Hepatic and serum branched-chain fatty acid profile in patients with nonalcoholic fatty liver disease: A case–control study

Objective Alterations in the hepatic lipidome are a crucial factor involved in the pathophysiology of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the serum and hepatic profile of branched-chain fatty acids (BCFAs) in patients with different stages of NAFLD. Methods This was a case–control study performed in 27 patients without NAFLD, 49 patients with nonalcoholic fatty liver, and 17 patients with nonalcoholic steatohepatitis, defined by liver biopsies. Serum and hepatic levels of BCFAs were analyzed by gas chromatography–mass spectrometry. The hepatic expression of genes involved in the endogenous synthesis of BCFAs was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Results A significant increase in hepatic BCFAs was found in subjects with NAFLD compared with those without NAFLD; no differences were observed in serum BCFAs between study groups. Trimethyl BCFAs, iso-BCFAs, and anteiso-BCFAs were increased in subjects with NAFLD (either nonalcoholic fatty liver or nonalcoholic steatohepatitis) compared with those without NAFLD. Correlation analysis showed a relationship between hepatic BCFAs and the histopathological diagnosis of NAFLD, as well as other histological and biochemical parameters related to this disease. Gene expression analysis in liver showed that the mRNA levels of BCAT1, BCAT2, and BCKDHA were upregulated in patients with NAFLD. Conclusions These results suggest that the increased production of liver BCFAs might be related to NAFLD development and progression.This work was funded by the Institute of Health “Carlos III” (ISCIII) and cofunded by the Fondo Europeo de Desarrollo Regional-FEDER (grant number PI20/00505). J.C.F-G was supported by an intensification research program (INT21/00078, ISCIII, Spain; cofunded by the Fondo Europeo de Desarrollo Regional-FEDER), M.A.M-S was supported by a PFIS predoctoral fellowship from the ISCIII (FI21/00003, ISCIII, Spain; cofunded by the Fondo Europeo de Desarrollo Regional-FEDER), and B.R-M was supported by the “Miguel Servet Type I” program (CP19/00098, ISCIII, Spain; cofunded by the Fondo Europeo de Desarrollo Regional-FEDER). The funding organizations played no role in the design of the study, review and interpretation of the data, or final approval of the manuscript. Funding for open access charge: Universidad de Málaga / CBU

Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a syndrome that occurs in cirrhosis characterized by organ failure(s) and high mortality rate. There are no biomarkers of ACLF. The LCN2 gene and its product, neutrophil gelatinase-associated lipocalin (NGAL), are upregulated in experimental models of liver injury and cultured hepatocytes as a result of injury by toxins or proinflammatory cytokines, particularly Interleukin-6. The aim of this study was to investigate whether NGAL could be a biomarker of ACLF and whether LCN2 gene may be upregulated in the liver in ACLF. METHODS: We analyzed urine and plasma NGAL levels in 716 patients hospitalized for complications of cirrhosis, 148 with ACLF. LCN2 expression was assessed in liver biopsies from 29 additional patients with decompensated cirrhosis with and without ACLF. RESULTS: Urine NGAL was markedly increased in ACLF vs. no ACLF patients (108(35-400) vs. 29(12-73)μg/g creatinine; p<0.001) and was an independent predictive factor of ACLF; the independent association persisted after adjustment for kidney function or exclusion of variables present in ACLF definition. Urine NGAL was also an independent predictive factor of 28day transplant-free mortality together with MELD score and leukocyte count (AUROC 0.88(0.83-0.92)). Urine NGAL improved significantly the accuracy of MELD in predicting prognosis. The LCN2 gene was markedly upregulated in the liver of patients with ACLF. Gene expression correlated directly with serum bilirubin and INR (r=0.79; p<0.001 and r=0.67; p<0.001), MELD (r=0.68; p<0.001) and Interleukin-6 (r=0.65; p<0.001). CONCLUSIONS: NGAL is a biomarker of ACLF and prognosis and correlates with liver failure and systemic inflammation. There is remarkable overexpression of LCN2 gene in the liver in ACLF syndrome. LAY SUMMARY: Urine NGAL is a biomarker of acute-on-chronic liver failure (ACLF). NGAL is a protein that may be expressed in several tissues in response to injury. The protein is filtered by the kidneys due to its small size and can be measured in the urine. Ariza, Graupera and colleagues found in a series of 716 patients with cirrhosis that urine NGAL was markedly increased in patients with ACLF and correlated with prognosis. Moreover, gene coding NGAL was markedly overexpressed in the liver tissue in ACLF

