Author: "Costantino E" / Publication Year Range: Last 10 years - Searchworks@Jio Institute Digital Library Search Results

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70 results on '"Costantino E"'

1. Adherence to GOLD guidelines in real-life COPD management in the Puglia region of Italy

Author: Palmiotti GA, Lacedonia D, Liotino V, Schino P, Satriano F, Di Napoli PL, Sabato E, Mastrosimone V, Scoditti A, Carone M, Costantino E, Resta E, Attolini E, and Foschino Barbaro MP
Subjects: COPD, appropriateness, web-platform, Health care spending, online survey, Diseases of the respiratory system, RC705-779
Abstract: Giuseppe Antonio Palmiotti,1 Donato Lacedonia,1 Vito Liotino,2 Pietro Schino,3 Francesco Satriano,4 Pier Luigi Di Napoli,3 Eugenio Sabato,5 Vincenzo Mastrosimone,6 Alfredo Scoditti,7 Mauro Carone,8 Elio Costantino,9 Emanuela Resta,2 Ettore Attolini,10 Maria Pia Foschino Barbaro1 1Department of Medical and Surgical Sciences, Institute of Respiratory Diseases, University of Foggia, Foggia, Italy; 2Department of Cardiac, Thoracic, and Vascular Science, Institute of Respiratory Diseases, School of Medicine, University of Bari, Bari, Italy; 3Physiopathology Respiratory Unit, F Miulli General Hospital, Acquaviva delle Fonti, Bari, Italy; 4Pneumology Clinic, Vito Fazzi Hospital, Lecce, Italy; 5UOC of Pneumology, “N Melli” Hospital, San Pietro Vernotico, Italy; 6Division of Pulmonary Disease, Medical Center of Rehabilitation, Foundation Salvatore Maugeri, IRCCS, Marina di Ginosa, Italy; 7Department of Respiratory Diseases, San Camillo Clinic, Taranto, Italy; 8Division of Pulmonary Disease, Medical Center of Rehabilitation, Foundation Salvatore Maugeri, IRCCS, Cassano delle Murge, Italy; 9UOC of Pneumology, Hospital “Madonna delle Grazie”, Matera, Italy; 10Regional Health Agency (ARES), Bari, Italy Background: COPD is a disease associated with significant economic burden. It was reported that Global initiative for chronic Obstructive Lung Disease (GOLD) guideline-oriented pharmacotherapy improves airflow limitation and reduces health care costs. However, several studies showed a significant dissociation between international recommendations and clinicians’ practices. The consequent reduced diagnostic and therapeutic inappropriateness has proved to be associated with an increase in costs and a waste of economic resources in the health sector. The aim of the study was to evaluate COPD management in the Puglia region. The study was performed in collaboration with the pulmonology centers and the Regional Health Agency (AReS Puglia). Methods: An IT platform allowed the pulmonologists to enter data via the Internet. All COPD patients who visited a pneumological outpatient clinic for the first time or for regular follow-ups or were admitted to a pneumological department for an exacerbation were considered eligible for the study. COPD’s diagnosis was confirmed by a pulmonologist at the moment of the visit. The project lasted 18 months and involved 17 centers located in the Puglia region. Results: Six hundred ninety-three patients were enrolled, evenly distributed throughout the region. The mean age was 71±9 years, and 85% of them were males. Approximately 23% were current smokers, 63% former smokers and 13.5% never smokers. The mean post-bronchodilator forced expiratory volume in 1 second was 59%±20% predicted. The platform allowed the classification of patients according to the GOLD guidelines (Group A: 20.6%, Group B: 32.3%, Group C: 5.9% and Group D: 39.2%), assessed the presence and severity of exacerbations (20% of the patients had an exacerbation defined as mild [13%], moderate [37%] and severe [49%]) and evaluated the appropriateness of inhalation therapy at the time of the visit. Forty-nine percent of Group A patients were following inappropriate therapy; in Group B, 45.8% were following a therapy in contrast with the guidelines. Among Group C patients, 41.46% resulted in triple combination therapy, while ~14% of Group D patients did not have a therapy or were following an inappropriate therapy. In conclusion, 30% of all patients evaluated had been following an inadequate therapy. Subsequently, an online survey was developed to inquire about the reasons for the results obtained. In particular, we investigated the reasons why 30% of our population did not follow the therapy suggested by the GOLD guidelines: 1) why was there an excessive use of inhaled corticosteroids, 2) why a significantly high percentage was inappropriately treated with triple therapy and 3) why a consistent percentage (11%) of Group D patients were not treated at all. Conclusion: The data provides an overview on the management of COPD in the region of Puglia (Italy) and represents a resource in order to improve appropriateness and reduce the waste of health resources. Keywords: COPD, appropriateness, web platform, health care spending, online survey
Published: 2018

2. The latent structure of the adult attachment interview: Large sample evidence from the collaboration on attachment transmission synthesis

Author: Lee Raby, K, Verhage, M, Pasco Fearon, R, Chris Fraley, R, Roisman, G, van IJzendoorn, M, Schuengel, C, Madigan, S, Oosterman, M, Bakermans-Kranenburg, M, Bernier, A, Ensink, K, Hautamaki, A, Mangelsdorf, S, Priddis, L, Wong, M, Aviezer, O, Behrens, K, Brisch, K, Cassibba, R, Cassidy, J, Coppola, G, Costantini, A, Dozier, M, Duschinsky, R, Ierardi, E, Finger, B, de Millan, S, Harder, S, Hazen, N, Jin, M, Myung, S, Jongenelen, I, Leerkes, E, Lionetti, F, Lyons-Ruth, K, Mcmahon, C, Meins, E, Pace, C, Pederson, D, Riva Crugnola, C, Sagi-Schwartz, A, Schoppe-Sullivan, S, Speranza, A, Steele, H, Tarabulsy, G, Vaever, M, Ward, M, Arnott, B, Bailey, H, Behringer, J, Brice, P, Castoro, G, Costantino, E, Cyr, C, George, C, Gloger-Tippelt, G, Howes, C, Jacobsen, H, Jacobvitz, D, Juffer, F, Kazui, M, Koppe, S, Millan, S, Murray, L, Simonelli, A, Solomon, J, Steele, M, Teti, D, Monique van Londen-Barentsen, W, Lee Raby K., Verhage M. L., Pasco Fearon R. M., Chris Fraley R., Roisman G. I., van IJzendoorn M. H., Schuengel C., Madigan S., Oosterman M., Bakermans-Kranenburg M. J., Bernier A., Ensink K., Hautamaki A., Mangelsdorf S., Priddis L. E., Wong M. S., Aviezer O., Behrens K. Y., Brisch K. -H., Cassibba R., Cassidy J., Coppola G., Costantini A., Dozier M., Duschinsky R., Ierardi E., Finger B., de Millan S. G., Harder S., Hazen N. L., Jin M. M., Myung S., Jongenelen I., Leerkes E. M., Lionetti F., Lyons-Ruth K., McMahon C., Meins E., Pace C. S., Pederson D. R., Riva Crugnola C., Sagi-Schwartz A., Schoppe-Sullivan S. J., Speranza A. M., Steele H., Tarabulsy G. M., Vaever M. S., Ward M. J., Arnott B., Bailey H., Behringer J., Brice P. J., Castoro G., Costantino E., Cyr C., George C., Gloger-Tippelt G., Howes C., Jacobsen H., Jacobvitz D., Juffer F., Kazui M., Koppe S., Millan S., Murray L., Simonelli A., Solomon J., Steele M., Teti D. M., Monique van Londen-Barentsen W., Lee Raby, K, Verhage, M, Pasco Fearon, R, Chris Fraley, R, Roisman, G, van IJzendoorn, M, Schuengel, C, Madigan, S, Oosterman, M, Bakermans-Kranenburg, M, Bernier, A, Ensink, K, Hautamaki, A, Mangelsdorf, S, Priddis, L, Wong, M, Aviezer, O, Behrens, K, Brisch, K, Cassibba, R, Cassidy, J, Coppola, G, Costantini, A, Dozier, M, Duschinsky, R, Ierardi, E, Finger, B, de Millan, S, Harder, S, Hazen, N, Jin, M, Myung, S, Jongenelen, I, Leerkes, E, Lionetti, F, Lyons-Ruth, K, Mcmahon, C, Meins, E, Pace, C, Pederson, D, Riva Crugnola, C, Sagi-Schwartz, A, Schoppe-Sullivan, S, Speranza, A, Steele, H, Tarabulsy, G, Vaever, M, Ward, M, Arnott, B, Bailey, H, Behringer, J, Brice, P, Castoro, G, Costantino, E, Cyr, C, George, C, Gloger-Tippelt, G, Howes, C, Jacobsen, H, Jacobvitz, D, Juffer, F, Kazui, M, Koppe, S, Millan, S, Murray, L, Simonelli, A, Solomon, J, Steele, M, Teti, D, Monique van Londen-Barentsen, W, Lee Raby K., Verhage M. L., Pasco Fearon R. M., Chris Fraley R., Roisman G. I., van IJzendoorn M. H., Schuengel C., Madigan S., Oosterman M., Bakermans-Kranenburg M. J., Bernier A., Ensink K., Hautamaki A., Mangelsdorf S., Priddis L. E., Wong M. S., Aviezer O., Behrens K. Y., Brisch K. -H., Cassibba R., Cassidy J., Coppola G., Costantini A., Dozier M., Duschinsky R., Ierardi E., Finger B., de Millan S. G., Harder S., Hazen N. L., Jin M. M., Myung S., Jongenelen I., Leerkes E. M., Lionetti F., Lyons-Ruth K., McMahon C., Meins E., Pace C. S., Pederson D. R., Riva Crugnola C., Sagi-Schwartz A., Schoppe-Sullivan S. J., Speranza A. M., Steele H., Tarabulsy G. M., Vaever M. S., Ward M. J., Arnott B., Bailey H., Behringer J., Brice P. J., Castoro G., Costantino E., Cyr C., George C., Gloger-Tippelt G., Howes C., Jacobsen H., Jacobvitz D., Juffer F., Kazui M., Koppe S., Millan S., Murray L., Simonelli A., Solomon J., Steele M., Teti D. M., and Monique van Londen-Barentsen W.
Abstract: The Adult Attachment Interview (AAI) is a widely used measure in developmental science that assesses adults' current states of mind regarding early attachment-related experiences with their primary caregivers. The standard system for coding the AAI recommends classifying individuals categorically as having an autonomous, dismissing, preoccupied, or unresolved attachment state of mind. However, previous factor and taxometric analyses suggest that: (a) adults' attachment states of mind are captured by two weakly correlated factors reflecting adults' dismissing and preoccupied states of mind and (b) individual differences on these factors are continuously rather than categorically distributed. The current study revisited these suggestions about the latent structure of AAI scales by leveraging individual participant data from 40 studies (N = 3,218), with a particular focus on the controversial observation from prior factor analytic work that indicators of preoccupied states of mind and indicators of unresolved states of mind about loss and trauma loaded on a common factor. Confirmatory factor analyses indicated that: (a) a 2-factor model with weakly correlated dismissing and preoccupied factors and (b) a 3-factor model that further distinguished unresolved from preoccupied states of mind were both compatible with the data. The preoccupied and unresolved factors in the 3-factor model were highly correlated. Taxometric analyses suggested that individual differences in dismissing, preoccupied, and unresolved states of mind were more consistent with a continuous than a categorical model. The importance of additional tests of predictive validity of the various models is emphasized.
Published: 2022

3. Conceptual comparison of constructs as first step in data harmonization: Parental sensitivity, child temperament, and social support as illustrations

Author: Verhage, M, Schuengel, C, Holopainen, A, Bakermans-Kranenburg, M, Bernier, A, Brown, G, Madigan, S, Roisman, G, Vaever, M, Wong, M, Barone, L, Behrens, K, Behringer, J, Bovenschen, I, Cassibba, R, Cassidy, J, Coppola, G, Costantini, A, Dozier, M, Ensink, K, Fearon, R, Finger, B, Hautamaki, A, Hazen, N, Ierardi, E, Jongenelen, I, Koppe, S, Lionetti, F, Mangelsdorf, S, Oosterman, M, Pace, C, Raby, K, Riva Crugnola, C, Simonelli, A, Spangler, G, Tarabulsy, G, Arnott, B, Bailey, H, Brice, P, Brisch, K, Castoro, G, Costantino, E, Cyr, C, George, C, Gloger-Tippelt, G, Gojman, S, Harder, S, Howes, C, Jacobsen, H, Jacobvitz, D, Jin, M, Juffer, F, Kazui, M, Leerkes, E, Lyons-Ruth, K, Mcmahon, C, Meins, E, Millan, S, Murray, L, Nowacki, K, Pederson, D, Priddis, L, Sagi-Schwartz, A, Schoppe-Sullivan, S, Solomon, J, Speranza, A, Steele, M, Steele, H, Teti, D, van IJzendoorn, M, van Londen-Barentsen, W, Ward, M, Verhage M. L., Schuengel C., Holopainen A., Bakermans-Kranenburg M. J., Bernier A., Brown G. L., Madigan S., Roisman G. I., Vaever M. S., Wong M. S., Barone L., Behrens K. Y., Behringer J., Bovenschen I., Cassibba R., Cassidy J., Coppola G., Costantini A., Dozier M., Ensink K., Fearon R. M. P., Finger B., Hautamaki A., Hazen N. L., Ierardi E., Jongenelen I., Koppe S., Lionetti F., Mangelsdorf S., Oosterman M., Pace C. S., Raby K. L., Riva Crugnola C., Simonelli A., Spangler G., Tarabulsy G. M., Arnott B., Bailey H., Brice P. J., Brisch K. -H., Castoro G., Costantino E., Cyr C., George C., Gloger-Tippelt G., Gojman S., Harder S., Howes C., Jacobsen H., Jacobvitz D., Jin M. K., Juffer F., Kazui M., Leerkes E. M., Lyons-Ruth K., McMahon C., Meins E., Millan S., Murray L., Nowacki K., Pederson D. R., Priddis L., Sagi-Schwartz A., Schoppe-Sullivan S. J., Solomon J., Speranza A. M., Steele M., Steele H., Teti D. M., van IJzendoorn M. H., van Londen-Barentsen W. M., Ward M. J., Verhage, M, Schuengel, C, Holopainen, A, Bakermans-Kranenburg, M, Bernier, A, Brown, G, Madigan, S, Roisman, G, Vaever, M, Wong, M, Barone, L, Behrens, K, Behringer, J, Bovenschen, I, Cassibba, R, Cassidy, J, Coppola, G, Costantini, A, Dozier, M, Ensink, K, Fearon, R, Finger, B, Hautamaki, A, Hazen, N, Ierardi, E, Jongenelen, I, Koppe, S, Lionetti, F, Mangelsdorf, S, Oosterman, M, Pace, C, Raby, K, Riva Crugnola, C, Simonelli, A, Spangler, G, Tarabulsy, G, Arnott, B, Bailey, H, Brice, P, Brisch, K, Castoro, G, Costantino, E, Cyr, C, George, C, Gloger-Tippelt, G, Gojman, S, Harder, S, Howes, C, Jacobsen, H, Jacobvitz, D, Jin, M, Juffer, F, Kazui, M, Leerkes, E, Lyons-Ruth, K, Mcmahon, C, Meins, E, Millan, S, Murray, L, Nowacki, K, Pederson, D, Priddis, L, Sagi-Schwartz, A, Schoppe-Sullivan, S, Solomon, J, Speranza, A, Steele, M, Steele, H, Teti, D, van IJzendoorn, M, van Londen-Barentsen, W, Ward, M, Verhage M. L., Schuengel C., Holopainen A., Bakermans-Kranenburg M. J., Bernier A., Brown G. L., Madigan S., Roisman G. I., Vaever M. S., Wong M. S., Barone L., Behrens K. Y., Behringer J., Bovenschen I., Cassibba R., Cassidy J., Coppola G., Costantini A., Dozier M., Ensink K., Fearon R. M. P., Finger B., Hautamaki A., Hazen N. L., Ierardi E., Jongenelen I., Koppe S., Lionetti F., Mangelsdorf S., Oosterman M., Pace C. S., Raby K. L., Riva Crugnola C., Simonelli A., Spangler G., Tarabulsy G. M., Arnott B., Bailey H., Brice P. J., Brisch K. -H., Castoro G., Costantino E., Cyr C., George C., Gloger-Tippelt G., Gojman S., Harder S., Howes C., Jacobsen H., Jacobvitz D., Jin M. K., Juffer F., Kazui M., Leerkes E. M., Lyons-Ruth K., McMahon C., Meins E., Millan S., Murray L., Nowacki K., Pederson D. R., Priddis L., Sagi-Schwartz A., Schoppe-Sullivan S. J., Solomon J., Speranza A. M., Steele M., Steele H., Teti D. M., van IJzendoorn M. H., van Londen-Barentsen W. M., and Ward M. J.
Abstract: This article presents a strategy for the initial step of data harmonization in Individual Participant Data syntheses, i.e., making decisions as to which measures operationalize the constructs of interest - and which do not. This step is vital in the process of data harmonization, because a study can only be as good as its measures. If the construct validity of the measures is in question, study results are questionable as well. Our proposed strategy for data harmonization consists of three steps. First, a unitary construct is defined based on the existing literature, preferably on the theoretical framework surrounding the construct. Second, the various instruments used to measure the construct are evaluated as operationalizations of this construct, and retained or excluded based on this evaluation. Third, the scores of the included measures are recoded on the same metric. We illustrate the use of this method with three example constructs focal to the Collaboration on Attachment Transmission Synthesis (CATS) study: parental sensitivity, child temperament, and social support. This process description may aid researchers in their data pooling studies, filling a gap in the literature on the first step of data harmonization. • Data harmonization in studies using combined datasets is of vital importance for the validity of the study results. • We have developed and illustrated a strategy on how to define a unitary construct and evaluate whether instruments are operationalizations of this construct as the initial step in the harmonization process. • This strategy is a transferable and reproducible method to apply to the data harmonization process.
Published: 2022

4. The latent structure of the adult attachment interview: Large sample evidence from the collaboration on attachment transmission synthesis

Author: Lee Raby K., Verhage M. L., Pasco Fearon R. M., Chris Fraley R., Roisman G. I., van IJzendoorn M. H., Schuengel C., Madigan S., Oosterman M., Bakermans-Kranenburg M. J., Bernier A., Ensink K., Hautamaki A., Mangelsdorf S., Priddis L. E., Wong M. S., Aviezer O., Behrens K. Y., Brisch K. -H., Cassibba R., Cassidy J., Coppola G., Costantini A., Dozier M., Duschinsky R., Ierardi E., Finger B., de Millan S. G., Harder S., Hazen N. L., Jin M. M., Myung S., Jongenelen I., Leerkes E. M., Lionetti F., Lyons-Ruth K., McMahon C., Meins E., Pace C. S., Pederson D. R., Riva Crugnola C., Sagi-Schwartz A., Schoppe-Sullivan S. J., Speranza A. M., Steele H., Tarabulsy G. M., Vaever M. S., Ward M. J., Arnott B., Bailey H., Behringer J., Brice P. J., Castoro G., Costantino E., Cyr C., George C., Gloger-Tippelt G., Howes C., Jacobsen H., Jacobvitz D., Juffer F., Kazui M., Koppe S., Millan S., Murray L., Simonelli A., Solomon J., Steele M., Teti D. M., Monique van Londen-Barentsen W., Lee Raby, K, Verhage, M, Pasco Fearon, R, Chris Fraley, R, Roisman, G, van IJzendoorn, M, Schuengel, C, Madigan, S, Oosterman, M, Bakermans-Kranenburg, M, Bernier, A, Ensink, K, Hautamaki, A, Mangelsdorf, S, Priddis, L, Wong, M, Aviezer, O, Behrens, K, Brisch, K, Cassibba, R, Cassidy, J, Coppola, G, Costantini, A, Dozier, M, Duschinsky, R, Ierardi, E, Finger, B, de Millan, S, Harder, S, Hazen, N, Jin, M, Myung, S, Jongenelen, I, Leerkes, E, Lionetti, F, Lyons-Ruth, K, Mcmahon, C, Meins, E, Pace, C, Pederson, D, Riva Crugnola, C, Sagi-Schwartz, A, Schoppe-Sullivan, S, Speranza, A, Steele, H, Tarabulsy, G, Vaever, M, Ward, M, Arnott, B, Bailey, H, Behringer, J, Brice, P, Castoro, G, Costantino, E, Cyr, C, George, C, Gloger-Tippelt, G, Howes, C, Jacobsen, H, Jacobvitz, D, Juffer, F, Kazui, M, Koppe, S, Millan, S, Murray, L, Simonelli, A, Solomon, J, Steele, M, Teti, D, and Monique van Londen-Barentsen, W
Subjects: Adult, Predictive validity, Individuality, 050109 social psychology, taxometric, Developmental Science, Developmental psychology, Interview, Psychological, Developmental and Educational Psychology, Categorical models, Humans, 0501 psychology and cognitive sciences, Latent structure, Individual participant data, 05 social sciences, 16. Peace & justice, Object Attachment, Large sample, Standard system, Psychiatry and Mental health, factor analysi, Psychology, latent structure, Attachment measures, Adult Attachment Interview, 050104 developmental & child psychology
Abstract: The Adult Attachment Interview (AAI) is a widely used measure in developmental science that assesses adults’ current states of mind regarding early attachment-related experiences with their primary caregivers. The standard system for coding the AAI recommends classifying individuals categorically as having an autonomous, dismissing, preoccupied, or unresolved attachment state of mind. However, previous factor and taxometric analyses suggest that: (a) adults’ attachment states of mind are captured by two weakly correlated factors reflecting adults’ dismissing and preoccupied states of mind and (b) individual differences on these factors are continuously rather than categorically distributed. The current study revisited these suggestions about the latent structure of AAI scales by leveraging individual participant data from 40 studies (N = 3,218), with a particular focus on the controversial observation from prior factor analytic work that indicators of preoccupied states of mind and indicators of unresolved states of mind about loss and trauma loaded on a common factor. Confirmatory factor analyses indicated that: (a) a 2-factor model with weakly correlated dismissing and preoccupied factors and (b) a 3-factor model that further distinguished unresolved from preoccupied states of mind were both compatible with the data. The preoccupied and unresolved factors in the 3-factor model were highly correlated. Taxometric analyses suggested that individual differences in dismissing, preoccupied, and unresolved states of mind were more consistent with a continuous than a categorical model. The importance of additional tests of predictive validity of the various models is emphasized.
Published: 2020

5. Risk factors and action thresholds for the novel coronavirus pandemic. Insights from the Italian Society of Nephrology COVID-19 Survey

Author: Nordio, M., Reboldi, G., Di Napoli, A., Quintaliani, G., Alberici, F., Postorino, M., Aucella, F., Messa, P., Brunori, G., Bosco, M., Malberti, F., Mandreoli, M., Mazzaferro, S., Movilli, E., Ravera, M., Salomone, M., Santoro, D., Postorinolimido, M. A., Bonomini, M., Stingone, A., Maccarone, M., Di Loreto, E., Stacchiotti, L., Malandra, R., Chiarella, S., D'Agostino, F., Fuiano, G., Nicodemo, L., Bonofiglio, R., Greco, S., Mallamaci, F., Barreca, E., Caserta, C., Bruzzese, V., Galati, D., Tramontana, D., Viscione, M., Chiuchiolo, L., Tuccillo, S., Sepe, M., Vitale, F., Ciriana, E., Martignetti, V., Caserta, D., Stizzo, A., Romano, A., Iulianiello, G., Cascone, E., Minicone, P., Chiricone, D., Delgado, G., Barbato, A., Celentano, S., Molfino, I., Coppola, S., Raiola, I., Abategiovanni, M., Borrelli, S., Margherita, C., Bruno, F., Ida, M., Aliperti, E., Potito, D., Cuomo, G., De Luca, M., Merola, M., Botta, C., Garofalo, G., Alinei, P., Paglionico, C., Roano, M., Vitale, S., Ierardi, R., Fimiani, V., Conte, G., Di Natale, G., Romano, M., Di Marino, V., Scafarto, A., Meccariello, S., Pecoraro, C., Di Stazio, E., Di Meglio, E., Cuomo, A., Maresca, B., Rotaia, E., Capasso, G., Auricchio, M., Pluvio, C., Maddalena, L., De Maio, A., Palladino, G., Buono, F., Gigliotti, G., Mancini, E., La Manna, G., Storari, A., Mosconi, G., Cappelli, G., Scarpioni, R., Gregorini, M., Rigotti, A., Mancini, W., Bianco, F., Boscutti, G., Amici, G., Tosto, M., Fini, R., Pace, G., Cioffi, A., Boccia, E., Di Lullo, L., Di Zazzo, G., Simonelli, R., Bondatti, F., Miglio, L., Rifici, N., Treglia, A., Muci, M., Baldinelli, G., Rizzi, E., Lonzi, M., De Cicco, C., Forte, F., De Paolis, P., Grandaliano, Giuseppe, Cuzziol, C., Torre, V. M., Sfregola, P., Rossi, V., Fabio, G., Flammini, A., Filippini, A., Onorato, L., Vendola, F., Di Daniela, N., Alfarone, C., Scabbia, L., Ferrazzano, M., Grotta, B. D., Gamberini, M., Fazzari, L., Mene, P., Morgia, A., Catucci, A., Palumbo, R., Puliti, M., Marinelli, R., Polito, P., Marrocco, F., Morabito, S., Rocca, R., Nazzaro, L., Lavini, R., Iamundo, V., Chiappini, M., Casarci, M., Morosetti, M., Hassan, S., Firmi, G., Galliani, M., Serraiocco, M., Feriozzi, S., Valentini, W., Sacco, P., Garibotto, G., Cappelli, V., Saffioti, C., Repetto, M., Rolla, D., Lorenz, M., Pedrini, L., Polonioli, D., Galli, E., Ruggenenti, P., Scolari, F., Bove, S., Costantino, E., Bracchi, M., Mangano, S., Depetri, G., La Milia, V., Farina, M., Zecchini, S., Savino, R., Melandri, M., Guastoni, C., Paparella, M., Gallieni, M., Minetti, E., Bisegna, S., Righetti, M., Badalamenti, S., Alberghini, E., Bertoli, S., Fabbrini, P., Albrizio, P., Rampino, T., Colturi, C., Rombola, G., Lucatello, A., Guerrini, E., Ranghino, A., Lenci, F., Fanciulli, E., Santarelli, S., Damiani, C., Garofalo, D., Sopranzi, F., Santoferrara, A., Di Luca, M., Galiotta, P., Brigante, M., Manganaro, M., Maffei, S., Berto, I., Besso, L., Viglino, G., Cusinato, S., Chiarinottichiappero, D. F., Tognarelli, G., Gianoglio, B., Forneris, G., Biancone, L., Savoldi, S., Vitale, C., Boero, R., Filiberti, O., Borzumati, M., Gesualdo, L., Lomonte, C., Gernone, G., Pallotta, G., Di Paolo, S., Vernaglione, L., Specchio, A., Stallone, G., Dell'Aquila, R., Sandri, G., Russo, F., Napoli, M., Marangi, A., Morrone, L., Di Stratis, C., Fresu, A., Cicu, F., Murtas, S., Manca, O., Pani, A., Pilloni, M., Pistis, R., Cadoni, M., Contu, B., Logias, F., Ivaldi, R., Fancello, S., Cossu, M., Lepori, G., Vittoria, S., Battiati, E., Arnone, M., Rome, M., Barbera, A., Granata, A., Collura, G., Dico, C. L., Pugliese, G., Di Natale, E., Rizzari, G., Cottone, L., Longo, N., Battaglia, G., Marcantoni, C., Giannetto, G., Tumino, G., Randazzo, F., Bellissimo, L., Faro, F. L., Grippaldi, F., Urso, S., Quattrone, G., Todaro, I., Vincenzo, D., Murgo, A., Masuzzo, M., Pisacane, A., Monardo, P., Pontorierro, M., Quari, C., Bauro, A., Chimenz, R. R., Alfio, D., Girasole, F., Cascio, A. L., Caviglia, A., Tornese, F., Sirna, F., Altieri, C., Cusumano, R., Saveriano, V., La Corte, A., Locascio, G., Rotolo, U., Musso, S., Risuglia, L., Blanco, G., Minardo, G., Castellino, S., Zappulla, Z., Randone, S., Di Francesca, M., Cassetti, C. C., Oddo, G., Buscaino, G., Mucaria, F., Barraco, V. I., Di Martino, A., Rallo, D., Dani, L., Campolo, G., Manescalchi, F., Biagini, M., Agate, M., Panichi, V., Casani, A., Traversari, L., Garosi, G., Tabbi, M., Selvi, A., Cencioni, L., Fagugli, R., Timio, F., Leveque, A., Manes, M., Mennella, G., Calo, L., Fiorini, F., Abaterusso, C., Calzavara, P., Meneghel, G., Bonesso, C., Gambaro, G., Gammaro, L., Rugiu, C., Ronco, C., Nordio M., Reboldi G., Di Napoli A., Quintaliani G., Alberici F., Postorino M., Aucella F., Messa P., Brunori G., Bosco M., Malberti F., Mandreoli M., Mazzaferro S., Movilli E., Ravera M., Salomone M., Santoro D., PostorinoLimido M.A., Bonomini M., Stingone A., Maccarone M., Di Loreto E., Stacchiotti L., Malandra R., Chiarella S., D'Agostino F., Fuiano G., Nicodemo L., Bonofiglio R., Greco S., Mallamaci F., Barreca E., Caserta C., Bruzzese V., Galati D., Tramontana D., Viscione M., Chiuchiolo L., Tuccillo S., Sepe M., Vitale F., Ciriana E., Martignetti V., Caserta D., Stizzo A., Romano A., Iulianiello G., Cascone E., Minicone P., Chiricone D., Delgado G., Barbato A., Celentano S., Molfino I., Coppola S., Raiola I., Abategiovanni M., Borrelli S., Margherita C., Bruno F., Ida M., Aliperti E., Potito D., Cuomo G., De Luca M., Merola M., Botta C., Garofalo G., Alinei P., Paglionico C., Roano M., Vitale S., Ierardi R., Fimiani V., Conte G., Di Natale G., Romano M., Di Marino V., Scafarto A., Meccariello S., Pecoraro C., Di Stazio E., Di Meglio E., Cuomo A., Maresca B., Rotaia E., Capasso G., Auricchio M., Pluvio C., Maddalena L., De Maio A., Palladino G., Buono F., Gigliotti G., Mancini E., La Manna G., Storari A., Mosconi G., Cappelli G., Scarpioni R., Gregorini M., Rigotti A., Mancini W., Bianco F., Boscutti G., Amici G., Tosto M., Fini R., Pace G., Cioffi A., Boccia E., Di Lullo L., Di Zazzo G., Simonelli R., Bondatti F., Miglio L., Rifici N., Treglia A., Muci M., Baldinelli G., Rizzi E., Lonzi M., De Cicco C., Forte F., De Paolis P., Grandaliano G., Cuzziol C., Torre V.M., Sfregola P., Rossi V., Fabio G., Flammini A., Filippini A., Onorato L., Vendola F., Di Daniela N., Alfarone C., Scabbia L., Ferrazzano M., Grotta B.D., Gamberini M., Fazzari L., Mene P., Morgia A., Catucci A., Palumbo R., Puliti M., Marinelli R., Polito P., Marrocco F., Morabito S., Rocca R., Nazzaro L., Lavini R., Iamundo V., Chiappini M., Casarci M., Morosetti M., Hassan S., Firmi G., Galliani M., Serraiocco M., Feriozzi S., Valentini W., Sacco P., Garibotto G., Cappelli V., Saffioti C., Repetto M., Rolla D., Lorenz M., Pedrini L., Polonioli D., Galli E., Ruggenenti P., Scolari F., Bove S., Costantino E., Bracchi M., Mangano S., Depetri G., La Milia V., Farina M., Zecchini S., Savino R., Melandri M., Guastoni C., Paparella M., Gallieni M., Minetti E., Bisegna S., Righetti M., Badalamenti S., Alberghini E., Bertoli S., Fabbrini P., Albrizio P., Rampino T., Colturi C., Rombola G., Lucatello A., Guerrini E., Ranghino A., Lenci F., Fanciulli E., Santarelli S., Damiani C., Garofalo D., Sopranzi F., Santoferrara A., Di Luca M., Galiotta P., Brigante M., Manganaro M., Maffei S., Berto I., Besso L., Viglino G., Cusinato S., ChiarinottiChiappero D.F., Tognarelli G., Gianoglio B., Forneris G., Biancone L., Savoldi S., Vitale C., Boero R., Filiberti O., Borzumati M., Gesualdo L., Lomonte C., Gernone G., Pallotta G., Di Paolo S., Vernaglione L., Specchio A., Stallone G., Dell'Aquila R., Sandri G., Russo F., Napoli M., Marangi A., Morrone L., Di Stratis C., Fresu A., Cicu F., Murtas S., Manca O., Pani A., Pilloni M., Pistis R., Cadoni M., Contu B., Logias F., Ivaldi R., Fancello S., Cossu M., Lepori G., Vittoria S., Battiati E., Arnone M., Rome M., Barbera A., Granata A., Collura G., Dico C.L., Pugliese G., Di Natale E., Rizzari G., Cottone L., Longo N., Battaglia G., Marcantoni C., Giannetto G., Tumino G., Randazzo F., Bellissimo L., Faro F.L., Grippaldi F., Urso S., Quattrone G., Todaro I., Vincenzo D., Murgo A., Masuzzo M., Pisacane A., Monardo P., Pontorierro M., Quari C., Bauro A., Chimenz R.R., Alfio D., Girasole F., Cascio A.L., Caviglia A., Tornese F., Sirna F., Altieri C., Cusumano R., Saveriano V., La Corte A., Locascio G., Rotolo U., Musso S., Risuglia L., Blanco G., Minardo G., Castellino S., Zappulla Z., Randone S., Di Francesca M., Cassetti C.C., Oddo G., Buscaino G., Mucaria F., Barraco V.I., Di Martino A., Rallo D., Dani L., Campolo G., Manescalchi F., Biagini M., Agate M., Panichi V., Casani A., Traversari L., Garosi G., Tabbi M., Selvi A., Cencioni L., Fagugli R., Timio F., Leveque A., Manes M., Mennella G., Calo L., Fiorini F., Abaterusso C., Calzavara P., Meneghel G., Bonesso C., Gambaro G., Gammaro L., Rugiu C., and Ronco C.
Subjects: Male, Contextual analysis, medicine.medical_treatment, Population, 030232 urology & nephrology, Recursive partitioning, 030204 cardiovascular system & hematology, Rate ratio, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Classification tree, COVID-19, Renal replacement therapy, Risk Factors, Medical, Surveys and Questionnaires, Health care, medicine, Settore MED/14 - NEFROLOGIA, Humans, education, Pandemics, Societies, Medical, Female, Italy, Nephrology, education.field_of_study, business.industry, Multilevel model, Decision rule, Confidence interval, Original Article, Hemodialysis, business, Contextual analysi, Societies, Demography
Abstract: Background and aim: Over 80% (365/454) of the nation’s centers participated in the Italian Society of Nephrology COVID-19 Survey. Out of 60,441 surveyed patients, 1368 were infected as of April 23rd, 2020. However, center-specific proportions showed substantial heterogeneity. We therefore undertook new analyses to identify explanatory factors, contextual effects, and decision rules for infection containment. Methods: We investigated fixed factors and contextual effects by multilevel modeling. Classification and Regression Tree (CART) analysis was used to develop decision rules. Results: Increased positivity among hemodialysis patients was predicted by center location [incidence rate ratio (IRR) 1.34, 95% confidence interval (CI) 1.20–1.51], positive healthcare workers (IRR 1.09, 95% CI 1.02–1.17), test-all policy (IRR 5.94, 95% CI 3.36–10.45), and infected proportion in the general population (IRR 1.002, 95% CI 1.001–1.003) (all p < 0.01). Conversely, lockdown duration exerted a protective effect (IRR 0.95, 95% CI 0.94–0.98) (p < 0.01). The province-contextual effects accounted for 10% of the total variability. Predictive factors for peritoneal dialysis and transplant cases were center location and infected proportion in the general population. Using recursive partitioning, we identified decision thresholds at general population incidence ≥ 229 per 100,000 and at ≥ 3 positive healthcare workers. Conclusions: Beyond fixed risk factors, shared with the general population, the increased and heterogeneous proportion of positive patients is related to the center’s testing policy, the number of positive patients and healthcare workers, and to contextual effects at the province level. Nephrology centers may adopt simple decision rules to strengthen containment measures timely.
Published: 2021

