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

A distal to proximal gradient of human choroid plexus development, with antagonistic expression of Glut1 and AQP1 in mature cells vs. calbindin and PCNA in proliferative cells

The choroid plexuses (ChP) are highly vascularized tissues suspended from each of the cerebral ventricles. Their main function is to secret CSF that fills the ventricles and the subarachnoid spaces, forming a crucial system for the development and maintenance of the CNS. However, despite the essential role of the ChP–CSF system to regulate the CNS in a global manner, it still remains one of the most understudied areas in neurobiology. Here we define by immunohistochemistry the expression of different proteins involved in the maturation and functionality of the ChP from the late embryological period to maturity. We found an opposite gradient of expression between AQP1 and Glut1 that define functional maturation in the ChP periphery, and PCNA and calbindin, present in the ChP roof zone with proliferative activity. We conclude that the maturation of the ChP matures from distal to proximal, starting in the areas nearest to the cortex, expressing in the distal, mature areas AQP1 and Glut1 (related to ChP functionality to support cortex development), and in the proximal immature areas (ChP root) calbindin and PCNA related to progenitor activity and proliferation

Respuesta de la embriogénesis somática directa en tres regiones foliares de Phalaenopsis amabilis

Fue explorado el efecto de ácido naftalenacético (ANA) y 1-fenil-3-(1,2,3-tiadiazol-5-il)urea (TDZ) en segmentos de hojas inmaduras de Phalaenopsis amabilis. Para este experimento, se emplearon tres regiones foliares de 12x1.7mm (basal, medial y apical) sobre diferentes concentraciones de ANA (0.00; 0.53 y 5.37 µM) y TDZ (0,00; 0,45; 4,50 y 13,60 µM), acompañado de sales minerales Murashige &amp; Skoog (1962) y suplementado con 10,0 mg/L Myo-inositol, 0,5 mg/L Pyridoxine, 0,1 mg/L Thiamine, 2,0 mg/L Glycine, 170,0 mg/L NaH2PO4, 2,0 g/L Peptona, 20,0 g/L de Sacarosa y 3,75 g/L de Agar, ajustado a un pH 5,2. Segmentos foliares fueron incubados en oscuridad sobre diferentes concentraciones y combinaciones hormonales por un lapso de 30-45 días y luego sometidos a luz. El porcentaje de inducción de callos evaluados en los tratamientos en estudio demuestra que a los 30 días de inducción existe un 100% de reactividad callogénica. La aparición de estadios globulares pro-embrionarios en segmentos de hoja de Phalaenopsis amabilis, fue posible en los tratamientos T1, T2, T5 y T6. De forma interesante la mayor formación de estructuras somáticas pro-embrionarias estuvieron presentes en la región basal, sin la necesidad de la adición independiente o combinatoria de ANA o TDZ. Sin embargo, la mayor cantidad de plantas regeneradas tan solo fue posible en estructuras pro-embrionarias de la región basal, conteniendo 0,53 µM de ANA.</p

Propagação in vitro de sacha inchi por meio da organogênese

The objective of this work was to evaluate hormonal balance in the phases of the in vitro organogenesis of apical meristems of sacha inchi (Plukenetia volubilis). For the establishment and multiplication phases, Murashige & Skoog (MS) media, with different concentrations of benzylaminopurine (BAP) and naphthaleneacetic acid (NAA), were used. For rooting, modified MS media was supplemented with different concentrations of NAA and indolebutyric acid. The differentiation of apical meristems was possible with 0.1 mg L-1 BAP and 0.05 mg L-1 NAA. The best rooting of seedlings is obtained with 0.5 mg L-1 naphthaleneacetic acid and 2.0 mg L-1 indolebutyric acid.O objetivo deste trabalho foi avaliar o balanço hormonal em fases da organogênese in vitro de ápices meristemáticos de sacha inchi (Plukenetia volubilis). Para as fases de estabelecimento e multiplicação, foi utilizado o meio de cultivo Murashige & Skoog (MS) com diferentes concentrações de benzilaminopurina (BAP) e ácido naftalenoacético (ANA). Para o enraizamento, o meio MS modificado foi suplementado com diferentes concentrações de ANA e ácido indolbutírico. A diferenciação dos ápices meristemáticos foi possível com a adição de 0,1 mg L-1 de BAP e 0,05 mg L-1 de ANA. O melhor desempenho do enraizamento de plântulas é obtido com a adição de 0,5 mg L-1 de ácido naftalenoacético e 2,0 mg L-1 de ácido indolbutírico

