80 results on '"Curado F"'
Search Results
2. Uma visão da trajetória da Rede Sergipana de Agroecologia
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OLIVEIRA, T. C. de, CALLE, A. C., CURADO, F. F., TAVARES, E. D., SIQUEIRA, E. R. de, TEREZA CRISTINA DE OLIVEIRA, CPATC, ANGEL COLLADO CALLE, FERNANDO FLEURY CURADO, CNAT, EDSON DIOGO TAVARES, CPATC, and EDMAR RAMOS DE SIQUEIRA, CPATC.
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Saber social ,Rede Sergipana de Agroecologia ,Agroecologia ,Politica pública - Abstract
Made available in DSpace on 2021-03-18T13:34:09Z (GMT). No. of bitstreams: 1 Uma-visao.cadernos-Agroecologia-Artigo-RESEA-14dez2020.pdf: 1793233 bytes, checksum: de249447313a579fb64fa594fcc15b30 (MD5) Previous issue date: 2020 Edição dos Anais do XI Congresso Brasileiro de Agroecologia, São Cristóvão, Sergipe, 2020.
- Published
- 2020
3. Combined treatment with vitamin E and colchicine in the early stages of Peyronieʼs disease
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PRIETO CASTRO, R. M., LEVA VALLEJO, M. E., REGUEIRO LOPEZ, J. C., ANGLADA CURADO, F. J., ALVAREZ KINDELAN, J., and Requena Tapia, M. J.
- Published
- 2003
4. Diálogos entre educação-pesquisa-extensão: contraponto ao processo convencional de transferência de tecnologia no território do alto sertão sergipano
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OLIVEIRA, T. C. de, TAVARES, E. D., COPORAL, F. R., CURADO, F. F., COLLADO, A. C., TEREZA CRISTINA DE OLIVEIRA, CPATC, EDSON DIOGO TAVARES, CPATC, FRANCISCO ROBERTO COPORAL, FERNANDO FLEURY CURADO, CPATC, and ANGEL CALLE COLLADO.
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Educação ambiental ,Agroecologia - Abstract
Made available in DSpace on 2017-10-05T10:31:20Z (GMT). No. of bitstreams: 1 Vista.pdf: 451028 bytes, checksum: 84925a0aa7f20405afdbb2178f360b9d (MD5) Previous issue date: 2017-09-29 Apresentado no SEMINÁRIO NACIONAL DE EDUCAÇÃO EM AGROECOLOGIA, 2., 2016, Seropédica. Educação em agroecologia: resistências e lutas pela democracia: anais. Seropédica: ABA, 2016.
- Published
- 2017
5. O movimento dos pequenos agricultores e a luta em defesa das sementes crioulas no alto sertão sergipano, Brasil
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AMORIM, L. O. do, PEREIRA, M. C. de B., CURADO, F. F., OLIVEIRA, L. C. L. de, VASCONCELOS, E. B. de, LUCAS OLIVEIRA DO AMORIM, MONICA COX DE BRITTO PERIEIRA, FERNANDO FLEURY CURADO, CPATC, LANNA CECILIA LIMA DE OLIVEIRA, and ELIELMA BARROS DE VASCONCELOS.
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Agricultor ,Semente crioula ,Agroviodiversidade ,Pequeno agricultor ,Semente - Abstract
O presente trabalho tem como objetivo analisar como o Movimento dos Pequenos Agricultores vem organizando sua luta em defesa das sementes crioulas no estado de Sergipe a partir de ações do Território do Alto Sertão Sergipano. As informações que foram analisadas neste trabalho partiram de leituras do Plano Camponês e do Plano Nacional de Sementes Crioula do MPA. Além isto, através da observação-participante, buscou-se ivenciar a realidade do Movimento durante o encontro de agricultores(as) guardiões e guardiãs das sementes crioulas (2016) no município de Poço Redondo/SE. O MPA vem realizando uma luta ampla contra o avanço do agronegócio no Alto Sertão Sergipano. Neste sentido, a defesa das sementes crioulas representa uma simbologia na resistência da agricultura camponesa, ao mesmo tempo que nos remete a um novo paradigma de desenvolvimento do campo baseado nos princípios da Agroecologia.
- Published
- 2017
6. Agroecologia: abordagens na busca da autonomia do campesinato brasileiro
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CURADO, F. F., TAVARES, E. D., FERNANDO FLEURY CURADO, CPATC, and EDSON DIOGO TAVARES, CPATC.
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Revolução verde ,Ecologia vegetal ,Agroecologia ,Campesinato ,Rural ,Desenvolvimento Rural - Published
- 2017
7. Protagonismo das mulheres nas unidades de experimentação agroecológica coletiva, no âmbito do Plano Brasil Sem Miséria (PBMS) em Sergipe
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OLIVEIRA, T. C. de, BRANDÃO, B. de O., CURADO, F. F., TAVARES, E. D., SANTOS, A. da S. dos, TEREZA CRISTINA DE OLIVEIRA, CPATC, FERNANDO FLEURY CURADO, CPATC, EDSON DIOGO TAVARES, CPATC, and AMAURY DA SILVA DOS SANTOS, CPATC.
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Brasil sem Miséria ,Agroecologia ,Mulher Rural - Abstract
Made available in DSpace on 2022-10-26T15:08:32Z (GMT). No. of bitstreams: 1 Mulher-nas-UEAC-publicado-pdf-IX-CBA-2015.pdf: 8899 bytes, checksum: 0f3389755155f9f911cd0f87b1ff00b1 (MD5) Previous issue date: 2015
- Published
- 2015
8. Caracterização e desenvolvimento de quintais produtivos agroecológicos na comunidade Mem de Sá, Itaporanga D'Ajuda - Sergipe
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SANTOS, A. da S. dos, OLIVEIRA, L. C. L. de, CURADO, F. F., AMORIM, L. O. do, AMAURY DA SILVA DOS SANTOS, CPATC, and FERNANDO FLEURY CURADO, CPATC.
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Itaporanga D'Ajuda ,Coco ,Manga ,Alimento ,Sergipe ,Quintal produtivo ,Agroecologia - Abstract
Este trabalho objetivou caracterizar os quintais produtivos da Ilha Mem de Sá, Itaporanga D?Ajuda, Sergipe (Brasil) e criar unidades demonstrativas (UD) com base na produção agroecológica. A partir de metodologias participativas foram caracterizadas plantas e animais existentes em 13 quintais, assim a forma de manejo realizada nesses espaços, observando a importância e a função exercida pelos quintais para os moradores. Foram constatadas 49 espécies vegetais sendo que o coco (Cocos nucifera L.) e a manga (Mangifera indica L.) se destacaram por suas freqüências. Foram encontrados animais de pequeno porte, principalmente aves, que são utilizados na dieta das famílias. Foi criada uma UD com o objetivo de trocar experiências de cunho agroecológico, valorizando o saber tradicional, no sentido de incrementar os quintais. Os quintais produtivos caracterizaram-se como um importante espaço para a disseminação de valores e conhecimentos, além da produção de alimentos que enriquecem a dieta dos moradores.
- Published
- 2013
9. Sistemas agropecuários sustentáveis (SAS): uma proposta metodológica para transferência de tecnologias agropecuárias
- Author
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SOUZA, S. F. de, CURADO, F. F., MOTA, P. S. S. da, MEDEIROS, S. dos S., MANOS, M. G. L., SAMUEL FIGUEIREDO DE SOUZA, CPATC, FERNANDO FLEURY CURADO, CPATC, PAULO SERGIO SANTOS DA MOTA, CPATC, SONISE DOS SANTOS MEDEIROS, CPATC, and MARIA GEOVANIA LIMA MANOS, CPATC.
