Optimization and quantification of stimulation parameters in subthalamic nucleus deep brain stimulation for Parkinson's disease

La estimulación cerebral profunda del núcleo subtalámico (ECP-NST) es un tratamiento seguro y eficaz en pacientes seleccionados con enfermedad de Parkinson (EP) avanzada. El éxito de la misma depende de la precisión en la implantación de los electrodos y una correcta programación de los parámetros de estimulación. Actualmente existen ciertas guías para la selección de los parámetros de estimulación. Éstas han asumido de forma empírica que el efecto agudo de la estimulación determinaría una buena evolución a largo plazo. El sitio óptimo de estimulación dentro del área subtalámica ha sido y continua siendo una cuestión ampliamente debatida. Conocer el sitio óptimo de estimulación tiene implicaciones en las estrategias de programación, ya que la información anatómica se podría utilizar para la selección del contacto del electrodo clínicamente más eficaz. Por último, oscilaciones en la banda beta de los potenciales de campo locales (PCL), son una marca de la parte sensitivomotora del NST que generalmente se acepta como la zona óptima de estimulación. Por tanto, la profundidad a la que se detecta un pico en la banda beta podría ser indicativo de la zona óptima de estimulación y dicha información podría integrarse también en las estrategias de programación. En este estudio evaluamos a 31 pacientes con EP tratados con ECP-NST durante al menos 12 meses. Estos pacientes realizaron un total de tres sesiones de ajustes de los parámetros de estimulación. En cada sesión se realizó una valoración basal, aguda (inmediatamente tras ajuste de los parámetros de estimulación) y crónica (1, 2 y 3 meses tras la valoración aguda para las sesiones de ajuste 1, 2, y 3). El factor que predijo de una forma más consistente un beneficio motor a largo plazo fue la mejoría aguda en los síntomas motores. Sin embargo, el efecto agudo necesita ser de una magnitud suficiente para asegurar un efecto a largo plazo. La magnitud del mismo depende de la optimización previa de la terapia de estimulación. Tras las sesiones de reprogramación de la estimulación el 42% de los pacientes obtuvieron beneficios adicionales de la terapia de ECP, mientras que el 43% se mantuvieron estables. Así mismo fue posible una reducción adicional del 30% en las necesidades de medicación dopaminérgica. Aquellos que obtuvieron mayores beneficios fueron los que requirieron un único cambio en el contacto estimulado, mientras que aquellos precisando múltiples cambios de contacto no mejoraron. Los pacientes más jóvenes, las mujeres y aquellos con síntomas motores más acusados al inicio del estudio mostraron una mayor probabilidad de mejorar al final del estudio. El sitio de estimulación evolucionó de la parte central de NST hasta su segmento superior, siendo ésta la localización mas frecuente después de las tres sesiones de optimización de la estimulación. Aquellos electrodos cuyos contactos estimulados se encontraban en la zona óptima de estimulación presentaron una mayor eficacia y eficiencia en la estimulación y menores requerimientos de medicación dopaminérgica. En un 70% de los casos el contacto seleccionado clínicamente correspondía al contacto mejor localizado anatómicamente (en las imágenes de RM). Cuando ambos contactos (RM/clínico) coincidían la optimización de la estimulación había sido mas sencilla. Si no existía coincidencia, la ECP era menos eficiente (en términos de energía eléctrica total liberada por el sistema o voltaje utilizado). En cuanto al estudio de los PCL obtuvimos que existe una buena correlación entra la profundidad a la que se registra el pico en la banda beta (generador beta, indicativo de la parte sensitivomotora del NST) y el contacto utilizado para la estimulación crónica. De forma que la estimulación era más eficiente cuando la distancia entre el generador beta y el contacto terapéutico era menor. Todos estos datos nos permiten concluir: 1) el efecto agudo de la estimulación sobre los síntomas motores es el mejor predictor del efecto a largo plazo; 2) se pueden obtener beneficios adicionales con la reprogramación en pacientes crónicamente tratados con ECP-NST; 3) el sitio óptimo de estimulación es la parte superior del NST; 4) la selección del contacto del electrodo de ECP puede implementarse con la información anatómica y el registro de los PCL intraoperatorios. La integración de la información anatómica y de los datos de los PCL pueden simplificar las actuales estrategias de programación

