Reducción de los tiempos de observación en la evaluación del observación en la evaluación del comportamiento de conejas en producción. Análisis metodológico.

El objetivo de este trabajo fue evaluar diferentes técnicas de muestreo que redujeran el tiempo total de observación necesario para estimar el comportamiento de conejas alojadas en dos tipos de jaulas (convencionales vs. enriquecidas) y en dos estados fisiológicos distintos (gestantes vs. lactantes). Para ello, se compararon grabaciones completas de 24 h (método control de referencia) con estimaciones obtenidas a partir de grabaciones de diferente duración y frecuencia (métodos regular corto y regular largo y métodos irregulares de 6h y de 8h). A partir de los resultados obtenidos se observa que los métodos regulares se ajustaron mejor al método de referencia de 24h que los irregulares. Desde un punto de vista práctico el método regular corto sería el ideal, al reducir considerablemente el número total de horas de observación y análisi

Recovering actives in multi-antitarget and target design of analogs of the myosin II inhibitor blebbistatin

In multitarget drug design, it is critical to identify active and inactive compounds against a variety of targets and antitargets. Multitarget strategies thus test the limits of available technology, be that in screening large databases of compounds vs a large number of targets, or in using in silica methods for understanding and reliably predicting these pharmacological outcomes In this paper, we have evaluated the potential of several in silica approaches to predict the target, antitarget and physicochemical profile of (S)-blebbistatin, the best-known myosin II ATPase inhibitor, and a series of analogs thereof Standard and augmented structure-based design techniques could not recover the observed activity profiles A ligand-based method using molecular fingerprints was, however, able to select actives for myosin II inhibition Using further ligand- and structure-based methods, we also evaluated toxicity through androgen receptor binding, affinity for an array of antitargets and the ADME profile (including assay-interfering compounds) of the series In conclusion, in the search for (S)-blebbistatin analogs, the dissimilarity distance of molecular fingerprints to known actives and the computed antitarget and physicochemical profile of the molecules can be used for compound design for molecules with potential as tools for modulating myosin II and motility-related diseases

Palladium-Catalyzed Remote ortho-C-H Alkenylation of Alkyl Aryl Sulfones: Access to Densely Functionalized Indane Derivatives

This is the peer-reviewed version of the following article: Advanced Synthesis and Catalysis 358.7 (2016): 1065-1072, which has been published in final form at http://dx.doi.org/10.1002/adsc.201501129. This article may be used for non-commercial purposes in accordance with Wiley-VCH Terms and Conditions for Self-ArchivingA practical method for the palladium-cat-alyzed ortho-olefination of benzyl and phenethyl 2-pyridyl sulfones with electron-deficient alkenes using N-fluoro-2,4,6-trimethylpyridinium triflate ([F+]) as the terminal oxidant is described. The che-lating auxiliary (2-pyridyl)sulfonyl unit was demon-strated to be the key to the success of this reaction, which occurs efficiently with excellent regioselectiv-ity and monosubstitution selectivity. A variety of steric and electronic changes to both coupling part-ners is tolerated, including substitution at the ben-zylic position of the sulfone compound. Further-more, no appreciable loss of enantiopurity is ob-served when using non-racemic substrates. This method provides access to indane derivatives hold-ing three contiguous stereogenic centers with high diastereocontrol. The indane framework was con-structed by intramolecular Michael addition of the a-sulfonyl carbanion to the electrophilic alkeneWe thank the Spanish Government (MINECO, CTQ2012- 35790) for financial support. P.D. L. thanks the Spanish Government (MINECO) for an FPU predoctoral fellowshi

Pure cervical radiculopathy due to spontaneous spinal epidural haematoma (SSEH): report of a case solved conservatively

Abstract Introduction: Spontaneous spinal epidural haematoma (SSEH) is widely recognised throughout the literature as a cause of myelopathy, radicular compression being very rarely reported. Surgical management is almost always recommended, especially in the cases of spinal cord compression. Conservative treatment is reported as a curiosity and only in the case of spontaneous improvement. This report presents the particular case of a 64-year-old patient undergoing anticoagulant therapy that had a cervical radiculopathy due to a SSEH confirmed by MRI. The patient improved spontaneously and symptoms were solved with unconventional conservative treatment and without stopping the anticoagulant therapy. Conclusions: Spontaneous epidural haematoma must be kept in mind when patients undergoing anticoagulant therapy have a sudden onset of cervicobrachialgia. Even though most spinal surgeons advocate surgical treatment, a conservative approach may lead to a complete recovery and may be considered as a good option in the case of radicular involvement. Discontinuation of the anticoagulant therapy may not always be needed, especially when the clinical syndrome improves spontaneously