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Agricultura Familiar ,Integração lavoura-pecuária ,Sistema agropecuário ,Cilagem - Abstract
O estudo teve por objetivo desenvolver, testar e implantar metodologias que subsidiem uma nova abordagem de transferência de tecnologias pela Embrapa Tabuleiros Costeiros, pautada na visão do diálogo e da construção coletiva de conhecimentos e na adoção de soluções tecnológicas de base sustentável para a agricultura familiar nos territórios rurais do Estado de Sergipe. A implantação dos Sistemas Agropecuários Sustentáveis atende a cinco diretrizes básicas, sendo elas: implantação em comunidades com baixo acesso a tecnologias; atendimento aos agricultores de base familiar; construção participativa; implantação de culturas variadas e implantação de culturas que realizem enriquecimento dos solos por meio da fixação e ciclagem de nutrientes. Com base nas experiências iniciadas, pode-se concluir que a metodologia tem alcançado alguns dos seus principais objetivos, emonstrando potencial para firmar-se como ferramenta de transferência de tecnologias e estimulando a organização social dos agricultores envolvidos. Uma fase de monitoramento da adoção das tecnologias disponibilizadas está em fase inicial e faz-se necessário para ajustes contínuos. Palavras-chave: agricultura familiar, ciclagem de nutrientes, construção participativa, integração lavoura-pecuária
- Published
- 2011
10. Identidade social: unidade e singularidade na luta pela terra no Brasil
- Author
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CURADO, F. F. and Embrapa Tabuleiros Costeiros.
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subjetividades ,trabalhadores rurais ,Reforma Agrária ,subjectivities ,agrarian reform ,agricultural workers ,land fight - Abstract
Este estudo procura analisar, a partir da leitura de diversos autores, algumas dimensões esclarecedoras das transformações ocorridas na vida de trabalhadores rurais que ingressaram no movimento de luta pela terra em diferentes experiências no País. Assim, aspectos relacionados com a origem e a trajetória dos trabalhadores, com a expressão de formas de resistência e pressão nos espaços de acampamento e assentamento, com a compreensão do processo que vivenciaram desde o início da experiência, com os avanços e os desafios na permanência na terra, com os mecanismos de organização interna e da participação dos mediadores e demais atores sociais permitiram a identificação de diferentes situações dessa luta, demonstrando a complexidade do vivido no interior desses espaços. Tais aspectos impediram, portanto, a visualização de caminhos únicos e pré-determinados na conformação desses atores sociais e permitiram o reconhecimento, nessas diversas leituras, de uma identidade social (de agricultor assentado) em construção, transitória, conflituosa e, nesse sentido, abarcada também por singularidades em suas formas de materialização. Made available in DSpace on 2011-04-09T12:40:50Z (GMT). No. of bitstreams: 1 v23n1p11.pdf: 132783 bytes, checksum: 1d4a20b4c2353c0d0d023a6013fae6e7 (MD5) Previous issue date: 2008-09-15
- Published
- 2006
11. Acetato de abiraterona prequimioterapia. Propuesta de un algoritmo de tratamiento en el carcinoma de próstata resistente a castración
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Arrabal-Martín, M., primary, Anglada-Curado, F., additional, Cózar-Olmo, J.M., additional, Soler-Martínez, J., additional, Moreno-Jiménez, J., additional, Castiñeiras-Fernández, J., additional, Ledo-Cepero, M.J., additional, Beardo-Villar, P., additional, Requena-Tapia, M.J., additional, and Zuluaga-Gómez, A., additional
- Published
- 2014
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12. Long-term Allograft Survival After Kidney Transplantation
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Gómez, E. Gómez, primary, Hernández, J.P. Campos, additional, López, F.J. Márquez, additional, Garcia, J. Ruiz, additional, Montemayor, V. Garcia, additional, Curado, F. Anglada, additional, Vallejo, M. Leva, additional, López, J.C. Regueiro, additional, Cabello, M.D. Navarro, additional, Aljama, P., additional, and Tapia, M.J. Requena, additional
- Published
- 2013
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13. Correlation Between Dual Kidney Biopsy in Expanded-Criteria Donors and Transplant Survival
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García-Rubio, J.H., primary, García, J. Ruiz, additional, Hernández, P. Campos, additional, López, J. Márquez, additional, Curado, F. Anglada, additional, Vallejo, M. Leva, additional, López, J.C. Regueiro, additional, Gómez, E. Gómez, additional, Aljama, P., additional, and Tapia, M.J. Requena, additional
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- 2013
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14. [Clinico-pathologic differences between bladder neoplasm with low malignant potential and low-grade carcinoma]
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Alvarez Kindelán J, Anglada Curado F, Jl, Carazo Carazo, Leva Vallejo M, López Beltrán A, Moreno Arcas P, Prieto Castro R, JUAN CARLOS REGUEIRO, and Mj, Requena Tapia
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Male ,Urinary Bladder Neoplasms ,Carcinoma ,Humans ,Female ,Middle Aged - Abstract
To determine if the morphologic subgrouping of grade I bladder tumors between papillary neoplasm of low malignant potential and low grade papillary carcinoma is of clinical and survival value.All 257 consecutive patients diagnosed of superficial bladder cancer between 1990 and 1995 in HU Reina Sofia of Cordoba were reviewed and further reclassified according to WHO/ISUP consensus classification of urothelial neoplasms of the bladder. Of the tumors 12 were urothelial papilloma, 51 were papillary neoplasm of low malignant potential, 43 were low grade papillary carcinoma Ta, 65 were low grade papillary carcinoma T1 and 37 were high grade papillary carcinoma. Eleven patients were reevaluated as T2 tumors and 38 (14.8%) were lost of control. All patients were reviewed with a follow-up at least of 5 years. We compare the results between groups with Fisher test and the risk factors for recurrence and progression are analyzed by multivariate analysis (Odds ratio). The survival function was calculated using Kaplan-Meier estimates and compared with the log-rank test.There are no differences between groups respect the age or sex distribution. The differences in the multiplicity are not significant and only the mean size is higher in papillary low grade carcinoma. About the risk factors for recurrence and progression of the disease, only is significative the tumor size. Rarely, the use of chemotherapy seems to play a role in the recurrence. There are no differences in recurrence and progression between the groups, although the percentages are always higher in the papillary low grade carcinoma group.There are enough clinical differences between the two groups and we consider them as distinct pathologic entities. Only the higher tumoral size is prognostic factor in each group. We think that the use of chemotherapy must be avoided in this low grade bladder tumors.
- Published
- 2002
15. INFLUENCE OF NITROGEN AND POTASSIUM FERTILIZATION ON MINERAL COMPOSITION OF KIWIFRUIT
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Pacheco, C., primary, Calouro, F., additional, Santos, F., additional, Vieira, S., additional, Neves, N., additional, Curado, F., additional, and Rodrigues, S., additional
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- 2010
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16. Underwater vehicle technology in the European Research Project VENUS
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Conte, G, primary, Gambella, L, additional, Scaradozzi, D, additional, Zanoli, S, additional, Caiti, A, additional, Calabrò, V, additional, Alcocer, A, additional, Alves, J, additional, Cardeira, B, additional, Cunha, R, additional, Curado, F, additional, Oliveira, P, additional, Oliveira, A, additional, Pascoal, A, additional, Rufino, M, additional, Sebastião, L, additional, and Silvestre, C, additional
- Published
- 2009
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17. 348: Superficial and Deep Cervical Plexus Block for Major Neck Surgery in a Patient With Severe COPD
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COUTINHO, A, primary, MOURATO, C, additional, ALMEIDA, V, additional, DIONISIO, E, additional, and CURADO, F, additional
- Published
- 2008
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18. Superficial and Deep Cervical Plexus Block for Major Neck Surgery in a Patient With Severe COPD
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Coutinho, A., primary, Mourato, C., additional, Almeida, V., additional, Dionísio, E., additional, and Curado, F., additional
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- 2008
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19. THE EFFECT OF CALCIUM APPLICATIONS ON KIWIFRUIT QUALITY PRESERVATION DURING STORAGE
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Antunes, M.D.C., primary, Neves, N., additional, Curado, F., additional, Rodrigues, S., additional, Franco, J., additional, and Panagopoulos, T., additional
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- 2007
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20. TASTE PANEL QUALITY EVALUATION OF 'HAYWARD' KIWIFRUIT OF DIFFERENT ORIGINS
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Franco, J., primary, Melo, F., additional, Guilherme, R., additional, Neves, N., additional, Curado, F., additional, and Antunes, D., additional
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- 2007
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21. THE EFFECT OF PRE- AND POSTHARVEST CALCIUM APPLICATIONS ON ´HAYWARD´ KIWIFRUIT STORAGE ABILITY
- Author
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Antunes, M.D.C., primary, Panagopoulos, T., additional, Rodrigues, S., additional, Neves, N., additional, and Curado, F., additional
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- 2005
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22. Diferencias clínico-patológicas entre neoplasia vesical de bajo potencial maligno y carcinoma de bajo grado
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Álvarez kindelán, J., primary, López beltrán, A., additional, Anglada curado, F., additional, Moreno arcas, P., additional, Carazo carazo, J.L., additional, Regueiro lópez, J.C., additional, Leva vallejo, M., additional, Prieto castro, R., additional, and Requena tapia, M.J., additional
- Published
- 2001
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23. Encrusted pyelitis. Lithiasic disease with infectious etiology,Pielitis incrustada. Una enfermedad litiásica de etiología infecciosa
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Moreno Arcas, P., Anglada Curado, F. J., Prieto Castro, R., Regueiro López, J. C., Leva Vallejo, M., Alvarez Kindelán, J., Carazo Carazo, J. L., António López-Beltrán, and Requena Tapia, M. J.
24. Searching for landslides in the stratigraphic record of the Tagus river delta as evidences for tsunami and earthquakes, using 3D seismic reflection,Em busca de deslizamentos submarinos no registro estratigráfico do delta do rio Tejo como evidências de sismos e tsunami, utilizando sísmica de reflexão 3D
- Author
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Noiva, J., Duarte, H., Terrinha, P., Brito, P., Vitor Magalhaes, Alves, P., Rosa, M., Oliveira, M., and Curado, F.
25. [Retrovesical hydatic cyst]
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Alvarez Kindelán J, Anglada Curado F, Ec, Carmona Campos, JUAN CARLOS REGUEIRO, Mj, Requena Tapia, and Jl, Saceda López
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Male ,Echinococcosis ,Urinary Bladder Diseases ,Humans ,Middle Aged ,Ultrasonography - Abstract
The hydatid disease is a common condition in endemic countries, generally involving the liver or the lungs. Genitourinary tract involvement is quite uncommon, and the organ most usually affected is the kidney. A retrovesical location is even more rare. The present paper contributes one case with no evidence of hydatidosis in any other abdominal organ and describes the diagnostic and therapeutic protocol followed.
26. [Bilharziasis and bladder cancer. A case report]
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Alameda Aragoneses V, Alvarez Kindelan J, Anglada Curado F, Carmona Campos E, López Rubio F, Prieto Castro R, JUAN CARLOS REGUEIRO, and Mj, Requena Tapia
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Adult ,Male ,Schistosomiasis haematobia ,Urinary Bladder Neoplasms ,Chronic Disease ,Palliative Care ,Carcinoma, Squamous Cell ,Humans ,Cystectomy ,Senegal ,Hematuria - Abstract
In our setting, the association between bilharziasis and bladder cancer is uncommon. However, the presence of recurrent haematuria in a patient from an endemic area of bilharziasis (east of Africa and Middle East), is highly suspicious of this disease. Lack of an adequate treatment by using anthelminthic drugs during the acute phase of disease, might lead to the onset of chronic bladder lesions and, on occasion, bladder cancer, of the epidermoid type in the majority of cases. Because of the high mortality and aggressivity of this type of cancer, an early diagnosis and appropriate treatment of acute lesions is mandatory. We report a 40-year-old black male from Senegal, presenting chronic bladder schistosomiasis and infiltrative epidermoid carcinoma of the bladder, diagnosed and treated in our department by palliative cystectomy.
27. [Extragonadal germ tumor]
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Alvarez Kindelán J, Anglada Curado F, Blanco Espinosa A, Ec, Carmona Campos, Prieto Castro R, JUAN CARLOS REGUEIRO, and Mj, Requena Tapia
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Adult ,Male ,Lung Neoplasms ,Humans ,Choriocarcinoma ,Retroperitoneal Neoplasms - Abstract
Extragonadal primary tumors are uncommon and account for 3 to 5% of all germ cells neoplasias. Preferentially found in middle line structures, such tumors are frequently in an advanced stage when diagnosed. Differentiation between primary extragonadal tumors and metastasis of testicular primary tumors is essential, but may be difficult in many instances.
28. [Management of obstructive renal candidiasis. Report of a clinical case]
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Alameda Aragonéses V, Alvarez Kindelán J, Anglada Curado F, Carmona Campos E, Prieto Castro R, JUAN CARLOS REGUEIRO, and Mj, Requena Tapia
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Male ,Candidiasis ,Infant, Newborn ,Humans ,Kidney Diseases ,Infant, Premature, Diseases - Abstract
Neonatal renal candidiasis is a rare complication but serious, associated with prematurity, immunodeficiency, parenteral nutrition and other risk factors, with a mortality rate until 50%. We describe a neonate premature of 28 weeks who developed septicaemia by Candida, complicated with bilateral ureterohydronephrosis and intrapelvic fungus ball. The patient was managed by bilateral nephrostomy drainage and amphotericin B local irrigation, anyway with systemic amphotericin B together with oral fluconazol, needing subsequently bilateral open surgery and external drainage. The infection was eradicated, reaching the patient a gradual healing.
29. Clinico-pathologic differences between bladder neoplasm with low malignant potential and low-grade carcinoma,Diferencias clínico-patológicas entre neoplasia vesical de bajo potencial maligno y carcinoma de bajo grado
- Author
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Alvarez Kindelán, J., António López-Beltrán, Anglada Curado, F., Moreno Arcas, P., Carazo Carazo, J. L., Regueiro López, J. C., Leva Vallejo, M., Prieto Castro, R., and Requena Tapia, M. J.
30. [Evaluation and treatment of closed renal trauma]
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Alvarez Kindelán J, Anglada Curado F, Ec, Carmona Campos, Gómez Bermudo J, Prieto Castro R, JUAN CARLOS REGUEIRO, and Mj, Requena Tapia
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Adult ,Male ,Trauma Severity Indices ,Adolescent ,Humans ,Female ,Middle Aged ,Kidney ,Wounds, Nonpenetrating ,Aged - Abstract
Renal trauma accounts for more than 50% of all genitourinary trauma cases, nearly 90% of them corresponding to blunt trauma. Incidence is higher in male (3:1 ratio); is more frequent between the second and third decades; and predominantly affects the left side. Our group analyzed 89 cases of blunt renal trauma seen in our service between 1983 and 1996 with the purpose of determining the choice imaging studies, indications and type of management. Based on severity, injuries were rated in 5 grades using the classification of the Organic Injuries Survey Committee (OIS) from the American Association of Surgery in Trauma (AAST). We analyzed the etiology, clinical findings, prior renal conditions, associated injuries, radiologic studies and treatment instituted. CAT was considered the choice diagnostic technique for trauma rating since it permits greater definition of renal injury grade, as well as the associated abdominal and thoracic injuries. Most renal traumas were mild in severity, and evolved favourably with conservative treatment. In renal trauma grades IV and V, surgery is the recommended therapeutic approach, always preferring the most conservative criteria.
31. Some problems of translating LOGO to a romance language
- Author
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Curado, F., primary and Valente, J. A., additional
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- 1978
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32. Digital reading strategies in computer English
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Curado Fuentes, Alejandro
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English language ,PE1-3729 ,English literature ,PR1-9680 - Abstract
This paper focuses on the use of web-based discourse by three Spanish undergraduate students in Computer Engineering. Key lexico-grammatical features in Computer English have been analysed by means of corpus linguistics techniques, for which word statistics and collocation functions in the WordSmith concordancer have been highly useful. The information was then used to compare the students' results. The students' reading skills have been evaluated in the documentation process of the three final projects, required prior to their graduation as engineers. Overall observations point to code-switching, re-wording, and key vocabulary identification as strategies that the students demonstrate to be able to operate with significantly after on-line reading. The students also rely more on Internet discourse as a main source of feedback for their projects and useful tool for work. Two of the projects have dealt with the design and use of interactive platforms for language learning (via two different approaches), while the third project has focused on the management of e-learning with the use of Squeak, a special language for programming. The assessment of the three students' reading / interpretation skills has taken place by means of written tasks and personal interviews.
- Published
- 2007
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33. Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson's disease study.
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Westenberger A, Skrahina V, Usnich T, Beetz C, Vollstedt EJ, Laabs BH, Paul JJ, Curado F, Skobalj S, Gaber H, Olmedillas M, Bogdanovic X, Ameziane N, Schell N, Aasly JO, Afshari M, Agarwal P, Aldred J, Alonso-Frech F, Anderson R, Araújo R, Arkadir D, Avenali M, Balal M, Benizri S, Bette S, Bhatia P, Bonello M, Braga-Neto P, Brauneis S, Cardoso FEC, Cavallieri F, Classen J, Cohen L, Coletta D, Crosiers D, Cullufi P, Dashtipour K, Demirkiran M, de Carvalho Aguiar P, De Rosa A, Djaldetti R, Dogu O, Dos Santos Ghilardi MG, Eggers C, Elibol B, Ellenbogen A, Ertan S, Fabiani G, Falkenburger BH, Farrow S, Fay-Karmon T, Ferencz GJ, Fonoff ET, Fragoso YD, Genç G, Gorospe A, Grandas F, Gruber D, Gudesblatt M, Gurevich T, Hagenah J, Hanagasi HA, Hassin-Baer S, Hauser RA, Hernández-Vara J, Herting B, Hinson VK, Hogg E, Hu MT, Hummelgen E, Hussey K, Infante J, Isaacson SH, Jauma S, Koleva-Alazeh N, Kuhlenbäumer G, Kühn A, Litvan I, López-Manzanares L, Luxmore M, Manandhar S, Marcaud V, Markopoulou K, Marras C, McKenzie M, Matarazzo M, Merello M, Mollenhauer B, Morgan JC, Mullin S, Musacchio T, Myers B, Negrotti A, Nieves A, Nitsan Z, Oskooilar N, Öztop-Çakmak Ö, Pal G, Pavese N, Percesepe A, Piccoli T, Pinto de Souza C, Prell T, Pulera M, Raw J, Reetz K, Reiner J, Rosenberg D, Ruiz-Lopez M, Ruiz Martinez J, Sammler E, Santos-Lobato BL, Saunders-Pullman R, Schlesinger I, Schofield CM, Schumacher-Schuh AF, Scott B, Sesar Á, Shafer SJ, Sheridan R, Silverdale M, Sophia R, Spitz M, Stathis P, Stocchi F, Tagliati M, Tai YF, Terwecoren A, Thonke S, Tönges L, Toschi G, Tumas V, Urban PP, Vacca L, Vandenberghe W, Valente EM, Valzania F, Vela-Desojo L, Weill C, Weise D, Wojcieszek J, Wolz M, Yahalom G, Yalcin-Cakmakli G, Zittel S, Zlotnik Y, Kandaswamy KK, Balck A, Hanssen H, Borsche M, Lange LM, Csoti I, Lohmann K, Kasten M, Brüggemann N, Rolfs A, Klein C, and Bauer P
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Glucosylceramidase genetics, alpha-Synuclein genetics, Genetic Predisposition to Disease, Ubiquitin-Protein Ligases genetics, Cohort Studies, Protein Kinases genetics, Mutation, Adult, Parkinson Disease genetics, Genetic Testing methods, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 genetics
- Abstract
Estimates of the spectrum and frequency of pathogenic variants in Parkinson's disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinson's disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (∼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 × 10-34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 × 10-35). Female patients were 22% more likely to have a positive PDGT (P = 3 × 10-4), and for individuals with FH+ this likelihood was 55% higher (P = 1 × 10-14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that ∼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2024
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34. Insights into the Value of Lyso-Gb1 as a Predictive Biomarker in Treatment-Naïve Patients with Gaucher Disease Type 1 in the LYSO-PROOF Study.
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Curado F, Rösner S, Zielke S, Westphal G, Grittner U, Skrahina V, Alasel M, Malik AM, Beetz C, Böttcher T, Barel G, Sah AP, Dinur T, Anjum N, Ichraf Q, Kriouile Y, Hadipour Z, Hadipour F, Revel-Vilk S, Cozma C, Hartkamp J, Cheema H, Zimran A, Bauer P, and Rolfs A
- Abstract
Gaucher disease (GD) is a rare autosomal recessive disorder arising from bi-allelic variants in the GBA1 gene, encoding glucocerebrosidase. Deficiency of this enzyme leads to progressive accumulation of the sphingolipid glucosylsphingosine (lyso-Gb1). The international, multicenter, observational "Lyso-Gb1 as a Long-term Prognostic Biomarker in Gaucher Disease"-LYSO-PROOF study succeeded in enrolling a cohort of 160 treatment-naïve GD patients from diverse geographic regions and evaluated the potential of lyso-Gb1 as a specific biomarker for GD. Using genotypes based on established classifications for clinical presentation, patients were stratified into type 1 GD ( n = 114) and further subdivided into mild ( n = 66) and severe type 1 GD ( n = 48). Due to having previously unreported genotypes, 46 patients could not be classified. Though lyso-Gb1 values at enrollment were widely distributed, they displayed a moderate and statistically highly significant correlation with disease severity measured by the GD-DS3 scoring system in all GD patients (r = 0.602, p < 0.0001). These findings support the utility of lyso-Gb1 as a sensitive biomarker for GD and indicate that it could help to predict the clinical course of patients with undescribed genotypes to improve personalized care in the future.
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- 2023
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35. The role of multiparametric magnetic resonance in active surveillance of a low-risk prostate cancer cohort from clinical practice.
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Chamorro Castillo L, García Morales L, Ruiz López D, Salguero Segura J, Valero Rosa J, Anglada Curado FJ, Mesa Quesada J, Blanca Pedregosa A, Carrasco Valiente J, and Gómez Gómez E
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- Male, Humans, Aged, Prostate pathology, Magnetic Resonance Imaging methods, Magnetic Resonance Spectroscopy, Disease Progression, Image-Guided Biopsy methods, Watchful Waiting, Prostatic Neoplasms pathology
- Abstract
Introduction: Active surveillance (AS) is considered a suitable management practice for those patients with low-risk prostate cancer (PCa). At present, however, the role of multiparametric magnetic resonance imaging (mpMRI) in AS protocols has not yet been clearly established., Outcomes: To determine the role of mpMRI and its ability to detect significant prostate cancer (SigPCa) in PCa patients enrolled in AS protocols., Materials and Methods: There were 229 patients enrolled in an AS protocol between 2011 and 2020 at Reina Sofía University Hospital. MRI interpretation was based on PIRADS v.1 or v.2/2.1 classification. Demographics, clinical, and analytical data were collected and analyzed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for mpMRI in different scenarios. We defined SigPCa and reclassification/progression as a Gleason score (GS) ≥ 3 + 4, a clinical stage ≥T2b, or an increase in PCa volume. Kaplan-Meier and log-rank tests were used to estimate progression-free survival time., Results: Median age was 69.02 (±7.73) at diagnosis, with a 0.15 (±0.08) PSA density (PSAD). Eighty-six patients were reclassified after confirmatory biopsy, with a suspicious mpMRI an indication for a clear reclassification and risk-predictor factor in disease progression (p < 0.05). During follow-up, 46 patients were changed from AS to active treatment mainly due to disease progression. Ninety patients underwent ≥2mpMRI during follow-up, with a median follow-up of 29 (15-49) months. Thirty-four patients had a baseline suspicious mpMRI (at diagnostic or confirmatory biopsy): 14 patients with a PIRADS 3 and 20 patients with ≥PIRADS 4. From 14 patients with a PIRADS 3 baseline mpMRI, 29% progressed radiologically, with a 50% progression rate versus 10% (1/10 patients) for those with similar or decreased mpMRI risk. Of the 56 patients with a non-suspicious baseline mpMRI (PIRADS < 2), 14 patients (25%) had an increased degree of radiological suspicion, with a detection rate of SigPCa of 29%. The mpMRI NPV during follow-up was 0.91., Conclusion: A suspicious mpMRI increases the reclassification and disease progression risk during follow-up and plays an important role in monitoring biopsies. In addition, a high NPV at mpMRI follow-up can help to decrease the need to monitor biopsies during AS., (© 2023 The Authors. The Prostate published by Wiley Periodicals LLC.)
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- 2023
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36. Frequency of non-motor symptoms in Parkinson's disease patients carrying the E326K and T369M GBA risk variants.
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Usnich T, Olmedillas M, Schell N, Paul JJ, Curado F, Skobalj S, Csoti I, Ertan S, Gruber D, Zittel S, Sammler E, Isaacson SH, Kühn AA, Pedrosa DJ, Reetz K, Kasten M, Rolfs A, Bauer P, Skrahina V, Klein C, and Brüggemann N
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- Humans, Genotype, Genetic Predisposition to Disease, Glucosylceramidase genetics, Mutation, Parkinson Disease complications, Parkinson Disease genetics
- Abstract
Competing Interests: Declaration of competing interest TU, NS, IC, SE, DG, ES, SHI, AAK, DJP, KR, MK report no conflict of interest. MO, AR, VS at the time of the study were employed by CENTOGENE GmbH. AR and VS are currently employed by Arcensus GmbH. JJP, FP, SS and PB are employed by CENTOGENE GmbH. SZ reports consultancies to Biomarin, receiving honoraria from Merz and Biomarin, and receiving funding from German Research Foundation and European Union; CK reports Medical advisor role to CENTOGENE GmbH for genetic testing of movement disorders excluding Parkinson's disease, and to Retromer Therapeutics; NB received honaria from Abbott, Abbvie, Biogen, Biomarin, Bridgebio, Centogene and Zambon.
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- 2023
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37. Quantitation of a Urinary Profile of Biomarkers in Gaucher Disease Type 1 Patients Using Tandem Mass Spectrometry.
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Menkovic I, Boutin M, Alayoubi A, Curado F, Bauer P, Mercier FE, and Auray-Blais C
- Abstract
Gaucher disease is a rare inherited disorder caused by a deficiency of the lysosomal acid beta-glucocerebrosidase enzyme. Metabolomic studies by our group targeted several new potential urinary biomarkers. Apart from lyso-Gb
1 , these studies highlighted lyso-Gb1 analogs -28, -26, -12 (A/B), +2, +14, +16 (A/B), +30, and +32 Da, and polycyclic lyso-Gb1 analogs 362, 366, 390, and 394 Da. The main objective of the current study was to develop and validate a robust UPLC-MS/MS method to study the urine distribution of these biomarkers in patients., Method: Urine samples were purified using solid-phase extraction. A 12 min UPLC-MS/MS method was developed., Results: Validation assays revealed high precision and accuracy for creatinine and lyso-Gb1 . Most lyso-Gb1 analogs had good recovery rates and high intra- and interday precision assays. Biomarker-estimated LOD and LOQ levels ranged from 56-109 pM to 186-354 pM, respectively. Comparison between GD patients and healthy controls showed significant differences in most biomarker levels. Typically, treated GD patients presented lower biomarker levels compared to untreated patients., Conclusions: These data suggest that the metabolites investigated might be interesting GD biomarkers. More studies with a larger cohort of patients will be needed to better understand the clinical significance of these GD biomarkers.- Published
- 2022
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38. Metabolomic Study Using Time-of-Flight Mass Spectrometry Reveals Novel Urinary Biomarkers for Gaucher Disease Type 1.
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Menkovic I, Boutin M, Alayoubi A, Curado F, Bauer P, Mercier FE, and Auray-Blais C
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- Biomarkers, Humans, Mass Spectrometry, Metabolomics, Prognosis, Gaucher Disease diagnosis, Gaucher Disease genetics
- Abstract
Gaucher disease (GD) is a lysosomal storage disorder resulting from a biallelic mutation in the gene GBA1 , leading to deficiencies in the enzyme β-glucocerebrosidase (Gcase). Inabilities of the Gcase to catabolize its substrate result in the accumulation of sphingolipids in macrophages, which impairs the cell functions and ultimately leads to multisystemic clinical manifestations. Important variability in symptoms and manifestations may lead to challenging diagnosis and patient care. Plasma glucosylsphingosine (lyso-Gb
1 ) is a biomarker frequently used for prognosis, monitoring, and patient follow-up. While lyso-Gb1 appears to be a valid biomarker, few studies have investigated other matrices for potential GD biomarkers. The main objective of this study was to investigate the urine matrix as a potential source of new GD biomarkers by performing a metabolomic study using time-of-flight mass spectrometry. Our study highlighted a significant increase of eight urinary lyso-Gb1 analogues. Moreover, a novel class of biomarkers, named polycyclic lyso-Gb1 analogues, was identified. These four new molecules were more elevated than lyso-Gb1 and related analogues in urine specimens of GD patients. Further investigations are warranted to validate the efficiency of these newly found biomarkers on a larger cohort of Gaucher patients and to compare them with plasma biomarkers currently quantified in clinical laboratories.- Published
- 2022
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39. Lysosphingolipid urine screening test using mass spectrometry for the early detection of lysosomal storage disorders.
