Arginine deprivation alters microglia polarity and synergises with radiation to eradicate non arginine auxotrophic glioblastoma tumors

New approaches for the management of glioblastoma (GBM) are an urgent and unmet clinical need. Here, we illustrate that the efficacy of radiotherapy for GBM is strikingly potentiated by concomitant therapy with the arginine depleting agent ADI-PEG20 in a non-arginine auxotrophic cellular background (Arginine Succinate Synthetase 1 positive). Moreover, this combination led to durable and complete radiological and pathological response with extended disease-free survival in an orthotopic immune competent model of GBM with no significant toxicity. ADI-PEG20 not only enhances the cellular sensitivity of Arginine succinate synthetase 1 positive GBM to ionising radiation by elevated production of nitric oxide (NO) and hence generation of cytotoxic peroxynitrites, but also promotes glioma-associated macrophages/microglia infiltration into tumors and turns their classical anti-inflammatory (pro-tumor) phenotype into a pro-inflammatory (anti-tumor) phenotype. Our results provide an effective, well-tolerated and simple strategy to improve GBM treatment which merits consideration for early evaluation in clinical trials

Integration of new biological and physical retrospective dosimetry methods into EU emergency response plans : joint RENEB and EURADOS inter-laboratory comparisons

Purpose: RENEB, 'Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,' is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and/or validate these candidate techniques and inter-comparison exercises are a well-established method for such validation. Materials and methods: The authors present details of inter-comparisons of four such new methods: dicentric chromosome analysis including telomere and centromere staining; the gene expression assay carried out in whole blood; Raman spectroscopy on blood lymphocytes, and detection of radiation induced thermoluminescent signals in glass screens taken from mobile phones. Results: In general the results show good agreement between the laboratories and methods within the expected levels of uncertainty, and thus demonstrate that there is a lot of potential for each of the candidate techniques. Conclusions: Further work is required before the new methods can be included within the suite of reliable dosimetry methods for use by RENEB partners and others in routine and emergency response scenarios

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Enhanced hydrogen production from thermochemical processes

To alleviate the pressing problem of greenhouse gas emissions, the development and deployment of sustainable energy technologies is necessary. One potentially viable approach for replacing fossil fuels is the development of a H2 economy. Not only can H2 be used to produce heat and electricity, it is also utilised in ammonia synthesis and hydrocracking. H2 is traditionally generated from thermochemical processes such as steam reforming of hydrocarbons and the water-gas-shift (WGS) reaction. However, these processes suffer from low H2 yields owing to their reversible nature. Removing H2 with membranes and/or extracting CO2 with solid sorbents in situ can overcome these issues by shifting the component equilibrium towards enhanced H2 production via Le Chatelier's principle. This can potentially result in reduced energy consumption, smaller reactor sizes and, therefore, lower capital costs. In light of this, a significant amount of work has been conducted over the past few decades to refine these processes through the development of novel materials and complex models. Here, we critically review the most recent developments in these studies, identify possible research gaps, and offer recommendations for future research

Effectiveness of hydroxycinamates and beta-glucans as dietary tools against obesity and its associated dysfunctions, and their application as nutraceuticals

[EN]: Over the last few years the prevalence of overweight and obesity has increased, affecting in certain parts of the World to more than half of the adult population. Obesity has been related to disorders such as type-2 diabetes, non-alcoholic fatty liver disease, and cardiovascular diseases, among others, which has made obesity the second cause of preventable death, only behind smoking. Bearing this in mind, it is necessary to find new strategies to overcome overweight/obesity and its associated pathologies. In this context, nutraceuticals and dietary supplements have become interesting tools thanks to their composition, rich in bioactive compounds beneficial to health. Among bioactive compounds, this study will focus on β-glucans, a type of soluble dietary fiber, and hydroxycinnamic acids, a group of phenols. Both types of compounds show complex and multifactorial effects, acting as hypolipemic, hypoglycemic, antioxidant, prebiotic and satiating agents. They act by modulating different metabolic pathways, affecting the absorption and metabolism of lipids and carbohydrates, reducing oxidative damage, promoting the proliferation of beneficial bacterial species, and reducing dietary intake. It may be concluded that both beta-glucans and hydroxycinnamates have potential as nutritional tools for the management of obesity and its associated metabolic dysfunctions.[ES]: Durante los últimos años se ha incrementado la incidencia de casos de sobrepeso/obesidad entre la población, afectando en ciertas partes del mundo a más de la mitad de la población adulta. La obesidad lleva asociada comorbilidades como la diabetes tipo 2, la esteatosis hepática no alcohólica y las enfermedades cardiovasculares entre otras muchas, que la han convertido en la segunda causa de muerte evitable en el mundo, solo por detrás del tabaquismo. Ante esta nueva realidad se hace necesaria la búsqueda de nuevas estrategias para combatir el sobrepeso/obesidad y sus patologías asociadas. Los nutracéuticos o suplementos dietéticos se han convertido en una herramienta dietética de sumo interés gracias a su contenido en compuestos bioactivos beneficiosos para la salud. De entre estos compuestos bioactivos, este estudio abordará en profundidad dos de ellos: una fibra soluble, los β-glucanos procedentes de la avena, y un tipo de compuesto fenólico, los hidroxicinamatos. Ambos tipos de compuestos presentan efectos complejos y multifactoriales al actuar como agentes hipolipemiantes, hipoglucemiantes, antioxidantes, prebióticos o saciantes. Ejercen su efecto modulando diferentes vías metabólicas que afectan tanto a la absorción como al metabolismo de los lípidos y los glúcidos, reduciendo el daño oxidativo, promoviendo la proliferación de especies bacterianas beneficiosas y reduciendo la ingesta dietética. Se puede concluir que tanto los beta-glucanos como los hidroxicinamatos presentan potencial como herramienta nutricional en el manejo de distintas disfunciones metabólicas asociadas a la obesidad.JGC agradece la beca predoctoral de la Comunidad de Madrid (PEJD-2018-PRE/ SAL-9104). SGR es una estudiante predoctoral financiada por ORIVA (Interprofesional del Aceite de Orujo de Oliva). Se agradece la financiación por la Agencia Estatal de Investigación del proyecto AGL2015-69986-R.Peer reviewe

Estudio dosis-respuesta sobre la eficacia de nuevos productos combinando hidroxicinamatos y fibra soluble como herramienta dietética frente a obesidad y disfunciones asociadas

Resumen del trabajo presentado a las III Jornadas Científicas CIAL Fórum, celebradas del 22 al 23 de noviembre de 2018 en el Instituto de Investigación en Ciencias de la Alimentación (CIAL).[Fundamento] El beta-glucano (BG) es una fibra soluble presente en diversos cereales como avena y cebada. Los hidroxicinamatos son un tipo de polifenoles (PF) con un alto poder antioxidante presentes en el café verde, entre otros alimentos. Ambos tipos de compuestos bioactivos presentan mecanismos de acción distintos, pero posen propiedades comunes como hipoliplemiantes, hipoglucemiantes, saciantes y prebióticos, lo que los convierte por separado en una herramienta dietética de gran potencial frente a la obesidad y sus patologías asociadas. Actualmente, no existe ningún nutraceutico que combine ambos compuestos. Por ello, el objetivo de este estudio fue establecer las dosis óptimas de hidroxicinamatos y beta-glucano que presenten un mayor efecto sobre distintos marcadores de obesidad.[Material y Métodos] Se realizó un estudio dosis-respuesta mediante el desarrollo de un ensayo de intervención clínica paralelo, randomizado, doble ciego de 6 semanas de duración en 60 voluntarios con sobrepeso/obesidad, divididos en cuatro grupos que tomaron las siguientes mezclas de BG con distinta riqueza (35 y 70%) y PF (extracto de café verde): 3 g/d BG (35%) + 600 mg/d PF, 3 g/d BG (70%) + 600 mg/d PP, 5 g/d BG (35%) + 600 mg/d PF y 5 g/d BG (70%) +600 mg/d PF suministrados como nutracéuticos. Tanto al inicio como al final del estudio se midieron el peso, porcentaje de grasa corporal, presión arterial, perfil lipídico y las concentraciones de glucosa, insulina y hemoglobina glicosilada.[Resultados] Tras el consumo del nutracéutico, se observaron cambios significativos en el perfil lipídico en todos los tratamientos, descendiendo los niveles de colesterol total (p=0,0001), triglicéridos (p=0,023), LDL-colesterol (p=0,01) y VLDL (p=0,014). Sin embargo, el tratamiento con 5 g/d BG (35%)+600 mg/d PP fue el más eficaz a la hora de modular positivamente el colesterol total y LDL, mientras que el tratamiento con 3 g/d BG (35%)+600 mg/d PF fue el que más bajó la concentración de triglicéridos y los niveles de VLDL. También se observaron cambios significativos al final del estudio en los niveles de hemoglobina glicosilada (p=0,001) y de insulina (p=0,002) independientemente del tratamiento, sin observase cambios en la concentración de glucosa. Por último, el estudio antropométrico no reveló cambios significativos en el peso, pero sí en el porcentaje de grasa corporal, observándose diferencias significativas entre los distintos productos.[Conclusión] El consumo de un nutracéutico combinando BG y PF ejerce efectos metabólicos beneficiosos en sujetos con sobrepeso/obesidad.Financiado por el proyecto AGL2015-69986-R (MEIC). JG-C agradece a la Comunidad de Madrid la concesión del contrato predoctoral PEJD-2017-PRE/BIO-4225.Peer reviewe

