2,630 research outputs found

    Cyberattacks Predictions Workflow using Machine Learning

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    This research aims to validate the effectiveness of a machine learning model composed of three classifiers: decision tree, logistic regression, and support vector machines. Through the design of a workflow, we demonstrate the effectiveness of the model. First, we execute a network attack, and then monitoring, processing, storage, visualization, and data transfer tools are implemented to create the most realistic environment possible and obtain more accurate predictions. © 2021 IEEE

    YarpTp Notebooks a Tool for Teaching Programming

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    This article shows the design, structure, and part of the functioning of YarpTP Notebooks, as a pedagogical proposal that has been evolving from the experience in the teaching practice of the course Fundamentals of Programming. It seeks to encourage students in the teaching of programming through interactive booklets designed with Jupyter Notebooks which, when executed, can control physical components (in this case, vehicles on a reduced scale). The student assumes a participatory role through these interactive booklets that leads them to develop a process of reflection on what, how, when it does it and what results it achieves with these. Analyzing the information received allowing you to identify and apply variables, expressions and general syntax of the Python language that leads them to understand a program, test the program, evaluate the data and the associated behavior to continue improving their development until formulating coherent and/or associated conclusions with the desired competencies in the course of Fundamentals of Programmin

    PI3Kα inhibition reduces obesity in mice

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    Partial inhibition of PI3K is one of the best-validated and evolutionary conserved manipulations to extend longevity. The best known health beneficial effects of reduced PI3K are related to metabolism and include increased energy expenditure, reduced nutrient storage, and protection from obesity. We have previously shown that a dual chemical inhibitor of the alpha and delta PI3K isoforms (CNIO-PI3Ki) reduces obesity in mice and monkeys, without evident toxic effects after long-term treatment. Here, we dissect the role of the alpha and delta PI3K isoforms by making use of selective inhibitors against PI3Kα (BYL-719 also known as alpelisib) or PI3Kδ (GS-9820 also known as acalisib). Treatment of mice with the above mentioned inhibitors indicated that BYL-719 increases energy expenditure in normal mice and efficiently reduces body weight in obese (ob/ob) mice, whereas these effects were not observed with GS-9820. Of note, the dose of BYL-719 required to reduce obesity was 10x higher than the equivalent dose of CNIO-PI3Ki, which could suggest that simultaneous inhibition of PI3K alpha and delta is more beneficial than single inhibition of the alpha isoform. In summary, we conclude that inhibition of PI3Kα is sufficient to increase energy expenditure and reduce obesity, and suggest that concomitant PI3Kα inhibition could play an auxiliary role

    The Mediterranean diet and incidence of hypertension: the Seguimiento Universidad de Navarra (SUN) Study

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    The Mediterranean diet is receiving increasing attention in cardiovascular epidemiology. The association of adherence to the Mediterranean diet with the incidence of hypertension was evaluated among 9,408 men and women enrolled in a dynamic Spanish prospective cohort study during 1999–2005. Dietary intake was assessed at baseline with a validated semiquantitative food frequency questionnaire, and a 9-point Mediterranean diet score was constructed. During a median follow-up period of 4.2 years (range, 1.9–7.9), 501 incident cases of hypertension were identified. After adjustment for major hypertension risk factors and nutritional covariates, adherence to the Mediterranean diet was not associated with hypertension (the hazard ratio was 1.10 (95% confidence interval (CI): 0.81, 1.41) for moderate adherence and 1.12 (95% CI: 0.79, 1.60) for high adherence). However, it was associated with reduced changes in mean levels of systolic blood pressure (moderate adherence, 2.4 mm Hg (95% CI: 4.0, 0.8); high adherence, 3.1 mm Hg (95% CI: 5.4, 0.8)) and diastolic blood pressure (moderate adherence, 1.3 mm Hg (95% CI: 2.5, 0.1); high adherence, 1.9 mm Hg (95% CI: 3.6, 0.1)) after 6 years of follow-up. These results suggest that adhering to a Mediterranean-type diet could contribute to the prevention of age-related changes in blood pressure

    A Novel, Quick, and Reliable Smartphone-Based Method for Serum PSA Quantification: Original Design of a Portable Microfluidic Immunosensor-Based System

