Occurrence of SARS-CoV-2 viremia is associated with genetic variants of genes related to COVID-19 pathogenesis

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si lo hubiere, y los autores pertenecientes a la UAMSARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity. Materials and methods: Retrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed. Results: The mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 (HMOX1; T/T genotype OR 9.9 p < 0.0001), rs78958998 (probably associated with SERPING1 expression; A/T genotype OR 2.3, p = 0.04 and T/T genotype OR 12.9, p < 0.0001), and rs713400 (eQTL for TMPRSS2; C/T + T/T genotype OR 1.86, p = 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 (CD69; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3, p = 0.01), rs2660 (OAS1; A/G genotype OR 0.6, p = 0.08), rs896 (VIPR1; T/T genotype OR 0.4, p = 0.02) and rs33980500 (TRAF3IP2; C/T + T/T genotype OR 0.3, p = 0.01) were associated with lower risk of viremia. Conclusion: Genetic variants in HMOX1 (rs2071746), SERPING1 (rs78958998), TMPRSS2 (rs713400), CD69 (rs11052877), TRAF3IP2 (rs33980500), OAS1 (rs2660) and VIPR1 (rs896) could explain heterogeneity in SARS-CoV-2 viremia in our populatio

Mesenchymal Stromal Cell Secretome for the Treatment of Immune-Mediated Inflammatory Diseases: Latest Trends in Isolation, Content Optimization and Delivery Avenues

Considering the high prevalence and the complex pharmacological management of immune-mediated inflammatory diseases (IMIDs), the search for new therapeutic approaches for their treatment is vital. Although the immunomodulatory and anti-inflammatory effects of mesenchymal stromal cells (MSCs) have been extensively studied as a potential therapy in this field, direct MSC implantation presents some limitations that could slow down the clinical translation. Since the beneficial effects of MSCs have been mainly attributed to their ability to secrete a plethora of bioactive factors, their secretome has been proposed as a new and promising pathway for the treatment of IMIDs. Formed from soluble factors and extracellular vesicles (EVs), the MSC-derived secretome has been proven to elicit immunomodulatory effects that control the inflammatory processes that occur in IMIDs. This article aims to review the available knowledge on the MSC secretome, evaluating the advances in this field in terms of its composition, production and application, as well as analyzing the pending challenges in the field. Moreover, the latest research involving secretome administration in IMIDs is discussed to provide an updated state-of-the-art for this field. Finally, novel secretome delivery alternatives are reviewed, paying special attention to hydrogel encapsulation as one of the most convenient and promising strategies.This research was funded by the projects SAF2017-82292-R (MINECO), AEI/FEDER, UE, ICTS “NANBIOSIS” Drug Formulation Unit (U10) and the Basque Country Government (Grupos Consolidados, No ref: IT907-16). Elena Munoz-Perez thanks the Basque Government for the predoctoral grant (PRE_2020_1_0279). A. Gonzalez-Pujana thanks the University of the Basque Country (UPV/EHU) for the postdoctoral grant (ESPDOC20/119)

High resolution and fidelity 3D printing of Laponite and alginate ink hydrogels for tunable biomedical applications

The formulation of hydrogels that meet the necessary flow characteristics for their extrusion-based 3D printing while providing good printability, resolution, accuracy and stability, requires long development processes. This work presents the technological development of a hydrogel-based ink of Laponite and alginate and evaluates its printing capacity. As a novelty, this article reports a standardizable protocol to quantitatively define the best printing parameters for the development of novel inks, providing new printability evaluation parameters such as the Printing Accuracy Escalation Index. As a result, this research develops a printable Laponite-Alginate hydrogel that presents printability characteristics. This ink is employed for the reproducible manufacture of 3D printed scaffolds with versatile and complex straight or curved printing patterns for a better adaptation to different final applications. Obtained constructs prove to be stable over time thanks to the optimization of a curing process. In addition, the study of the swelling and degradation behavior of the Laponite and alginate 3D printed scaffolds in different culture media allows the prediction of their behavior in future in vitro or in vivo developments. Finally, this study demonstrates the absence of cytotoxicity of the printed formulations, hence, setting the stage for their use in the field of biomedicine.This project has been partially supported by Spanish government Ministerio de Ciencia e Innovación Grant PID2021-122577OB-I00 funded by MCIN/AEI/ 10.13039/501100011033 and by “ERDF A way of making Europe”. Grant IT1448-22 funded by Basque Government and Fundación Vital Fundazioa (vital21/28). Elena Munoz-Perez thanks the Basque Government for the predoctoral grant (PRE_2022_2_0115). Arantza Perez-Valle thanks the Spanish Government for the postdoctoral grant (MARSA55/21)

Design of a case management model for people with chronic disease (Heart Failure and COPD). Phase I: modeling and identification of the main components of the intervention through their actors: patients and professionals (DELTA-ICE-PRO Study

Background Chronic diseases account for nearly 60% of deaths around the world. The extent of this silent epidemic has not met determined responses in governments, policies or professionals in order to transform old Health Care Systems, configured for acute diseases. There is a large list of research about alternative models for people with chronic conditions, many of them with an advanced practice nurse as a key provider, as case management. But some methodological concerns raise, above all, the design of the intervention (intensity, frequency, components, etc). Methods/Design Objectives: General: To develop the first and second phases (theorization and modeling) for designing a multifaceted case-management intervention in people with chronic conditions (COPD and heart failure) and their caregivers. Specific aims: 1) To identify key events in people living with chronic disease and their relation with the Health Care System, from their point of view. 2) To know the coping mechanisms developed by patients and their caregivers along the story with the disease. 3) To know the information processing and its utilization in their interactions with health care providers. 4) To detect potential unmet needs and the ways deployed by patients and their caregivers to resolve them. 5) To obtain a description from patients and caregivers, about their itineraries along the Health Care System, in terms of continuity, accessibility and comprehensiveness of care. 6) To build up a list of promising case-management interventions in patients with Heart Failure and COPD with this information in order to frame it into theoretical models for its reproducibility and conceptualization. 7) To undergo this list to expert judgment to assess its feasibility and pertinence in the Andalusian Health Care. Design: Qualitative research with two phases: For the first five objectives, a qualitative technique with biographic stories will be developed and, for the remaining objectives, an expert consensus through Delphi technique, on the possible interventions yielded from the first phase. The study will be developed in the provinces of Almería, Málaga and Granada in the Southern Spain, from patients included in the Andalusian Health Care Service database with the diagnosis of COPD or Heart Failure, with the collaboration of case manager nurses and general practitioners for the assessment of their suitability to inclusion criteria. Patients and caregivers will be interviewed in their homes or their Health Centers, with their family or their case manager nurse as mediator. Discussion First of a series of studies intended to design a case-management service for people with heart failure and COPD, in the Andalusian Health Care System, where case management has been implemented since 2002. Accordingly with the steps of a theoretical model for complex interventions, in this study, theorization and intervention modeling phases will be developed.This research was carried out with the support of one research grant, awarded by the Regional Health Ministry of Andalusia (Exp. 0222/2008

Estudio epidemiológico de las cefaleas en edad pediátrica en las consultas de Neuropediatría en un Hospital de Tercer Nivel

La cefalea, sensación de malestar o dolor de cabeza, es un síntoma clínico muy común durante la infancia en los países desarrollados. La prevalencia ha ido incrementando a lo largo de las últimas décadas y ya es de un 14% antes de los 7 años, pudiendo aumentar, según diversos estudios, hasta el 60-80% en la adolescencia. En los niños y adolescentes, la migraña y la cefalea tensional, que son los dos tipos de cefaleas más prevalentes, causan un impacto sustancial en la salud física y mental, así como en el rendimiento escolar, ya que genera absentismo, y en la calidad de vida, con mal funcionamiento cognitivo y disminución de la coordinación motora. Todo ello genera un nivel elevado de estrés en los padres y en los cuidadores. El objetivo principal de este estudio consiste en conocer las características y el perfil de los pacientes valorados en las consultas de Neuropediatría de un hospital español de tercer nivel en un periodo de 6 meses (Julio-Diciembre 2013). Para ello, hemos realizado un estudio transversal descriptivo de toda la población de pacientes atendidos en la consulta de Neuropediatría, entre las fechas ya mencionadas, revisando y seleccionando un total de 84 historias clínicas. Para la clasificación de las cefaleas, se emplearon los criterios de la Clasificación Internaciones de Cefaleas (ICHD-III beta), publicados en Junio de 2013 por la Sociedad Internacional de Cefaleas (IHS). Se han estudiado variables personales (edad, sexo…), variables relacionadas con las características de las cefaleas, con la consulta de Neuropediatría y relacionadas con el tratamiento médico. Resultados: la edad media de los pacientes atendidos en las consultas de Neuropediatría fue de 10.42 años (DS 2.79) y la media de edad de inicio de los episodios 8.21años (DS 2.75). La prevalencia de las cefaleas en las consultas de Neuropediatría es del 62%. El 36% de los niños fue diagnosticado de migraña, el 54.7% de cefalea tensional y el 9.3% fue diagnosticado de “otro tipo de cefalea”. En cuanto al rendimiento escolar, el 81% de los pacientes tenía un rendimiento bueno, pero casi en un 20% de los casos el rendimiento era regular/malo. La cefalea supone, por tanto, un motivo de consulta muy frecuente en la práctica clínica diaria. Dados los datos analizados, resulta evidente que se debe realizar un diagnóstico precoz de esta patología en edades pediátricas y realizar un abordaje adecuado. De esta forma evitaremos consecuencias que de esta patología se derivan, como el absentismo escolar, el bajo rendimiento y los conflictos sociales, mejorando la calidad de vida de estos niño

Indicators of Good Practices of Service-Learning University

The proliferation of innovative experiences in university education has been confirmed in different forums, as well as the evidence of their impact in research. However, the available tools are limited when trying to address the quality assessment of University Service-Learning (USL) projects. We present a tool for the evaluation of your SL projects. The goal of the Matrix is to specify the essential and secondary indicators needed to develop good practices in USL: IM_USL. A protocol is established to carry out its assessment. Dimensions and phases indicators of a project are specied, as well as the agents or people involved in it. This tool tries to guide the development of USL projects and to specify different points to improve. The application of the IM_USL will allow you to explore, exhaustively, each of the dimensions and indicators that make up a USL project, regarding both the AGENTS involved and the PHASES that make up a programme. In order to gather information on the reality of the projects, the phases and agents involved in a USL project will be reviewed in particular, determining the level of achievement of the indicators that compose it and of the dimensions that specify the particularities of each indicator. Finally, a series of questions are proposed to guide the process of analysis and reflection on the quality of the evaluated project. As a result, we will be able to obtain an X-ray of the quality of the project and the possible aspects for improvement.Funding: Spanish Ministry of Science and Innovation. Grant: I+D 2019. REFERENCIA DEL PROYECTO/AEI/10.13039/50110001103

On the Biomimetic Design of Agile-Robot Legs

The development of functional legged robots has encountered its limits in human-made actuation technology. This paper describes research on the biomimetic design of legs for agile quadrupeds. A biomimetic leg concept that extracts key principles from horse legs which are responsible for the agile and powerful locomotion of these animals is presented. The proposed biomimetic leg model defines the effective leg length, leg kinematics, limb mass distribution, actuator power, and elastic energy recovery as determinants of agile locomotion, and values for these five key elements are given. The transfer of the extracted principles to technological instantiations is analyzed in detail, considering the availability of current materials, structures and actuators. A real leg prototype has been developed following the biomimetic leg concept proposed. The actuation system is based on the hybrid use of series elasticity and magneto-rheological dampers which provides variable compliance for natural motion. From the experimental evaluation of this prototype, conclusions on the current technological barriers to achieve real functional legged robots to walk dynamically in agile locomotion are presented

Validity of prognostic models of critical COVID-19 is variable. A systematic review with external validation

Objectives: To identify prognostic models which estimate the risk of critical COVID-19 in hospitalized patients and to assess their validation properties. Study design and setting: We conducted a systematic review in Medline (up to January 2021) of studies developing or updating a model that estimated the risk of critical COVID-19, defined as death, admission to intensive care unit, and/or use of mechanical ventilation during admission. Models were validated in two datasets with different backgrounds (HM [private Spanish hospital network], n = 1,753, and ICS [public Catalan health system], n = 1,104), by assessing discrimination (area under the curve [AUC]) and calibration (plots). Results: We validated 18 prognostic models. Discrimination was good in nine of them (AUCs ≥ 80%) and higher in those predicting mortality (AUCs 65%-87%) than those predicting intensive care unit admission or a composite outcome (AUCs 53%-78%). Calibration was poor in all models providing outcome's probabilities and good in four models providing a point-based score. These four models used mortality as outcome and included age, oxygen saturation, and C-reactive protein among their predictors. Conclusion: The validity of models predicting critical COVID-19 by using only routinely collected predictors is variable. Four models showed good discrimination and calibration when externally validated and are recommended for their use

Validity of prognostic models of critical COVID-19 is variable. A systematic review with external validation

To identify prognostic models that estimate the risk of critical COVID-19 in hospitalised patients and to assess their validation properties. We conducted a systematic review in Medline (up to January 2021) of studies developing or updating a model that estimated the risk of critical COVID-19, defined as death, admission to intensive care unit (ICU), and/or use of mechanical ventilation during admission. Models were validated in two datasets with different backgrounds (HM [private Spanish hospital network], n=1,753, and ICS [public Catalan health system], n=1,104); by assessing discrimination (area under the curve [AUC]) and calibration (plots). We validated 18 prognostic models. Discrimination was good in 9 of them (AUCs≥80%) and higher in those predicting mortality (AUCs 65-87%) than those predicting ICU admission or a composite outcome (AUCs 53-78%). Calibration was poor in all models providing outcome's probabilities and good in 4 models providing a point-based score. These four models used mortality as outcome, and included age, oxygen saturation, and C-reactive protein among their predictors. The validity of models predicting critical COVID-19 by using only routinely collected predictors is variable. Four models showed good discrimination and calibration when externally validated and are recommended for their use