Estudio gonioscópico del ángulo iridocorneal del Perro de Agua Español

Realizamos un estudio gonioscópico de 46 Perros de Agua Español sanos, apreciando un ángulo iridocorneal abierto en todos los cuadrantes. Describimos las diferentes estructuras del ángulo iridocorneal en esta raza: las dos filas de fibras. del ligamento pectinado, la red trabecular uveal con los espacios de Fontana, y las bandas pigmentadas superficial y profunda. El ángulo iridocorneal en el Perro de Agua Español no presenta características peculiares para esta raza. Hemos observado grandes diferencias entre ojos de distintos perros, menores entre los del mismo perro, y escasas entre los distintos cuadrantes del mismo ojo. El grado de pigmentación de las estructuras del ángulo iridocorneal no depende del sexo ni de la edad, sino sólo de la pigmentación de la capa y del iris.In the present work, we have realized a gonioscopic study in 46 Spanish Water's Dogs. We have seen an iridocorneal angle always open in all quadrants and we have noticed different structures of the iridocorneal angie. the two rows of fibres of the pectinate ligament, the uveal trabecular meshwork with the Fontana's spaces and the deep and superficial pigrnent bands. The iridocorneal angle of the Spanish Water's Dog does not exhibit peculiar characteristics for this race. We have observed large differences between eyes of different dogs, lesser differences between the eyes of the same dog, and rares differences between the different quadrants of the same eye. We have found that the degree of pigmentation of the structures of iridocorneal angle does not depend of the age, only of the pigmentation of the coat and iris

Computationally Guided Design of a Readily Assembled Phosphite- Thioether Ligand for a Broad Range of Pd-Catalyzed Asymmetric Allylic Substitutions

A modular approach employing indene as common starting material, has enabled the straightforward preparation in three reaction steps of P-thioether ligands for the Pd-catalyzed asymmetric allylic substitution. The analysis of a starting library of P-thioether ligands based on rational design and theoretical calculations has led to the discovery of an optimized anthracenethiol derivative with excellent behavior in the reaction of choice. Improving most approaches reported to date, this ligand presents a broad substrate and nucleophile scope. Excellent enantioselectivities have been achieved for a range of linear and cyclic allylic substrates using a large number of C-, N-, and O-nucleophiles (40 compounds in total). The species responsible for the catalytic activity have been further investigated by NMR in order to clearly establish the origin of the enantioselectivity. The resulting products have been derivatized by means of ring-closing metathesis or Pauson–Khand reactions to further prove the synthetic versatility of the methodology for preparing enantiopure complex structures

Small Molecules as Toll-like Receptor 4 Modulators Drug and In-House Computational Repurposing

The innate immunity toll-like receptor 4 (TLR4) system is a receptor of paramount importance as a therapeutic target. Virtual screening following a “computer-aided drug repurposing” approach was applied to the discovery of novel TLR4 modulators with a non-lipopolysaccharide-like structure. We screened almost 29,000 approved drugs and drug-like molecules from commercial, public, and in-house academia chemical libraries and, after biological assays, identified several compounds with TLR4 antagonist activity. Our computational protocol showed to be a robust approach for the identification of hits with drug-like scaffolds as possible inhibitors of the TLR4 innate immune pathways. Our collaborative work broadens the chemical diversity for inspiration of new classes of TLR4 modulators.This work was financially supported by the Spanish Ministry for Science and Innovation (grants CTQ2014-57141-R, CTQ2017-88353-R, and PID2020-113588RB-I00 for S.M.S.; grants BES-2012-053653 for L.P.R., BES-2015-071588 for J.G.C. and PID2021-124983OB-I00 for J.C.M.), the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (MINECO/FEDER; SAF2016-75988-R), and the Community of Madrid (S-2010/BMD-2332) for M.F

Sanguiin H-6 Fractionated from Cloudberry (Rubus chamaemorus) Seeds Can Prevent the Methicillin-Resistant Staphylococcus aureus Biofilm Development during Wound Infection

Staphylococcus aureus is the most common cause of surgical site infections and its treatment is challenging due to the emergence of multi-drug resistant strains such as methicillin-resistant S. aureus (MRSA). Natural berry-derived compounds have shown antimicrobial potential, e.g., ellagitannins such as sanguiin H-6 and lambertianin C, the main phenolic compounds in Rubus seeds, have shown antimicrobial activity. The aim of this study was to evaluate the effect of sanguiin H-6 and lambertianin C fractionated from cloudberry seeds, on the MRSA growth, and as treatment of a MRSA biofilm development in different growth media in vitro and in vivo by using a murine wound infection model where sanguiin H-6 and lambertianin C were used to prevent the MRSA infection. Sanguiin H-6 and lambertianin C inhibited the in vitro biofilm development and growth of MRSA. Furthermore, sanguiin H-6 showed significant anti-MRSA effect in the in vivo wound model. Our study shows the possible use of sanguiin H-6 as a preventive measure in surgical sites to avoid postoperative infections, whilst lambertianin C showed no anti-MRSA activity

Sanguiin H-6 Fractionated from Cloudberry (Rubus chamaemorus) Seeds Can Prevent the Methicillin-Resistant Staphylococcus aureus Biofilm Development during Wound Infection

Staphylococcus aureus is the most common cause of surgical site infections and its treatment is challenging due to the emergence of multi-drug resistant strains such as methicillin-resistant S. aureus (MRSA). Natural berry-derived compounds have shown antimicrobial potential, e.g., ellagitannins such as sanguiin H-6 and lambertianin C, the main phenolic compounds in Rubus seeds, have shown antimicrobial activity. The aim of this study was to evaluate the effect of sanguiin H-6 and lambertianin C fractionated from cloudberry seeds, on the MRSA growth, and as treatment of a MRSA biofilm development in different growth media in vitro and in vivo by using a murine wound infection model where sanguiin H-6 and lambertianin C were used to prevent the MRSA infection. Sanguiin H-6 and lambertianin C inhibited the in vitro biofilm development and growth of MRSA. Furthermore, sanguiin H-6 showed significant anti-MRSA effect in the in vivo wound model. Our study shows the possible use of sanguiin H-6 as a preventive measure in surgical sites to avoid postoperative infections, whilst lambertianin C showed no anti-MRSA activity

Optimization of Invasion-Specific Effects of Betulin Derivatives on Prostate Cancer Cells through Lead Development

The anti-invasive and anti-proliferative effects of betulins and abietane derivatives was systematically tested using an organotypic model system of advanced, castration-resistant prostate cancers. A preliminary screen of the initial set of 93 compounds was performed in two-dimensional (2D) growth conditions using non-transformed prostate epithelial cells (EP156T), an androgen-sensitive prostate cancer cell line (LNCaP), and the castration-resistant, highly invasive cell line PC-3. The 25 most promising compounds were all betulin derivatives. These were selected for a focused secondary screen in three-dimensional (3D) growth conditions, with the goal to identify the most effective and specific anti-invasive compounds. Additional sensitivity and cytotoxicity tests were then performed using an extended cell line panel. The effects of these compounds on cell cycle progression, mitosis, proliferation and unspecific cytotoxicity, versus their ability to specifically interfere with cell motility and tumor cell invasion was addressed. To identify potential mechanisms of action and likely compound targets, multiplex profiling of compound effects on a panel of 43 human protein kinases was performed. These target de-convolution studies, combined with the phenotypic analyses of multicellular organoids in 3D models, revealed specific inhibition of AKT signaling linked to effects on the organization of the actin cytoskeleton as the most likely driver of altered cell morphology and motility.</p

Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson’s Disease

COPPADIS Study Group.[Introduction] The aim of the present study was to examine the frequency of self-reported sleep problems and their associated factors in a large cohort of PD patients.[Methods] PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort were included in this cross-sectional study. Sleep problems were assessed by the Spanish version of the Parkinson’s disease Sleep Scale version 1 (PDSS-1). An overall score below 82 or a score below 5 on at least 1 item was defined as sleep problems.[Results] The frequency of sleep problems was nearly double in PD patients compared to controls: 65.8% (448/681) vs 33.5% (65/206) (p < 0.0001). Mean total PDSS score was lower in PD patients than controls: 114.9 ± 28.8 vs 132.8 ± 16.3 (p < 0.0001). Quality of life (QoL) was worse in PD patients with sleep problems compared to those without: PDQ-39SI, 19.3 ± 14 vs 13 ± 11.6 (p < 0.0001); EUROHIS-QoL8, 3.7 ± 0.5 vs 3.9 ± 0.5 (p < 0.0001). Non-motor symptoms burden (NMSS; OR = 1.029; 95%CI 1.015–1.043; p < 0.0001) and impulse control behaviors (QUIP-RS; OR = 1.054; 95%CI 1.009–1.101; p = 0.018) were associated with sleep problems after adjustment for age, gender, disease duration, daily equivalent levodopa dose, H&Y, UPDRS-III, UPDRS-IV, PD-CRS, BDI-II, NPI, VAS-Pain, VAFS, FOGQ, and total number of non-antiparkinsonian treatments.[Conclusion] Sleep problems were frequent in PD patients and were related to both a worse QoL and a greater non-motor symptoms burden in PD. These findings call for increased awareness of sleep problems in PD patients.Peer reviewe

Litterfall, litter decomposition and associated nutrient fluxes in Pinus halepensis: influence of tree removal intensity in a Mediterranean forest

The online version of this article (doi:10.1007/s10342-015-0893-z) contains supplementary material, which is available to authorized users[EN] Our knowledge about the influence of silvicultural treatments on nutrient cycling processes in Mediterranean forests is still limited. Four levels of tree removal were compared in an Aleppo pine forest in eastern Spain to determine the effects on litterfall, litter decomposition and the associated nutrient fluxes after 12 years. Removal treatments included clearfelling, two shelterwood intensities (60 and 75 % of basal area removed) and untreated controls. Twelve years later, the basal area removed still explained 60 % of litterfall mass variance and 60 % of C, 52 % of N, 45 % of P, 17 % of K, 47 % of Ca and 60 % of Mg return variances. Litter decomposed somewhat more slowly in clearfellings compared to controls (p = 0.049), accumulated more Ca and released less K compared to the other three treatments. This was explained by contamination with mineral particles due to the poorly developed O horizon in clearfellings. We conclude that the management practices reduced the nutrient return via litterfall, but the nutrient release through decomposition seems poorly sensitive to canopy disturbance. In order to accurately quantify the harvesting impacts on nutrient cycling in this Mediterranean forest system, it is necessary to measure the litterfall of the understory layer.This work has been supported by a fellowship from the Generalitat Valenciana, Conselleria de Educacion, Formacion y Empleo awarded to L. Lado-Monserrat (BFPI/2008/041). Silvicultural treatments were carried out by the Mediterranean Centre for Environmental Studies (CEAM) through programme "I + D en relacion con la restauracion de la cubierta vegetal y otros aspectos de investigacion forestal". Dataloggers and probes were provided by the Generalitat Valenciana through Project "Efecto de diferentes sistemas de aclareo de masa forestal sobre la disponibilidad de agua, nutrientes y la regeneracion de la masa arborea y arbustiva en parcelas de pinar" (GV06/126). We acknowledge Joana Oliver, Ruth M. Tavera and Daniel Fortanet for their help in the laboratory and in the field. The authors wish to thank Francisco Galiana for his assistance, including help in fieldwork and providing information about the experimental design of the silvicultural treatments. Thanks also go to Rafael Herrera from the Centro de Ecologia, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela and two anonymous reviewers for critically reviewing the manuscript.Lado Monserrat, L.; Lidón, A.; Bautista, I. (2015). Litterfall, litter decomposition and associated nutrient fluxes in Pinus halepensis: influence of tree removal intensity in a Mediterranean forest. 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The Euro Imbalances and Financial Deregulation: A Post-Keynesian Interpretation of the European Debt Crisis

Conventional wisdom suggests that the European debt crisis, which has thus far led to severe adjustment programs crafted by the European Union and the International Monetary Fund in both Greece and Ireland, was caused by fiscal profligacy on the part of peripheral, or noncore, countries in combination with a welfare state model, and that the role of the common currency - the euro - was at best minimal.This paper aims to show that, contrary to conventional wisdom, the crisis in Europe is the result of an imbalance between core and noncore countries that is inherent in the euro economic model. Underpinned by a process of monetary unification and financial deregulation, core eurozone countries pursued export-led growth policies - or, more specifically, beggar thy neighbor policies - at the expense of mounting disequilibria and debt accumulation in the periphery. This imbalance became unsustainable, and this unsustainability was a causal factor in the global financial crisis of 2007-08. The paper also maintains that the eurozone could avoid cumulative imbalances by adopting John Maynard Keynes's notion of the generalized banking principle (a fundamental principle of his clearing union proposal) as a central element of its monetary integration arrangement