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Kelkel MA, Boutin M, Curado F, Bauer P, Beauregard-Lacroix É, Mercier FE, Maranda B, Menkovic I, Martineau T, and Auray-Blais C
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- Chromatography, High Pressure Liquid methods, Chromatography, Liquid methods, Humans, Lysosomes, Sphingolipids, Solid Phase Extraction, Tandem Mass Spectrometry methods
- Abstract
Background: Sphingolipidoses are caused by a defective sphingolipid catabolism, leading to an accumulation of several glycolipid species in tissues and resulting in neurotoxicity and severe systemic manifestations. Methods & results: Urine samples from controls and patients were purified by solid-phase extraction prior to the analysis by ultra-high-performance liquid chromatography (UPLC) combined with MS/MS. A UPLC-MS/MS method for the analysis of 21 urinary creatinine-normalized biomarkers for eight diseases was developed and validated. Conclusion: Considering the growing demand to identify patients with different sphingolipidoses early and reliably, this methodology will be applied for high-risk screening to target efficiently patients with various sphingolipidoses.
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- 2022
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40. Quantitation of a plasma biomarker profile for the early detection of Gaucher disease type 1 patients.
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Menkovic I, Boutin M, Alayoubi A, Curado F, Bauer P, Mercier FE, Rivard GÉ, and Auray-Blais C
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- Early Diagnosis, Humans, Biomarkers blood, Gaucher Disease blood, Gaucher Disease diagnosis
- Abstract
Aim: Gaucher disease (GD) is caused by a deficiency of the lysosomal enzyme acid β-glucocerebrosidase. Recent metabolomic studies highlighted several new metabolites increased in the plasma of GD patients. We aimed to develop and validate a UPLC-MS/MS method allowing a relative quantitation of lyso-Gb
1 and lyso-Gb1 analogs -28, -12, -2, +14, +16 and +18 Da in addition to sphingosylphosphorylcholine, N -palmitoyl- O -phosphocholine to study potential correlations with clinical manifestations. Methodology & results: Following solid-phase extraction, plasma samples were evaporated and resuspended in 100 μl of resuspension solution. Three microliter is injected into the UPLC-MS/MS for analysis. Conclusion: All biomarkers studied were increased in GD patients. Significant correlations were observed between specific analogs and hematological, and visceral complications, as well as overall disease severity.- Published
- 2022
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41. Exploring Silent Speech Interfaces Based on Frequency-Modulated Continuous-Wave Radar.
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Ferreira D, Silva S, Curado F, and Teixeira A
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- Algorithms, Electromyography, Noise, Radar, Speech
- Abstract
Speech is our most natural and efficient form of communication and offers a strong potential to improve how we interact with machines. However, speech communication can sometimes be limited by environmental (e.g., ambient noise), contextual (e.g., need for privacy), or health conditions (e.g., laryngectomy), preventing the consideration of audible speech. In this regard, silent speech interfaces (SSI) have been proposed as an alternative, considering technologies that do not require the production of acoustic signals (e.g., electromyography and video). Unfortunately, despite their plentitude, many still face limitations regarding their everyday use, e.g., being intrusive, non-portable, or raising technical (e.g., lighting conditions for video) or privacy concerns. In line with this necessity, this article explores the consideration of contactless continuous-wave radar to assess its potential for SSI development. A corpus of 13 European Portuguese words was acquired for four speakers and three of them enrolled in a second acquisition session, three months later. Regarding the speaker-dependent models, trained and tested with data from each speaker while using 5-fold cross-validation, average accuracies of 84.50% and 88.00% were respectively obtained from Bagging (BAG) and Linear Regression (LR) classifiers, respectively. Additionally, recognition accuracies of 81.79% and 81.80% were also, respectively, achieved for the session and speaker-independent experiments, establishing promising grounds for further exploring this technology towards silent speech recognition.
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- 2022
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42. The Rostock International Parkinson's Disease (ROPAD) Study: Protocol and Initial Findings.
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Skrahina V, Gaber H, Vollstedt EJ, Förster TM, Usnich T, Curado F, Brüggemann N, Paul J, Bogdanovic X, Zülbahar S, Olmedillas M, Skobalj S, Ameziane N, Bauer P, Csoti I, Koleva-Alazeh N, Grittner U, Westenberger A, Kasten M, Beetz C, Klein C, and Rolfs A
- Subjects
- Cohort Studies, Glucosylceramidase genetics, Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 genetics, Mutation, Observational Studies as Topic, Parkinson Disease diagnosis, Parkinson Disease epidemiology, Parkinson Disease genetics
- Abstract
Background: Genetic stratification of Parkinson's disease (PD) patients facilitates gene-tailored research studies and clinical trials. The objective of this study was to describe the design of and the initial data from the Rostock International Parkinson's Disease (ROPAD) study, an epidemiological observational study aiming to genetically characterize ~10,000 participants., Methods: Recruitment criteria included (1) clinical diagnosis of PD, (2) relative of participant with a reportable LRRK2 variant, or (3) North African Berber or Ashkenazi Jew. DNA analysis involved up to 3 successive steps: (1) variant (LRRK2) and gene (GBA) screening, (2) panel sequencing of 68 PD-linked genes, and (3) genome sequencing., Results: Initial data based on the first 1360 participants indicated that the ROPAD enrollment strategy revealed a genetic diagnostic yield of ~14% among a PD cohort from tertiary referral centers., Conclusions: The ROPAD screening protocol is feasible for high-throughput genetic characterization of PD participants and subsequent prioritization for gene-focused research efforts and clinical trials. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
- Published
- 2021
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43. Rapid Large-Scale COVID-19 Testing During Shortages.
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Beetz C, Skrahina V, Förster TM, Gaber H, Paul JJ, Curado F, Rolfs A, Bauer P, Schäfer S, Weckesser V, Lieu V, Radefeldt M, Pöppel C, Krake S, Kandaswamy KK, Bruesehafer K, and Vogel F
- Abstract
The Coronavirus disease 2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in economic and social lockdowns in most countries all over the globe. Early identification of infected individuals is regarded as one of the most important prerequisites for fighting the pandemic and for returning to a 'New Normal'. Large-scale testing is therefore crucial, but is facing several challenges including shortage of sample collection tools and of molecular biological reagents, and the need for safe electronic communication of medical reports. We present the successful establishment of a holistic SARS-CoV-2 testing platform that covers proband registration, sample collection and shipment, sample testing, and report issuing. The RT-PCR-based virus detection, being central to the platform, was extensively validated: sensitivity and specificity were defined as 96.8% and 100%, respectively; intra-run and inter-run precision were <3%. A novel type of sample swab and an in-house-developed RNA extraction system were shown to perform as good as commercially available products. The resulting flexibility guarantees independence from the current bottlenecks in SARS-CoV-2 testing. Based on our technology, we offered testing at local, national, and global levels. In the present study, we report the results from approx. 18,000 SARS-CoV-2 tests in almost 10,000 individuals from a low-frequency SARS-CoV-2 pandemic area in a homogenous geographical region in north-eastern Germany for a period of 10 weeks (21 March to 31 May 2020). Among the probands, five SARS-CoV-2 positive cases were identified. Comparative analysis of corresponding virus genomes revealed a diverse origin from three of the five currently recognized SARS-CoV-2 phylogenetic clades. Our study exemplifies how preventive SARS-CoV-2 testing can be set up in a rapid and flexible manner. The application of our test has enabled a safe maintenance/resume of critical local infrastructure, e.g., nursing homes where more than 5000 elderlies and caretakers got tested. The strategy outlined by the present study may serve as a blueprint for the implementation of large-scale preventive SARS-CoV-2 testing elsewhere.
- Published
- 2020
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44. Regulation of podosome formation in aortic endothelial cells vessels by physiological extracellular cues.
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Alonso F, Spuul P, Decossas M, Egaña I, Curado F, Fremaux I, Daubon T, and Génot E
- Subjects
- Humans, Aorta anatomy & histology, Endothelial Cells metabolism, Podosomes metabolism
- Abstract
Invadosomes are specialised actin-based dynamic microdomains of the plasma membrane. Their occurrence has been associated with cell adhesion, matrix degrading and mechanosensory functions that make them crucial regulators of cell migration and invasion. Monocytic, cancer cell and Src-transformed cell invadosomes have been extensively described. Less well defined are the structures which form in other cell types, i.e., non-haematopoietic and non-transformed cells, exposed to specific stimuli. We herein describe the specificities of podosomes induced in aortic endothelial cells stimulated with TGFβ in vitro and in conditions that more closely resemble the in vivo situation. These podosomes display the typical architecture of monocytic podosomes. They organise into large rosette-shape superstructures where they exhibit collective dynamic behavior consisting in cycles of formation and regression. At the ultrastructural level, microfilament arrangements in individual podosomes were revealed. Oxygen levels and hemodynamic forces, which are key players in endothelial cell biology, both influence the process. In 3D environment, podosomes appear as globular structures along cellular extensions. A better characterization of endothelial podosomes has far-reaching implications in the understanding and, possibly, in the treatment of some vascular diseases., Competing Interests: Declaration of Competing Interest The authors do not disclose any competing interests., (Copyright © 2020 Elsevier GmbH. All rights reserved.)
- Published
- 2020
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45. New Approach to Guide Target Prostate Biopsy: Technique and Initial Experience.
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Gómez Gómez E, Valero Rosa J, Carrasco Valiente J, Triviño Tarradas F, Anglada Curado F, López Ruiz D, and Requena Tapia MJ
- Abstract
Objective: To describe the technique of transrectal biopsy with a new device that fuses multiparametric magnetic resonance (mpMRI) and ultrasound images in real time to guide target biopsies and to evaluate our initial experience., Methods: Patients with persistent suspicion of prostate cancer despite a previous negative biopsy and who had an mpMRI before the biopsy were selected. All patients underwent target biopsy plus standard systematic biopsy. Significant prostate cancer (sig PCa) was defined according to the Epstein criteria for standard biopsy and Gleason grade of ≥7 and a positive core length of ≥5 mm for target biopsy., Results: The first 40 patients were evaluated. The median age was 65 years old. In a sagittal isotropic sequence, the fusion process was started. The fusion can be improved by using different tools such as concordant points and Global Positioning System corrections tools. In the target biopsy, a median of 4 cores was taken, whereas in the standard biopsy, 12 cores were taken. Twenty-two patients were diagnosed with prostate cancer; of these patients, 17 were diagnosed with sig PCa. The fusion target biopsy diagnosed more sig PCa than the standard biopsy; however, it was not statistically significant (37.5% vs 25%, P=.08). The probability of being diagnosed with cancer increased in correlation with the Prostate Imaging Reporting and Data System score, without reaching statistical significance (k=0.45, P=.08)., Conclusions: This new device is a useful tool to guide biopsy in patients with target lesions in an mpMRI to increase the detection of sig PCa. A larger cohort would be required to show significant differences., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
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46. A Rho signaling network links microtubules to PKD controlled carrier transport to focal adhesions.
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Eisler SA, Curado F, Link G, Schulz S, Noack M, Steinke M, Olayioye MA, and Hausser A
- Subjects
- Cytoskeleton, HEK293 Cells, HeLa Cells, Humans, Phosphoinositide Phospholipase C genetics, Phosphoinositide Phospholipase C metabolism, Protein Transport, Rho Guanine Nucleotide Exchange Factors genetics, Rho Guanine Nucleotide Exchange Factors metabolism, TRPP Cation Channels genetics, TRPP Cation Channels metabolism, rab GTP-Binding Proteins genetics, rab GTP-Binding Proteins metabolism, rhoA GTP-Binding Protein genetics, rhoA GTP-Binding Protein metabolism, Focal Adhesions physiology, Microtubules metabolism, Protein Kinase C metabolism, Signal Transduction, trans-Golgi Network metabolism
- Abstract
Protein kinase D (PKD) is a family of serine/threonine kinases that is required for the structural integrity and function of the Golgi complex. Despite its importance in the regulation of Golgi function, the molecular mechanisms regulating PKD activity are still incompletely understood. Using the genetically encoded PKD activity reporter G-PKDrep we now uncover a Rho signaling network comprising GEF-H1, the RhoGAP DLC3, and the Rho effector PLCε that regulate the activation of PKD at trans-Golgi membranes. We further show that this molecular network coordinates the formation of TGN-derived Rab6-positive transport carriers delivering cargo for localized exocytosis at focal adhesions., Competing Interests: SE, FC, GL, SS, MN, MS, MO, AH No competing interests declared, (© 2018, Eisler et al.)
- Published
- 2018
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47. Impact of 3D vision on mental workload and laparoscopic performance in inexperienced subjects.
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Gómez-Gómez E, Carrasco-Valiente J, Valero-Rosa J, Campos-Hernández JP, Anglada-Curado FJ, Carazo-Carazo JL, Font-Ugalde P, and Requena-Tapia MJ
- Subjects
- Clinical Competence, Cross-Over Studies, Female, Headache etiology, Humans, Laparoscopy methods, Male, Mental Fatigue etiology, Prospective Studies, Psychomotor Performance, Surveys and Questionnaires, Vision Disorders etiology, Young Adult, Imaging, Three-Dimensional adverse effects, Laparoscopy psychology, Simulation Training, Surgeons psychology, Urologic Surgical Procedures
- Abstract
Objective: To assess the effect of vision in three dimensions (3D) versus two dimensions (2D) on mental workload and laparoscopic performance during simulation-based training., Materials and Methods: A prospective, randomized crossover study on inexperienced students in operative laparoscopy was conducted. Forty-six candidates executed five standardized exercises on a pelvitrainer with both vision systems (3D and 2D). Laparoscopy performance was assessed using the total time (in seconds) and the number of failed attempts. For workload assessment, the validated NASA-TLX questionnaire was administered., Results: 3D vision improves the performance reducing the time (3D = 1006.08 ± 315.94 vs. 2D = 1309.17 ± 300.28; P < .001) and the total number of failed attempts (3D = .84 ± 1.26 vs. 2D = 1.86 ± 1.60; P < .001). For each exercise, 3D vision also shows better performance times: "transfer objects" (P = .001), "single knot" (P < .001), "clip and cut" (P < .05), and "needle guidance" (P < .001). Besides, according to the NASA-TLX results, less mental workload is experienced with the use of 3D (P < .001). However, 3D vision was associated with greater visual impairment (P < .01) and headaches (P < .05)., Conclusion: The incorporation of 3D systems in laparoscopic training programs would facilitate the acquisition of laparoscopic skills, because they reduce mental workload and improve the performance on inexperienced surgeons. However, some undesirable effects such as visual discomfort or headache are identified initially., (Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)
- Published
- 2015
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48. Influence of surgical complications on kidney graft survival in recipients of simultaneous pancreas kidney transplantation.
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Campos Hernández JP, Gómez Gómez E, Carrasco Valiente J, Márquez López FJ, Ruiz García J, Anglada Curado FJ, Prieto Castro R, Ruiz Rabelo J, Navarro Cabello ML, and Requena Tapia MJ
- Subjects
- Adult, Aged, Diabetes Mellitus, Type 1 complications, Female, Humans, Incidence, Kaplan-Meier Estimate, Kidney Failure, Chronic etiology, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, Retrospective Studies, Risk Factors, Severity of Illness Index, Treatment Outcome, Diabetes Mellitus, Type 1 surgery, Graft Survival, Kidney Failure, Chronic surgery, Kidney Transplantation methods, Pancreas Transplantation methods, Postoperative Complications diagnosis, Postoperative Complications epidemiology
- Abstract
Purpose: Simultaneous pancreas-kidney transplantation is the gold standard treatment for patients with end-stage renal failure secondary to insulin-dependent diabetes mellitus. This kind of transplantation is a complex operation associated with a high incidence of surgical complications and mortality risk which could influence graft survival. The aim of this study was to establish the influence of different grades of postoperative complications, classified according to Clavien-Dindo, on the rate of kidney graft loss., Methods: We performed an observational retrospective review of all simultaneous transplantations performed between February 1989 and May 2012. Factors examined were related to recipient and donor characteristics, surgical procedures, and postoperative outcomes. For this purpose, Kaplan-Meier analyses and Cox-Regression tests are used., Results: One hundred thirty-nine transplantations were performed. Complications grades I, II, and IIIa were experienced in 81 (58.3%) patients, and grades IIIb and IVa-b in 55 (39.6%). Multivariate analysis showed an influence of panel reactive antibody (hazard ratio [HR]: 10.79; P = .003), incidence of acute rejection (HR: 2.55; P = .03), and complications grouped into grades IIIb and IVa-b (HR: 3.63; P = .02). Kaplan Meier analysis showed worse kidney graft survival rate in groups grades IIIb and IVa-b compared to grades I, II, and IIIa (86.6% vs 98.7% at 1 year and 81.8% vs 97.3% at 5 years; P = .001)., Conclusions: Despite being the gold standard treatment for these patients, pancreas and kidney transplantations have numerous complications which could influence the prognosis of graft kidney survival., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
49. ALK5 and ALK1 play antagonistic roles in transforming growth factor β-induced podosome formation in aortic endothelial cells.
- Author
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Curado F, Spuul P, Egaña I, Rottiers P, Daubon T, Veillat V, Duhamel P, Leclercq A, Gontier E, and Génot E
- Subjects
- Animals, Aorta cytology, Cattle, Endothelial Cells metabolism, Growth Differentiation Factor 2 metabolism, Mice, Mice, Inbred C57BL, Mice, Transgenic, Receptor, Transforming Growth Factor-beta Type I, Signal Transduction, Smad Proteins, Receptor-Regulated metabolism, Actin Cytoskeleton metabolism, Activin Receptors metabolism, Aorta metabolism, Protein Serine-Threonine Kinases metabolism, Receptors, Transforming Growth Factor beta metabolism, Transforming Growth Factor beta metabolism
- Abstract
Transforming growth factor β (TGF-β) and related cytokines play a central role in the vascular system. In vitro, TGF-β induces aortic endothelial cells to assemble subcellular actin-rich structures specialized for matrix degradation called podosomes. To explore further this TGF-β-specific response and determine in which context podosomes form, ALK5 and ALK1 TGF-β receptor signaling pathways were investigated in bovine aortic endothelial cells. We report that TGF-β drives podosome formation through ALK5 and the downstream effectors Smad2 and Smad3. Concurrent TGF-β-induced ALK1 signaling mitigates ALK5 responses through Smad1. ALK1 signaling induced by BMP9 also antagonizes TGF-β-induced podosome formation, but this occurs through both Smad1 and Smad5. Whereas ALK1 neutralization brings ALK5 signals to full potency for TGF-β-induced podosome formation, ALK1 depletion leads to cell disturbances not compatible with podosome assembly. Thus, ALK1 possesses passive and active modalities. Altogether, our results reveal specific features of ALK1 and ALK5 signaling with potential clinical implications., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
- Published
- 2014
- Full Text
- View/download PDF
50. Variations in initial renal transplant function by type of organ retrieval.
- Author
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Alfaro AG, Hernández PC, Gómez EG, Garcia JR, Carazo JL, López FM, Curado FJ, Vallejo ML, López JC, Aljama P, and Tapia MJ
- Subjects
- Adult, Chi-Square Distribution, Delayed Graft Function etiology, Delayed Graft Function physiopathology, Female, Graft Survival, Humans, Kidney physiopathology, Kidney Transplantation adverse effects, Liver Transplantation, Logistic Models, Male, Middle Aged, Multivariate Analysis, Nephrectomy adverse effects, Retrospective Studies, Risk Factors, Spain, Time Factors, Tissue and Organ Harvesting adverse effects, Treatment Outcome, Kidney surgery, Kidney Transplantation methods, Nephrectomy methods, Tissue and Organ Harvesting methods
- Abstract
Background: Numerous factors have been associated with early delay in kidney function and thence the graft survival. However, few data are derived from different types of donation: single or multiorgan. Our goal was to analyze the association of type of retrieval with the early function of the renal graft., Methods: A retrospective analysis of transplantations performed in the Reina Sofia Hospital from January 2004 to June 2012 from local deceased donors was carried out. We performed a descriptive analysis of the variables and univariate and multivariate analyses with the use of logistic regression to determine the association of type of retrieval (kidney-only [KO], kidney-liver [KL], and multiorgan [MO]) with delayed graft function (DGF) and early graft failure (EGF)., Results: We analyzed 287 kidney transplantations from 182 deceased donors, of which 25 (13.7%) were KO, 80 (43.9%) KL, and 77 (42.3%) MO. DGF was higher in MO retrievals compared with KL and KO (25.8% vs 24% vs 20.5%), though without reaching significance (P = .81). EGF at 3 months was 17.6% in KO compared with 10.5% in KL and 5.3% in MO (P = .2). Regarding DGF, in the multivariate analysis, donor age (P = .049) and donor sex (P = .029) appeared to be related to DGF. There were no differences by type of retrieval. Multivariate logistic regression analysis established a significant relationship between KO retrieval and EGF at 3 months (P = .005) compared with MO., Conclusions: Early graft function at 3 months decreases when the allograft is from KO retrievals compared with MO, probably related to the more unfavorable characteristics of these donors and their corresponding recipients., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
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