Diseño de algoritmos de cálculo de retardo de ondas ultrasónicas para la determinación del módulo elástico del hormigón reforzado con fibra de vidrio y propuesta de dosificación óptima

Con el fin de poder convertir el hormigón reforzado con fibra de vidrio en un material competitivo y de aprovechar su potencial, se proponen en este estudio diversas dosificaciones con cantidades de fibra de vidrio mucho menores de las habituales (en concreto, desde 0,4% hasta 1,5%) y con longitudes de dibras diferentes (12 mm y 36 mm). Los hormigones reforzados con fibra de vidrio fabricaso son estudiados de forma comparativa entre sí, con el propósito de concer la dosis óptima de fibra de vidrio, y respecto a un hormigón convencional sin fibras, confeccionado pra ver las mejoras sobre éste. La comparación entre las distintas dosificaciones se ha llevado a cabo fundamentalmente analizando los resultados de los módulos elásticos de las muestras de hormigón confeccionadas, y que han sido obtenidos mediante la aplicación de técnicas no destructivas, en concreto, ultrasonidos. En este sentido, se han aportado diversos algoritmos de cálculo de retardo (o tiempo de vuelo) de ondas ultrasónicas, y se ha realizado una comparación entre todos ellos y que existen en el mercado con el fin de hallar de la manera más exacta ciertas propiedades físicas y elásticas del hormigón que se necesitan conocer para deducir cuál de las dosificaciones es la finalmente elegida.Universidad de Granada. Departamento de Mecánica de Estructuras e Ingeniería Hidráulica. Máster Universitario en Estructuras, curso 2011-201

Bond strength of galvanized steel : experimental and numerical study based on pull-out tests

Congreso celebrado en la Escuela de Arquitectura de la Universidad de Sevilla desde el 24 hasta el 26 de junio de 2015.The construction of more durable structures is becoming a mandatory requirement. Different alternatives are followed in reinforced concrete structures, as the use of galvanized reinforcement to increase the service life. Due to the fact that the interaction between concrete and galvanized steel is different from the carbon steel case, the bond strength might call into question. The present article studies the bond stress development of conventional and hot-dip galvanized steel reinforcement embedded in concrete made with Ordinary Portland Cement (OPC). Results indicate that maximum bond stress measured for galvanized steel is similar to that of conventional reinforcement. Furthermore, the numerical model developed with ABAQUS notably reproduces the contact between concrete and galvanized steel with the help of the experimental pull out tests carried out, showing a practical implementation for future structural element analysis

Bioactive compounds isolated from microalgae in chronic inflammation and cancer

The risk of onset of cancer is influenced by poorly controlled chronic inflammatory processes. Inflammatory diseases related to cancer development include inflammatory bowel disease, which can lead to colon cancer, or actinic keratosis, associated with chronic exposure to ultraviolet light, which can progress to squamous cell carcinoma. Chronic inflammatory states expose these patients to a number of signals with tumorigenic effects, including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPK) activation, pro-inflammatory cytokines and prostaglandins release and ROS production. In addition, the participation of inflammasomes, autophagy and sirtuins has been demonstrated in pathological processes such as inflammation and cancer. Chemoprevention consists in the use of drugs, vitamins, or nutritional supplements to reduce the risk of developing or having a recurrence of cancer. Numerous in vitro and animal studies have established the potential colon and skin cáncer. Numerous in vitro and animal studies have established the potential colon and skin cancer chemopreventive properties of substances from marine environment, including microalgae species and their products (carotenoids, fatty acids, glycolipids, polysaccharides and proteins). This review summarizes the main mechanisms of actions of these compounds in the chemoprevention of these cancers. These actions include suppression of cell proliferation, induction of apoptosis, stimulation of antimetastatic and antiangiogenic responses and increased antioxidant and anti-inflammatory activity