Evidence for a chemically differentiated outflow in Mrk 231

Aims: Our goal is to study the chemical composition of the outflows of active galactic nuclei and starburst galaxies. Methods: We obtained high-resolution interferometric observations of HCN and HCO$^+$ $J=1\rightarrow0$ and $J=2\rightarrow1$ of the ultraluminous infrared galaxy Mrk~231 with the IRAM Plateau de Bure Interferometer. We also use previously published observations of HCN and HCO$^+$ $J=1\rightarrow0$ and $J=3\rightarrow2$, and HNC $J=1\rightarrow0$ in the same source. Results: In the line wings of the HCN, HCO$^+$, and HNC emission, we find that these three molecular species exhibit features at distinct velocities which differ between the species. The features are not consistent with emission lines of other molecular species. Through radiative transfer modelling of the HCN and HCO$^+$ outflow emission we find an average abundance ratio $X(\mathrm{HCN})/X(\mathrm{HCO}^+)\gtrsim1000$. Assuming a clumpy outflow, modelling of the HCN and HCO$^+$ emission produces strongly inconsistent outflow masses. Conclusions: Both the anti-correlated outflow features of HCN and HCO$^+$ and the different outflow masses calculated from the radiative transfer models of the HCN and HCO$^+$ emission suggest that the outflow is chemically differentiated. The separation between HCN and HCO$^+$ could be an indicator of shock fronts present in the outflow, since the HCN/HCO$^+$ ratio is expected to be elevated in shocked regions. Our result shows that studies of the chemistry in large-scale galactic outflows can be used to better understand the physical properties of these outflows and their effects on the interstellar medium (ISM) in the galaxy.Comment: 12 pages, 8 figures, accepted for publication in A&

Efecto del tipo de jaula sobre el comportamiento de conejas

El objetivo de este ensayo fue evaluar el efecto del tipo de jaula (convencional vs. enriquecida) y el estado fisiológico de las conejas (gestación vs. lactación) sobre su comportamiento. Se realizaron grabaciones de 12 conejas multíparas durante 24 h en dos momentos distintos. Los comportamientos observados se clasificaron en tres grupos independientes (localización, locomoción y acciones). Se observó una predominancia clara por el uso del reposapatas (principalmente en la fase de lactación), pero este tiempo disminuyó significativamente en jaulas enriquecidas debido al uso de la plataforma (67,1 vs. 48,2%; Pmenor que0,05). Las conejas permanecieron tumbadas y sentadas el 78,4 y 20,7% del día, respectivamente, sin tener efecto ni el tipo de jaula ni el estado fisiológico. Las conejas se ponían de pie únicamente para comer u oler las heces retenidas sobre la plataforma. Las conejas se mostraron más nerviosas en la fase de lactación tratando de huir de los gazapos, siendo esta huida exitosa cuando las conejas tenían la posibilidad de utilizar la plataforma. Las conejas gestantes estuvieron significativamente más tiempo que las lactantes acicalándose, mordiendo barrotes e interaccionando con las vecinas (Pmenor que0,01; 0,05 y 0,05, respectivamente). Las conejas lactantes dedicaron más tiempo a beber (Pmenor que0,05) que las gestantes. De este trabajo se desprende que el aumento del espacio disponible con la colocación de una plataforma elevada podría ser una buena alternativa para la mejora del bienestar de las conejas, sobre todo en la fase final de la lactación, aunque la retención de heces sobre la plataforma y las deyecciones pueden ocasionar problemas de higiene

Consumo de tabaco y pseudoartrosis en cirugía lumbar instrumentada: Estudio comparativo

El objetivo de este estudio fue determinar si en los pacientes fumadores de más de 20 cigarrillos al día había una incidencia más alta de pseudoartrosis que en los pacientes no fumadores. El estudio retrospectivo se efectuó en un grupo de 100 pacientes (50 fumadores y 50 no fumadores), intervenidos por problemas degenerativos del caquis mediante artrodesis instrumentada y posterolateral a nivel lumbosacro. Cincuenta y tres pacientes eran varones y 47 mujeres, con una edad media de 49+-10 años. Para determinar la incidencia de pseudoartrosis se valoraron las masas de fusión a los 6 y 24 meses de la intervención y la situación clínica del paciente. A siete de los 100 pacientes se les diagnosticó pseudoartrosis (2 no fumadores y 5 fumadores); los 93 restantes que no presentaron pseudoartrosis, 48 correspondían a pacientes no fumadores y 45 eran fumadores (p=0,24). No hemos podido demostrar la asociación entre consumo de tabaco y mayor índice de pseudoartrosis en pacientes intervenidos de artrodesis lumbosacra.The aim of this study was to determine whether smokers (more than 20 cigarettes per day) had higher rate of pseudoarthrosis than the non-smokers after lumbar fusion. A retrospective study was designed with 100 patients (50 smokers and 50 non-smokers). All the patients were operated on, by doing a posterolateral fusion with instrumentation (transpedicular fixation), due to degenerative pathology of the lumbar spine. Fifty-three patients were males and 47 were females, with an average age of 49+-10 years. To determinate pseudoarthrosis two types of evaluation were performed: Radiographic evaluation in plain radiographs at 6 and 24 months after surgery and clinical assessment. Seven out of 100 patients were diagnosed as pseudoarthrosis (2 non-smokers and 5 smokers) and, of the remaining 93 patients, 48 were non-smokers and 28 smokers (p=0.24). No evidence was found of correlation between cigarette smoking and a higher rate of pseudoarthrosis in patients with an instrumental arthrodesis of the lumbar spine