La autoestima y su relación en el desarrollo de la comprensión lectora de los alumnos y alumnas del V ciclo del nivel primario de la Institución Educativa N° 2096 “Perú-Japón”

El presente trabajo de investigación tiene como propósito establecer la correlación existente entre el grado de desarrollo de la autoestima y los procesos de comprensión lectora, de ahí que se planteó la hipótesis de que el nivel de autoestima influye en el grado de comprensión lectora de los alumnos del Quinto Ciclo de la Institución Educativa N° 2096 “Perú-Japón”. La investigación se desarrolló dentro del enfoque cuantitativo, asumiendo el tipo de investigación no experimental sustantivo de diseño descriptivo correlaciona! con la finalidad de establecer la relación de las dos variables, este procedimiento permitió hacer uso de la técnica de la encuesta aplicación del test inventario de Coopersmith de autoestima y un cuestionario sobre evaluación de niveles de comprensión lectora. Los datos analizados se realizaron mediante la aplicación del paquete estadístico para Ciencias Sociales SPSS 15 versión en español. Como conclusión se tiene que el proceso de comprensión lectora esta directamente ligado al grado de desarrollo de la autoestima en los estudiantes de educación primaria. A mayor grado de desarrollo de la autoestima, mayor grado de comprensión lectora; es decir, que cuando la autoestima aumenta, también aumenta la comprensión lectora, en forma proporcional. Contrariamente, se demuestra que un porcentaje reducido de niños con un bajo desarrollo de su autoestima, obtienen bajos resultados en el proceso de comprensión lectora

Varenicline in smokers with severe or very severe COPD after 24 weeks of treatment. A descriptive analysis: VALUE study

A large number of COPD patients are smokers. The particular characteristics of this group as well as their need to quit usually require psychological counselling and pharmacological treatment to achieve abstinence and, often, intensively. Little information is available about this issue.  The main objective of the study was to evaluate the effectiveness of varenicline after 24 weeks of treatment, with continuous abstinence between weeks 9 and 24.  This study was a post-authorization, open label, observational study of prospective follow-up. Patients included were smokers with severe or very severe COPD criteria who were treated with varenicline for 24 weeks, i.e. with a 12-week extension over the usual treatment.  The outcomes in the population of subjects completing 24 weeks of follow-up were at week 24: continuous abstinence 36.8%, 7 days point prevalence abstinence 65.7%, and continuous smoking 31.5%.The outcomes in the intention-to-treat population included at baseline were: continuous abstinence 17.7% of patients, 7 days point prevalence abstinence 31.6%, continuous smoking 15.1% and not valid/unknown 51.8%.  The mean CAT score at week 24 was 15 and reduction from the baseline was 3.77 (paired T test, p<0.01). The most common adverse events reported were nausea, vivid dreams, stomach ache, insomnia, headache and vomiting.  Patients included in VALUE were active smokers despite all of them had a severe COPD which suggests a very high degree of dependence. Although the study do not allow to infer the results to the global population of smokers with severe COPD, the outcomes have shown that, at 24 weeks follow up 36.8% of the patients were successful in quitting but from 79 patients enrolled initially only 17.7% quit.

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

IntroductionSARS-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 methodsRetrospective 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.ResultsThe 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 &lt; 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 &lt; 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.ConclusionGenetic 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 population

IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study

Background: Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. Objective: We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. Methods: A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality. Results: One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients. Conclusions: Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administrationThis study was funded by Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and Instituto de Salud Carlos III (grant nos. RD16/0011/0012 and PI18/ 0371 to I.G.A., grant no. PI19/00549 to A.A., and grant no. SAF2017-82886-R to F.S.-M.) and co-funded by the European Regional Development Fund. The study was also funded by ‘‘La Caixa Banking Foundation’’ (grant no. HR17-00016 to F.S.-M.) and ‘‘Fondos Supera COVID19’’ by Banco de Santander and CRUE. None of these sponsors have had any role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publicatio

Integrando escalas y métodos LTER para comprender la dinámica global de un espacio protegido de montaña: el Parque Nacional de Ordesa y Monte Perdido

Los espacios protegidos, por el hecho de albergar una gran geo-biodiversidad y asegurar una baja intervención humana, constituyen lugares muy adecuados para el seguimiento de organismos y procesos a escala ecológica, así como para la obtención de series temporales largas a escala geológica. En el marco de la red LTER-España, el Parque Nacional de Ordesa y Monte Perdido (PNOMP) y el Instituto Pirenaico de Ecología-CSIC están impulsando estudios para la detección de cambios a distintas escalas mediante variados métodos y aproximaciones. Destacamos aquí los más consolidados, entre los que se encuentran los análisis de registros de sedimentos en lagos, espeleotemas en cuevas, la dinámica de uno de los pocos glaciares activos de la Península ibérica, el análisis físico-químico de aguas corrientes e ibones de alta montaña, el registro del cambio climático actual en árboles longevos, la afección que éste ejerce sobre masas actuales de pinos en el límite superior del bosque y de abetales en zonas húmedas, la matorralización de algunos pastos y los procesos mecanicistas que subyacen, la reorganización de la diversidad florística en pastos tras el abandono paulatino o drástico de la ganadería, la biodiversidad de las comunidades alpinas y la dinámica poblacional de especies amenazadas o indicadoras de hábitats o de motores de cambio global. Los seguimientos ecológicos actuales muestran que tanto el cambio climático como el de usos del suelo están teniendo una considerable trascendencia en la fisionomía y la estructura de algunos de los ambientes más icónicos y frecuentes del parque (deterioro del glaciar, termofilización de la flora en cumbres alpinas, densificación del bosque en su límite superior, pérdida de productividad en algunos pastos supraforestales, etc.). También sugieren una importante variabilidad espacial en los procesos (por ej. en el PNOMP conviven pastos matorralizados y pastos muy estables), y evidencian que los cambios observados no siempre siguen los paradigmas establecidos (por ej., las especies amenazadas mantienen dinámicas poblacionales estables). La integración de resultados parciales proporcionados por cada aproximación relativiza la importancia de las percepciones que cada estudio destaca por separado, y permite medir los cambios actuales en el marco de referencia de los cambios a escala geológica. Predecir la resistencia y resiliencia de los ecosistemas o las poblaciones de seres vivos para enfrentarse a los futuros cambios ambientales es complicado, no sólo por la falta de conocimientos disponibles sino también porque las respuestas que observamos no siempre son tan rápidas o lineales como se espera. La modelización constituye una herramienta cada vez más utilizada, pero requiere de evidencias reales para validar sus pronósticos, por lo que la observación de los procesos que actúan en el PNOMP ha de incluir un esfuerzo continuado de monitorización multiescalar y multidisciplinar de los distintos componentes de la geo, hidro-, crio- y biosfera, sin olvidar el componente humano. Entender la complejidad supone conectar las interacciones que existen entre todos los sistemas y ponderar sus efectos según las escalas de trabajo.Instituto Pirenaico de Ecología, Consejo Superior de Investigaciones Científicas, EspañaEmpresa pública SARGA, EspañaJOLUBE Consultor Botánico, Editor y Fotógrafo, EspañaDepartament d’Ecologia, Universitat de Barcelona, EspañaUnidad de Tres Cantos, Instituto Geológico y Minero de España, EspañaInstitut de Recerca de Biodiversitat, Universitat de Barcelona, EspañaParque Nacional de Ordesa y Monte Perdido, Españ

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research