Cannabidiol Enhances the Passage of Lipid Nanocapsules across the Blood–Brain Barrier Both in Vitro and in Vivo

Diseases affecting the central nervous system (CNS) should be regarded as a major health challenge due to the current lack of effective treatments given the hindrance to brain drug delivery imposed by the blood–brain barrier (BBB). Since efficient brain drug delivery should not solely rely on passive targeting, active targeting of nanomedicines into the CNS is being explored. The present study is devoted to the development of lipid nanocapsules (LNCs) decorated with nonpsychotropic cannabinoids as pioneering nonimmunogenic brain-targeting molecules and to the evaluation of their brain-targeting ability both in vitro and in vivo. Noticeably, both the permeability experiments across the hCMEC/D3 cell-based in vitro BBB model and the biodistribution experiments in mice consistently demonstrated that the highest brain-targeting ability was achieved with the smallest-sized cannabinoid-decorated LNCs. Importantly, the enhancement in brain targeting achieved with the conjugation of cannabidiol to LNCs outperformed by 6-fold the enhancement observed for the G-Technology (the main brain active strategy that has already entered clinical trials for the treatment of CNS diseases). As the transport efficiency across the BBB certainly determines the efficacy of the treatments for brain disorders, small cannabinoid-decorated LNCs represent auspicious platforms for the design and development of novel therapies for CNS diseases

An Overview of Quantum Software Engineering in Latin America

Quantum computing represents a revolutionary computational paradigm with the potential to address challenges beyond classical computers' capabilities. The development of robust quantum software is indispensable to unlock the full potential of quantum computing. Like classical software, quantum software is expected to be complex and extensive, needing the establishment of a specialized field known as Quantum Software Engineering. Recognizing the regional focus on Latin America within this special issue, we have boarded on an in-depth inquiry encompassing a systematic mapping study of existing literature and a comprehensive survey of experts in the field. This rigorous research effort aims to illuminate the current landscape of Quantum Software Engineering initiatives undertaken by universities, research institutes, and companies across Latin America. This exhaustive study aims to provide information on the progress, challenges, and opportunities in Quantum Software Engineering in the Latin American context. By promoting a more in-depth understanding of cutting-edge developments in this burgeoning field, our research aims to serve as a potential stimulus to initiate pioneering initiatives and encourage collaborative efforts among Latin American researchers.Comment: 27 pages, 9 figure

A Method for LiDAR and fisheye camera system calibration

[Resumen] El uso de sistemas de percepción que combinan sensores LiDAR y cámaras se está haciendo cada vez más frecuente, pues la fusión de sus datos proporciona una ayuda para la percepción del entorno. Además, las tareas de detección de objetos o la segmentación semántica del entorno precisan, frecuentemente, la combinación de sensores de diferente naturaleza con el objetivo de mejorar sus resultados. La calibración de estos sistemas es un paso fundamental para la correcta fusión de los datos. En este artículo se propone un método de calibración basado en un patrón para este tipo de sistemas, formados por una cámara fisheye y un LiDAR. El método evita transformar las imágenes a un modelo pin-hole, realizando una calibración a partir de la proyección esférica de la imagen, obtenida mediante los parámetros de calibración y la nube de puntos correspondiente.[Abstract] The usage of LiDAR and camera systems is increasing rapidly, since the fusion of their information may provide a better undestanding of the environment. In particular, the correct fusion of the data provided by both sensor types allows to improve the results in terms of object detection or semantic segmentation. The calibration of these systems is crucial for the correct fusion of data. This article proposes a target-based calibration method for such systems, formed by a LiDAR and a fisheye camera. The method avoids transforming the images to a pin-hole camera model, performing a calibration based on the spherical projection of the image, obtained with the calibration parameters and the corresponding point cloud.Ministerio de Educación y Formación Profesional; TED2021-130901B-I00Generalitat Valenciana; PROMETEO/2021/07

A novel procedure for protein extraction from formalin-fixed paraffin-embedded tissues

Most of the archived pathological specimens in hospitals are kept as formalin-fixed paraffin-embedded tissues (FFPE) for long-term preservation. Up to now, these samples are only used for immunohistochemistry in a clinical routine as it is difficult to recover intact protein from these FFPE tissues. Here, we report a novel, short time-consuming and cost-effective method to extract full-length, non-degraded proteins from FFPE tissues. This procedure is combined with an effective and non-toxic deparaffinisation process and an extraction method based on antigen-retrieval, high concentration of SDS and high temperature. We have obtained enough intact protein to be detected by Western blotting analysis. This technique will allow utilising these stored FFPE tissues in several applications for protein analysis helping to advance the translational studies in cancer and other diseases

Interannual variability of the early summer circulation around the Balearic Islands: driving factors and potential effects on the marine ecosystem

Six summer surveys conducted from 2001 to 2005 and in 2012 by the Spanish Institute of Oceanography (IEO) reveal that the hydrographic early summer scenarios around the Balearic Islands are related to the winter atmospheric forcing in the northwestern Mediterranean Sea. The Balearic Islands (western Mediterranean Sea) lie at the transition between the southern, fresher, newly arrived Atlantic Waters (AW) and the northern, saltier, resident AW. The meridional position of the salinity driven oceanic density front separating the new from the resident AW is determined by the presence/absence of Western Intermediate Water (WIW) in the Mallorca and Ibiza channels. When WIW is present in the channels, the oceanic density front is found either at the south of the islands, or along the Emil Boudot escarpment. In contrast, when WIW is absent, new AW progresses northwards crossing the Ibiza channel and/or the Mallorca channel. In this later scenario, the oceanic density front is closer to the Balearic Islands. A good correspondence exists between standardized winter air temperature anomaly in the Gulf ofLions and the presence of WIW in the channels. We discuss the use of a regional climatic index based on these parameters to forecast in a first-order approach the position of the oceanic front, as it is expected to have high impact on the regional marine ecosystem.Post-print

Emotional Processing Profile in Patients with First Episode Schizophrenia:The Influence of Neurocognition

This study sought to investigate the influence of neurocognition on the emotional processing profiles of patients with first-episode schizophrenia, using the 4-branch Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) (Perceiving Emotions; Facilitating Emotions; Understanding Emotions and Managing Emotions). A sample of 78 patients with first-episode schizophrenia and a group of 90 non-psychiatric control subjects were included in this work. The initial results showed that patients had lower scores than controls for the "Understanding Emotions" and "Managing Emotions" MSCEIT branches. However, after controlling for neurocognition, the only deficits were found on the "Managing Emotions" branch of the MSCEIT. This branch can be considered as measuring a more sophisticated level of emotional processing, which may constitute a deficit in itself. In conclusion, patients with first-episode schizophrenia present deficits in social cognition at the highest level that seem to be independent from neurocognition. These findings support the inclusion of the "Managing Emotions" branch of the MSCEIT as part of the MCCB.Instituto de Salud Carlos III (PI16/00359)Instituto de Salud Carlos III (PI19/00766)Comunidad de Madrid (S2017/BMD-3740)Ministry of Health (MOH-000013)4.242 JCR (2020) Q1, 39/167 Medicine, general & internal1.040 SJR (2021) Q1, 438/2489 Medicine (miscellaneous)No data IDR 2020UE

3D DIGITAL CATALOGING OF LITHIC MATERIALS FROM “COVES DE SANTA MAIRA” AND “CUEVA DE NERJA”

[EN] The aim of this Project consists on obtaining textured and geometric high accuracy 3D models from archaeological pieces of the following archaeological sites: Coves de Santa Maira (Castell de Castells, Alacant) and Cueva de Nerja (Nerja, Málaga). They are part of a project wich has been developed by Prehistoric and Archaeology Dept. at University of Valencia. This Project is based on the state-of-the-art technology applied to preservation, dissemination, study and architectural and archaeological management.[ES] El objetivo del proyecto consiste en la obtención de los modelos tridimensionales de gran precisión geométrica y texturizados de piezas arqueológicas recuperadas en dos yacimientos: les Coves de Santa Maira (Castell de Castells, Alacant) y la cueva de Nerja (Nerja, Málaga) y que forman parte de un proyecto desarrollado desde el Departamento de Prehistoria y Arqueología de la Universitat de València. Para la realización de dicho modelo se ha estimado utilizar las últimas tecnologías aplicadas a la conservación, difusión, estudio y gestión de espacios y elementos arqueológicos y arquitectónicos.Tortosa Garcia, R.; Blaco Senabre, J.; Aparicio González, Ó.; Gimeno Martínez, L.; Vilaplana Selles, A.; Aura Tortosa, JE. (2016). CATALOGACIÓN DIGITAL 3D DE MACROÚTILES LÍTICOS PROCEDENTES DE COVES DE SANTA MAIRA Y CUEVA DE NERJA. En 8th International congress on archaeology, computer graphics, cultural heritage and innovation. Editorial Universitat Politècnica de València. 327-329. https://doi.org/10.4995/arqueologica8.2015.3547OCS32732

Coordination of mitochondrial and lysosomal homeostasis mitigates inflammation and muscle atrophy during aging

Sarcopenia is one of the main factors contributing to disability of aged people. Among the possible molecular determinants of sarcopenia, increasing evidences suggest that chronic inflammation contributes to its development. However, a key unresolved question is the nature of the factors that drive inflammation during aging and that participate in the development of sarcopenia. In this regard, mitochondrial dysfunction and alterations in mitophagy induce inflammatory responses in a wide range of cells and tissues. However, whether accumulation of damaged mitochondria in muscle could trigger inflammation in the context of aging is still unknown. Here, we demonstrate that BNIP3 plays a key role in the control of mitochondrial and lysosomal homeostasis, and mitigates muscle inflammation and atrophy during aging. We show that muscle BNIP3 expression increases during aging in mice and in some humans. BNIP3 deficiency alters mitochondrial function, decreases mitophagic flux and, surprisingly, induces lysosomal dysfunction, leading to an upregulation of TLR9-dependent inflammation and activation of the NLRP3 inflammasome in muscle cells and mouse muscle. Importantly, downregulation of muscle BNIP3 in aged mice exacerbates inflammation and muscle atrophy, and high BNIP3 expression in aged human subjects associates with a low inflammatory profile, suggesting a protective role for BNIP3 against age-induced muscle inflammation in mouse and humans. Taken together, our data allows us to propose a new adaptive mechanism involving the mitophagy protein BNIP3, which links mitochondrial and lysosomal homeostasis with inflammation and is key in maintaining muscle health during aging

Efficacy and safety of intramuscular administration of allogeneic adipose tissue derived and expanded mesenchymal stromal cells in diabetic patients with critical limb ischemia with no possibility of revascularization: study protocol for a randomized controlled double-blind phase II clinical trial (The NOMA Trial)

Background: Chronic lower limb ischemia develops earlier and more frequently in patients with type 2 diabetes mellitus. Diabetes remains the main cause of lower-extremity non-traumatic amputations. Current medical treatment, based on antiplatelet therapy and statins, has demonstrated deficient improvement of the disease. In recent years, research has shown that it is possible to improve tissue perfusion through therapeutic angiogenesis. Both in animal models and humans, it has been shown that cell therapy can induce therapeutic angiogenesis, making mesenchymal stromal cell-based therapy one of the most promising therapeutic alternatives. The aim of this study is to evaluate the feasibility, safety, and efficacy of cell therapy based on mesenchymal stromal cells derived from adipose tissue intramuscular administration to patients with type 2 diabetes mellitus with critical limb ischemia and without possibility of revascularization. Methods: A multicenter, randomized double-blind, placebo-controlled trial has been designed. Ninety eligible patients will be randomly assigned at a ratio 1:1:1 to one of the following: control group (n = 30), low-cell dose treatment group (n = 30), and high-cell dose treatment group (n = 30). Treatment will be administered in a singledose way and patients will be followed for 12 months. Primary outcome (safety) will be evaluated by measuring the rate of adverse events within the study period. Secondary outcomes (efficacy) will be measured by assessing clinical, analytical, and imaging-test parameters. Tertiary outcome (quality of life) will be evaluated with SF-12 and VascuQol-6 scales. Discussion: Chronic lower limb ischemia has limited therapeutic options and constitutes a public health problem in both developed and underdeveloped countries. Given that the current treatment is not established in daily clinical practice, it is essential to provide evidence-based data that allow taking a step forward in its clinical development. Also, the multidisciplinary coordination exercise needed to develop this clinical trial protocol will undoubtfully be useful to conduct academic clinical trials in the field of cell therapy in the near future. Trial registration: ClinicalTrials.gov NCT04466007. Registered on January 07, 2020. All items from the World Health Organization Trial Registration Data Set are included within the body of the protocol