Open innovation in Starbucks Corporation

El acortamiento del ciclo de vida de los productos y la presencia activa del consumidor en fases previas a su comercialización ha supuesto un cambio en la visión empresarial. Asimismo, la generalización de las TIC supone el principal factor evolutivo del análisis de la información. Haciendo uso de estas nuevas tecnologías surge la innovación abierta u open innovation, que es una forma de externalizar el proceso de innovación de una empresa. Dicho proceso se basa en involucrar al cliente en los procesos de innovación. En lugar de ser la empresa quien crea las innovaciones y las ofrece a los clientes, el proceso de innovación abierta supone que los consumidores toman un papel activo en el desarrollo de las innovaciones junto con la empresa. El objetivo de este trabajo es analizar en qué consiste y cómo se llevan a cabo los procesos de innovación abierta. Como caso de estudio se ha analizado la web utilizada por una empresa de la hostelería, Starbucks Corporation, que está haciendo uso de una comunidad de innovación abierta. El trabajo detalla las principales características de este portal, las posibilidades de participación de los usuarios y los procesos de evaluación colectiva para discriminar las mejores innovacionesThe shortening of the life cycle of the products and the consumer's active presence in pre-commercialization phases has been a change in the corporate vision. Also, the spread of ICT is the main evolutionary factor analysis of information. Making use of these new technologies open innovation arises. This is a way of externalizing the innovation process of a firm. This process is based on customer involvement in the innovation process. Instead of being the company who make innovations and offers customers, the open innovation process means that consumers take an active role in the development of innovations with the company. The aim of this paper is to analyze what it is and how open innovation processes are held. As a case study we have analyzed the website used by a company in the hostelry sector, Starbucks Corporation, which is using an open innovation community. The paper describes the main features of this portal, the possibilities of user participation and collective assessment processes to discriminate the best innovation

Competencia por el alimento entre el cormorán moñudo, el cormorán grande y la pesca artesanal: un caso de estudio

The Mediterranean shag (Phalacrocorax aristotelis desmarestii) and the great cormorant (P. carbo sinensis) are syntopic birds in an area encompassing Grosa Island and the Mar Menor coastal lagoon (SE Spain, western Mediterranean) during the breeding season of the former and the wintering period of the latter. Diet composition of both birds was studied through pellet analysis and otolith identification. Competition for fish resources between these two seabirds and with local artisanal fisheries was assessed. Shags preyed preferentially on small pelagic fish, and great cormorants mainly consumed demersal fish. Shag diet consisted of marine fish strictly, but great cormorant fed in all the available environments in the study area, including marine, transitional (coastal lagoon) and freshwater reservoirs. The great dissimilarity observed between shag and great cormorant diet composition showed no competition between them. The low shag population density and fishing effort in their foraging area suggested no competition with fisheries. Conversely, great cormorant population density in the study area was very high, and they foraged on fish of high commercial value. However, competition between great cormorant and artisanal fisheries only affected some of the less abundant species fished.El cormorán moñudo (Phalacrocorax aristotelis desmarestii) y el cormorán grande (P. carbo sinensis) son especies sintópicas en el entorno de Isla Grosa y la laguna costera del Mar Menor (SE de España, Mediterráneo occidental) durante la época de reproducción del primero que coincide con la invernada del segundo. Se estudia la composición de la dieta de ambas especies mediante la identificación de otolitos en sus egagrópilas, y se evalúa la competencia entre ambas especies y con la pesca artesanal local. El cormorán moñudo se alimentó mayoritariamente de pequeños peces pelágicos, y el cormorán grande consumió principalmente peces demersales. La dieta del cormorán moñudo consistió estrictamente de peces marinos, mientras que el cormorán grande capturó peces en los diferentes ambientes acuáticos de la zona de estudio, incluyendo especies marinas, de lagunas costeras e incluso de embalses de agua dulce. La gran disimilitud observada entre la composición de la dieta de ambas aves nos indica que no existe competencia por el alimento entre ellas. Asimismo, la baja densidad poblacional de cormorán moñudo y su esfuerzo pesquero en la zona de estudio tampoco demuestran competencia con la pesca artesanal local. Por el contrario, la abundancia de cormorán grande en la zona de estudio es muy alta, y se alimentaron principalmente de especies de alto valor comercial para los pescadores locales. No obstante, solo se observó competencia con la pesca artesanal local por alguna especie de pez de las menos abundantemente capturadas por los pescadores

Method Effects Associated to Item Valence: Evidence From the 10-Item Big-Five Inventory in Older Adults

The objective of this study is to analyze the factor structure of the BFI-10 considering item valence effects when applied to measure older adults. Likewise, this study aims to estimate the factorial structure, internal consistency of the scale, to assess the nomological validity, and the association of the Big Five traits with age. 75,078 participants with mean age of 68.27 from the 7th Wave of the SHARE study were included. Confirmatory Factor Analyses, omega coefficients and Pearson correlations were estimated. The best-fit model identified a five-factor structure with two valence effects, internal consistency ranged from .26 to .64, the nomological network showed that loneliness is negatively associated to neuroticism and positively with the other four traits, and the opposite direction in the associations with the five traits and satisfaction and quality of life. Consciousness, Extraversion and Openness have been found as dimensions that tend to decrease with age

