Ternary Quantum Dots in Chemical Analysis. Synthesis and Detection Mechanisms

Ternary quantum dots (QDs) are novel nanomaterials that can be used in chemical analysis due their unique physicochemical and spectroscopic properties. These properties are size-dependent and can be adjusted in the synthetic protocol modifying the reaction medium, time, source of heat, and the ligand used for stabilization. In the last decade, several spectroscopic methods have been developed for the analysis of organic and inorganic analytes in biological, drug, environmental, and food samples, in which different sensing schemes have been applied using ternary quantum dots. This review addresses the different synthetic approaches of ternary quantum dots, the sensing mechanisms involved in the analyte detection, and the predominant areas in which these nanomaterials are usedThe authors give thanks to the CONACYT support for the grant number 771019S

Activation of lysophosphatidic acid receptor type 1 (LPA1) contributes to pathophysiology of spinal cord injury

Altres ajuts: NIH/NS084398Lysophosphatidic acid (LPA) is an extracellular lipid mediator involved in many physiological functions that signals through six known G-protein-coupled receptors (LPA1-LPA6). A wide range of LPA effects have been identified in the CNS, including neural progenitor cell physiology, astrocyte and microglia activation, neuronal cell death, axonal retraction, and development of neuropathic pain. However, little is known about the involvement of LPA in CNS pathologies. Herein, we demonstrate for the first time that LPA signaling via LPA1 contributes to secondary damage after spinal cord injury. LPA levels increase in the contused spinal cord parenchyma during the first 14 d. To model this potential contribution of LPA in the spinal cord, we injected LPA into the normal spinal cord, revealing that LPA induces microglia/macrophage activation and demyelination. Use of a selective LPA1 antagonist or mice lacking LPA1 linked receptor-mediated signaling to demyelination, which was in part mediated by microglia. Finally, we demonstrate that selective blockade of LPA1 after spinal cord injury results in reduced demyelination and improvement in locomotor recovery. Overall, these results support LPA-LPA1 signaling as a novel pathway that contributes to secondary damage after spinal cord contusion in mice and suggest that LPA1 antagonism might be useful for the treatment of acute spinal cord injur

Easing the questioning of semantic biomedical data

Researchers have been using semantic technologies as essential tools to structure knowledge. This is particularly relevant in the biomedical domain, where large dataset are continuously generated. Semantic technologies offer the ability to describe data and to map and linking distributed repositories, creating a network where the searching interface is a single entry point. However, the increasing number of semantic data repositories that are publicly available is creating new challenges related to its exploration. Despite being human and machine-readable, these technologies are much more challenging for end-users. Querying services usually require mastering formal languages and that knowledge is beyond the typical user’s expertise, being a critical issue in adopting semantic web information systems. In particular, the questioning of biomedical data presents specific challenges for which there are still no mature proposals for production environments. This paper presents a solution to query biomedical semantic databases using natural language. The system is at the intersection between semantic parsing and the use of templates. It makes it possible to extract information in a friendly way for users who are not experts in semantic queries.FCT - Portuguese Foundation for Science and Technology supports Arnaldo Pereira (Ph.D. Grant PD/BD/142877/2018).info:eu-repo/semantics/publishedVersio

A virtual reality approach to the Trier Social Stress Test: Contrasting two distinct protocols

Virtual reality adaptations of the Trier Social Stress Test (TSST-VR) constitute useful tools for studying the physiologic axes involved in the stress response. Here, we aimed to determine the most appropriate experimental approach to the TSST-VR when investigating the modulation of the axes involved in the stress response. We compared the use of goggles versus a screen projection in the TSST-VR paradigm. Forty-five healthy participants were divided into two groups: the first one (goggles condition; 13 females, 11 males) wore goggles while performing the TSST-VR; the second (screen condition; 15 females, six males) was exposed to the TSST-VR projected on a screen. Sympathetic reactivity to stress was measured by continuously recording skin conductance (SC), while the hypothalamic-pituitary-adrenal axis (HPA) was evaluated by sampling salivary cortisol throughout the experiment. At the end of the task, there was an increase in SC and cortisol level for both means of delivering the TSST-VR, although the increase in SC was greater in the goggles condition, while salivary cortisol was comparable in both groups. Immersion levels were reportedly higher in the screen presentation than in the goggles group. In terms of sex differences, females experienced greater involvement and spatial presence, though comparatively less experienced realism, than their male counterparts. These findings help us determine which protocol of the TSST-VR is most suitable for the stress response under study. They also emphasize the need to consider the sex of participants, as males and females show distinct responses in each protocol.This study is a part of a Thesis Doctoral and was supported by the I+D Project “PSI2010-15780” of the Spanish Ministry of Science and Innovation

The relationship between the menstrual cycle and cortisol secretion: Daily and stress-invoked cortisol patterns