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    We describe a versatile, portable, and simple platform that includes a microfluidic electrochemical immunosensor for prostate-specific antigen (PSA) detection. It is based on the covalent immobilization of the anti-PSA monoclonal antibody on magnetic microbeads retained in the central channel of a microfluidic device. Image flow cytometry and scanning electron microscopy were used to characterize the magnetic microbeads. A direct sandwich immunoassay (with horseradish peroxidase-conjugated PSA antibody) served to quantify the cancer biomarker in serum samples. The enzymatic product was detected at -100 mV by amperometry on sputtered thin-film electrodes. Electrochemical reaction produced a current proportional to the PSA level, with a linear range from 10 pg mL(-1) to 1500 pg mL(-1). The sensitivity was demonstrated by a detection limit of 2 pg mL(-1) and the reproducibility by a coefficient of variation of 6.16%. The clinical performance of this platform was tested in serum samples from patients with prostate cancer (PCa), observing high specificity and full correlation with gold standard determinations. In conclusion, this analytical platform is a promising tool for measuring PSA levels in patients with PCa, offering a high sensitivity and reduced variability. The small platform size and low cost of this quantitative methodology support its suitability for the fast and sensitive analysis of PSA and other circulating biomarkers in patients. Further research is warranted to verify these findings and explore its potential application at all healthcare levels.Universidad Nacional de San Luis PROICO 22/Q241ANPCyT PICT 2018-04443 PICT-2015-2246 PICT-2015-1575 PICT-2014-1184 PICT-2014-0375 PICT-2018-04443Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET) PIP 11220150100004COGENYOCentre for Genomics and Oncological Research: Pfizer-University of GranadaAndalusian Regional Government (Granada, Spain)ISCIII Health Research Institute P17/00989La Caixa FoundationHealth and Family Secretariat of the Andalusian Regional GovernmentSpanish GovernmentH2020-MSCA-IF-2019-89566

