Glucocorticoid receptor intestinal epithelial knockout mice show attenuated colonic inflammatory response but unaffected permeability in early experimental sepsis

Introduction: Sepsis is defined as an organic dysfunction that threatens the life of patients due to an abnormally regulated response to infection [1]. The initial phase of sepsis is dominated by an increased production of proinflammatory cytokines, which leads to augmented capillary permeability, extravasation, hypercoagulability and myelopoiesis. One of the main sources of infection in sepsis is believed to be the intestinal microbiota via traslocation through the mucosa to the bloodstream. Systemic inflammation weakens intestinal barrier function (IBF) in animal models, resulting in increased bacterial traslocation [2]. Even if the management of sepsis has advanced in the last decades, mortality is still high and there are blanks in terms of pathological systems and long-term consequences. Thus, the search for effective treatments is clearly justified. Glucocorticoids (GC) are part of the drugs used in sepsis, but they have only shown a moderate therapeutic effect. This fact may be caused by harmful effects of GCs on IBF, whose compromise may limit GC clinical benefit by facilitating luminal translocation of microorganisms. Besides, GC treatment impairs epithelial healing in experimental colitis in mice [3]. Previous results of our research group have shown that mice with induced deletion of the GC receptor (GR) in intestinal epithelial cells (i.e. NR3C1ΔIEC mice) are protected against dextran sulphate sodium (DSS)-induced colitis [4]. In turn, gene deletion results in a short lived inflammatory response in the colon [5]. Objective: Understanding the role of the intestinal epithelial GR and its involvement in IBF regulation in experimental sepsis, with the ultimate goal of improving the management of sepsis with GCs. Matherial and methods: The cecal ligation and puncture (CLP) model of sepsis was applied to WT C57BL/6J and NR3C1ΔIEC mice. Ceacum-exposed mice were used as control (Sham). Mice were sacrificed 24 hours after surgery. Four hours before sacrifice, mice were administered 4 kD FITC-dextran, a fluorescent marker of permeability. Colon, jejunum, adrenes, kidney and liver RT-qPCRs were performed as well as determination of plasma FITC-dextran and corticosterone plasma levels. Results: After 24 h, CLP mice exhibited elevated corticosterone plasma levels with hypoglycemia and splenomegaly. Intestinal barrier function was weakened, as indicated by increased FITC-dextran plasma levels. A modest increase in inflammatory markers (S100a8, Cxcl1) was noted in the colon and jejunum. The expression of Tjp1, involved in barrier function, was downregulated in CLP mice. Similarly, the colonic expression of Cyp11a1 and Lrh1, involved in local steroidogenesis, was lower in CLP mice, regardless of genotype. Markers of inflammation were also augmented in the lung and kidney. CLP mice exhibited hypercorticosteronemia, which was associated to increased Cyp11a1 in the adrenes. Of note, both parameters were less pronounced in KO mice. The latter also exhibited dampened inflammatory response in the colon but not the jejunum. FITC-dextran plasma levels were similarly increased in WT and KO mice. Conclusions: In the early stages of the CLP model of sepsis the colon and jejunum are inflamed, and epithelial deletion of the glucocorticoid receptor appears to modulate inflammation in the former, with no change in barrier function. Further studies will characterize the microbiota composition and phenotype in later stages and in the response to glucocorticoid treatment

El efecto del capital social en la violencia en la pareja adolescente desde una perspectiva de interseccionalidad

Antecedentes: La violencia de pareja (VP) es un fenómeno social complejo ampliamente estudiado. Sin embargo, pocos de estos estudios consideran el capital social y la interseccionalidad. Nuestro objetivo fue describir el efecto del capital social en la victimización por VP entre estudiantes de secundaria, considerando tres factores de interseccionalidad (sexo asignado al nacer, orientación sexual y origen migratorio) en dos ciudades de España en 2019-2020. Métodos: Se analizó una muestra transversal de 640 adolescentes con pareja, de 13 a 16 años, de un programa de promoción de relaciones equitativas en Alicante y Terrassa. La variable resultado fue haber sufrido violencia en la pareja (control, miedo, física o sexual) en algún momento de la vida. Se utilizaron variables individuales y relacionales para calcular la razón de prevalencia ajustada (RPa) a partir de modelos multivariable construidos mediante regresión robusta de Poisson, y estratificados por sexo, orientación sexual y origen migratorio. Resultados: La mayor prevalencia de VP (56,25%) se encontró en adolescentes lesbianas, gays o bisexuales (LGB) sin actividad social. La orientación LGB se asoció significativamente con la victimización por VP en los adolescentes con origen en países de bajos ingresos (PBI) (aPR: 1,93) y en las chicas (aPR: 1,53). Por último, la procedencia de un PBI fue un determinante significativo de la VP en los chicos (aPR: 1,76) y en los estudiantes, independientemente de la orientación sexual. Una mayor actividad social mostró un efecto protector para los estudiantes de origen en países de altos ingresos (PAI) y de orientación sexual LGB, independientemente del sexo y la orientación sexual. Conclusiones: La actividad social se asocia de forma desigual con una menor victimización por violencia de la pareja en algún momento de la vida adolescente. La fuerte asociación del origen migratorio y la orientación sexual con la VPI refuerza el enfoque de su prevención en los adolescentes desde una perspectiva de interseccionalidad.Background: Intimate partner violence (IPV) is a complex social phenomenon widely studied. However, few of these studies consider social capital and intersectionality. Our aim was to describe the effect of social capital in IPV victimisation among secondary students, considering three factors of intersectionality (sex assigned at birth, sexual orientation and migration background) in two cities of Spain in 2019-2020. Methods: We analysed a cross-sectional sample of 640 ever-partnered adolescents aged 13–16 years who had taken part in a programme for positive relationship. The main outcome was lifetime IPV (control, fear, physical or sexual violence). Individual and relational variables (bonding social capital) were used to calculate adjusted prevalence ratios (aPR) from multivariate Robust Poisson regression models stratified by sex assigned at birth, sexual orientation and migration background (factors of intersectionality). Results: The highest IPV prevalence (56.25%) was found in lesbian, gay or bisexual (LGB) adolescents without social activity. LGB orientation was significantly associated with IPV victimisation in adolescents with low-income country (LIC) backgrounds (aPR: 1.93) and in girls (1.53). Finally, a LIC background was a significant determinant of IPV in boys (aPR: 1.76) and in students independently of sexual orientation. Higher social activity showed a protective effect for students with HIC backgrounds and LGB-sexual orientations. A possible protective effect of social support in HIC backgrounds and regardless of sex and sexual orientation must be considered. Conclusions: Social activity is unequally associated with less lifetime IPV. The strong association of migration background and sexual orientation with IPV reinforces the approach to its prevention in adolescents from an intersectionality perspective.This study was funded by the multi-centre project "Promotion of protective assets against gender violence in adolescence and preadolescence" (Grant reference PI18/00590 and PI18/00544) of the Carlos III Institute of Health, as an intermediary body of the European Regional Development Fund (ERDF) and the European Social Fund (ESF). The project was also supported by the Centro de Investigación Biomédica en Red de Epidemiología Salud Pública (CIBERESP) through the subprogramme on Prevention of Gender Violence of the Programme on Social Determinants of Health (no grant award number specified)

Sandwich-Type Electrochemical Paper-Based Immunosensor for Claudin 7 and CD81 Dual Determination on Extracellular Vesicles from Breast Cancer Patients

This study is focused on identifying novel epithelial markers in circulating extracellular vesicles (EVs) through the development of a dual sandwich-type electrochemical paper-based immunosensor for Claudin 7 and CD81 determination, as well as its validation in breast cancer (BC) patients. This immunosensor allows for rapid, sensitive, and label-free detection of these two relevant BC biomarkers. Under optimum conditions, the limit of detection for Claudin 7 was 0.4 pg mL-1, with a wide linear range of 2 to 1000 pg mL-1, while for CD81, the limit of detection was 3 pg mL-1, with a wide linear range of 0.01 to 10 ng mL-1. Finally, we validated Claudin 7 and CD81 determination in EVs from 60 BC patients and 20 healthy volunteers, reporting higher diagnostic accuracy than the one observed with classical diagnostic markers. This analysis provides a low-cost, specific, versatile, and user-friendly strategy as a robust and reliable tool for early BC diagnosis.Fil: Ortega, Francisco G.. Balearic Islands Health Research Institute; EspañaFil: Regiart, Matías D.. Universidade de Sao Paulo; BrasilFil: Rodríguez Martínez, Alba. Universidad de Granada; EspañaFil: De Miguel-Pérez, Diego. Universidad de Granada; EspañaFil: Serrano, María J.. Universidad de Granada; EspañaFil: Lorente, José A.. Universidad de Granada; EspañaFil: Tortella, Gonzalo. Universidad de La Frontera; ChileFil: Rubilar, Olga. Universidad de La Frontera; ChileFil: Sapag, Manuel Karim. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Física Aplicada "Dr. Jorge Andrés Zgrablich". Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto de Física Aplicada "Dr. Jorge Andrés Zgrablich"; ArgentinaFil: Bertotti, Mauro. Universidade de Sao Paulo; BrasilFil: Fernández Baldo, Martín Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; Argentin

Discovery of a nitrogen-enhanced mildly metal-poor binary system: Possible evidence for pollution from an extinct AGB star

We report the serendipitous discovery of a nitrogen-rich, mildly metal-poor ([Fe/H] = -1.08) giant star in a single-lined spectroscopic binary system found in the SDSS-IV Apache Point Observatory Galactic Evolution Experiment (APOGEE-2) survey, Data Release 14 (DR14). Previous work has assumed that two percent of halo giants with unusual elemental abundances have been evaporated from globular clusters, but other origins for their abundance signatures, including binary mass transfer, must also be explored. We present the results of an abundance reanalysis of the APOGEE-2 high-resolution near-infrared spectrum of 2M12451043+1217401 with the Brussels Automatic Stellar Parameter (BACCHUS) automated spectral analysis code. We manually re-derive the main element families, namely light elements (C, N), elements (O, Mg, Si), the iron-peak element (Fe), s-process element (Ce), and light odd-Z element (Al). Our analysis confirms the N-rich nature of 2M12451043+1217401, which has a [N/Fe] ratio of +0.69, and shows that the abundances of C and Al are slightly discrepant from those of a typical mildly metal-poor red giant branch star, but exhibit Mg, Si, O and s-process abundances (Ce) of typical field stars. We also detect a particularly large variability in the radial velocity of this star over the period of the APOGEE-2 observations; the most likely orbit fit to the radial velocity data has a period of 730.89 +/- 106.86 days, a velocity semi-amplitude of 9.92 +/- 0.14 km s(-1), and an eccentricity of similar to 0.1276 +/- 0.1174. These data support the hypothesis of a binary companion, which has probably been polluted by a now-extinct asymptotic giant branch star

Haga su diagnóstico

Fil: Parra, Viviana Gladys. Hospital Luis Lagomaggiore (Mendoza, Argentina). Servicio de DermatologíaFil: Aguirre, Marta. Hospital Luis Lagomaggiore (Mendoza, Argentina). Servicio de DermatologíaFil: Aredes, Ángeles. Universidad Nacional de Cuyo. Facultad de Ciencias Médica

Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis

Peer reviewedPublisher PD

Food and nutrition security discursive frames in the context of the Spanish economic crisis

[EN] The recent economic crisis in Spain has provoked a number of food and nutrition security (FNS) impacts that have fuelled a fragmented landscape of food-related debates, although these have not taken the form of a coherent and allembracing public discussion on national food security. This paper is an inductive analysis of such debates, mostly based on media coverage, in an attempt to disentangle the different discourse frames on FNS in Spain, and the role played by the economic crisis in the shaping and underpinning of such frames. For this purpose a frame matrix was constructed, paying particular attention to the stakeholders governance claims in order to confront frame-specific problems. Results show how stakeholders have used elements of the crisis to underpin or reinterpret their core arguments. In addition, governance claims have concentrated on the malfunctioning of the food chain, mostly due to unequal bargaining power, and the way this could be putting at risk crucial components of the food system and future FNS. Also, the short-termism of most stakeholders approaches obscures the long run threats to the Spanish food system.This research is part of the project "Assessment of the impact of global drivers of change on Europe's food security" (TRANSMANGO), granted by the EU under 7th Framework Programme, theme KBBE.2013.2.5-01, Grant agreement no: 613532. Authors gratefully appreciate the comments and suggestions made by the three anonymous reviewers and the editors of the Journal.OOrtiz Miranda, D.; Moreno Pérez, OM.; Arnalte Alegre, EV. (2016). Food and nutrition security discursive frames in the context of the Spanish economic crisis. Food Security. 8(3):665-677. https://doi.org/10.1007/s12571-016-0574-xS66567783Antentas, J. M., & Vivas, E. (2014). Impacto de la crisis en el derecho a una alimentación sana y saludable. Informe SESPAS 2014. Gaceta Sanitaria, 28(S1), 58–61.Brunori, G., Malandrin, V., & Rossi, A. (2013). Trade-off or convergence? The role of food security in the evolution of food discourse in Italy. Journal of Rural Studies, 29, 19–29.Candel, J. J., Breeman, G. E., Stiller, S. J., & Termeer, C. J. (2014). Disentangling the consensus frame of food security: the case of the EU common agricultural policy reform debate. Food Policy, 44, 47–58.CFS – Committee on World Food Security (2012). Coming to Terms with Terminology. http://www.fao.org/fsnforum/sites/default/files/file/Terminology/MD776(CFS___Coming_to_terms_with_Terminology).pdf . Accessed 6 Oct 2015.Cussó, X., & Garrabou, R. (2009). Dieta mediterránea y transición nutricional moderna en España. In L. G. Zubero, R. H. García, & J. M. Lázaro (Eds.), Economía Alimentaria en España durante el siglo XX (pp. 25–63). Madrid: MARM.De Schutter, O. (2014). The specter of productivism and food democracy. Wisconsin Law Review, 199, 199–233.DEFRA (2008). Ensuring the UK’s food security in a changing world. London: A Defra Discussion Paper.Díaz-Méndez, C., & Gómez-Benito, C. (2010). Nutrition and the Mediterranean diet. A historical and sociological analysis of the concept of a “healthy diet” in Spanish society. Food Policy, 35(5), 437–447.Dibden, J., Gibbs, D., & Cocklin, C. (2013). Framing GM crops as food security solution. Journal of Rural Studies, 29, 59–70.Ericksen, P. J. (2008). Conceptualizing food systems for global environmental change research. Global Environmental Change, 18, 234–245.FAO (2014). The State of the World’s Land and Water Resources for Food and Agriculture. http://www.fao.org/nr/solaw/maps-and-graphs/en/ . Accessed 25 Feb 2015.Fish, R., Lobley, M., & Winter, M. (2013). A license to produce? Farmer interpretations of the new food security agenda. Journal of Rural Studies, 29, 40–49.Grando, S., & Colombo, L. (2015). National Report. Italy. WP2 report Transmango EU-FP7.GREENPEACE (2014). Alimentos bajo amenaza. Valor económico de la polinización y vulnerabilidad de la agricultura española ante el declive de las abejas y otros polinizadores. Madrid: Greenpeace.Hertel, T. W. (2015). The challenges of sustainably feeding a growing planet. Food Security, 7, 185–198.Hispacoop (2012). Estudio sobre desperdicio de alimentos en los hogares. Madrid: Confederación Española de Cooperativas de Consumidores y Usuarios.Lang, T., & Heasman, M. (2004). Food wars. The global battle for mouths, Minds and Markets. London: Earthscan.Lawrence, G., & McMichael, P. (2012). The question of food security. International Journal of Sociology of Agriculture & Food, 19(2), 135–142.MAGRAMA. (2014). La balanza commercial agroalimentaria en 2013. Madrid.Maye, D., & Kirwan, J. (2013). Food security: a fractured consensus. Journal of Rural Studies, 29, 1–6.McKeon, N. (2015). Food security governance: empowering communities, regulating corporations. New York: Routledge.Mooney, P. H., & Hunt, S. A. (2009). Food security: the elaboration of contested claims to a consensus frame. Rural Sociology, 74(4), 469–497.Moreno, O. (2013). Reproducing productivism in Spanish agricultural systems. In D. Ortiz, A. Moragues, & E. Arnalte (Eds.), Agriculture in Mediterranean Europe: between old and new paradigms. Research in rural sociology and development (pp. 121–147). Bingley: Emerald Group Publishing Limited.Muñoz, C., & Sosvilla, S. (2014). Alimentamos el futuro. Informe económico 2013. Madrid: FIAB.OECC - Oficina Española de Cambio Climático (2006). Plan Nacional de Adaptación al Cambio Climático. Madrid.OECC-UCLM (2005). Evaluación Preliminar de los Impactos en España por Efecto del Cambio Climático. Madrid: MAGRAMA.Pangaribowo, E. H., Gerber, N., & Torero, M. (2013). Food and Nutrition Security Indicators: A Review. ZEF working paper no 108. Bonn: ZEF.Sáez-Almendros, S., Obrador, B., Bach-Faig, A., & Serra-Majem, L. (2013). Environmental footprints of Mediterranean versus Western dietary patterns: beyond the health benefits of the Mediterranean diet. Environmental Health, 12, 118.Shepherd, B. (2012). Thinking critically about food security. Security Dialogue, 43(3), 195–212.Sineiro, F. (2012). Situación actual, retos y perspectivas del vacuno de leche. Available at http://www.eumedia.es/portales/files/documentos/2-FSineiro.pdf . Accessed 19 Nov 2015.Van Gorp, B. (2007). The constructionist approach to framing: bringing culture back. Journal of Communication, 57, 60–78.Van Gorp, B., & van der Goot, M. J. (2012). Sustainable food and agriculture: Stakeholder’s frames. Communication, Culture & Critique, 5, 127–148.Vidal, R., Moliner, E., Pikula, A., Mena-Nieto, A., & Ortega, A. (2015). Comparison of the carbon footprint of different patient diets in a Spanish hospital. Journal of Health Services Research & Policy, 20(1), 39–44