The menstrual cycle involves significant changes in hormone levels, causing physical and psychological changes in women that are further influenced by stress. The aim of this study was to understand the relationship between menstrual cycle phase and salivary cortisol patterns during the day as well as the salivary cortisol response to the Virtual Reality Version of the Trier Social Stress Test (TSST-VR). Forty two women not taking oral contraceptives (24 in follicular phase and 18 in luteal phase) participated in the study. Five samples of salivary cortisol collected during the day and another five samples of cortisol during the TSST-VR were analyzed. Psychological stress measures and psychopathological symptomatology were also evaluated. A 2 × 4 mixed ANCOVA showed an interaction between the two groups on the TSST-RV invoked cortisol response to the [F(3,42) = 3.681; p = 0.023) where women in luteal phase showed higher cortisol post exposure levels (5.96 ± 3.76 nmol/L) than women in follicular phase (4.31 ± 2.23 nmol/L). No other significant differences were found. Our findings provide evidence that menstrual cycle phase tended to influence cortisol response to laboratory-induced mental stress, with more reactivity observed in the luteal phase.This study is a part of a Thesis Doctoral and was supported by the I+D Project “PSI2010-15780”, funded by the Spanish Ministry of Economy and Competitiveness

Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome

MSCs products as well as their derived extracellular vesicles, are currently being explored as advanced biologics in cell-based therapies with high expectations for their clinical use in the next few years. In recent years, various strategies designed for improving the therapeutic potential of mesenchymal stromal cells (MSCs), including pre-conditioning for enhanced cytokine production, improved cell homing and strengthening of immunomodulatory properties, have been developed but the manufacture and handling of these cells for their use as advanced therapy medicinal products (ATMPs) remains insufficiently studied, and available data are mainly related to non-industrial processes. In the present article, we will review this topic, analyzing current information on the specific regulations, the selection of living donors as well as MSCs from different sources (bone marrow, adipose tissue, umbilical cord, etc.), in-process quality controls for ensuring cell efficiency and safety during all stages of the manual and automatic (bioreactors) manufacturing process, including cryopreservation, the use of cell banks, handling medicines, transport systems of ATMPs, among other related aspects, according to European and US legislation. Our aim is to provide a guide for a better, homogeneous manufacturing of therapeutic cellular products with special reference to MSCsThis manuscript has been supported by the Instituto de Salud Carlos III (ISCIII) through the project “RD16/0011: Red de Terapia Celular” (Groups: 0001, 0002, 0004, 0005, 0013, 0015, and 0029), fromthe sub-programme RETICS, integrated in the “Plan Estatal de I+D+I 2013-2016” and co-financed by the European Regional Development Fund (ERDF) “A way to make Europe”, and also by the ISCIII through the project RICORS “RD21/0017;TERAV” (Groups: 001, 002, 003, 006, 009 and 010) that is supported by the Next Generation EU program (Plan de Recuperación, Transformación y Resiliencia); and the Regional Government of Madrid (S2017/BMD-3962, Avancell-CM

Maresin 1 promotes inflammatory resolution, neuroprotection, and functional neurological recovery after Spinal Cord Injury

Resolution of inflammation is defective after spinal cord injury (SCI), which impairs tissue integrity and remodeling and leads to functional deficits. Effective pharmacological treatments for SCI are not currently available. Maresin 1 (MaR1) is a highly conserved specialized proresolving mediator (SPM) hosting potent anti-inflammatory and proresolving properties with potent tissue regenerative actions. Here, we provide evidence that the inappropriate biosynthesis of SPM in the lesioned spinal cord hampers the resolution of inflammation and leads to deleterious consequences on neurological outcome in adult female mice. We report that, after spinal cord contusion injury in adult female mice, the biosynthesis of SPM is not induced in the lesion site up to 2 weeks after injury. Exogenous administration of MaR1, a highly conserved SPM, propagated inflammatory resolution after SCI, as revealed by accelerated clearance of neutrophils and a reduction in macrophage accumulation at the lesion site. In the search of mechanisms underlying the proresolving actions of MaR1 in SCI, we found that this SPM facilitated several hallmarks of resolution of inflammation, including reduction of proinflammatory cytokines (CXCL1, CXCL2, CCL3, CCL4, IL6, and CSF3), silencing of major inflammatory intracellular signaling cascades (STAT1, STAT3, STAT5, p38, and ERK1/2), redirection of macrophage activation toward a prorepair phenotype, and increase of the phagocytic engulfment of neutrophils by macrophages. Interestingly, MaR1 administration improved locomotor recovery significantly and mitigated secondary injury progression in a clinical relevant model of SCI. These findings suggest that proresolution, immunoresolvent therapies constitute a novel approach to improving neurological recovery after acute SCI.SIGNIFICANCE STATEMENT Inflammation is a protective response to injury or infection. To result in tissue homeostasis, inflammation has to resolve over time. Incomplete or delayed resolution leads to detrimental effects, including propagated tissue damage and impaired wound healing, as occurs after spinal cord injury (SCI). We report that inflammation after SCI is dysregulated in part due to inappropriate synthesis of proresolving lipid mediators. We demonstrate that the administration of the resolution agonist referred to as maresin 1 (MaR1) after SCI actively propagates resolution processes at the lesion site and improves neurological outcome. MaR1 is identified as an interventional candidate to attenuate dysregulated lesional inflammation and to restore functional recovery after SCI

Red de investigación en docencia universitaria de la UA: “Universidad, Docencia, Género e Igualdad” (II)

La Red de investigación en docencia universitaria “Universidad, docencia, genero e igualdad” persigue avanzar en la calidad e innovación de las enseñanzas universitarias a partir de la inclusión de la perspectiva de género. Se busca dar cumplimiento a las directrices generales de los nuevos planes de estudio respecto del principio de igualdad de oportunidades entre hombres y mujeres en la formación universitaria (Real Decreto 1393/2007. BOE nº 260, 30 de octubre de 2007). En la tercera edición de la Red, y dada su composición multidisciplinar, se desarrollaron dos líneas de investigación: por un lado, se continuó trabajando en el mantenimiento del “Portal web con recursos docentes con perspectiva de género”, proyecto financiado por el Instituto de la Mujer (PACUI, 2012) e iniciado en el curso 2012-2013, incrementándose en un 36% la colección de recursos; y, por otro, se inició una nueva línea de investigación con la que se busca desarrollar una herramienta informática de ayuda para la redacción de textos con lenguaje inclusivo

Combination of Tocilizumab and Steroids to Improve Mortality in Patients with Severe COVID-19 Infection : A Spanish, Multicenter, Cohort Study

We aimed to determine the impact of tocilizumab use on severe COVID-19 (coronavirus disease 19) pneumonia mortality. We performed a multicentre retrospective cohort study in 18 tertiary hospitals in Spain from March to April 2020. Consecutive patients admitted with severe COVID-19 treated with tocilizumab were compared to patients not treated with tocilizumab, adjusting by inverse probability of the treatment weights (IPTW). Tocilizumab's effect in patients receiving steroids during the 48 h following inclusion was analysed. During the study period, 506 patients with severe COVID-19 fulfilled the inclusion criteria. Among them, 268 were treated with tocilizumab and 238 patients were not. Median time to tocilizumab treatment from onset of symptoms was 11 days [interquartile range (IQR) 8-14]. Global mortality was 23.7%. Mortality was lower in patients treated with tocilizumab than in controls: 16.8% versus 31.5%, hazard ratio (HR) 0.514 [95% confidence interval (95% CI) 0.355-0.744], p < 0.001; weighted HR 0.741 (95% CI 0.619-0.887), p = 0.001. Tocilizumab treatment reduced mortality by 14.7% relative to no tocilizumab treatment [relative risk reduction (RRR) 46.7%]. We calculated a number necessary to treat of 7. Among patients treated with steroids, mortality was lower in those treated with tocilizumab than in those treated with steroids alone [10.9% versus 40.2%, HR 0.511 (95% CI 0.352-0.741), p = 0.036; weighted HR 0.6 (95% CI 0.449-0.804), p < 0.001] (interaction p = 0.094). These results show that survival of patients with severe COVID-19 is higher in those treated with tocilizumab than in those not treated and that tocilizumab's effect adds to that of steroids administered to non-intubated patients with COVID-19 during the first 48 h of presenting with respiratory failure despite oxygen therapy. Randomised controlled studies are needed to confirm these results. European Union electronic Register of Post-Authorization Studies (EU PAS Register) identifier, EUPAS34415 The online version of this article (10.1007/s40121-020-00373-8) contains supplementary material, which is available to authorized users

Preparation of a questionnaire to detect cases of hate violence in emergency rooms.

In the context of the SIVIVO project, the development of a tool to facilitate the detection, recording and description of cases of hate violence and its consequences on health was proposed. A two-round Delphi method was used with experts from clinical-care, public health, epidemiological, academic, administration and non-governmental organizations to assess the relevance of different items using a Likert scale, presenting the results with medians and coefficients of variation. The best evaluated questions, with scores equal to or greater than 4, and which make up the final version of the questionnaire are the relative socio-demographic characteristics of the victim, the injuries, description of the incident, the motivations perceived by the aggrieved person, possible evidence of hatred, the intention to denounce and the perception of the health personnel of the motive for the aggression. The piloting showed the adequacy of the questions that were finally selected. The systematic incorporation of this tool can help us to learn the magnitude and characteristics of hate violence and its impact on health. This information would allow the elaboration of prevention and intervention strategies aimed, specifically, at the sectors of the population most exposed to this type of violence.Acción Estratégica en Salud 2013: PI13/02267. Cofinanciado con fondos FEDER.S