    Drug delivery nanosystems for the localized treatment of glioblastoma multiforme

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    [EN] Glioblastoma multiforme is one of the most prevalent and malignant forms of central nervous system tumors. The treatment of glioblastoma remains a great challenge due to its location in the intracranial space and the presence of the blood-brain tumor barrier. There is an urgent need to develop novel therapy approaches for this tumor, to improve the clinical outcomes, and to reduce the rate of recurrence and adverse effects associated with present options. The formulation of therapeutic agents in nanostructures is one of the most promising approaches to treat glioblastoma due to the increased availability at the target site, and the possibility to co-deliver a range of drugs and diagnostic agents. Moreover, the local administration of nanostructures presents significant additional advantages, since it overcomes blood-brain barrier penetration issues to reach higher concentrations of therapeutic agents in the tumor area with minimal side effects. In this paper, we aim to review the attempts to develop nanostructures as local drug delivery systems able to deliver multiple agents for both therapeutic and diagnostic functions for the management of glioblastoma.This research was funded by an Ussher start-up funding award (School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin) and the European Union’s Horizon 2020 research and innovation program under Grant agreement No. 708036.Nam, L.; Coll Merino, MC.; Erthal, L.; De La Torre-Paredes, C.; Serrano, D.; Martínez-Máñez, R.; Santos-Martinez, M.... (2018). Drug delivery nanosystems for the localized treatment of glioblastoma multiforme. Materials. 11(5). https://doi.org/10.3390/ma11050779S115Goodenberger, M. L., & Jenkins, R. B. (2012). Genetics of adult glioma. Cancer Genetics, 205(12), 613-621. doi:10.1016/j.cancergen.2012.10.009Louis, D. N., Ohgaki, H., Wiestler, O. D., Cavenee, W. K., Burger, P. C., Jouvet, A., … Kleihues, P. (2007). The 2007 WHO Classification of Tumours of the Central Nervous System. Acta Neuropathologica, 114(2), 97-109. doi:10.1007/s00401-007-0243-4Gutkin, A., Cohen, Z. R., & Peer, D. (2016). Harnessing nanomedicine for therapeutic intervention in glioblastoma. Expert Opinion on Drug Delivery, 13(11), 1573-1582. doi:10.1080/17425247.2016.1200557Omuro, A. (2013). Glioblastoma and Other Malignant Gliomas. JAMA, 310(17), 1842. doi:10.1001/jama.2013.280319Wang, Y., & Jiang, T. (2013). Understanding high grade glioma: Molecular mechanism, therapy and comprehensive management. Cancer Letters, 331(2), 139-146. doi:10.1016/j.canlet.2012.12.024Gallego, O. (2015). Nonsurgical treatment of recurrent glioblastoma. Current Oncology, 22(4), 273. doi:10.3747/co.22.2436Carlsson, S. K., Brothers, S. P., & Wahlestedt, C. (2014). Emerging treatment strategies for glioblastoma multiforme. EMBO Molecular Medicine, 6(11), 1359-1370. doi:10.15252/emmm.201302627Yamasaki, F., Kurisu, K., Satoh, K., Arita, K., Sugiyama, K., Ohtaki, M., … Thohar, M. A. (2005). Apparent Diffusion Coefficient of Human Brain Tumors at MR Imaging. Radiology, 235(3), 985-991. doi:10.1148/radiol.2353031338Gupta, A., Young, R. J., Shah, A. D., Schweitzer, A. D., Graber, J. J., Shi, W., … Omuro, A. M. P. (2014). Pretreatment Dynamic Susceptibility Contrast MRI Perfusion in Glioblastoma: Prediction of EGFR Gene Amplification. Clinical Neuroradiology, 25(2), 143-150. doi:10.1007/s00062-014-0289-3Fakhoury, M. (2015). Drug delivery approaches for the treatment of glioblastoma multiforme. Artificial Cells, Nanomedicine, and Biotechnology, 44(6), 1365-1373. doi:10.3109/21691401.2015.1052467Štolc, S., Jakubíková, L., & Kukurová, I. (2011). Body distribution of 11C-methionine and 18FDG in rat measured by microPET. Interdisciplinary Toxicology, 4(1). doi:10.2478/v10102-011-0010-1Galldiks, N., Dunkl, V., Kracht, L. W., Vollmar, S., Jacobs, A. H., Fink, G. R., & Schroeter, M. (2012). Volumetry of [11C]-Methionine Positron Emission Tomographic Uptake as a Prognostic Marker before Treatment of Patients with Malignant Glioma. Molecular Imaging, 11(6), 7290.2012.00022. doi:10.2310/7290.2012.00022Louis, D. N., Perry, A., Reifenberger, G., von Deimling, A., Figarella-Branger, D., Cavenee, W. K., … Ellison, D. W. (2016). The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathologica, 131(6), 803-820. doi:10.1007/s00401-016-1545-1Martínez-Garcia, M., Álvarez-Linera, J., Carrato, C., Ley, L., Luque, R., Maldonado, X., … Gil-Gil, M. (2017). SEOM clinical guidelines for diagnosis and treatment of glioblastoma (2017). Clinical and Translational Oncology, 20(1), 22-28. doi:10.1007/s12094-017-1763-6WILSON, C. B. (1964). Glioblastoma Multiforme. Archives of Neurology, 11(5), 562. doi:10.1001/archneur.1964.00460230112012Juratli, T. A., Schackert, G., & Krex, D. (2013). Current status of local therapy in malignant gliomas — A clinical review of three selected approaches. Pharmacology & Therapeutics, 139(3), 341-358. doi:10.1016/j.pharmthera.2013.05.003Westphal, M., Hilt, D. C., Bortey, E., Delavault, P., Olivares, R., Warnke, P. C., … Ram, Z. (2003). A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro-Oncology, 5(2), 79-88. doi:10.1093/neuonc/5.2.79Chamberlain, M., Rhun, E., & Taillibert, S. (2015). The future of high-grade glioma: Where we are and where are we going. Surgical Neurology International, 6(2), 9. doi:10.4103/2152-7806.151331Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J. B., … Mirimanoff, R. O. (2005). Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. New England Journal of Medicine, 352(10), 987-996. doi:10.1056/nejmoa043330Lee, C. Y. (2017). Strategies of temozolomide in future glioblastoma treatment. OncoTargets and Therapy, Volume 10, 265-270. doi:10.2147/ott.s120662Mun, E. J., Babiker, H. M., Weinberg, U., Kirson, E. D., & Von Hoff, D. D. (2017). Tumor-Treating Fields: A Fourth Modality in Cancer Treatment. Clinical Cancer Research, 24(2), 266-275. doi:10.1158/1078-0432.ccr-17-1117Stupp, R., Taillibert, S., Kanner, A., Kesari, S., Toms, S. A., Barnett, G. H., … Ram, Z. (2015). Tumor treating fields (TTFields): A novel treatment modality added to standard chemo- and radiotherapy in newly diagnosed glioblastoma—First report of the full dataset of the EF14 randomized phase III trial. Journal of Clinical Oncology, 33(15_suppl), 2000-2000. doi:10.1200/jco.2015.33.15_suppl.2000Bernard-Arnoux, F., Lamure, M., Ducray, F., Aulagner, G., Honnorat, J., & Armoiry, X. (2016). The cost-effectiveness of tumor-treating fields therapy in patients with newly diagnosed glioblastoma. Neuro-Oncology, 18(8), 1129-1136. doi:10.1093/neuonc/now102Stupp, R., Hegi, M. E., Mason, W. P., van den Bent, M. J., Taphoorn, M. J., Janzer, R. C., … Mirimanoff, R.-O. (2009). Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. The Lancet Oncology, 10(5), 459-466. doi:10.1016/s1470-2045(09)70025-7Preusser, M., de Ribaupierre, S., Wöhrer, A., Erridge, S. C., Hegi, M., Weller, M., & Stupp, R. (2011). Current concepts and management of glioblastoma. Annals of Neurology, 70(1), 9-21. doi:10.1002/ana.22425FDA Grants Genentech’s Avastin Full Approval for Most Aggressive Form of Brain Cancerhttps://www.gene.com/media/press-releases/14695/2017-12-05/fda-grants-genentechs-avastin-full-approWick, W., Stupp, R., Gorlia, T., Bendszus, M., Sahm, F., Bromberg, J. E., … Van Den Bent, M. J. (2016). Phase II part of EORTC study 26101: The sequence of bevacizumab and lomustine in patients with first recurrence of a glioblastoma. Journal of Clinical Oncology, 34(15_suppl), 2019-2019. doi:10.1200/jco.2016.34.15_suppl.2019Liu, W.-Y., Wang, Z.-B., Zhang, L.-C., Wei, X., & Li, L. (2012). Tight Junction in Blood-Brain Barrier: An Overview of Structure, Regulation, and Regulator Substances. CNS Neuroscience & Therapeutics, 18(8), 609-615. doi:10.1111/j.1755-5949.2012.00340.xRonaldson, P. T., & Davis, T. P. (2011). Targeting blood–brain barrier changes during inflammatory pain: an opportunity for optimizing CNS drug delivery. Therapeutic Delivery, 2(8), 1015-1041. doi:10.4155/tde.11.67S. Hersh, D., S. Wadajkar, A., B. Roberts, N., G. Perez, J., P. Connolly, N., Frenkel, V., … J. Kim, A. (2016). Evolving Drug Delivery Strategies to Overcome the Blood Brain Barrier. Current Pharmaceutical Design, 22(9), 1177-1193. doi:10.2174/1381612822666151221150733Patel, M. M., Goyal, B. R., Bhadada, S. V., Bhatt, J. S., & Amin, A. F. (2009). Getting into the Brain. CNS Drugs, 23(1), 35-58. doi:10.2165/0023210-200923010-00003Clark, D. E. (2003). In silico prediction of blood–brain barrier permeation. Drug Discovery Today, 8(20), 927-933. doi:10.1016/s1359-6446(03)02827-7Gleeson, M. P. (2008). Generation of a Set of Simple, Interpretable ADMET Rules of Thumb. Journal of Medicinal Chemistry, 51(4), 817-834. doi:10.1021/jm701122qHervé, F., Ghinea, N., & Scherrmann, J.-M. (2008). CNS Delivery Via Adsorptive Transcytosis. The AAPS Journal, 10(3), 455-472. doi:10.1208/s12248-008-9055-2Van Tellingen, O., Yetkin-Arik, B., de Gooijer, M. C., Wesseling, P., Wurdinger, T., & de Vries, H. E. (2015). Overcoming the blood–brain tumor barrier for effective glioblastoma treatment. Drug Resistance Updates, 19, 1-12. doi:10.1016/j.drup.2015.02.002Ostermann, S. (2004). Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Temozolomide in Malignant Glioma Patients. Clinical Cancer Research, 10(11), 3728-3736. doi:10.1158/1078-0432.ccr-03-0807Laquintana, V., Trapani, A., Denora, N., Wang, F., Gallo, J. M., & Trapani, G. (2009). New strategies to deliver anticancer drugs to brain tumors. Expert Opinion on Drug Delivery, 6(10), 1017-1032. doi:10.1517/17425240903167942Zhan, C., Gu, B., Xie, C., Li, J., Liu, Y., & Lu, W. (2010). Cyclic RGD conjugated poly(ethylene glycol)-co-poly(lactic acid) micelle enhances paclitaxel anti-glioblastoma effect. Journal of Controlled Release, 143(1), 136-142. doi:10.1016/j.jconrel.2009.12.020Kondo, Y., Kondo, S., Tanaka, Y., Haqqi, T., Barna, B. P., & Cowell, J. K. (1998). Inhibition of telomerase increases the susceptibility of human malignant glioblastoma cells to cisplatin-induced apoptosis. Oncogene, 16(17), 2243-2248. doi:10.1038/sj.onc.1201754Wang, P. P., Frazier, J., & Brem, H. (2002). Local drug delivery to the brain. Advanced Drug Delivery Reviews, 54(7), 987-1013. doi:10.1016/s0169-409x(02)00054-6De Souza, R., Zahedi, P., Allen, C. J., & Piquette-Miller, M. (2010). Polymeric drug delivery systems for localized cancer chemotherapy. Drug Delivery, 17(6), 365-375. doi:10.3109/10717541003762854Wolinsky, J. B., Colson, Y. L., & Grinstaff, M. W. (2012). Local drug delivery strategies for cancer treatment: Gels, nanoparticles, polymeric films, rods, and wafers. Journal of Controlled Release, 159(1), 14-26. doi:10.1016/j.jconrel.2011.11.031Chakroun, R. W., Zhang, P., Lin, R., Schiapparelli, P., Quinones-Hinojosa, A., & Cui, H. (2017). Nanotherapeutic systems for local treatment of brain tumors. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 10(1), e1479. doi:10.1002/wnan.1479Mathios, D., Kim, J. E., Mangraviti, A., Phallen, J., Park, C.-K., Jackson, C. M., … Lim, M. (2016). Anti-PD-1 antitumor immunity is enhanced by local and abrogated by systemic chemotherapy in GBM. Science Translational Medicine, 8(370), 370ra180-370ra180. doi:10.1126/scitranslmed.aag2942Chaichana, K. L., Pinheiro, L., & Brem, H. (2015). Delivery of local therapeutics to the brain: working toward advancing treatment for malignant gliomas. Therapeutic Delivery, 6(3), 353-369. doi:10.4155/tde.14.114Patchell, R. A., Regine, W. F., Ashton, P., Tibbs, P. A., Wilson, D., Shappley, D., & Young, B. (2002). Journal of Neuro-Oncology, 60(1), 37-42. doi:10.1023/a:1020291229317Hassenbusch, S. J., Nardone, E. M., Levin, V. A., Leeds, N., & Pietronigro, D. (2003). Stereotactic Injection of DTI-015 into Recurrent Malignant Gliomas: Phase I/II Trial. Neoplasia, 5(1), 9-16. doi:10.1016/s1476-5586(03)80012-xBoiardi, A., Eoli, M., Salmaggi, A., Zappacosta, B., Fariselli, L., Milanesi, I., … Silvani, A. (2001). Journal of Neuro-Oncology, 54(1), 39-47. doi:10.1023/a:1012510513780Lidar, Z., Mardor, Y., Jonas, T., Pfeffer, R., Faibel, M., Nass, D., … Ram, Z. (2004). Convection-enhanced delivery of paclitaxel for the treatment of recurrent malignant glioma: a Phase I/II clinical study. Journal of Neurosurgery, 100(3), 472-479. doi:10.3171/jns.2004.100.3.0472Bruce, J. N., Fine, R. L., Canoll, P., Yun, J., Kennedy, B. C., Rosenfeld, S. S., … DeLaPaz, R. L. (2011). Regression of Recurrent Malignant Gliomas With Convection-Enhanced Delivery of Topotecan. Neurosurgery, 69(6), 1272-1280. doi:10.1227/neu.0b013e3182233e24Carpentier, A., Metellus, P., Ursu, R., Zohar, S., Lafitte, F., Barrie, M., … Carpentier, A. F. (2010). Intracerebral administration of CpG oligonucleotide for patients with recurrent glioblastoma: a phase II study. Neuro-Oncology, 12(4), 401-408. doi:10.1093/neuonc/nop047Bogdahn, U., Hau, P., Stockhammer, G., Venkataramana, N. K., Mahapatra, A. K., … Suri, A. (2010). Targeted therapy for high-grade glioma with the TGF- 2 inhibitor trabedersen: results of a randomized and controlled phase IIb study. Neuro-Oncology, 13(1), 132-142. doi:10.1093/neuonc/noq142Iwamoto, F. M., Lamborn, K. R., Robins, H. I., Mehta, M. P., Chang, S. M., Butowski, N. A., … Fine, H. A. (2010). Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06-02). Neuro-Oncology, 12(8), 855-861. doi:10.1093/neuonc/noq025Brem, S., Tyler, B., Li, K., Pradilla, G., Legnani, F., Caplan, J., & Brem, H. (2007). Local delivery of temozolomide by biodegradable polymers is superior to oral administration in a rodent glioma model. Cancer Chemotherapy and Pharmacology, 60(5), 643-650. doi:10.1007/s00280-006-0407-2Recinos, V. R., Tyler, B. M., Bekelis, K., Sunshine, S. B., Vellimana, A., Li, K. W., & Brem, H. (2010). Combination of Intracranial Temozolomide With Intracranial Carmustine Improves Survival When Compared With Either Treatment Alone in a Rodent Glioma Model. Neurosurgery, 66(3), 530-537. doi:10.1227/01.neu.0000365263.14725.39Storm, P. B., Moriarity, J. L., Tyler, B., Burger, P. C., Brem, H., & Weingart, J. (2002). Journal of Neuro-Oncology, 56(3), 209-217. doi:10.1023/a:1015003232713Scott, A. W., Tyler, B. M., Masi, B. C., Upadhyay, U. M., Patta, Y. R., Grossman, R., … Cima, M. J. (2011). Intracranial microcapsule drug delivery device for the treatment of an experimental gliosarcoma model. Biomaterials, 32(10), 2532-2539. doi:10.1016/j.biomaterials.2010.12.020Kim, G. Y., Tyler, B. M., Tupper, M. M., Karp, J. M., Langer, R. S., Brem, H., & Cima, M. J. (2007). Resorbable polymer microchips releasing BCNU inhibit tumor growth in the rat 9L flank model. Journal of Controlled Release, 123(2), 172-178. doi:10.1016/j.jconrel.2007.08.003Masi, B. C., Tyler, B. M., Bow, H., Wicks, R. T., Xue, Y., Brem, H., … Cima, M. J. (2012). Intracranial MEMS based temozolomide delivery in a 9L rat gliosarcoma model. Biomaterials, 33(23), 5768-5775. doi:10.1016/j.biomaterials.2012.04.048Li, X., Tsibouklis, J., Weng, T., Zhang, B., Yin, G., Feng, G., … Mikhalovsky, S. V. (2016). Nano carriers for drug transport across the blood–brain barrier. Journal of Drug Targeting, 25(1), 17-28. doi:10.1080/1061186x.2016.1184272Mangraviti, A., Gullotti, D., Tyler, B., & Brem, H. (2016). Nanobiotechnology-based delivery strategies: New frontiers in brain tumor targeted therapies. Journal of Controlled Release, 240, 443-453. doi:10.1016/j.jconrel.2016.03.031Torchilin, V. P. (2009). Passive and Active Drug Targeting: Drug Delivery to Tumors as an Example. Handbook of Experimental Pharmacology, 3-53. doi:10.1007/978-3-642-00477-3_1Rippe, B., Rosengren, B.