6. Current Concepts in the Treatment of Giant Cell Tumor of Bone: An Update

Author: Shinji Tsukamoto, Andreas F. Mavrogenis, Tomoya Masunaga, Kanya Honoki, Hiromasa Fujii, Akira Kido, Yasuhito Tanaka, and Costantino Errani
Subjects: giant cell tumor of bone, extremity, pelvis, sacrum, spine, denosumab, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Curettage is recommended for the treatment of Campanacci stages 1–2 giant cell tumor of bone (GCTB) in the extremities, pelvis, sacrum, and spine, without preoperative denosumab treatment. In the distal femur, bone chips and plate fixation are utilized to reduce damage to the subchondral bone and prevent pathological fracture, respectively. For local recurrence, re-curettage may be utilized when feasible. En bloc resection is an option for very aggressive Campanacci stage 3 GCTB in the extremities, pelvis, sacrum, and spine, combined with 1–3 doses of preoperative denosumab treatment. Denosumab monotherapy once every 3 months is currently the standard strategy for inoperable patients and those with metastatic GCTB. However, in case of tumor growth, a possible malignant transformation should be considered. Zoledronic acid appears to be as effective as denosumab; nevertheless, it is a more cost-effective option. Therefore, zoledronic acid may be an alternative treatment option, particularly in developing countries. Surgery is the mainstay treatment for malignant GCTB.
Published: 2024
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7. Health-Related Lifestyle Profiles in Healthy Adults: Associations with Sociodemographic Indicators, Dispositional Optimism, and Sense of Coherence

Author: Adorni, R, Zanatta, F, D'Addario, M, Atella, F, Costantino, E, Iaderosa, C, Petarle, G, Steca, P, Adorni, Roberta, Zanatta, Francesco, D'Addario, Marco, Atella, Francesca, Costantino, Elena, Iaderosa, Caterina, Petarle, Giulia, Steca, Patrizia, Adorni, R, Zanatta, F, D'Addario, M, Atella, F, Costantino, E, Iaderosa, C, Petarle, G, Steca, P, Adorni, Roberta, Zanatta, Francesco, D'Addario, Marco, Atella, Francesca, Costantino, Elena, Iaderosa, Caterina, Petarle, Giulia, and Steca, Patrizia
Abstract: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. Promoting healthy behaviors throughout life is an essential prevention tool. This study investigated the associations among lifestyle profiles (including diet, alcohol consumption, physical activity, cigarette smoking, and cardiovascular screening), sociodemographic factors (gender, age, education, and family history of CVDs), and psychological factors (sense of coherence and dispositional optimism). In total, 676 healthy adults (mean age = 35 years; range = 19–57; 46% male) participated in an online survey. Lifestyle profiles were identified through cluster analysis, and a multinomial logistic regression was then performed to explore their association with sociodemographic and psychological variables. Results show that men were more likely than women to belong to the lifestyle profile with the highest amount of physical activity (OR = 2.40; p < 0.001) and the greatest attention to cardiovascular screening (OR = 2.09; p < 0.01). Lower dispositional optimism was associated with the profile paying the greatest attention to cardiovascular screening (OR = 0.67; p < 0.05). Sense of coherence, in terms of lower comprehensibility (OR = 0.67; p < 0.05) and higher manageability (OR = 1.43; p < 0.05), was associated with the lifestyle profile characterized by an unhealthy diet, sedentary lifestyle, and nonsmoking. This study shed light on factors associated with different co-occurring health-related behaviors that should be considered in planning effective communication strategies promoting adherence to health claims.
Published: 2021

8. Biopsy Techniques for Musculoskeletal Tumors: Basic Principles and Specialized Techniques

Author: Andreas F. Mavrogenis, Pavlos Altsitzioglou, Shinji Tsukamoto, and Costantino Errani
Subjects: biopsy, percutaneous, incisional, liquid, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Biopsy is a pivotal component in the diagnostic process of bone and soft tissue tumors. The objective is to obtain adequate tissue without compromising local tumor dissemination and the patient’s survival. This review explores contemporary principles and practices in musculoskeletal biopsies, emphasizing the critical role of diagnostic accuracy while also delving into the evolving landscape of liquid biopsies as a promising alternative in the field. A thorough literature search was done in PubMed and Google Scholar as well as in physical books in libraries to summarize the available biopsy techniques for musculoskeletal tumors, discuss the available methods, risk factors, and complications, and to emphasize the challenges related to biopsies in oncology. Research articles that studied the basic principles and specialized techniques of biopsy techniques in tumor patients were deemed eligible. Their advantages and disadvantages, technical and pathophysiological mechanisms, and possible risks and complications were reviewed, summarized, and discussed. An inadequately executed biopsy may hinder diagnosis and subsequently impact treatment outcomes. All lesions should be approached with a presumption of malignancy until proven otherwise. Liquid biopsies have emerged as a potent non-invasive tool for analyzing tumor phenotype, progression, and drug resistance and guiding treatment decisions in bone sarcomas and metastases. Despite advancements, several barriers remain in biopsies, including challenges related to costs, scalability, reproducibility, and isolation methods. It is paramount that orthopedic oncologists work together with radiologists and pathologists to enhance diagnosis, patient outcomes, and healthcare costs.
Published: 2024
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9. A Systematic Review of Adjuvant Chemotherapy in Localized Dedifferentiated Chondrosarcoma

Author: Shinji Tsukamoto, Andreas F. Mavrogenis, Yuji Nitta, Alberto Righi, Tomoya Masunaga, Kanya Honoki, Hiromasa Fujii, Akira Kido, Yuu Tanaka, Yasuhito Tanaka, and Costantino Errani
Subjects: dedifferentiated, chondrosarcoma, adjuvant, chemotherapy, surgery, prognosis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Dedifferentiated chondrosarcoma (DDCS) is a high-grade subtype of chondrosarcoma with the bimorphic histological appearance of a conventional chondrosarcoma component with abrupt transition to a high-grade, non-cartilaginous sarcoma. DDCS can be radiographically divided into central and peripheral types. Wide resection is currently the main therapeutic option for localized DDCS. Moreover, the effectiveness of adjuvant chemotherapy remains controversial. Therefore, we performed a systematic review of available evidence to evaluate the effect of adjuvant chemotherapy on localized DDCS. The purpose was to compare the 5-year survival rate among patients treated with surgery plus adjuvant chemotherapy or surgery alone for localized DDCS. The search was conducted in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Of the 217 studies shortlisted, 11 retrospective non-randomized studies (comprising 556 patients with localized DDCS) were selected. The 5-year survival rates were similar between the two treatment groups (28.2% (51/181) vs. 24.0% (90/375), respectively). The overall pooled odds ratio was 1.25 (95% confidence interval: 0.80–1.94; p = 0.324), and heterogeneity I2 was 2%. However, when limited to peripheral DDCS, adjuvant chemotherapy was associated with prolonged survival (p = 0.03). Due to the paucity of included studies and the absence of prospective comparative studies, no conclusions can be drawn regarding the effectiveness or ineffectiveness of adjuvant chemotherapy for localized DDCS.
Published: 2024
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10. Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials

Author: van Eijk, Ruben P. A, Jones, Ashley R., Sproviero, William, Shatunov, Aleksey, Shaw, Pamela J., Leigh, P. Nigel, Young, Carolyn A., Shaw, Christopher E., Mora, Gabriele, Mandrioli, Jessica, Borghero, Giuseppe, Volanti, Paolo, Diekstra, Frank P., van Rheenen, Wouter, Verstraete, Esther, Eijkemans, Marinus J. C, Veldink, Jan H., Chio, Adriano, Al-Chalabi, Ammar, van den Berg, Leonard H., van Es, Michael A, For UKMND-LiCALS and LITALS Study Group: Allen C, Counsell C, Farrin A, Al-Chalabi A, Dickie B, Kelly J, Leigh PN, Murphy CL, Payan C, Reynolds G, Shaw P, Steen IN, Thornhill M, Waters J, Zajicek J, Shaw PJ, Young CA, Morrison KE, Dhariwal S, Hornabrook R, Savage L, Burn DJ, Khoo TK, Dougherty A, Wijesekera L, Ellis CM, Ali R, O'Hanlon K, Panicker J, Pate L, Ray P, Wyatt L, Copeland L, Ealing J, Hamdalla H, Leroi I, Murphy C, O'Keeffe F, Oughton E, Partington L, Paterson P, Rog D, Sathish A, Sexton D, Smith J, Vanek H, Dodds S, Williams TL, Clarke J, Eziefula C, Howard R, Orrell R, Sidle K, Sylvester R, Barrett W, Merritt C, Talbot K, Turner MR, Whatley C, Williams C, Williams J, Cosby C, Hanemann CO, Imam I, Phillips C, Timings L, Crawford SE, Hewamadduma C, Hibberd R, Hollinger H, McDermott C, Mills G, Rafiq M, Taylor A, Waines E, Walsh T, Addison-Jones R, Birt J, Hare M, Majid T, Tortelli R, D'Errico E, Bartolomei I, Barbarossa E, Depau B, Costantino E, D'Amico E, Uncini A, Manzoli C, Quatrale R, Sette E, Montanari E, Merello M, Zarcone D, Mascolo M, Vignolo M, Messina S, Morelli C, Marinou K, Papetti L, Lunetta C, Gorni K, De Cicco D, Pipia C, Sola P, Georgoulopoulou E, Sagnelli A, Tedeschi, Gioacchino, Oggioni G, Nasuelli N, D'Ascenzo C, Cima V, Aiello M, Rizzi R, Rinaldi E, Luigetti M, Conte A, Torzini A, Greco G, Mutani R, Fuda G, Tommasi MA, van Eijk, Ruben P. A, Jones, Ashley R., Sproviero, William, Shatunov, Aleksey, Shaw, Pamela J., Leigh, P. Nigel, Young, Carolyn A., Shaw, Christopher E., Mora, Gabriele, Mandrioli, Jessica, Borghero, Giuseppe, Volanti, Paolo, Diekstra, Frank P., van Rheenen, Wouter, Verstraete, Esther, Eijkemans, Marinus J. C, Veldink, Jan H., Chio, Adriano, Al-Chalabi, Ammar, van den Berg, Leonard H., van Es, Michael A, For UKMND-LiCALS and LITALS Study Group: Allen, C, Counsell, C, Farrin, A, Al-Chalabi, A, Dickie, B, Kelly, J, Leigh, Pn, Murphy, Cl, Payan, C, Reynolds, G, Shaw, P, Steen, In, Thornhill, M, Waters, J, Zajicek, J, Shaw, Pj, Young, Ca, Morrison, Ke, Dhariwal, S, Hornabrook, R, Savage, L, Burn, Dj, Khoo, Tk, Dougherty, A, Wijesekera, L, Ellis, Cm, Ali, R, O'Hanlon, K, Panicker, J, Pate, L, Ray, P, Wyatt, L, Copeland, L, Ealing, J, Hamdalla, H, Leroi, I, Murphy, C, O'Keeffe, F, Oughton, E, Partington, L, Paterson, P, Rog, D, Sathish, A, Sexton, D, Smith, J, Vanek, H, Dodds, S, Williams, Tl, Clarke, J, Eziefula, C, Howard, R, Orrell, R, Sidle, K, Sylvester, R, Barrett, W, Merritt, C, Talbot, K, Turner, Mr, Whatley, C, Williams, C, Williams, J, Cosby, C, Hanemann, Co, Imam, I, Phillips, C, Timings, L, Crawford, Se, Hewamadduma, C, Hibberd, R, Hollinger, H, Mcdermott, C, Mills, G, Rafiq, M, Taylor, A, Waines, E, Walsh, T, Addison-Jones, R, Birt, J, Hare, M, Majid, T, Tortelli, R, D'Errico, E, Bartolomei, I, Barbarossa, E, Depau, B, Costantino, E, D'Amico, E, Uncini, A, Manzoli, C, Quatrale, R, Sette, E, Montanari, E, Merello, M, Zarcone, D, Mascolo, M, Vignolo, M, Messina, S, Morelli, C, Marinou, K, Papetti, L, Lunetta, C, Gorni, K, De Cicco, D, Pipia, C, Sola, P, Georgoulopoulou, E, Sagnelli, A, Tedeschi, Gioacchino, Oggioni, G, Nasuelli, N, D'Ascenzo, C, Cima, V, Aiello, M, Rizzi, R, Rinaldi, E, Luigetti, M, Conte, A, Torzini, A, Greco, G, Mutani, R, Fuda, G, and Tommasi, Ma
Subjects: Oncology, R853.C55, medicine.medical_specialty, Genotype, Neuroprotective Agent, Clinical Neurology, Nerve Tissue Proteins, Review, Amyotrophic Lateral Sclerosis, C9orf72 Protein, Lithium Carbonate, Neuroprotective Agents, Proportional Hazards Models, Proteins, Pharmacogenetics, Randomized Controlled Trials as Topic, Neurology (clinical), Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Journal Article, 030212 general & internal medicine, Amyotrophic lateral sclerosis, business.industry, Protein, Pharmacogenetic, medicine.disease, Clinical trial, RC0346, Meta-analysis, Nerve Tissue Protein, Proportional Hazards Model, business, 030217 neurology & neurosurgery, Meta-Analysis, Amyotrophic Lateral Sclerosi
Abstract: OBJECTIVE\ud \ud To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders.\ud \ud METHODS\ud \ud Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months. On an exploratory basis, we assessed whether the effect of lithium depended on the genotype.\ud \ud RESULTS\ud \ud Clinical data were available for 518 of the 606 participants. Overall, treatment with lithium carbonate did not improve 12-month survival (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.7-1.4; p = 0.96). Both the UNC13A and C9orf72 genotype were independent predictors of survival (HR 2.4, 95% CI 1.3-4.3; p = 0.006 and HR 2.5, 95% CI 1.1-5.2; p = 0.032, respectively). The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3).\ud \ud CONCLUSIONS\ud \ud This study incorporated genetic data into past ALS trials to determine treatment effects in a genetic post hoc analysis. Our results suggest that we should reorient our strategies toward finding treatments for ALS, start focusing on genotype-targeted treatments, and standardize genotyping in order to optimize randomization and analysis for future clinical trials.
Published: 2017

11. Examining Ecological Constraints on the Intergenerational Transmission of Attachment Via Individual Participant Data Meta-analysis

Author: Verhage, M, Fearon, R, Schuengel, C, van IJzendoorn, M, Bakermans-Kranenburg, M, Madigan, S, Roisman, G, Oosterman, M, Behrens, K, Wong, M, Mangelsdorf, S, Priddis, L, Brisch, K, Arnott, B, Aviezer, O, Bailey, H, Behringer, J, Bernier, A, Cassibba, R, Cassidy, J, Coppola, G, Costantini, A, Cyr, C, Dozier, M, Ensink, K, Finger, B, Gojman, S, Harder, S, Hautamaki, A, Hazen, N, Ierardi, E, Jin, M, Jongenelen, I, Leerkes, E, Lionetti, F, Lyons-Ruth, K, Mcmahon, C, Meins, E, Pace, C, Raby, K, Riva Crugnola, C, Sagi-Schwartz, A, Schoppe-Sullivan, S, Steele, H, Steele, M, Tarabulsy, G, Væver, M, Brice, P, Castoro, G, Costantino, E, George, C, Gloger-Tippelt, G, Howes, C, Jacobvitz, D, Juffer, F, Kazui, M, Køppe, S, Millán, S, Murray, L, Pederson, D, Simonelli, A, Solomon, J, Speranza, A, Teti, D, van Londen-Barentsen, W, Ward, M, The Collaboration on Attachment Transmission, S, Verhage, Marije L., Fearon, R. M. Pasco, Schuengel, Carlo, van IJzendoorn, Marinus H., Bakermans-Kranenburg, Marian J., Madigan, Sheri, Roisman, Glenn I., Oosterman, Mirjam, Behrens, Kazuko Y., Wong, Maria S., Mangelsdorf, Sarah, Priddis, Lynn E., Brisch, Karl-Heinz, Arnott, B., Aviezer, O., Bailey, H., Behringer, J., Bernier, A., Cassibba, R., Cassidy, J., Coppola, G., Costantini, A., Cyr, C., Dozier, M., Ensink, K., Finger, B., Gojman, S., Harder, S., Hautamaki, A., Hazen, N. L., Ierardi, E., Jin, M. K., Jongenelen, I., Leerkes, E. M., Lionetti, F., Lyons-Ruth, K., McMahon, C., Meins, E., Pace, C. S., Priddis, L., Raby, K. L., Riva Crugnola, C., Sagi-Schwartz, A., Schoppe-Sullivan, S. J., Steele, H., Steele, M., Tarabulsy, G. M., Væver, M. S., Brice, P. J., Castoro, G., Costantino, E., George, C., Gloger-Tippelt, G., Howes, C., Jacobvitz, D., Juffer, F., Kazui, M., Køppe, S., Millán, S., Murray, L., Pederson, D. R., Simonelli, A., Solomon J., Speranza A. M., Teti, D. M., van Londen-Barentsen, W. M., Ward, M. J., The Collaboration on Attachment Transmission Synthesis, Verhage, M, Fearon, R, Schuengel, C, van IJzendoorn, M, Bakermans-Kranenburg, M, Madigan, S, Roisman, G, Oosterman, M, Behrens, K, Wong, M, Mangelsdorf, S, Priddis, L, Brisch, K, Arnott, B, Aviezer, O, Bailey, H, Behringer, J, Bernier, A, Cassibba, R, Cassidy, J, Coppola, G, Costantini, A, Cyr, C, Dozier, M, Ensink, K, Finger, B, Gojman, S, Harder, S, Hautamaki, A, Hazen, N, Ierardi, E, Jin, M, Jongenelen, I, Leerkes, E, Lionetti, F, Lyons-Ruth, K, Mcmahon, C, Meins, E, Pace, C, Raby, K, Riva Crugnola, C, Sagi-Schwartz, A, Schoppe-Sullivan, S, Steele, H, Steele, M, Tarabulsy, G, Væver, M, Brice, P, Castoro, G, Costantino, E, George, C, Gloger-Tippelt, G, Howes, C, Jacobvitz, D, Juffer, F, Kazui, M, Køppe, S, Millán, S, Murray, L, Pederson, D, Simonelli, A, Solomon, J, Speranza, A, Teti, D, van Londen-Barentsen, W, Ward, M, The Collaboration on Attachment Transmission, S, Verhage, Marije L., Fearon, R. M. Pasco, Schuengel, Carlo, van IJzendoorn, Marinus H., Bakermans-Kranenburg, Marian J., Madigan, Sheri, Roisman, Glenn I., Oosterman, Mirjam, Behrens, Kazuko Y., Wong, Maria S., Mangelsdorf, Sarah, Priddis, Lynn E., Brisch, Karl-Heinz, Arnott, B., Aviezer, O., Bailey, H., Behringer, J., Bernier, A., Cassibba, R., Cassidy, J., Coppola, G., Costantini, A., Cyr, C., Dozier, M., Ensink, K., Finger, B., Gojman, S., Harder, S., Hautamaki, A., Hazen, N. L., Ierardi, E., Jin, M. K., Jongenelen, I., Leerkes, E. M., Lionetti, F., Lyons-Ruth, K., McMahon, C., Meins, E., Pace, C. S., Priddis, L., Raby, K. L., Riva Crugnola, C., Sagi-Schwartz, A., Schoppe-Sullivan, S. J., Steele, H., Steele, M., Tarabulsy, G. M., Væver, M. S., Brice, P. J., Castoro, G., Costantino, E., George, C., Gloger-Tippelt, G., Howes, C., Jacobvitz, D., Juffer, F., Kazui, M., Køppe, S., Millán, S., Murray, L., Pederson, D. R., Simonelli, A., Solomon J., Speranza A. M., Teti, D. M., van Londen-Barentsen, W. M., Ward, M. J., and The Collaboration on Attachment Transmission Synthesis
Abstract: Parents’ attachment representations and child–parent attachment have been shown to be associated, but these associations vary across populations (Verhage et al., 2016). The current study examined whether ecological factors may explain variability in the strength of intergenerational transmission of attachment, using individual participant data (IPD) meta-analysis. Analyses on 4,396 parent–child dyads (58 studies, child age 11–96 months) revealed a combined effect size of r =.29. IPD meta-analyses revealed that effect sizes for the transmission of autonomous-secure representations to secure attachments were weaker under risk conditions and weaker in adolescent parent–child dyads, whereas transmission was stronger for older children. Findings support the ecological constraints hypothesis on attachment transmission. Implications for attachment theory and the use of IPD meta-analysis are discussed.
Published: 2018

12. Examining Ecological Constraints on the Intergenerational Transmission of Attachment Via Individual Participant Data Meta-analysis

Author: Verhage, Marije L., Fearon, R. M. Pasco, Schuengel, Carlo, van IJzendoorn, Marinus H., Bakermans-Kranenburg, Marian J., Madigan, Sheri, Roisman, Glenn I., Oosterman, Mirjam, Behrens, Kazuko Y., Wong, Maria S., Mangelsdorf, Sarah, Priddis, Lynn E., Brisch, Karl-Heinz, Arnott, B., Aviezer, O., Bailey, H., Behringer, J., Bernier, A., Cassibba, R., Cassidy, J., Coppola, G., Costantini, A., Cyr, C., Dozier, M., Ensink, K., Finger, B., Gojman, S., Harder, S., Hautamaki, A., Hazen, N. L., Ierardi, E., Jin, M. K., Jongenelen, I., Leerkes, E. M., Lionetti, F., Lyons-Ruth, K., McMahon, C., Meins, E., Pace, C. S., Priddis, L., Raby, K. L., Riva Crugnola, C., Sagi-Schwartz, A., Schoppe-Sullivan, S. J., Steele, H., Steele, M., Tarabulsy, G. M., Væver, M. S., Brice, P. J., Castoro, G., Costantino, E., George, C., Gloger-Tippelt, G., Howes, C., Jacobvitz, D., Juffer, F., Kazui, M., Køppe, S., Millán, S., Murray, L., Pederson, D. R., Simonelli, A., Solomon J., Speranza A. M., Teti, D. M., van Londen-Barentsen, W. M., Ward, M. J., The Collaboration on Attachment Transmission Synthesis, Verhage, M, Fearon, R, Schuengel, C, van IJzendoorn, M, Bakermans-Kranenburg, M, Madigan, S, Roisman, G, Oosterman, M, Behrens, K, Wong, M, Mangelsdorf, S, Priddis, L, Brisch, K, Arnott, B, Aviezer, O, Bailey, H, Behringer, J, Bernier, A, Cassibba, R, Cassidy, J, Coppola, G, Costantini, A, Cyr, C, Dozier, M, Ensink, K, Finger, B, Gojman, S, Harder, S, Hautamaki, A, Hazen, N, Ierardi, E, Jin, M, Jongenelen, I, Leerkes, E, Lionetti, F, Lyons-Ruth, K, Mcmahon, C, Meins, E, Pace, C, Raby, K, Riva Crugnola, C, Sagi-Schwartz, A, Schoppe-Sullivan, S, Steele, H, Steele, M, Tarabulsy, G, Væver, M, Brice, P, Castoro, G, Costantino, E, George, C, Gloger-Tippelt, G, Howes, C, Jacobvitz, D, Juffer, F, Kazui, M, Køppe, S, Millán, S, Murray, L, Pederson, D, Simonelli, A, Solomon, J, Speranza, A, Teti, D, van Londen-Barentsen, W, Ward, M, The Collaboration on Attachment Transmission, S, Clinical Child and Family Studies, APH - Mental Health, LEARN! - Social cognition and learning, and LEARN! - Brain, learning and development
Subjects: Male, Parents, Adolescent, Child age, Education, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, Sex factors, Developmental and Educational Psychology, Attachment theory, Humans, 0501 psychology and cognitive sciences, 030212 general & internal medicine, Parent-Child Relations, Child, Object Attachment, Intergenerational transmission, Parenting, Ecology, Individual participant data, 05 social sciences, Age Factors, Intergenerational Transmission of Attachment, Meta-analysis, Child, Preschool, Pediatrics, Perinatology and Child Health, Educational Status, Female, Psychology, 050104 developmental & child psychology
Abstract: Parents' attachment representations and child-parent attachment have been shown to be associated, but these associations vary across populations (Verhage et al., 2016). The current study examined whether ecological factors may explain variability in the strength of intergenerational transmission of attachment, using individual participant data (IPD) meta-analysis. Analyses on 4,396 parent-child dyads (58 studies, child age 11-96 months) revealed a combined effect size of r = .29. IPD meta-analyses revealed that effect sizes for the transmission of autonomous-secure representations to secure attachments were weaker under risk conditions and weaker in adolescent parent-child dyads, whereas transmission was stronger for older children. Findings support the ecological constraints hypothesis on attachment transmission. Implications for attachment theory and the use of IPD meta-analysis are discussed.
Published: 2018

13. Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis

Author: Bandres‐Ciga, S, Noyce, AJ, Hemani, G, Nicolas, A, Calvo, A, Mora, G, Arosio, A, Barberis, M, Bartolomei, I, Battistini, S, Benigni, M, Borghero, G, Brunetti, M, Cammarosano, S, Cannas, A, Canosa, A, Capasso, M, Caponnetto, C, Caredda, C, Carrera, P, Casale, F, Cavallaro, S, Chiò, A, Colletti, T, Conforti, FL, Conte, A, Corrado, L, Costantino, E, D'Alfonso, S, Fasano, A, Femiano, C, Ferrarese, C, Fini, N, Floris, G, Fuda, G, Giannini, F, Grassano, M, Ilardi, A, La Bella, V, Lattante, S, Logroscino, G, Logullo, FO, Loi, D, Lunetta, C, Mancardi, G, Mandich, P, Mandrioli, J, Manera, U, Marangi, G, Marinou, K, Marrali, G, Marrosu, MG, Mazzini, L, Melis, M, Messina, S, Moglia, C, Monsurro, MR, Mosca, L, Occhineri, P, Origone, P, Pani, C, Penco, S, Petrucci, A, Piccirillo, G, Pirisi, A, Pisano, F, Pugliatti, M, Restagno, G, Ricci, C, Rita Murru, M, Riva, N, Sabatelli, M, Salvi, F, Santarelli, M, Sideri, R, Simone, I, Spataro, R, Tanel, R, Tedeschi, G, Tranquilli, S, Tremolizzo, L, Trojsi, F, Volanti, P, Zollino, M, Abramzon, Y, Arepalli, S, Baloh, RH, Bowser, R, Brady, CB, Brice, A, Broach, J, Campbell, RH, Camu, W, Chia, R, Cooper‐Knock, J, Cusi, D, Ding, J, Drepper, C, Drory, VE, Dunckley, TL, Eicher, JD, Faghri, F, Feldman, E, Kay Floeter, M, Fratta, P, Geiger, JT, Gerhard, G, Gibbs, JR, Gibson, SB, Glass, JD, Hardy, J, Harms, MB, Heiman‐Patterson, TD, Hernandez, DG, Jansson, L, Kamel, F, Kirby, J, Kowall, NW, Laaksovirta, H, Landi, F, Le Ber, I, Lumbroso, S, MacGowan, DJL, Maragakis, NJ, Mouzat, K, Murphy, NA, Myllykangas, L, Nalls, MA, Orrell, RW, Ostrow, LW, Pamphlett, R, Pickering‐Brown, S, Pioro, E, Pliner, HA, Pulst, SM, Ravits, JM, Renton, AE, Rivera, A, Robbrecht, W, Rogaeva, E, Rollinson, S, Rothstein, JD, Salvi, E, Scholz, SW, Sendtner, M, Shaw, PJ, Sidle, KC, Simmons, Z, Singleton, AB, Stone, DC, Sulkava, R, Tienari, PJ, Traynor, BJ, Trojanowski, JQ, Troncoso, JC, Van Damme, P, Van Deerlin, VM, Van Den Bosch, L, Zinman, L, Stone, DJ, Bandres-Ciga, Sara, Noyce, Alastair J., Hemani, Gibran, Nicolas, Aude, Calvo, Andrea, Mora, Gabriele, Arosio, Alessandro, Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Benigni, Michele, Borghero, Giuseppe, Brunetti, Maura, Cammarosano, Stefania, Cannas, Antonino, Canosa, Antonio, Capasso, Margherita, Caponnetto, Claudia, Caredda, Carla, Carrera, Paola, Casale, Federico, Cavallaro, Sebastiano, Chiò, Adriano, Colletti, Tiziana, Conforti, Francesca L., Conte, Amelia, Corrado, Lucia, Costantino, Emanuela, D'Alfonso, Sandra, Fasano, Antonio, Femiano, Cinzia, Ferrarese, Carlo, Fini, Nicola, Floris, Gianluca, Fuda, Giuseppe, Giannini, Fabio, Grassano, Maurizio, Ilardi, Antonio, La Bella, Vincenzo, Lattante, Serena, Logroscino, Giancarlo, Logullo, Francesco O., Loi, Daniela, Lunetta, Christian, Mancardi, Gianluigi, Mandich, Paola, Mandrioli, Jessica, Manera, Umberto, Marangi, Giuseppe, Marinou, Kalliopi, Marrali, Giuseppe, Marrosu, Maria Giovanna, Mazzini, Letizia, Melis, Maurizio, Messina, Sonia, Moglia, Cristina, Monsurro, Maria Rosaria, Mosca, Lorena, Occhineri, Patrizia, Origone, Paola, Pani, Carla, Penco, Silvana, Petrucci, Antonio, Piccirillo, Giovanni, Pirisi, Angelo, Pisano, Fabrizio, Pugliatti, Maura, Restagno, Gabriella, Ricci, Claudia, Rita Murru, Maria, Riva, Nilo, Sabatelli, Mario, Salvi, Fabrizio, Santarelli, Marialuisa, Sideri, Riccardo, Simone, Isabella, Spataro, Rossella, Tanel, Raffaella, Tedeschi, Gioacchino, Tranquilli, Stefania, Tremolizzo, Lucio, Trojsi, Francesca, Volanti, Paolo, Zollino, Marcella, Abramzon, Yevgeniya, Arepalli, Sampath, Baloh, Robert H., Bowser, Robert, Brady, Christopher B., Brice, Alexi, Broach, Jame, Campbell, Roy H., Camu, William, Chia, Ruth, Cooper-Knock, John, Cusi, Daniele, Ding, Jinhui, Drepper, Carsten, Drory, Vivian E., Dunckley, Travis L., Eicher, John D., Faghri, Faraz, Feldman, Eva, Kay Floeter, Mary, Fratta, Pietro, Geiger, Joshua T., Gerhard, Glenn, Gibbs, J. Raphael, Gibson, Summer B., Glass, Jonathan D., Hardy, John, Harms, Matthew B., Heiman-Patterson, Terry D., Hernandez, Dena G., Jansson, Lilja, Kamel, Freya, Kirby, Janine, Kowall, Neil W., Laaksovirta, Hannu, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, Macgowan, Daniel J. L., Maragakis, Nicholas J., Mouzat, Kevin, Murphy, Natalie A., Myllykangas, Liisa, Nalls, Mike A., Orrell, Richard W., Ostrow, Lyle W., Pamphlett, Roger, Pickering-Brown, Stuart, Pioro, Erik, Pliner, Hannah A., Pulst, Stefan M., Ravits, John M., Renton, Alan E., Rivera, Alberto, Robbrecht, Wim, Rogaeva, Ekaterina, Rollinson, Sara, Rothstein, Jeffrey D., Salvi, Erika, Scholz, Sonja W., Sendtner, Michael, Shaw, Pamela J., Sidle, Katie C., Simmons, Zachary, Singleton, Andrew B., Stone, David C., Sulkava, Raimo, Tienari, Pentti J., Traynor, Bryan J., Trojanowski, John Q., Troncoso, Juan C., Van Damme, Philip, Van Deerlin, Vivianna M., Van Den Bosch, Ludo, Zinman, Lorne, Stone, David J., Van Damme, P, Bandres-Ciga, S, Noyce, A, Hemani, G, Nicolas, A, Calvo, A, Mora, G, Tienari, P, Stone, D, Nalls, M, Singleton, A, Chiò, A, Traynor, Bryan, J, Tremolizzo, L, Department of Neurosciences, Neurologian yksikkö, Clinicum, HUS Neurocenter, Translational neuroradiology unit [Bethesda], National Institute of Neurological Disorders and Stroke [Bethesda] (NINDS), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Univ Granada, Hosp Univ Granada, Inst Invest Biosanitaria Ibs GRANADA, Escuela Andaluza Salud Publ, Granada, Spain, Partenaires INRAE, Queen Mary University of London (QMUL), University College of London [London] (UCL), University of Bristol [Bristol], Département de Physique, Université de Genève, Université de Genève (UNIGE), Università degli studi di Torino (UNITO), University G. d'Annunzio, Chieti, Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Department of Neurology, A.O.U. Maggiore della Carità, and IRCAD, Novara, Department of Health Sciences, UPO University, UPO University, Dipartimento di Matematica 'Ulisse Dini', Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Neurology, Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Department of Neuroscience, University of Siena, Siena, Università cattolica del Sacro Cuore [Roma] (Unicatt), Università degli studi di Bari Aldo Moro (UNIBA), Istituto di Genetica Medica, Centro Sclerosi Multipla, Ospedale Binaghi, Via Is Guadazzonis 2, Cagliari, Italy, University of Novara, IRCCS-Istituti Clinici Scientifici Maugeri, University of Milan, Milan, Italy, Department of Biomedical and Specialty Surgical Sciences, Università degli Studi di Ferrara (UniFE), S. Anna Hospital, Department of Neuroscience, Catholic University, Roma, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Institute of Medical Genetics, Catholic University, Rome, Italy, Department of Clinical Genetics, Department of Pathology University of Pittsburgh School of Medicine, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Princeton University, University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, Centre référent Sclérose Latérale Amyotrophique [CHRU Montpellier] (SLA CHRU Montpellier), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Università degli Studi di Milano [Milano] (UNIMI), Laboratory of Neurogenetics, National Institute of Aging, Tel Aviv Sourasky Medical Center [Te Aviv], University of New Haven [Connecticut], Emory University [Atlanta, GA], UCL Institute of neurology, UCL Institute of Neurology, Cardiovascular, Renal and Metabolism, IMED Biotech Unit, AstraZeneca, Genomic Research Laboratory, Service of Infectious Disease, Hôpitaux Universitaires de Genève (HUG), Boston University [Boston] (BU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Biochimie [CHRU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, University of California [Davis] (UC Davis), University of California-University of California, Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Johns Hopkins University, School of Medicine, Department of Medicine, Surgery, and Dentistry, University of Milano, Institute for Clinical Neurobiology, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Penn State Hershey Medical Center, Penn State Health Milton S. Hershey Medical Center, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Penn State System-Pennsylvania Commonwealth System of Higher Education (PCSHE)-Penn State System, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Perelman School of Medicine, University of Pennsylvania [Philadelphia], Metacohorts Consortium, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Helsinki, Merck Research Laboratories, National Institutes of Health [Bethesda] (NIH), Center for Neuroscience and Regenerative Medicine [Bethesda] (CNRM), and Henry M. Jackson Foundation for the Advancement of Military Medicine (HJM)
Subjects: 0301 basic medicine, Linkage disequilibrium, Multifactorial Inheritance, Multivariate analysis, LD SCORE REGRESSION, DYSLIPIDEMIA, Genome-wide association study, 3124 Neurology and psychiatry, 0302 clinical medicine, PROTECTIVE FACTOR, Mendelian Randomization Analysis, 3. Good health, ALZHEIMERS-DISEASE, Settore MED/26 - NEUROLOGIA, risk factor, BIAS, Neurology, CARDIOVASCULAR-DISEASE, MENDELIAN RANDOMIZATION, Amyotrophic lateral Sclerosis, LD score regression, Mendelian randomization, amyotrophic lateral sclerosis, public resource, Life Sciences & Biomedicine, Clinical psychology, Human, Clinical Neurology, Biology, NO, 03 medical and health sciences, Humans, Genetic Predisposition to Disease, Mendelian Randomization Analysi, MESH: Amyotrophic Lateral Sclerosis, Genetic Predisposition to Disease / genetics, Genome-Wide Association Study / methods, Mendolian Randomization Analysis / methods, Exercise, Genetic association, Science & Technology, [SCCO.NEUR]Cognitive science/Neuroscience, Amyotrophic Lateral Sclerosis, 3112 Neurosciences, Neurosciences, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, CHOLESTEROL HOMEOSTASIS, Causal inference, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurosciences & Neurology, Neurology (clinical), Genome-Wide Association Study, ALS, 030217 neurology & neurosurgery, Amyotrophic Lateral Sclerosi
Abstract: OBJECTIVE: To identify shared polygenic risk and causal associations in amyotrophic lateral sclerosis (ALS). METHODS: Linkage disequilibrium score regression and Mendelian randomization were applied in a large-scale, data-driven manner to explore genetic correlations and causal relationships between >700 phenotypic traits and ALS. Exposures consisted of publicly available genome-wide association studies (GWASes) summary statistics from MR Base and LD-hub. The outcome data came from the recently published ALS GWAS involving 20,806 cases and 59,804 controls. Multivariate analyses, genetic risk profiling, and Bayesian colocalization analyses were also performed. RESULTS: We have shown, by linkage disequilibrium score regression, that ALS shares polygenic risk genetic factors with a number of traits and conditions, including positive correlations with smoking status and moderate levels of physical activity, and negative correlations with higher cognitive performance, higher educational attainment, and light levels of physical activity. Using Mendelian randomization, we found evidence that hyperlipidemia is a causal risk factor for ALS and localized putative functional signals within loci of interest. INTERPRETATION: Here, we have developed a public resource (https://lng-nia.shinyapps.io/mrshiny) which we hope will become a valuable tool for the ALS community, and that will be expanded and updated as new data become available. Shared polygenic risk exists between ALS and educational attainment, physical activity, smoking, and tenseness/restlessness. We also found evidence that elevated low-desnity lipoprotein cholesterol is a causal risk factor for ALS. Future randomized controlled trials should be considered as a proof of causality. Ann Neurol 2019;85:470-481. ispartof: ANNALS OF NEUROLOGY vol:85 issue:4 pages:470-481 ispartof: location:United States status: published
Published: 2019

14. Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis

Author: Bandres-Ciga, S., Noyce, A. J., Hemani, G., Nicolas, A., Calvo, A., Mora, G., Arosio, A., Barberis, M., Bartolomei, I., Battistini, S., Benigni, M., Borghero, G., Brunetti, M., Cammarosano, S., Cannas, A., Canosa, A., Capasso, Monica, Caponnetto, C., Caredda, C., Carrera, P., Casale, F., Cavallaro, S., Chio, A., Colletti, T., Conforti, F. L., Conte, Amelia, Corrado, L., Costantino, E., D'Alfonso, Sandra, Fasano, Alfonso, Femiano, C., Ferrarese, C., Fini, N., Floris, G., Fuda, G., Giannini, F., Grassano, M., Ilardi, A., La Bella, V., Lattante, Serena, Logroscino, Giandomenico, Logullo, F. O., Loi, D., Lunetta, C., Mancardi, G., Mandich, P., Mandrioli, J., Manera, U., Marangi, Giuseppe, Marinou, K., Marrali, G., Marrosu, M. G., Mazzini, L., Melis, M., Messina, S., Moglia, C., Monsurro, M. R., Mosca, Luigi, Occhineri, P., Origone, P., Pani, C., Penco, S., Petrucci, A., Piccirillo, G., Pirisi, A., Pisano, F., Pugliatti, M., Restagno, G., Ricci, C., Rita Murru, M., Riva, N., Sabatelli, Mario, Salvi, F., Santarelli, M., Sideri, R., De Simone, Idor, Spataro, R., Tanel, R., Tedeschi, G., Tranquilli, S., Tremolizzo, L., Trojsi, F., Volanti, P., Zollino, Marcella, Abramzon, Y., Arepalli, S., Baloh, R. H., Bowser, R., Brady, C. B., Brice, A., Broach, J., Campbell, R. H., Camu, W., Chia, R., Cooper-Knock, J., Cusi, D., Ding, J., Drepper, C., Drory, V. E., Dunckley, T. L., Eicher, J. D., Faghri, F., Feldman, E., Kay Floeter, M., Fratta, P., Geiger, J. T., Gerhard, G., Gibbs, J. R., Gibson, S. B., Glass, J. D., Hardy, J., Harms, M. B., Heiman-Patterson, T. D., Hernandez, D. G., Jansson, L., Kamel, F., Kirby, J., Kowall, N. W., Laaksovirta, H., Landi, Francesco, Le Ber, I., Lumbroso, S., Macgowan, D. J. L., Maragakis, N. J., Mouzat, K., Murphy, N. A., Myllykangas, L., Nalls, M. A., Orrell, R. W., Ostrow, L. W., Pamphlett, R., Pickering-Brown, S., Pioro, E., Pliner, H. A., Pulst, S. M., Ravits, J. M., Renton, A. E., Rivera, A., Robbrecht, W., Rogaeva, E., Rollinson, S., Rothstein, J. D., Salvi, E., Scholz, S. W., Sendtner, M., Shaw, P. J., Sidle, K. C., Simmons, Z., Singleton, A. B., Stone, D. C., Sulkava, R., Tienari, P. J., Traynor, B. J., Trojanowski, J. Q., Troncoso, J. C., Van Damme, P., Van Deerlin, V. M., Van Den Bosch, L., Zinman, L., Stone, D. J., Capasso M., Conte A., D'Alfonso S., Fasano A., Lattante S. (ORCID:0000-0003-2891-0340), Logroscino G. (ORCID:0000-0003-1301-5343), Marangi G. (ORCID:0000-0002-6898-8882), Mosca L. (ORCID:0000-0003-4641-0841), Sabatelli M. (ORCID:0000-0001-6635-4985), Zollino M. (ORCID:0000-0003-4871-9519), Landi F. (ORCID:0000-0002-3472-1389), Bandres-Ciga, S., Noyce, A. J., Hemani, G., Nicolas, A., Calvo, A., Mora, G., Arosio, A., Barberis, M., Bartolomei, I., Battistini, S., Benigni, M., Borghero, G., Brunetti, M., Cammarosano, S., Cannas, A., Canosa, A., Capasso, Monica, Caponnetto, C., Caredda, C., Carrera, P., Casale, F., Cavallaro, S., Chio, A., Colletti, T., Conforti, F. L., Conte, Amelia, Corrado, L., Costantino, E., D'Alfonso, Sandra, Fasano, Alfonso, Femiano, C., Ferrarese, C., Fini, N., Floris, G., Fuda, G., Giannini, F., Grassano, M., Ilardi, A., La Bella, V., Lattante, Serena, Logroscino, Giandomenico, Logullo, F. O., Loi, D., Lunetta, C., Mancardi, G., Mandich, P., Mandrioli, J., Manera, U., Marangi, Giuseppe, Marinou, K., Marrali, G., Marrosu, M. G., Mazzini, L., Melis, M., Messina, S., Moglia, C., Monsurro, M. R., Mosca, Luigi, Occhineri, P., Origone, P., Pani, C., Penco, S., Petrucci, A., Piccirillo, G., Pirisi, A., Pisano, F., Pugliatti, M., Restagno, G., Ricci, C., Rita Murru, M., Riva, N., Sabatelli, Mario, Salvi, F., Santarelli, M., Sideri, R., De Simone, Idor, Spataro, R., Tanel, R., Tedeschi, G., Tranquilli, S., Tremolizzo, L., Trojsi, F., Volanti, P., Zollino, Marcella, Abramzon, Y., Arepalli, S., Baloh, R. H., Bowser, R., Brady, C. B., Brice, A., Broach, J., Campbell, R. H., Camu, W., Chia, R., Cooper-Knock, J., Cusi, D., Ding, J., Drepper, C., Drory, V. E., Dunckley, T. L., Eicher, J. D., Faghri, F., Feldman, E., Kay Floeter, M., Fratta, P., Geiger, J. T., Gerhard, G., Gibbs, J. R., Gibson, S. B., Glass, J. D., Hardy, J., Harms, M. B., Heiman-Patterson, T. D., Hernandez, D. G., Jansson, L., Kamel, F., Kirby, J., Kowall, N. W., Laaksovirta, H., Landi, Francesco, Le Ber, I., Lumbroso, S., Macgowan, D. J. L., Maragakis, N. J., Mouzat, K., Murphy, N. A., Myllykangas, L., Nalls, M. A., Orrell, R. W., Ostrow, L. W., Pamphlett, R., Pickering-Brown, S., Pioro, E., Pliner, H. A., Pulst, S. M., Ravits, J. M., Renton, A. E., Rivera, A., Robbrecht, W., Rogaeva, E., Rollinson, S., Rothstein, J. D., Salvi, E., Scholz, S. W., Sendtner, M., Shaw, P. J., Sidle, K. C., Simmons, Z., Singleton, A. B., Stone, D. C., Sulkava, R., Tienari, P. J., Traynor, B. J., Trojanowski, J. Q., Troncoso, J. C., Van Damme, P., Van Deerlin, V. M., Van Den Bosch, L., Zinman, L., Stone, D. J., Capasso M., Conte A., D'Alfonso S., Fasano A., Lattante S. (ORCID:0000-0003-2891-0340), Logroscino G. (ORCID:0000-0003-1301-5343), Marangi G. (ORCID:0000-0002-6898-8882), Mosca L. (ORCID:0000-0003-4641-0841), Sabatelli M. (ORCID:0000-0001-6635-4985), Zollino M. (ORCID:0000-0003-4871-9519), and Landi F. (ORCID:0000-0002-3472-1389)
Abstract: Objective: To identify shared polygenic risk and causal associations in amyotrophic lateral sclerosis (ALS). Methods: Linkage disequilibrium score regression and Mendelian randomization were applied in a large-scale, data-driven manner to explore genetic correlations and causal relationships between >700 phenotypic traits and ALS. Exposures consisted of publicly available genome-wide association studies (GWASes) summary statistics from MR Base and LD-hub. The outcome data came from the recently published ALS GWAS involving 20,806 cases and 59,804 controls. Multivariate analyses, genetic risk profiling, and Bayesian colocalization analyses were also performed. Results: We have shown, by linkage disequilibrium score regression, that ALS shares polygenic risk genetic factors with a number of traits and conditions, including positive correlations with smoking status and moderate levels of physical activity, and negative correlations with higher cognitive performance, higher educational attainment, and light levels of physical activity. Using Mendelian randomization, we found evidence that hyperlipidemia is a causal risk factor for ALS and localized putative functional signals within loci of interest. Interpretation: Here, we have developed a public resource (https://lng-nia.shinyapps.io/mrshiny) which we hope will become a valuable tool for the ALS community, and that will be expanded and updated as new data become available. Shared polygenic risk exists between ALS and educational attainment, physical activity, smoking, and tenseness/restlessness. We also found evidence that elevated low-desnity lipoprotein cholesterol is a causal risk factor for ALS. Future randomized controlled trials should be considered as a proof of causality. Ann Neurol 2019;85:470–481.
Published: 2019

15. The New Ice Age of Musculoskeletal Intervention: Role of Percutaneous Cryoablation in Bone and Soft Tissue Tumors

Author: Nicolas Papalexis, Leonor Garbin Savarese, Giuliano Peta, Costantino Errani, Gianmarco Tuzzato, Paolo Spinnato, Federico Ponti, Marco Miceli, and Giancarlo Facchini
Subjects: interventional radiology, metastatic neoplasms, orthopedic surgery, palliative medicine, cryoablation, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: In the rapidly evolving field of interventional oncology, minimally invasive methods, including CT-guided cryoablation, play an increasingly important role in tumor treatment, notably in bone and soft tissue cancers. Cryoablation works using compressed gas-filled probes to freeze tumor cells to temperatures below −20 °C, exploiting the Joule–Thompson effect. This cooling causes cell destruction by forming intracellular ice crystals and disrupting blood flow through endothelial cell damage, leading to local ischemia and devascularization. Coupling this with CT technology enables precise tumor targeting, preserving healthy surrounding tissues and decreasing postoperative complications. This review reports the most important literature on CT-guided cryoablation’s application in musculoskeletal oncology, including sarcoma, bone metastases, and bone and soft tissue benign primary tumors, reporting on the success rate, recurrence rate, complications, and technical aspects to maximize success for cryoablation in the musculoskeletal system.
Published: 2023
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16. The Prognostic Value of Serum Biomarkers for Survival of Children with Osteosarcoma of the Extremities

Author: Stefano Basoli, Monica Cosentino, Matteo Traversari, Marco Manfrini, Shinji Tsukamoto, Andreas F. Mavrogenis, Barbara Bordini, Davide Maria Donati, and Costantino Errani
Subjects: serological biomarker, C-reactive protein, alkaline phosphatase, osteosarcoma, children, prognosis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background: Osteosarcoma is a highly aggressive malignant bone tumor that affects mainly adolescents and young adults. We analyzed serum biomarkers for their prognostic significance in children with osteosarcoma. Methods: In this retrospective study, we investigated the prognostic factors in 210 children who were treated for appendicular osteosarcoma, including patient age and sex, tumor site and size (≥8 cm or p < 0.05). Inadequate surgical margins [HR 11.28; 95% CI, 1.37 to 92.79] and high levels of ESR [HR 3.58; 95% CI, 1.29 to 9.98] showed a greater risk of local recurrence at 5 years follow-up (p < 0.05). Conclusions: AP and ESR can identify osteosarcoma-diagnosed children with a greater risk of death and local recurrence, respectively.
Published: 2023
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17. Current Concepts in the Resection of Bone Tumors Using a Patient-Specific Three-Dimensional Printed Cutting Guide

Author: Hisaki Aiba, Benedetta Spazzoli, Shinji Tsukamoto, Andreas F. Mavrogenis, Tomas Hermann, Hiroaki Kimura, Hideki Murakami, Davide Maria Donati, and Costantino Errani
Subjects: three-dimensional printed guide, patients-specific guide, bone tumor, limb-sparing surgery, orthopedic oncology, pelvic tumor, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Orthopedic oncology has begun to use three-dimensional-printing technology, which is expected to improve the accuracy of osteotomies, ensure a safe margin, and facilitate precise surgery. However, several difficulties should be considered. Cadaver and clinical studies have reported more accurate osteotomies for bone-tumor resection using patient-specific cutting guides, especially in challenging areas such as the sacrum and pelvis, compared to manual osteotomies. Patient-specific cutting guides can help surgeons achieve resection with negative margins and reduce blood loss and operating time. Furthermore, this patient-specific cutting guide could be combined with more precise reconstruction using patient-specific implants or massive bone allografts. This review provides an overview of the basic technologies used in the production of patient-specific cutting guides and discusses their current status, advantages, and limitations. Moreover, we summarize cadaveric and clinical studies on the use of these guides in orthopedic oncology.
Published: 2023
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18. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