Olive Pomace oil: an unforgotten source of vitamin E

Póster presentado a la XXVIII Reunión Científica de la Sociedad Española de la Nutrición (SEÑ), celebrada en Soria del 20 al 22 de junio de 2019.[Background]: Olive-pomace oil (OPO), obtained from the solid by-product generated during olive oil extraction, is nutritionally relevant due to its high oleic acid (C18:1) content and a wide range of minor bioactive components, such as the powerful antioxidant vitamin E. In Europe, EFSA established the recommended intake of vitamin E for adults at 13 and 11 mg/day for men and women, respectively. As worldwide dietary values are below these recommendations, strategies to cover the daily recommendations of this vitamin are essential. Therefore, this situation represents an opportunity for OPO. [Methods]: We have carried out a human study to evaluate the possible beneficial role of OPO on cardiovascular health and associated pathologies (hypertension, diabetes and obesity) in comparison with high oleic sunflower oil (HOSO). Volunteers were recruited attending to their cholesterol levels and then, a randomized, cross-over, controlled clinical trial was carried out in 64 subjects [34 normocholesterolaemic (<200mg/dL) and 30 hypercholesterolaemic (200-280 mg/dL) men and women, aged 18-55y with BMI 18-30kg/m2], consisting in two 4-week interventions with OPO and HOSO preceded each by 3-week run-in/wash-out steps. Participants consumed daily 50 mL of OPO or HOSO, containing 357 and 420 ppm vitamin E, respectively, to meet the nutritional requirements of fat intake. Dietary suggestions will be provided to help volunteers achieve the recommended intake of monounsaturated fat equivalent to 20% (50 mL of OPO dairy). The consumption of nuts, avocado, olives and other dietary fat different from that the provided in the study was restricted. Dietary and lifestyle habits will be controlled during the study. Intake of macronutrients and micronutrients. [Results]: Results showed an increased average vitamin E consumption from 9.61 mg/day in the run-in period to 17.76 mg/day and 18.45 mg/day after OPO and HOSO, respectively. Sensory analysis showed that consumers preference for OPO was higher than that for HOSO. [Conclusions]: OPO was well accepted and, thus, constitutes an important dietary source of vitamin E covering the recommended daily intake. It is worth considering OPO as part of a healthy diet.This study has been funded by the Interprofesional del Aceite de Orujo de Oliva (ORIVA). SGR is a predoctoral student funded by ORIVA (Interprofesional del Aceite de Orujo de Oliva). JGC has a predoctoral grant funded by Comunidad de Madrid (PEJD-2019-PRE/SAL-9104)

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease