics in terms of applied force with respect to the declared one and in terms of force degradation.

Published
2022
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10. Associations of autozygosity with a broad range of human phenotypes

Author

David W Clark, Yukinori Okada, Kristjan H S Moore, Dan Mason, Nicola Pirastu, Ilaria Gandin, Hannele Mattsson, Catriona L K Barnes, Kuang Lin, Jing Hua Zhao, Patrick Deelen, Rebecca Rohde, Claudia Schurmann, Xiuqing Guo, Franco Giulianini, Weihua Zhang, Carolina Medina-Gomez, Robert Karlsson, Yanchun Bao, Traci M Bartz, Clemens Baumbach, Ginevra Biino, Matthew J Bixley, Marco Brumat, Jin-Fang Chai, Tanguy Corre, Diana L Cousminer, Annelot M Dekker, David A Eccles, Kristel R van Eijk, Christian Fuchsberger, He Gao, Marine Germain, Scott D Gordon, Hugoline G de Haan, Sarah E Harris, Edith Hofer, Alicia Huerta-Chagoya, Catherine Igartua, Iris E Jansen, Yucheng Jia, Tim Kacprowski, Torgny Karlsson, Marcus E Kleber, Shengchao Alfred Li, Ruifang Li-Gao, Anubha Mahajan, Koichi Matsuda, Karina Meidtner, Weihua Meng, May E Montasser, Peter J van der Most, Matthias Munz, Teresa Nutile, Teemu Palviainen, Gauri Prasad, Rashmi B Prasad, Tallapragada Divya Sri Priyanka, Federica Rizzi, Erika Salvi, Bishwa R Sapkota, Daniel Shriner, Line Skotte, Melissa C Smart, Albert Vernon Smith, Ashley van der Spek, Cassandra N Spracklen, Rona J Strawbridge, Salman M Tajuddin, Stella Trompet, Constance Turman, Niek Verweij, Clara Viberti, Lihua Wang, Helen R Warren, Robyn E Wootton, Lisa R Yanek, Jie Yao, Noha A Yousri, Wei Zhao, Adebowale A Adeyemo, Saima Afaq, Carlos Alberto Aguilar-Salinas, Masato Akiyama, Matthew L Albert, Matthew A Allison, Maris Alver, Tin Aung, Fereidoun Azizi, Amy R Bentley, Heiner Boeing, Eric Boerwinkle, Judith B Borja, Gert J de Borst, Erwin P Bottinger, Linda Broer, Harry Campbell, Stephen Chanock, Miao-Li Chee, Guanjie Chen, Yii-Der I Chen, Zhengming Chen, Yen-Feng Chiu, Massimiliano Cocca, Francis S Collins, Maria Pina Concas, Janie Corley, Giovanni Cugliari, Rob M van Dam, Anna Damulina, Maryam S Daneshpour, Felix R Day, Graciela E Delgado, Klodian Dhana, Alexander S F Doney, Marcus Dörr, Ayo P Doumatey, Nduna Dzimiri, S Sunna Ebenesersdóttir, Joshua Elliott, Paul Elliott, Ralf Ewert, Janine F Felix, Krista Fischer, Barry I Freedman, Giorgia Girotto, Anuj Goel, Martin Gögele, Mark O Goodarzi, Mariaelisa Graff, Einat Granot-Hershkovitz, Francine Grodstein, Simonetta Guarrera, Daniel F Gudbjartsson, Kamran Guity, Bjarni Gunnarsson, Yu Guo, Saskia P Hagenaars, Christopher A Haiman, Avner Halevy, Tamara B Harris, Mehdi Hedayati, David A van Heel, Makoto Hirata, Imo Höfer, Chao Agnes Hsiung, Jinyan Huang, Yi-Jen Hung, M Arfan Ikram, Anuradha Jagadeesan, Pekka Jousilahti, Yoichiro Kamatani, Masahiro Kanai, Nicola D Kerrison, Thorsten Kessler, Kay-Tee Khaw, Chiea Chuen Khor, Dominique P V de Kleijn, Woon-Puay Koh, Ivana Kolcic, Peter Kraft, Bernhard K Krämer, Zoltán Kutalik, Johanna Kuusisto, Claudia Langenberg, Lenore J Launer, Deborah A Lawlor, I-Te Lee, Wen-Jane Lee, Markus M Lerch, Liming Li, Jianjun Liu, Marie Loh, Stephanie J London, Stephanie Loomis, Yingchang Lu, Jian’an Luan, Reedik Mägi, Ani W Manichaikul, Paolo Manunta, Gísli Másson, Nana Matoba, Xue W Mei, Christa Meisinger, Thomas Meitinger, Massimo Mezzavilla, Lili Milani, Iona Y Millwood, Yukihide Momozawa, Amy Moore, Pierre-Emmanuel Morange, Hortensia Moreno-Macías, Trevor A Mori, Alanna C Morrison, Taulant Muka, Yoshinori Murakami, Alison D Murray, Renée de Mutsert, Josyf C Mychaleckyj, Mike A Nalls, Matthias Nauck, Matt J Neville, Ilja M Nolte, Ken K Ong, Lorena Orozco, Sandosh Padmanabhan, Gunnar Pálsson, James S Pankow, Cristian Pattaro, Alison Pattie, Ozren Polasek, Neil Poulter, Peter P Pramstaller, Lluis Quintana-Murci, Katri Räikkönen, Sarju Ralhan, Dabeeru C Rao, Wouter van Rheenen, Stephen S Rich, Paul M Ridker, Cornelius A Rietveld, Antonietta Robino, Frank J A van Rooij, Daniela Ruggiero, Yasaman Saba, Charumathi Sabanayagam, Maria Sabater-Lleal, Cinzia Felicita Sala, Veikko Salomaa, Kevin Sandow, Helena Schmidt, Laura J Scott, William R Scott, Bahareh Sedaghati-Khayat, Bengt Sennblad, Jessica van Setten, Peter J Sever, Wayne H-H Sheu, Yuan Shi, Smeeta Shrestha, Sharvari Rahul Shukla, Jon K Sigurdsson, Timo Tonis Sikka, Jai Rup Singh, Blair H Smith, Alena Stančáková, Alice Stanton, John M Starr, Lilja Stefansdottir, Leon Straker, Patrick Sulem, Gardar Sveinbjornsson, Morris A Swertz, Adele M Taylor, Kent D Taylor, Natalie Terzikhan, Yih-Chung Tham, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Annika Tillander, Russell P Tracy, Teresa Tusié-Luna, Ioanna Tzoulaki, Simona Vaccargiu, Jagadish Vangipurapu, Jan H Veldink, Veronique Vitart, Uwe Völker, Eero Vuoksimaa, Salma M Wakil, Melanie Waldenberger, Gurpreet S Wander, Ya Xing Wang, Nicholas J Wareham, Sarah Wild, Chittaranjan S Yajnik, Jian-Min Yuan, Lingyao Zeng, Liang Zhang, Jie Zhou, Najaf Amin, Folkert W Asselbergs, Stephan J L Bakker, Diane M Becker, Benjamin Lehne, David A Bennett, Leonard H van den Berg, Sonja I Berndt, Dwaipayan Bharadwaj, Lawrence F Bielak, Murielle Bochud, Mike Boehnke, Claude Bouchard, Jonathan P Bradfield, Jennifer A Brody, Archie Campbell, Shai Carmi, Mark J Caulfield, David Cesarini, John C Chambers, Giriraj Ratan Chandak, Ching-Yu Cheng, Marina Ciullo, Marilyn Cornelis, Daniele Cusi, George Davey Smith, Ian J Deary, Rajkumar Dorajoo, Cornelia M van Duijn, David Ellinghaus, Jeanette Erdmann, Johan G Eriksson, Evangelos Evangelou, Michele K Evans, Jessica D Faul, Bjarke Feenstra, Mary Feitosa, Sylvain Foisy, Andre Franke, Yechiel Friedlander, Paolo Gasparini, Christian Gieger, Clicerio Gonzalez, Philippe Goyette, Struan F A Grant, Lyn R Griffiths, Leif Groop, Vilmundur Gudnason, Ulf Gyllensten, Hakon Hakonarson, Anders Hamsten, Pim van der Harst, Chew-Kiat Heng, Andrew A Hicks, Hagit Hochner, Heikki Huikuri, Steven C Hunt, Vincent W V Jaddoe, Philip L De Jager, Magnus Johannesson, Åsa Johansson, Jost B Jonas, J Wouter Jukema, Juhani Junttila, Jaakko Kaprio, Sharon L. R. Kardia, Fredrik Karpe, Meena Kumari, Markku Laakso, Sander W van der Laan, Jari Lahti, Matthias Laudes, Rodney A Lea, Wolfgang Lieb, Thomas Lumley, Nicholas G Martin, Winfried März, Giuseppe Matullo, Mark I McCarthy, Sarah E Medland, Tony R Merriman, Andres Metspalu, Brian F Meyer, Karen L Mohlke, Grant W Montgomery, Dennis Mook-Kanamori, Patricia B Munroe, Kari E North, Dale R Nyholt, Jeffery R O’connell, Carole Ober, Albertine J Oldehinkel, Walter Palmas, Colin Palmer, Gerard G Pasterkamp, Etienne Patin, Craig E Pennell, Louis Perusse, Patricia A Peyser, Mario Pirastu, Tinca J. C. Polderman, David J Porteous, Danielle Posthuma, Bruce M Psaty, John D Rioux, Fernando Rivadeneira, Charles Rotimi, Jerome I Rotter, Igor Rudan, Hester M Den Ruijter, Dharambir K Sanghera, Naveed Sattar, Reinhold Schmidt, Matthias B Schulze, Heribert Schunkert, Robert A Scott, Alan R Shuldiner, Xueling Sim, Neil Small, Jennifer A Smith, Nona Sotoodehnia, E-Shyong Tai, Alexander Teumer, Nicholas J Timpson, Daniela Toniolo, David-Alexandre Tregouet, Tiinamaija Tuomi, Peter Vollenweider, Carol A Wang, David R Weir, John B Whitfield, Cisca Wijmenga, Tien-Yin Wong, John Wright, Jingyun Yang, Lei Yu, Babette S Zemel, Alan B Zonderman, Markus Perola, Patrik K. E. Magnusson, André G Uitterlinden, Jaspal S Kooner, Daniel I Chasman, Ruth J. F. Loos, Nora Franceschini, Lude Franke, Chris S Haley, Caroline Hayward, Robin G Walters, John R. B. Perry, Tōnu Esko, Agnar Helgason, Kari Stefansson, Peter K Joshi, Michiaki Kubo, and James F Wilson

Subjects
Science
Abstract

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Published
2019
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11. Lower Molar Distalization Using Clear Aligners: Bodily Movement or Uprighting? A Preliminary Study

Author

Elisa Rota, Simone Parrini, Kamy Malekian, Giovanni Cugliari, Gianluca Mampieri, Andrea Deregibus, and Tommaso Castroflorio

Subjects
class III, distalization, clear aligners, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract

Background: Lower molar distalization is considered to be one of the most difficult movements to obtain with clear aligners. The aim of this study was to evaluate the possibility to distalize the lower molars using clear aligners in adults without miniscrews. Material and methods: rx cephalograms of 16 patients (8 males, 8 females; mean age of 25.6 years), who underwent lower molar distalization, were analyzed. Cephalograms were taken before the beginning of treatment (T0) and after the end of treatment (T1). Dental and skeletal changes between T0 and T1 were evaluated. The level of significance was set at p < 0.05. Results: At T1, the lower second molar moved distally 2.47 mm, but there was a significant tipping (p = 0.027); the same result was found at the first molar, with a mean distal movement of 1.16 mm and a significant tipping (p = 0.003). No significant changes were detected on the sagittal and vertical skeletal variables. Conclusion: Clear aligner therapy can provide more distal tipping than bodily movement in the lower molars when a distalization is programmed. This movement could be sufficient to correct the initial malocclusion and gain a class I molar relationship.

Published
2022
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12. Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adultsResearch in context

Author

Priyanka Parmar, Estelle Lowry, Giovanni Cugliari, Matthew Suderman, Rory Wilson, Ville Karhunen, Toby Andrew, Petri Wiklund, Matthias Wielscher, Simonetta Guarrera, Alexander Teumer, Benjamin Lehne, Lili Milani, Niek de Klein, Pashupati P. Mishra, Phillip E. Melton, Pooja R. Mandaviya, Silva Kasela, Jana Nano, Weihua Zhang, Yan Zhang, Andre G. Uitterlinden, Annette Peters, Ben Schöttker, Christian Gieger, Denise Anderson, Dorret I. Boomsma, Hans J. Grabe, Salvatore Panico, Jan H. Veldink, Joyce B.J. van Meurs, Leonard van den Berg, Lawrence J. Beilin, Lude Franke, Marie Loh, Marleen M.J. van Greevenbroek, Matthias Nauck, Mika Kähönen, Mikko A. Hurme, Olli T. Raitakari, Oscar H. Franco, P.Eline Slagboom, Pim van der Harst, Sonja Kunze, Stephan B. Felix, Tao Zhang, Wei Chen, Trevor A. Mori, Amelie Bonnefond, Bastiaan T. Heijmans, Taulant Muka, Jaspal S. Kooner, Krista Fischer, Melanie Waldenberger, Philippe Froguel, Rae-Chi Huang, Terho Lehtimäki, Wolfgang Rathmann, Caroline L. Relton, Giuseppe Matullo, Hermann Brenner, Niek Verweij, Shengxu Li, John C. Chambers, Marjo-Riitta Järvelin, and Sylvain Sebert

Subjects
Medicine, Medicine (General), R5-920
Abstract

Background: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. Methods: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n = 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL—C), triglycerides (TG), diastolic, and systolic blood pressure (BP). Findings: Lower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P

Published
2018
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13. Root resorption during orthodontic treatment with Invisalign®: a radiometric study

Author

Giulia Gay, Serena Ravera, Tommaso Castroflorio, Francesco Garino, Gabriele Rossini, Simone Parrini, Giovanni Cugliari, and Andrea Deregibus

Subjects
Adult patients, Aligners, Root resorption, Dentistry, RK1-715
Abstract

Abstract Background Root resorption (RR) is described as a permanent loss of tooth structure from the root apex. Many reports in the literature indicate that orthodontically treated patients are more likely to have severe apical root shortening, interesting mostly maxillary, followed by mandibular incisors. The aim of the study was to investigate the incidence and severity of RR in adult patients treated with aligners. The study group consisted of 71 class I adult healthy patients (mean age 32.8 ± 12.7) treated with aligners (Invisalign®, Align Technologies, Santa Clara, CA, USA). All incisors, canines, upper first premolars, and first molars were assessed. Root and crown lengths of 1083 teeth were measured in panoramic radiographs at the beginning (T0) and at the end (T1) of clear aligner therapy. Individual root-crown ratio (RCR) of each tooth and therefore the relative changes of RCR (rRCR) were determined. A decrease of rRCR was assessed as a reduction of the root length during treatment. Results All patients had a minimum of one teeth affected with a reduction of root length, on average 6.38 ± 2.28 teeth per patient. Forty one, 81% of the 1083, measured teeth presented a reduction of the pre-treatment root length. A reduction in percentage of >0% up to 10% was found in 25.94% (n = 281), a distinct reduction of >10% up to 20% in 12.18% (n = 132) of the sample. 3.69% (n = 40) of the teeth were affected with a considerable reduction (>20%). Conclusions Orthodontic treatment with Invisalign® aligners could lead to RR. However, its incidence resulted to be very similar to that described for orthodontic light forces, with an average percentage of RR

Published
2017
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14. Maxillary molar distalization with aligners in adult patients: a multicenter retrospective study

Author

Serena Ravera, Tommaso Castroflorio, Francesco Garino, Sam Daher, Giovanni Cugliari, and Andrea Deregibus

Subjects
Class II, Aligners, Molar distalization, Adult patients, Dentistry, RK1-715
Abstract

Abstract Background The aim of the present study was to test the hypothesis that bodily maxillary molar distalization was not achievable in aligner orthodontics. Methods Forty lateral cephalograms obtained from 20 non-growing subjects (9 male, 11 female; average age 29.73 years) (group S), who underwent bilateral distalization of their maxillary dentition with Invisalign aligners (Align Technology, Inc., San José, CA, USA), were considered for the study. Skeletal class I or class II malocclusion and a bilateral end-to-end class II molar relationship were the main inclusion criteria. Cephalograms were taken at two time points: (T0) pretreatment and (T2) post-treatment. Treatment changes were evaluated between the time points using 39 variables by means of paired t test. The level of significance was set at P

Published
2016
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15. The Adapted Italian Version of the Baller Identity Measurement Scale to Evaluate the Student-Athletes' Identity in Relation to Gender, Age, Type of Sport, and Competition Level.

Author

Corrado Lupo, Cristina Onesta Mosso, Flavia Guidotti, Giovanni Cugliari, Luisa Pizzigalli, and Alberto Rainoldi

Subjects
Medicine, Science
Abstract

The purpose of this paper is twofold: to validate the properties of the Italian version of the Baller Identity Measurement Scale (i.e., BIMS-IT), a self-report questionnaire based on the athletic and academic identities; and to investigate differences in psychosocial factors such as gender, age, type of sport, and competition level. The dimensionality of the BIMS-IT was explored by means of the exploratory factor analysis, considering the scale's internal consistency too (Confirmatory Factor Analysis). Results related to exploratory and confirmatory factor analysis supported a model of measurement composed of two correlated factors: the athletic and academic identities and affectivity related to identities. For both factors, differences emerged between age, and competition level sub groups. In particular, higher identity scores emerged for ≤ 24 years old student-athletes with respect to their age counterparts. National sub-elite student-athletes reported lower identity values than those of national elite and international levels. Results suggest that the Italian version of the BIMS-IT is psychometrically robust and could be adopted for empirical uses. The higher identity scores reported by younger and higher competition level participants suggest a correspondent higher involvement into the student-athlete role. However, BIMS-IT represents a distinct model with respect to the original American BIMS, determining the need of further research on the student-athletes' identity to better clarify any socio-cultural contest effects.

Published
2017
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16. Advances in the Genetics of Hypertension: The Effect of Rare Variants

Author

Alessia Russo, Cornelia Di Gaetano, Giovanni Cugliari, and Giuseppe Matullo

Subjects
essential hypertension, blood pressure, genome-wide association studies, exome microarray, next-generation sequencing, rare variants, rare-variants association testing, burden test, sequence kernel association test, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Worldwide, hypertension still represents a serious health burden with nine million people dying as a consequence of hypertension-related complications. Essential hypertension is a complex trait supported by multifactorial genetic inheritance together with environmental factors. The heritability of blood pressure (BP) is estimated to be 30–50%. A great effort was made to find genetic variants affecting BP levels through Genome-Wide Association Studies (GWAS). This approach relies on the “common disease–common variant” hypothesis and led to the identification of multiple genetic variants which explain, in aggregate, only 2–3% of the genetic variance of hypertension. Part of the missing genetic information could be caused by variants too rare to be detected by GWAS. The use of exome chips and Next-Generation Sequencing facilitated the discovery of causative variants. Here, we report the advances in the detection of novel rare variants, genes, and/or pathways through the most promising approaches, and the recent statistical tests that have emerged to handle rare variants. We also discuss the need to further support rare novel variants with replication studies within larger consortia and with deeper functional studies to better understand how new genes might improve patient care and the stratification of the response to antihypertensive treatments.

Published
2018
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18. The association between genetically elevated polyunsaturated fatty acids and risk of cancer

Author

Philip C. Haycock, Maria Carolina Borges, Kimberley Burrows, Rozenn N. Lemaitre, Stephen Burgess, Nikhil K. Khankari, Konstantinos K. Tsilidis, Tom R. Gaunt, Gibran Hemani, Jie Zheng, Therese Truong, Brenda M. Birmann, Tracy OMara, Amanda B. Spurdle, Mark M. Iles, Matthew H. Law, Susan L. Slager, Fatemeh Saberi Hosnijeh, Daniela Mariosa, Michelle Cotterchio, James R. Cerhan, Ulrike Peters, Stefan Enroth, Puya Gharahkhani, Loic Le Marchand, Ann C. Williams, Robert C. Block, Christopher I. Amos, Rayjean J. Hung, Wei Zheng, Marc J. Gunter, George Davey Smith, Caroline Relton, Richard M. Martin, Nathan Tintle, Terri Rice, Iona Cheng, Mark Jenkins, Steve Gallinger, Alex J. Cornish, Amit Sud, Jayaram Vijayakrishnan, Margaret Wrensch, Mattias Johansson, Aaron D. Norman, Alison Klein, Alyssa Clay-Gilmour, Andre Franke, Andres V. Ardisson Korat, Bill Wheeler, Björn Nilsson, Caren Smith, Chew-Kiat Heng, Ci Song, David Riadi, Elizabeth B. Claus, Eva Ellinghaus, Evgenia Ostroumova, null Hosnijeh, Florent de Vathaire, Giovanni Cugliari, Giuseppe Matullo, Irene Oi-Lin Ng, Jeanette E. Passow, Jia Nee Foo, Jiali Han, Jianjun Liu, Jill Barnholtz-Sloan, Joellen M. Schildkraut, John Maris, Joseph L. Wiemels, Kari Hemminki, Keming Yang, Lambertus A. Kiemeney, Lang Wu, Laufey Amundadottir, Marc-Henri Stern, Marie-Christine Boutron, Mark Martin Iles, Mark P. Purdue, Martin Stanulla, Melissa Bondy, Mia Gaudet, Lenha Mobuchon, Nicola J. Camp, Pak Chung Sham, Pascal Guénel, Paul Brennan, Philip R. Taylor, Quinn Ostrom, Rachael Stolzenberg-Solomon, Rajkumar Dorajoo, Richard Houlston, Robert B. Jenkins, Sharon Diskin, Sonja I. Berndt, Spiridon Tsavachidis, Stephen J. Channock, Tabitha Harrison, Tessel Galesloot, Ulf Gyllensten, Vijai Joseph, Y. Shi, Wenjian Yang, Yi Lin, and Stephen K. Van Den Eeden

Subjects
Cancer och onkologi, General Practice, Delta-5 desaturase, General Medicine, General Biochemistry, Genetics and Molecular Biology, Omega 6, Allmänmedicin, Cancer risk, Omega 3, Cancer and Oncology, Mendelian randomization, Delta-6 desaturase, Polyunsaturated fatty acids, Bristol Population Health Science Institute
Abstract

BackgroundThe causal relevance of polyunsaturated fatty acids (PUFAs) for risk of site-specific cancers remains uncertain.MethodsUsing a Mendelian randomization (MR) framework, we assessed the causal relevance of PUFAs for risk of cancer in European and East Asian ancestry individuals. We defined the primary exposure as PUFA desaturase activity, proxied by rs174546 at the FADS locus. Secondary exposures were defined as omega 3 and omega 6 PUFAs that could be proxied by genetic polymorphisms outside the FADS region. Our study used summary genetic data on 10 PUFAs and 67 cancers, corresponding to 562,871 cases and 1,619,465 controls, collected by the Fatty Acids in Cancer Mendelian Randomization Collaboration. We estimated odds ratios (ORs) for cancer per standard deviation increase in genetically proxied PUFA exposures.FindingsGenetically elevated PUFA desaturase activity was associated (P < 0.0007) with higher risk (OR [95% confidence interval]) of colorectal cancer (1.09 [1.07–1.11]), esophageal squamous cell carcinoma (1.16 [1.06–1.26]), lung cancer (1.06 [1.03–1.08]) and basal cell carcinoma (1.05 [1.02–1.07]). There was little evidence for associations with reproductive cancers (OR = 1.00 [95% CI: 0.99–1.01]; Pheterogeneity = 0.25), urinary system cancers (1.03 [0.99–1.06], Pheterogeneity = 0.51), nervous system cancers (0.99 [0.95–1.03], Pheterogeneity = 0.92) or blood cancers (1.01 [0.98–1.04], Pheterogeneity = 0.09). Findings for colorectal cancer and esophageal squamous cell carcinoma remained compatible with causality in sensitivity analyses for violations of assumptions. Secondary MR analyses highlighted higher omega 6 PUFAs (arachidonic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid) as potential mediators. PUFA biosynthesis is known to interact with aspirin, which increases risk of bleeding and inflammatory bowel disease. In a phenome-wide MR study of non-neoplastic diseases, we found that genetic lowering of PUFA desaturase activity, mimicking a hypothetical intervention to reduce cancer risk, was associated (P < 0.0006) with increased risk of inflammatory bowel disease but not bleeding.InterpretationThe PUFA biosynthesis pathway may be an intervention target for prevention of colorectal cancer and esophageal squamous cell carcinoma but with potential for increased risk of inflammatory bowel disease.FundingCancer Resesrch UK (C52724/A20138, C18281/A19169). UK Medical Research Council (MR/P014054/1). National Institute for Health Research (NIHR202411). UK Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_00011/4). National Cancer Institute (R00 CA215360). National Institutes of Health (U01 CA164973, R01 CA60987, R01 CA72520, U01 CA74806, R01 CA55874, U01 CA164973 and U01 CA164973).

Published
2023

19. Blood cell DNA methylation biomarkers in preclinical malignant pleural mesothelioma: The EPIC prospective cohort

Author

Alessandra Allione, Clara Viberti, Ilaria Cotellessa, Chiara Catalano, Elisabetta Casalone, Giovanni Cugliari, Alessia Russo, Simonetta Guarrera, Dario Mirabelli, Carlotta Sacerdote, Marco Gentile, Fabian Eichelmann, Matthias B. Schulze, Sophia Harlid, Anne Kirstine Eriksen, Anne Tjønneland, Martin Andersson, Martijn E.T. Dollé, Heleen Van Puyvelde, Elisabete Weiderpass, Miguel Rodriguez‐Barranco, Antonio Agudo, Alicia K. Heath, María‐Dolores Chirlaque, Thérèse Truong, Dzevka Dragic, Gianluca Severi, Sabina Sieri, Torkjel M. Sandanger, Eva Ardanaz, Paolo Vineis, and Giuseppe Matullo

Subjects
Cancer Research, DNA methylation, Oncology, cancer biomarkers, mesothelioma, prospective nested case-control study
Abstract

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer mainly caused by asbestos exposure. Specific and sensitive non-invasive biomarkers may facilitate and enhance screening programs for the early detection of cancer. We investigated DNA methylation (DNAm) profiles in MPM pre-diagnostic blood samples in a case-control study nested in the European Prospective Investigation into Cancer and nutrition (EPIC) cohort, aiming to characterise DNAm biomarkers associated with MPM. From the EPIC cohort, we included samples from 135 participants who developed MPM during 20 years of follow up and from 135 matched, cancer-free, controls. For the discovery phase we selected EPIC participants who developed MPM within five years from enrolment (n=36) with matched controls. We identified nine differentially methylated CpGs, selected by 10-fold cross-validation and correlation analyses: cg25755428 (MRI1), cg20389709 (KLF11), cg23870316, cg13862711 (LHX6), cg06417478 (HOOK2), cg00667948, cg01879420 (AMD1), cg25317025 (RPL17) and cg06205333 (RAP1A). Receiver operating characteristic (ROC) analysis showed that the model including baseline characteristics (age, sex, PC1wbc) along with the nine MPM-related CpGs has a better predictive value for MPM occurrence than the baseline model alone, maintaining some performance also at more than five years before diagnosis [AUC (area under the curve) 10 years=0.75; baseline AUC range=0.63-0.67)]. DNAm changes as non-invasive biomarkers in pre-diagnostic blood samples of MPM cases were investigated for the first time. Their application can improve the identification of asbestos-exposed individuals at higher MPM risk in order to possibly adopt more intensive monitoring for early disease identification.

Published
2022

20. Interleukin-3-Receptor-α in Triple-Negative Breast Cancer (TNBC): An Additional Novel Biomarker of TNBC Aggressiveness and a Therapeutic Target

Author

Malvina Koni, Isabella Castellano, Emilio Venturelli, Alessandro Sarcinella, Tatiana Lopatina, Cristina Grange, Massimo Cedrino, Saveria Femminò, Paolo Cossu-Rocca, Sandra Orrù, Fabrizio D’Ascenzo, Ilaria Cotellessa, Cristian Tampieri, Carla Debernardi, Giovanni Cugliari, Giuseppe Matullo, Giovanni Camussi, Maria Rosaria De Miglio, and Maria Felice Brizzi

Subjects
Cancer Research, Oncology, interleukin-3/interleukin-3 receptor α, triple-negative breast cancer, vascular mimicry, programmed cell death-ligand 1
Abstract

Tumour molecular annotation is mandatory for biomarker discovery and personalised approaches, particularly in triple-negative breast cancer (TNBC) lacking effective treatment options. In this study, the interleukin-3 receptor α (IL-3Rα) was investigated as a prognostic biomarker and therapeutic target in TNBC. IL-3Rα expression and patients’ clinical and pathological features were retrospectively analysed in 421 TNBC patients. IL-3Rα was expressed in 69% human TNBC samples, and its expression was associated with nodal metastases (p = 0.026) and poor overall survival (hazard ratio = 1.50; 95% CI = 1.01–2.2; p = 0.04). The bioinformatics analysis on the Breast Invasive Carcinoma dataset of The Cancer Genome Atlas (TCGA) proved that IL-3Rα was highly expressed in TNBC compared with luminal breast cancers (p = 0.017, padj = 0.026). Functional studies demonstrated that IL-3Rα activation induced epithelial-to-endothelial and epithelial-to-mesenchymal transition, promoted large blood lacunae and lung metastasis formation, and increased programmed-cell death ligand-1 (PD-L1) in primary tumours and metastases. Based on the TCGA data, IL-3Rα, PD-L1, and EMT coding genes were proposed to discriminate against TNBC aggressiveness (AUC = 0.86 95% CI = 0.82–0.89). Overall, this study identified IL-3Rα as an additional novel biomarker of TNBC aggressiveness and provided the rationale to further investigate its relevance as a therapeutic target.

Published
2022

21. Functional and clinical implications of genetic structure in 1686 Italian exomes

Author

Elisabetta Casalone, Rosanna Asselta, Elvezia Maria Paraboschi, Giovanni Cugliari, Elisa Giorgio, Alessia Russo, Diego Ardissino, Serena Aneli, Giovanni Birolo, Giuseppe Matullo, Cornelia Di Gaetano, Alessandra Allione, and Stefano Duga

Subjects
medicine.medical_specialty, Population, Biology, genetic frequency database, 03 medical and health sciences, symbols.namesake, Exome Sequencing, Genetics, medicine, Humans, Italian population, Exome, whole-exome sequencing, education, genomic medicine, pathogenic variants, rare variants, Gene, Genetics (clinical), Exome sequencing, 030304 developmental biology, 0303 health sciences, education.field_of_study, 030305 genetics & heredity, Genetic Variation, Europe, Italy, Genetic structure, Mendelian inheritance, symbols, Medical genetics, DPYD
Abstract

To reconstruct the phenotypical and clinical implications of the Italian genetic structure, we thoroughly analyzed a whole-exome sequencing data set comprised of 1686 healthy Italian individuals. We found six previously unreported variants with remarkable frequency differences between Northern and Southern Italy in the HERC2, OR52R1, ADH1B, and THBS4 genes. We reported 36 clinically relevant variants (submitted as pathogenic, risk factors, or drug response in ClinVar) with significant frequency differences between Italy and Europe. We then explored putatively pathogenic variants in the Italian exome. On average, our Italian individuals carried 16.6 protein-truncating variants (PTVs), with 2.5% of the population having a PTV in one of the 59 American College of Medical Genetics (ACMG) actionable genes. Lastly, we looked for PTVs that are likely to cause Mendelian diseases. We found four heterozygous PTVs in haploinsufficient genes (KAT6A, PTCH1, and STXBP1) and three homozygous PTVs in genes causing recessive diseases (DPYD, FLG, and PYGM). Comparing frequencies from our data set to other public databases, like gnomAD, we showed the importance of population-specific databases for a more accurate assessment of variant pathogenicity. For this reason, we made aggregated frequencies from our data set publicly available as a tool for both clinicians and researchers (http://nigdb.cineca.it; NIG-ExIT).

Published
2021

22. Effects of nutritional intake on performance in master athletes during an extreme ultra-trail

Author

Marcello Lucchese, Marco Ivaldi, Giovanni Cugliari, and Felicina Biorci

Subjects
master athlete, 030209 endocrinology & metabolism, Physical Therapy, Sports Therapy and Rehabilitation, Nutrient intake, Body composition, 03 medical and health sciences, 0302 clinical medicine, Animal science, Ultra-trail, Educación Física y Deportiva, Medicine, Blood glucose, blood glucose, sleep, lcsh:Sports medicine, body composition, ultra-trail, biology, nutrient intake, Athletes, business.industry, Master athlete, 030229 sport sciences, biology.organism_classification, business, Sleep, lcsh:RC1200-1245
Abstract

The purpose of our study was to monitor a well-trained master athlete who competed in the race, keeping under review his performance outcomes. TransPyrenea (La Grande Traversée des Pyrénées) is an Ultra Trail 13-16-d race, 866 km long, 53200 meters of elevation gain, performed for the first time in 2016, becoming the longest race in the world. At every checkpoint, a member of the team ascertained total macronutrients intake and body composition. A wearable device was used to monitor glycemia during all the race. The athlete completed the race with an average speed of 2.6 Km/h, including 26 hours and 30 minutes of sleeping. Multiple regression analysis showed that the increase of the speed (β: 0.5 km/h, 95% CI: 0.07 | 1.02 km/h, p-value: 0.035 and β: 1.32 km/h, 95% CI: 0.53 | 2.11 km/h, p-value: 0.004) was related to the increase of one hour of sleep and one kg of weight respectively. This evidence could induce the use of specific nutritional supplements and the analysis of body composition on the management strategies of the race, with eventually the planning of a greater number of hours of sleep to acquire greater speed.

Published
2020

23. Effects on Sleep Bruxism Activity of Three Different Oral Appliances: One Year Longitudinal Cohort Study

Author

Andrea Bargellini, Vanessa Graziano, Giovanni Cugliari, Andrea Deregibus, and Tommaso Castroflorio

Subjects
Pharmaceutical Science
Abstract

Background: Different oral appliances (OAs) have been proposed to control sleep bruxism (SB) detrimental effects on the stomatognathic system. Objective: The aim of the study was evaluate the effect of different OAs on SB activity and masticatory muscle activity (sMMA) measured by EMG. Method: This longitudinal cohort study was conducted on 51 patients (21 M, 30 F, mean age 26,5 ± 3,5) suffering from SB diagnosed with a validated portable EMG-ECG holter and wearing different OAs: occlusal splints, functional appliance with metallic bites and clear aligners followed after 1 week, 1 month, 3 months, 6 months and 12 months from delivery. A control group of 16 non-treated SB patients (6 M, 10 F mean age 27,1 ± 1,4) was used as reference. A multiple regression analysis was performed to estimate the differences between groups. Significance was set as P value Results: Occlusal splint reduced sleep bruxism index after 1 week, 3, 6 and 12 months from delivery while functional appliance only after 12 months. Occlusal splints reduced general phasic contractions only in the first week and sleep bruxism-related phasic contractions at 1 week, 3 and 6 months after delivery with no significant reductions after 12 months. Patients wearing clear aligners showed reduction in general tonic contractions after 6 and 12 months. Conclusion: Resin and metal bites can reduce sleep bruxism index, while resin bites can reduce sleep bruxism-related phasic contractions. Clear aligners do not influence sleep bruxism index but can reduce tonic contractions.

Published
2022

24. Variations in athletic performance with occlusal splint in track and field athletes: a randomized clinical trial

Author

Simone Parrini, Andrea Deregibus, Tommaso Castroflorio, Gabriele Rossini, Marco Airale, Alberto Franceschi, Bianca Nebiolo, and Giovanni Cugliari

Subjects
Orthodontics, biology, Dental occlusion, Athletes, business.industry, medicine.medical_treatment, Track and Field, Occlusal Splints, Physical Therapy, Sports Therapy and Rehabilitation, Athletic Performance, biology.organism_classification, law.invention, Randomized controlled trial, Sprint, law, Untreated control, medicine, Jump, Humans, Orthopedics and Sports Medicine, Muscle Strength, Track and field athletics, Splint (medicine), business
Abstract

Background Several studies have been proposed with the aim to demonstrate correlations between the dento-mandibular apparatus and the skeletal muscle system of the human body even in regions distant from the oral cavity. However, a definite conclusion cannot be drawn. The aim of this paper is to demonstrate a possible correlation between dental occlusion and sport performances in track and field athletes. Methods 16 track and field athletes were enrolled for the study and were randomly divided in three groups: Untreated control group, Placebo group (with a lower plaque without occlusal coverage) and Treated group (with occlusal splint). Changes in sprint and jump performance were assessed on a weekly basis for 5 consecutive weeks, during which athletes had to wear oral devices, except for the first week of baseline, for at least 3 trainings lasting 2 hours per week. All participants performed the countermovement jump (CMJ), the drop jump (DJ), the 10m and 30m sprint tests, always on the same day on the week. Results No statistically significant difference resulted between Control group and Placebo group and between Control group and Treated group. However it was possible to observe a clinical improvement of measurements obtained, especially for CMJ, 10m and 30m sprint tests. No variation neither statistical neither clinical was observed in DJ test analysis. Conclusions Even if statistically it was not possible to demonstrate an improvement in sport performance, most of the athlete analyzed showed better results during training session with occlusal splint compared to athlete without occlusal splint, in countermovement jump, in 10m and 30m sprint tests.

Published
2022

25. Micro computed tomography evaluation of Invisalign aligner thickness homogeneity

Author

Simone Parrini, Damiano Pasqualini, Andrea Deregibus, Nicola Scotti, Tommaso Castroflorio, Emanuele Coda, Edoardo Mantovani, and Giovanni Cugliari

Subjects
Aligners, Orthodontics, Molar, Materials science, Tooth Movement Techniques, Thickness, Homogeneity (statistics), Micro computed tomography, Significant difference, Original Articles, X-Ray Microtomography, Mean difference, Incisor, medicine.anatomical_structure, stomatognathic system, Orthodontic Appliances, Removable, medicine, Humans, Tomography
Abstract

Objectives To measure the thickness homogeneity of Invisalign (Align Technology Inc, San José, Calif) aligners with micro-computed tomography (micro-CT) scans. Materials and Methods Starting from micro-CT scanning of 20 different aligners, multiplanar reconstructions were obtained. An orthodontist blinded about the study measured aligner thickness in different regions (molar, canine, incisor) and in different sites (gingival–buccal, buccal, occlusal, lingual, and gingival–lingual). To assess various thicknesses in different aligner sites and regions, the sample was stratified into subgroups and linear regression analysis was performed. Results Descriptive analysis showed that mean thickness of aligners in the incisor region ranged from 0.582 mm to 0.639 mm, in the canine region from 0.569 mm to 0.644 mm, and in the molar region from 0.566 mm to 0.634 mm. Student's t-tests showed no significant differences in the aligner thickness of different regions when data were stratified by different sites. Student's t-tests showed significant differences in thickness homogeneity for the molar region when the data were stratified by tooth (mean difference = 0.068 mm; 95% confidence interval, 0.009–0.126 mm; P = .024). Conclusions Invisalign aligner thickness is characterized by small differences. The only significant difference was revealed in the molar region where thickness of the gingival–lingual edge is significantly thinner than that measured at the occlusal aspect. From a clinical perspective, the results of the present study could be considered to explain the reduced predictability of several orthodontic tooth movements in the molar region.

Published
2021

26. New DNA methylation signals for malignant pleural mesothelioma risk assessment

Author

Federica Grosso, Marika Sculco, Roberta Libener, Corrado Magnani, Giuseppe Matullo, Alessia Russo, Dario Mirabelli, Alessandra Allione, Daniela Ferrante, Chiara Pirazzini, Marta La Vecchia, Elisabetta Casalone, Chiara Catalano, Simonetta Guarrera, Giovanni Cugliari, and Irma Dianzani

Subjects
0301 basic medicine, Oncology, False discovery rate, Cancer Research, medicine.medical_specialty, Malignant pleural mesothelioma, medicine.disease_cause, Asbestos, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, RC254-282, Epigenome-wide analysis, DNA methylation, business.industry, Confounding, Area under the curve, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, dNaM, Asbestos exposure, Interaction analysis, Odds ratio, 030104 developmental biology, 030220 oncology & carcinogenesis, business, Risk assessment
Abstract

Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm. Patients are usually diagnosed when current treatments have limited benefits, highlighting the need for noninvasive tests aimed at an MPM risk assessment tool that might improve life expectancy. Three hundred asbestos-exposed subjects (163 MPM cases and 137 cancer-free controls), from the same geographical region in Italy, were recruited. The evaluation of asbestos exposure was conducted considering the frequency, the duration and the intensity of occupational, environmental and domestic exposure. A genome-wide methylation array was performed to identify novel blood DNA methylation (DNAm) markers of MPM. Multiple regression analyses adjusting for potential confounding factors and interaction between asbestos exposure and DNAm on the MPM odds ratio were applied. Epigenome-wide analysis (EWAS) revealed 12 single-CpGs associated with the disease. Two of these showed high statistical power (99%) and effect size (&gt, 0.05) after false discovery rate (FDR) multiple comparison corrections: (i) cg03546163 in FKBP5, significantly hypomethylated in cases (Mean Difference in beta values (MD) = −0.09, 95% CI = −0.12|−0.06, p = 1.2 × 10−7), and (ii) cg06633438 in MLLT1, statistically hypermethylated in cases (MD = 0.07, 95% CI = 0.04|0.10, p = 1.0 × 10−6). Based on the interaction analysis, asbestos exposure and epigenetic profile together may improve MPM risk assessment. Above-median asbestos exposure and hypomethylation of cg03546163 in FKBP5 (OR = 20.84, 95% CI = 8.71|53.96, p = 5.5 × 10−11) and hypermethylation of cg06633438 in MLLT1 (OR = 11.71, 95% CI = 4.97|29.64, p = 5.9 × 10−8) genes compared to below-median asbestos exposure and hyper/hypomethylation of single-CpG DNAm, respectively. Receiver Operation Characteristics (ROC) for Case-Control Discrimination showed a significant increase in MPM discrimination when DNAm information was added in the model (baseline model, BM: asbestos exposure, age, gender and white blood cells), area under the curve, AUC = 0.75, BM + cg03546163 at FKBP5. AUC = 0.89, 2.1 × 10−7, BM + cg06633438 at MLLT1. AUC = 0.89, 6.3 × 10−8. Validation and replication procedures, considering independent sample size and a different DNAm analysis technique, confirmed the observed associations. Our results suggest the potential application of DNAm profiles in blood to develop noninvasive tests for MPM risk assessment in asbestos-exposed subjects.

Published
2021

27. Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation

Author

Giuseppe Matullo, John R. B. Perry, Meena Kumari, Gemma C Sharp, Tomáš Paus, E. Giralt-Steinhauer, Marta E. Alarcón-Riquelme, Koen F. Dekkers, F. Gagnon, Simonetta Guarrera, Cilla Söderhäll, Rosie M. Walker, Therese Tillin, M. Smarts, Juan E. Castillo-Fernandez, John M. Starr, Jean Shin, Dan Mason, T Esko, Christopher Shaw, Hannah R Elliott, Manon Bernard, David L. Corcoran, Yvonne Awaloff, Ahmad Al Khleifat, Bert Brunekreef, Clara Viberti, John Wright, Gibran Hemani, Kathryn L. Evans, Camilla Schmidt Morgen, Jouke J. Hottenga, Susan M. Ring, Terrie E. Moffitt, Silva Kasela, C. Hale, Idil Yet, Katri Räikkönen, René Luijk, Vanessa Schmoll, Kimberley Burrows, Annelot M. Dekker, D. VanHeemst, Jordana T. Bell, Jordi Jimenez-Conde, Carlotta Sacerdote, Salvatore Panico, Lili Milani, Nabila Kazmi, Torben Hansen, Aleksey Shatunov, J L Min, Richa Gupta, Henning Tiemeier, Grant W. Montgomery, Vincent W. V. Jaddoe, E.J.C. de Geus, Fernando Rivadeneira, Debbie A Lawlor, Carol A. Wang, Toni-Kim Clarke, Susanne Lucae, Nicholas J. Wareham, Jordi Sunyer, Felix R. Day, C. Soriano-Tarraga, Christoph Bock, Juan R. González, D. Aissi, J.B. van Meurs, Ian J. Deary, Ken K. Ong, Louise Arseneault, Eilis Hannon, Bastiaan T. Heijmans, Philip E. Melton, Ashok Kumar, Pierre-Emmanuel Morange, Zdenka Pausova, T.D. Spector, Nicholas G. Martin, J. Mill, Francesc Català-Moll, Alun D. Hughes, Leonard C. Schalkwyk, Giovanni Cugliari, Carlos Ruiz-Arenas, Elena Carnero-Montoro, Marine Germain, Yanni Zeng, Andrew M. McIntosh, Riccardo E. Marioni, Wilfried Karmaus, Ikram, Gonneke Willemsen, Miina Ollikainen, Karen M Ho, Craig E. Pennell, F.I. Rezwan, Darina Czamara, Ramona A. J. Zwamborn, Dorret I. Boomsma, Wendy L. McArdle, J. M. van Dongen, Guillermo Barturen, Matthew Suderman, Richie Poulton, Daniel Lawson, A. Metspalu, David-Alexandre Trégouët, Marian Beekman, Andrew D. Bretherick, Johanna Klughammer, Hongmei Zhang, M.H. van IJzendoorn, Nish Chaturvedi, Jari Lahti, Karen Sugden, Jan H. Veldink, Mariona Bustamante, Avshalom Caspi, Pooja R. Mandaviya, Judith M. Vonk, Tom R. Gaunt, Cheng-Jian Xu, John W. Holloway, Tian Lin, Tom G. Richardson, Caroline L Relton, Naomi R. Wray, Allan F. McRae, George Davey Smith, Erik Melén, Valentina Iotchkova, Ellen A. Nohr, Jaakko Kaprio, Göran Pershagen, Elisabeth B. Binder, A. al Chalabi, T.J. Gorrie-Stone, K. van Eijk, Gerard H. Koppelman, M. Lerro, Alexia Cardona, Sailalitha Bollepalli, P.E. Slagboom, Thorkild I. A. Sørensen, André G. Uitterlinden, Jaume Roquer, Peter M. Visscher, Janine F. Felix, Martin Kerick, Gail Davies, Rae-Chi Huang, Alfredo Iacoangeli, Alison D. Murray, Helsinki Institute of Life Science HiLIFE, Institute for Molecular Medicine Finland, Epigenetics of Complex Diseases and Traits, Department of Public Health, Department of Psychology and Logopedics, Biological Psychology, APH - Mental Health, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, APH - Methodology, Groningen Research Institute for Asthma and COPD (GRIAC), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Epidemiology, Internal Medicine, Pediatrics, Child and Adolescent Psychiatry / Psychology, and Clinical Child and Family Studies

Subjects
Multifactorial Inheritance, ADN, Quantitative Trait Loci, Genome-wide association study, VARIANTS, Biology, Quantitative trait locus, Polymorphism, Single Nucleotide, LINKS, Epigenesis, Genetic, 03 medical and health sciences, 0302 clinical medicine, Quantitative Trait, Heritable, Genetic variation, Genetics, WIDE ASSOCIATION, GWAS, Humans, Genetic Predisposition to Disease, Genotip, METAANALYSIS, EQTL, 030304 developmental biology, Epigenesis, SNP ANALYSIS, 0303 health sciences, COMPLEX, dNaM, Chromosome Mapping, DNA, DNA Methylation, Phenotype, Genetic architecture, MODEL, Fenotip, Gene Expression Regulation, DNA methylation, MENDELIAN RANDOMIZATION, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 3111 Biomedicine, Metilació, Transcriptome, Genètica, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

DNA methylation quantitative trait locus (mQTL) analyses on 32,851 participants identify genetic variants associated with DNA methylation at 420,509 sites in blood, resulting in a database of >270,000 independent mQTLs. Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype-phenotype map than previously anticipated.

Published
2020

28. DNA Methylation of

Author

Giovanni, Cugliari, Chiara, Catalano, Simonetta, Guarrera, Alessandra, Allione, Elisabetta, Casalone, Alessia, Russo, Federica, Grosso, Daniela, Ferrante, Clara, Viberti, Anna, Aspesi, Marika, Sculco, Chiara, Pirazzini, Roberta, Libener, Dario, Mirabelli, Corrado, Magnani, Irma, Dianzani, and Giuseppe, Matullo

Subjects
asbestos exposure, DNA methylation, epigenome-wide analysis, lymphocyte-to-monocyte ratio, malignant pleural mesothelioma, Article, survival analysis
Abstract

Simple Summary Our study is the first one to investigate DNA methylation changes in white blood cells (WBCs) from easily accessible peripheral blood as malignant pleural mesothelioma (MPM) survival biomarker. The Cox proportional hazards regression model highlighted that the methylation status of the CpG dinucleotide cg03546163 is an independent marker of prognosis in MPM patients with a better performance than traditional inflammation-based scores such as lymphocyte-to-monocyte ratio (LMR). Biological validation and replication showed that epigenetic changes at the FKBP5 gene were robustly associated with overall survival (OS) in MPM cases. The identification of simple and valuable prognostic markers for MPM will enable clinicians to select patients who are most likely to benefit from aggressive therapies and avoid subjecting non-responder patients to ineffective treatment. Abstract Malignant pleural mesothelioma (MPM) is an aggressive tumor with median survival of 12 months and limited effective treatments. The scope of this study was to study the relationship between blood DNA methylation (DNAm) and overall survival (OS) aiming at a noninvasive prognostic test. We investigated a cohort of 159 incident asbestos exposed MPM cases enrolled in an Italian area with high incidence of mesothelioma. Considering 12 months as a cut-off for OS, epigenome-wide association study (EWAS) revealed statistically significant (p value = 7.7 × 10−9) OS-related differential methylation of a single-CpG (cg03546163), located in the 5′UTR region of the FKBP5 gene. This is an independent marker of prognosis in MPM patients with a better performance than traditional inflammation-based scores such as lymphocyte-to-monocyte ratio (LMR). Cases with DNAm < 0.45 at the cg03546163 had significantly poor survival compared with those showing DNAm ≥ 0.45 (mean: 243 versus 534 days; p value< 0.001). Epigenetic changes at the FKBP5 gene were robustly associated with OS in MPM cases. Our results showed that blood DNA methylation levels could be promising and dynamic prognostic biomarkers in MPM.

Published
2020

29. Genomic and phenomic insights from an atlas of genetic effects on DNA methylation

Author

Carol A. Wang, Simonetta Guarrera, Avshalom Caspi, Eilis Hannon, Marta E. Alarcón-Riquelme, P. Eline Slagboom, Pooja R. Mandaviya, Koen F. Dekkers, Cheng-Jian Xu, Jari Lahti, Juan E. Castillo-Fernandez, Dan Mason, Dylan Aïssi, Jan H. Veldink, Mariona Bustamante, Melissa C. Smart, Guillermo Barturen, Zdenka Pausova, Jenny van Dongen, Jordi Jimenez-Conde, Craig E. Pennell, Gibran Hemani, Tom R. Gaunt, Camilla Schmidt Morgen, Ken K. Ong, Toni-Kim Clarke, Alexia Cardona, Susanne Lucae, René Luijk, T.J. Gorrie-Stone, Phillip E. Melton, Thorkild I. A. Sørensen, André G. Uitterlinden, Jordana T. Bell, Jouke-Jan Hottenga, Meena Kumari, Francesc Català-Moll, Jonathan Mill, Tõnu Esko, Sailalitha Bollepalli, Dorret I. Boomsma, Torben Hansen, Hongmei Zhang, Yanni Zeng, John Wright, Wilfried Karmaus, Martin Kerick, Carolina Soriano-Tárraga, Jaakko Kaprio, Miina Ollikainen, Eco J. C. de Geus, Jordi Sunyer, Therese Tillin, Juan R. González, Yvonne Awaloff, Faisal I. Rezwan, Karen Sugden, Nicholas G. Martin, Karen M Ho, Andres Metspalu, Marine Germain, Kristel R. van Eijk, Ramona A. J. Zwamborn, George Davey Smith, Judith M. Vonk, Tian Lin, Henning Tiemeier, Grant W. Montgomery, Naomi R. Wray, Rae-Chi Huang, Alfredo Iacoangeli, Wendy L. McArdle, Jean Shin, Michael Lerro, Darina Czamara, Valentina Iotchkova, David-Alexandre Trégouët, Johanna Klughammer, Elena Carnero-Montoro, Pierre-Emmanuel Morange, Andrew M. McIntosh, Gemma C Sharp, Alun D. Hughes, Carlos Ruiz-Arenas, John M. Starr, Riccardo E. Marioni, Peter M. Visscher, Nabila Kazmi, Ian J. Deary, Kathryn L. Evans, Terrie E. Moffitt, Janine F. Felix, Tomáš Paus, Ashok Kumar, Jaume Roquer, Christopher Shaw, Hannah R Elliott, Susan M. Ring, Nish Chaturvedi, Giovanni Cugliari, Ahmad Al Khleifat, Joyce B. J. van Meurs, Kimberley Burrows, Bert Brunekreef, Debbie A Lawlor, Clara Viberti, Louise Arseneault, Silva Kasela, Cilla Söderhäll, Idil Yet, Manon Bernard, Christoph Bock, Vincent W. V. Jaddoe, Felix R. Day, Diana van Heemst, Alison D. Murray, Nicholas J. Wareham, Giuseppe Matullo, John R. B. Perry, Gerard H. Koppelman, M. Arfan Ikram, Ammar Al Chalabi, Gonneke Willemsen, Richie Poulton, Daniel Lawson, Andrew D. Bretherick, Vanessa Schmoll, Carlotta Sacerdote, Annelot M. Dekker, Lili Milani, Fernando Rivadeneira, Erik Melén, John W. Holloway, Gareth E. Davies, Tom G. Richardson, Caroline L Relton, Josine L. Min, Göran Pershagen, Elisabeth B. Binder, Marian Beekman, Chris Haley, Richa Gupta, Bastiaan T. Heijmans, Ellen A. Nohr, Allan F. McRae, Matthew Suderman, Rosie M. Walker, David L. Corcoran, Katri Räikkönen, Marinus H. van IJzendoorn, Eva Giralt-Steinhauer, Leonard C. Schalkwyk, Aleksey Shatunov, and Tim D. Spector

Subjects
Genetics, Regulation of gene expression, 0303 health sciences, Natural selection, dNaM, Biology, Genetic architecture, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Genetic variation, DNA methylation, Trait, 030217 neurology & neurosurgery, DNA, 030304 developmental biology
Abstract

Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. Here we describe results of DNA methylation-quantitative trait loci (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTL of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We reveal that the genetic architecture of DNAm levels is highly polygenic and DNAm exhibits signatures of negative and positive natural selection. Using shared genetic control between distal DNAm sites we construct networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic factors are associated with both blood DNAm levels and complex diseases but in most cases these associations do not reflect causal relationships from DNAm to trait or vice versa indicating a more complex genotype-phenotype map than has previously been hypothesised.

Published
2020

30. Does occlusal splint affect posture? A randomized controlled trial

Author

Andrea Deregibus Md, Tommaso Castroflorio, Giovanni Cugliari, and Ilaria De Giorgi

Subjects
musculoskeletal diseases, medicine.medical_treatment, Posture, body posture, Temporomandibular disorders, Affect (psychology), law.invention, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, Randomized controlled trial, law, occlusal splint, Humans, Medicine, rasterstereography, Otorhinolaryngology2734 Pathology and Forensic Medicine, Dentistry (all), General Dentistry, Orthodontics, Body posture, business.industry, Occlusal Splints, 030206 dentistry, Temporomandibular Joint Disorders, Temporomandibular joint, stomatognathic diseases, medicine.anatomical_structure, Otorhinolaryngology, Lordosis, Female, business, Splint (medicine), 030217 neurology & neurosurgery
Abstract

The aim of this study was to evaluate the effect of an occlusal splint on body posture of intra-articular temporomandibular joint (TMJ) disorders patients.The study was performed on 45 women affected by TMJ disorders divided into an occlusal splint group and a control group. Rasterstereographic recordings were performed at baseline and after 1, 3, and 6 months, in order to analyze the following postural parameters: trunk inclination, cervical and lumbar arrows, kyphotic and lordotic angles, trunk imbalance, pelvic tilt and torsion.Regarding the postural parameters in the intragroup analysis, no significant differences were detected. The analysis between the two groups revealed significant differences concerning the cervical arrow, the kyphotic and lordotic angles.Even if some differences were found between the control and the occlusal splint group, the low range of statistical significance made these results not significant from a clinical point of view.

Published
2018

31. Relationship of chlorophyll supplement and platelet-related measures in endurance athletes: a randomized, double-blind, placebo-controlled study

Author

Fabrizio Messina, Felicina Biorci, Valter Canavero, Marco Ivaldi, and Giovanni Cugliari

Subjects
medicine.medical_specialty, medicine.diagnostic_test, Sports medicine, biology, business.industry, Athletes, Platelet Distribution Width, Placebo-controlled study, 030204 cardiovascular system & hematology, Placebo, biology.organism_classification, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Serum iron, medicine, Orthopedics and Sports Medicine, Platelet, Mean platelet volume, business
Abstract

The aim of this study was to verify the effects of protracted intake of chlorophyll on blood counts’ parameters and iron levels in endurance athletes, investigating supposed anti-anemic properties. Twenty-two endurance athletes were randomly assigned into two groups in a double-blind study: the experimental group (EG) consumed chlorophyll, while the control group (CG) consumed a placebo, at a dose of 1.6 drops × kg per day for 120 days. Blood cell count and the serum iron analyses were carried out before starting the experiment, after 30 days and after 120 days. EG showed statistically significant increase in platelet distribution width (PDW, MD = 0.83, 95% CI 0.41, 1.38), mean platelet volume (MPV, MD = 0.41, 95% CI 0.19, 0.67) and platelet/large cell ratio (P-LCR, MD = 3.28, 95% CI 1.51, 5.25) after 120 days. No variations in CG were found during the follow-up. The increase of platelet-related measures could positively influence the endurance performance by reducing pain and fatigue. The supposed ergogenic effects and anti-anemic properties however require further study.

Published
2018

32. Electrocortical activity during stretch reflex in athletes

Author

Francesca Pretari, Giovanni Cugliari, and Marco Ivaldi

Subjects
medicine.medical_specialty, Supine position, Brain activity and meditation, business.industry, 030229 sport sciences, Neurophysiology, medicine.disease, Time–frequency analysis, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Physical medicine and rehabilitation, Concussion, medicine, Orthopedics and Sports Medicine, Analysis of variance, Stretch reflex, business, 030217 neurology & neurosurgery, Reflex hammer
Abstract

To evaluate timing and characteristics of electrocortical activity during stretch reflex evocation of the quadriceps femoris at different body postures. Twenty athletes were subjected to reflex hammer percussions on patellar tendon, in a random time sequence, in seated and supine decubitus postures. 745 ms of acquisition were evaluated for data analysis: 200 ms of pre-stimulation, 45 ms relative to the elapsed time from stimulation to the end of the muscular contraction, and 500 ms of post-stimulation. First, a scalp-map analysis, considering channels data, was performed; second, independent component analysis decomposition was applied to all 16 channels. To highlight the differences among two conditions (pre- and post-stimulation) and two sessions (seated and supine decubitus postures), a two-way analysis of variance was used. Time–frequency analysis has been applied to identify the density of the frequencies as a function of the time, instant by instant. Fast alpha, beta, and gamma frequency bands showed a greater electroencephalographic activity after the stimulation. Seated posture showed a greater activation than the decubitus supine posture. Time frequency analysis highlighted an higher electrocortical activation for 160 ms as well as from about 250–300 ms at all frequency bands after the stimulation. Our findings improve the understanding of the neurophysiological dynamics following the stretch reflex after concussion of the patellar tendon, executed in different postures, considering scalp-map, power spectra, and timing of activation. The use of scalp-map and power spectra analysis techniques represents a sophisticated use of advanced signal processing methodologies to analyze brain activity during movement and in specificity in sport science.

Published
2018

33. Delta and alpha rhythms are modulated by the physical movement knowledge in acrobatic gymnastics: an EEG study in visual context

Author

Giovanni Cugliari, Alberto Rainoldi, Eleonora Fiorenti, and Marco Ivaldi

Subjects
medicine.medical_specialty, Visual perception, medicine.diagnostic_test, Movement (music), Context (language use), 030229 sport sciences, Audiology, Electroencephalography, Expert group, 03 medical and health sciences, 0302 clinical medicine, Eeg activity, Alpha rhythm, medicine, Orthopedics and Sports Medicine, Experience level, Psychology, 030217 neurology & neurosurgery
Abstract

The evaluation of electrocortical activity (EEG) during visual stimuli may reveal differences depending on experience level. Fourteen volunteers, seven belonging to the expert group (high experience in the field of the acrobatic gymnastics) and seven to the control one, took part in the study. Ten videos recorded during the execution of specific physical movements of acrobatic gymnastics have been included in the execution task. Power spectrum as indicator of the electrocortical activity was used. Expert group showed lower power spectra levels in delta (MD = − 2.23) and higher power spectra levels in slow alpha (MD = 2.17) bands, compared to control group during the vision of the videos with errors; during the vision of the videos without errors, expert group showed lower power spectra levels in delta (MD = − 1.04) and higher power spectra levels in slow alpha (MD = 1.88) bands compared to control group. Generally, occipital, frontal and central areas showed differences between groups in regard to power spectra levels. These findings confirm the relationship between EEG activity and vision of specific physical movements and extend knowledge on the electrocortical response to visual stimuli emphasizing the difference between experienced and inexperienced subjects, relative to the field analyzed.

Published
2018

35. Sleep bruxism and related risk factors in adults: A systematic literature review

Author

Gabriele Rossini, Tommaso Castroflorio, Giovanni Cugliari, Andrea Bargellini, and Andrea Deregibus

Subjects
Adult, medicine.medical_specialty, Adults, Review, Risk factors, Sleep bruxism, Otorhinolaryngology, 2734, Pathology and Forensic Medicine, Dentistry (all), Cell Biology, Psychological intervention, Protective factor, Sleep Bruxism, Disease, law.invention, 03 medical and health sciences, 0302 clinical medicine, Chronic Migraine, Randomized controlled trial, Otorhinolaryngology2734 Pathology and Forensic Medicine, law, Internal medicine, medicine, Humans, General Dentistry, business.industry, 030206 dentistry, General Medicine, medicine.disease, Systematic review, Physical therapy, GERD, business, 030217 neurology & neurosurgery
Abstract

Objective The aim of this article was to systematically review the literature to assess the relationship between risk factors and sleep bruxism (SB) in adults (age ≥18 years). Design A systematic search of the following databases was carried out: PubMed, Embase, Scopus, Cochrane Oral Health Group’s Trial Register and Cochrane Register of Controlled Trials, Web of Science, LILACs and SciELO. Nine out of the 4583 initially identified articles were selected. This review was conducted according to the guidelines from the Cochrane Handbook for Systematic Reviews of Interventions, with reporting in agreement to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Results Among the nine analyzed articles, associations between SB and gastro-esophageal reflux disease (GERD) (OR = 6.6, CI = 1.4–30.9) was found in one randomized clinical trial (RCT). Four cross-sectional studies suggested history of SB during childhood (OR = 8.1 CI = 5.4–12–2), age (OR = 3.1, CI = 2.3–4.1) and chronic migraine (OR = 3.8, C.I = 1.8–7.8) as determinant factors for the development of SB. In one case-control study, patients with genetic polymorphisms were more likely to present SB (OR = 4.3, CI = 1.6–11.3). Smoking (OR = 2.8, CI = 2.2–3.5) and alcohol intake (OR = 1.9, CI = 1.2–2.8) showed moderate association in two case-control studies. Conclusions History of SB during childhood, gastro-esophageal reflux disease and genetic polymorphisms seem to be important risk factors associated to SB in adults. Dry mouth on awakening seems to be a protective factor. Association does not infer with causality. Even if the evidence emerged from the considered studies was clinically relevant, further studies are requested to better understand the biological mechanisms behind the described associations.

Published
2017

36. Familiarity affects electrocortical power spectra during dance imagery, listening to different music genres: independent component analysis of Alpha and Beta rhythms

Author

Alberto Rainoldi, Marco Ivaldi, Sara Peracchione, and Giovanni Cugliari

Subjects
Dance, medicine.diagnostic_test, 05 social sciences, Electroencephalography, Independent component analysis, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Motor imagery, Neuroimaging, medicine, Auditory imagery, 0501 psychology and cognitive sciences, Orthopedics and Sports Medicine, Active listening, Beta Rhythm, Psychology, 030217 neurology & neurosurgery, Cognitive psychology
Abstract

Changes in electrocortical activity during motor imagery are among the most interesting findings in the recent neuroscientific studies; existing studies, however, do not focus specifically on Alpha and Beta rhythms, in relationship with the motor experience and verifying if the style of music can influence the cortical activity during motor imagery task. Power spectra analysis was used to compare the EEG activity during dance imagery tasks in a group of dancers and in a control group. Twenty-one volunteers performed a dance imagery task listening to three kinds of music. For EEG acquisition an 8-channel headset with wireless amplifier was used. This study used independent component analysis (ICA) to assess EEG frequency spectrum associated with the musical genre. High Alpha (10.0–11.5 Hz) and Low Beta (12.0–15.5 Hz) EEG frequency spectra were analyzed. Considering EEG power spectra analysis, no statistically significant differences were found between groups at baseline. Statistically significant difference (p

Published
2017

37. Core Muscle Activation in Suspension Training Exercises

Author

Gennaro Boccia and Giovanni Cugliari

Subjects
electromyography, medicine.medical_specialty, Physical Therapy, Strength training, Physical Therapy, Sports Therapy and Rehabilitation, Sports Therapy and Rehabilitation, Isometric exercise, Electromyography, Concentric, 03 medical and health sciences, abdominal muscles, core stability, 0302 clinical medicine, Physical medicine and rehabilitation, Physiology (medical), Erector spinae muscles, Medicine, Core (anatomy), medicine.diagnostic_test, business.industry, Repeated measures design, Core stability, 030229 sport sciences, core strength, Section I – Kinesiology, business, 030217 neurology & neurosurgery
Abstract

A quantitative observational laboratory study was conducted to characterize and classify core training exercises executed in a suspension modality on the base of muscle activation. In a prospective single-group repeated measures design, seventeen active male participants performed four suspension exercises typically associated with core training (roll-out, bodysaw, pike and knee-tuck). Surface electromyographic signals were recorded from lower and upper parts of rectus abdominis, external oblique, internal oblique, lower and upper parts of erector spinae muscles using concentric bipolar electrodes. The average rectified values of electromyographic signals were normalized with respect to individual maximum voluntary isometric contraction of each muscle. Roll-out exercise showed the highest activation of rectus abdominis and oblique muscles compared to the other exercises. The rectus abdominis and external oblique reached an activation higher than 60% of the maximal voluntary contraction (or very close to that threshold, 55%) in roll-out and bodysaw exercises. Findings from this study allow the selection of suspension core training exercises on the basis of quantitative information about the activation of muscles of interest. Roll-out and bodysaw exercises can be considered as suitable for strength training of rectus abdominis and external oblique muscles.

Published
2017

38. Associations of autozygosity with a broad range of human phenotypes

Author

Dennis O. Mook-Kanamori, Salma M. Wakil, Lisa R. Yanek, Dominique P.V. de Kleijn, Gert J. de Borst, Alison D. Murray, Kamran Guity, Vincent W. V. Jaddoe, Mario Pirastu, Carole Ober, Giuseppe Matullo, Charles N. Rotimi, Daniela Ruggiero, Teresa Tusié-Luna, Wolfgang Lieb, Chew-Kiat Heng, John R. B. Perry, Hortensia Moreno-Macías, Jie Zhou, John M. Starr, Juhani Junttila, Lei Yu, Danielle Posthuma, Marcus Dörr, Yingchang Lu, Jonathan P. Bradfield, Einat Granot-Hershkovitz, Karina Meidtner, Wouter van Rheenen, T Esko, Maris Alver, Wen-Jane Lee, Zhengming Chen, Jennifer A. Brody, Paolo Gasparini, Yii-Der Ida Chen, Cinzia Sala, Peter P. Pramstaller, Gauri Prasad, Nana Matoba, Natalie Terzikhan, Simonetta Guarrera, Bjarke Feenstra, Peter Vollenweider, Smeeta Shrestha, Yi-Jen Hung, Lilja Stefansdottir, David R. Weir, Felix R. Day, Antonietta Robino, Liang Zhang, Lluis Quintana-Murci, Nicholas J. Timpson, Robyn E Wootton, Xue W. Mei, Dharambir K. Sanghera, Gisli Masson, Debbie A Lawlor, Thomas Meitinger, Sharon L.R. Kardia, Peter K. Joshi, Frank J. A. van Rooij, Claude Bouchard, Cassandra N. Spracklen, Ken K. Ong, Taulant Muka, Guanjie Chen, Laura J. Scott, Walter Palmas, Daniel I. Chasman, Sarah E. Medland, Krista Fischer, Blair H. Smith, Jon K. Sigurdsson, Leon Straker, Clara Viberti, Yuan Shi, Louis Pérusse, Peter J. van der Most, Timo Tõnis Sikka, Chris Haley, Kuang Lin, Leif Groop, Hester M. den Ruijter, Hakon Hakonarson, Masato Akiyama, Stephan J. L. Bakker, Sonja I. Berndt, Jeffery R. O'Connell, Cisca Wijmenga, Daniele Cusi, Lorena Orozco, Kristjan H. S. Moore, Kevin Sandow, Stephen S. Rich, Stephanie J. Loomis, George Davey Smith, Cornelia M. van Duijn, Sharvari Rahul Shukla, Agnar Helgason, Thorsten Kessler, Anuj Goel, Dan Mason, David W. Clark, James S. Pankow, Simona Vaccargiu, Uwe Völker, Tamara B. Harris, Matthew A. Allison, Clicerio Gonzalez, Sarju Ralhan, I-Te Lee, Matthias Laudes, Yen-Feng Chiu, Neil Poulter, Benjamin Lehne, John Wright, Lawrence F. Bielak, Philip L. De Jager, Reinhold Schmidt, Ya Xing Wang, Matthias Nauck, Diana L. Cousminer, Patrick Deelen, Ani Manichaikul, Stephen J. Chanock, Anders Hamsten, Barry I. Freedman, Gudmar Thorleifsson, Peter Kraft, Ozren Polasek, Jie Yao, Yoshinori Murakami, Paul M. Ridker, Anubha Mahajan, Struan F.A. Grant, Claudia Schurmann, Bjarni Gunnarsson, Catriona L. K. Barnes, Jessica van Setten, Sandosh Padmanabhan, Alena Stančáková, Markus M. Lerch, Anuradha Jagadeesan, Franco Giulianini, Daniel F. Gudbjartsson, Dwaipayan Bharadwaj, Shengchao Alfred Li, Peter S. Sever, Trevor A. Mori, Albertine J. Oldehinkel, Koichi Matsuda, Xueling Sim, Evangelos Evangelou, André G. Uitterlinden, Pekka Jousilahti, Yukihide Momozawa, Ioanna Tzoulaki, Chao A. Hsiung, Ginevra Biino, Murielle Bochud, Hannele Mattsson, Ilja M. Nolte, Sarah H. Wild, Patricia B. Munroe, Jianjun Liu, Bruce M. Psaty, Giriraj R. Chandak, Masahiro Kanai, Tony R. Merriman, Teemu Palviainen, Rodney A. Lea, Janie Corley, Nicholas J. Wareham, Alan B. Zonderman, Makoto Hirata, Matthew J. Bixley, Caroline Hayward, Nora Franceschini, Kristel R van Eijk, Etienne Patin, Daniel Shriner, Niek Verweij, Xiuqing Guo, Fredrik Karpe, Ruth J. F. Loos, Tiinamaija Tuomi, Ashley van der Spek, Patricia A. Peyser, Jessica D. Faul, Christian Fuchsberger, David Cesarini, Alex S. F. Doney, Janine F. Felix, Cornelius A. Rietveld, Jagadish Vangipurapu, Tanguy Corre, Line Skotte, Rajkumar Dorajoo, Catherine Igartua, Meena Kumari, Nona Sotoodehnia, Leonard H. van den Berg, Najaf Amin, Dale R. Nyholt, Harry Campbell, Massimiliano Cocca, Scott D. Gordon, Patrik K. E. Magnusson, John C. Chambers, Traci M. Bartz, Mike A. Nalls, Tin Aung, Nduna Dzimiri, Colin N. A. Palmer, Rob M. van Dam, Johanna Kuusisto, Russell P. Tracy, Anna Damulina, Pierre-Emmanuel Morange, Sylvain Foisy, Jing Hua Zhao, Nicholas G. Martin, Ching-Yu Cheng, Mariaelisa Graff, Rashmi B. Prasad, Alice Stanton, David-Alexandre Trégouët, Yu Guo, Helen R. Warren, Lyn R. Griffiths, Weihua Meng, Annika Tillander, Christa Meisinger, Albert V. Smith, Mark I. McCarthy, Jingyun Yang, Marine Germain, Neil Small, Linda Broer, Vilmundur Gudnason, Gunnar K. Pálsson, Michele K. Evans, Alexander Teumer, Mark J. Caulfield, Giorgia Girotto, Thomas Lumley, Tinca J. C. Polderman, Wei Zhao, Carlos A. Aguilar-Salinas, Jari Lahti, Matthew L. Albert, Yechiel Friedlander, Veikko Salomaa, Iona Y Millwood, Jan H. Veldink, Archie Campbell, Andres Metspalu, Ulf Gyllensten, Grant W. Montgomery, Veronique Vitart, Jai Rup Singh, Saima Afaq, Alan R. Shuldiner, Miao-Li Chee, Adebowale Adeyemo, Jennifer A. Smith, David A. van Heel, Jaspal S. Kooner, Daniela Toniolo, Cristian Pattaro, Jerome I. Rotter, John Whitfield, Melissa C. Smart, Kari E. North, Salman M. Tajuddin, Tallapragada Divya Sri Priyanka, Christopher A. Haiman, Diane M. Becker, Bernhard K. Krämer, Paul Elliott, Lihua Wang, He Gao, Patrick Sulem, Jinyan Huang, Chiea Chuen Khor, Ruifang Li-Gao, Åsa Johansson, Winfried März, Shai Carmi, Ilaria Gandin, Eric Boerwinkle, Gardar Sveinbjornsson, Saskia P. Hagenaars, Sander W. van der Laan, Gerard Pasterkamp, E-Shyong Tai, Hagit Hochner, Yih Chung Tham, Kent D. Taylor, Kari Stefansson, Matt J. Neville, Craig E. Pennell, Yanchun Bao, Annelot M. Dekker, Helena Schmidt, Mehdi Hedayati, Joshua Elliott, Ian J. Deary, Iris E. Jansen, Judith B. Borja, Edith Hofer, Martin Gögele, Igor Rudan, Lude Franke, Matthias Munz, Folkert W. Asselbergs, Bengt Sennblad, Imo Hofer, John D. Rioux, Pim van der Harst, Bahareh Sedaghati-khayat, Giovanni Cugliari, Morris A. Swertz, Francine Grodstein, Erwin P. Bottinger, Carol A. Wang, Andre Franke, Brian F. Meyer, Adele M. Taylor, Klodian Dhana, Jian'an Luan, Constance Turman, Robert A. Scott, May E. Montasser, Alison Pattie, Marco Brumat, Liming Li, Heiner Boeing, Karen L. Mohlke, Clemens Baumbach, Bishwa Raj Sapkota, Unnur Thorsteinsdottir, Naveed Sattar, Amy R. Bentley, Matthias B. Schulze, Ivana Kolcic, Stella Trompet, Sarah E. Harris, Ayo P. Doumatey, Charumathi Sabanayagam, David Eccles, Mary F. Feitosa, Jost B. Jonas, Massimo Mezzavilla, Mark O. Goodarzi, David Ellinghaus, Heribert Schunkert, Christian Gieger, Heikki V. Huikuri, Lingyao Zeng, Johan G. Eriksson, Woon-Puay Koh, Yucheng Jia, Gurpreet Singh Wander, James F. Wilson, Torgny Karlsson, Steven C. Hunt, Weihua Zhang, Maria Pina Concas, Zoltán Kutalik, Rebecca Rohde, Chittaranjan S. Yajnik, Yasaman Saba, Dabeeru C. Rao, Robin G. Walters, Reedik Mägi, Marie Loh, Eero Vuoksimaa, Josyf C. Mychaleckyj, Katri Räikkönen, Philippe Goyette, M. Arfan Ikram, Alicia Huerta-Chagoya, David J. Porteous, Teresa Nutile, J. Wouter Jukema, Noha A. Yousri, Yoichiro Kamatani, Maryam S. Daneshpour, Babette S. Zemel, Rona J. Strawbridge, Tien Yin Wong, Claudia Langenberg, Amy Moore, Marcus E. Kleber, Fereidoun Azizi, Avner Halevy, Erika Salvi, Francis S. Collins, Markku Laakso, Tim Kacprowski, S. Sunna Ebenesersdóttir, William R. Scott, Michael Boehnke, Jin-Fang Chai, Markus Perola, Nicola Pirastu, Wayne Huey-Herng Sheu, Robert Karlsson, Lenore J. Launer, Lili Milani, Renée de Mutsert, Fernando Rivadeneira, David A. Bennett, Nicola D. Kerrison, Paolo Manunta, Graciela E. Delgado, Magnus Johannesson, Carolina Medina-Gomez, Alanna C. Morrison, Kay-Tee Khaw, Jian-Min Yuan, Jaakko Kaprio, Melanie Waldenberger, Ralf Ewert, Hugoline G. de Haan, Andrew A. Hicks, Yukinori Okada, Maria Sabater-Lleal, Marilyn C. Cornelis, Stephanie J. London, Federica Rizzi, Jeanette Erdmann, Marina Ciullo, Michiaki Kubo, University of Edinburgh, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Osaka University Graduate School of Medicine, Laboratory for Cardiovascular Genomics and Informatics [Yokohama] (RIKEN IMS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), deCODE genetics [Reykjavik], Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK (BIHR), Area Science Park, Università degli studi di Trieste = University of Trieste, MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Harbor UCLA Medical Center [Torrance, Ca.], Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, Department of Electrical and Computer Engineering [Waterloo] (ECE), University of Waterloo [Waterloo], Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Institute of Pop. Genetics, CNR, Sassari, Shardna life science Pula Cagliari, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), Medstar Research Institute, Florida State University [Tallahassee] (FSU), University Medical Center [Utrecht], Centre for Population Health Sciences, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), California State University [Sacramento], Department of Thrombosis and Haemostasis, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Medical University Graz, Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Heidelberg, Frederick National Laboratory for Cancer Research (FNLCR), Wellcome Trust Centre of Human Genetics, University of Oxford, Department of Epidemiology, German Institute of Human Nutrition, University Medical Center Groningen [Groningen] (UMCG), Institute of Genetics and Biophysics, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Department of Medicine, Surgery, and Dentistry, University of Milano, Icelandic Heart Association, Kopavogur, Iceland., Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Glasgow, Department of Cardiology, Leiden University Medical Center, Leiden, Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, Queen Mary University of London (QMUL), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP), Genentech, Inc., Genentech, Inc. [San Francisco], University of Tartu, Duke-NUS Medical School [Singapore], Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association, Human Genome Sequencing Center, Baylor College of Medicine, Baylor College of Medicine (BCM), Baylor University-Baylor University, University of San Carlos, Office of Population Studies Foundation, Icahn School of Medicine at Mount Sinai [New York] (MSSM), King‘s College London, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), University of Oxford, Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, Department of Internal Medicine B, University Medicine Greifswald, Greifswald, University of Chicago, University of Huddersfield, Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Section on Nephrology [Winston-Salem, NC, USA] (Department of Internal Medicine), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center-Wake Forest Baptist Medical Center, Radcliffe Department of Medicine [Oxford], Harvard School of Public Health, Kunming University of Science and Technology (KMUST), Sans affiliation, University of Southern California (USC), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), MRC Centrer for Nutritional Epidemiology and Cancer Prevention and Survival, University of Cambridge [UK] (CAM), National University of Singapore (NUS), Experimental Cardiology Laboratory (ECL), Unirversity Medical Center, Department of Medical Statistics, Epidemiology and Medical Informatics, University of Zagreb, Department of Medical Genetics, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Capital Normal University [Beijing], Saw Swee Hock School of Public Health, National Institute for Environmental Health Sciences Research Triangle Park, Brown University, MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, Toyota Research Institute, Helmholtz Zentrum München = German Research Center for Environmental Health, Department of Chemistry and Biochemistry [Boulder], University of Colorado [Boulder], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Timone [CHU - APHM] (TIMONE), Metacohorts Consortium, Universiteit Leiden, Institute of Clinical Chemistry and Laboratory Medicine, University of Groningen [Groningen], Medical Research Concil Epidemiology Unit, Institute of Medical Science, Faculty of Medicine, Genetics and Pathology, Imperial College London, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Brigham and Women's Hospital [Boston], Erasmus University Rotterdam, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Stockholm Bioinformatics Center (SBC), Stockholm University, Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, University of Utrecht, Utrecht, INRH, Department of Genetics, Los Angeles Biomedical Research Institute (LA BioMed), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Western General Hospital, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Medical Research Council, Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute-University of Pittsburgh Graduate School of Public Health, Zhengzhou University of Light Industry, Department of Electrical and Electronic Engineering [Niigata Univ.], Niigata University, Genetic Epidemiology Unit, University College of London [London] (UCL), Aston Business School, Aston University [Birmingham], Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], Centre Hospitalier Universitaire Vaudois (CHUV), Pennington Biomedical Research Center, University of Washington [Seattle], Guy's and St Thomas' Hospitals, Northwestern Polytechnical University [Xi'an] (NPU), Department of Social Medicine, University of Bristol [Bristol], Department of Genomics of Common Disease [London, UK], Imperial College London-Hammersmith Hospital NHS Imperial College Healthcare, Department of Internal Medicine, Institute of Clinical Molecular Biology, Kiel University, Medizinische Klinik II, Universität zu Lübeck = University of Lübeck [Lübeck], Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina, Institute for Social Research, University of Michigan System-University of Michigan System, Division of Statistical Genomics, Washington University School of Medicine, Institute for Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel (CAU), Department of Physics, RISSC-Lab-University of Naples Federico II = Università degli studi di Napoli Federico II, Lund University [Lund], Icelandic Heart Association, Heart Preventive Clinic and Research Institute, The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Medical Research Center Oulu, University of Oulu, University of Utah School of Medicine [Salt Lake City], The Generation R Study, Pediatrics, Epidemiology, Center for Translational and Computational Neuroimmunology [New York, NY, États-Unis] (CTCN), Department of Neurology [New York, NY, États-Unis], Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York]-Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York], Universität Heidelberg [Heidelberg] = Heidelberg University, Interuniversity Cardiology Institute Netherlands, School of Public Health, University of Michigan [Dearborn], Department of Epidemiology and Public Health, University of Kuopio, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Institute of Epidemiology and Biobank PopGen, Department of Biostatistics, University of Washington, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Clinical Institute of Medical and Chemical Laboratory Diagnostics, Karl-Franzens-Universität Graz, Department of Genetics, Biology and Biochemistry, Università degli studi di Torino = University of Turin (UNITO), Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), QIMR Berghofer Medical Research Institute, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, University of Illinois [Chicago] (UIC), University of Illinois System, Experimental Cardiology Laboratory, Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Functional Genomics, Erasmus Medical Centre, National Human Genome Research Institute (NHGRI), School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Department of Pathological Biochemistry, Royal Infirmary, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Institute of Metabolic Science, MRC, University of Maryland School of Medicine [Baltimore, MD, USA], Centre for Molecular Epidemiology, Centre for Causal Analyses in Translational Epidemiology, University of Bristol [Bristol]-Medical Research Council, IRCCS San Raffaele Scientific Institute [Milan, Italie], U937, Génomique cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Michigan System, HMNC Brain Health, Singapore Eye Research Institute, Partenaires INRAE, Institut d'Électronique et des Technologies du numéRique (IETR), Université de Nantes (UN)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, University of Groningen, Department of Genomics of Common Disease, Department of Microbiology, The Freeman Hospital, Department Biostatistics University of North Carolina, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Clark, D. 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M., Trompet, S., Turman, C., Verweij, N., Viberti, C., Wang, L., Warren, H. R., Wootton, R. E., Yanek, L. R., Yao, J., Yousri, N. A., Zhao, W., Adeyemo, A. A., Afaq, S., Aguilar-Salinas, C. A., Akiyama, M., Albert, M. L., Allison, M. A., Alver, M., Aung, T., Azizi, F., Bentley, A. R., Boeing, H., Boerwinkle, E., Borja, J. B., de Borst, G. J., Bottinger, E. P., Broer, L., Campbell, H., Chanock, S., Chee, M. -L., Chen, G., Chen, Y. -D. I., Chen, Z., Chiu, Y. -F., Cocca, M., Collins, F. S., Concas, M. P., Corley, J., Cugliari, G., van Dam, R. M., Damulina, A., Daneshpour, M. S., Day, F. R., Delgado, G. E., Dhana, K., Doney, A. S. F., Dorr, M., Doumatey, A. P., Dzimiri, N., Ebenesersdottir, S. S., Elliott, J., Elliott, P., Ewert, R., Felix, J. F., Fischer, K., Freedman, B. I., Girotto, G., Goel, A., Gogele, M., Goodarzi, M. O., Graff, M., Granot-Hershkovitz, E., Grodstein, F., Guarrera, S., Gudbjartsson, D. F., Guity, K., Gunnarsson, B., Guo, Y., Hagenaars, S. P., Haiman, C. A., Halevy, A., Harris, T. B., Hedayati, M., van Heel, D. A., Hirata, M., Hofer, I., Hsiung, C. A., Huang, J., Hung, Y. -J., Ikram, M. A., Jagadeesan, A., Jousilahti, P., Kamatani, Y., Kanai, M., Kerrison, N. D., Kessler, T., Khaw, K. -T., Khor, C. C., de Kleijn, D. P. V., Koh, W. -P., Kolcic, I., Kraft, P., Kramer, B. K., Kutalik, Z., Kuusisto, J., Langenberg, C., Launer, L. J., Lawlor, D. A., Lee, I. -T., Lee, W. -J., Lerch, M. M., Li, L., Liu, J., Loh, M., London, S. J., Loomis, S., Lu, Y., Luan, J., Magi, R., Manichaikul, A. W., Manunta, P., Masson, G., Matoba, N., Mei, X. W., Meisinger, C., Meitinger, T., Mezzavilla, M., Milani, L., Millwood, I. Y., Momozawa, Y., Moore, A., Morange, P. -E., Moreno-Macias, H., Mori, T. A., Morrison, A. C., Muka, T., Murakami, Y., Murray, A. D., de Mutsert, R., Mychaleckyj, J. C., Nalls, M. A., Nauck, M., Neville, M. J., Nolte, I. M., Ong, K. K., Orozco, L., Padmanabhan, S., Palsson, G., Pankow, J. S., Pattaro, C., Pattie, A., Polasek, O., Poulter, N., Pramstaller, P. P., Quintana-Murci, L., Raikkonen, K., Ralhan, S., Rao, D. C., van Rheenen, W., Rich, S. S., Ridker, P. M., Rietveld, C. A., Robino, A., van Rooij, F. J. A., Ruggiero, D., Saba, Y., Sabanayagam, C., Sabater-Lleal, M., Sala, C. F., Salomaa, V., Sandow, K., Schmidt, H., Scott, L. J., Scott, W. R., Sedaghati-Khayat, B., Sennblad, B., van Setten, J., Sever, P. J., Sheu, W. H. -H., Shi, Y., Shrestha, S., Shukla, S. R., Sigurdsson, J. K., Sikka, T. T., Singh, J. R., Smith, B. H., Stancakova, A., Stanton, A., Starr, J. M., Stefansdottir, L., Straker, L., Sulem, P., Sveinbjornsson, G., Swertz, M. A., Taylor, A. M., Taylor, K. D., Terzikhan, N., Tham, Y. -C., Thorleifsson, G., Thorsteinsdottir, U., Tillander, A., Tracy, R. P., Tusie-Luna, T., Tzoulaki, I., Vaccargiu, S., Vangipurapu, J., Veldink, J. H., Vitart, V., Volker, U., Vuoksimaa, E., Wakil, S. M., Waldenberger, M., Wander, G. S., Wang, Y. X., Wareham, N. J., Wild, S., Yajnik, C. S., Yuan, J. -M., Zeng, L., Zhang, L., Zhou, J., Amin, N., Asselbergs, F. W., Bakker, S. J. L., Becker, D. M., Lehne, B., Bennett, D. A., van den Berg, L. H., Berndt, S. I., Bharadwaj, D., Bielak, L. F., Bochud, M., Boehnke, M., Bouchard, C., Bradfield, J. P., Brody, J. A., Campbell, A., Carmi, S., Caulfield, M. J., Cesarini, D., Chambers, J. C., Chandak, G. R., Cheng, C. -Y., Ciullo, M., Cornelis, M., Cusi, D., Smith, G. D., Deary, I. J., Dorajoo, R., van Duijn, C. M., Ellinghaus, D., Erdmann, J., Eriksson, J. G., Evangelou, E., Evans, M. K., Faul, J. D., Feenstra, B., Feitosa, M., Foisy, S., Franke, A., Friedlander, Y., Gasparini, P., Gieger, C., Gonzalez, C., Goyette, P., Grant, S. F. A., Griffiths, L. R., Groop, L., Gudnason, V., Gyllensten, U., Hakonarson, H., Hamsten, A., van der Harst, P., Heng, C. -K., Hicks, A. A., Hochner, H., Huikuri, H., Hunt, S. C., Jaddoe, V. W. V., De Jager, P. L., Johannesson, M., Johansson, A., Jonas, J. B., Jukema, J. W., Junttila, J., Kaprio, J., Kardia, S. L. R., Karpe, F., Kumari, M., Laakso, M., van der Laan, S. W., Lahti, J., Laudes, M., Lea, R. A., Lieb, W., Lumley, T., Martin, N. G., Marz, W., Matullo, G., Mccarthy, M. I., Medland, S. E., Merriman, T. R., Metspalu, A., Meyer, B. F., Mohlke, K. L., Montgomery, G. W., Mook-Kanamori, D., Munroe, P. B., North, K. E., Nyholt, D. R., O'Connell, J. R., Ober, C., Oldehinkel, A. J., Palmas, W., Palmer, C., Pasterkamp, G. G., Patin, E., Pennell, C. E., Perusse, L., Peyser, P. A., Pirastu, M., Polderman, T. J. C., Porteous, D. J., Posthuma, D., Psaty, B. M., Rioux, J. D., Rivadeneira, F., Rotimi, C., Rotter, J. I., Rudan, I., Den Ruijter, H. M., Sanghera, D. K., Sattar, N., Schmidt, R., Schulze, M. B., Schunkert, H., Scott, R. A., Shuldiner, A. R., Sim, X., Small, N., Smith, J. A., Sotoodehnia, N., Tai, E. -S., Teumer, A., Timpson, N. J., Toniolo, D., Tregouet, D. -A., Tuomi, T., Vollenweider, P., Wang, C. A., Weir, D. R., Whitfield, J. B., Wijmenga, C., Wong, T. -Y., Wright, J., Yang, J., Yu, L., Zemel, B. S., Zonderman, A. B., Perola, M., Magnusson, P. K. E., Uitterlinden, A. G., Kooner, J. S., Chasman, D. I., Loos, R. J. F., Franceschini, N., Franke, L., Haley, C. S., Hayward, C., Walters, R. G., Perry, J. R. B., Esko, T., Helgason, A., Stefansson, K., Joshi, P. K., Kubo, M., Wilson, J. F., Læknadeild (HÍ), Faculty of Medicine (UI), Félagsfræði-, mannfræði- og þjóðfræðideild (HÍ), Faculty of Sociology, Anthropology and Folkloristics (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), School of Engineering and Natural Sciences (UI), Verkfræði- og náttúruvísindasvið (HÍ), Félagsvísindasvið (HÍ), School of Social Sciences (UI), Háskóli Íslands, University of Iceland, Clark, David W [0000-0002-1025-9185], Okada, Yukinori [0000-0002-0311-8472], Moore, Kristjan H S [0000-0002-9579-4362], Mason, Dan [0000-0002-0026-9216], Pirastu, Nicola [0000-0002-5363-3886], Gandin, Ilaria [0000-0003-3196-2491], Deelen, Patrick [0000-0002-5654-3966], Schurmann, Claudia [0000-0003-4158-9192], Medina-Gomez, Carolina [0000-0001-7999-5538], Karlsson, Robert [0000-0002-8949-2587], Bao, Yanchun [0000-0002-6102-5098], Biino, Ginevra [0000-0002-9936-946X], Brumat, Marco [0000-0003-3268-039X], Chai, Jin-Fang [0000-0003-3770-1137], Eccles, David A [0000-0003-4634-4995], Gordon, Scott D [0000-0001-7623-328X], Harris, Sarah E [0000-0002-4941-5106], Kacprowski, Tim [0000-0002-5393-2413], Karlsson, Torgny [0000-0001-8095-6149], Kleber, Marcus E [0000-0003-0663-7275], Mahajan, Anubha [0000-0001-5585-3420], Matsuda, Koichi [0000-0001-7292-2686], Meng, Weihua [0000-0001-5388-8494], van der Most, Peter J [0000-0001-8450-3518], Munz, Matthias [0000-0002-4728-3357], Palviainen, Teemu [0000-0002-7847-8384], Prasad, Rashmi B [0000-0002-4400-6741], Salvi, Erika [0000-0002-2724-2291], Skotte, Line [0000-0002-7398-1271], van der Spek, Ashley [0000-0001-7136-0159], Spracklen, Cassandra N [0000-0003-3590-7182], Strawbridge, Rona J [0000-0001-8506-3585], Tajuddin, Salman M [0000-0002-7919-8528], Verweij, Niek [0000-0002-4303-7685], Yanek, Lisa R [0000-0001-7117-1075], Zhao, Wei [0000-0001-7388-0692], Albert, Matthew L [0000-0001-7285-6973], Bentley, Amy R [0000-0002-0827-9101], Chanock, Stephen [0000-0002-2324-3393], Chen, Zhengming [0000-0001-6423-105X], Chiu, Yen-Feng [0000-0002-3352-4500], Cocca, Massimiliano [0000-0002-1127-7596], Collins, Francis S [0000-0002-1023-7410], Cugliari, Giovanni [0000-0002-6080-0718], Damulina, Anna [0000-0001-8241-2727], Day, Felix R [0000-0003-3789-7651], Dhana, Klodian [0000-0002-6397-7009], Dzimiri, Nduna [0000-0003-3395-5754], Elliott, Paul [0000-0002-7511-5684], Felix, Janine F [0000-0002-9801-5774], Freedman, Barry I [0000-0003-0275-5530], Girotto, Giorgia [0000-0003-4507-6589], Goel, Anuj [0000-0003-2307-4021], Goodarzi, Mark O [0000-0001-6364-5103], Gudbjartsson, Daniel F [0000-0002-5222-9857], Guity, Kamran [0000-0002-8379-9668], van Heel, David A [0000-0002-0637-2265], Hirata, Makoto [0000-0002-9994-9958], Ikram, M Arfan [0000-0003-0372-8585], Kamatani, Yoichiro [0000-0001-8748-5597], Kanai, Masahiro [0000-0001-5165-4408], Khor, Chiea Chuen [0000-0002-1128-4729], Kolcic, Ivana [0000-0001-7918-6052], Langenberg, Claudia [0000-0002-5017-7344], Lawlor, Deborah A [0000-0002-6793-2262], Liu, Jianjun [0000-0002-3255-3019], London, Stephanie J [0000-0003-4911-5290], Luan, Jian’an [0000-0003-3137-6337], Matoba, Nana [0000-0001-5329-0134], Mei, Xue W [0000-0002-6279-4884], Mezzavilla, Massimo [0000-0002-9000-4595], Milani, Lili [0000-0002-5323-3102], Mori, Trevor A [0000-0002-5264-9229], Murakami, Yoshinori [0000-0002-2826-4396], Murray, Alison D [0000-0003-4915-4847], Mychaleckyj, Josyf C [0000-0003-2595-0005], Neville, Matt J [0000-0002-6004-5433], Nolte, Ilja M [0000-0001-5047-4077], Ong, Ken K [0000-0003-4689-7530], Pálsson, Gunnar [0000-0002-8231-3961], Pankow, James S [0000-0001-7076-483X], Pattaro, Cristian [0000-0002-4119-0109], Quintana-Murci, Lluis [0000-0003-2429-6320], van Rheenen, Wouter [0000-0002-5860-1533], Rich, Stephen S [0000-0003-3872-7793], Rietveld, Cornelius A [0000-0003-4053-1861], Ruggiero, Daniela [0000-0003-3898-7827], Sabanayagam, Charumathi [0000-0002-4042-4719], Sabater-Lleal, Maria [0000-0002-0128-379X], Sala, Cinzia Felicita [0000-0003-2514-2075], Salomaa, Veikko [0000-0001-7563-5324], Scott, Laura J [0000-0002-4886-5084], Sedaghati-Khayat, Bahareh [0000-0002-7665-8648], Sennblad, Bengt [0000-0002-4360-8003], van Setten, Jessica [0000-0002-4934-7510], Smith, Blair H [0000-0002-5362-9430], Stančáková, Alena [0000-0002-1375-0252], Stanton, Alice [0000-0002-4961-165X], Straker, Leon [0000-0002-7786-4128], Sulem, Patrick [0000-0001-7123-6123], Swertz, Morris A [0000-0002-0979-3401], Taylor, Kent D [0000-0002-2756-4370], Tzoulaki, Ioanna [0000-0002-4275-9328], Veldink, Jan H [0000-0001-5572-9657], Vitart, Veronique [0000-0002-4991-3797], Völker, Uwe [0000-0002-5689-3448], Wander, Gurpreet S [0000-0002-4596-4247], Wang, Ya Xing [0000-0003-2749-7793], Wild, Sarah [0000-0001-7824-2569], Yuan, Jian-Min [0000-0002-4620-3108], Asselbergs, Folkert W [0000-0002-1692-8669], Boehnke, Mike [0000-0002-6442-7754], Bouchard, Claude [0000-0002-0048-491X], Brody, Jennifer A [0000-0001-8509-148X], Campbell, Archie [0000-0003-0198-5078], Caulfield, Mark J [0000-0001-9295-3594], Smith, George Davey [0000-0002-1407-8314], Dorajoo, Rajkumar [0000-0001-6608-2051], Ellinghaus, David [0000-0002-4332-6110], Erdmann, Jeanette [0000-0002-4486-6231], Evangelou, Evangelos [0000-0002-5488-2999], Feenstra, Bjarke [0000-0003-1478-649X], Feitosa, Mary [0000-0002-0933-2410], Franke, Andre [0000-0003-1530-5811], Grant, Struan F A [0000-0003-2025-5302], Griffiths, Lyn R [0000-0002-6774-5475], Groop, Leif [0000-0002-0187-3263], Gudnason, Vilmundur [0000-0001-5696-0084], van der Harst, Pim [0000-0002-2713-686X], Heng, Chew-Kiat [0000-0002-7309-9473], Hicks, Andrew A [0000-0001-6320-0411], Jaddoe, Vincent W V [0000-0003-2939-0041], De Jager, Philip L [0000-0002-8057-2505], Johannesson, Magnus [0000-0001-8759-6393], Johansson, Åsa [0000-0002-2915-4498], Jonas, Jost B [0000-0003-2972-5227], Jukema, J Wouter [0000-0002-3246-8359], Kaprio, Jaakko [0000-0002-3716-2455], Laakso, Markku [0000-0002-3394-7749], van der Laan, Sander W [0000-0001-6888-1404], Lahti, Jari [0000-0002-4310-5297], Martin, Nicholas G [0000-0003-4069-8020], Medland, Sarah E [0000-0003-1382-380X], Merriman, Tony R [0000-0003-0844-8726], Metspalu, Andres [0000-0002-3718-796X], Mohlke, Karen L [0000-0001-6721-153X], Montgomery, Grant W [0000-0002-4140-8139], Munroe, Patricia B [0000-0002-4176-2947], Nyholt, Dale R [0000-0001-7159-3040], Ober, Carole [0000-0003-4626-9809], Oldehinkel, Albertine J [0000-0003-3925-3913], Palmer, Colin [0000-0002-6415-6560], Perusse, Louis [0000-0001-6440-9698], Polderman, Tinca J. C. [0000-0001-5564-301X], Porteous, David J [0000-0003-1249-6106], Rioux, John D [0000-0001-7560-8326], Rivadeneira, Fernando [0000-0001-9435-9441], Rotimi, Charles [0000-0001-5759-053X], Rotter, Jerome I [0000-0001-7191-1723], Rudan, Igor [0000-0001-6993-6884], Sattar, Naveed [0000-0002-1604-2593], Sim, Xueling [0000-0002-1233-7642], Smith, Jennifer A [0000-0002-3575-5468], Teumer, Alexander [0000-0002-8309-094X], Timpson, Nicholas J [0000-0002-7141-9189], Tuomi, Tiinamaija [0000-0002-8306-6202], Wang, Carol A [0000-0002-4301-3974], Weir, David R [0000-0002-1661-2402], Whitfield, John B [0000-0002-1103-0876], Magnusson, Patrik K. E. [0000-0002-7315-7899], Uitterlinden, André G [0000-0002-7276-3387], Loos, Ruth J. F. [0000-0002-8532-5087], Franke, Lude [0000-0002-5159-8802], Haley, Chris S [0000-0002-9811-0210], Hayward, Caroline [0000-0002-9405-9550], Walters, Robin G [0000-0002-9179-0321], Joshi, Peter K [0000-0002-6361-5059], Wilson, James F [0000-0001-5751-9178], Apollo - University of Cambridge Repository, Moore, Kristjan HS [0000-0002-9579-4362], Luan, Jian'an [0000-0003-3137-6337], Grant, Struan FA [0000-0003-2025-5302], Jaddoe, Vincent WV [0000-0003-2939-0041], Polderman, Tinca JC [0000-0001-5564-301X], Magnusson, Patrik KE [0000-0002-7315-7899], Loos, Ruth JF [0000-0002-8532-5087], Neurology, Human genetics, Amsterdam Reproduction & Development (AR&D), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Stem Cell Aging Leukemia and Lymphoma (SALL), Institute for Molecular Medicine Finland, Department of Psychology and Logopedics, University Management, Developmental Psychology Research Group, Staff Services, Cognitive and Brain Aging, Research Programs Unit, Diabetes and Obesity Research Program, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Clinicum, University of Helsinki, Centre of Excellence in Complex Disease Genetics, Department of Public Health, Genetic Epidemiology, Helsinki Collegium for Advanced Studies, HUS Abdominal Center, Endokrinologian yksikkö, Bradford Teaching Hospitals NHS Foundation Trust [Bradford, UK] (BTHFT), University of Trieste, Université de Lausanne (UNIL), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Consiglio Nazionale delle Ricerche (CNR), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Pasteur [Paris], University of Oxford [Oxford], Medical Genetics, Dept. RSD and Public Health, IRCCS-Burlo Garofolo/University of Trieste, sans affiliation, Helmholtz-Zentrum München (HZM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institute of Cardiovascular Science, University College London, Hammersmith Hospital NHS Imperial College Healthcare-Imperial College London, Universität zu Lübeck [Lübeck], University of Ioannina Medical School, Università degli studi di Napoli Federico II-RISSC-Lab, Universität Heidelberg [Heidelberg], University of Turin, University of California-University of California, Nantes Université (NU)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), University of Helsinki-University of Helsinki, Université de Nantes (UN)-Université de Rennes 1 (UR1), Erasmus MC other, Internal Medicine, and Applied Economics

Subjects
0301 basic medicine, 631/208/1397, Chemistry(all), Health Status, [SDV]Life Sciences [q-bio], LOCI, General Physics and Astronomy, MESH: Haplotype, MESH: Cognition, 030105 genetics & heredity, Runs of Homozygosity, Biochemistry, Consanguinity, Cognition, Inbreeding depression, 2.1 Biological and endogenous factors, Body Size, Inbreeding, Skyldleikarækt, Aetiology, Human phenotypes, lcsh:Science, MESH: Health Status, Genetics, Multidisciplinary, Inbreeding Depression, Confounding, Homozygote, RUNS, 631/208/205, 631/208/721, 3. Good health, genomic inbreeding coefficients, MESH: Risk-Taking, 631/208/730, Autozygosit, homozygosity, Erfðarannsóknir, Medical Genetics, genomic inbreeding coefficient, MESH: Homozygote, Offspring, Science, Autozygosity, Blóðsifjar, 610 Medicine & health, Biology, INBREEDING DEPRESSION, HOMOZYGOSITY, FERTILITY, QUANTIFICATION, Physics and Astronomy(all), General Biochemistry, Genetics and Molecular Biology, Article, Association, 03 medical and health sciences, Risk-Taking, 360 Social problems & social services, Journal Article, Humans, ddc:610, Allele, Alleles, Medicinsk genetik, Genetic association study, MESH: Consanguinity, MESH: Body Size, MESH: Humans, Biochemistry, Genetics and Molecular Biology(all), MESH: Alleles, Haplotype, MESH: Fertility, General Chemistry, Brain Disorders, MESH: Inbreeding Depression, 030104 developmental biology, Fertility, Haplotypes, Genetic markers, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 3111 Biomedicine, Genetics and Molecular Biology(all)
Abstract

Publisher's version (útgefin grein)., In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding., This paper is the work of the ROHgen consortium. We thank the Sigma T2D Consortium, whose members are detailed in Supplementary Note 3. We thank the UK Biobank Resource, approved under application 19655; we acknowledge funding from the UK Medical Research Council Human Genetics Unit and MRC Doctoral Training Programme in Precision Medicine. We also thank Neil Robertson, Wellcome Trust Centre for Human Genetics, Oxford, for use of his author details management software, Authorial. Finally, we thank all the participants, researchers and funders of ROHgen cohorts. Cohort-specific acknowledgements are in Supplementary Data 2; personal acknowledgements and disclosures are in Supplementary Note 2. We thank Rachel Edwards for administrative assistance.

Published
2019

39. Improving the prediction of cardiovascular risk with machine-learning and DNA methylation data

Author

Simonetta Guarrera, Paolo Vineis, Carlotta Sacerdote, Giuseppe Matullo, Rosario Tumino, Giovanni Cugliari, Vittorio Krogh, Piero Fariselli, Silvia Benevenuta, and Salvatore Panico

Subjects
0301 basic medicine, Epigenetic biomarkers, 030109 nutrition & dietetics, business.industry, Computer science, Machine learning, computer.software_genre, Random forest, 03 medical and health sciences, 030104 developmental biology, DNA methylation, Computational statistics, Artificial intelligence, business, computer, Reliability (statistics)
Abstract

Classically, the cardiovascular risk of individual is evaluated using phenomenological variables (PV)such as blood pressure, body mass, smoker status, gender, age etc. Here we show that, on prospective study (after 10–15 years)these PV display a poor agreement with case-control samples. We were able to obtain more accurate predictions using both DNA methylation data and PV as input features of a Random Forest model, achieving a ROC-AUC of 0.74. Furthermore, the Random Forest output correlates with the reliability of the predictions producing a ROC-AUC of 0.90 when only the most reliable predictions are taken into consideration.

Published
2019

40. DNA repair and cancer in colon and rectum: Novel players in genetic susceptibility

Author

Mark A. Jenkins, Alessio Naccarati, Alda Corrado, Giovanni Cugliari, John L. Hopper, Michael Hoffmeister, Robert E. Schoen, Polly A. Newcomb, Manish Gala, Jenny Chang-Claude, Elisa Paolicchi, Stefano Landi, Li Hsu, Peter T. Campbell, Robert W. Haile, Michelle Cotterchio, Martha L. Slattery, Stephanie A. Bien, Veronika Vymetalkova, Ludmila Vodickova, Hermann Brenner, Barbara Pardini, Loic Le Marchand, Andrew T. Chan, Jeroen R. Huyghe, Hongmei Nan, Emily White, Ulrike Peters, Sonja I. Berndt, Richard B. Hayes, Steven Gallinger, Noralane M. Lindor, Stéphane Bézieau, Graham Casey, Yi Lin, Pavel Vodicka, Shuji Ogino, John D. Potter, Bette J. Caan, Federica Gemignani, and Tabitha A. Harrison

Subjects
Oncology, Male, Cancer Research, DNA Repair, Colorectal cancer, Carcinogenesis, medicine.disease_cause, single nucleotide polymorphisms, 0302 clinical medicine, Registries, DNA Modification Methylases, Biological Variation, Single Nucleotide, Middle Aged, cancer susceptibility, DNA-Binding Proteins, medicine.anatomical_structure, colon cancer, 030220 oncology & carcinogenesis, Colonic Neoplasms, DNA mismatch repair, Female, MutL Protein Homolog 1, Adult, medicine.medical_specialty, DNA repair, Colon, Population, Rectum, Single-nucleotide polymorphism, MLH1, Polymorphism, Single Nucleotide, Risk Assessment, Article, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Polymorphism, rectal cancer, Aged, genome-wide association studies, Biological Variation, Population, Case-Control Studies, DNA Repair Enzymes, Rectal Neoplasms, Tumor Suppressor Proteins, business.industry, Cancer, medicine.disease, digestive system diseases, business
Abstract

Interindividual differences in DNA repair systems may play a role in modulating the individual risk of developing colorectal cancer. To better ascertain the role of DNA repair gene polymorphisms on colon and rectal cancer risk individually, we evaluated 15,419 single nucleotide polymorphisms (SNPs) within 185 DNA repair genes using GWAS data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), which included 8,178 colon cancer, 2,936 rectum cancer cases and 14,659 controls. Rs1800734 (in MLH1 gene) was associated with colon cancer risk (p-value = 3.5 × 10-6 ) and rs2189517 (in RAD51B) with rectal cancer risk (p-value = 5.7 × 10-6 ). The results had statistical significance close to the Bonferroni corrected p-value of 5.8 × 10-6 . Ninety-four SNPs were significantly associated with colorectal cancer risk after Binomial Sequential Goodness of Fit (BSGoF) procedure and confirmed the relevance of DNA mismatch repair (MMR) and homologous recombination pathways for colon and rectum cancer, respectively. Defects in MMR genes are known to be crucial for familial form of colorectal cancer but our findings suggest that specific genetic variations in MLH1 are important also in the individual predisposition to sporadic colon cancer. Other SNPs associated with the risk of colon cancer (e.g., rs16906252 in MGMT) were found to affect mRNA expression levels in colon transverse and therefore working as possible cis-eQTL suggesting possible mechanisms of carcinogenesis.

Published
2019

41. Peripheral Blood DNA Methylation as Potential Biomarker of Malignant Pleural Mesothelioma in Asbestos-Exposed Subjects

Author

Giuseppe Matullo, E. Piccolini, Daniela Ferrante, Giovanni Cugliari, Irma Dianzani, Elisabetta Casalone, Roberta Libener, Corrado Magnani, Anna Aspesi, Marta Betti, Simonetta Guarrera, Clara Viberti, Federica Grosso, Caterina Casadio, Dario Mirabelli, and Alessandra Allione

Subjects
Male, Mesothelioma, 0301 basic medicine, Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, Lung Neoplasms, Pleural Neoplasms, Malignant pleural mesothelioma, medicine.disease_cause, Case-control discrimination, Asbestos, 03 medical and health sciences, 0302 clinical medicine, Occupational Exposure, Internal medicine, Biomarkers, Tumor, medicine, Humans, Prospective cohort study, Aged, Whole blood, Early biomarker, Pleural mesothelioma, business.industry, Mesothelioma, Malignant, DNA, Methylation, DNA Methylation, Prognosis, Peripheral blood, 030104 developmental biology, ROC Curve, Case-Control Studies, 030220 oncology & carcinogenesis, Potential biomarkers, Asbestos exposure, DNA-methylation, DNA methylation, Carcinogens, Female, business, Follow-Up Studies
Abstract

Introduction Malignant pleural mesothelioma (MPM) is an aggressive tumor strongly associated with asbestos exposure. Patients are usually diagnosed when current treatments have limited benefits, highlighting the need for noninvasive early diagnostic tests to monitor asbestos-exposed people. Methods We used a genome-wide methylation array to identify, in asbestos-exposed subjects, novel blood DNA methylation markers of MPM in 163 MPM cases and 137 cancer-free controls (82 MPM cases and 68 controls, training set; replication in 81 MPM cases and 69 controls, test set) sampled from the same areas. Results Evidence of differential methylation between MPM cases and controls was found (more than 800 cytosine-guanine dinucleotide sites, false discovery rate p value (pfdr) Conclusions We identified signatures of differential methylation in DNA from whole blood between asbestos exposed MPM cases and controls. Our results provide the rationale to further investigate, in prospective studies, the potential use of blood DNA methylation profiles for the identification of early changes related to the MPM carcinogenic process.

Published
2019

42. Motivation toward dual career of Italian student-athletes enrolled in different university paths

Author

Cristina Onesta Mosso, Luisa Pizzigalli, Corrado Lupo, Alberto Rainoldi, Giovanni Cugliari, and Flavia Guidotti

Subjects
medicine.medical_specialty, Sports medicine, Team sport, Individual sport, 05 social sciences, Attendance, Athletic career, SAMSAQ-IT/A, Validity, Athletic career, 030229 sport sciences, Confirmatory factor analysis, Exploratory factor analysis, Validity, Test (assessment), 03 medical and health sciences, 0302 clinical medicine, Cronbach's alpha, 0502 economics and business, medicine, Orthopedics and Sports Medicine, Psychology, Social psychology, SAMSAQ-IT/A, 050212 sport, leisure & tourism, Clinical psychology
Abstract

The present study aimed to investigate motivations for the dual career of Italian student-athletes attending different university courses. For this purpose, the Italian Harmonized version of the Student-athletes’ Motivation toward Sports and Academics Questionnaire (SAMSAQ-IT/A) was administered to 760 Italian student-athletes. Exploratory Factor Analysis (EFA) and Cronbach’s alpha coefficients were applied to test the factor structure and the reliability of the SAMSAQ-IT/A, respectively. Furthermore, the Confirmatory Factor Analysis (CFA) assessed the fit of the model. A multivariate approach was applied to verify subgroups effects (P ≤ 0.05) in relation to gender (i.e., female, male), competition level (i.e., elite, sub-elite), type of sport (i.e., individual sport, team sport, disciplines performed both as individual and team), educational area (i.e., economical/law, humanistic, mathematics/engineering, medical, movement/sport sciences), and year of attendance (i.e., Bachelor 1st, 2nd, 3rd year, Master degree 1st and 2nd year, off course). EFA highlighted a three-factor model (i.e., Sport Motivation, SM; Academic Motivation, AM; Dual Career Motivation, CM) with acceptable reliability estimates (SM = 0.93; AM = 0.85; CM = 0.90) and good CFA indexes. Furthermore, differences between subgroups were found for gender (SM, P = 0.02; AM, P = 0.007), type of sport (AM, P = 0.039), competition level (SM, P

Published
2016

43. Frequenza alle lezioni e percezione di utilità delle esercitazioni pratiche nei corsi di laurea in Scienze delle attività motorie e sportive

Author

Marco Ivaldi, A Scotton, Giovanni Cugliari, and Claudio Giovanni Scotton

Subjects
autovalutazione, 05 social sciences, 050301 education, Objective analysis, 030229 sport sciences, Experiential learning, apprendimento tradizionale, Education, Epistemology, insegnamento capovolto, 03 medical and health sciences, 0302 clinical medicine, Apprendimento attivo, apprendimento tradizionale, insegnamento capovolto, autovalutazione, scienze del movimento, scienze motorie, scienze del movimento, Active learning, Apprendimento attivo, Sports activity, Psychology, 0503 education, scienze motorie
Abstract

Providing an explanatory, unambiguous and definitive discussion on the role of the speculative and practices components in the teaching of a discipline is complex. It might seem obvious that scientific and technical disciplines require different learning activity, sometimes more practical, sometimes more theoretical. But these conventional approaches actually are not fully proven. Regarding Human Movement Sciences, historically assigned to the technical-scientific branch, for long time the need to support the practical experiential with theoretical notions was discussed about, with a proper crosscutting approach. The present study aims to investigate these characteristics, specifically trying to clarify some aspects of teaching a practical matter, Artistic Gymnastic, in the course of study in Science of motor and sports activities. Specifically, the results show that students who attend classes getting a final vote higher than non-attending, and those who believe in the utility of active learning of this discipline have a final vote higher than those who believe that the matter has little or no utility. The study tries to provide an objective analysis in a highly subjective area, highlighting details purely related to the conduct of practical exercises in the teaching of sciencetechnique matter.

Published
2016

44. DNA Methylation of FKBP5 as Predictor of Overall Survival in Malignant Pleural Mesothelioma

Author

Roberta Libener, Chiara Catalano, Anna Aspesi, Federica Grosso, Dario Mirabelli, Irma Dianzani, Clara Viberti, Giuseppe Matullo, Alessia Russo, Marika Sculco, Corrado Magnani, Elisabetta Casalone, Alessandra Allione, Giovanni Cugliari, Chiara Pirazzini, Simonetta Guarrera, and Daniela Ferrante

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, lymphocyte-to-monocyte ratio, medicine.disease_cause, lcsh:RC254-282, Asbestos, survival analysis, asbestos exposure, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, malignant pleural mesothelioma, Medicine, Mesothelioma, Epigenetics, Survival analysis, DNA methylation, business.industry, dNaM, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 030104 developmental biology, epigenome-wide analysis, 030220 oncology & carcinogenesis, Cohort, FKBP5, business, Asbestos exposure, Epigenome-wide analysis, Lymphocyte-to-monocyte ratio, Malignant pleural mesothelioma
Abstract

Malignant pleural mesothelioma (MPM) is an aggressive tumor with median survival of 12 months and limited effective treatments. The scope of this study was to study the relationship between blood DNA methylation (DNAm) and overall survival (OS) aiming at a noninvasive prognostic test. We investigated a cohort of 159 incident asbestos exposed MPM cases enrolled in an Italian area with high incidence of mesothelioma. Considering 12 months as a cut-off for OS, epigenome-wide association study (EWAS) revealed statistically significant (p value = 7.7 &times, 10&minus, 9) OS-related differential methylation of a single-CpG (cg03546163), located in the 5&prime, UTR region of the FKBP5 gene. This is an independent marker of prognosis in MPM patients with a better performance than traditional inflammation-based scores such as lymphocyte-to-monocyte ratio (LMR). Cases with DNAm &lt, 0.45 at the cg03546163 had significantly poor survival compared with those showing DNAm &ge, 0.45 (mean: 243 versus 534 days, p value&lt, 0.001). Epigenetic changes at the FKBP5 gene were robustly associated with OS in MPM cases. Our results showed that blood DNA methylation levels could be promising and dynamic prognostic biomarkers in MPM.

Published
2020

45. Meta-Analysis of Maternal Prenatal Smoking GFI1-Locus and Cardio-Metabolic Phenotypes in Adults

Author

Ben Schöttker, Oscar H. Franco, Philippe Froguel, Eline Slagboom, Jana Nano, Mika Kähönen, Annette Peters, Stephan B. Felix, Niek Verweij, Dorret I. Boomsma, Taulant Muka, Lude Franke, Leonard H. van den Berg, Giuseppe Matullo, Pashupati P. Mishra, Hans J. Grabe, Toby Andrew, Jan H. Veldink, Matthias Wielscher, Marjo-Riitta Järvelin, Krista Fischer, Mikko Hurme, Rae-Chi Huang, Jaspal S. Kooner, Marleen M.J. van Greevenbroek, Hermann Brenner, Silva Kasela, Caroline L Relton, Shengxu Li, Weihua Zhang, André G. Uitterlinden, Yan Zhang, Trevor A. Mori, Wolfgang Rathmann, Pooja R. Mandaviya, Wei Chen, Amélie Bonnefond, Bastiaan T. Heijmans, Denise Anderson, Olli T. Raitakari, Sylvain Sebert, Lawrence J. Beilin, Ville Karhunen, Priyanka Parmar, Alexander Teumer, Sonja Kunze, Estelle Lowry, Phillip E. Melton, Matthew Suderman, Marie Loh, Benjamin Lehne, M. Waldenberger, Matthias Nauck, John C. Chambers, Pim van der Harst, Giovanni Cugliari, Joyce B. J. van Meurs, Simonetta Guarrera, Petri Wiklund, Terho Lehtimäki, Lili Milani, Christian Gieger, Rory P. Wilson, Tao Zhang, and Niek de Klein

Subjects
education.field_of_study, Waist, business.industry, Offspring, Population, Physiology, Blood pressure, Meta-analysis, DNA methylation, Medicine, Epigenetics, education, business, Body mass index
Abstract

Background: DNA methylation at GFI1-locus has been repeatedly associated with exposure to smoking from foetal period onwards. We explored whether DNA methylation maybe a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. Methods: We meta-analysed the association between methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n=18212). DNA methylation at GFI1-locus was measured in whole-blood. Multivariable regression analyses were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), diastolic, and systolic blood pressure (BP). Findings: Hypomethylation at four out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Cg14179389 hypomethylation, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P < 0·012. In contrast, hypomethylation at cg09935388, the strongest adult own smoking locus, was associated with decreased BMI, WC, and BP (adjusted 1 x 10 - 7 < P < 0·01). Similarly, hypo-methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 x 10 - 8 < P < 0·001). Hypomethylation at all the CpGs was consistently associated with higher TG levels. Interpretation: Epigenetic changes at GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors. This introduces a molecular mechanism and biomarker of smoking exposure. Funding: Not applicable Declaration of interests: The authors declare no competing interests. Ethical Approval Statement: Ethical approval for the study was obtained from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees.

Published
2018

46. Scanning electron microscopy evaluation of aligner fit on teeth

Author

Enrico Castroflorio, Gabriele Rossini, Andrea Deregibus, Francesco Garino, Giovanni Cugliari, Edoardo Mantovani, and Tommaso Castroflorio

Subjects
0301 basic medicine, Molar, Materials science, Stereolithography, Scanning electron microscope, Aligners, CA-Clear Aligner, Fitting, Invisalign, Microscopy, SEM, Orthodontics, law.invention, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, law, Orthodontic Appliances, Removable, Humans, Maxillary central incisor, Dental Casting Technique, 030206 dentistry, Original Articles, stomatognathic diseases, 030104 developmental biology, Microscopy, Electron, Scanning
Abstract

Objectives: The fitting of aligners on anchorage teeth is a crucial factor in clear aligner orthodontics. The purpose of this experimental study was to evaluate the fitting of two aligner systems, Invisalign and CA-Clear Aligner, using scanning electron microscopy (SEM). Materials and Methods: Passive aligners (Invisalign and CA-Clear Aligner) were adapted on resin casts obtained by stereolithography (STL) files of a patient, and then sectioned buccolingually. Upper and lower central incisors, upper and lower first premolars, and upper and lower first molars were the regions analyzed. Representative microphotographs of sections were taken with a scanning electron microscope (SEM); a total of 160 micrometric measurements were obtained and analyzed with ANOVA tests. Results: Invisalign provided an overall better fit on lower incisors (F = 11.48, P = .0095) and on lower molars (F = 19.93, P = .0012). Considering the different regions, Invisalign provided better fit at the gingival edge of the buccal aspect on lower incisors (F = 11.33, P = 0.0056) and at the gingival edge of the lingual aspect on upper premolars (F =5.34, P = 0.0047). On the upper molars, Invisalign provided better fit at the gingival edge of the buccal aspect, while CA-Clear Aligner provided better fit at the buccal maximum convexity, on the buccal cusp, on the occlusal groove and at the palatal cusp. On lower molars, Invisalign showed a more accurate fit at the buccal aspect points. Conclusions: Invisalign and CA-Clear Aligner exhibited comparable fit on anchorage teeth. Invisalign provided better fit at the gingival edges of aligners, while the CA-Clear Aligner provided better fit on complex occlusal surfaces.

Published
2018

47. Postural changes in orthodontic patients treated with clear aligners: A rasterstereographic study

Author

Simone Parrini, Gabriele Rossini, Serena Ravera, Andrea Deregibus, Benedetta Comba, Giovanni Cugliari, Ilaria De Giorgi, and Tommaso Castroflorio

Subjects
Male, Orthodontic Brackets, Posture, Kyphosis, Neuroscience (miscellaneous), Biophysics, Dentistry, Orthodontics, Spinal Curvatures, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pelvic inclination, Untreated control, Humans, Medicine, business.industry, Body posture, Rasterstereography, 030206 dentistry, medicine.disease, Spine, Clear aligners, Neurology (clinical), Orthodontic brackets, Female, Malocclusion, business, 030217 neurology & neurosurgery
Abstract

Background Correlation between malocclusions and body posture has been discussed in the last decades, but there is still a lack of consensus in existing literature. Rasterstereography allows tridimensional reconstruction of the spine, starting from the back surface analysis. So far studies which tested modifications of rasterstereographic parameters during orthodontic treatment, comparing with those obtained from untreated control group, are not available. Clear aligner treatment produces alteration of vertical height due to the occlusal coverage and, subsequently, a stimulation of periodontal receptors which causes an inhibition of the jaw closing muscles and, hypothetically, changes in mandibular posture. Objectives Evaluate possible correlations between orthodontic treatment and posture. Materials and methods Rasterstereographic values of 15 untreated patients and of 15 patients treated with clear aligners were compared at baseline, after 1, 3 and 6 months. Rasterstereographic parameters considered were the following: the kyphotic angle, the lordotic angle, the upper thoracic inclination, and the pelvic inclination. Results Correlations between Kyphosis Angle, Upper Toracic Inclination and Pelvic Inclination and body posture were found after 6 months of treatment with clear aligners. Conclusions Occlusal coverage caused by aligners could influence body posture not only for upper spine sections but also lower spine sections.

Published
2018

48. Root Resorption in Mandibular Incisors During Orthodontic Treatment with Invisalign®: A Radiometric Study

Author

Giulia Gay, Serena Ravera, Tommaso Castroflorio, Francesco Garino, Giovanni Cugliari, and Andrea Deregibus

Subjects
Orthodontics, Adult patients, business.industry, medicine.medical_treatment, Incidence (epidemiology), Radiography, Mean age, Root resorption, medicine.disease, Crown (dentistry), stomatognathic diseases, Intrusion, stomatognathic system, Root length, Medicine, business
Abstract

Background: Existing literature indicates that orthodontics patients are more likely to have severe apical root shortening, interesting mostly maxillary, followed by mandibular incisors. Objectives: The aim of the present study was to investigate the incidence and severity of root resorption (RR) in mandibular incisors of adult patients treated with aligners. Methods: The study group consisted of 71 adult healthy patients (mean age 32.8 ± 12.7) treated with aligners (Invisalign®, Align Technologies, San Jose, CA, USA) for the intrusion of the lower incisors. Root and crown lengths of a total of 279 lower incisors were measured in panoramic radiographs at the beginning (T0) and at the end (T1) of aligner therapy. Individual root-crown-ratio (RCR) of each tooth and therefore the relative changes of RCR (rRCR) were determined. Results: 44% of the 279 measured teeth presented a reduction of the pre-treatment root length. A reduction in percentage of > 0% up to 10% was found in 26.76% (n = 76), a distinct reduction of > 10% up to 20% in 12.32% (n = 35) of the sample. 4.58% (n = 13) of the teeth were affected by a clinically relevant reduction (> 20%). Conclusions: Orthodontic treatment with Invisalign® aligners could led to RR in cases in which intrusion of the lower incisors is planned. However, the incidence of RR is comparable to data described in case of application of light forces with fixed appliances, and considerably lower than what has been described for traditional comprehensive orthodontic treatments.

Published
2017

49. Sleep bruxism in adolescents: A systematic literature review of related risk factors

Author

Gabriele Rossini, Tommaso Castroflorio, Andrea Deregibus, Giovanni Cugliari, and Andrea Bargellini

Subjects
Pathology, medicine.medical_specialty, Adolescent, business.industry, MEDLINE, Scopus, Psychological intervention, Headache, Sleep Bruxism, Orthodontics, 030206 dentistry, Checklist, 03 medical and health sciences, 0302 clinical medicine, Systematic review, Risk Factors, Etiology, medicine, Humans, Grading (education), business, 030217 neurology & neurosurgery, Clinical psychology
Abstract

Background: Multiple risk factors have been associated to sleep bruxism (SB). Nevertheless, there are still many unsolved issues concerning the etiology of SB that have consequences on the clinical management strategies. Objective: Systematically review the literature to assess the relationship between risk factors and SB symptoms in adolescents (age 11–19 years). Search methods and selection criteria: PubMed, Embase, Scopus, Cochrane Oral Health Group’s Trial Register and Cochrane Register of Controlled Trials, Web of Science, LILACs, and SciELO were searched to identify all peer-reviewed articles potentially relevant to the review. Data collection and analysis: The risk of bias was assessed according to the guidelines from the Cochrane handbook for systematic reviews of interventions, with reporting in agreement to the preferred reporting items for systematic reviews and meta-analyses guidelines. Results: Four out of the 4546 initially identified articles were selected. According to the grading of recommendations assessment, development and evaluation assessment (GRADE), the magnitude of agreement was almost perfect for all checklist items. Sleep disturbances, and snoring in particular, headache, jaw muscle fatigue, and tooth wear seem to be associated to SB in adolescents from 11 to 19 years old. Limitations: Despite the large interest of the scientific community in the field of oral parafunctions, only four articles met the eligibility criteria. Furthermore only associations and not definite cause–effect relationships were highlighted in the selected articles. Conclusions: Sleep disturbances presented the strongest association with SB while very few occlusal features had a moderate association. As a common sense the investigation of sleep respiratory disorders could be of great help in the management of SB in adolescents.

Published
2017

50. Short Term Evaluation of the Effects of Orthodontic Clear Aligners on Sleep Bruxism Activity

Author

Francesco Garino, Federica Casasco, Andrea Deregibus, Tommaso Castroflorio, Andrea Bargellini, Maria Giacone, and Giovanni Cugliari

Subjects
Occlusal Splints, Orthodontics, Masseter muscle, business.industry, Tooth wear, Heart rate, Anova test, Medicine, Sleep Bruxism, In patient, business, Heart frequency
Abstract

Background: In the last years an increasing number of patients have sought for comfortable and aesthetic alternatives to fixed appliances. Aligners, due to the protection against tooth wear, can be compared to occlusal splints used in patients suffering from sleep bruxism (SB). The aim of the study was to analyze the effects of clear aligners on SB episodes using a validated portable device (Bruxoff®, OTBioelettronica, Torino, Italy) allowing a simultaneous recording of electromyographic signals from both the masseter muscles as well as heart frequency to evaluate variation on SB activity. Methods: Forty patients were analyzed for the study. Twenty of them were assigned to orthodontic treatment with clear aligners (Invisalign®, Align Technology). The other twenty patients were used as control group observed for a period of twelve months. Intra-group and inter-group variances were analyzed by using a two-way ANOVA test. For each analysis a P < 0.05 was set. Results: After the first month of clear aligners therapy, all patients in the case group showed a significant reduction in the number of SB episodes (P < 0.05). However, after three months SB values returned to baseline levels. The number of tonic contractions were reduced even after three months of orthodontic treatment (P < 0.05). Conclusions: While clear aligners seem to be capable to reduce clenching, i.e. occlusal load, in SB patients, the grinding activity seems to be not influenced by those appliances at least in the short term of the present investigation.

Published
2016

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