The CNIC-Polypill reduces recurrent major cardiovascular events in real-life secondary prevention patients in Spain: The NEPTUNO study.

To evaluate the effectiveness of a cardiovascular polypill including aspirin, ramipril and atorvastatin (CNIC-Polypill), on the incidence of recurrent major cardiovascular events (MACE) and risk factor control in patients with established atherosclerotic cardiovascular disease (ASCVD) vs different pharmacological therapeutic strategies. Retrospective, observational study using data from electronic-health records. Patients were distributed into 4 different cohorts: CNIC-Polypill (case cohort) vs 3 control cohorts: same monocomponents taken separately (Monocomponents), equipotent drugs (Equipotent) and other drugs not included in the previous cohorts (Other therapies). Patients were followed for 2 years or until MACE or death. After propensity score matching, a total of 6456 patients (1614 patients per cohort) were analysed. After 2 years, the risk of recurrent MACE was lower in the CNIC-Polypill cohort compared to the control groups (22%; p = 0.017, 25%; p = 0.002, 27%; p = 0.001, higher in the Monocomponents, Equipotent and Other therapies cohorts, respectively). The incremental proportion of patients who achieved blood pressure (BP) and low-density lipoprotein cholesterol (LDLc) control from baseline was higher in the CNIC-Polypill cohort vs control cohorts (BP controlled patients: +12.5% vs + 6.3%; p < 0.05, +2.2%; p < 0.01, +2.4%; p < 0.01, LDLc controlled patients: +10.3% vs + 4.9%; p < 0.001, +5.7%; p < 0.001, +4.9%; p < 0.001, respectively). Medication persistence was higher in patients treated with the CNIC-Polypill (72.1% vs 62.2%, 60.0% and 54.2%, respectively; p < 0.001) at study end. In secondary prevention patients, compared with control groups, treatment with the CNIC-Polypill was associated with significant reductions in the accumulated incidence of recurrent MACE, improved BP and LDLc control rates, and increased medication persistence.FerrerS

Bacillus subtilis IAB/BS03 as a potential biological control agent

[EN] We describe the efficacy of Bacillus subtilis strain IAB/BS03 in reducing disease incidence of B. subtilis IAB/BS03 as a foliar treatment against Botrytis cinerea and Pseudomonas syringae on greenhouse-grown tomato (Solanum lycopersicon) plants. We also tested the effect of foliar treatments on lettuce (Lactuca sativa) against lettuce downy mildew caused by Bremia lactucae in multiple trials under different field conditions. All the assays indicated that B. subtilis IAB/BS03 reduced disease. To ascertain the mechanism of action, the induction of pathogenesis-related (PR) proteins, the accumulation of salicylic acid and the activation of peroxidase caused by foliar or root treatments with B. subtilis IAB/BS03 were studied in tomato. A salicylic acid-independent induction of the antifungal protein PR1 was observed after treatment with B. subtilis IAB/BS03, with the strongest induction due to root treatment compared with foliar application. A metabolic analysis of B. subtilis IAB/BS03 culture broth using Ultra Performance Liquid Chromatography coupled with ultraviolet and mass spectrometric detection determined surfactin and iturin A isomers. These compounds have been described as antifungal and antibiotic lipopeptides. The results indicated that B. subtilis IAB/BS03 could be effectively used as a biocontrol agent.This work was funded by IAB S. L. (Investigaciones y Aplicaciones Biotecnologicas, S. L.), and by grant BIO2012-33419 from the Spanish Ministry of Economy and Competitiveness. Mayte Castellano was the recipient of a research grant also funded by IAB S. L. The authors would like to thank Cristina Torres (IBMCP, UPV-CSIC) for her excellent technical assistance.Hinarejos, E.; Castellano Pérez, M.; Rodrigo Bravo, I.; Belles Albert, JM.; Conejero Tomás, V.; López-Gresa, MP.; Lisón, P. (2016). Bacillus subtilis IAB/BS03 as a potential biological control agent. European Journal of Plant Pathology. 146(3):597-608. https://doi.org/10.1007/s10658-016-0945-3S5976081463Abbott, W. S. (1925). A method for computing the effectiveness of an insecticide. Journal Economic Entomology, 18, 265–267.Chen, H., Wang, L., Su, C.X., Gong, G. H., Wang, P., Yu, Z. L. (2008). Isolation and characterization of lipopeptide antibiotics produced by Bacillus subtilis. Letters in Applied Microbiology. 47, 180–186.Cho, S. J., Lee, S. K., Cha, B. J., Kim, Y. H., & Shin, K. S. (2003). Detection and characterization of the Gloeosporium gloeosporioides growth inhibitory compound iturin a from Bacillus subtilis strain KS03. FEMS Microbiology Letters, 223, 47–51.Choudhary, D. K., & Johri, B. N. (2009). Interactions of Bacillus spp. and plants with special reference to induced systemic resistance (ISR). Microbiology Research, 164, 493–513.Coego, A., Ramírez, V., Ellul, P., Mayda, E., & Vera, P. (2005). The H2O2-regulated Ep5C gene encodes a peroxidase required for bacterial speck susceptibility in tomato. The Plant Journal, 42, 283–293.Conrath, U., Pieterse, C. M. J., & Mauch-Mani, B. (2002). Priming in plant-pathogen interactions. Trends in Plant Science, 7, 210–216.Fleming, A. J., Mandel, T., Roth, I., & Kuhlemier, C. (1993). The patterns of gene expression in the tomato shoot apical meristem. The Plant Cell, 5, 297–309.Fravel, D. R. (2005). Commercialization and implementation of biocontrol. Annual Review of Phytopathology, 43, 337–359.Hammerschmidt, R., Nuckles, E. M., & Kuc, J. (1982). Association of enhanced peroxidase activity with induced systemic resistance of cucumber to Colletotrichum lagenarium. Physiological Plant Pathology, 20, 73–76.Kawagoe, Y., Shiraishi, S., Kondo, H., Yamamoto, S., Aoki, Y., & Suzuki, S. (2015). Cyclic lipopeptide iturin a structure-dependently induces defense response in Arabidopsis plants by activating SA and JA signaling pathways. Biochemical and Biophysical Research Communications, 460, 1015–1020.Kloepper, J. W., Ryu, C. M., & Zhang, S. A. (2004). Induced systemic resistance and promotion of plant growth by Bacillus spp. Phytopathology, 94, 1259–1266.Liu, H.-X., Li, S.-M., Luo, Y.-M., Luo, L.-X., Li, J.-Q., & Guo, J.-H. (2014). Biological control of Ralstonia wilt, Phytophthora blight, Meloidogyne root-knot on bell pepper by the combination of Bacillus subtilis AR12, Bacillus subtilis SM21 and Chryseobacterium sp. R89. European Journal of Plant Pathology, 139, 107–116.Mohammadi, M., & Kazemi, H. (2002). Changes in peroxidase and polyphenol oxidase activities in susceptible and resistant wheat heads inoculated with Fusarium graminearum and induced resistance. Plant Science, 162, 491–498.Niderman, T., Genetet, I., Bruyere, T., Gees, R., Stintzi, A., Legrand, M., et al. (1995). Pathogenesis-related PR-1 proteins are antifungal - isolation and characterization of 3 14-Kilodalton proteins of tomato and of a basic PR-1 of tobacco with inhibitory activity against Phytophthora infestans. Plant Physiology, 108, 17–27.Ohno, A., Ano, T., & Shoda, M. (1995). Effect of temperature on production of lipopeptide antibiotics, iturin a and surfactin by a dual producer, Bacillus subtilis Rb14, in solid-state fermentation. Journal of Fermentation and Bioengineering, 80, 517–519.Ongena, M., & Jacques, P. (2008). Bacillus lipopeptides: versatile weapons for plant disease biocontrol. Trends in Microbiology, 16, 115–125.Pérez-García, A., Romero, D., & De Vicente, A. (2011). Plant protection and growth stimulation by microorganisms: biotechnological applications of bacilli in agriculture. Current Opinion in Biotechnology, 22, 187–193.Phister, T. G., O’Sullivan, D. J., & McKay, L. L. (2004). Identification of bacilysin, chlorotetaine, and iturin a produced by Bacillus sp strain CS93 isolated from pozol, a Mexican fermented maize dough. Applied Environmental Microbiology, 70, 631–634.Pieterse, C. M. J., vanWees, S. C. M., Hoffland, E., Van Pelt, J. A., & Van Loon, L. C. (1996). Systemic resistance in Arabidopsis induced by biocontrol bacteria is independent of salicylic acid accumulation and pathogenesis-related gene expression. The Plant Cell, 8, 1225–1237.Pryor, S. W., Gibson, D. M., Krasnoff, S. B., & Walker, L. P. (2006). Identification of antifungal compounds in a biological control product using a microplate inhibition bioassay. Transactions of the ASAE, 49, 1643–1649.Robert-Seilaniantz, A., Navarro, L., Bari, R., & Jones, J. D. (2007). Pathological hormone imbalances. Current Opinion in Plant Biology, 10, 372–379.Rudrappa, T., Biedrzycki, M. L., Kunjeti, S. G., Donofrio, N. M., Czymmek, K. J., Paul W, P., et al. (2010). The rhizobacterial elicitor acetoin induces systemic resistance in Arabidopsis thaliana. Communicative and Integrative Biology, 3, 130–138.Summermatter, K., Sticher, L., & Métraux, J. P. (1995). Systemic responses in Arabidopsis thaliana infected and challenged with Pseudomonas syringae pv syringae. Plant Physiology, 108, 1379–1385.Tang, J. S., Zhao, F., Gao, H., Dai, Y., Yao, Z. H., Hong, K., et al. (2010). Characterization and online detection of surfactin isomers based on HPLC-MSn analyses and their inhibitory effects on the overproduction of nitric oxide and the release of TNF-α and IL-6 in LPS induced macrophages. Marine Drugs, 8, 2605–2618.Tornero, P., Gadea, J., Conejero, V., & Vera, P. (1997). Two PR-1 genes from tomato are differentially regulated and reveal a novel mode of expression for a pathogenesis-related gene during the hypersensitive response and development. Molecular Plant-Microbe Interactions, 10, 624–634.Tsavkelova, E. A., Klimova, S. Y., Cherdyntseva, T. A., & Netrusov, A. I. (2006). Microbial producers of plant growth stimulators and their practical use: a review. Applied Biochemistry and Microbiology, 42, 117–126.Van Loon, L. C. (2007). Plant responses to plant growth-promoting rhizobacteria. European Journal of Plant Pathology, 119, 243–254.Verhagen, B. W. M., Glazebrook, J., Zhu, T., Chang, H. S., Van Loon, L. C., & Pieterse, C. M. J. (2004). The transcriptome of rhizobacteria-induced systemic resistance in Arabidopsis. Molecular Plant-Microbe Interactions, 17, 895–908.Wulff, B. B. H., Horvath, D. M., & Ward, E. R. (2011). Improving immunity in crops: new tactics in an old game. Current Opinion in Plant Biology, 14, 468–476.Yáñez-Mendizábal, V., Zeriouh, H., Viñas, I., Torres, R., Usall, J., de Vicente, A., et al. (2012). Biological control of peach brown rot (Monilinia spp.) by Bacillus subtilis CPA-8 is based on production of fengycin-like lipopeptides. European Journal of Plant Pathology, 132, 609–619.Zacarés, L., López-Gresa, M. P., Fayos, J., Primo, J., Bellés, J. M., & Conejero, V. (2007). Induction of p-coumaroyldopamine and feruloyldopamine, two novel metabolites, in tomato by the bacterial pathogen Pseudomonas syringae. Molecular Plant-Microbe Interactions, 20, 1439–1448.Zadoks, J. C., Chang, T. T., & Konzak, C. F. (1974). A decimal code for the growth stages of cereals. Weed Research, 14, 415–421.Zeriouh, H., Romero, D., García-Gutiérrez, L., Cazorla, F. M., De Vicente, A., & Pérez-García, A. (2011). The iturin-like lipopeptides are essential components in the biological control arsenal of Bacillus subtilis against bacterial diseases of cucurbits. Molecular Plant-Microbe Interactions, 24, 1540–1552

Economic Burden Associated with the Treatment with a Cardiovascular Polypill in Secondary Prevention in Spain: Cost-Effectiveness Results of the NEPTUNO Study.

PURPOSE The aim of this study was to estimate health-care resources utilization, costs and cost-effectiveness associated with the treatment with CNIC-Polypill as secondary prevention of atherosclerotic cardiovascular disease (ASCVD) compared to other treatments, in clinical practice in Spain. PATIENTS AND METHODS An observational, retrospective study was performed using medical records (economic results [healthcare perspective], NEPTUNO-study; BIG-PAC-database) of patients who initiated secondary prevention between 2015 and 2018. Patients were followed up to 2 years (maximum). Four cohorts were balanced with a propensity-score-matching (PSM): 1) CNIC-Polypill (aspirin+atorvastatin+ramipril), 2) Monocomponents (same separate drugs), 3) Equipotent (equipotent drugs) and 4) Other therapies ([OT], other cardiovascular drugs). Incidence of cardiovascular events, health-care resources utilization and healthcare and non-healthcare costs (2020 Euros) were compared. Incremental cost-effectiveness ratios per cardiovascular event avoided were estimated. RESULTS After PSM, 1614 patients were recruited in each study cohort. The accumulated incidence of cardiovascular events during the 24-month follow-up was lower in the CNIC-Polypill cohort vs the other cohorts (19.8% vs Monocomponents: 23.3%, Equipotent: 25.5% and OT: 26.8%; p<0.01). During the follow-up period, the CNIC-Polypill cohort also reduced the health-care resources utilization per patient compared to the other cohorts, particularly primary care visits (16.6 vs Monocomponents: 18.7, Equipotent: 18.9 and OT: 21.0; p<0.001) and hospitalization days (2.3 vs Monocomponents: 3.4, Equipotent: 3.7 and OT: 4.0; p<0.001). The treatment cost in the CNIC-Polypill cohort was lower than that in the other cohorts (€4668 vs Monocomponents: €5587; Equipotent: €5682 and OT: €6016; p<0.001) (Difference: -€919, -€1014 and -€1348, respectively). Due to the reduction of cardiovascular events and costs, the CNIC-Polypill is a dominant alternative compared to the other treatments. CONCLUSION CNIC-Polypill reduces recurrent major cardiovascular events and costs, being a cost-saving strategy as secondary prevention of ASCVD.This study was funded by Ferrer.S

In vitro evaluation of graphene oxide nanosheets on immune function

Graphene oxide (GO) has attracted the scientific community attention due to its novel properties and wide range of potential applications including hyperthermia cancer therapy. However, little is known about the GO effects on the immune function which involves both innate and adaptive defence mechanisms through the activation of different cell populations and secretion of several cytokines. The effect of different GO nanosheets designed for hyperthermia cancer therapy on macrophage and lymphocyte function should be determined before using GO for this application. Experiments The effects of GO nanosheets with 1 (1-GOs) and 6 arms (6-GOs) of polyethylene glycol on RAW-264.7 macrophages and primary splenocytes (as approximation to the in vivo situation) were evaluated through the proinflammatory cytokine secretion and the modulation of cell proliferation in the presence of specific stimuli for either T-lymphocytes (concanavalin A, anti-CD3 antibody) or B-lymphocytes/macrophages (lipopolysaccharide). Findings 6-GOs significantly increased the secretion of TNF-α by RAW-264.7 macrophages without alteration of IL-6 and IL-1β levels. The treatment of primary splenocytes with 1-GOs and 6-GOs in the presence of concanavalin A, anti-CD3 antibody and lipopolysaccharide, produced significant dose-dependent decreases of cell proliferation and IL-6 levels, revealing weak inflammatory properties of GOs which are favourable for hyperthermia cancer therapy

Derecho y tecnologías avanzadas

¿Están reñidos el Derecho y las Administraciones Públicas con las tecno- logías más avanzadas de la información y la comunicación? La respuesta negativa a esta pregunta fue la conclusión de las aportaciones de los participantes en las IV Jornadas sobre Derecho y Tecnología y en el XIV Encuentro Ibero-Latino-Americano sobre Gobierno Electrónico e Inclusión Digital, celebrados en Zaragoza los días 18 y 19 de junio de 2012. Cada uno, desde su perspectiva y campo de actividad, trató de aportar pruebas de cómo las tecnologías de la información y la comunicación más avanzadas aportan soluciones en el campo del Derecho y las Admi- nistraciones Públicas. Estas aportaciones están recogidas en este libro, agrupadas en tres blo- ques diferentes. En el primero, bajo el título Tecnologías avanzadas y Derecho se encuen- tran los trabajos aportados sobre el uso de tecnologías avanzadas en actividades relacionadas con el Derecho y la Administración de Justicia, con casos concretos de Brasil y España, o de tipo general, aplicable en cualquier país. En el segundo, el título Administración electrónica: acceso de los ciudadanos a los servicios públicos reúne experiencias concretas llevadas a cabo en España, Unión Europea y Brasil. Por último, y no menos importante, el título Aprendizaje y tecnologías recoge propuestas para fomentar el uso de las nuevas tecnologías en la docencia, tanto en Derecho como en otros campos de la docencia universitaria

re-habitar El Carmen : Un proyecto sobre patrimonio contemporáneo

El proyecto _re-HABITAR suponía para el propio proceder de la institución un avance más allá del reconocimiento, registro, inventario o protección patrimonial de la arquitectura del siglo XX y del Movimiento Moderno para posicionarse en la acción preventiva y conservativa de ese legado contemporáneo. Para ello, la praxis patrimonial se aferraba a un modelo: el de la vivienda social en España en la segunda mitad del siglo XX; a un caso concreto: el de la barriada de Nuestra Señora del Carmen (Recasens Méndez-Queipo de Llano, 1958); y a un requisito fundamental: analizar un objeto vivo y en uso, aún con la presencia de quienes lo vivieron y usaron desde su origen

GC-FID determination and pharmacokinetic studies of oleanolic acid in human serum

© 2015 John Wiley & Sons, Ltd. Analytical interest of OA determination in human serum has increased owing to the increasing interest in pharmaceutical research by pharmaceutical properties. A simple, specific, precise and accurate GC method with flame ionization detector (FID) developed and validated for the determination of oleanolic acid (OA) in human serum (HS). To an aliquot of HS, internal standard was added and a combination of liquid-liquid extraction with a mixture of diethyl ether-isopropyl alcohol, filtration and consecutive GC resulted in separation and quantification of OA. The organic phase was analyzed using a GC system equipped with a 30×0.25mm i.d. Rtx-65TG capillary column and FID detection. Total chromatographic time was 10min and no interfering peaks from endogenous components in blank serum were observed. The OA/internal standard peak area ratio was linearly fitted to the OA concentration (r=0.992) over the range 10-1500ng/mL. The mean serum extraction recovery of OA was 96.7±1.0% and the lower limit of quantification based on 5mL of serum was 10.7ng/mL. The intra-day coefficient of variation ranged from 1.3 to 3.6% and inter-day varied from 1.4 to 4.5%. The developed method was used to study the pharmacokinetics of OA after oral administration in humans. The assay was simple, sensitive, precise and accurate for the use in the study of the mechanisms of absorption and distribution of OA in humans.This work was supported in part by grants from Comisión Interministerial de Ciencia y Tecnología (CICYT, AGL2008-02258) and Instituto de Salud Carlos III (FIS-ISCIII, PI010/01415) partially financed by the European Regional Development Fund of the EU. The authors also express their gratitude to Dr Ruiz-Gutierrez for the supply of human serum samples for the pharmacokinetic study.Peer Reviewe

Procedimiento de obtención de oleuropeína

Procedimiento de obtención de oleuropeína. La presente invención se refiere a un procedimiento de obtención de oleuropeína a partir de hojas de olivo que comprende las siguientes etapas: a) secado de las hojas de olivo; b) peletizado de las hojas secas obtenidas en la etapa (a); y c) extracción sólido/líquido de los pellets obtenidos en la etapa (b) con un disolvente seleccionado de agua, metanol, etanol y cualquiera de sus mezclas.Peer reviewedConsejo Superior de Investigaciones Científicas (España)A2 Solicitud de patente sin informe sobre el estado de la técnic

Procedimiento de obtención de oleuropeína

Procedimiento de obtención de oleuropeína. La presente invención se refiere a un procedimiento de obtención de oleuropeína a partir de hojas de olivo que comprende las siguientes etapas: a) secado de las hojas de olivo; b) peletizado de las hojas secas obtenidas en la etapa (a); y c) extracción sólido/líquido de los pellets obtenidos en la etapa (b) con un disolvente seleccionado de agua, metanol, etanol y cualquiera de sus mezclas.Peer reviewedProcedimiento de obtención de oleuropeína. La presente invención se refiere a un procedimiento de obtención de oleuropeína a partir de hojas de olivo que comprende las siguientes etapas: a) secado de las hojas de olivo; b) peletizado de las hojas secas obtenidas en la etapa (a); y c) extracción sólido/líquido de los pellets obtenidos en la etapa (b) con un disolvente seleccionado de agua, metanol, etanol y cualquiera de sus mezclas.B1 Patente sin examen previ

Procedimiento de obtención de oleuropeína

Procedimiento de obtención de oleuropeína. La presente invención se refiere a un procedimiento de obtención de oleuropeína a partir de hojas de olivo que comprende las siguientes etapas: a) secado de las hojas de olivo; b) peletizado de las hojas secas obtenidas en la etapa (a); y c) extracción sólido/líquido de los pellets obtenidos en la etapa (b) con un disolvente seleccionado de agua, metanol, etanol y cualquiera de sus mezclas.Peer reviewedConsejo Superior de Investigaciones Científicas (España)R1 Informe sobre el estado de la técnic