Vibrational properties of CdGa2S4 at high pressure

[EN] Raman scattering measurements have been performed in cadmium digallium sulphide (CdGa2S4) with defect chalcopyrite structure up to 25 GPa in order to study its pressure-induced phase transitions. These measurements have been complemented and compared with latticedynamics ab initio calculations including the TO-LO splitting at high pressures in order to provide a better assignment of experimental Raman modes. In addition, experimental and theoretical Gruneisen parameters have been reported in order to calculate the molar heat capacity and thermal expansion coefficient of CdGa2S4. Our measurements provide evidence that CdGa2S4 undergoes an irreversible phase transition above 15 GPa to a Raman-inactive phase, likely with a disordered rock salt structure. Moreover, the Raman spectrum observed on downstroke from 25 GPa to 2 GPa has been attributed to a new phase, tentatively identified as a disordered zinc blende structure, that undergoes a reversible phase transition to the Raman-inactive phase above 10 GPa. Published under license by AIP Publishing.The authors thank the financial support of the Spanish Ministerio de Economia y Competitividad (MINECO) under Grant Nos. MAT2016-75586-C4-2/3-P and MAT2015-71070-REDC (MALTA Consolider) and the Generalitat Valenciana under Project No. PROMETEO/2018/123-EFIMAT. E. P.-G., A. M., and P. R.-H. acknowledge computing time provided by Red Espanola de Supercomputacion (RES) and MALTA-Cluster.Gallego-Parra, S.; Gomis, O.; Vilaplana Cerda, RI.; Ortiz, H.; Perez-Gonzalez, E.; Luna Molina, R.; Rodríguez-Hernández, P.... (2019). Vibrational properties of CdGa2S4 at high pressure. Journal of Applied Physics. 125(11):1-12. https://doi.org/10.1063/1.5080503S11212511Gomis, O., Santamaría-Pérez, D., Vilaplana, R., Luna, R., Sans, J. A., Manjón, F. J., … Ursaki, V. V. (2014). Structural and elastic properties of defect chalcopyrite HgGa2S4 under high pressure. Journal of Alloys and Compounds, 583, 70-78. doi:10.1016/j.jallcom.2013.08.123Cohen, M. L. (1985). Calculation of bulk moduli of diamond and zinc-blende solids. Physical Review B, 32(12), 7988-7991. doi:10.1103/physrevb.32.7988Kim, J. W., & Kim, Y. J. (2007). Optical Properties of Eu Doped M-Ga2S4 (M:Zn, Ca, Sr) Phosphors for White Light Emitting Diodes. Journal of Nanoscience and Nanotechnology, 7(11), 4065-4068. doi:10.1166/jnn.2007.066Yu, R., Noh, H. M., Moon, B. K., Choi, B. C., Jeong, J. H., Jang, K., … Jang, J. K. (2013). Photoluminescence properties of a new red-emitting Mn-activated ZnGa2S4 phosphor. Materials Research Bulletin, 48(6), 2154-2158. doi:10.1016/j.materresbull.2013.02.017Liang, F., Kang, L., Lin, Z., Wu, Y., & Chen, C. (2017). Analysis and prediction of mid-IR nonlinear optical metal sulfides with diamond-like structures. Coordination Chemistry Reviews, 333, 57-70. doi:10.1016/j.ccr.2016.11.012Sahariya, J., Kumar, P., & Soni, A. (2017). Structural and optical investigations of ZnGa2X4 (X = S, Se) compounds for solar photovoltaic applications. Materials Chemistry and Physics, 199, 257-264. doi:10.1016/j.matchemphys.2017.07.003Syrbu, N. N., Tiron, A. V., Parvan, V. I., Zalamai, V. V., & Tiginyanu, I. M. (2015). Interference of birefractive waves in CdGa2S4 crystals. Physica B: Condensed Matter, 463, 88-92. doi:10.1016/j.physb.2015.02.007Vilaplana, R., Gomis, O., Manjón, F. J., Ortiz, H. M., Pérez-González, E., López-Solano, J., … Tiginyanu, I. M. (2013). Lattice Dynamics Study of HgGa2Se4at High Pressures. The Journal of Physical Chemistry C, 117(30), 15773-15781. doi:10.1021/jp402493rGrzechnik, A., Ursaki, V. V., Syassen, K., Loa, I., Tiginyanu, I. M., & Hanfland, M. (2001). Pressure-Induced Phase Transitions in Cadmium Thiogallate CdGa2Se4. Journal of Solid State Chemistry, 160(1), 205-211. doi:10.1006/jssc.2001.9224Gomis, O., Vilaplana, R., Manjón, F. J., Ruiz-Fuertes, J., Pérez-González, E., López-Solano, J., … Tiginyanu, I. M. (2015). HgGa2 Se4 under high pressure: An optical absorption study. physica status solidi (b), 252(9), 2043-2051. doi:10.1002/pssb.201451714Rahnamaye Aliabad, H. A., Basirat, S., & Ahmad, I. (2017). Structural, electronical and thermoelectric properties of CdGa2S4 compound under high pressures by mBJ approach. Journal of Materials Science: Materials in Electronics, 28(21), 16476-16483. doi:10.1007/s10854-017-7559-1Ursaki, V. V., Burlakov, I. I., Tiginyanu, I. M., Raptis, Y. S., Anastassakis, E., & Anedda, A. (1999). Phase transitions in defect chalcopyrite compounds under hydrostatic pressure. Physical Review B, 59(1), 257-268. doi:10.1103/physrevb.59.257Klotz, S., Chervin, J.-C., Munsch, P., & Le Marchand, G. (2009). Hydrostatic limits of 11 pressure transmitting media. Journal of Physics D: Applied Physics, 42(7), 075413. doi:10.1088/0022-3727/42/7/075413Blöchl, P. E. (1994). Projector augmented-wave method. Physical Review B, 50(24), 17953-17979. doi:10.1103/physrevb.50.17953Kresse, G., & Furthmüller, J. (1996). Efficient iterative schemes forab initiototal-energy calculations using a plane-wave basis set. Physical Review B, 54(16), 11169-11186. doi:10.1103/physrevb.54.11169Baroni, S., de Gironcoli, S., Dal Corso, A., & Giannozzi, P. (2001). Phonons and related crystal properties from density-functional perturbation theory. Reviews of Modern Physics, 73(2), 515-562. doi:10.1103/revmodphys.73.515Perdew, J. P., Ruzsinszky, A., Csonka, G. I., Vydrov, O. A., Scuseria, G. E., Constantin, L. A., … Burke, K. (2008). Restoring the Density-Gradient Expansion for Exchange in Solids and Surfaces. Physical Review Letters, 100(13). doi:10.1103/physrevlett.100.136406Sans, J. Á., Santamaría-Pérez, D., Popescu, C., Gomis, O., Manjón, F. J., Vilaplana, R., … Tiginyanu, I. M. (2014). Structural and Vibrational Properties of CdAl2S4under High Pressure: Experimental and Theoretical Approach. The Journal of Physical Chemistry C, 118(28), 15363-15374. doi:10.1021/jp5037926Lottici, P. P., & Razzetti, C. (1984). Raman scattering in mixed defect chalcopyrite crystals. Journal of Molecular Structure, 115, 133-136. doi:10.1016/0022-2860(84)80032-0Kerimova, T. G., Abdullaev, N. A., Mamedova, I. A., Badalova, Z. I., Guliev, R. A., Paucar, R., … Mamedov, N. T. (2013). Optical phonons in CdGa2S4x Se4(1 − x) alloys. Semiconductors, 47(6), 761-766. doi:10.1134/s1063782613060110Tiginyanu, I. M., Lottici, P. P., Razzetti, C., & Gennari, S. (1993). Effects of the Cations on the Raman Spectra of Sulphur Defect Chalcopyrites. Japanese Journal of Applied Physics, 32(S3), 561. doi:10.7567/jjaps.32s3.561Kerimova, T. G., Mamedova, I. A., Abdullayev, N. A., Asadullayeva, S. Q., & Badalova, Z. I. (2014). Raman scattering in ZnGa2Se4 single crystals. Semiconductors, 48(7), 868-871. doi:10.1134/s1063782614070112Razzetti, C., & Lottici, P. P. (1993). Raman Scattering in Defective AIIB2IIIX4VICompounds and Alloys. Japanese Journal of Applied Physics, 32(S3), 431. doi:10.7567/jjaps.32s3.431Syrbu, N. N., Nemerenco, L. L., & Cojocaru, O. (2002). Vibrational and Polariton Spectra of CdGa2S4 and CdAl2S4 Crystals. Crystal Research and Technology, 37(1), 101-110. doi:10.1002/1521-4079(200202)37:13.0.co;2-dGomis, O., Vilaplana, R., Manjón, F. J., Santamaría-Pérez, D., Errandonea, D., Pérez-González, E., … Ursaki, V. V. (2013). High-pressure study of the structural and elastic properties of defect-chalcopyrite HgGa2Se4. Journal of Applied Physics, 113(7), 073510. doi:10.1063/1.4792495Gomis, O., Ortiz, H. M., Sans, J. A., Manjón, F. J., Santamaría-Pérez, D., Rodríguez-Hernández, P., & Muñoz, A. (2016). InBO3 and ScBO3 at high pressures: An ab initio study of elastic and thermodynamic properties. Journal of Physics and Chemistry of Solids, 98, 198-208. doi:10.1016/j.jpcs.2016.07.002K. R. Allakhverdiev, Frontiers of High Pressure Research II: Application of High Pressure to Low-Dimensional Novel Electronic Materials (Springer, 2001), p. 99.Lottici, P. P., & Razzetti, C. (1983). A comparison of the raman spectra of ZnGa2Se4 and other gallium defect chalcopyrites. Solid State Communications, 46(9), 681-684. doi:10.1016/0038-1098(83)90506-9Sanjuán, M. L., & Morón, M. C. (2002). Raman study of Zn1−xMnxGa2Se4 diluted magnetic semiconductors: disorder and resonance effects. Physica B: Condensed Matter, 316-317, 565-567. doi:10.1016/s0921-4526(02)00574-4Radautsan, S. I., Tiginyanu, I. M., Ursakii, V. V., Fomin, V. M., & Pokatilov, E. P. (1990). The Peculiarities of the Temperature Broadening of Raman Light Scattering Lines in Zn(Cd)Ga2Se4 Single Crystals. physica status solidi (b), 162(1), K63-K66. doi:10.1002/pssb.2221620143Bernard, J. E., & Zunger, A. (1988). Ordered-vacancy-compound semiconductors: PseudocubicCdIn2Se4. Physical Review B, 37(12), 6835-6856. doi:10.1103/physrevb.37.6835Manjón, F. J., Gomis, O., Vilaplana, R., Sans, J. A., & Ortiz, H. M. (2013). Order-disorder processes in adamantine ternary ordered-vacancy compounds. physica status solidi (b), 250(8), 1496-1504. doi:10.1002/pssb.201248596Mitani, T., Naitou, T., Matsuishi, K., Onari, S., Allakhverdiev, K., Gashimzade, F., & Kerimova, T. (2003). Raman scattering in CdGa2Se4 under pressure. physica status solidi (b), 235(2), 321-325. doi:10.1002/pssb.200301579Meenakshi, S., Vijyakumar, V., Godwal, B. K., Eifler, A., Orgzall, I., Tkachev, S., & Hochheimer, H. D. (2006). High pressure X-ray diffraction study of CdAl2Se4 and Raman study of AAl2Se4 (A=Hg, Zn) and CdAl2X4 (X=Se, S). Journal of Physics and Chemistry of Solids, 67(8), 1660-1667. doi:10.1016/j.jpcs.2006.02.015Manjón, F. J., Marí, B., Serrano, J., & Romero, A. H. (2005). Silent Raman modes in zinc oxide and related nitrides. Journal of Applied Physics, 97(5), 053516. doi:10.1063/1.1856222H. Bilz and W. Kress, Phonon Dispersion Relations in Insulators (Springer, 1979), p. 110.Cheng, Y. C., Jin, C. Q., Gao, F., Wu, X. L., Zhong, W., Li, S. H., & Chu, P. K. (2009). Raman scattering study of zinc blende and wurtzite ZnS. Journal of Applied Physics, 106(12), 123505. doi:10.1063/1.3270401(2017). Theoretical Analysis of Elastic, Mechanical and Phonon Properties of Wurtzite Zinc Sulfide under Pressure. Crystals, 7(6), 161. doi:10.3390/cryst7060161González, J., Fernández, B. J., Besson, J. M., Gauthier, M., & Polian, A. (1992). High-pressure behavior of Raman modes inCuGaS2. Physical Review B, 46(23), 15092-15101. doi:10.1103/physrevb.46.15092Talwar, D. N., Vandevyver, M., Kunc, K., & Zigone, M. (1981). Lattice dynamics of zinc chalcogenides under compression: Phonon dispersion, mode Grüneisen, and thermal expansion. Physical Review B, 24(2), 741-753. doi:10.1103/physrevb.24.741Griesinger, A., Spindler, K., & Hahne, E. (1999). Measurements and theoretical modelling of the effective thermal conductivity of zeolites. International Journal of Heat and Mass Transfer, 42(23), 4363-4374. doi:10.1016/s0017-9310(99)00096-4Hofmeister, A. M., & Mao, H. -k. (2002). Redefinition of the mode Gruneisen parameter for polyatomic substances and thermodynamic implications. Proceedings of the National Academy of Sciences, 99(2), 559-564. doi:10.1073/pnas.241631698Miller, S. A., Gorai, P., Ortiz, B. R., Goyal, A., Gao, D., Barnett, S. A., … Toberer, E. S. (2017). Capturing Anharmonicity in a Lattice Thermal Conductivity Model for High-Throughput Predictions. Chemistry of Materials, 29(6), 2494-2501. doi:10.1021/acs.chemmater.6b04179Zeier, W. G., Zevalkink, A., Gibbs, Z. M., Hautier, G., Kanatzidis, M. G., & Snyder, G. J. (2016). Thinking Like a Chemist: Intuition in Thermoelectric Materials. Angewandte Chemie International Edition, 55(24), 6826-6841. doi:10.1002/anie.201508381Barron, T. H. . (1957). Grüneisen parameters for the equation of state of solids. Annals of Physics, 1(1), 77-90. doi:10.1016/0003-4916(57)90006-4Arora, A. K. (1990). Grüneisen parameter of soft phonons and high pressure phase transitions in semiconductors. Journal of Physics and Chemistry of Solids, 51(4), 373-375. doi:10.1016/0022-3697(90)90122-vGrüneisen, E. (1912). Theorie des festen Zustandes einatomiger Elemente. Annalen der Physik, 344(12), 257-306. doi:10.1002/andp.19123441202Mishra, K. K., Bevara, S., Ravindran, T. R., Patwe, S. J., Gupta, M. K., Mittal, R., … Tyagi, A. K. (2018). High pressure behavior of complex phosphate K2Ce[PO4]2: Grüneisen parameter and anharmonicity properties. Journal of Solid State Chemistry, 258, 845-853. doi:10.1016/j.jssc.2017.12.022Manjon, F. J., Tiginyanu, I., & Ursaki, V. (Eds.). (2014). Pressure-Induced Phase Transitions in AB2X4 Chalcogenide Compounds. Springer Series in Materials Science. doi:10.1007/978-3-642-40367-5Allakhverdiev, K., Gashimzade, F., Kerimova, T., Mitani, T., Naitou, T., Matsuishi, K., & Onari, S. (2003). Raman scattering under pressure in ZnGa2Se4. Journal of Physics and Chemistry of Solids, 64(9-10), 1597-1601. doi:10.1016/s0022-3697(03)00077-5Parlak, C., & Eryiğit, R. (2006). Ab initiovolume-dependent elastic and lattice dynamical properties of chalcopyriteCuGaSe2. Physical Review B, 73(24). doi:10.1103/physrevb.73.245217Kern, G., Kresse, G., & Hafner, J. (1999). Ab initiocalculation of the lattice dynamics and phase diagram of boron nitride. Physical Review B, 59(13), 8551-8559. doi:10.1103/physrevb.59.8551B. A. Weinstein and R. Zallen, Light Scattering in Solids IV (Springer, 1984), p. 463.Schwer, H., & Krämer, V. (1990). The crystal structures of CdAl2S4, HgAl2S4, and HgGa2S4. Zeitschrift für Kristallographie, 190(1-2), 103-110. doi:10.1524/zkri.1990.190.1-2.103Mamedov, K. K., Aliev, M. M., Kerimov, I. G., & Kh. Nani, R. (1972). Heat capacity of AIIB2IIIC4VI-type ternary semiconducting compounds at low temperatures. Physica Status Solidi (a), 9(2), K149-K152. doi:10.1002/pssa.2210090255Quintero, M., Morocoima, M., Guerrero, E., & Ruiz, J. (1994). Temperature variation of lattice parameters and thermal expansion coefficients of the compound MnGa2Se4. Physica Status Solidi (a), 146(2), 587-593. doi:10.1002/pssa.2211460203Ravindran, T. R., Arora, A. K., & Mary, T. A. (2000). High Pressure Behavior ofZrW2O8: Grüneisen Parameter and Thermal Properties. Physical Review Letters, 84(17), 3879-3882. doi:10.1103/physrevlett.84.3879Morocoima, M., Quintero, M., Guerrero, E., Tovar, R., & Conflant, P. (1997). Temperature variation of lattice parameters and thermal expansion coefficients of the compound ZnGa2Se4. Journal of Physics and Chemistry of Solids, 58(3), 503-507. doi:10.1016/s0022-3697(96)00048-

Neuroanatomic-based detection algorithm for automatic labeling of brain structures in brain injury

The number and grade of injured neuroanatomic structures and the type of injury determine the degree of impairment after a brain injury event and the recovery options of the patient. However, the body of knowledge and clinical intervention guides are basically focused on functional disorder and they still do not take into account the location of injuries. The prognostic value of location information is not known in detail either. This paper proposes a feature-based detection algorithm, named Neuroanatomic-Based Detection Algorithm (NBDA), based on SURF (Speeded Up Robust Feature) to label anatomical brain structures on cortical and sub-cortical areas. Themain goal is to register injured neuroanatomic structures to generate a database containing patient?s structural impairment profile. This kind of information permits to establish a relation with functional disorders and the prognostic evolution during neurorehabilitation procedures

Recommendations of the GARIN group for dietary managing of patient with chronic kidney disease

[ES] Introducción y objetivos: en el tratamiento dietético de los pacientes con enfermedad renal crónica (ERC) existen muchas áreas de incertidumbre. El grupo de trabajo GARIN tiene como objetivo defi nir su posición en este campo. Material y métodos: revisión bibliográfi ca previa y reunión presencial en la que se discutieron y contestaron preguntas específi cas sobre el tema. Resultados: la actuación terapéutica debe ser individualizada y atendiendo al grado de enfermedad renal que presente el paciente y a sus comorbilidades. En cuanto a la terapia médica nutricional, nuestro grupo propone tres niveles diferentes de actuación, en los que las recomendaciones de ingesta proteica, fi bra, ácidos grasos o potasio son distintas. Además, sugerimos utilizar el concepto ratio fósforo/proteína en el ajuste de la dieta del paciente con ERC. Damos recomendaciones en cuanto al tratamiento en diabetes y en suplementación artifi cial. Conclusiones: estas recomendaciones aportan respuestas concretas sobre cuestiones comunes en la asistencia a pacientes con ERC.[EN] Background and objectives: by means of this update, the GARIN working group aims to defi ne its position regarding the dietary treatment of patients with chronic kidney disease (CKD). In this area there are many aspects of uncertainty. Material and methods: bibliographical review and specifi c questions in advance were discussed and answered at a meeting in the form of conclusions. Results: the therapeutic action must be individualized and taking into account the degree of renal failure that the patient presents and their comorbidities. Regarding nutritional medical therapy, our group proposes three different levels of action, in which the recommendations of protein intake, fi ber, fatty acids or potassium are different. In addition, we suggest using the phosphorus/protein ratio concept in adjusting the diet of the patient with CKD. We give recommendations regarding treatment in diabetes and artifi cial supplementation. Conclusions: these recommendations about dietary issues in patients with CKD can add value to clinical work.Nestlé Health Nutrition cubrió todos los gastos de transporte y de alquiler de salones para las sesiones físicas, pero no ha tomado parte en el desarrollo, diseño o manuscrito del artículo

Melatonin protects rats from radiotherapy-induced small intestine toxicity

Radiotherapy-induced gut toxicity is among the most prevalent dose-limiting toxicities following radiotherapy. Prevention of radiation enteropathy requires protection of the small intestine. However, despite the prevalence and burden of this pathology, there are currently no effective treatments for radiotherapy-induced gut toxicity, and this pathology remains unclear. The present study aimed to investigate the changes induced in the rat small intestine after external irradiation of the tongue, and to explore the potential radio-protective effects of melatonin gel. Male Wistar rats were subjected to irradiation of their tongues with an X-Ray YXLON Y.Tu 320-D03 irradiator, receiving a dose of 7.5 Gy/day for 5 days. For 21 days post-irradiation, rats were treated with 45 mg/day melatonin gel or vehicle, by local application into their mouths. Our results showed that mitochondrial oxidative stress, bioenergetic impairment, and subsequent NLRP3 inflammasome activation were involved in the development of radiotherapy-induced gut toxicity. Oral treatment with melatonin gel had a protective effect in the small intestine, which was associated with mitochondrial protection and, consequently, with a reduced inflammatory response, blunting the NF-κB/NLRP3 inflammasome signaling activation. Thus, rats treated with melatonin gel showed reduced intestinal apoptosis, relieving mucosal dysfunction and facilitating intestinal mucosa recovery. Our findings suggest that oral treatment with melatonin gel may be a potential preventive therapy for radiotherapy-induced gut toxicity in cancer patients.This study was partially supported by grant no. SAF2009-14037 from the Spanish Ministry of Economy and Competitivity (MINECO), GREIB.PT_2010_04 from the CEIBiotic Program of the University of Granada, Spain, and CTS-101 from the Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía, Spain

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research