Open innovation in Starbucks Corporation

El acortamiento del ciclo de vida de los productos y la presencia activa del consumidor en fases previas a su comercialización ha supuesto un cambio en la visión empresarial. Asimismo, la generalización de las TIC supone el principal factor evolutivo del análisis de la información. Haciendo uso de estas nuevas tecnologías surge la innovación abierta u open innovation, que es una forma de externalizar el proceso de innovación de una empresa. Dicho proceso se basa en involucrar al cliente en los procesos de innovación. En lugar de ser la empresa quien crea las innovaciones y las ofrece a los clientes, el proceso de innovación abierta supone que los consumidores toman un papel activo en el desarrollo de las innovaciones junto con la empresa. El objetivo de este trabajo es analizar en qué consiste y cómo se llevan a cabo los procesos de innovación abierta. Como caso de estudio se ha analizado la web utilizada por una empresa de la hostelería, Starbucks Corporation, que está haciendo uso de una comunidad de innovación abierta. El trabajo detalla las principales características de este portal, las posibilidades de participación de los usuarios y los procesos de evaluación colectiva para discriminar las mejores innovaciones.The shortening of the life cycle of the products and the consumer's active presence in pre-commercialization phases has been a change in the corporate vision. Also, the spread of ICT is the main evolutionary factor analysis of information. Making use of these new technologies open innovation arises. This is a way of externalizing the innovation process of a firm. This process is based on customer involvement in the innovation process. Instead of being the company who make innovations and offers customers, the open innovation process means that consumers take an active role in the development of innovations with the company. The aim of this paper is to analyze what it is and how open innovation processes are held. As a case study we have analyzed the website used by a company in the hostelry sector, Starbucks Corporation, which is using an open innovation community. The paper describes the main features of this portal, the possibilities of user participation and collective assessment processes to discriminate the best innovations

Fracturas juveniles de tobillo

Este trabajo es una revisión bibliográfica sobre las fracturas juveniles de tobillo, cuyo objetivo es recoger los datos más relevantes para que el diagnóstico y tratamiento sean lo más específicos e individualizados posible. Se profundiza en el sistema de clasificación más habitual, así como en las fracturas que son más frecuentes en los niños y adolescentes. Es de gran importancia saber cómo manejar cada fractura para evitar complicaciones a corto y largo plazo.<br /

Psychometric properties of the EURO-D scale of depressive symptomatology: Evidence from SHARE wave 8

Background The EURO-D is a short scale to measure symptoms of depression, very used in large population surveys. Although there are numerous validation studies, its psychometric properties remain unclear. The two-factor structure (Affective Suffering and Lack of Motivation) is replicated in several studies but with different item compositions, and none reported reliability indices for both factors. For that reason, the aim of this study is to examine the factorial validity of the scale, the reliability of the dimensions, the gender differential item functioning (DIF), and the nomological validity. Methods 46,317 participants aged 50 and over (M = 71.33), from which 57.4 % were females, in Wave 8 of the Survey of Health, Aging and Retirement in Europe (SHARE) were included. Instruments: EURO-D, R-UCLA, Self-perceived health index, and indicator of taking drugs for anxiety or depression. Factor Analyses, DIF, Reliability Index and Spearman correlations were estimated. Results Factor analysis identified a bifactor structure: a general factor of Depression and two specific factors of Affective Suffering and Lack of Motivation, which reliabilities were 0.83, 0.83 and 0.79 respectively. No relevant DIF item by gender was found, but higher scores were found in women in all factors. Both factors had positive relations with loneliness, taking drugs and self-perceived health. Limitations this study has a cross-sectional design; future research may consider the longitudinal stability of the scale. Conclusions EURO-D shows adequate psychometric properties when a general factor of depression and two specific factors are considered. Women have higher scores on all dimensions

Rotavirus infection beyond the gut

The landscape of rotavirus (RV) infection has changed substantially in recent years. Autoimmune triggering has been added to clinical spectrum of this pathology, which is now known to be much broader than diarrhea. The impact of RV vaccines in these other conditions is becoming a growing field of research. The importance of host genetic background in RV susceptibility has been revealed, therefore increasing our understanding of vaccine effectiveness and giving some clues about the limited efficacy of RV vaccines in low-income settings. Also, interaction of RV with intestinal microbiota seems to play a key role in the process of infection vaccine effect. This article reviews current findings on the extraintestinal impact of RV infection and their widening clinical picture, and the recently described mechanisms of host susceptibility to infection and vaccine effectiveness. RV infection is a systemic disease with clinical and pathophysiological implications beyond the gut. We propose an "iceberg" model for this pathology with almost hidden clinical implications away from the gastrointestinal tract and eventually triggering the development of autoimmune diseases. Impact of current vaccines is being influenced by host genetics and gut microbiota interactions and these factors must be taken into account in the development of public health programs

Real-Time In Vivo Detection of Cellular Senescence through the Controlled Release of the NIR Fluorescent Dye Nile Blue

This is the peer reviewed version of the following article: B. Lozano-Torres, J. F. Blandez, I. Galiana, A. García-Fernández, M. Alfonso, M. D. Marcos, M. Orzáez, F. Sancenón, R. Martínez-Máñez, Angew. Chem. Int. Ed. 2020, 59, 15152., which has been published in final form at https://doi.org/10.1002/anie.202004142. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.[EN] In vivo detection of cellular senescence is accomplished by using mesoporous silica nanoparticles loaded with the NIR-FDA approved Nile blue (NB) dye and capped with a galactohexasaccharide (S3). NB emission at 672 nm is highly quenched inside S3, yet a remarkable emission enhancement is observed upon cap hydrolysis in the presence of beta-galactosidase and dye release. The efficacy of the probe to detect cellular senescence is tested in vitro in melanoma SK-Mel-103 and breast cancer 4T1 cells and in vivo in palbociclib-treated BALB/cByJ mice bearing breast cancer tumor.R.M. thanks financial support from the Spanish Government (RTI2018-100910-B-C41 and RTI2018-101599-B-C22 (MCUI/AEI/FEDER, UE)) and the Generalitat Valenciana (PROMETEO 2018/024). M.O. thanks the financial support from SAF2017-84689-R project and MINECO/AEI/FEDER, UE and the Generalitat Valenciana (PROMETEO/2019/065). B.L.-T. is grateful to the Spanish Ministry of Economy for her PhD grant. I.G. thanks her contract from IDM. J.F.-B. and M.A. thank the UPV for their postdoctoral fellowship.Lozano-Torres, B.; Blandez, JF.; Galiana, I.; García-Fernández, A.; Alfonso-Navarro, M.; Marcos Martínez, MD.; Orzáez, M.... (2020). Real-Time In Vivo Detection of Cellular Senescence through the Controlled Release of the NIR Fluorescent Dye Nile Blue. 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Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic

[EN] The induction of senescence produces a stable cell cycle arrest in cancer cells, thereby inhibiting tumor growth; however, the incomplete immune cell-mediated clearance of senescent cells may favor tumor relapse, limiting the long-term anti-tumorigenic effect of such drugs. A combination of senescence induction and the elimination of senescent cells may, therefore, represent an efficient means to inhibit tumor relapse. In this study, we explored the antitumor efficacy of a combinatory senogenic and targeted senolytic therapy in an immunocompetent orthotopic mouse model of the aggressive triple negative breast cancer subtype. Following palbociclib-induced senogenesis and senolysis by treatment with nano-encapsulated senolytic agent navitoclax, we observed inhibited tumor growth, reduced metastases, and a reduction in the systemic toxicity of navitoclax. We believe that this combination treatment approach may have relevance to other senescence-inducing chemotherapeutic drugs and additional tumor types. Significance: While the application of senescence inducers represents a successful treatment strategy in breast cancer patients, some patients still relapse, perhaps due to the subsequent accumulation of senescent cells in the body that can promote tumor recurrence. We now demonstrate that a combination treatment of a senescence inducer and a senolytic nanoparticle selectively eliminates senescent cells, delays tumor growth, and reduces metastases in a mouse model of aggressive breast cancer. Collectively, our results support targeted senolysis as a new therapeutic opportunity to improve outcomes in breast cancer patients.The M.O. laboratory members thank the financial support from the Spanish Government (project SAF2017-84689-R (MINECO/AEI/FEDER, EU)) and the Generalitat Valenciana (project PROMETEO/2019/065). The R.M. laboratory members thank the financial support from the Spanish Government (projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22 (MCUI/FEDER, EU) and the Generalitat Valenciana (project PROMETEO 2018/024). Both I.G. and B.L-T. are grateful to the Generalitat Valenciana and the Spanish Ministry of Economy, respectively, for their Ph.D. grants. I.G. would like to thank I. Borreda and J. Forteza and the Instituto Valenciano de Patologia for their special collaboration and F. Sancenon for his appreciated helpGaliana, I.; Lozano-Torres, B.; Sancho, M.; Alfonso-Navarro, M.; Bernardos Bau, A.; Bisbal, V.; Serrano, M.... (2020). Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic. Journal of Controlled Release. 323:624-634. https://doi.org/10.1016/j.jconrel.2020.04.045S624634323Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018). Hallmarks of Cellular Senescence. 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