-I., Carlsson, O., & Venturoli, D. (2002). Transendothelial Transport: The Vesicle Controversy. Journal of Vascular Research, 39(5), 375-390. doi:10.1159/000064521Hobbs, S. K., Monsky, W. L., Yuan, F., Roberts, W. G., Griffith, L., Torchilin, V. P., & Jain, R. K. (1998). Regulation of transport pathways in tumor vessels: Role of tumor type and microenvironment. Proceedings of the National Academy of Sciences, 95(8), 4607-4612. doi:10.1073/pnas.95.8.4607Lammers, T., Kiessling, F., Hennink, W. E., & Storm, G. (2012). Drug targeting to tumors: Principles, pitfalls and (pre-) clinical progress. Journal of Controlled Release, 161(2), 175-187. doi:10.1016/j.jconrel.2011.09.063Danhier, F. (2016). To exploit the tumor microenvironment: Since the EPR effect fails in the clinic, what is the future of nanomedicine? Journal of Controlled Release, 244, 108-121. doi:10.1016/j.jconrel.2016.11.015Petros, R. A., & DeSimone, J. M. (2010). Strategies in the design of nanoparticles for therapeutic applications. Nature Reviews Drug Discovery, 9(8), 615-627. doi:10.1038/nrd2591Chouly, C., Pouliquen, D., Lucet, I., Jeune, J. J., & Jallet, P. (1996). Development of superparamagnetic nanoparticles for MRI: effect of particle size, charge and surface nature on biodistribution. Journal of Microencapsulation, 13(3), 245-255. doi:10.3109/02652049609026013OWENSIII, D., & PEPPAS, N. (2006). Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. International Journal of Pharmaceutics, 307(1), 93-102. doi:10.1016/j.ijpharm.2005.10.010Salvador-Morales, C., Zhang, L., Langer, R., & Farokhzad, O. C. (2009). Immunocompatibility properties of lipid–polymer hybrid nanoparticles with heterogeneous surface functional groups. Biomaterials, 30(12), 2231-2240. doi:10.1016/j.biomaterials.2009.01.005Zhan, C., & Lu, W. (2012). The Blood-Brain/Tumor Barriers: Challenges and Chances for Malignant Gliomas Targeted Drug Delivery. Current Pharmaceutical Biotechnology, 13(12), 2380-2387. doi:10.2174/138920112803341798Steiniger, S. C. J., Kreuter, J., Khalansky, A. S., Skidan, I. N., Bobruskin, A. I., Smirnova, Z. S., … Gelperina, S. E. (2004). Chemotherapy of glioblastoma in rats using doxorubicin-loaded nanoparticles. International Journal of Cancer, 109(5), 759-767. doi:10.1002/ijc.20048Wohlfart, S., Khalansky, A. S., Bernreuther, C., Michaelis, M., Cinatl, J., Glatzel, M., & Kreuter, J. (2011). Treatment of glioblastoma with poly(isohexyl cyanoacrylate) nanoparticles. International Journal of Pharmaceutics, 415(1-2), 244-251. doi:10.1016/j.ijpharm.2011.05.046Zanotto-Filho, A., Coradini, K., Braganhol, E., Schröder, R., de Oliveira, C. M., Simões-Pires, A., … Moreira, J. C. F. (2013). Curcumin-loaded lipid-core nanocapsules as a strategy to improve pharmacological efficacy of curcumin in glioma treatment. European Journal of Pharmaceutics and Biopharmaceutics, 83(2), 156-167. doi:10.1016/j.ejpb.2012.10.019Gao, H. (2016). Perspectives on Dual Targeting Delivery Systems for Brain Tumors. Journal of Neuroimmune Pharmacology, 12(1), 6-16. doi:10.1007/s11481-016-9687-4Pinto, M. P., Arce, M., Yameen, B., & Vilos, C. (2017). Targeted brain delivery nanoparticles for malignant gliomas. Nanomedicine, 12(1), 59-72. doi:10.2217/nnm-2016-0307Fang, C., Wang, K., Stephen, Z. R., Mu, Q., Kievit, F. M., Chiu, D. T., … Zhang, M. (2015). Temozolomide Nanoparticles for Targeted Glioblastoma Therapy. ACS Applied Materials & Interfaces, 7(12), 6674-6682. doi:10.1021/am5092165Ke, W., Shao, K., Huang, R., Han, L., Liu, Y., Li, J., … Jiang, C. (2009). Gene delivery targeted to the brain using an Angiopep-conjugated polyethyleneglycol-modified polyamidoamine dendrimer. Biomaterials, 30(36), 6976-6985. doi:10.1016/j.biomaterials.2009.08.049Xin, H., Jiang, X., Gu, J., Sha, X., Chen, L., Law, K., … Fang, X. (2011). Angiopep-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) nanoparticles as dual-targeting drug delivery system for brain glioma. Biomaterials, 32(18), 4293-4305. doi:10.1016/j.biomaterials.2011.02.044Zhang, B., Wang, H., Liao, Z., Wang, Y., Hu, Y., Yang, J., … Jiang, X. (2014). EGFP–EGF1-conjugated nanoparticles for targeting both neovascular and glioma cells in therapy of brain glioma. Biomaterials, 35(13), 4133-4145. doi:10.1016/j.biomaterials.2014.01.071Zhang, P., Hu, L., Yin, Q., Feng, L., & Li, Y. (2012). Transferrin-Modified c[RGDfK]-Paclitaxel Loaded Hybrid Micelle for Sequential Blood-Brain Barrier Penetration and Glioma Targeting Therapy. Molecular Pharmaceutics, 9(6), 1590-1598. doi:10.1021/mp200600tMa, D. (2014). Enhancing endosomal escape for nanoparticle mediated siRNA delivery. Nanoscale, 6(12), 6415. doi:10.1039/c4nr00018hShim, M. S., & Kwon, Y. J. (2012). Stimuli-responsive polymers and nanomaterials for gene delivery and imaging applications. Advanced Drug Delivery Reviews, 64(11), 1046-1059. doi:10.1016/j.addr.2012.01.018Zarebkohan, A., Najafi, F., Moghimi, H. R., Hemmati, M., Deevband, M. R., & Kazemi, B. (2015). Synthesis and characterization of a PAMAM dendrimer nanocarrier functionalized by SRL peptide for targeted gene delivery to the brain. European Journal of Pharmaceutical Sciences, 78, 19-30. doi:10.1016/j.ejps.2015.06.024Hynynen, K., McDannold, N., Vykhodtseva, N., & Jolesz, F. A. (2001). Noninvasive MR Imaging–guided Focal Opening of the Blood-Brain Barrier in Rabbits. Radiology, 220(3), 640-646. doi:10.1148/radiol.2202001804Nance, E., Timbie, K., Miller, G. W., Song, J., Louttit, C., Klibanov, A. L., … Price, R. J. (2014). Non-invasive delivery of stealth, brain-penetrating nanoparticles across the blood − brain barrier using MRI-guided focused ultrasound. Journal of Controlled Release, 189, 123-132. doi:10.1016/j.jconrel.2014.06.031Mead,

    Study of vascular risk in Navarre: objectives and design. Prevalence of metabolic syndrome and of vascular risk factors

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    BACKGROUND: To determine in a representative sample of the population the prevalence of risk factors and metabolic syndrome; their association with sub-clinical atherosclerotic lesions and their impact on cardiocerebrovascular disease 10 years after. MATERIAL AND METHODS: (Phase 1) Cross sectional survey of a random sample stratified by age and sex of the population of Navarre aged between 35 and 84. Antecedents, risk factors, physical and analytical exploration. (Phase II) Ten year follow-up cohort study, in 500 exposed to MS and 500 not exposed persons, aged between 45 and 74 years; with an 82.25% power to detect a risk ratio of 2; with analytical and image markers of sub-clinical atherosclerosis. (Phase III) Follow up of vascular events at ten years. RESULTS: The subjects recruited were 6,553; excluded or not found 871; the final sample was 5,682 (2,644 men and 3,038 women); 4,168 (73,4%) took part in the study. The prevalence of MS was 22.1% (95%CI 20.5 - 23.7) for men and 17,2% (95%CI 15.8 - 18.5) for women. The main cardiovascular RF were high compared to other geographical areas except for HDL cholesterol. The rate was 8.5% (95%CI 7.4 - 9.6) for men and 1.7% (95%CI 1.3 - 2.2) CONCLUSIONS: There are important differences in risk between sex, being worst for men. The high figures for HDL cholesterol and the low prevalence of MS might mean a lower risk of vascular events in Navarra

    Association between adherence to the Mediterranean diet and prevalence of cardiovascular risk factors

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    Objective: to determine the prevalence of cardiovascular risk factors in a cohort of workers and to quantify its association with compliance with the Mediterranean diet follow-up. Method: a cross-sectional descriptive study was carried out on a cohort of 23, 729 workers. Clinical data from annual medical examinations and the Mediterranean Diet Adherence Screener were used to assess adherence to the Mediterranean diet. Results: 51.3% of the participants showed good adherence to the Mediterranean diet. The multivariate analysis showed an inverse and significant association between the follow-up of the Mediterranean diet and the prevalence of abdominal obesity (Odds Ratio = 0.64, 95% CI 0.56; 0.73), dyslipidemia (Odds Ratio = 0.55, 95% CI 0.42; 0.73), and metabolic syndrome (Odds Ratio = 0.76, 95% CI 0.67; 0.86). Conclusions: our results suggest that the Mediterranean diet is potentially effective in promoting cardiovascular health. Implementing the interventions promoting the Mediterranean diet in the working population seems justified. Objetivo: determinar la prevalencia de factores de riesgo cardiovascular en una cohorte de trabajadores y cuantificar su asociación con el seguimiento de la dieta mediterránea. Método: se llevó a cabo un estudio descriptivo transversal sobre una cohorte de 23.729 trabajadores. Se utilizaron los datos clínicos procedentes de los exámenes médicos anuales y el Mediterranean Diet Adherence Screener para evaluar la adherencia a la dieta mediterránea. Resultados: el 51, 3% de los participantes presentó una buena adherencia a la dieta mediterránea. El análisis multivariante evidenció una asociación inversa y significativa entre el seguimiento de la dieta mediterránea y la prevalencia de obesidad abdominal (Odds Ratio = 0, 64, IC 95% 0, 56; 0, 73), dislipidemia (Odds Ratio = 0, 55, IC 95% 0, 42; 0, 73) y de síndrome metabólico (Odds Ratio = 0, 76, IC 95% 0, 67; 0, 86). Conclusión: nuestros resultados sugieren que la dieta mediterránea es potencialmente eficaz en la promoción de la salud cardiovascular. Parece justificada la implementación de intervenciones que promuevan la dieta mediterránea en la población trabajadora

    Selective Fractionation And Isolation Of Allelopathic Compounds From Helianthus Annuus L. Leaves By Means Of High-Pressure Techniques

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    The allelopathic potential of Helianthus annuus L. leaves was study based on bio-directed chemical fractionation approach. Aerial parts of H. annuus were extracted by means of SFE using supercritical carbon dioxide (scCO2) and ESE using CO2+50% EtOH/H2O (varying ethanol in water from 0 to 100%). Extractions were carried out at 400 bar, 55 °C, 20 g/min and for 4 h. Then, extracts were fractionated in three separators at the following conditions: S1: 200 bar/45 °C; S2: 90 bar/40 °C; and S3: 1 atm/30 °C. ESE obtained higher overall yields than scCO2 and the use of water as cosolvent (CO2+50% H2O) resulted in a S3 fraction free from chlorophylls and rich in bioactive compounds. 14 compounds, including fatty acids, terpenes, flavonoids and heliannuols, were isolated from this fraction. After performing the bioassay on pure compounds, heliannuol D, tambulin, pinoresinol and sesquiterpene 10-oxo-isodauc-3-en-15-al showed the most effective inhibitor profiles
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