Author: Nicolas, A, Kenna, K, Renton, A, Ticozzi, N, Faghri, F, Chia, R, Dominov, J, Kenna, B, Nalls, M, Keagle, P, Rivera, A, van Rheenen, W, Murphy, N, van Vugt, J, Geiger, J, van der Spek, R, Pliner, H, Shankaracharya, N, Smith, B, Marangi, G, Topp, S, Abramzon, Y, Gkazi, A, Eicher, J, Kenna, A, Logullo, F, Simone, I, Logroscino, G, Salvi, F, Bartolomei, I, Borghero, G, Murru, M, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M, Floris, G, Cannas, A, Capasso, M, Caponnetto, C, Mancardi, G, Origone, P, Mandich, P, Conforti, F, Cavallaro, S, Mora, G, Marinou, K, Sideri, R, Penco, S, Mosca, L, Lunetta, C, Pinter, G, Corbo, M, Riva, N, Carrera, P, Volanti, P, Mandrioli, J, Fini, N, Fasano, A, Tremolizzo, L, Arosio, A, Ferrarese, C, Trojsi, F, Tedeschi, G, Monsurrò, M, Piccirillo, G, Femiano, C, Ticca, A, Ortu, E, La Bella, V, Spataro, R, Colletti, T, Sabatelli, M, Zollino, M, Conte, A, Luigetti, M, Lattante, S, Santarelli, M, Petrucci, A, Pugliatti, M, Pirisi, A, Parish, L, Occhineri, P, Giannini, F, Battistini, S, Ricci, C, Benigni, M, Cau, T, Loi, D, Calvo, A, Moglia, C, Brunetti, M, Barberis, M, Restagno, G, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Canosa, A, Ilardi, A, Manera, U, Grassano, M, Tanel, R, Pisano, F, Mazzini, L, Messina, S, D'Alfonso, S, Corrado, L, Ferrucci, L, Harms, M, Goldstein, D, Shneider, N, Goutman, S, Simmons, Z, Miller, T, Chandran, S, Pal, S, Manousakis, G, Appel, S, Simpson, E, Wang, L, Baloh, R, Gibson, S, Bedlack, R, Lacomis, D, Sareen, D, Sherman, A, Bruijn, L, Penny, M, Moreno, C, Kamalakaran, S, Allen, A, Boone, B, Brown, R, Carulli, J, Chesi, A, Chung, W, Cirulli, E, Cooper, G, Couthouis, J, Day-Williams, A, Dion, P, Gitler, A, Glass, J, Han, Y, Harris, T, Hayes, S, Jones, A, Keebler, J, Krueger, B, Lasseigne, B, Levy, S, Lu, Y, Maniatis, T, McKenna-Yasek, D, Myers, R, Petrovski, S, Pulst, S, Raphael, A, Ravits, J, Ren, Z, Rouleau, G, Sapp, P, Sims, K, Staropoli, J, Waite, L, Wang, Q, Wimbish, J, Xin, W, Phatnani, H, Kwan, J, Broach, J, Arcila-Londono, X, Lee, E, Van Deerlin, V, Fraenkel, E, Ostrow, L, Baas, F, Zaitlen, N, Berry, J, Malaspina, A, Fratta, P, Cox, G, Thompson, L, Finkbeiner, S, Dardiotis, E, Hornstein, E, Macgowan, D, Heiman-Patterson, T, Hammell, M, Patsopoulos, N, Dubnau, J, Nath, A, Musunuri, R, Evani, U, Abhyankar, A, Zody, M, Kaye, J, Wyman, S, Lenail, A, Lima, L, Rothstein, J, Svendsen, C, Van Eyk, J, Maragakis, N, Kolb, S, Cudkowicz, M, Baxi, E, Benatar, M, Taylor, J, Wu, G, Rampersaud, E, Wuu, J, Rademakers, R, Züchner, S, Schule, R, Mccauley, J, Hussain, S, Cooley, A, Wallace, M, Clayman, C, Barohn, R, Statland, J, Swenson, A, Jackson, C, Trivedi, J, Khan, S, Katz, J, Jenkins, L, Burns, T, Gwathmey, K, Caress, J, Mcmillan, C, Elman, L, Pioro, E, Heckmann, J, So, Y, Walk, D, Maiser, S, Zhang, J, Silani, V, Gellera, C, Ratti, A, Taroni, F, Lauria, G, Verde, F, Fogh, I, Tiloca, C, Comi, G, Sorarù, G, Cereda, C, De Marchi, F, Corti, S, Ceroni, M, Siciliano, G, Filosto, M, Inghilleri, M, Peverelli, S, Colombrita, C, Poletti, B, Maderna, L, Del Bo, R, Gagliardi, S, Querin, G, Bertolin, C, Pensato, V, Castellotti, B, Camu, W, Mouzat, K, Lumbroso, S, Corcia, P, Meininger, V, Besson, G, Lagrange, E, Clavelou, P, Guy, N, Couratier, P, Vourch, P, Danel, V, Bernard, E, Lemasson, G, Laaksovirta, H, Myllykangas, L, Jansson, L, Valori, M, Ealing, J, Hamdalla, H, Rollinson, S, Pickering-Brown, S, Orrell, R, Sidle, K, Hardy, J, Singleton, A, Johnson, J, Arepalli, S, Polak, M, Asress, S, Al-Sarraj, S, King, A, Troakes, C, Vance, C, de Belleroche, J, ten Asbroek, A, Muñoz-Blanco, J, Hernandez, D, Ding, J, Gibbs, J, Scholz, S, Floeter, M, Campbell, R, Landi, F, Bowser, R, Kirby, J, Pamphlett, R, Gerhard, G, Dunckley, T, Brady, C, Kowall, N, Troncoso, J, Le Ber, I, Kamel, F, Van Den Bosch, L, Strom, T, Meitinger, T, Shatunov, A, Van Eijk, K, de Carvalho, M, Kooyman, M, Middelkoop, B, Moisse, M, Mclaughlin, R, Van Es, M, Weber, M, Boylan, K, Van Blitterswijk, M, Morrison, K, Basak, A, Mora, J, Drory, V, Shaw, P, Turner, M, Talbot, K, Hardiman, O, Williams, K, Fifita, J, Nicholson, G, Blair, I, Esteban-Pérez, J, García-Redondo, A, Al-Chalabi, A, Al Kheifat, A, Andersen, P, Chio, A, Cooper-Knock, J, Dekker, A, Redondo, A, Gotkine, M, Hide, W, Iacoangeli, A, Kiernan, M, Landers, J, Mill, J, Neto, M, Pardina, J, Newhouse, S, Pinto, S, Pulit, S, Robberecht, W, Shaw, C, Sproviero, W, Tazelaar, G, van Damme, P, van den Berg, L, van Eijk, K, van Es, M, Veldink, J, Zatz, M, Bauer, D, Twine, N, Rogaeva, E, Zinman, L, Brice, A, Feldman, E, Ludolph, A, Weishaupt, J, Trojanowski, J, Stone, D, Tienari, P, Chiò, A, Traynor, B, Nicolas, Aude, Kenna, Kevin P., Renton, Alan E., Ticozzi, Nicola, Faghri, Faraz, Chia, Ruth, Dominov, Janice A., Kenna, Brendan J., Nalls, Mike A., Keagle, Pamela, Rivera, Alberto M., van Rheenen, Wouter, Murphy, Natalie A., van Vugt, Joke J. F. A., Geiger, Joshua T., van der Spek, Rick, Pliner, Hannah A., Shankaracharya, null, Smith, Bradley N., Marangi, Giuseppe, Topp, Simon D., Abramzon, Yevgeniya, Gkazi, Athina Soragia, Eicher, John D., Kenna, Aoife, Logullo, Francesco O., Simone, Isabella, Logroscino, Giancarlo, Salvi, Fabrizio, Bartolomei, Ilaria, Borghero, Giuseppe, Murru, Maria Rita, Costantino, Emanuela, Pani, Carla, Puddu, Roberta, Caredda, Carla, Piras, Valeria, Tranquilli, Stefania, Cuccu, Stefania, Corongiu, Daniela, Melis, Maurizio, Milia, Antonio, Marrosu, Francesco, Marrosu, Maria Giovanna, Floris, Gianluca, Cannas, Antonino, Capasso, Margherita, Caponnetto, Claudia, Mancardi, Gianluigi, Origone, Paola, Mandich, Paola, Conforti, Francesca L., Cavallaro, Sebastiano, Mora, Gabriele, Marinou, Kalliopi, Sideri, Riccardo, Penco, Silvana, Mosca, Lorena, Lunetta, Christian, Pinter, Giuseppe Lauria, Corbo, Massimo, Riva, Nilo, Carrera, Paola, Volanti, Paolo, Mandrioli, Jessica, Fini, Nicola, Fasano, Antonio, Tremolizzo, Lucio, Arosio, Alessandro, Ferrarese, Carlo, Trojsi, Francesca, Tedeschi, Gioacchino, Monsurrò, Maria Rosaria, Piccirillo, Giovanni, Femiano, Cinzia, Ticca, Anna, Ortu, Enzo, La Bella, Vincenzo, Spataro, Rossella, Colletti, Tiziana, Sabatelli, Mario, Zollino, Marcella, Conte, Amelia, Luigetti, Marco, Lattante, Serena, Santarelli, Marialuisa, Petrucci, Antonio, Pugliatti, Maura, Pirisi, Angelo, Parish, Leslie D., Occhineri, Patrizia, Giannini, Fabio, Battistini, Stefania, Ricci, Claudia, Benigni, Michele, Cau, Tea B., Loi, Daniela, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Barberis, Marco, Restagno, Gabriella, Casale, Federico, Marrali, Giuseppe, Fuda, Giuseppe, Ossola, Irene, Cammarosano, Stefania, Canosa, Antonio, Ilardi, Antonio, Manera, Umberto, Grassano, Maurizio, Tanel, Raffaella, Pisano, Fabrizio, Mazzini, Letizia, Messina, Sonia, D'Alfonso, Sandra, Corrado, Lucia, Ferrucci, Luigi, Harms, Matthew B., Goldstein, David B., Shneider, Neil A., Goutman, Stephen, Simmons, Zachary, Miller, Timothy M., Chandran, Siddharthan, Pal, Suvankar, Manousakis, George, Appel, Stanley, Simpson, Ericka, Wang, Leo, Baloh, Robert H., Gibson, Summer, Bedlack, Richard S., Lacomis, David, Sareen, Dhruv, Sherman, Alexander, Bruijn, Lucie, Penny, Michelle, Moreno, Cristiane de Araujo Martins, Kamalakaran, Sitharthan, Allen, Andrew S., Boone, Braden E., Brown, Robert, Carulli, John P., Chesi, Alessandra, Chung, Wendy K., Cirulli, Elizabeth T., Cooper, Gregory M., Couthouis, Julien, Day-Williams, Aaron G., Dion, Patrick A., Gitler, Aaron D., Glass, Jonathan D., Han, Yujun, Harris, Tim, Hayes, Sebastian D., Jones, Angela L., Keebler, Jonathan, Krueger, Brian J., Lasseigne, Brittany N., Levy, Shawn E., Lu, Yi-Fan, Maniatis, Tom, McKenna-Yasek, Diane, Myers, Richard M., Petrovski, Slavé, Pulst, Stefan M., Raphael, Alya R., Ravits, John M., Ren, Zhong, Rouleau, Guy A., Sapp, Peter C., Sims, Katherine B., Staropoli, John F., Waite, Lindsay L., Wang, Quanli, Wimbish, Jack R., Xin, Winnie W., Phatnani, Hemali, Kwan, Justin, Broach, James R., Arcila-Londono, Ximena, Lee, Edward B., Van Deerlin, Vivianna M., Fraenkel, Ernest, Ostrow, Lyle W., Baas, Frank, Zaitlen, Noah, Berry, James D., Malaspina, Andrea, Fratta, Pietro, Cox, Gregory A., Thompson, Leslie M., Finkbeiner, Steven, Dardiotis, Efthimios, Hornstein, Eran, MacGowan, Daniel J., Heiman-Patterson, Terry, Hammell, Molly G., Patsopoulos, Nikolaos A., Dubnau, Joshua, Nath, Avindra, Musunuri, Rajeeva Lochan, Evani, Uday Shankar, Abhyankar, Avinash, Zody, Michael C., Kaye, Julia, Wyman, Stacia, LeNail, Alexander, Lima, Leandro, Rothstein, Jeffrey D., Svendsen, Clive N., Van Eyk, Jenny, Maragakis, Nicholas J., Kolb, Stephen J., Cudkowicz, Merit, Baxi, Emily, Wyman, Stacia K., Van Eyk, Jennifer E., Benatar, Michael, Taylor, J. Paul, Wu, Gang, Rampersaud, Evadnie, Wuu, Joanne, Rademakers, Rosa, Züchner, Stephan, Schule, Rebecca, McCauley, Jacob, Hussain, Sumaira, Cooley, Anne, Wallace, Marielle, Clayman, Christine, Barohn, Richard, Statland, Jeffrey, Ravits, John, Swenson, Andrea, Jackson, Carlayne, Trivedi, Jaya, Khan, Shaida, Katz, Jonathan, Jenkins, Liberty, Burns, Ted, Gwathmey, Kelly, Caress, James, McMillan, Corey, Elman, Lauren, Pioro, Erik, Heckmann, Jeannine, So, Yuen, Walk, David, Maiser, Samuel, Zhang, Jinghui, Silani, Vincenzo, Gellera, Cinzia, Ratti, Antonia, Taroni, Franco, Lauria, Giuseppe, Verde, Federico, Fogh, Isabella, Tiloca, Cinzia, Comi, Giacomo P., Sorarù, Gianni, Cereda, Cristina, De Marchi, Fabiola, Corti, Stefania, Ceroni, Mauro, Siciliano, Gabriele, Filosto, Massimiliano, Inghilleri, Maurizio, Peverelli, Silvia, Colombrita, Claudia, Poletti, Barbara, Maderna, Luca, Del Bo, Roberto, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, Pensato, Viviana, Castellotti, Barbara, Camu, William, Mouzat, Kevin, Lumbroso, Serge, Corcia, Philippe, Meininger, Vincent, Besson, Gérard, Lagrange, Emmeline, Clavelou, Pierre, Guy, Nathalie, Couratier, Philippe, Vourch, Patrick, Danel, Véronique, Bernard, Emilien, Lemasson, Gwendal, Laaksovirta, Hannu, Myllykangas, Liisa, Jansson, Lilja, Valori, Miko, Ealing, John, Hamdalla, Hisham, Rollinson, Sara, Pickering-Brown, Stuart, Orrell, Richard W., Sidle, Katie C., Hardy, John, Singleton, Andrew B., Johnson, Janel O., Arepalli, Sampath, Polak, Meraida, Asress, Seneshaw, Al-Sarraj, Safa, King, Andrew, Troakes, Claire, Vance, Caroline, de Belleroche, Jacqueline, ten Asbroek, Anneloor L. M. A., Muñoz-Blanco, José Luis, Hernandez, Dena G., Ding, Jinhui, Gibbs, J. Raphael, Scholz, Sonja W., Floeter, Mary Kay, Campbell, Roy H., Landi, Francesco, Bowser, Robert, MacGowan, Daniel J. L., Kirby, Janine, Pioro, Erik P., Pamphlett, Roger, Broach, James, Gerhard, Glenn, Dunckley, Travis L., Brady, Christopher B., Kowall, Neil W., Troncoso, Juan C., Le Ber, Isabelle, Heiman-Patterson, Terry D., Kamel, Freya, Van Den Bosch, Ludo, Strom, Tim M., Meitinger, Thomas, Shatunov, Aleksey, Van Eijk, Kristel R., de Carvalho, Mamede, Kooyman, Maarten, Middelkoop, Bas, Moisse, Mattieu, McLaughlin, Russell L., Van Es, Michael A., Weber, Markus, Boylan, Kevin B., Van Blitterswijk, Marka, Morrison, Karen E., Basak, A. Nazli, Mora, Jesús S., Drory, Vivian E., Shaw, Pamela J., Turner, Martin R., Talbot, Kevin, Hardiman, Orla, Williams, Kelly L., Fifita, Jennifer A., Nicholson, Garth A., Blair, Ian P., Esteban-Pérez, Jesús, García-Redondo, Alberto, Al-Chalabi, Ammar, Al Kheifat, Ahmad, Andersen, Peter, Chio, Adriano, Cooper-Knock, Jonathan, Dekker, Annelot, Drory, Vivian, Redondo, Alberto Garcia, Gotkine, Marc, Hide, Winston, Iacoangeli, Alfredo, Glass, Jonathan, Kenna, Kevin, Kiernan, Matthew, Landers, John, McLaughlin, Russell, Mill, Jonathan, Neto, Miguel Mitne, Pardina, Jesus Mora, Morrison, Karen, Newhouse, Stephen, Pinto, Susana, Pulit, Sara, Robberecht, Wim, Shaw, Pamela, Shaw, Chris, Sproviero, William, Tazelaar, Gijs, van Damme, Philip, van den Berg, Leonard, van Eijk, Kristel, van Es, Michael, van Vugt, Joke, Veldink, Jan, Zatz, Mayana, Bauer, Denis C., Twine, Natalie A., Rogaeva, Ekaterina, Zinman, Lorne, Brice, Alexis, Goutman, Stephen A., Feldman, Eva L., Gibson, Summer B., Ludolph, Albert C., Andersen, Peter M., Weishaupt, Jochen H., Trojanowski, John Q., Brown, Robert H., van den Berg, Leonard H., Veldink, Jan H., Stone, David J., Tienari, Pentti, Chiò, Adriano, Shaw, Christopher E., Traynor, Bryan J., Landers, John E., Nicolas, A, Kenna, K, Renton, A, Ticozzi, N, Faghri, F, Chia, R, Dominov, J, Kenna, B, Nalls, M, Keagle, P, Rivera, A, van Rheenen, W, Murphy, N, van Vugt, J, Geiger, J, van der Spek, R, Pliner, H, Shankaracharya, N, Smith, B, Marangi, G, Topp, S, Abramzon, Y, Gkazi, A, Eicher, J, Kenna, A, Logullo, F, Simone, I, Logroscino, G, Salvi, F, Bartolomei, I, Borghero, G, Murru, M, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M, Floris, G, Cannas, A, Capasso, M, Caponnetto, C, Mancardi, G, Origone, P, Mandich, P, Conforti, F, Cavallaro, S, Mora, G, Marinou, K, Sideri, R, Penco, S, Mosca, L, Lunetta, C, Pinter, G, Corbo, M, Riva, N, Carrera, P, Volanti, P, Mandrioli, J, Fini, N, Fasano, A, Tremolizzo, L, Arosio, A, Ferrarese, C, Trojsi, F, Tedeschi, G, Monsurrò, M, Piccirillo, G, Femiano, C, Ticca, A, Ortu, E, La Bella, V, Spataro, R, Colletti, T, Sabatelli, M, Zollino, M, Conte, A, Luigetti, M, Lattante, S, Santarelli, M, Petrucci, A, Pugliatti, M, Pirisi, A, Parish, L, Occhineri, P, Giannini, F, Battistini, S, Ricci, C, Benigni, M, Cau, T, Loi, D, Calvo, A, Moglia, C, Brunetti, M, Barberis, M, Restagno, G, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Canosa, A, Ilardi, A, Manera, U, Grassano, M, Tanel, R, Pisano, F, Mazzini, L, Messina, S, D'Alfonso, S, Corrado, L, Ferrucci, L, Harms, M, Goldstein, D, Shneider, N, Goutman, S, Simmons, Z, Miller, T, Chandran, S, Pal, S, Manousakis, G, Appel, S, Simpson, E, Wang, L, Baloh, R, Gibson, S, Bedlack, R, Lacomis, D, Sareen, D, Sherman, A, Bruijn, L, Penny, M, Moreno, C, Kamalakaran, S, Allen, A, Boone, B, Brown, R, Carulli, J, Chesi, A, Chung, W, Cirulli, E, Cooper, G, Couthouis, J, Day-Williams, A, Dion, P, Gitler, A, Glass, J, Han, Y, Harris, T, Hayes, S, Jones, A, Keebler, J, Krueger, B, Lasseigne, B, Levy, S, Lu, Y, Maniatis, T, McKenna-Yasek, D, Myers, R, Petrovski, S, Pulst, S, Raphael, A, Ravits, J, Ren, Z, Rouleau, G, Sapp, P, Sims, K, Staropoli, J, Waite, L, Wang, Q, Wimbish, J, Xin, W, Phatnani, H, Kwan, J, Broach, J, Arcila-Londono, X, Lee, E, Van Deerlin, V, Fraenkel, E, Ostrow, L, Baas, F, Zaitlen, N, Berry, J, Malaspina, A, Fratta, P, Cox, G, Thompson, L, Finkbeiner, S, Dardiotis, E, Hornstein, E, Macgowan, D, Heiman-Patterson, T, Hammell, M, Patsopoulos, N, Dubnau, J, Nath, A, Musunuri, R, Evani, U, Abhyankar, A, Zody, M, Kaye, J, Wyman, S, Lenail, A, Lima, L, Rothstein, J, Svendsen, C, Van Eyk, J, Maragakis, N, Kolb, S, Cudkowicz, M, Baxi, E, Benatar, M, Taylor, J, Wu, G, Rampersaud, E, Wuu, J, Rademakers, R, Züchner, S, Schule, R, Mccauley, J, Hussain, S, Cooley, A, Wallace, M, Clayman, C, Barohn, R, Statland, J, Swenson, A, Jackson, C, Trivedi, J, Khan, S, Katz, J, Jenkins, L, Burns, T, Gwathmey, K, Caress, J, Mcmillan, C, Elman, L, Pioro, E, Heckmann, J, So, Y, Walk, D, Maiser, S, Zhang, J, Silani, V, Gellera, C, Ratti, A, Taroni, F, Lauria, G, Verde, F, Fogh, I, Tiloca, C, Comi, G, Sorarù, G, Cereda, C, De Marchi, F, Corti, S, Ceroni, M, Siciliano, G, Filosto, M, Inghilleri, M, Peverelli, S, Colombrita, C, Poletti, B, Maderna, L, Del Bo, R, Gagliardi, S, Querin, G, Bertolin, C, Pensato, V, Castellotti, B, Camu, W, Mouzat, K, Lumbroso, S, Corcia, P, Meininger, V, Besson, G, Lagrange, E, Clavelou, P, Guy, N, Couratier, P, Vourch, P, Danel, V, Bernard, E, Lemasson, G, Laaksovirta, H, Myllykangas, L, Jansson, L, Valori, M, Ealing, J, Hamdalla, H, Rollinson, S, Pickering-Brown, S, Orrell, R, Sidle, K, Hardy, J, Singleton, A, Johnson, J, Arepalli, S, Polak, M, Asress, S, Al-Sarraj, S, King, A, Troakes, C, Vance, C, de Belleroche, J, ten Asbroek, A, Muñoz-Blanco, J, Hernandez, D, Ding, J, Gibbs, J, Scholz, S, Floeter, M, Campbell, R, Landi, F, Bowser, R, Kirby, J, Pamphlett, R, Gerhard, G, Dunckley, T, Brady, C, Kowall, N, Troncoso, J, Le Ber, I, Kamel, F, Van Den Bosch, L, Strom, T, Meitinger, T, Shatunov, A, Van Eijk, K, de Carvalho, M, Kooyman, M, Middelkoop, B, Moisse, M, Mclaughlin, R, Van Es, M, Weber, M, Boylan, K, Van Blitterswijk, M, Morrison, K, Basak, A, Mora, J, Drory, V, Shaw, P, Turner, M, Talbot, K, Hardiman, O, Williams, K, Fifita, J, Nicholson, G, Blair, I, Esteban-Pérez, J, García-Redondo, A, Al-Chalabi, A, Al Kheifat, A, Andersen, P, Chio, A, Cooper-Knock, J, Dekker, A, Redondo, A, Gotkine, M, Hide, W, Iacoangeli, A, Kiernan, M, Landers, J, Mill, J, Neto, M, Pardina, J, Newhouse, S, Pinto, S, Pulit, S, Robberecht, W, Shaw, C, Sproviero, W, Tazelaar, G, van Damme, P, van den Berg, L, van Eijk, K, van Es, M, Veldink, J, Zatz, M, Bauer, D, Twine, N, Rogaeva, E, Zinman, L, Brice, A, Feldman, E, Ludolph, A, Weishaupt, J, Trojanowski, J, Stone, D, Tienari, P, Chiò, A, Traynor, B, Nicolas, Aude, Kenna, Kevin P., Renton, Alan E., Ticozzi, Nicola, Faghri, Faraz, Chia, Ruth, Dominov, Janice A., Kenna, Brendan J., Nalls, Mike A., Keagle, Pamela, Rivera, Alberto M., van Rheenen, Wouter, Murphy, Natalie A., van Vugt, Joke J. F. A., Geiger, Joshua T., van der Spek, Rick, Pliner, Hannah A., Shankaracharya, null, Smith, Bradley N., Marangi, Giuseppe, Topp, Simon D., Abramzon, Yevgeniya, Gkazi, Athina Soragia, Eicher, John D., Kenna, Aoife, Logullo, Francesco O., Simone, Isabella, Logroscino, Giancarlo, Salvi, Fabrizio, Bartolomei, Ilaria, Borghero, Giuseppe, Murru, Maria Rita, Costantino, Emanuela, Pani, Carla, Puddu, Roberta, Caredda, Carla, Piras, Valeria, Tranquilli, Stefania, Cuccu, Stefania, Corongiu, Daniela, Melis, Maurizio, Milia, Antonio, Marrosu, Francesco, Marrosu, Maria Giovanna, Floris, Gianluca, Cannas, Antonino, Capasso, Margherita, Caponnetto, Claudia, Mancardi, Gianluigi, Origone, Paola, Mandich, Paola, Conforti, Francesca L., Cavallaro, Sebastiano, Mora, Gabriele, Marinou, Kalliopi, Sideri, Riccardo, Penco, Silvana, Mosca, Lorena, Lunetta, Christian, Pinter, Giuseppe Lauria, Corbo, Massimo, Riva, Nilo, Carrera, Paola, Volanti, Paolo, Mandrioli, Jessica, Fini, Nicola, Fasano, Antonio, Tremolizzo, Lucio, Arosio, Alessandro, Ferrarese, Carlo, Trojsi, Francesca, Tedeschi, Gioacchino, Monsurrò, Maria Rosaria, Piccirillo, Giovanni, Femiano, Cinzia, Ticca, Anna, Ortu, Enzo, La Bella, Vincenzo, Spataro, Rossella, Colletti, Tiziana, Sabatelli, Mario, Zollino, Marcella, Conte, Amelia, Luigetti, Marco, Lattante, Serena, Santarelli, Marialuisa, Petrucci, Antonio, Pugliatti, Maura, Pirisi, Angelo, Parish, Leslie D., Occhineri, Patrizia, Giannini, Fabio, Battistini, Stefania, Ricci, Claudia, Benigni, Michele, Cau, Tea B., Loi, Daniela, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Barberis, Marco, Restagno, Gabriella, Casale, Federico, Marrali, Giuseppe, Fuda, Giuseppe, Ossola, Irene, Cammarosano, Stefania, Canosa, Antonio, Ilardi, Antonio, Manera, Umberto, Grassano, Maurizio, Tanel, Raffaella, Pisano, Fabrizio, Mazzini, Letizia, Messina, Sonia, D'Alfonso, Sandra, Corrado, Lucia, Ferrucci, Luigi, Harms, Matthew B., Goldstein, David B., Shneider, Neil A., Goutman, Stephen, Simmons, Zachary, Miller, Timothy M., Chandran, Siddharthan, Pal, Suvankar, Manousakis, George, Appel, Stanley, Simpson, Ericka, Wang, Leo, Baloh, Robert H., Gibson, Summer, Bedlack, Richard S., Lacomis, David, Sareen, Dhruv, Sherman, Alexander, Bruijn, Lucie, Penny, Michelle, Moreno, Cristiane de Araujo Martins, Kamalakaran, Sitharthan, Allen, Andrew S., Boone, Braden E., Brown, Robert, Carulli, John P., Chesi, Alessandra, Chung, Wendy K., Cirulli, Elizabeth T., Cooper, Gregory M., Couthouis, Julien, Day-Williams, Aaron G., Dion, Patrick A., Gitler, Aaron D., Glass, Jonathan D., Han, Yujun, Harris, Tim, Hayes, Sebastian D., Jones, Angela L., Keebler, Jonathan, Krueger, Brian J., Lasseigne, Brittany N., Levy, Shawn E., Lu, Yi-Fan, Maniatis, Tom, McKenna-Yasek, Diane, Myers, Richard M., Petrovski, Slavé, Pulst, Stefan M., Raphael, Alya R., Ravits, John M., Ren, Zhong, Rouleau, Guy A., Sapp, Peter C., Sims, Katherine B., Staropoli, John F., Waite, Lindsay L., Wang, Quanli, Wimbish, Jack R., Xin, Winnie W., Phatnani, Hemali, Kwan, Justin, Broach, James R., Arcila-Londono, Ximena, Lee, Edward B., Van Deerlin, Vivianna M., Fraenkel, Ernest, Ostrow, Lyle W., Baas, Frank, Zaitlen, Noah, Berry, James D., Malaspina, Andrea, Fratta, Pietro, Cox, Gregory A., Thompson, Leslie M., Finkbeiner, Steven, Dardiotis, Efthimios, Hornstein, Eran, MacGowan, Daniel J., Heiman-Patterson, Terry, Hammell, Molly G., Patsopoulos, Nikolaos A., Dubnau, Joshua, Nath, Avindra, Musunuri, Rajeeva Lochan, Evani, Uday Shankar, Abhyankar, Avinash, Zody, Michael C., Kaye, Julia, Wyman, Stacia, LeNail, Alexander, Lima, Leandro, Rothstein, Jeffrey D., Svendsen, Clive N., Van Eyk, Jenny, Maragakis, Nicholas J., Kolb, Stephen J., Cudkowicz, Merit, Baxi, Emily, Wyman, Stacia K., Van Eyk, Jennifer E., Benatar, Michael, Taylor, J. Paul, Wu, Gang, Rampersaud, Evadnie, Wuu, Joanne, Rademakers, Rosa, Züchner, Stephan, Schule, Rebecca, McCauley, Jacob, Hussain, Sumaira, Cooley, Anne, Wallace, Marielle, Clayman, Christine, Barohn, Richard, Statland, Jeffrey, Ravits, John, Swenson, Andrea, Jackson, Carlayne, Trivedi, Jaya, Khan, Shaida, Katz, Jonathan, Jenkins, Liberty, Burns, Ted, Gwathmey, Kelly, Caress, James, McMillan, Corey, Elman, Lauren, Pioro, Erik, Heckmann, Jeannine, So, Yuen, Walk, David, Maiser, Samuel, Zhang, Jinghui, Silani, Vincenzo, Gellera, Cinzia, Ratti, Antonia, Taroni, Franco, Lauria, Giuseppe, Verde, Federico, Fogh, Isabella, Tiloca, Cinzia, Comi, Giacomo P., Sorarù, Gianni, Cereda, Cristina, De Marchi, Fabiola, Corti, Stefania, Ceroni, Mauro, Siciliano, Gabriele, Filosto, Massimiliano, Inghilleri, Maurizio, Peverelli, Silvia, Colombrita, Claudia, Poletti, Barbara, Maderna, Luca, Del Bo, Roberto, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, Pensato, Viviana, Castellotti, Barbara, Camu, William, Mouzat, Kevin, Lumbroso, Serge, Corcia, Philippe, Meininger, Vincent, Besson, Gérard, Lagrange, Emmeline, Clavelou, Pierre, Guy, Nathalie, Couratier, Philippe, Vourch, Patrick, Danel, Véronique, Bernard, Emilien, Lemasson, Gwendal, Laaksovirta, Hannu, Myllykangas, Liisa, Jansson, Lilja, Valori, Miko, Ealing, John, Hamdalla, Hisham, Rollinson, Sara, Pickering-Brown, Stuart, Orrell, Richard W., Sidle, Katie C., Hardy, John, Singleton, Andrew B., Johnson, Janel O., Arepalli, Sampath, Polak, Meraida, Asress, Seneshaw, Al-Sarraj, Safa, King, Andrew, Troakes, Claire, Vance, Caroline, de Belleroche, Jacqueline, ten Asbroek, Anneloor L. M. A., Muñoz-Blanco, José Luis, Hernandez, Dena G., Ding, Jinhui, Gibbs, J. Raphael, Scholz, Sonja W., Floeter, Mary Kay, Campbell, Roy H., Landi, Francesco, Bowser, Robert, MacGowan, Daniel J. L., Kirby, Janine, Pioro, Erik P., Pamphlett, Roger, Broach, James, Gerhard, Glenn, Dunckley, Travis L., Brady, Christopher B., Kowall, Neil W., Troncoso, Juan C., Le Ber, Isabelle, Heiman-Patterson, Terry D., Kamel, Freya, Van Den Bosch, Ludo, Strom, Tim M., Meitinger, Thomas, Shatunov, Aleksey, Van Eijk, Kristel R., de Carvalho, Mamede, Kooyman, Maarten, Middelkoop, Bas, Moisse, Mattieu, McLaughlin, Russell L., Van Es, Michael A., Weber, Markus, Boylan, Kevin B., Van Blitterswijk, Marka, Morrison, Karen E., Basak, A. Nazli, Mora, Jesús S., Drory, Vivian E., Shaw, Pamela J., Turner, Martin R., Talbot, Kevin, Hardiman, Orla, Williams, Kelly L., Fifita, Jennifer A., Nicholson, Garth A., Blair, Ian P., Esteban-Pérez, Jesús, García-Redondo, Alberto, Al-Chalabi, Ammar, Al Kheifat, Ahmad, Andersen, Peter, Chio, Adriano, Cooper-Knock, Jonathan, Dekker, Annelot, Drory, Vivian, Redondo, Alberto Garcia, Gotkine, Marc, Hide, Winston, Iacoangeli, Alfredo, Glass, Jonathan, Kenna, Kevin, Kiernan, Matthew, Landers, John, McLaughlin, Russell, Mill, Jonathan, Neto, Miguel Mitne, Pardina, Jesus Mora, Morrison, Karen, Newhouse, Stephen, Pinto, Susana, Pulit, Sara, Robberecht, Wim, Shaw, Pamela, Shaw, Chris, Sproviero, William, Tazelaar, Gijs, van Damme, Philip, van den Berg, Leonard, van Eijk, Kristel, van Es, Michael, van Vugt, Joke, Veldink, Jan, Zatz, Mayana, Bauer, Denis C., Twine, Natalie A., Rogaeva, Ekaterina, Zinman, Lorne, Brice, Alexis, Goutman, Stephen A., Feldman, Eva L., Gibson, Summer B., Ludolph, Albert C., Andersen, Peter M., Weishaupt, Jochen H., Trojanowski, John Q., Brown, Robert H., van den Berg, Leonard H., Veldink, Jan H., Stone, David J., Tienari, Pentti, Chiò, Adriano, Shaw, Christopher E., Traynor, Bryan J., and Landers, John E.
Abstract: To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS. Using a large-scale genome-wide association study and exome sequencing, we identified KIF5A as a novel gene associated with ALS. Our data broaden the phenotype resulting from mutations in KIF5A and highlight the importance of cytoskeletal defects in the pathogenesis of ALS.
Published: 2018

19. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

Author: Nicolas, A., Kenna, K. P., Renton, A. E., Ticozzi, N., Faghri, F., Chia, R., Dominov, J. A., Kenna, B. J., Nalls, M. A., Keagle, P., Rivera, A. M., van Rheenen, W., Murphy, N. A., van Vugt, J. J. F. A., Geiger, J. T., Van der Spek, R. A., Pliner, H. A., Shankaracharya, Smith, B. N., Marangi, Giuseppe, Topp, S. D., Abramzon, Y., Gkazi, A. S., Eicher, J. D., Kenna, A., Logullo, F. O., Simone, I. L., Logroscino, Giandomenico, Salvi, F., Bartolomei, I., Borghero, G., Murru, M. R., Costantino, E., Pani, C., Puddu, R., Caredda, C., Piras, V., Tranquilli, S., Cuccu, S., Corongiu, D., Melis, M., Milia, A., Marrosu, F., Marrosu, M. G., Floris, G., Cannas, A., Capasso, Monica, Caponnetto, C., Mancardi, G., Origone, P., Mandich, P., Conforti, F. L., Cavallaro, S., Mora, G., Marinou, K., Sideri, R., Penco, S., Mosca, Luigi, Lunetta, C., Pinter, G. L., Corbo, M., Riva, N., Carrera, P., Volanti, P., Mandrioli, J., Fini, N., Fasano, Alfonso, Tremolizzo, L., Arosio, A., Ferrarese, C., Trojsi, F., Tedeschi, G., Monsurro, M. R., Piccirillo, G., Femiano, C., Ticca, A., Ortu, E., La Bella, V., Spataro, R., Colletti, T., Sabatelli, Mario, Zollino, Marcella, Conte, Amelia, Luigetti, Marco, Lattante, Serena, Santarelli, M., Petrucci, A., Pugliatti, M., Pirisi, A., Parish, L. D., Occhineri, P., Giannini, F., Battistini, S., Ricci, C., Benigni, M., Cau, T. B., Loi, D., Calvo, A., Moglia, C., Brunetti, M., Barberis, M., Restagno, G., Casale, F., Marrali, G., Fuda, G., Ossola, I., Cammarosano, S., Canosa, A., Ilardi, A., Manera, U., Grassano, M., Tanel, R., Pisano, F., Mazzini, L., Messina, S., D'Alfonso, Sandra, Corrado, L., Ferrucci, L., Harms, M. B., Goldstein, D. B., Shneider, N. A., Goutman, S. A., Simmons, Z., Miller, T. M., Chandran, S., Pal, S., Manousakis, G., Appel, S. H., Simpson, E., Wang, L., Baloh, R. H., Gibson, S. B., Bedlack, R., Lacomis, D., Sareen, D., Sherman, A., Bruijn, L., Penny, M., Moreno, C. D. A. M., Kamalakaran, S., Allen, A. S., Boone, B. E., Brown, R. H., Carulli, J. P., Chesi, A., Chung, W. K., Cirulli, E. T., Cooper, G. M., Couthouis, J., Day-Williams, A. G., Dion, P. A., Gitler, A. D., Glass, J. D., Han, Y., Harris, T., Hayes, S. D., Jones, A. L., Keebler, J., Krueger, B. J., Lasseigne, B. N., Levy, S. E., Lu, Y. -F., Maniatis, T., McKenna-Yasek, D., Myers, R. M., Petrovski, S., Pulst, S. M., Raphael, A. R., Ravits, J. M., Ren, Z., Rouleau, G. A., Sapp, P. C., Sims, K. B., Staropoli, J. F., Waite, L. L., Wang, Quanquan, Wimbish, J. R., Xin, W. W., Phatnani, H., Kwan, J., Broach, J., Arcila-Londono, X., Lee, E. B., Van Deerlin, V. M., Fraenkel, E., Ostrow, L. W., Baas, F., Zaitlen, N., Berry, J. D., Malaspina, A., Fratta, P., Cox, G. A., Thompson, L. M., Finkbeiner, S., Dardiotis, E., Hornstein, E., Macgowan, D. J. L., Heiman-Patterson, T., Hammell, M. G., Patsopoulos, N. A., Dubnau, J., Nath, A., Musunuri, R. L., Evani, U. S., Abhyankar, A., Zody, M. C., Kaye, J., Wyman, S. K., Lenail, A., Lima, L., Rothstein, J. D., Svendsen, C. N., Van Eyk, J. E., Maragakis, N. J., Kolb, S. J., Cudkowicz, M., Baxi, E., Benatar, M., Taylor, J. P., Wu, G., Rampersaud, E., Wuu, J., Rademakers, R., Zuchner, S., Schule, R., Mccauley, J., Hussain, S., Cooley, A., Wallace, M., Clayman, C., Barohn, R., Statland, J., Swenson, A., Jackson, C., Trivedi, J., Khan, S., Katz, J., Jenkins, L., Burns, T., Gwathmey, K., Caress, J., Mcmillan, C., Elman, L., Pioro, E. P., Heckmann, J., So, Y., Walk, D., Maiser, S., Zhang, J., Silani, V., Gellera, C., Ratti, A., Taroni, F., Lauria, G., Verde, F., Fogh, I., Tiloca, C., Comi, G. P., Soraru, G., Cereda, C., De Marchi, F., Corti, S., Ceroni, M., Siciliano, Giovanni, Filosto, M., Inghilleri, M., Peverelli, S., Colombrita, C., Poletti, B., Maderna, L., Del Bo, R., Gagliardi, S., Querin, G., Bertolin, C., Pensato, V., Castellotti, B., Camu, W., Mouzat, K., Lumbroso, S., Corcia, P., Meininger, V., Besson, G., Lagrange, E., Clavelou, P., Guy, N., Couratier, P., Vourch, P., Danel, V., Bernard, E., Lemasson, G., Laaksovirta, H., Myllykangas, L., Jansson, L., Valori, Vanna Maria, Ealing, J., Hamdalla, H., Rollinson, S., Pickering-Brown, S., Orrell, R. W., Sidle, K. C., Hardy, J., Singleton, A. B., Johnson, J. O., Arepalli, S., Polak, M., Asress, S., Al-Sarraj, S., King, A., Troakes, C., Vance, C., de Belleroche, J., ten Asbroek, A. L. M. A., Munoz-Blanco, J. L., Hernandez, D. G., Ding, J., Gibbs, J. R., Scholz, S. W., Floeter, M. K., Campbell, R. H., Landi, Francesco, Bowser, R., Kirby, J., Pamphlett, R., Gerhard, G., Dunckley, T. L., Brady, C. B., Kowall, N. W., Troncoso, J. C., Le Ber, I., Heiman-Patterson, T. D., Kamel, F., Van Den Bosch, L., Strom, T. M., Meitinger, T., Shatunov, A., Van Eijk, K. R., de Carvalho, M., Kooyman, M., Middelkoop, B., Moisse, M., Mclaughlin, R. L., Van Es, M. A., Weber, M., Boylan, K. B., Van Blitterswijk, M., Morrison, K. E., Basak, A. N., Mora, J. S., Drory, V. E., Shaw, P. J., Turner, M. R., Talbot, K., Hardiman, O., Williams, K. L., Fifita, J. A., Nicholson, G. A., Blair, I. P., Esteban-Perez, J., Garcia-Redondo, A., Al-Chalabi, A., Al Kheifat, A., Andersen, P. M., Chio, A., Cooper-Knock, J., Dekker, A., Redondo, A. G., Gotkine, M., Hide, W., Iacoangeli, A., Kiernan, M., Landers, J. E., Mill, J., Neto, M. M., Pardina, J. M., Newhouse, S., Pinto, S., Pulit, S., Robberecht, W., Shaw, C., Sproviero, W., Tazelaar, G., Van Damme, P., van den Berg, L. H., van Vugt, J., Veldink, J. H., Zatz, M., Bauer, D. C., Twine, N. A., Rogaeva, E., Zinman, L., Brice, A., Feldman, E. L., Ludolph, A. C., Weishaupt, J. H., Trojanowski, J. Q., Stone, D. J., Tienari, P., Shaw, C. E., Traynor, B. J., Marangi G. (ORCID:0000-0002-6898-8882), Logroscino G. (ORCID:0000-0003-1301-5343), Capasso M., Mosca L. (ORCID:0000-0003-4641-0841), Fasano A., Sabatelli M. (ORCID:0000-0001-6635-4985), Zollino M. (ORCID:0000-0003-4871-9519), Conte A., Luigetti M. (ORCID:0000-0001-7539-505X), Lattante S. (ORCID:0000-0003-2891-0340), D'Alfonso S., Siciliano G., Valori M., Landi F. (ORCID:0000-0002-3472-1389), Nicolas, A., Kenna, K. P., Renton, A. E., Ticozzi, N., Faghri, F., Chia, R., Dominov, J. A., Kenna, B. J., Nalls, M. A., Keagle, P., Rivera, A. M., van Rheenen, W., Murphy, N. A., van Vugt, J. J. F. A., Geiger, J. T., Van der Spek, R. A., Pliner, H. A., Shankaracharya, Smith, B. N., Marangi, Giuseppe, Topp, S. D., Abramzon, Y., Gkazi, A. S., Eicher, J. D., Kenna, A., Logullo, F. O., Simone, I. L., Logroscino, Giandomenico, Salvi, F., Bartolomei, I., Borghero, G., Murru, M. R., Costantino, E., Pani, C., Puddu, R., Caredda, C., Piras, V., Tranquilli, S., Cuccu, S., Corongiu, D., Melis, M., Milia, A., Marrosu, F., Marrosu, M. G., Floris, G., Cannas, A., Capasso, Monica, Caponnetto, C., Mancardi, G., Origone, P., Mandich, P., Conforti, F. L., Cavallaro, S., Mora, G., Marinou, K., Sideri, R., Penco, S., Mosca, Luigi, Lunetta, C., Pinter, G. L., Corbo, M., Riva, N., Carrera, P., Volanti, P., Mandrioli, J., Fini, N., Fasano, Alfonso, Tremolizzo, L., Arosio, A., Ferrarese, C., Trojsi, F., Tedeschi, G., Monsurro, M. R., Piccirillo, G., Femiano, C., Ticca, A., Ortu, E., La Bella, V., Spataro, R., Colletti, T., Sabatelli, Mario, Zollino, Marcella, Conte, Amelia, Luigetti, Marco, Lattante, Serena, Santarelli, M., Petrucci, A., Pugliatti, M., Pirisi, A., Parish, L. D., Occhineri, P., Giannini, F., Battistini, S., Ricci, C., Benigni, M., Cau, T. B., Loi, D., Calvo, A., Moglia, C., Brunetti, M., Barberis, M., Restagno, G., Casale, F., Marrali, G., Fuda, G., Ossola, I., Cammarosano, S., Canosa, A., Ilardi, A., Manera, U., Grassano, M., Tanel, R., Pisano, F., Mazzini, L., Messina, S., D'Alfonso, Sandra, Corrado, L., Ferrucci, L., Harms, M. B., Goldstein, D. B., Shneider, N. A., Goutman, S. A., Simmons, Z., Miller, T. M., Chandran, S., Pal, S., Manousakis, G., Appel, S. H., Simpson, E., Wang, L., Baloh, R. H., Gibson, S. B., Bedlack, R., Lacomis, D., Sareen, D., Sherman, A., Bruijn, L., Penny, M., Moreno, C. D. A. M., Kamalakaran, S., Allen, A. S., Boone, B. E., Brown, R. H., Carulli, J. P., Chesi, A., Chung, W. K., Cirulli, E. T., Cooper, G. M., Couthouis, J., Day-Williams, A. G., Dion, P. A., Gitler, A. D., Glass, J. D., Han, Y., Harris, T., Hayes, S. D., Jones, A. L., Keebler, J., Krueger, B. J., Lasseigne, B. N., Levy, S. E., Lu, Y. -F., Maniatis, T., McKenna-Yasek, D., Myers, R. M., Petrovski, S., Pulst, S. M., Raphael, A. R., Ravits, J. M., Ren, Z., Rouleau, G. A., Sapp, P. C., Sims, K. B., Staropoli, J. F., Waite, L. L., Wang, Quanquan, Wimbish, J. R., Xin, W. W., Phatnani, H., Kwan, J., Broach, J., Arcila-Londono, X., Lee, E. B., Van Deerlin, V. M., Fraenkel, E., Ostrow, L. W., Baas, F., Zaitlen, N., Berry, J. D., Malaspina, A., Fratta, P., Cox, G. A., Thompson, L. M., Finkbeiner, S., Dardiotis, E., Hornstein, E., Macgowan, D. J. L., Heiman-Patterson, T., Hammell, M. G., Patsopoulos, N. A., Dubnau, J., Nath, A., Musunuri, R. L., Evani, U. S., Abhyankar, A., Zody, M. C., Kaye, J., Wyman, S. K., Lenail, A., Lima, L., Rothstein, J. D., Svendsen, C. N., Van Eyk, J. E., Maragakis, N. J., Kolb, S. J., Cudkowicz, M., Baxi, E., Benatar, M., Taylor, J. P., Wu, G., Rampersaud, E., Wuu, J., Rademakers, R., Zuchner, S., Schule, R., Mccauley, J., Hussain, S., Cooley, A., Wallace, M., Clayman, C., Barohn, R., Statland, J., Swenson, A., Jackson, C., Trivedi, J., Khan, S., Katz, J., Jenkins, L., Burns, T., Gwathmey, K., Caress, J., Mcmillan, C., Elman, L., Pioro, E. P., Heckmann, J., So, Y., Walk, D., Maiser, S., Zhang, J., Silani, V., Gellera, C., Ratti, A., Taroni, F., Lauria, G., Verde, F., Fogh, I., Tiloca, C., Comi, G. P., Soraru, G., Cereda, C., De Marchi, F., Corti, S., Ceroni, M., Siciliano, Giovanni, Filosto, M., Inghilleri, M., Peverelli, S., Colombrita, C., Poletti, B., Maderna, L., Del Bo, R., Gagliardi, S., Querin, G., Bertolin, C., Pensato, V., Castellotti, B., Camu, W., Mouzat, K., Lumbroso, S., Corcia, P., Meininger, V., Besson, G., Lagrange, E., Clavelou, P., Guy, N., Couratier, P., Vourch, P., Danel, V., Bernard, E., Lemasson, G., Laaksovirta, H., Myllykangas, L., Jansson, L., Valori, Vanna Maria, Ealing, J., Hamdalla, H., Rollinson, S., Pickering-Brown, S., Orrell, R. W., Sidle, K. C., Hardy, J., Singleton, A. B., Johnson, J. O., Arepalli, S., Polak, M., Asress, S., Al-Sarraj, S., King, A., Troakes, C., Vance, C., de Belleroche, J., ten Asbroek, A. L. M. A., Munoz-Blanco, J. L., Hernandez, D. G., Ding, J., Gibbs, J. R., Scholz, S. W., Floeter, M. K., Campbell, R. H., Landi, Francesco, Bowser, R., Kirby, J., Pamphlett, R., Gerhard, G., Dunckley, T. L., Brady, C. B., Kowall, N. W., Troncoso, J. C., Le Ber, I., Heiman-Patterson, T. D., Kamel, F., Van Den Bosch, L., Strom, T. M., Meitinger, T., Shatunov, A., Van Eijk, K. R., de Carvalho, M., Kooyman, M., Middelkoop, B., Moisse, M., Mclaughlin, R. L., Van Es, M. A., Weber, M., Boylan, K. B., Van Blitterswijk, M., Morrison, K. E., Basak, A. N., Mora, J. S., Drory, V. E., Shaw, P. J., Turner, M. R., Talbot, K., Hardiman, O., Williams, K. L., Fifita, J. A., Nicholson, G. A., Blair, I. P., Esteban-Perez, J., Garcia-Redondo, A., Al-Chalabi, A., Al Kheifat, A., Andersen, P. M., Chio, A., Cooper-Knock, J., Dekker, A., Redondo, A. G., Gotkine, M., Hide, W., Iacoangeli, A., Kiernan, M., Landers, J. E., Mill, J., Neto, M. M., Pardina, J. M., Newhouse, S., Pinto, S., Pulit, S., Robberecht, W., Shaw, C., Sproviero, W., Tazelaar, G., Van Damme, P., van den Berg, L. H., van Vugt, J., Veldink, J. H., Zatz, M., Bauer, D. C., Twine, N. A., Rogaeva, E., Zinman, L., Brice, A., Feldman, E. L., Ludolph, A. C., Weishaupt, J. H., Trojanowski, J. Q., Stone, D. J., Tienari, P., Shaw, C. E., Traynor, B. J., Marangi G. (ORCID:0000-0002-6898-8882), Logroscino G. (ORCID:0000-0003-1301-5343), Capasso M., Mosca L. (ORCID:0000-0003-4641-0841), Fasano A., Sabatelli M. (ORCID:0000-0001-6635-4985), Zollino M. (ORCID:0000-0003-4871-9519), Conte A., Luigetti M. (ORCID:0000-0001-7539-505X), Lattante S. (ORCID:0000-0003-2891-0340), D'Alfonso S., Siciliano G., Valori M., and Landi F. (ORCID:0000-0002-3472-1389)
Abstract: To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS. Using a large-scale genome-wide association study and exome sequencing, we identified KIF5A as a novel gene associated with ALS. Our data broaden the phenotype resulting from mutations in KIF5A and highlight the importance of cytoskeletal defects in the pathogenesis of ALS.
Published: 2018

20. HFE p.H63D polymorphism does not influence ALS phenotype and survival

Author: Chio, A, Mora, G, Sabatelli, M, Caponnetto, C, Lunetta, C, Traynor, B, Johnson, J, Nalls, M, Calvo, A, Moglia, C, Borghero, G, Monsurro, M, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, F, Nilo, R, Giannini, F, Mandrioli, J, Tanel, R, Murru, M, Mandich, P, Zollino, M, Conforti, F, Penco, S, Brunetti, M, Barberis, M, Restagno, G, Logroscino, G, Bartolomei, I, Capasso, M, Mancardi, G, Origone, P, Marinou, K, Sideri, R, Mosca, L, Pinter, G, Corbo, M, Fini, N, Georgoulopoulou, E, Tremolizzo, L, Tedeschi, G, Trojsi, F, Piccirillo, G, Cristillo, V, Spataro, R, Colletti, T, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Battistini, S, Ricci, C, Benigni, M, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Bertuzzo, D, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M, Floris, G, Cannas, A, Ticca, A, Pugliatti, M, Pirisi, A, Parish, L, Occhineri, P, Ortu, E, Cau, T, Loi, D, Chio A., Mora G., Sabatelli M., Caponnetto C., Lunetta C., Traynor B. J., Johnson J. O., Nalls M. A., Calvo A., Moglia C., Borghero G., Monsurro M. R., La Bella V., Volanti P., Simone I., Salvi F., Logullo F. O., Nilo R., Giannini F., Mandrioli J., Tanel R., Murru M. R., Mandich P., Zollino M., Conforti F. L., Penco S., Brunetti M., Barberis M., Restagno G., Logroscino G., Bartolomei I., Capasso M., Mancardi G., Origone P., Marinou K., Sideri R., Mosca L., Pinter G. L., Corbo M., Fini N., Georgoulopoulou E., Tremolizzo L., Tedeschi G., Trojsi F., Piccirillo G., Cristillo V., Spataro R., Colletti T., Conte A., Luigetti M., Lattante S., Marangi G., Santarelli M., Petrucci A., Battistini S., Ricci C., Benigni M., Casale F., Marrali G., Fuda G., Ossola I., Cammarosano S., Ilardi A., Bertuzzo D., Pisano F., Costantino E., Pani C., Puddu R., Caredda C., Piras V., Tranquilli S., Cuccu S., Corongiu D., Melis M., Milia A., Marrosu F., Marrosu M. G., Floris G., Cannas A., Ticca A., Pugliatti M., Pirisi A., Parish L. D., Occhineri P., Ortu E., Cau T. B., Loi D., Chio, A, Mora, G, Sabatelli, M, Caponnetto, C, Lunetta, C, Traynor, B, Johnson, J, Nalls, M, Calvo, A, Moglia, C, Borghero, G, Monsurro, M, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, F, Nilo, R, Giannini, F, Mandrioli, J, Tanel, R, Murru, M, Mandich, P, Zollino, M, Conforti, F, Penco, S, Brunetti, M, Barberis, M, Restagno, G, Logroscino, G, Bartolomei, I, Capasso, M, Mancardi, G, Origone, P, Marinou, K, Sideri, R, Mosca, L, Pinter, G, Corbo, M, Fini, N, Georgoulopoulou, E, Tremolizzo, L, Tedeschi, G, Trojsi, F, Piccirillo, G, Cristillo, V, Spataro, R, Colletti, T, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Battistini, S, Ricci, C, Benigni, M, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Bertuzzo, D, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M, Floris, G, Cannas, A, Ticca, A, Pugliatti, M, Pirisi, A, Parish, L, Occhineri, P, Ortu, E, Cau, T, Loi, D, Chio A., Mora G., Sabatelli M., Caponnetto C., Lunetta C., Traynor B. J., Johnson J. O., Nalls M. A., Calvo A., Moglia C., Borghero G., Monsurro M. R., La Bella V., Volanti P., Simone I., Salvi F., Logullo F. O., Nilo R., Giannini F., Mandrioli J., Tanel R., Murru M. R., Mandich P., Zollino M., Conforti F. L., Penco S., Brunetti M., Barberis M., Restagno G., Logroscino G., Bartolomei I., Capasso M., Mancardi G., Origone P., Marinou K., Sideri R., Mosca L., Pinter G. L., Corbo M., Fini N., Georgoulopoulou E., Tremolizzo L., Tedeschi G., Trojsi F., Piccirillo G., Cristillo V., Spataro R., Colletti T., Conte A., Luigetti M., Lattante S., Marangi G., Santarelli M., Petrucci A., Battistini S., Ricci C., Benigni M., Casale F., Marrali G., Fuda G., Ossola I., Cammarosano S., Ilardi A., Bertuzzo D., Pisano F., Costantino E., Pani C., Puddu R., Caredda C., Piras V., Tranquilli S., Cuccu S., Corongiu D., Melis M., Milia A., Marrosu F., Marrosu M. G., Floris G., Cannas A., Ticca A., Pugliatti M., Pirisi A., Parish L. D., Occhineri P., Ortu E., Cau T. B., and Loi D.
Abstract: It has been recently reported that the p.His63Asp polymorphism of the HFE gene accelerates disease progression both in the SOD1 transgenic mouse and in amyotrophic lateral sclerosis (ALS) patients. We have evaluated the effect of HFE p.His63Asp polymorphism on the phenotype in 1351 Italian ALS patients (232 of Sardinian ancestry). Patients were genotyped for the HFE p.His63Asp polymorphism (CC, GC, and GG). All patients were also assessed for C9ORF72, TARDBP, SOD1, and FUS mutations. Of the 1351 ALS patients, 363 (29.2%) were heterozygous (GC) for the p.His63Asp polymorphism and 30 (2.2%) were homozygous for the minor allele (GG). Patients with CC, GC, and GG polymorphisms did not significantly differ by age at onset, site of onset of symptoms, and survival; however, in SOD1 patients with CG or GG polymorphism had a significantly longer survival than those with a CC polymorphism. Differently from what observed in the mouse model of ALS, the HFE p.His63Asp polymorphism has no effect on ALS phenotype in this large series of Italian ALS patients.
Published: 2015

21. CHE COSA CI FA CONOSCERE LA BELLEZZA

Author: Costantino Esposito
Subjects: Conoscenza, Bellezza, Filosofia, Christianity, BR1-1725, Doctrinal Theology, BT10-1480, The Bible, BS1-2970
Abstract: Il titolo di questo mio intervento può essere inteso in due modi diversi ma complementari: esso si riferisce in primo luogo (secondo una più immediata comprensione) a quelle condizioni dell’esperienza e a quei fattori della soggettività umana che ci permettono di giudicare qualcosa come “bella”, o più in generale ci fanno conoscere la realtà della bellezza. Ma in secondo luogo il titolo si riferisce a ciò che la bellezza stessa ci permette di conoscere, o meglio quella specifica conoscenza della realtà – di noi stessi e del mondo – che acquisiamo grazie alla bellezza. Tutto il problema della bellezza nella nostra epoca può essere sintetizatto nel fatto che i due sensi di questo titolo sembrano essere ormai definitivamente divaricati l’uno rispetto all’altro. Di modo che nell’esperienza soggettiva del bello (in quello che da Kant in poi chiamiamo il “gusto” del bello) si indebolisce, fino a perdersi, ogni pretesa di conoscenza; e a sua volta la conoscenza oggettiva delle cose si identifica progressivamente con la loro misurabilità e la loro costruibilità. Per questo vale la pena riaprire una questione che sembrerebbe essere già stata risolta e archiviata, vale a dire: qual è la dimensione conoscitiva del bello? Ci permette esso di allargare la nostra conoscenza del mondo e di noi stessi o dev’essere confinata all’interno di un sentimento soggettivo?
Published: 2023
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22. REPORT SUI DATI RACCOLTI DURANTE LA GIORNATA MONDIALE DEL RENE IN ITALIA NEGLI ANNI 2015-2016- Report for the World Kidney Days in Italy 2015-2016

Author: Esposito, P, Battaglia, Yuri, Caramella, E, Russo, D, Balducci, A., Aucella, F, Avino, D, Borzumati, M, Botti, P, Brizzi, F, Castellino, S, Cuomo, V, Dagostino, F, De Simone, W, Di Loreto, P, Fiorini, F, Garibotto, G, Iulianiello, G, La Peccerella, L, Mancini, C, Mereu, Mc, Passaghe, M, Prati, E, Re, A, Rondanini, V, Pergamo, O, Simeoni, Ma, Storari, A, Carlini, A, Tedesco, A, Amato, M, Costantino, E, D'Alessandro, V, Montagna, E, Sozzo, E, Lomonte, C, Lisi, P, Parsi, R, Saffiotti, S, Santoro, D, Tira, P, Tosini, R, Gianni, S, Sessa, C, Scafarto, A, Chiarinotti, D, Boero, R, Buonfantino, A, D'Amaro, E, Lus, G, D'Alessandro, A, Cossu, M, Ballestri, M, Gasparro, V, and Vernaglione, L.
Subjects: World Kidney Day, Prevention, Hypertension, Urinalysis
Published: 2017

23. Megaprosthetic reconstruction of the distal femur with a short residual proximal femur following bone tumor resection: a systematic review

Author: Shinji Tsukamoto, Andreas F. Mavrogenis, Tomoya Masunaga, Akira Kido, Kanya Honoki, Yuu Tanaka, Hiromasa Fujii, Yasuhito Tanaka, and Costantino Errani
Subjects: Distal femur replacement, Distal femoral tumor, Short proximal femur, Compressive osseointegration, Allograft prosthetic composite, Custom-made megaprosthesis, Orthopedic surgery, RD701-811, Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract Background To investigate the risk of postoperative function and complications associated with reconstruction methods in patients with short residual proximal femurs (
Published: 2023
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24. Association between Inflammatory Markers and Local Recurrence in Patients with Giant Cell Tumor of Bone: A Preliminary Result

Author: Shinji Tsukamoto, Andreas F. Mavrogenis, Rebeca Angulo Alvarado, Matteo Traversari, Manabu Akahane, Kanya Honoki, Yasuhito Tanaka, Davide Maria Donati, and Costantino Errani
Subjects: giant cell tumor of bone, neutrophil-lymphocyte ratio, modified Glasgow prognostic score, prognostic nutrient index, lymphocyte-monocyte ratio, platelet-lymphocyte ratio, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Giant cell tumor of bone (GCTB) has a high local recurrence rate of approximately 20%. Systemic inflammatory markers, such as neutrophil-lymphocyte ratio (NLR), modified Glasgow prognostic score (mGPS), prognostic nutritional index (PNI), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), hemoglobin (Hb), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH), have been reported as prognostic markers in patients with malignant tumors. This study aimed to investigate the correlation between these markers and the local recurrence rate of GCTB. In total, 103 patients with GCTB who underwent surgery at the authors’ institutions between 1993 and 2021 were included. Thirty patients experienced local recurrence. Univariate and multivariate analysis showed that tumor site, preoperative and postoperative denosumab treatment, and surgery were significantly associated with local recurrence-free survival. LDH was associated with local recurrence-free survival on univariate analysis only. NLR, mGPS, PNI, LMR, and PLR score did not correlate with the local recurrence rate. In conclusion, NLR, mGPS, PNI, LMR, PLR score, Hb, ALP, and LDH levels are not correlated with the local recurrence rate of GCTB. However, due to the small number of patients included in this study, this result should be re-evaluated in a multicenter study with a larger sample size.
Published: 2023
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25. Reconstruction after Talar Tumor Resection: A Systematic Review

Author: Shinji Tsukamoto, Andreas F. Mavrogenis, Kanya Honoki, Akira Kido, Yuu Tanaka, Hiromasa Fujii, Yoshinori Takakura, Yasuhito Tanaka, and Costantino Errani
Subjects: talus, tumor, reconstruction, talar prosthesis, tibiocalcaneal fusion, arthrodesis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: This systematic review investigated the functional outcomes and complications of reconstruction methods after talar tumor resection. A systematic search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases identified 156 studies, of which 20 (23 patients) were ultimately included. The mean Musculoskeletal Tumor Society scores in the groups reconstructed using tibiocalcaneal fusion (n = 17), frozen autograft (n = 1), and talar prosthesis (n = 5) were 77.6 (range 66–90), 70, and 90 (range 87–93), respectively. Regarding complications, sensory deficits were observed in one patient (6%) and venous thrombosis in two patients (12%) in the tibiocalcaneal fusion group, while osteoarthritis was observed in one patient (100%) in the frozen autograft group. No complications were observed in the talar prosthesis group. Reconstruction with talar prosthesis seems preferable to conventional tibiocalcaneal fusion after talar tumor resection because it offers better function and fewer complications. However, as this systematic review included only retrospective studies with a small number of patients, its results require re-evaluation in future randomized controlled trials with larger numbers of patients.
Published: 2022
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26. ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion

Author: Chiò, A, Mora, G, Sabatelli, M, Caponnetto, C, Lunetta, C, Traynor, B. J, Johnson, J. O, Nalls, M. A, Calvo, A, Moglia, C, Borghero, G, Trojsi, F, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, F. O, Riva, N, Carrera, P, Giannini, F, Mandrioli, J, Tanel, R, Capasso, M, Tremolizzo, L, Battistini, S, Murru, M. R, Origone, P, Zollino, M, Penco, S, Mazzini, L, D'Alfonso, S, Restagno, G, Brunetti, M, Barberis, M, Conforti, F. L, Logroscino, G, Bartolomei, I, Mancardi, G, Mandich, P, Marinou, K, Sideri, R, Mosca, L, Lauria Pinter, G, Corbo, M, Fini, N, Fasano, A, Arosio, A, Ferrarese, C, Tedeschi, G, Monsurrò, M. R, Piccirillo, G, Femiano, C, Bersano, A, Corrado, L, Bagarotti, A, Spataro, R, Colletti, T, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Ricci, C, Benigni, M, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Manera, U, Bertuzzo, D, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M. G, Floris, G, Cannas, A, Ticca, A, Pugliatti, M, Pirisi, A, Parish, L. D, Occhineri, P, Ortu, E, Cau, T. B, Loi, D, Chiò, A., Mora, G., Sabatelli, M., Caponnetto, C., Lunetta, C., Traynor, B., Johnson, J., Nalls, M., Calvo, A., Moglia, C., Borghero, G., Trojsi, F., LA BELLA, V., Volanti, P., Simone, I., Salvi, F., Logullo, F., Riva, N., Carrera, P., Giannini, F., Mandrioli, J., Tanel, R., Capasso, M., Tremolizzo, L., Battistini, S., Murru, M., Origone, P., Zollino, M., Penco, S., Mazzini, L., D'Alfonso, S., Restagno, G., Brunetti, M., Barberis, M., Conforti, F., Chiò, Adriano, Mora, Gabriele, Sabatelli, Mario, Caponnetto, Claudia, Lunetta, Christian, Traynor, Bryan J, Johnson, Janel O, Nalls, Mike A, Calvo, Andrea, Moglia, Cristina, Borghero, Giuseppe, Trojsi, Francesca, La Bella, Vincenzo, Volanti, Paolo, Simone, Isabella, Salvi, Fabrizio, Logullo, Francesco O, Riva, Nilo, Carrera, Paola, Giannini, Fabio, Mandrioli, Jessica, Tanel, Raffaella, Capasso, Margherita, Tremolizzo, Lucio, Battistini, Stefania, Murru, Maria Rita, Origone, Paola, Zollino, Marcella, Penco, Silvana, Logroscino, G, Bartolomei, I, Mancardi, G, Mandich, P, Marinou, K, Sideri, R, Mosca, L, Pinter, Gl, Corbo, M, Fini, N, Fasano, A, Arosio, A, Ferrarese, C, Tedeschi, Gioacchino, Monsurro', Maria Rosaria, Piccirillo, G, Femiano, C, Bersano, A, Corrado, L, Bagarotti, A, Spataro, R, Colletti, T, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Ricci, C, Benigni, M, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Manera, U, Bertuzzo, D, Tanel, R, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, Mg, Floris, G, Cannas, A, Ticca, A, Pugliatti, M, Pirisi, A, Parish, Ld, Occhineri, P, Ortu, E, Cau, Tb, Loi, D, Mazzini, Letizia, D'Alfonso, Sandra, Restagno, Gabriella, Brunetti, Maura, Barberis, Marco, Conforti, Francesca L., Chiò, A, Mora, G, Sabatelli, M, Caponnetto, C, Lunetta, C, Traynor, B, Johnson, J, Nalls, M, Calvo, A, Moglia, C, Borghero, G, Trojsi, F, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, F, Riva, N, Carrera, P, Giannini, F, Mandrioli, J, Capasso, M, Tremolizzo, L, Battistini, S, Murru, M, Origone, P, Zollino, M, Penco, S, Mazzini, L, D'Alfonso, S, Restagno, G, Brunetti, M, Barberis, M, Conforti, F, Lauria Pinter, G, Tedeschi, G, Monsurrò, M, Marrosu, M, Parish, L, and Cau, T
Subjects: Male, 0301 basic medicine, Aging, C9ORF72, Genetic Association Studie, 030105 genetics & heredity, Biology, Settore MED/03 - GENETICA MEDICA, 03 medical and health sciences, 0302 clinical medicine, C9orf72, medicine, Allele, Amyotrophic lateral sclerosis, Amyotrophic lateral sclerosi, Aged, Ataxin-2, Regulator gene, ATXN2, Phenotype, Neuroscience (all), Medicine (all), Developmental Biology, Geriatrics and Gerontology, Neurology (clinical), Genetics, DNA Repeat Expansion, Protein, General Neuroscience, Middle Aged, medicine.disease, 3. Good health, C9orf72 Protein, Italy, Population study, Female, Settore MED/26 - Neurologia, Trinucleotide repeat expansion, 030217 neurology & neurosurgery, Human
Abstract: There are indications that both familial amyotrophic lateral sclerosis (ALS) and sporadic ALS phenotype and prognosis are partly regulated by genetic and environmental factors, supporting the theory that ALS is a multifactorial disease. The aim of this article was to assess the role of ATXN2 intermediate length repeats in a large series of Italian and Sardinian ALS patients and controls carrying a pathogenetic C9ORF72 GGGGCC hexanucleotide repeat. A total of 1972 ALS cases were identified through the database of the Italian ALS Genetic consortium, a collaborative effort including 18 ALS centers throughout Italy. The study population included: (1) 276 Italian and 57 Sardinian ALS cases who carried the C9ORF72 expansion; (2) 1340 Italian and 299 Sardinian ALS cases not carrying the C9ORF72 expansion. A total of healthy 1043 controls were also assessed. Most Italian and Sardinian cases and controls were homozygous for 22/22 or 23/23 repeats or heterozygous for 22/23 repeats of the ATXN2 gene. ATXN2 intermediate length repeats alleles (≥28) were detected in 3 (0.6%) Italian ALS cases carrying the C9ORF72 expansion, in none of the Sardinian ALS cases carrying the expansion, in 60 (4.3%) Italian cases not carrying the expansion, and in 6 (2.0%) Sardinian ALS cases without C9ORF72 expansion. Intermediate length repeat alleles were found in 12 (1.5%) Italian controls and 1 (0.84%) Sardinian controls. Therefore, ALS patients with C9ORF72 expansion showed a lower frequency of ATXN2 polyQ intermediate length repeats than both controls (Italian cases, p = 0.137; Sardinian cases, p = 0.0001) and ALS patients without C9ORF72 expansion (Italian cases, p = 0.005; Sardinian cases, p = 0.178). In our large study on Italian and Sardinian ALS patients with C9ORF72 GGGGCC hexanucleotide repeat expansion, compared to age-, gender- and ethnic-matched controls, ATXN2 polyQ intermediate length does not represent a modifier of ALS risk, differently from non- C9ORF72 mutated patients.
Published: 2015

27. Outcome of Reoperation for Local Recurrence Following En Bloc Resection for Bone Giant Cell Tumor of the Extremity

Author: Shinji Tsukamoto, Andreas F. Mavrogenis, Suraj Hindiskere, Kanya Honoki, Akira Kido, Hiromasa Fujii, Tomoya Masunaga, Yasuhito Tanaka, Pramod S. Chinder, Davide Maria Donati, and Costantino Errani
Subjects: giant cell tumor of bone, en bloc resection, denosumab, local recurrence, MSTS score, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: En bloc resection is typically performed to treat giant cell tumors of bone (GCTB), particularly when curettage can be challenging owing to extensive bone cortex destruction with soft tissue extension. Few reports have addressed the clinical outcomes after reoperation for local recurrence in patients with GCTB who underwent en bloc resection. In this multicenter retrospective study, we investigated local recurrence, distant metastasis, malignant transformation, mortality, and limb function in patients treated for local recurrence following en bloc resection for GCTB. Among 205 patients who underwent en bloc resection for GCTB of the extremities between 1980 and 2021, we included 29 with local recurrence. En bloc resection was performed for large tumors with soft tissue extension, pathological fractures with joint invasion, complex fractures, and dispensable bones, such as the proximal fibula and distal ulna. Local re-recurrence, distant metastasis, malignant transformation, and mortality rates were 41.4% (12/29), 34.5% (10/29), 6.9% (2/29), and 6.9% (2/29), respectively. The median Musculoskeletal Tumor Society score was 26 (interquartile range, 23–28). The median follow-up period after surgery for local recurrence was 70.1 months (interquartile range, 40.5–123.8 months). Local recurrence following en bloc resection for GCTB could indicate an aggressive GCTB, necessitating careful follow-up.
Published: 2022
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28. Complex decongestive therapy in lymphedema: report from an Interdisciplinary Center

Author: Costantino Eretta, Elisa Tridoni, Serena Isaia, Arianna Pigoni, Azzurra Vatteroni, Laura Impieri, and Claudio Bianchi
Subjects: Lymphedema, disability, Complex Decongestive Therapy (CDT), complex decongestive physiotherapy, Manual Lymphatic Drainage (MLD), Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Lymphedema is a chronic and worsening disease due to an abnormal accumulation of liquids, with a high protein content in the interstitial space. The disease is characterized by an insufficient flow of lymphatic fluid, which manifests as edema, inflammation, and fibrosis, all the way up to the stiffening of the affected tissues. Because it's a chronic and increasing disease, the treatment is highly complex. The literature shows that the treatment must be multidisciplinary and it is necessary to combine multiple techniques, such as manual lymphatic drainage, mechanical lymphatic drainage, elasto-compressive bandages and other complementary techniques up to surgical treatment in the most advanced forms which are not responsive to physical therapy. Furthermore, the disease is characterized by episodes of cellulitis, that may lead to infectious complications because the lymphatic function becomes insufficient. A condition of local immunodeficiency is created due to the crucial role that the lymphatic system covers with immune defenses, therefore creates a fertile ground for infections caused by small skin wounds, insect bites, animal scratches, nail fungus, blood draws. Therefore, particular attention is paid to skin folds and interdigital spaces for which hygiene is necessary using neutral detergents, drying by dabbing, and applying emollient creams for skin hydration. Unfortunately, such practices of prevention and care are often underestimated. We provide education of the patient on self-care, such as the self-bandage and the correct application of the elasto-compressed stoking. For wrapping the bandage, it is advisable to wear a glove or a special sock. The multilayer bandages are used in the first decongestant phase while over time the elastic stocking is the best aid for the management of lymphedema. Our clinic is a referral center for diagnosis, treatment and surgical therapy, where patients come for surgical evaluation. Since 2016 we have systematically collected clinical data and volume evaluation of more than 600 cases affected by lymphedema and lipoedema of all stages. They have been treated with complex decongestive therapy for 4 hours a day, 15 consecutive days, subsequently a maintenance of once a week for 3 months, then once a month for 6 months. Of more than 600 patients treated, only 150 were submitted to surgery (lymphatic venous anastomosis, fasciotomy or liposuction, chylothorax and chyloperitoneal shunt, reconstructive plastic of external genitalia). Complex decongestive interdisciplinary therapy, when properly performed can stabilize the lymphedema patient situation, reducing the stage and ensuring a good quality of life.
Published: 2023
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29. CHCH10 mutations in an Italian cohort of familial and sporadic amyotrophic lateral sclerosis patients

Author: Chiò, A, Mora, G, Sabatelli, M, Caponnetto, C, Traynor, B. J, Johnson, J. O, Nalls, M. A, Calvo, A, Moglia, C, Borghero, G, Monsurrò, M. R, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, F. O, Nilo, R, Battistini, S, Mandrioli, J, Tanel, R, Murru, M. R, Mandich, P, Zollino, M, Conforti, F. L, Brunetti, M, Barberis, M, Restagno, G, Penco, S, Lunetta, C, Giannini, F, Ricci, C, Mancardi, G, Bartolomei, I, Corbo, M, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Ossola, I, Logroscino, G, Tedeschi, G, Pugliatti, M, Pinter, G. L, Glynn, S, Gibbs, J. R, Cammarosano, S, Canosa, A, Manera, U, Bertuzzo, D, Ilardi, A, Marinou, K, Sideri, R, Pisano, F, Spataro, R, Colletti, T, Floris, G, Cannas, A, Piras, V, Marrosu, F, Marrosu, M. G, Parish, L. D, Ticca, A, Pirisi, A, Ortu, E, Cau, T. B, Loi, D, Traccis, S, Fini, N, Georgoulopoulou, E, Casale, F, Marrali, G, Fuda, G, Solamone, P, Maestri, E, Mazzei, R, Cristillo, V, Puddu, R, Costantino, E, Pani, C, Caredda, C, Origone, P, Mosca, L, Capasso, M, Turri, M, Petrucci, A, Tremolizzo, L, Santarelli, M., Chiò, A, Mora, G, Sabatelli, M, Caponnetto, C, Traynor, B, Johnson, J, Nalls, M, Calvo, A, Moglia, C, Borghero, G, Monsurrò, M, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, F, Nilo, R, Battistini, S, Mandrioli, J, Tanel, R, Murru, M, Mandich, P, Zollino, M, Conforti, F, Brunetti, M, Barberis, M, Restagno, G, Penco, S, Lunetta, C, Giannini, F, Ricci, C, Mancardi, G, Bartolomei, I, Corbo, M, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Ossola, I, Logroscino, G, Tedeschi, G, Pugliatti, M, Pinter, G, Glynn, S, Gibbs, J, Cammarosano, S, Canosa, A, Manera, U, Bertuzzo, D, Ilardi, A, Marinou, K, Sideri, R, Pisano, F, Spataro, R, Colletti, T, Floris, G, Cannas, A, Piras, V, Marrosu, F, Marrosu, M, Parish, L, Ticca, A, Pirisi, A, Ortu, E, Cau, T, Loi, D, Traccis, S, Fini, N, Georgoulopoulou, E, Casale, F, Marrali, G, Fuda, G, Solamone, P, Maestri, E, Mazzei, R, Cristillo, V, Puddu, R, Costantino, E, Pani, C, Caredda, C, Origone, P, Mosca, L, Capasso, M, Turri, M, Petrucci, A, Tremolizzo, L, Santarelli, M, Chiò, Adriano, Mora, Gabriele, Sabatelli, Mario, Caponnetto, Claudia, Traynor, Bryan J., Johnson, Janel O., Nalls, Mike A., Calvo, Andrea, Moglia, Cristina, Borghero, Giuseppe, Monsurro', Maria Rosaria, La Bella, Vincenzo, Volanti, Paolo, Simone, Isabella, Salvi, Fabrizio, Logullo, Francesco O., Nilo, Riva, Battistini, Stefania, Mandrioli, Jessica, Tanel, Raffaella, Murru, Maria Rita, Mandich, Paola, Zollino, Marcella, Conforti, Francesca L., Brunetti, Maura, Barberis, Marco, Restagno, Gabriella, Penco, Silvana, Lunetta, Christian, Giannini, Fabio, Ricci, Claudia, Mancardi, Gianluigi, Bartolomei, Ilaria, Corbo, Massimo, Conte, Amelia, Luigetti, Marco, Lattante, Serena, Marangi, Giuseppe, Ossola, Irene, Logroscino, Giancarlo, Tedeschi, Gioacchino, Pugliatti, Maura, Pinter, Giuseppe Lauria, Glynn, Shannon, Gibbs, J. Raphael, Cammarosano, Stefania, Canosa, Antonio, Manera, Umberto, Bertuzzo, Davide, Ilardi, Altonio, Marinou, Kalliopi, Sideri, Riccardo, Pisano, Fabrizio, Spataro, Rossella, Colletti, Tiziana, Floris, Gianluca, Cannas, Antonino, Piras, Valeria, Marrosu, Francesco, Marrosu, Maria Giovanna, Parish, Leslie D., Ticca, Anna, Pirisi, Angelo, Ortu, Enzo, Cau, Tea B., Loi, Daniela, Traccis, Sebastiano, Fini, Nicola, Georgoulopoulou, Eleni, Casale, Federico, Marrali, Giuseppe, Fuda, Giuseppe, Solamone, Paolina, Maestri, Eleonora, Mazzei, Rosalucia, Cristillo, Viviana, Puddu, Roberta, Costantino, Emanuela, Pani, Carla, Caredda, Carla, Origone, Paola, Mosca, Lorena, Capasso, Margherita, Turri, Mara, Petrucci, Antonio, Tremolizzo, Luico, Santarelli, Marialaura, Chiò, A., Mora, G., Sabatelli, M., Caponnetto, C., Traynor, B., Johnson, J., Nalls, M., Calvo, A., Moglia, C., Borghero, G., Monsurrò, M., LA BELLA, V., Volanti, P., Simone, I., Salvi, F., Logullo, F., Nilo, R., Battistini, S., Mandrioli, J., Tanel, R., Murru, M., Mandich, P., Zollino, M., Conforti, F., Brunetti, M., Barberis, M., Restagno, G., Penco, S., Lunetta, C., Giannini, F., Ricci, C., Mancardi, G., Bartolomei, I., Corbo, M., Conte, A., Luigetti, M., Lattante, S., Marangi, G., Ossola, I., Logroscino, G., Tedeschi, G., Pugliatti, M., Pinter, G., Glynn, S., Gibbs, J., Cammarosano, S., Canosa, A., Manera, U., Bertuzzo, D., Ilardi, A., Marinou, K., Sideri, R., Pisano, F., Spataro, R., Colletti, T., Floris, G., Cannas, A., Piras, V., Marrosu, F., Marrosu, M., Parish, L., Ticca, A., Pirisi, A., Ortu, E., Cau, T., Loi, D., Traccis, S., Fini, N., Georgoulopoulou, E., Casale, F., Marrali, G., Fuda, G., Solamone, P., Maestri, E., Mazzei, R., Cristillo, V., Puddu, R., Costantino, E., Pani, C., Caredda, C., Origone, P., Mosca, L., Capasso, M., Turri, M., Petrucci, A., Tremolizzo, L., and Santarelli, M.
Subjects: Male, Aging, Pediatrics, medicine.medical_specialty, Pathology, Amyotrophic lateral sclerosis, CHCHD10, Familial, Sporadic, Aged, Amyotrophic Lateral Sclerosis, Cohort Studies, Female, Frontotemporal Dementia, Genetic Predisposition to Disease, Humans, Italy, Middle Aged, Mitochondrial Proteins, Genetic Association Studies, Mutation, Genetic Association Studie, Disease, Settore MED/03 - GENETICA MEDICA, medicine.disease_cause, Exon, mental disorders, medicine, Mitochondrial Protein, Dementia, Neurology (clinical), Neuroscience (all), Developmental Biology, Geriatrics and Gerontology, Amyotrophic lateral sclerosi, business.industry, General Neuroscience, medicine.disease, 3. Good health, Cohort, Cohort Studie, business, Human, Frontotemporal dementia, Cohort study
Abstract: Mutations in CHCHD10 have recently been described as a cause of frontotemporal dementia (FTD) comorbid with amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the frequency and clinical characteristics of CHCHD10 mutations in Italian patients diagnosed with familial (n= 64) and apparently sporadic ALS (n= 224). Three apparently sporadic patients were found to carry c.100C>T (p.Pro34Ser) heterozygous variant in the exon 2 of CHCHD10. This mutation had been previously described in 2 unrelated French patients with FTD-ALS. However, our patients had a typical ALS, without evidence of FTD, cerebellar or extrapyramidal signs, or sensorineural deficits. We confirm that CHCHD10 mutations account for ~1% of Italian ALS patients and are a cause of disease in subjects without dementia or other atypical clinical signs.
Published: 2015

30. Union, complication, reintervention and failure rates of surgical techniques for large diaphyseal defects: a systematic review and meta-analysis

Author: Pietro Feltri, Luca Solaro, Alessandro Di Martino, Christian Candrian, Costantino Errani, and Giuseppe Filardo
Subjects: Medicine, Science
Abstract: Abstract To understand the potential and limitations of the different available surgical techniques used to treat large, long-bone diaphyseal defects by focusing on union, complication, re-intervention, and failure rates, summarizing the pros and cons of each technique. A literature search was performed on PubMed, Web of Science, and Cochrane databases up to March 16th, 2022; Inclusion criteria were clinical studies written in English, of any level of evidence, with more than five patients, describing the treatment of diaphyseal bone defects. The primary outcome was the analysis of results in terms of primary union, complication, reintervention, and failure rate of the four major groups of techniques: bone allograft and autograft, bone transport, vascularized and non-vascularized fibular graft, and endoprosthesis. The statistical analysis was carried out according to Neyeloff et al., and the Mantel–Haenszel method was used to provide pooled rates across the studies. The influence of the various techniques on union rates, complication rates, and reintervention rates was assessed by a z test on the pooled rates with their corresponding 95% CIs. Assessment of risk of bias and quality of evidence was based on Downs and Black’s “Checklist for Measuring Quality” and Rob 2.0 tool. Certainty of yielded evidence was evaluated with the GRADE system. Seventy-four articles were included on 1781 patients treated for the reconstruction of diaphyseal bone defects, 1496 cases in the inferior limb, and 285 in the upper limb, with trauma being the main cause of bone defect. The meta-analysis identified different outcomes in terms of results and risks. Primary union, complications, and reinterventions were 75%, 26% and 23% for bone allografts and autografts, 91%, 62% and 19% for the bone transport group, and 78%, 38% and 23% for fibular grafts; mean time to union was between 7.8 and 8.9 months in all these groups. Results varied according to the different aetiologies, endoprosthesis was the best solution for tumour, although with a 22% failure rate, while trauma presented a more composite outcome, with fibular grafts providing a faster time to union (6.9 months), while cancellous and cortical-cancellous grafts caused less complications, reinterventions, and failures. The literature about this topic has overall limited quality. However, important conclusions can be made: Many options are available to treat critical-size defects of the diaphysis, but no one appears to be an optimal solution in terms of a safe, satisfactory, and long-lasting outcome. Regardless of the bone defect cause, bone transport techniques showed a better primary union rate, but bone allograft and autograft had fewer complication, reintervention, and failure rates than the other techniques. The specific lesion aetiology represents a critical aspect influencing potential and limitations and therefore the choice of the most suitable technique to address the challenging large diaphyseal defects.
Published: 2022
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31. Enhancing maternal sensitivity and infant attachment security with video feedback: An exploratory study in Italy

Author: Cassibba, R., Castoro, G., Costantino, E., Sette, G., and IJzendoorn, M.H. van
Abstract: This study aims to explore whether a short-term and attachment-based video-feedback intervention, the Video-Feedback Intervention to Promote Positive Parenting With Discussions on the Representational Level (VIPP-R; F. Juffer, M.J. Bakermans-Kranenburg, & M.H. van IJzendoorn, 2008), might be effective in enhancing maternal sensitivity and in promoting infants' attachment security in an Italian sample of dyads with primiparous mothers. Moreover, we explore whether the effectiveness of VIPP-R might be different for parents with insecure attachment representations who might be most in need of preventive intervention, as compared to parents who already have a more balanced and secure state of mind. Thirty-two infants (40% female) and their mothers participated in the study. The sample was divided into an intervention group (n = 16) and a comparison group (n = 16). At 6 and 13 months of age, the Adult Attachment Interview (AAI; M. Main, N. Kaplan, & J. Cassidy, 1985) was administered. Moreover, a 30-min mother-infant play situation was videotaped and coded for maternal sensitivity with the Emotional Availability Scales (Z. Biringen, J. Robinson, & R.N. Emde, 2000). At 13 months of age, the Strange Situation Procedure (M.D.S. Ainsworth, M.D. Blehar, E. Waters, & S. Wall, 1978) was used to assess the security of mother-infant attachment. Results revealed a significant interaction effect between intervention and AAI security for infant attachment security; moreover, main effects of AAI security and intervention for maternal sensitivity were found. The VIPP-R appears effective in enhancing maternal sensitivity and infant attachment security, although only mothers with an insecure attachment representation may benefit from the intervention.
Published: 2014

32. Risk factors of fracture following curettage for bone giant cell tumors of the extremities

Author: Shinji Tsukamoto, Andreas F. Mavrogenis, Manabu Akahane, Kanya Honoki, Akira Kido, Yasuhito Tanaka, Davide Maria Donati, and Costantino Errani
Subjects: Giant cell tumor of bone, Curettage, Fracture, Denosumab, Cement, Bone grafting, Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract Background Following curettage of giant cell tumor of bone (GCTB), it is common to fill the cavity with polymethylmethacrylate (PMMA) bone cement, bone allograft, or artificial bone to maintain bone strength; however, there is a 2–14% risk of postoperative fractures. We conducted this retrospective study to clarify the risk factors for fractures after curettage for GCTB of the extremities. Methods This study included 284 patients with GCTBs of the extremities who underwent curettage at our institutions between 1980 and 2018 after excluding patients whose cavities were not filled with anything or who had additional plate fixation. The tumor cavity was filled with PMMA bone cement alone (n = 124), PMMA bone cement and bone allograft (n = 81), bone allograft alone (n = 63), or hydroxyapatite graft alone (n = 16). Results Fractures after curettage occurred in 10 (3.5%) patients, and the median time from the curettage to fracture was 3.5 months (interquartile range [IQR], 1.8–8.3 months). The median postoperative follow-up period was 86.5 months (IQR, 50.3–118.8 months). On univariate analysis, patients who had GCTB of the proximal or distal femur (1-year fracture-free survival, 92.5%; 95% confidence interval [CI]: 85.8–96.2) presented a higher risk for postoperative fracture than those who had GCTB at another site (100%; p = 0.0005). Patients with a pathological fracture at presentation (1-year fracture-free survival, 88.2%; 95% CI: 63.2–97.0) presented a higher risk for postoperative fracture than those without a pathological fracture at presentation (97.8%; 95% CI: 95.1–99.0; p = 0.048). Patients who received bone grafting (1-year fracture-free survival, 99.4%; 95% CI: 95.7–99.9) had a lower risk of postoperative fracture than those who did not receive bone grafting (94.4%; 95% CI: 88.7–97.3; p = 0.003). Conclusions For GCTBs of the femur, especially those with pathological fracture at presentation, bone grafting after curettage is recommended to reduce the risk of postoperative fracture. Additional plate fixation should be considered when curettage and cement filling without bone grafting are performed in patients with GCTB of the femur. This should be specially performed for those patients with a pathological fracture at presentation.
Published: 2022
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33. Bone Targeting Agents in Patients with Prostate Cancer: General Toxicities and Osteonecrosis of the Jaw

Author: Veronica Mollica, Giacomo Nuvola, Elisa Tassinari, Maria Concetta Nigro, Andrea Marchetti, Matteo Rosellini, Alessandro Rizzo, Costantino Errani, and Francesco Massari
Subjects: bone metastasis, bone targeting agents, CRPC, denosumab, HSPC, osteonecrosis of the jaw, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Introduction: Bone metastases are the most frequent site of secondary localization of prostate cancer (PCa) and are present in about 90% of cases of advanced disease. Consequently, an adequate management of bone involvement is of pivotal importance in the therapeutic approach and skeletal-related events (SREs) need to be closely monitored and promptly assessed and treated. Bone targeting agents (BTAs), consisting in bisphosphonates and denosumab, are an essential part of the treatment of metastatic prostate cancer that accompanies systemic treatments throughout the most part of the history of the disease. Activity and safety of bone targeting agents: These treatments are correlated to better outcomes in terms of reduction of SREs and, in metastatic castration resistant setting, of increased overall survival (OS), but several important adverse events have to be managed and prevented. Of these, osteonecrosis of the jaw (ONJ) is extremely invalidating and should be managed with a special attention. Discussion: The role of BTAs in prostate cancer is pivotal throughout many stages of the disease, but several toxicities should be quickly recognized and treated. We aim at recollecting evidence on clinical benefit of BTAs, common and specific toxicities, and explore the pathophysiology and clinical aspects of osteonecrosis of the jaw. We present a review of the literature to report the role of the different types of bone targeting agents in the management of prostate cancer with bone metastases with a particular focus on common toxicities and ONJ to recollect current evidences on the activity of these compounds and the correct management of their adverse events.
Published: 2022
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34. ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion

Author: Chiò, A, Mora, G, Sabatelli, M, Caponnetto, C, Lunetta, C, Traynor, B, Johnson, J, Nalls, M, Calvo, A, Moglia, C, Borghero, G, Trojsi, F, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, F, Riva, N, Carrera, P, Giannini, F, Mandrioli, J, Tanel, R, Capasso, M, Tremolizzo, L, Battistini, S, Murru, M, Origone, P, Zollino, M, Penco, S, Mazzini, L, D'Alfonso, S, Restagno, G, Brunetti, M, Barberis, M, Conforti, F, Logroscino, G, Bartolomei, I, Mancardi, G, Mandich, P, Marinou, K, Sideri, R, Mosca, L, Lauria Pinter, G, Corbo, M, Fini, N, Fasano, A, Arosio, A, Ferrarese, C, Tedeschi, G, Monsurrò, M, Piccirillo, G, Femiano, C, Bersano, A, Corrado, L, Bagarotti, A, Spataro, R, Colletti, T, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Ricci, C, Benigni, M, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Manera, U, Bertuzzo, D, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M, Floris, G, Cannas, A, Ticca, A, Pugliatti, M, Pirisi, A, Parish, L, Occhineri, P, Ortu, E, Cau, T, Loi, D, TREMOLIZZO, LUCIO, AROSIO, ALESSANDRO, FERRARESE, CARLO, Loi, D., Chiò, A, Mora, G, Sabatelli, M, Caponnetto, C, Lunetta, C, Traynor, B, Johnson, J, Nalls, M, Calvo, A, Moglia, C, Borghero, G, Trojsi, F, La Bella, V, Volanti, P, Simone, I, Salvi, F, Logullo, F, Riva, N, Carrera, P, Giannini, F, Mandrioli, J, Tanel, R, Capasso, M, Tremolizzo, L, Battistini, S, Murru, M, Origone, P, Zollino, M, Penco, S, Mazzini, L, D'Alfonso, S, Restagno, G, Brunetti, M, Barberis, M, Conforti, F, Logroscino, G, Bartolomei, I, Mancardi, G, Mandich, P, Marinou, K, Sideri, R, Mosca, L, Lauria Pinter, G, Corbo, M, Fini, N, Fasano, A, Arosio, A, Ferrarese, C, Tedeschi, G, Monsurrò, M, Piccirillo, G, Femiano, C, Bersano, A, Corrado, L, Bagarotti, A, Spataro, R, Colletti, T, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Ricci, C, Benigni, M, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Manera, U, Bertuzzo, D, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M, Floris, G, Cannas, A, Ticca, A, Pugliatti, M, Pirisi, A, Parish, L, Occhineri, P, Ortu, E, Cau, T, Loi, D, TREMOLIZZO, LUCIO, AROSIO, ALESSANDRO, FERRARESE, CARLO, and Loi, D.
Abstract: There are indications that both familial amyotrophic lateral sclerosis (ALS) and sporadic ALS phenotype and prognosis are partly regulated by genetic and environmental factors, supporting the theory that ALS is a multifactorial disease. The aim of this article was to assess the role of ATXN2 intermediate length repeats in a large series of Italian and Sardinian ALS patients and controls carrying a pathogenetic C9ORF72 GGGGCC hexanucleotide repeat. A total of 1972 ALS cases were identified through the database of the Italian ALS Genetic consortium, a collaborative effort including 18 ALS centers throughout Italy. The study population included: (1) 276 Italian and 57 Sardinian ALS cases who carried the C9ORF72 expansion; (2) 1340 Italian and 299 Sardinian ALS cases not carrying the C9ORF72 expansion. A total of healthy 1043 controls were also assessed. Most Italian and Sardinian cases and controls were homozygous for 22/22 or 23/23 repeats or heterozygous for 22/23 repeats of the ATXN2 gene. ATXN2 intermediate length repeats alleles (≥28) were detected in 3 (0.6%) Italian ALS cases carrying the C9ORF72 expansion, in none of the Sardinian ALS cases carrying the expansion, in 60 (4.3%) Italian cases not carrying the expansion, and in 6 (2.0%) Sardinian ALS cases without C9ORF72 expansion. Intermediate length repeat alleles were found in 12 (1.5%) Italian controls and 1 (0.84%) Sardinian controls. Therefore, ALS patients with C9ORF72 expansion showed a lower frequency of ATXN2 polyQ intermediate length repeats than both controls (Italian cases, p = 0.137; Sardinian cases, p = 0.0001) and ALS patients without C9ORF72 expansion (Italian cases, p = 0.005; Sardinian cases, p = 0.178). In our large study on Italian and Sardinian ALS patients with C9ORF72 GGGGCC hexanucleotide repeat expansion, compared to age-, gender- and ethnic-matched controls, ATXN2 polyQ intermediate length does not represent a modifier of ALS risk, differently from non-C9ORF72 mutated patients.
Published: 2016

35. Intralesional nerve-sparing surgery versus non-surgical treatment for giant cell tumor of the sacrum

Author: Shinji Tsukamoto, Nikolin Ali, Andreas F. Mavrogenis, Kanya Honoki, Yasuhito Tanaka, Paolo Spinnato, Davide Maria Donati, and Costantino Errani
Subjects: Giant cell tumor of bone, Sacrum, Denosumab, Embolization, Surgery, Intralesional nerve sparing surgery, Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract Background There is no standard treatment for giant cell tumors of the sacrum. We compared the outcomes and complications in patients with sacral giant cell tumors who underwent intralesional nerve-sparing surgery with or without (neo-) adjuvant therapies versus those who underwent non-surgical treatment (denosumab therapy and/or embolization). Methods We retrospectively investigated 15 cases of sacral giant cell tumors treated at two institutions between 2005 and 2020. Nine patients underwent intralesional nerve-sparing surgery with or without (neo-) adjuvant therapies, and six patients received non-surgical treatment. The mean follow-up period was 85 months for the surgical group (range, 25–154 months) and 59 months (range, 17–94 months) for the non-surgical group. Results The local recurrence rate was 44% in the surgical group, and the tumor progression rate was 0% in the non-surgical group. There were two surgery-related complications (infection and bladder laceration) and three denosumab-related complications (apical granuloma of the tooth, stress fracture of the sacroiliac joint, and osteonecrosis of the jaw). In the surgical group, the mean modified Biagini score (bowel, bladder, and motor function) was 0.9; in the non-surgical group, it was 0.5. None of the 11 female patients became pregnant or delivered a baby after developing a sacral giant cell tumor. Conclusions The cure rate of intralesional nerve-sparing surgery is over 50%. Non-surgical treatment has a similar risk of complications to intralesional nerve-sparing surgery and has better functional outcomes than intralesional nerve-sparing surgery, but patients must remain on therapy over time. Based on our results, the decision on the choice of treatment for sacral giant cell tumors could be discussed between the surgeon and the patient based on the tumor size and location.
Published: 2021
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36. Treatment of Bone Metastasis

Author: Costantino Errani
Subjects: n/a, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: The incidence of metastatic bone disease is increasing, as patients with cancer are living longer [...]
Published: 2022
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37. TBK1 is associated with ALS and ALS-FTD in Sardinian patients

Author: Borghero, G, Pugliatti, M, Marrosu, F, Marrosu, M, Murru, M, Floris, G, Cannas, A, Occhineri, P, Cau, T, Loi, D, Ticca, A, Traccis, S, Manera, U, Canosa, A, Moglia, C, Calvo, A, Barberis, M, Brunetti, M, Gibbs, J, Renton, A, Errichiello, E, Zoledziewska, M, Mulas, A, Qian, Y, Din, J, Pliner, H, Traynor, B, Chiò, A, Logullo, F, Simone, I, Logroscino, G, Salvi, F, Bartolomei, I, Capasso, M, Caponnetto, C, Mandich, P, Mancardi, G, Origone, P, Conforti, F, Vita, G, Messina, S, Russo, M, Mora, G, Marinou, K, Sideri, R, Lunetta, C, Penco, S, Mosca, L, Pinter, G, Corbo, M, Riva, N, Carrera, P, Volanti, P, Tremolizzo, L, Ferrarese, C, Fini, N, Fasano, A, Monsurrò, M, Tedeschi, G, Trojsi, F, Piccirillo, G, Cristillo, V, Mazzini, L, D'Alfonso, S, Bersano, A, Corrado, L, Bagarotti, A, La Bella, V, Spataro, R, Colletti, T, Sabatelli, M, Zollino, M, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Giannini, F, Battistini, S, Ricci, C, Benigni, M, Restagno, G, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Bertuzzo, D, Tanel, R, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Pirisi, A, Parish, L, Ortu, E, Ortu, E., TREMOLIZZO, LUCIO, FERRARESE, CARLO, Borghero, G, Pugliatti, M, Marrosu, F, Marrosu, M, Murru, M, Floris, G, Cannas, A, Occhineri, P, Cau, T, Loi, D, Ticca, A, Traccis, S, Manera, U, Canosa, A, Moglia, C, Calvo, A, Barberis, M, Brunetti, M, Gibbs, J, Renton, A, Errichiello, E, Zoledziewska, M, Mulas, A, Qian, Y, Din, J, Pliner, H, Traynor, B, Chiò, A, Logullo, F, Simone, I, Logroscino, G, Salvi, F, Bartolomei, I, Capasso, M, Caponnetto, C, Mandich, P, Mancardi, G, Origone, P, Conforti, F, Vita, G, Messina, S, Russo, M, Mora, G, Marinou, K, Sideri, R, Lunetta, C, Penco, S, Mosca, L, Pinter, G, Corbo, M, Riva, N, Carrera, P, Volanti, P, Tremolizzo, L, Ferrarese, C, Fini, N, Fasano, A, Monsurrò, M, Tedeschi, G, Trojsi, F, Piccirillo, G, Cristillo, V, Mazzini, L, D'Alfonso, S, Bersano, A, Corrado, L, Bagarotti, A, La Bella, V, Spataro, R, Colletti, T, Sabatelli, M, Zollino, M, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Giannini, F, Battistini, S, Ricci, C, Benigni, M, Restagno, G, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Bertuzzo, D, Tanel, R, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Pirisi, A, Parish, L, Ortu, E, Ortu, E., TREMOLIZZO, LUCIO, and FERRARESE, CARLO
Abstract: Recently, mutations in the TANK-binding kinase 1 (TBK1) gene were identified as a cause for amyotrophic lateral sclerosis (ALS) with or without comorbid frontotemporal dementia. We have assessed the frequency and clinical characteristics of TBK1 mutations in a cohort of ALS patients of Sardinian ancestry. Whole-exome sequencing was performed on Hiseq2000 platform (Illumina). Genome analysis Toolkit was used to align and to code variants according to Human Genome (UCSC hg19). Mutation was confirmed with Sanger sequence. In our screening of 186 Sardinian ALS cases, we found 3 (1.6%) patients carrying 3 distinct novel genetic variants: a nonsynonymous SNV c.1150C>T leading to a p.Arg384Thr change in exon 9; a nonsynonymous SNV c.1331G>A causes a p.Arg444Gln change in exon 11; and a frameshift deletion c.2070delG (p.Met690fs) at the exon 20 of the gene leading to a stop at 693 codon. The latter patients also carried missense mutation c.98C>T of the SQSTM1 gene causing a substitution of an arginine with a valine at the position 33 (p.Arg33Val). All variants were found to be deleterious according to in silico predictions. All cases were apparently sporadic and one of them showed frontotemporal dementia associated to ALS. These mutations were not found in 2 cohorts of 6780 ethnic-matched controls. We have found that TBK1 mutations account for 1.6% of Sardinian ALS cases. Our data support the notion that TBK1 is a novel ALS gene, providing important evidence complementary to the first descriptions.
Published: 2015

38. ATXN2 is a modifier of phenotype in ALS patients of Sardinian ancestry

Author: Borghero, G, Pugliatti, M, Marrosu, F, Marrosu, M, Murru, M, Floris, G, Cannas, A, Parish, L, Cau, T, Loi, D, Ticca, A, Traccis, S, Manera, U, Canosa, A, Moglia, C, Calvo, A, Barberis, M, Brunetti, M, Renton, A, Nalls, M, Traynor, B, Restagno, G, Chiò, A, Logullo, F, Simone, I, Logroscino, G, Salvi, F, Bartolomei, I, Capasso, M, Caponnetto, C, Mancardi, G, Mandich, P, Origone, P, Conforti, F, Mora, G, Marinou, K, Sideri, R, Lunetta, C, Penco, S, Mosca, L, Nilo, R, Pinter, G, Corbo, M, Volanti, P, Mandrioli, J, Fini, N, Georgoulopoulou, E, Tremolizzo, L, Monsurròad, M, Tedeschi, G, Cristillo, V, la Bella, V, Spataro, R, Colletti, T, Sabatelli, M, Zollino, M, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Giannini, F, Battistini, S, Ricci, C, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Bertuzzo, D, Tanel, R, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Pirisi, A, Occhineri, P, Ortu, E, Logullo, FO, Conforti, FL, Pinter, GL, Monsurròad, MR, Borghero, G, Pugliatti, M, Marrosu, F, Marrosu, M, Murru, M, Floris, G, Cannas, A, Parish, L, Cau, T, Loi, D, Ticca, A, Traccis, S, Manera, U, Canosa, A, Moglia, C, Calvo, A, Barberis, M, Brunetti, M, Renton, A, Nalls, M, Traynor, B, Restagno, G, Chiò, A, Logullo, F, Simone, I, Logroscino, G, Salvi, F, Bartolomei, I, Capasso, M, Caponnetto, C, Mancardi, G, Mandich, P, Origone, P, Conforti, F, Mora, G, Marinou, K, Sideri, R, Lunetta, C, Penco, S, Mosca, L, Nilo, R, Pinter, G, Corbo, M, Volanti, P, Mandrioli, J, Fini, N, Georgoulopoulou, E, Tremolizzo, L, Monsurròad, M, Tedeschi, G, Cristillo, V, la Bella, V, Spataro, R, Colletti, T, Sabatelli, M, Zollino, M, Conte, A, Luigetti, M, Lattante, S, Marangi, G, Santarelli, M, Petrucci, A, Giannini, F, Battistini, S, Ricci, C, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Ilardi, A, Bertuzzo, D, Tanel, R, Pisano, F, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Pirisi, A, Occhineri, P, Ortu, E, Logullo, FO, Conforti, FL, Pinter, GL, and Monsurròad, MR
Abstract: Intermediate-length CAG expansions (encoding 27-33 glutamines, polyQ) of the Ataxin2 (ATXN2) gene represent a risk factor for amyotrophic lateral sclerosis (ALS). Recently, it has been proposed that ≥31 CAG expansions may influence ALS phenotype. We assessed whether ATXN2 intermediate-length polyQ expansions influence ALS phenotype in a series of 375 patients of Sardinian ancestry. Controls were 247 neurologically healthy subjects, resident in the study area, age- and gender-matched to cases. The frequency of ≥31 polyQ ATNX2 repeats was significantly more common in ALS cases (4 patients vs. no control, p = 0.0001). All patients with ≥31 polyQ repeats had a spinal onset versus 73.3% of patients with <31 polyQ repeats. Patients with an increased number of polyQ repeats have a shorter survival than those with <31 repeats (1.2 vs. 4.2 years, p = 0.035). In this large series of ALS patients of Sardinian ancestry, we have found that ≥31 polyQ repeats of the ATXN2 gene influenced patients' phenotype, being associated to a spinal onset and a significantly shorter survival.
Published: 2015

39. What’s new in musculoskeletal oncology

Author: Costantino Errani, Andreas F. Mavrogenis, and Shinji Tsukamoto
Subjects: Musculoskeletal tumors, Bone tumors, Soft tissue tumors, Soft tissue sarcomas, Bone sarcomas, Metastatic bone tumor, Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract We reviewed the recent literature related to primary musculoskeletal tumors and metastatic bone tumors. With regard to primary bone tumors, computer navigation systems and three-dimensional-printed prostheses seem to be new treatment options, especially in challenging anatomical locations, such as the sacrum and pelvis. Regarding the treatment of giant cell tumor of bone, recent studies have suggested that denosumab administration is related to a higher local recurrence rate following curettage, but a lower local recurrence rate following en bloc resection. In addition, there was no difference in the local recurrence rate at five years after surgery between short-term and long-term denosumab therapy. With regard to soft tissue tumors, percutaneous cryoablation appears to be a new treatment option for extra-abdominal desmoid tumors, with encouraging results. Regarding soft tissue sarcomas, a negative surgical margin of
Published: 2021
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40. Upfront surgery is not advantageous compared to more conservative treatments such as observation or medical treatment for patients with desmoid tumors

Author: Shinji Tsukamoto, Piergiuseppe Tanzi, Andreas F. Mavrogenis, Manabu Akahane, Akira Kido, Yasuhito Tanaka, Marilena Cesari, Davide Maria Donati, Alessandra Longhi, and Costantino Errani
Subjects: Desmoid tumor, Aggressive fibromatosis, Active surveillance, Surgery, MSTS functional score, Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract Background This study compared the clinical and functional outcomes of patients initially treated with observation or medical treatment with those of patients treated with local treatment (surgery alone or surgery with adjuvant radiotherapy) to confirm whether observation or medical treatment is an appropriate first-line management approach for patients with desmoid tumors. Methods We retrospectively reviewed the medical records of 99 patients with histologically confirmed primary desmoid tumors treated between 1978 and 2018. The median follow-up period was 57 months. We evaluated event-free survival, defined as the time interval from the date of initial diagnosis to the date of specific change in treatment strategy or recurrence or the last follow-up. Results An event (specific change in treatment strategy or recurrence) occurred in 28 patients (28.3%). No significant difference in event-free survival was found between the first-line observation/medical treatment and local treatment groups (p = 0.509). The median Musculoskeletal Tumor Society score of the patients treated with first-line local treatment was 29 (interquartile range [IQR], 23–30), whereas that of the patients managed with first-line observation or medical treatment was 21 (IQR, 19–29.5). First-line observation or medical treatment was more frequently chosen for larger tumors (p = 0.045). In the patients treated with local treatment, local recurrence was not related to the surgical margin (p = 0.976). Conclusion Upfront surgery is not advantageous compared to more conservative treatments such as observation or medical treatment for patients with desmoid tumors.
Published: 2021
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41. Outcome of lung metastases due to bone giant cell tumor initially managed with observation

Author: Shinji Tsukamoto, Giovanni Ciani, Andreas F. Mavrogenis, Cristina Ferrari, Manabu Akahane, Yasuhito Tanaka, Michele Rocca, Alessandra Longhi, and Costantino Errani
Subjects: Giant cell tumor of bone, Observation, Metastasectomy, Denosumab, Metastasis, Lungs, Orthopedic surgery, RD701-811, Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract Background The outcomes of patients with lung metastases from giant cell tumor of bone (GCTB) vary from spontaneous regression to uncontrolled growth. To investigate whether observation is an appropriate first-line management approach for patients with lung metastases from GCTB, we evaluated the outcomes of patients who were initially managed by observation. Methods We retrospectively reviewed the data of 22 patients with lung metastases from histologically confirmed GCTB who received observation as a first-line treatment approach. The median follow-up period was 116 months. Results Disease progression occurred in 12 patients (54.5%). The median interval between the discovery of lung metastases and progression was 8 months. Eight patients underwent metastasectomy following initial observation. The median interval between the discovery of lung metastases and treatment by metastasectomy was 13.5 months. None of the patients experienced spontaneous regression. Of the 22 patients, 36.4% needed a metastasectomy, and 9.1% required denosumab treatment during the course of the follow-up period. Disease progression occurred in 45.5% of the 11 patients with lung nodules ≤ 5 mm, while all five of the patients with lung nodules > 5 mm experienced disease progression. Progression-free survival was significantly worse in the group with lung nodules > 5 mm compared to the group with lung nodules ≤ 5 mm (p = 0.022). Conclusions Observation is a safe first-line method of managing patients with lung metastases from GCTB. According to radiological imaging, approximately half of the patients progressed, and approximately half required a metastasectomy or denosumab treatment. However, patients with lung nodules > 5 mm should receive careful observation because of the high rate of disease progression in this group.
Published: 2020
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42. Infections of Tumor Prostheses: An Updated Review on Risk Factors, Microbiology, Diagnosis, and Treatment Strategies

Author: Andreas G. Tsantes, Pavlos Altsitzioglou, Dimitrios V. Papadopoulos, Drago Lorenzo, Carlo Luca Romanò, Thami Benzakour, Shinji Tsukamoto, Costantino Errani, Andrea Angelini, and Andreas F. Mavrogenis
Subjects: tumor prostheses, infections, diagnosis, management, prevention, Biology (General), QH301-705.5
Abstract: Several causes contribute to the high infection rate in tumor prostheses, including extensive tissue dissection and patients’ immunosuppression due to the neoplastic disease. Most of these infections develop within the first 2 years following surgery with 70% of them occurring during the first year, while they are often associated with a low pathogen burden. The pathogenesis of infections in tumor prostheses is linked to bacteria developing in biofilms. Approximately half of them are caused by Staphylococcus spp., followed by Streptococcus spp., Enterococcus spp., and Enterobacteriaceae spp., while multiple pathogens may be isolated in up to 25% of the cases, with coagulase-negative Staphylococci (CoNS) and Enterococccus spp. being the most frequent pair. Although early detection and timely management are essential for complete resolution of these challenging infections, prompt diagnosis is problematic due to the highly varying clinical symptoms and the lack of specific preoperative and intraoperative diagnostic tests. Surgical management with one- or two-stage revision surgery is the mainstay for successful eradication of these infections. The recent advances in laboratory diagnostics and the development of biofilm-resistant prostheses over the past years have been areas of great interest, as research is now focused on prevention strategies. The aim of this study is to review and consolidate the current knowledge regarding the epidemiology, risk factors, microbiology, and diagnosis of infections of tumor prostheses, and to review the current concepts for their treatment and outcomes.
Published: 2023
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43. A new computerized tomography classification to evaluate response to Denosumab in giant cell tumors in the extremities

Author: Laura Campanacci, Andrea Sambri, Manuel Ricardo Medellin, Pietro Cimatti, Costantino Errani, and Davide Maria Donati
Subjects: Orthopedic surgery, RD701-811
Abstract: Objectives: The aim of this study was to describe the cohort of patients who have been treated with Denosumab as neoadjuvant therapy prior to surgery for aggressive giant cell tumor of bone in the extremities, to evaluate the radiological responses to Denosumab comparing Choi criteria and a newly described computerized tomography (CT) classification, and to evaluate the risk of local recurrence after intralesional curettage or radical excision. Methods: We retrospectively evaluated 36 patients (20 females and 16 males; mean age at diagnosis 36 years (range, 18–64)) treated with neoadjuvant Denosumab therapy prior to surgery for aggressive giant cell tumor of bone in the extremities. The radiological responses to Denosumab treatment were analyzed on the preoperative images after the neoadjuvant course with the Choi criteria and with a newly proposed classification based on CT. All these images were independently reviewed by two of the researchers. Surgical intervention methods were noted and local recurrence rates were evaluated. The correlation between radiological response amount and local recurrence were analyzed for both Choi criteria and the new CT classification. Results: Denosumab was administered for a mean of 21 weeks (range 7–133). Five patients also had a short postoperative course. According to Choi criteria there was a radiological response in 32 patients (89%), while the new CT classification identified responses in all the 36 patients (100%). The identification of changes after 7 weeks of treatment was higher using the CT classification compared to Choi criteria (p = 0.043 vs p = 0.462). The surgical interventions after Denosumab comprised curettage in 29 patients (74%) and resection in 7 (26%). Local recurrence was higher in patients managed with intralesional curettage than in those treated with en bloc resection (55.1% vs 0%, p
Published: 2019
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44. Acid-Induced Inflammatory Cytokines in Osteoblasts: A Guided Path to Osteolysis in Bone Metastasis

Author: Gemma Di Pompo, Costantino Errani, Robert Gillies, Laura Mercatali, Toni Ibrahim, Jacopo Tamanti, Nicola Baldini, and Sofia Avnet
Subjects: bone metastasis, intratumoral acidosis, osteoclasts, osteoblasts, interleukin 8, interleukin 6, Biology (General), QH301-705.5
Abstract: Bone metastasis (BM) is a dismal complication of cancer that frequently occurs in patients with advanced carcinomas and that often manifests as an osteolytic lesion. In bone, tumor cells promote an imbalance in bone remodeling via the release of growth factors that, directly or indirectly, stimulate osteoclast resorption activity. However, carcinoma cells are also characterized by an altered metabolism responsible for a decrease of extracellular pH, which, in turn, directly intensifies osteoclast bone erosion. Here, we speculated that tumor-derived acidosis causes the osteoblast–osteoclast uncoupling in BM by modulating the pro-osteoclastogenic phenotype of osteoblasts. According to our results, a low pH recruits osteoclast precursors and promotes their differentiation through the secretome of acid-stressed osteoblasts that includes pro-osteoclastogenic factors and inflammatory mediators, such as RANKL, M-CSF, TNF, IL-6, and, above the others, IL-8. The treatment with the anti-IL-6R antibody tocilizumab or with an anti-IL-8 antibody reverted this effect. Finally, in a series of BM patients, circulating levels of the osteolytic marker TRACP5b significantly correlated with IL-8. Our findings brought out that tumor-derived acidosis promotes excessive osteolysis at least in part by inducing an inflammatory phenotype in osteoblasts, and these results strengthen the use of anti-IL-6 or anti-IL-8 strategies to treat osteolysis in BM.
Published: 2021
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45. Suárez, filósofo barroco / Suárez, baroque philosophe

Author: Costantino Esposito
Subjects: Philosophy. Psychology. Religion, Christianity, BR1-1725
Abstract: ResumenMi intervención desea verificar la posibilidad de delinear algunos rasgos característicos de un pensamiento “barroco” (siglos XVI-XVII), sin limitarse por un lado a una analogía débil con el estilo arquitectónico y pictórico, y por otro lado sin tener la presunción de proponer una etiqueta historiográfica demasiado general e indistinta. La perspectiva escogida por el autor es la de centrase en algunos problemas que emergen en las obras de algunos teólogos y filósofos jesuitas operantes en la época posterior al Concilio de Trento (como Roberto Bellarmino y Francisco Suárez). En particular, se afronta el problema de la relación entre “lo natural” y “lo sobrenatural”, en el intento de tomar distancias tanto de la solución luterana como de la solución “pelagiana” (o semi-pelagiana). Siguiendo a Bellarmino se saca a la luz la discusión sobre el estado de la naturaleza humana: si incluso después del pecado es posible rastrear en el hombre la justicia original, esto es, si el hombre pecador es todavía capax Dei. Siguiendo a Suárez se saca a la luz la tentativa de institucionalizar el nexo entre naturaleza/sobrenaturaleza mediante la relación circular entre metafísica y teología: por un lado la metafísica –la scientia transcendens que tiene como objeto propio el concepto generalísimo de ens ut sic y la essentia del ente como aptitudo ad existendum– es la condición de posibilidad noética de la teología (entendida como teología natural o filosófica); de otra parte la teología (revelada) es la secreta condición de posibilidad de la metafísica en su totalidad. En este plexo de problemas se delinea el posible carácter “barroco” de un pensamiento a la vez tardo-escolástico y moderno.Palabras clave: Pensamiento barroco; Roberto Bellarmino S.J.; Francisco Suárez S.J.; Martín Lutero; Concilio de Trento; Metafísica jesuítica; Teología jesuítica; Ontologia moderna; Natural y Sobrenatural. AbstractThe contribution aims at verifying the possibility to outline some distinctive characteristics of a “baroque” thought (16th-17th centuries), trying nor to reduce it in a weak analogy with the architectural or pictorial style neither labelling it with a too general and vague sense. The author intends to focus some questions raised in the works of some jesuit theologians and philosophers in the period after the Council of Trent, as Roberto Bellarmino and Francisco Suárez. In particular, the relationship between “natural” and “supernatural” will be put forward, getting some distance from both the “lutheran” and the “pelagian” solution. According to Bellarmino we highlight the late-scholastic problem of the constitution of human nature: if it is possible, after the fall due to the original sin, to retrace the original justice and so if the man remains "capax Dei”. Following Suárez’ thought is highlighted the attempt to "institutionalize" the link between nature and supernature, through the circular relationship between metaphysics and theology. On one side, the metaphysics – the scientia transcendens whose object is the supergeneral concept of ens ut sic and the essence of being as aptitudo ad existendum – is the epistemological condition of possibility of theology (intended as natural or philosophical theology); on the other side, the revealed theology is the secret condition of the possibility of the whole metaphysics. Thus, from the interweaving of these problems emerges the "baroque" feature of a philosophical thought, which is at the same time scholastic and early modern.Keywords: Baroque Thought; Roberto Bellarmino S.J.; Francisco Suárez S.J.; Martin Luther; Council of Trent; Jesuit Metaphysics; Jesuit Theology; Modern Ontology; Natural and Supernatural.DOI: https://doi.org/10.17398/1886-4945.12.25
Published: 2017

46. Staphylococcus aureus colonization modulates tic expression and the host immune response in a girl with Tourette syndrome

Author: Costantino eEftimiadi, Gemma eEftimiadi, and PierGiuseppe eVinai
Subjects: Staphylococcus aureus, Streptococcus pyogenes, Tourette Syndrome, pandas, ASO, Dopamine receptor autoantibodies, Psychiatry, RC435-571
Abstract: A 9-year-old girl with Tourette syndrome and increased antibody levels against Streptococcus pyogenes was monitored longitudinally for the presence of nasopharyngeal bacteria, specific antibody titers, and autoimmunity directed against brain antigens. Microbiological monitoring indicated that the child was an intermittent Staphylococcus aureus nasopharyngeal carrier. Clinical improvements in motor tic frequency and severity were observed during the S. aureus colonization phase, and were temporally correlated with the downregulation of anti-streptococcal and anti-D1/D2 dopamine receptor antibody production. After decolonization, clinical conditions reverted to the poor scores previously observed, suggesting a possible role of the immune response in bacterial clearance as a trigger of symptom recrudescence. These findings imply that a cause-effect relationship exists between S. aureus colonization and tic improvement, as well as between bacterial decolonization and tic exacerbation. Understanding the impact of S. aureus on the host adaptive immune response and the function of autoantibodies in the pathogenesis of Tourette syndrome may alter approaches for managing autoimmune neuropsychiatric and tic disorders.
Published: 2016
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47. Impaired Aβ Clearance: A Potential Link between Atherosclerosis and Alzheimer’s Disease

Author: Ajay eGupta and Costantino eIadecola
Subjects: Atherosclerosis, Dementia, Vascular, A beta peptide, Alzheimer's disease (AD), A beta clearance, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Alzheimer’s Disease (AD) and atherosclerosis remain two of the largest public health burdens in the world today. Although traditionally considered distinct pathological entities, mounting epidemiologic, clinical and experimental evidence suggests that cerebrovascular atherosclerosis and AD interact reciprocally to disrupt brain structure and function. Whereas the hypoperfusion and hypoxia caused by atherosclerosis of cerebral vessels may enhance the production of Aβ, a peptide central to AD pathology, Aβ, in turn, may promote formation of atherosclerotic lesions through vascular oxidative stress and endothelial dysfunction leading to additional vascular damage. Here, we briefly review evidence suggesting that impaired clearance of Aβ is an additional, simultaneously occurring mechanism by which AD and cerebrovascular disease may be causally linked. We examine the literature supporting mechanisms by which flow-limiting large-artery stenosis, arterial stiffening and microvascular dysfunction could contribute to AD pathophysiology by impairing Aβ clearance and elevating brain levels of Aβ. Finally, we highlight the need for further research to improve our understanding of the complex interactions of AD and atherosclerosis with Aβ clearance, which may ultimately serve to guide the development of novel diagnostic and therapeutic approaches for this devastating and highly prevalent condition.
Published: 2015
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48. The role of microglia and myeloid immune cells in acute cerebral ischemia

Author: Corinne eBenakis, Lidia eGarcia-Bonilla, Costantino eIadecola, and Josef eAnrather
Subjects: Microglia, Monocytes, Myeloid Cells, Neutrophils, cerebral ischemia, tissue macrophages, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: The immune response to acute cerebral ischemia is a major contributor to stroke pathobiology. The inflammatory response is characterized by the participation of brain resident cells and peripheral leukocytes. Microglia in the brain and monocytes/neutrophils in the periphery, have a prominent role in initiating, sustaining and resolving post-ischemic inflammation. In this review we aim to summarize recent literature concerning the origins, fate and role of microglia, monocyte and neutrophil in models of cerebral ischemia and to discuss their relevance for human stroke.
Published: 2015
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49. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

Author: Aude Nicolas, Kevin P. Kenna, Alan E. Renton, Nicola Ticozzi, Faraz Faghri, Ruth Chia, Janice A. Dominov, Brendan J. Kenna, Mike A. Nalls, Pamela Keagle, Alberto M. Rivera, Wouter van Rheenen, Natalie A. Murphy, Joke J.F.A. van Vugt, Joshua T. Geiger, Rick A. Van der Spek, Hannah A. Pliner, null Shankaracharya, Bradley N. Smith, Giuseppe Marangi, Simon D. Topp, Yevgeniya Abramzon, Athina Soragia Gkazi, John D. Eicher, Aoife Kenna, Gabriele Mora, Andrea Calvo, Letizia Mazzini, Nilo Riva, Jessica Mandrioli, Claudia Caponnetto, Stefania Battistini, Paolo Volanti, Vincenzo La Bella, Francesca L. Conforti, Giuseppe Borghero, Sonia Messina, Isabella L. Simone, Francesca Trojsi, Fabrizio Salvi, Francesco O. Logullo, Sandra D’Alfonso, Lucia Corrado, Margherita Capasso, Luigi Ferrucci, Cristiane de Araujo Martins Moreno, Sitharthan Kamalakaran, David B. Goldstein, Aaron D. Gitler, Tim Harris, Richard M. Myers, Hemali Phatnani, Rajeeva Lochan Musunuri, Uday Shankar Evani, Avinash Abhyankar, Michael C. Zody, Julia Kaye, Steven Finkbeiner, Stacia K. Wyman, Alex LeNail, Leandro Lima, Ernest Fraenkel, Clive N. Svendsen, Leslie M. Thompson, Jennifer E. Van Eyk, James D. Berry, Timothy M. Miller, Stephen J. Kolb, Merit Cudkowicz, Emily Baxi, Michael Benatar, J. Paul Taylor, Evadnie Rampersaud, Gang Wu, Joanne Wuu, Giuseppe Lauria, Federico Verde, Isabella Fogh, Cinzia Tiloca, Giacomo P. Comi, Gianni Sorarù, Cristina Cereda, Philippe Corcia, Hannu Laaksovirta, Liisa Myllykangas, Lilja Jansson, Miko Valori, John Ealing, Hisham Hamdalla, Sara Rollinson, Stuart Pickering-Brown, Richard W. Orrell, Katie C. Sidle, Andrea Malaspina, John Hardy, Andrew B. Singleton, Janel O. Johnson, Sampath Arepalli, Peter C. Sapp, Diane McKenna-Yasek, Meraida Polak, Seneshaw Asress, Safa Al-Sarraj, Andrew King, Claire Troakes, Caroline Vance, Jacqueline de Belleroche, Frank Baas, Anneloor L.M.A. ten Asbroek, José Luis Muñoz-Blanco, Dena G. Hernandez, Jinhui Ding, J. Raphael Gibbs, Sonja W. Scholz, Mary Kay Floeter, Roy H. Campbell, Francesco Landi, Robert Bowser, Stefan M. Pulst, John M. Ravits, Daniel J.L. MacGowan, Janine Kirby, Erik P. Pioro, Roger Pamphlett, James Broach, Glenn Gerhard, Travis L. Dunckley, Christopher B. Brady, Neil W. Kowall, Juan C. Troncoso, Isabelle Le Ber, Kevin Mouzat, Serge Lumbroso, Terry D. Heiman-Patterson, Freya Kamel, Ludo Van Den Bosch, Robert H. Baloh, Tim M. Strom, Thomas Meitinger, Aleksey Shatunov, Kristel R. Van Eijk, Mamede de Carvalho, Maarten Kooyman, Bas Middelkoop, Matthieu Moisse, Russell L. McLaughlin, Michael A. Van Es, Markus Weber, Kevin B. Boylan, Marka Van Blitterswijk, Rosa Rademakers, Karen E. Morrison, A. Nazli Basak, Jesús S. Mora, Vivian E. Drory, Pamela J. Shaw, Martin R. Turner, Kevin Talbot, Orla Hardiman, Kelly L. Williams, Jennifer A. Fifita, Garth A. Nicholson, Ian P. Blair, Guy A. Rouleau, Jesús Esteban-Pérez, Alberto García-Redondo, Ammar Al-Chalabi, Ekaterina Rogaeva, Lorne Zinman, Lyle W. Ostrow, Nicholas J. Maragakis, Jeffrey D. Rothstein, Zachary Simmons, Johnathan Cooper-Knock, Alexis Brice, Stephen A. Goutman, Eva L. Feldman, Summer B. Gibson, Franco Taroni, Antonia Ratti, Cinzia Gellera, Philip Van Damme, Wim Robberecht, Pietro Fratta, Mario Sabatelli, Christian Lunetta, Albert C. Ludolph, Peter M. Andersen, Jochen H. Weishaupt, William Camu, John Q. Trojanowski, Vivianna M. Van Deerlin, Robert H. Brown, Leonard H. van den Berg, Jan H. Veldink, Matthew B. Harms, Jonathan D. Glass, David J. Stone, Pentti Tienari, Vincenzo Silani, Adriano Chiò, Christopher E. Shaw, Bryan J. Traynor, John E. Landers, Isabella Simone, Giancarlo Logroscino, Ilaria Bartolomei, Maria Rita Murru, Emanuela Costantino, Carla Pani, Roberta Puddu, Carla Caredda, Valeria Piras, Stefania Tranquilli, Stefania Cuccu, Daniela Corongiu, Maurizio Melis, Antonio Milia, Francesco Marrosu, Maria Giovanna Marrosu, Gianluca Floris, Antonino Cannas, Gianluigi Mancardi, Paola Origone, Paola Mandich, Sebastiano Cavallaro, Kalliopi Marinou, Riccardo Sideri, Silvana Penco, Lorena Mosca, Giuseppe Lauria Pinter, Massimo Corbo, Paola Carrera, Nicola Fini, Antonio Fasano, Lucio Tremolizzo, Alessandro Arosio, Carlo Ferrarese, Gioacchino Tedeschi, Maria Rosaria Monsurrò, Giovanni Piccirillo, Cinzia Femiano, Anna Ticca, Enzo Ortu, Rossella Spataro, Tiziana Colletti, Marcella Zollino, Amelia Conte, Marco Luigetti, Serena Lattante, Marialuisa Santarelli, Antonio Petrucci, Maura Pugliatti, Angelo Pirisi, Leslie D. Parish, Patrizia Occhineri, Fabio Giannini, Claudia Ricci, Michele Benigni, Tea B. Cau, Daniela Loi, Cristina Moglia, Maura Brunetti, Marco Barberis, Gabriella Restagno, Federico Casale, Giuseppe Marrali, Giuseppe Fuda, Irene Ossola, Stefania Cammarosano, Antonio Canosa, Antonio Ilardi, Umberto Manera, Maurizio Grassano, Raffaella Tanel, Fabrizio Pisano, Neil A. Shneider, Stephen Goutman, Siddharthan Chandran, Suvankar Pal, George Manousakis, Stanley H. Appel, Ericka Simpson, Leo Wang, Summer Gibson, Richard Bedlack, David Lacomis, Dhruv Sareen, Alexander Sherman, Lucie Bruijn, Michelle Penny, Andrew S. Allen, Stanley Appel, Richard S. Bedlack, Braden E. Boone, Robert Brown, John P. Carulli, Alessandra Chesi, Wendy K. Chung, Elizabeth T. Cirulli, Gregory M. Cooper, Julien Couthouis, Aaron G. Day-Williams, Patrick A. Dion, Yujun Han, Sebastian D. Hayes, Angela L. Jones, Jonathan Keebler, Brian J. Krueger, Brittany N. Lasseigne, Shawn E. Levy, Yi-Fan Lu, Tom Maniatis, Slavé Petrovski, Alya R. Raphael, Zhong Ren, Katherine B. Sims, John F. Staropoli, Lindsay L. Waite, Quanli Wang, Jack R. Wimbish, Winnie W. Xin, Justin Kwan, James R. Broach, Ximena Arcila-Londono, Edward B. Lee, Noah Zaitlen, Gregory A. Cox, Steve Finkbeiner, Efthimios Dardiotis, Eran Hornstein, Daniel J. MacGowan, Terry Heiman-Patterson, Molly G. Hammell, Nikolaos A. Patsopoulos, Joshua Dubnau, Avindra Nath, Stacia Wyman, Alexander LeNail, Jenny Van Eyk, Stephan Züchner, Rebecca Schule, Jacob McCauley, Sumaira Hussain, Anne Cooley, Marielle Wallace, Christine Clayman, Richard Barohn, Jeffrey Statland, John Ravits, Andrea Swenson, Carlayne Jackson, Jaya Trivedi, Shaida Khan, Jonathan Katz, Liberty Jenkins, Ted Burns, Kelly Gwathmey, James Caress, Corey McMillan, Lauren Elman, Erik Pioro, Jeannine Heckmann, Yuen So, David Walk, Samuel Maiser, Jinghui Zhang, Fabiola De Marchi, Stefania Corti, Mauro Ceroni, Gabriele Siciliano, Massimiliano Filosto, Maurizio Inghilleri, Silvia Peverelli, Claudia Colombrita, Barbara Poletti, Luca Maderna, Roberto Del Bo, Stella Gagliardi, Giorgia Querin, Cinzia Bertolin, Viviana Pensato, Barbara Castellotti, Vincent Meininger, Gérard Besson, Emmeline Lagrange, Pierre Clavelou, Nathalie Guy, Philippe Couratier, Patrick Vourch, Véronique Danel, Emilien Bernard, Gwendal Lemasson, Ahmad Al Kheifat, Peter Andersen, Adriano Chio, Jonathan Cooper-Knock, Annelot Dekker, Vivian Drory, Alberto Garcia Redondo, Marc Gotkine, Winston Hide, Alfredo Iacoangeli, Jonathan Glass, Kevin Kenna, Matthew Kiernan, John Landers, Russell McLaughlin, Jonathan Mill, Miguel Mitne Neto, Mattieu Moisse, Jesus Mora Pardina, Karen Morrison, Stephen Newhouse, Susana Pinto, Sara Pulit, Pamela Shaw, Chris Shaw, William Sproviero, Gijs Tazelaar, Philip van Damme, Leonard van den Berg, Rick van der Spek, Kristel van Eijk, Michael van Es, Joke van Vugt, Jan Veldink, Mayana Zatz, Denis C. Bauer, Natalie A. Twine, Department of Neurosciences, Pentti Tienari / Principal Investigator, Neurologian yksikkö, Research Programs Unit, Clinicum, Research Programme for Molecular Neurology, University of Helsinki, Medicum, Department of Pathology, HUS Neurocenter, Nicolas A., Kenna K.P., Renton A.E., Ticozzi N., Faghri F., Chia R., Dominov J.A., Kenna B.J., Nalls M.A., Keagle P., Rivera A.M., van Rheenen W., Murphy N.A., van Vugt J.J.F.A., Geiger J.T., Van der Spek R.A., Pliner H.A., Shankaracharya, Smith B.N., Marangi G., Topp S.D., Abramzon Y., Gkazi A.S., Eicher J.D., Kenna A., Logullo F.O., Simone I.L., Logroscino G., Salvi F., Bartolomei I., Borghero G., Murru M.R., Costantino E., Pani C., Puddu R., Caredda C., Piras V., Tranquilli S., Cuccu S., Corongiu D., Melis M., Milia A., Marrosu F., Marrosu M.G., Floris G., Cannas A., Capasso M., Caponnetto C., Mancardi G., Origone P., Mandich P., Conforti F.L., Cavallaro S., Mora G., Marinou K., Sideri R., Penco S., Mosca L., Lunetta C., Pinter G.L., Corbo M., Riva N., Carrera P., Volanti P., Mandrioli J., Fini N., Fasano A., Tremolizzo L., Arosio A., Ferrarese C., Trojsi F., Tedeschi G., Monsurro M.R., Piccirillo G., Femiano C., Ticca A., Ortu E., La Bella V., Spataro R., Colletti T., Sabatelli M., Zollino M., Conte A., Luigetti M., Lattante S., Santarelli M., Petrucci A., Pugliatti M., Pirisi A., Parish L.D., Occhineri P., Giannini F., Battistini S., Ricci C., Benigni M., Cau T.B., Loi D., Calvo A., Moglia C., Brunetti M., Barberis M., Restagno G., Casale F., Marrali G., Fuda G., Ossola I., Cammarosano S., Canosa A., Ilardi A., Manera U., Grassano M., Tanel R., Pisano F., Mazzini L., Messina S., D'Alfonso S., Corrado L., Ferrucci L., Harms M.B., Goldstein D.B., Shneider N.A., Goutman S.A., Simmons Z., Miller T.M., Chandran S., Pal S., Manousakis G., Appel S.H., Simpson E., Wang L., Baloh R.H., Gibson S.B., Bedlack R., Lacomis D., Sareen D., Sherman A., Bruijn L., Penny M., Moreno C.D.A.M., Kamalakaran S., Allen A.S., Boone B.E., Brown R.H., Carulli J.P., Chesi A., Chung W.K., Cirulli E.T., Cooper G.M., Couthouis J., Day-Williams A.G., Dion P.A., Gitler A.D., Glass J.D., Han Y., Harris T., Hayes S.D., Jones A.L., Keebler J., Krueger B.J., Lasseigne B.N., Levy S.E., Lu Y.-F., Maniatis T., McKenna-Yasek D., Myers R.M., Petrovski S., Pulst S.M., Raphael A.R., Ravits J.M., Ren Z., Rouleau G.A., Sapp P.C., Sims K.B., Staropoli J.F., Waite L.L., Wang Q., Wimbish J.R., Xin W.W., Phatnani H., Kwan J., Broach J., Arcila-Londono X., Lee E.B., Van Deerlin V.M., Fraenkel E., Ostrow L.W., Baas F., Zaitlen N., Berry J.D., Malaspina A., Fratta P., Cox G.A., Thompson L.M., Finkbeiner S., Dardiotis E., Hornstein E., MacGowan D.J.L., Heiman-Patterson T., Hammell M.G., Patsopoulos N.A., Dubnau J., Nath A., Musunuri R.L., Evani U.S., Abhyankar A., Zody M.C., Kaye J., Wyman S.K., LeNail A., Lima L., Rothstein J.D., Svendsen C.N., Van Eyk J.E., Maragakis N.J., Kolb S.J., Cudkowicz M., Baxi E., Benatar M., Taylor J.P., Wu G., Rampersaud E., Wuu J., Rademakers R., Zuchner S., Schule R., McCauley J., Hussain S., Cooley A., Wallace M., Clayman C., Barohn R., Statland J., Swenson A., Jackson C., Trivedi J., Khan S., Katz J., Jenkins L., Burns T., Gwathmey K., Caress J., McMillan C., Elman L., Pioro E.P., Heckmann J., So Y., Walk D., Maiser S., Zhang J., Silani V., Gellera C., Ratti A., Taroni F., Lauria G., Verde F., Fogh I., Tiloca C., Comi G.P., Soraru G., Cereda C., De Marchi F., Corti S., Ceroni M., Siciliano G., Filosto M., Inghilleri M., Peverelli S., Colombrita C., Poletti B., Maderna L., Del Bo R., Gagliardi S., Querin G., Bertolin C., Pensato V., Castellotti B., Camu W., Mouzat K., Lumbroso S., Corcia P., Meininger V., Besson G., Lagrange E., Clavelou P., Guy N., Couratier P., Vourch P., Danel V., Bernard E., Lemasson G., Laaksovirta H., Myllykangas L., Jansson L., Valori M., Ealing J., Hamdalla H., Rollinson S., Pickering-Brown S., Orrell R.W., Sidle K.C., Hardy J., Singleton A.B., Johnson J.O., Arepalli S., Polak M., Asress S., Al-Sarraj S., King A., Troakes C., Vance C., de Belleroche J., ten Asbroek A.L.M.A., Munoz-Blanco J.L., Hernandez D.G., Ding J., Gibbs J.R., Scholz S.W., Floeter M.K., Campbell R.H., Landi F., Bowser R., Kirby J., Pamphlett R., Gerhard G., Dunckley T.L., Brady C.B., Kowall N.W., Troncoso J.C., Le Ber I., Heiman-Patterson T.D., Kamel F., Van Den Bosch L., Strom T.M., Meitinger T., Shatunov A., Van Eijk K.R., de Carvalho M., Kooyman M., Middelkoop B., Moisse M., McLaughlin R.L., Van Es M.A., Weber M., Boylan K.B., Van Blitterswijk M., Morrison K.E., Basak A.N., Mora J.S., Drory V.E., Shaw P.J., Turner M.R., Talbot K., Hardiman O., Williams K.L., Fifita J.A., Nicholson G.A., Blair I.P., Esteban-Perez J., Garcia-Redondo A., Al-Chalabi A., Al Kheifat A., Andersen P.M., Chio A., Cooper-Knock J., Dekker A., Redondo A.G., Gotkine M., Hide W., Iacoangeli A., Kiernan M., Landers J.E., Mill J., Neto M.M., Pardina J.M., Newhouse S., Pinto S., Pulit S., Robberecht W., Shaw C., Sproviero W., Tazelaar G., Van Damme P., van den Berg L.H., van Vugt J., Veldink J.H., Zatz M., Bauer D.C., Twine N.A., Rogaeva E., Zinman L., Brice A., Feldman E.L., Ludolph A.C., Weishaupt J.H., Trojanowski J.Q., Stone D.J., Tienari P., Shaw C.E., Traynor B.J., ITALSGEN Consortium, Genomic Translation ALS Care GTAC, ALS Sequencing Consortium, NYGC ALS Consortium, Answer ALS Fdn, Clinical Res ALS Related Disorders, SLAGEN Consortium, French ALS Consortium, Project MinE ALS Sequencing Consor, Medical Research Council (MRC), ANS - Complex Trait Genetics, Human Genetics, ARD - Amsterdam Reproduction and Development, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Università cattolica del Sacro Cuore [Roma] (Unicatt), Centre référent Sclérose Latérale Amyotrophique [CHRU Montpellier] (SLA CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1), Lunar and Planetary Laboratory [Tucson] (LPL), University of Arizona, Università degli studi di Torino (UNITO), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), New York Genome Center [New York], New York Genome Center, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), St Jude Children's Research Hospital, Howard Hughes Medical Institute [Chevy Chase] (HHMI), Howard Hughes Medical Institute (HHMI), Centre de compétence de la Sclérose Latérale Amyotrophique [CHRU Tours] (SLA CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), University College of London [London] (UCL), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), King‘s College London, University of New Haven [Connecticut], Princeton University, Laboratoire de Biochimie [CHRU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Helmholtz-Zentrum München (HZM), University Medical Center [Utrecht], Deutsches Forschungszentrum für Künstliche Intelligenz GmbH = German Research Center for Artificial Intelligence (DFKI), Mayo Clinic [Jacksonville], Trinity College Dublin, Maurice Wohl Clinical Neuroscience Institut, Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Repositório da Universidade de Lisboa, Nicolas, A, Kenna, K, Renton, A, Ticozzi, N, Faghri, F, Chia, R, Dominov, J, Kenna, B, Nalls, M, Keagle, P, Rivera, A, van Rheenen, W, Murphy, N, van Vugt, J, Geiger, J, van der Spek, R, Pliner, H, Shankaracharya, N, Smith, B, Marangi, G, Topp, S, Abramzon, Y, Gkazi, A, Eicher, J, Kenna, A, Logullo, F, Simone, I, Logroscino, G, Salvi, F, Bartolomei, I, Borghero, G, Murru, M, Costantino, E, Pani, C, Puddu, R, Caredda, C, Piras, V, Tranquilli, S, Cuccu, S, Corongiu, D, Melis, M, Milia, A, Marrosu, F, Marrosu, M, Floris, G, Cannas, A, Capasso, M, Caponnetto, C, Mancardi, G, Origone, P, Mandich, P, Conforti, F, Cavallaro, S, Mora, G, Marinou, K, Sideri, R, Penco, S, Mosca, L, Lunetta, C, Pinter, G, Corbo, M, Riva, N, Carrera, P, Volanti, P, Mandrioli, J, Fini, N, Fasano, A, Tremolizzo, L, Arosio, A, Ferrarese, C, Trojsi, F, Tedeschi, G, Monsurrò, M, Piccirillo, G, Femiano, C, Ticca, A, Ortu, E, La Bella, V, Spataro, R, Colletti, T, Sabatelli, M, Zollino, M, Conte, A, Luigetti, M, Lattante, S, Santarelli, M, Petrucci, A, Pugliatti, M, Pirisi, A, Parish, L, Occhineri, P, Giannini, F, Battistini, S, Ricci, C, Benigni, M, Cau, T, Loi, D, Calvo, A, Moglia, C, Brunetti, M, Barberis, M, Restagno, G, Casale, F, Marrali, G, Fuda, G, Ossola, I, Cammarosano, S, Canosa, A, Ilardi, A, Manera, U, Grassano, M, Tanel, R, Pisano, F, Mazzini, L, Messina, S, D'Alfonso, S, Corrado, L, Ferrucci, L, Harms, M, Goldstein, D, Shneider, N, Goutman, S, Simmons, Z, Miller, T, Chandran, S, Pal, S, Manousakis, G, Appel, S, Simpson, E, Wang, L, Baloh, R, Gibson, S, Bedlack, R, Lacomis, D, Sareen, D, Sherman, A, Bruijn, L, Penny, M, Moreno, C, Kamalakaran, S, Allen, A, Boone, B, Brown, R, Carulli, J, Chesi, A, Chung, W, Cirulli, E, Cooper, G, Couthouis, J, Day-Williams, A, Dion, P, Gitler, A, Glass, J, Han, Y, Harris, T, Hayes, S, Jones, A, Keebler, J, Krueger, B, Lasseigne, B, Levy, S, Lu, Y, Maniatis, T, McKenna-Yasek, D, Myers, R, Petrovski, S, Pulst, S, Raphael, A, Ravits, J, Ren, Z, Rouleau, G, Sapp, P, Sims, K, Staropoli, J, Waite, L, Wang, Q, Wimbish, J, Xin, W, Phatnani, H, Kwan, J, Broach, J, Arcila-Londono, X, Lee, E, Van Deerlin, V, Fraenkel, E, Ostrow, L, Baas, F, Zaitlen, N, Berry, J, Malaspina, A, Fratta, P, Cox, G, Thompson, L, Finkbeiner, S, Dardiotis, E, Hornstein, E, Macgowan, D, Heiman-Patterson, T, Hammell, M, Patsopoulos, N, Dubnau, J, Nath, A, Musunuri, R, Evani, U, Abhyankar, A, Zody, M, Kaye, J, Wyman, S, Lenail, A, Lima, L, Rothstein, J, Svendsen, C, Van Eyk, J, Maragakis, N, Kolb, S, Cudkowicz, M, Baxi, E, Benatar, M, Taylor, J, Wu, G, Rampersaud, E, Wuu, J, Rademakers, R, Züchner, S, Schule, R, Mccauley, J, Hussain, S, Cooley, A, Wallace, M, Clayman, C, Barohn, R, Statland, J, Swenson, A, Jackson, C, Trivedi, J, Khan, S, Katz, J, Jenkins, L, Burns, T, Gwathmey, K, Caress, J, Mcmillan, C, Elman, L, Pioro, E, Heckmann, J, So, Y, Walk, D, Maiser, S, Zhang, J, Silani, V, Gellera, C, Ratti, A, Taroni, F, Lauria, G, Verde, F, Fogh, I, Tiloca, C, Comi, G, Sorarù, G, Cereda, C, De Marchi, F, Corti, S, Ceroni, M, Siciliano, G, Filosto, M, Inghilleri, M, Peverelli, S, Colombrita, C, Poletti, B, Maderna, L, Del Bo, R, Gagliardi, S, Querin, G, Bertolin, C, Pensato, V, Castellotti, B, Camu, W, Mouzat, K, Lumbroso, S, Corcia, P, Meininger, V, Besson, G, Lagrange, E, Clavelou, P, Guy, N, Couratier, P, Vourch, P, Danel, V, Bernard, E, Lemasson, G, Laaksovirta, H, Myllykangas, L, Jansson, L, Valori, M, Ealing, J, Hamdalla, H, Rollinson, S, Pickering-Brown, S, Orrell, R, Sidle, K, Hardy, J, Singleton, A, Johnson, J, Arepalli, S, Polak, M, Asress, S, Al-Sarraj, S, King, A, Troakes, C, Vance, C, de Belleroche, J, ten Asbroek, A, Muñoz-Blanco, J, Hernandez, D, Ding, J, Gibbs, J, Scholz, S, Floeter, M, Campbell, R, Landi, F, Bowser, R, Kirby, J, Pamphlett, R, Gerhard, G, Dunckley, T, Brady, C, Kowall, N, Troncoso, J, Le Ber, I, Kamel, F, Van Den Bosch, L, Strom, T, Meitinger, T, Shatunov, A, Van Eijk, K, de Carvalho, M, Kooyman, M, Middelkoop, B, Moisse, M, Mclaughlin, R, Van Es, M, Weber, M, Boylan, K, Van Blitterswijk, M, Morrison, K, Basak, A, Mora, J, Drory, V, Shaw, P, Turner, M, Talbot, K, Hardiman, O, Williams, K, Fifita, J, Nicholson, G, Blair, I, Esteban-Pérez, J, García-Redondo, A, Al-Chalabi, A, Al Kheifat, A, Andersen, P, Chio, A, Cooper-Knock, J, Dekker, A, Redondo, A, Gotkine, M, Hide, W, Iacoangeli, A, Kiernan, M, Landers, J, Mill, J, Neto, M, Pardina, J, Newhouse, S, Pinto, S, Pulit, S, Robberecht, W, Shaw, C, Sproviero, W, Tazelaar, G, van Damme, P, van den Berg, L, van Eijk, K, van Es, M, Veldink, J, Zatz, M, Bauer, D, Twine, N, Rogaeva, E, Zinman, L, Brice, A, Feldman, E, Ludolph, A, Weishaupt, J, Trojanowski, J, Stone, D, Tienari, P, Chiò, A, Traynor, B, Nicolas, Aude, Kenna, Kevin P, Renton, Alan E, Ticozzi, Nicola, Faghri, Faraz, Chia, Ruth, Dominov, Janice A, Kenna, Brendan J, Nalls, Mike A, Keagle, Pamela, Rivera, Alberto M, van Rheenen, Wouter, Murphy, Natalie A, van Vugt, Joke J F A, Geiger, Joshua T, Van der Spek, Rick A, Pliner, Hannah A, Shankaracharya, Null, Smith, Bradley N, Marangi, Giuseppe, Topp, Simon D, Abramzon, Yevgeniya, Gkazi, Athina Soragia, Eicher, John D, Kenna, Aoife, Mora, Gabriele, Calvo, Andrea, Mazzini, Letizia, Riva, Nilo, Mandrioli, Jessica, Caponnetto, Claudia, Battistini, Stefania, Volanti, Paolo, La Bella, Vincenzo, Conforti, Francesca L, Borghero, Giuseppe, Messina, Sonia, Simone, Isabella L, Trojsi, Francesca, Salvi, Fabrizio, Logullo, Francesco O, D'Alfonso, Sandra, Corrado, Lucia, Capasso, Margherita, Ferrucci, Luigi, Logullo, Fo, Murru, Mr, Marrosu, Mg, Conforti, Fl, Pinter, Gl, Tedeschi, Gioacchino, Monsurrò, Maria Rosaria, Parish, Ld, Cau, Tb, Moreno, Cristiane de Araujo Martin, Kamalakaran, Sitharthan, Goldstein, David B, Gitler, Aaron D, Harris, Tim, Myers, Richard M, Phatnani, Hemali, Musunuri, Rajeeva Lochan, Evani, Uday Shankar, Abhyankar, Avinash, Zody, Michael C, Kaye, Julia, Finkbeiner, Steven, Wyman, Stacia K, Lenail, Alex, Lima, Leandro, Fraenkel, Ernest, Svendsen, Clive N, Thompson, Leslie M, Van Eyk, Jennifer E, Berry, James D, Miller, Timothy M, Kolb, Stephen J, Cudkowicz, Merit, Baxi, Emily, Benatar, Michael, Taylor, J Paul, Rampersaud, Evadnie, Wu, Gang, Wuu, Joanne, Lauria, Giuseppe, Verde, Federico, Fogh, Isabella, Tiloca, Cinzia, Comi, Giacomo P, Sorarù, Gianni, Cereda, Cristina, Corcia, Philippe, Laaksovirta, Hannu, Myllykangas, Liisa, Jansson, Lilja, Valori, Miko, Ealing, John, Hamdalla, Hisham, Rollinson, Sara, Pickering-Brown, Stuart, Orrell, Richard W, Sidle, Katie C, Malaspina, Andrea, Hardy, John, Singleton, Andrew B, Johnson, Janel O, Arepalli, Sampath, Sapp, Peter C, McKenna-Yasek, Diane, Polak, Meraida, Asress, Seneshaw, Al-Sarraj, Safa, King, Andrew, Troakes, Claire, Vance, Caroline, de Belleroche, Jacqueline, Baas, Frank, Ten Asbroek, Anneloor L M A, Muñoz-Blanco, José Lui, Hernandez, Dena G, Ding, Jinhui, Gibbs, J Raphael, Scholz, Sonja W, Floeter, Mary Kay, Campbell, Roy H, Landi, Francesco, Bowser, Robert, Pulst, Stefan M, Ravits, John M, Macgowan, Daniel J L, Kirby, Janine, Pioro, Erik P, Pamphlett, Roger, Broach, Jame, Gerhard, Glenn, Dunckley, Travis L, Brady, Christopher B, Kowall, Neil W, Troncoso, Juan C, Le Ber, Isabelle, Mouzat, Kevin, Lumbroso, Serge, Heiman-Patterson, Terry D, Kamel, Freya, Van Den Bosch, Ludo, Baloh, Robert H, Strom, Tim M, Meitinger, Thoma, Shatunov, Aleksey, Van Eijk, Kristel R, de Carvalho, Mamede, Kooyman, Maarten, Middelkoop, Ba, Moisse, Matthieu, Mclaughlin, Russell L, Van Es, Michael A, Weber, Marku, Boylan, Kevin B, Van Blitterswijk, Marka, Rademakers, Rosa, Morrison, Karen E, Basak, A Nazli, Mora, Jesús S, Drory, Vivian E, Shaw, Pamela J, Turner, Martin R, Talbot, Kevin, Hardiman, Orla, Williams, Kelly L, Fifita, Jennifer A, Nicholson, Garth A, Blair, Ian P, Rouleau, Guy A, Esteban-Pérez, Jesú, García-Redondo, Alberto, Al-Chalabi, Ammar, Rogaeva, Ekaterina, Zinman, Lorne, Ostrow, Lyle W, Maragakis, Nicholas J, Rothstein, Jeffrey D, Simmons, Zachary, Cooper-Knock, Johnathan, Brice, Alexi, Goutman, Stephen A, Feldman, Eva L, Gibson, Summer B, Taroni, Franco, Ratti, Antonia, Gellera, Cinzia, Van Damme, Philip, Robberecht, Wim, Fratta, Pietro, Sabatelli, Mario, Lunetta, Christian, Ludolph, Albert C, Andersen, Peter M, Weishaupt, Jochen H, Camu, William, Trojanowski, John Q, Van Deerlin, Vivianna M, Brown, Robert H, van den Berg, Leonard H, Veldink, Jan H, Harms, Matthew B, Glass, Jonathan D, Stone, David J, Tienari, Pentti, Silani, Vincenzo, Chiò, Adriano, Shaw, Christopher E, Traynor, Bryan J, Landers, John E, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Male, Als gene, Genome-wide association study, FAMILIAL ALS, ALS, axonal transport, cargo, GWAS, KIF5A, WES, WGS, 0302 clinical medicine, 80 and over, Psychology, Aetiology, Aged, 80 and over, 0303 health sciences, French ALS Consortium, Kinesin, KINESIN HEAVY-CHAIN, Cognitive Sciences, Human, Hereditary spastic paraplegia, Neuroscience(all), Single-nucleotide polymorphism, TARGETED DISRUPTION, Article, 03 medical and health sciences, Genetics, Humans, Amino Acid Sequence, Loss function, Aged, HEXANUCLEOTIDE REPEAT, Neuroscience (all), MUTATIONS, Amyotrophic Lateral Sclerosis, 3112 Neurosciences, 1702 Cognitive Science, medicine.disease, ITALSGEN Consortium, Answer ALS Foundation, 030104 developmental biology, ALS Sequencing Consortium, Human medicine, 1109 Neurosciences, 030217 neurology & neurosurgery, 0301 basic medicine, [SDV]Life Sciences [q-bio], Kinesins, Neurodegenerative, Genetic analysis, Genome, AMYOTROPHIC-LATERAL-SCLEROSIS, 3124 Neurology and psychiatry, Cohort Studies, Pathogenesis, Loss of Function Mutation, Missense mutation, 2.1 Biological and endogenous factors, Amyotrophic lateral sclerosis, NYGC ALS Consortium, General Neuroscience, ALS, axonal transport, cargo, GWAS, KIF5A, WES, WGS, Middle Aged, Phenotype, Settore MED/26 - NEUROLOGIA, Neurological, Project MinE ALS Sequencing Consortium, Female, Adult, Biology, GENOTYPE IMPUTATION, Genome-Wide Association Study, Young Adult, NO, Rare Diseases, medicine, SLAGEN Consortium, Gene, 030304 developmental biology, Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium, Neurology & Neurosurgery, Human Genome, Neurosciences, AXONAL-TRANSPORT, Brain Disorders, Family member, DNA-DAMAGE, MOTOR-NEURONS, 3111 Biomedicine, Cohort Studie, Genomic Translation for ALS Care (GTAC) Consortium, Amyotrophic Lateral Sclerosi
Abstract: © 2018 Elsevier Inc., To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
Published: 2018

50. Health-Related Lifestyle Profiles in Healthy Adults: Associations with Sociodemographic Indicators, Dispositional Optimism, and Sense of Coherence

Author: Roberta Adorni, Marco D’Addario, Francesca Atella, Patrizia Steca, Caterina Iaderosa, Francesco Zanatta, Elena Costantino, Giulia Petarle, Adorni, R, Zanatta, F, D'Addario, M, Atella, F, Costantino, E, Iaderosa, C, Petarle, G, and Steca, P
Subjects: Adult, Male, lifestyle, Sociodemographic Factors, alcohol consumption, Health Behavior, physical activity, cigarette smoking, Dispositional optimism, Disease, Disease cluster, Article, Young Adult, Cigarette smoking, Surveys and Questionnaires, Humans, Medicine, TX341-641, Healthy Lifestyle, Family history, Exercise, Multinomial logistic regression, Sedentary lifestyle, Optimism, Nutrition and Dietetics, Nutrition. Foods and food supply, business.industry, Gender, Middle Aged, Healthy Volunteers, Cardiovascular Diseases, Sense of coherence, Female, cardiovascular screening, M-PSI/01 - PSICOLOGIA GENERALE, diet, business, Attitude to Health, Food Science, Demography
Abstract: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. Promoting healthy behaviors throughout life is an essential prevention tool. This study investigated the associations among lifestyle profiles (including diet, alcohol consumption, physical activity, cigarette smoking, and cardiovascular screening), sociodemographic factors (gender, age, education, and family history of CVDs), and psychological factors (sense of coherence and dispositional optimism). In total, 676 healthy adults (mean age = 35 years, range = 19–57, 46% male) participated in an online survey. Lifestyle profiles were identified through cluster analysis, and a multinomial logistic regression was then performed to explore their association with sociodemographic and psychological variables. Results show that men were more likely than women to belong to the lifestyle profile with the highest amount of physical activity (OR = 2.40, p &lt, 0.001) and the greatest attention to cardiovascular screening (OR = 2.09, 0.01). Lower dispositional optimism was associated with the profile paying the greatest attention to cardiovascular screening (OR = 0.67, 0.05). Sense of coherence, in terms of lower comprehensibility (OR = 0.67, 0.05) and higher manageability (OR = 1.43, 0.05), was associated with the lifestyle profile characterized by an unhealthy diet, sedentary lifestyle, and nonsmoking. This study shed light on factors associated with different co-occurring health-related behaviors that should be considered in planning effective communication strategies promoting adherence to health claims.
Published: 2021

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