Evaluation of a New Monoclonal Chemiluminescent Immunoassay Stool Antigen Test for the Diagnosis of Helicobacter pylori Infection: A Spanish Multicentre Study

The stool antigen test (SAT) represents an attractive alternative for detection of Helicobacter pylori. The aim of this study was to assess the accuracy of a new SAT, the automated LIAISON(R) Meridian H. pylori SA based on monoclonal antibodies, compared to the defined gold standard C-13-urea breath test (UBT). This prospective multicentre study (nine Spanish centres) enrolled patients >= 18 years of age with clinical indication to perform UBT for the initial diagnosis and for confirmation of bacterial eradication. Two UBT methods were used: mass spectrometry (MS) including citric acid (CA) or infrared spectrophotometry (IRS) without CA. Overall, 307 patients (145 naive, 162 with confirmation of eradication) were analysed. Using recommended cut-off values (negative SAT = 1.10) the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 67%, 97%, 86%, 92% and 91%, respectively, obtaining an area under the receiver operating characteristic (ROC) curve (AUC) of 0.85. Twenty-eight patients, including seven false positives and 21 false negatives, presented a discordant result between SAT and UBT. Among the 21 false negatives, four of six tested with MS and 11 of 15 tested with IRS presented a borderline UBT delta value. In 25 discordant samples, PCR targeting H. pylori DNA was performed to re-assess positivity and SAT accuracy was re-analysed: sensitivity, specificity, positive predictive value, negative predictive value, accuracy and AUC were 94%, 97%, 86%, 99%, 97% and 0.96, respectively. The new LIAISON(R) Meridian H. pylori SA SAT showed a good accuracy for diagnosis of H. pylori infection

The Baryon Oscillation Spectroscopic Survey of SDSS-III

The Baryon Oscillation Spectroscopic Survey (BOSS) is designed to measure the scale of baryon acoustic oscillations (BAO) in the clustering of matter over a larger volume than the combined efforts of all previous spectroscopic surveys of large scale structure. BOSS uses 1.5 million luminous galaxies as faint as i=19.9 over 10,000 square degrees to measure BAO to redshifts z<0.7. Observations of neutral hydrogen in the Lyman alpha forest in more than 150,000 quasar spectra (g<22) will constrain BAO over the redshift range 2.15<z<3.5. Early results from BOSS include the first detection of the large-scale three-dimensional clustering of the Lyman alpha forest and a strong detection from the Data Release 9 data set of the BAO in the clustering of massive galaxies at an effective redshift z = 0.57. We project that BOSS will yield measurements of the angular diameter distance D_A to an accuracy of 1.0% at redshifts z=0.3 and z=0.57 and measurements of H(z) to 1.8% and 1.7% at the same redshifts. Forecasts for Lyman alpha forest constraints predict a measurement of an overall dilation factor that scales the highly degenerate D_A(z) and H^{-1}(z) parameters to an accuracy of 1.9% at z~2.5 when the survey is complete. Here, we provide an overview of the selection of spectroscopic targets, planning of observations, and analysis of data and data quality of BOSS.Comment: 49 pages, 16 figures, accepted by A

C-Terminal Extension of the Yeast Mitochondrial DNA Polymerase Determines the Balance between Synthesis and Degradation

Saccharomyces cerevisiae mitochondrial DNA polymerase (Mip1) contains a C-terminal extension (CTE) of 279 amino acid residues. The CTE is required for mitochondrial DNA maintenance in yeast but is absent in higher eukaryotes. Here we use recombinant Mip1 C-terminal deletion mutants to investigate functional importance of the CTE. We show that partial removal of the CTE in Mip1Δ216 results in strong preference for exonucleolytic degradation rather than DNA polymerization. This disbalance in exonuclease and polymerase activities is prominent at suboptimal dNTP concentrations and in the absence of correctly pairing nucleotide. Mip1Δ216 also displays reduced ability to synthesize DNA through double-stranded regions. Full removal of the CTE in Mip1Δ279 results in complete loss of Mip1 polymerase activity, however the mutant retains its exonuclease activity. These results allow us to propose that CTE functions as a part of Mip1 polymerase domain that stabilizes the substrate primer end at the polymerase active site, and is therefore required for efficient mitochondrial DNA replication in vivo