Effectiveness and safety of first-generation protease inhibitors in clinical practice: Hepatitis C virus patients with advanced fibrosis

AIM: To evaluates the effectiveness and safety of the first generation, NS3/4A protease inhibitors (PIs) in clinical practice against chronic C virus, especially in patients with advanced fibrosis. METHODS: Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1, treatment-nai¨ve (TN) or treatment-experienced (TE), who underwent triple therapy with the first generation NS3/4A protease inhibitors, boceprevir (BOC) and telaprevir (TVR), in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings. Data on the study population and on adverse clinical and virologic effects were compiled during the treatment period and during follow up. RESULTS: One thousand and fifty seven patients were included, 405 (38%) were treated with BOC and 652 (62%) with TVR. Of this total, 30% (n = 319) were TN and the remaining were TE: 28% (n = 298) relapsers, 12% (n = 123) partial responders (PR), 25% (n = 260) null-responders (NR) and for 5% (n = 57) with prior response unknown. The rate of sustained virologic response (SVR) by intention-to-treatment (ITT) was greater in those treated with TVR (65%) than in those treated with BOC (52%) (P < 0.0001), whereas by modified intention-to-treatment (mITT) no were found significant differences. By degree of fibrosis, 56% of patients were F4 and the highest SVR rates were recorded in the non-F4 patients, both TN and TE. In the analysis by groups, the TN patients treated with TVR by ITT showed a higher SVR (P = 0.005). However, by mITT there were no significant differences between BOC and TVR. In the multivariate analysis by mITT, the significant SVR factors were relapsers, IL28B CC and non-F4; the type of treatment (BOC or TVR) was not significant. The lowest SVR values were presented by the F4-NR patients, treated with BOC (46%) or with TVR (45%). 28% of the patients interrupted the treatment, mainly by non-viral response (51%): this outcome was more frequent in the TE than in the TN patients (57% vs 40%, P = 0.01). With respect to severe haematological disorders, neutropaenia was more likely to affect the patients treated with BOC (33% vs 20%, P = 0.0001), and thrombocytopaenia and anaemia, the F4 patients (P = 0.000, P = 0.025, respectively). CONCLUSION: In a real clinical practice setting with a high proportion of patients with advanced fibrosis, effectiveness of first-generation PIs was high except for NR patients, with similar SVR rates being achieved by BOC and TVR

Sesquiterpenoids lactones: benefits to plants and people

Sesquiterpenoids, and specifically sesquiterpene lactones from Asteraceae, may play a highly significant role in human health, both as part of a balanced diet and as pharmaceutical agents, due to their potential for the treatment of cardiovascular disease and cancer. This review highlights the role of sesquiterpene lactones endogenously in the plants that produce them, and explores mechanisms by which they interact in animal and human consumers of these plants. Several mechanisms are proposed for the reduction of inflammation and tumorigenesis at potentially achievable levels in humans. Plants can be classified by their specific array of produced sesquiterpene lactones, showing high levels of translational control. Studies of folk medicines implicate sesquiterpene lactones as the active ingredient in many treatments for other ailments such as diarrhea, burns, influenza, and neurodegradation. In addition to the anti-inflammatory response, sesquiterpene lactones have been found to sensitize tumor cells to conventional drug treatments. This review explores the varied ecological roles of sesquiterpenes in the plant producer, depending upon the plant and the compound. These include allelopathy with other plants, insects, and microbes, thereby causing behavioural or developmental modification to these secondary organisms to the benefit of the sesquiterpenoid producer. Some sesquiterpenoid lactones are antimicrobial, disrupting the cell wall of fungi and invasive bacteria, whereas others protect the plant from environmental stresses that would otherwise cause oxidative damage. Many of the compounds are effective due to their bitter flavor, which has obvious implications for human consumers. The implications of sesquiterpenoid lactone qualitiesfor future crop production are discussed

Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639

Botones de uniforme. España, 1791-2011: apéndice suplementario I

Como primera actualización del libro BOTONES DE UNIFORME. ESPAÑA, 1791-2011, presentamos a continuación una serie de botones aparecidos tras la publicación de éste, los cuales, se organizan siguiendo, obviamente, la numeración utilizada en el libro

La Informática y el uso del ordenador como motivación hacia el trabajo escolar en niños internos en una institución de acción social

Estudiar las posibilidades que presenta el ordenador y, en concreto el lenguaje LOGO, como elemento motivador en el aprendizaje escolar para una población constituida principalmente por niños con problemas de adaptación y bajo rendimiento escolar. Realizar un estudio psicológico, de antecedentes sociales y académicos de la población de la experiencia. Averiguar sus conocimientos iniciales que tienen sobre Informática. Sembrar conceptos pre-informáticos básicos. Proponer una metodología de trabajo para la introducción de la informática en los primeros niveles de la Enseñanza Obligatoria. Niños del Centro San Juan Bautista, comprendidos entre 10 y 13 años, pertenecientes a los ciclos inicial y medio de EGB. Los niños se situan en los cursos por niveles de conocimiento, no por edad cronológica. Se parte de la siguiente hipótesis: el ordenador y concretamente el LOGO motiva el aprendizaje escolar en poblaciones constituidas por niños con problemas de adaptación y bajo rendimiento escolar. Tras varias reuniones, se tomaron unas decisiones: puesta al día de profesorado sobre el funcionamiento del aula piloto de Informática con un seminario de LOGO. Se pasaron a los alumnos unas pruebas de conocimientos informáticos básicos, una prueba de actitud frente a la clase, y un estudio psicológico de los niños. A partir de aquí se formó un grupo de alumnos con bajo rendimiento escolar, se programaron un conjunto de juegos, se analizaron varios modelos de robots, y se plantearon actividades y situaciones de trabajo, todo ello en cuatro fases: 1.-Previa en la que se reformarían los conceptos en los que los niños estaban más flojos. 2.-Vivencial: el niño con su propio cuerpo, realizó un conjunto de movimientos para establecer e interiorizar sus propios ejes. 3.-Intermedia: el niño tuvo que proyectar sus ejes sobre objetos concretos: los robots electrónicos. 4.-Simulación: el niño proyecto ya sus ejes sobre objetos abstractos: la tortuga de luz del ordenador, simulada por un triángulo. Del estudio psicológico se detectan mejoras en la inteligencia y en aspectos como: comprensión del lenguaje, conceptos fundamentales, asimilación de los conceptos relativos al tiempo, pero no obteniendo mejoras significativas en aspectos como la interiorización de los conceptos de lateralidad y la proyección de ejes sobre objetos orientados. Los conocimientos informáticos de los alumnos eran prácticamente inexistentes. La dramatización sobre el funcionamiento del ordenador les acercó a su comprensión, pasando a ser éste un elemento más familiar al saber ya como funcionaba. Se apreció una gran motivación hacia la lectura y escritura.ExtremaduraBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5 - 3 Planta; 28014 Madrid; Tel. +34917748000; Fax +34917748026; [email protected]

Libro de Actas de las III Jornadas ScienCity 2020: Fomento de la Cultura Científica, Tecnológica y de Innovación en Ciudades Inteligentes

Editorial: Kindle Direct Publishing, Seattle, WS (USA)Actualmente, nuestras ciudades están experimentando una verdadera transformación digital que requiere una atención inmediata en energía, transporte, movilidad, comunicación, seguridad, educación, turismo y aspectos sociales, así como fomentar todas aquellas actuaciones que persigan mejorar la calidad de vida y el desarrollo económico-ambiental sostenible. ScienCity es un foro científico-tecnológico que pretende dar a conocer a la sociedad los conocimientos y tecnologías emergentes siendo investigados en las universidades, informar de experiencias, servicios e iniciativas puestas ya en marcha por instituciones y empresas, llegar hasta decisores políticos que podrían crear sinergias, incentivar la creación de ideas y posibilidades de desarrollo conjuntas, implicar y provocar la participación ciudadana.Junta de Andalucía, Universidad de Huelva y Consejo Social de la Universidad de Huelv

Dietary α-linolenic acid, marine ω-3 fatty acids, and mortality in a population with high fish consumption: Findings from the PREvención con DIeta MEDiterránea (PREDIMED) Study

12 Páginas.-- 6 Tablas.-- 1 FiguraBackground-Epidemiological evidence suggests a cardioprotective role of α-linolenic acid (ALA), a plant-derived ω-3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω-3 fatty acids (long-chain n-3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all-cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long-chain n-3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results-We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable-adjusted Cox regressionmodels were fitted to estimate hazard ratios. ALA intake correlated towalnut consumption (r=0.94). During a 5.9-y follow-up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios formeeting ALArecommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56-0.92) for all-causemortality and 0.95 (95% CI 0.58-1.57) for fatal cardiovascular disease. The hazard ratios formeeting the recommendation for long-chain n-3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67-1.05) for all-causemortality, 0.61 (95% CI 0.39-0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29-0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22-1.01) for sudden cardiac death. The highest reduction in all-cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45-0.87]). Conclusions-In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all-cause mortality, whereas protection from cardiac mortality is limited to fish-derived long-chain n-3 polyunsaturated fatty acids.This study was funded in part by Instituto de Salud Carlos III (ISCIII) (Spanish Ministry of Economy) through grants RTIC G03/140, RTIC RD 06/0045, Centro Nacional de Investigaciones Cardiovasculares CNIC 06/2007, ISCIII FIS PS09/01292, the Spanish Ministry of Science and Innovation (MICINN) AGL2010‐22319‐C03‐02 and AGL2009‐13906‐C02‐02, and an unrestricted grant from the California Walnut Commission. Sala‐Vila holds a Miguel Servet I fellowship from the Ministry of Economy and Competitiveness through the ISCIII

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function.Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien-Dindo classification system.Results: A total of 3288 patients were included in the analysis, of whom 301 (9.2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4-7) and 7 (6-8) days respectively (P &lt; 0.001). There were no significant differences in rates of readmission between these groups (6.6 versus 8.0 per cent; P = 0.499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0.90, 95 per cent c.i. 0.55 to 1.46; P = 0.659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34.7 versus 39.5 per cent; major 3.3 versus 3.4 per cent; P = 0.110).Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients