Exploring the ring-closing metathesis for the construction of the solomonamide macrocyclic core: identification of bioactive precursors

New synthetic strategies directed toward the novel cyclopeptides solomonamides have been explored utilizing an olefin metathesis as the key reaction. In the various strategies investigated, we worked on minimally oxidized systems, and the olefin metathesis reaction demonstrated efficiency and validity for the construction of the macrocyclic core. The described synthetic strategies toward the solomonamides are well suited for the subsequent access to the natural products and represent flexible and diversityoriented routes that allow for the generation of a variety of analogues via oxidative transformations. In addition, preliminary biological evaluations of the generated solomonamide precursors revealed antitumor activity against various tumor cell lines.This work was financially supported by the Ministerio de Economía y Competitividad (MINECO) (ref BIO2014-56092-R, CTQ2014-60223-R and CTQ2016-76311-R) and Junta de Andalucía and “Fondo Europeo de Desarrollo Regional-FEDER” (P12 CTS-1507). I.C.-S. thanks Ministerio de Educación, Cultura y Deporte for a predoctoral fellowship (FPU programme)

“COMPETENCIAS PROFESIONALES Y DESEMPEÑO LABORAL DE LOS TRABAJADORES DE LA DIRECCIÓN REGIONAL DE EDUCACIÓN DE TUMBES, 2019”

La presente investigación tuvo como objetivo determinar cómo las competencias profesionales se relacionan con el desempeño laboral de los trabajadores de la Dirección Regional de Educación de Tumbes, 2019. La investigación fue de tipo descriptivo-correlacional, de diseño no experimental, con enfoque cuantitativo, de corte transversal. Entre los resultados presenta que, el 2% de los trabajadores en la Dirección Regional de Educación de Tumbes, tiene poca competencia técnica. Según los jefes de área, el 4% de los trabajadores de la Dirección Regional de Educación tienen poca eficacia. De la misma forma, se encontró que, el 52% de los entrevistados manifestaron que los trabajadores tienen mucho conocimiento de los diversos procedimientos utilizados. El 4% consideraron que el trabajador tiene poco conocimiento de los procedimientos utilizados en su espacio de trabajo, y el 44% lo indicó regular. A diferencia de lo encontrado por (Púm, 2018) en su investigación, en la que el 77% de las competencias relacionadas con el conocimiento se desarrollan muy bien. Concluyendo que, existe una relación positiva media entre la competencia técnica, competencia metodológica, competencia social, y el desempeño laboral.

Absorción sonora en cristales de sonido: aplicación en el lanzamiento de cohetes espaciales

[EN] The high acoustic pressure levels experienced by spacecrafts and launchers during the lift-off are due, among other factors, to the reflection of the sound waves in the launch pad. We propose in this work the use of sonic crystals in the launch pad, with the aim of reducing the effect of vibrations induced by the shock wave generated during the lift-off of the space vehicle. The effect of viscothermal losses in sonic crystals in sound absorption during the first stages of the rocket launch is studied. For this purpose, this kind of losses are modelled considering the sonic crystal as a rigid perforated panel and proposing an specific configuration for its placement in the launch pad.[ES] Los elevados niveles de presión acústica experimentados por cohetes espaciales y lanzaderas durante el despegue son debidos, entre otros factores, a la reflexión de las ondas de sonido en la plataforma de lanzamiento. Se propone el uso de cristales de sonido en la base de lanzamiento para reducir el efecto de las vibraciones inducidas por la onda de choque generada en el despegue del vehículo espacial. En este trabajo se estudia el efecto de las pérdidas viscotérmicas en cristales de sonido en la absorción del sonido durante las primeras fases del lanzamiento de cohetes espaciales. Para ello, se modelan este tipo de pérdidas considerando el cristal de sonido como un panel rígido perforado y proponiendo una configuración específica para su ubicación en la base de lanzamiento.Los autores agradecen el apoyo de European Space Agency (ESA) a través del doctorando cofinanciado 441- 2015 «Acoustic Noise Reduction Methods for the Launch Pad», el Ministerio de Economía y Competitividad a través del Proyecto Coordinado «Ondas de luz y sonido en cristales, medios estructurados y metamateriales», y la Conselleria de Educación, Investigación, Cultura y Deporte a través del Proyecto AICO/2016/060.Herrero Durá, I.; Picó Vila, R.; Sánchez Morcillo, VJ.; García Raffi, LM.; Romero García, V. (2017). Absorción sonora en cristales de sonido: aplicación en el lanzamiento de cohetes espaciales. REVISTA DE ACÚSTICA. 48(1):12-16. http://hdl.handle.net/10251/89684S121648

The Development of the Bengamides as New Antibiotics against Drug-Resistant Bacteria

The bengamides comprise an interesting family of natural products isolated from sponges belonging to the prolific Jaspidae family. Their outstanding antitumor properties, coupled with their unique mechanism of action and unprecedented molecular structures, have prompted an intense research activity directed towards their total syntheses, analogue design, and biological evaluations for their development as new anticancer agents. Together with these biological studies in cancer research, in recent years, the bengamides have been identified as potential antibiotics by their impressive biological activities against various drug-resistant bacteria such as Mycobacterium tuberculosis and Staphylococcus aureus. This review reports on the new advances in the chemistry and biology of the bengamides during the last years, paying special attention to their development as promising new antibiotics. Thus, the evolution of the bengamides from their initial exploration as antitumor agents up to their current status as antibiotics is described in detail, highlighting the manifold value of these marine natural products as valid hits in medicinal chemistry.Supported by grants RTI2018-098296-BI00 (Ministerio de Ciencia e Innovación), PI19/01478 from Instituto de Salud Carlos III (ISCIII) (FEDER), P20_00540 (Andalusian Government and FEDER), K99GM138758 and R35GM136286 (National Institute of General Medical Sciences of the National Institutes of Health), A-CTS-666-UGR20 (University of Granada) (FEDER), CTS-107 (Andalusian Government) and 2021-GRIN-30998 (University of Castilla-La Mancha). Partial funding for open access charge: Universidad de Málag

Synthesis, characterization and biological evaluation of octyltrimethylammonium tetrathiotungstate

Octyltrimethylammonium tetrathiotungstate salt (ATT-C8) was synthesized and its ability to chelate copper was evaluated. The biological and toxic aspects were evaluated by in vitro and in vivo assays, using bovine aorta endothelial cells (BAEC) and zebrafish (Danio rerio) embryos. The obtained results suggest that ATT-C8 has better biocompatibility, showing a significantly lower lethal concentration 50 (LC50) value in comparison to ammonium tetrathiotungstate (ATT). Zebrafish embryos assay results indicate that both tetrathiotungstate salts at the studied concentrations increase the hatching time. Even more, an in vivo assay showed that synthesized materials behave as copper antagonists and have the ability to inhibit its toxicological effects. Also, both materials were found to be active for the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The characterization of the materials was carried out using the following spectroscopic techniques: Ultraviolet–Visible (UV–Vis), Fourier Transform Infrared (FTIR) and proton nuclear magnetic resonance (1H-NRM).The authors gratefully acknowledge the financial support provided by the UABC-UNAM SENERCONACYT 117373 project. Authors thank David Navas Fernandez for excellent technical support in these experiments, as well as Dr. Raúl Romero Rivera for his valuable comments. The scientific work developed by MAM’s group is supported by grants PID2019-105010RB-I00 (Spanish Ministry of Science, Innovation and Universities), and UMA18- FEDERJA-220 (Andalusian Government and FEDER) and funds from group BIO 267 (Andalusian Government), as well as funds from ‘‘Plan Propio de Investigación y Transferencia’’ (U. Málaga)

Tocilizumab in visual involvement of giant cell arteritis: a multicenter study of 471 patients

Background: Visual involvement is the most feared complication of giant cell arteritis (GCA). Information on the efficacy of tocilizumab (TCZ) for this complication is scarce and controversial. Objective: We assessed a wide series of GCA treated with TCZ, to evaluate its role in the prevention of new visual complications and its efficacy when this manifestation was already present before the initiation of TCZ. Design: This is an observational multicenter study of patients with GCA treated with TCZ. Methods: Patients were divided into two subgroups according to the presence or absence of visual involvement before TCZ onset. Visual manifestations were classified into the following categories: transient visual loss (TVL), permanent visual loss (PVL), diplopia, and blurred vision. Results: Four hundred seventy-one GCA patients (mean age, 74 +/- 9 years) were treated with TCZ. Visual manifestations were observed in 122 cases (26%), of which 81 were present at TCZ onset: PVL (n = 60; unilateral/bilateral: 48/12), TVL (n = 17; unilateral/bilateral: 11/6), diplopia (n = 2), and blurred vision (n = 2). None of the patients without previous visual involvement or with TVL had new episodes after initiation of TCZ, while only 11 out of 60 (18%) patients with PVL experienced some improvement. The two patients with diplopia and one of the two patients with blurred vision improved. Conclusion: TCZ may have a protective effect against the development of visual complications or new episodes of TVL in GCA. However, once PVL was established, only a few patients improved

Memorias : Coloquio los Métodos en el Diseño y la Arquitectura

1 archivo PDF (190 páginas)Memorias del Coloquio Departamental Los Métodos en el Diseño y la Arquitectura, el cual tuvo dos objetivos: el primero, mostrar las reflexiones en tomo a las metodologías en el diseño y la arquitectura que utilizan los profesores tanto en la investigación como en la docencia, y el segundo, exponer ante los alumnos el trabajo previo que los profesores realizan para impartir las Unidades de Enseñanza Aprendizaje en el salón de clases

