Nanoparticles for the tratment of osteoporosis

Osteoporosis is by far the most frequent metabolic disease affecting bone. Current clinical therapeutic treatments are not able to offer long-term solutions. Most of the clinically used antiosteoporotic drugs are administered systemically, which might lead to side effects in non-skeletal tissues. Therefore, to solve these disadvantages, researchers have turned to nanotechnologies and nanomaterials to create innovative and alternative treatments. One of the innovative approaches to enhance osteoporosis therapy and prevent potential adverse effects is the development of bonetargeting drug delivery technologies. It minimizes the systemic toxicity and also improves the pharmacokinetic profile and therapeutic efficacy of chemical drugs. This paper reviews the current available bone targeting drug delivery systems, focusing on nanoparticles, proposed for osteoporosis treatment. Bone targeting delivery systems is still in its infancy, thus, challenges are ahead of us, including the stability and the toxicity issues. Newly developed biomaterials and technologies with potential for safer and more effective drug delivery, require multidisciplinary collaboration between scientists from many different areas, such as chemistry, biology, engineering, medicine, etc, in order to facilitate their clinical applications

Automated Playtesting in Collectible Card Games using Evolutionary Algorithms: a Case Study in HearthStone

Collectible card games have been among the most popular and profitable products of the entertainment industry since the early days of Magic: The GatheringTM in the nineties. Digital versions have also appeared, with HearthStone: Heroes of WarCraftTM being one of the most popular. In Hearthstone, every player can play as a hero, from a set of nine, and build his/her deck before the game from a big pool of available cards, including both neutral and hero-specific cards. This kind of games offers several challenges for researchers in artificial intelligence since they involve hidden information, unpredictable behaviour, and a large and rugged search space. Besides, an important part of player engagement in such games is a periodical input of new cards in the system, which mainly opens the door to new strategies for the players. Playtesting is the method used to check the new card sets for possible design flaws, and it is usually performed manually or via exhaustive search; in the case of Hearthstone, such test plays must take into account the chosen hero, with its specific kind of cards. In this paper, we present a novel idea to improve and accelerate the playtesting process, systematically exploring the space of possible decks using an Evolutionary Algorithm (EA). This EA creates HearthStone decks which are then played by an AI versus established human-designed decks. Since the space of possible combinations that are play-tested is huge, search through the space of possible decks has been shortened via a new heuristic mutation operator, which is based on the behaviour of human players modifying their decks. Results show the viability of our method for exploring the space of possible decks and automating the play-testing phase of game design. The resulting decks, that have been examined for balancedness by an expert player, outperform human-made ones when played by the AI; the introduction of the new heuristic operator helps to improve the obtained solutions, and basing the study on the whole set of heroes shows its validity through the whole range of decks

Estudio baropodométrico en pacientes tratados mediante artroplastia total de rodilla

La patología artrósica de la rodilla condiciona una disminución de la carga del miembro afecto y un patrón de apoyo con predominio generalmente del arco externo. El propósito de este estudio es determinar si existe una modificación significativa de este patrón tras la implantación de una artroplastia total de rodilla (ATR) primaria, recogiendo las presiones plantares de ambos pies mediante baropodometría electrónica previamente y 4 meses tras la cirugía, tanto en estática como en dinámica. Así, se analizan las presiones plantares de 30 pacientes, 21 mujeres y 9 hombres, intervenidos de ATR primaria en el Hospital Universitario Doctor Peset entre los años 2013 y 2015. También se ha determinado si existe una corrección del eje anatómico tras la cirugía. Utilizando test no paramétricos (test de Wilcoxon para datos apareados, U de Mann-Whitney), observamos una modificación significativa de dicho ángulo desde valores medianos de 1.2º de varo a 4.9º de valgo en el postoperatorio, una disminución mediana de la presión plantar en ambos pies y una redistribución de la carga axial, aumentando en el miembro intervenido. Concluimos que, 4 meses tras la cirugía, se produce una tendencia a la “normalización” de la pisada en pacientes en los que se ha implantado una ATR, condicionado tanto por la mejora del dolor y la funcionalidad como por la realineación del eje.Knee osteoarthritis determines a decrease of the load of the affected limb and a pattern usually dominance of external support plantar arc. The purpose of this study is to determine whether a significant change in this pattern is? after implantation of a primary total knee arthroplasty (TKA), measuring plantar pressures in both feet by electronic baropodometry previously and 4 months after surgery, in static and dynamic. Plantar pressures of 30 patients are analyzed, who underwent primary TKA at the University Hospital Doctor Peset between 2013 and 2015. In addition, it has also been determined if there is a correction on the anatomical axis after surgery. Using nonparametric test (Wilcoxon test for paired data, U Mann Whitney), we observed a significant change in the angle from median values of 1.2º varus to 4.9º valgus postoperatively, a median decrease of plantar pressure in both feet and a redistribution of axial load, increasing in the operated limb. We conclude that, 4 months after surgery, there is a tendency to “normalization” of the tread in patients undergoing TKA. This is conditioned by improving pain and function as axis realignment occurs

Collagen-laponite nanoclay hydrogels for tumor spheroid growth

The extracellular matrix (ECM) plays an important regulatory role in the development and progression of tumoral tissue. Its functions and properties are crucial in determining tumor cell behavior such as invasion, migration, and malignancy development. Our study explores the role of collagen type I in cancer development and spread using engineered tumor models like multicellular spheroids grown in collagen-based hydrogels to simulate early tumor formation. We employ microfluidic techniques to test the hypothesis that (i) adding Laponite nanoclay to collagen hydrogels modifies mechanical and rheological properties and (ii) changing the stiffness of the collagen microenvironment affects tumor spheroid growth. Our findings support our theories and suggest the use of ECM components and engineered tumor models in cancer research, offering a biocompatible and biomimetic method to tailor the mechanical properties of conventional collagen hydrogels

Chronic bovine besnoitiosis: histopathological findings and parasite distribution and load in subclinical cases [abstract]

PublishedPoster 50, Apicowplexa 201

Proteomic Characterization of Host-Pathogen Interactions during Bovine Trophoblast Cell Line Infection by

Despite the importance of bovine neosporosis, relevant knowledge gaps remain concerning the pathogenic mechanisms of . Infection of the placenta is a crucial event in the pathogenesis of the disease; however, very little is known about the relation of the parasite with this target organ. Recent studies have shown that isolates with important variations in virulence also show different interactions with the bovine trophoblast cell line F3 in terms of proliferative capacity and transcriptome host cell modulation. Herein, we used the same model of infection to study the interaction of with these target cells at the proteomic level using LC-MS/MS over the course of the parasite lytic cycle. We also analysed the proteome differences between high- (Nc-Spain7) and low-virulence (Nc-Spain1H) isolates. The results showed that mitochondrial processes and metabolism were the main points of -host interactions. Interestingly, Nc-Spain1H infection showed a higher level of influence on the host cell proteome than Nc-Spain7 infection

Clinical relevance of the transcriptional signature regulated by CDC42 in colorectal cancer.

CDC42 is an oncogenic Rho GTPase overexpressed in colorectal cancer (CRC). Although CDC42 has been shown to regulate gene transcription, the specific molecular mechanisms regulating the oncogenic ability of CDC42 remain unknown. Here, we have characterized the transcriptional networks governed by CDC42 in the CRC SW620 cell line using gene expression analysis. Our results establish that several cancer-related signaling pathways, including cell migration and cell proliferation, are regulated by CDC42. This transcriptional signature was validated in two large cohorts of CRC patients and its clinical relevance was also studied. We demonstrate that three CDC42-regulated genes offered a better prognostic value when combined with CDC42 compared to CDC42 alone. In particular, the concordant overexpression of CDC42 and silencing of the putative tumor suppressor gene CACNA2D2 dramatically improved the prognostic value. The CACNA2D2/CDC42 prognostic classifier was further validated in a third CRC cohort as well as in vitro and in vivo CRC models. Altogether, we show that CDC42 has an active oncogenic role in CRC via the transcriptional regulation of multiple cancer-related pathways and that CDC42-mediated silencing of CACNA2D2 is clinically relevant. Our results further support the use of CDC42 specific inhibitors for the treatment of the most aggressive types of CRC