Echocardiographic Changes with Positive Airway Pressure Therapy in Obesity Hypoventilation Syndrome. Long-Term Pickwick Randomized Controlled Clinical Trial

Spanish Sleep Network.[Rationale] Obesity hypoventilation syndrome (OHS) has been associated with cardiac dysfunction. However, randomized trials assessing the impact of long-term noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) on cardiac structure and function assessed by echocardiography are lacking. Rationale: Obesity hypoventilation syndrome (OHS) has been associated with cardiac dysfunction. However, randomized trials assessing the impact of long-term noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) on cardiac structure and function assessed by echocardiography are lacking.[Objectives] In a prespecified secondary analysis of the largest multicenter randomized controlled trial of OHS (Pickwick Project; N = 221 patients with OHS and coexistent severe obstructive sleep apnea), we compared the effectiveness of three years of NIV and CPAP on structural and functional echocardiographic changes.[Methods] At baseline and annually during three sequential years, patients underwent transthoracic two-dimensional and Doppler echocardiography. Echocardiographers at each site were blinded to the treatment allocation. Statistical analysis was performed using a linear mixed-effects model with a treatment group and repeated measures interaction to determine the differential effect between CPAP and NIV. Measurements and Main Results: A total of 196 patients were analyzed: 102 were treated with CPAP and 94 were treated with NIV. Systolic pulmonary artery pressure decreased from 40.5 ± 1.47 mm Hg at baseline to 35.3 ± 1.33 mm Hg at three years with CPAP, and from 41.5 ± 1.56 mm Hg to 35.5 ± 1.42 with NIV (P < 0.0001 for longitudinal intragroup changes for both treatment arms). However, there were no significant differences between groups. NIV and CPAP therapies similarly improved left ventricular diastolic dysfunction and reduced left atrial diameter. Both NIV and CPAP improved respiratory function and dyspnea.[Conclusions] In patients with OHS who have concomitant severe obstructive sleep apnea, long-term treatment with NIV and CPAP led to similar degrees of improvement in pulmonary hypertension and left ventricular diastolic dysfunction

Tocilizumab in refractory Caucasian Takayasu's arteritis: a multicenter study of 54 patients and literature review

Objective: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu's arteritis (TAK) in clinical practice. Methods: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZMONO) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZCOMBO) was performed. Results: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5-50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0-31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5-50.0) to 5.0 (0.0-5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0-14.0) months. Twenty-three (42.6%) patients were on TCZMONO and 31 (57.4%) on TCZCOMBO: MTX (n = 28), cyclosporine A (n = 2), azathioprine (n = 1). Patients on TCZCOMBO were younger [38.0 (27.0-46.0) versus 45.0 (38.0-57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0-38.0) versus 6.0 (1.0-23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7-5.6) versus 1.3 (0.3-3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal. Conclusion: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin.Funding: This work was partially supported by RETICS Programs, RD08/0075 (RIER), RD12/0009/0013 and RD16/0012 from “Instituto de Salud Carlos III” (ISCIII) (Spain)

Obstetricia integral siglo XXI. Tomo II

El libro Obstetricia Integral siglo XXI, Tomo II, es una publicación virtual de la Facultad de Medicina, se trata de la continuación sobre el análisis detallado de los principales tópicos en el área de la obstetricia, realizada por un grupo interdisciplinario de investigadores comprometidos con el mejoramiento de la calidad en el cuidado de la salud de la mujer gestante. Se ha procurado un balance entre los aspectos básicos de fisiopatología y las guías de atención clínica soportadas en evidencias científicas, con el ánimo de brindarle al lector un equilibrio entre las bases biopsico-sociales de la salud y la enfermedad y los aspectos prácticos de la atención clínica.Vargas Fiesco, Diana Carolina and Rubio Romero, Jorge Andrés and Ruiz Parra, Ariel Iván and Rodríguez, Luis Martín and Aragón, Miguel Eduardo and Arteaga Díaz, Clara Eugenia and Riaño, Jorge Enrique and Arenas Gamboa, Jaime and Ramírez Martínez, Javier Andrés and Amaya Guío, Jairo and Gaitán , Magda Alexandry and Gallego Arbeláez, Jaime and Cortés Díaz, Daniel Otálvaro and Ángel Müller, Edith and Bracho Ch., Alcides C. and Bautista Charry, Alejandro and Rodríguez Ramos, Marcela and Navarro Milanés, Alfonso and Díaz Cruz, Luz Amparo and Mercado Pedroza, Manuel Esteban and Gaitán Duarte, Hernando and Gómez Sánchez, Pio Iván and Peña, Diana Marcela and Calvo Gómez, José Manuel and Parra Pineda, Mario Orlando and Cárdenas Muñoz, María Luisa (2010) Obstetricia integral siglo XXI. Tomo II. Facultad de Medicina, Universidad Nacional de Colombia, Bogotá. ISBN 978958447618