Revisitando el cine documental: de Flaherty al webdoc

En los últimos tiempos, y propiciado por el auge de la imagen digital, el género documental ha liderado una importante renovación en sus formas cinematográficas indagando en nuevos lenguajes para la imagen contemporánea. Desdibujando por completo los límites entre la ficción y la no ficción, el documental contemporáneo ha fraccionado algunas de las convenciones asociadas al género, encontrando fácil acomodo entre lo narrativo, lo observacional, lo etnográfico, lo ensayístico, la videocreación, lo autobiográfico y, obviamente, lo experimental. Tras décadas de constante mutación, el cine documental se nos presenta como un fascinante territorio de exploración fílmica, aportando una reflexión sobre las fronteras actuales del lenguaje cinematográfico y que requiere a su vez un nuevo tipo de mirada desde el ámbito académico. Dispuestas así las cosas, el presente libro se propone revisitar el género documental y recoger experiencias e investigaciones que, desde diferentes planteamientos, buscan reflexionar sobre la evolución del propio género desde un enfoque multidisciplinar. De este modo, se pretende establecer un estado de la cuestión con textos vinculados a los disímiles modos de abordar el documental a lo largo de su dilatada historia: estudios historiográficos, análisis fílmicos sustentados en ejemplos concretos de películas o directores de especial interés, investigaciones que ponen en relieve la influencia y consecuencia de la evolución de la tecnología digital e Internet, así como la evolución e innovación en los modos de producción, exhibición y/o distribución por los que el documental ha transitado.Este Libro se ha realizado dentro del Grupo de Investigación GIU 13/21 (2013-2016), MAC (Mutaciones del Audiovisual Contemporáneo) de la Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU).La redacción del capítulo "Un lugar ético para las imágenes documentales (en el contexto de las ciencias sociales) / Josetxo Cerdán Los Arcos" fue posible gracias al proyecto de investigación CSO2010/15798 (TRANSCINE), financiado por el Ministerio de Ciencia e Innovación del Gobierno de España. -- La redacción del capítulo "Documentalidad. Cine sin autoría, pedagogías visuales colectivas y valor afectivo / Virginia Villaplana Ruiz" fue posible gracias al proyecto de investigación eDCINEMA: "Hacia el Espacio Digital Europeo", financiado por el Plan Nacional de I+D+i del Ministerio de Economía y Competitividad. Ref. CSO2012-35784. -- La redacción del capítulo "Cosas que hacen crack. Emociones y cinefilia en Color perro que huye (Andrés Duque, 2011) / Miguel Fernández Labayen y Elena Oroz" se ha realizado en el marco del proyecto de investigación CSO2010-15798 (TRANSCINE), "El audiovisual español contemporáneo en el contexto transnacional: aproximaciones cualitativas a sus relaciones transfronterizas", financiado por el Ministerio de Economía y Competitividad del Gobierno de España. -- El capítulo "Aproximación a la no ficción interactiva: panorámica del webdocumental español en la era digital / Robert Arnau Roselló" ha sido financiado con la ayuda del Proyecto de Investigación de la convocatoria Universitat Jaume I-Bancaja, con el título "Análisis de los flujos de transferencia de conocimiento entre los sistemas educativos superiores y la industria del videojuego", código 11I301.01/1, bajo la dirección del Dr. Javier Marzal Felici.Prólogo / J.M. Català Domènech (pp. 9-14). -- Un lugar ético para las imágenes documentales (en el contexto de las ciencias sociales) / Josetxo Cerdán Los Arcos (pp. 17-32). -- Documentalidad. Cine sin autoría, pedagogías visuales colectivas y valor afectivo / Virginia Villaplana Ruiz (pp. 33-54). -- Diseño de títulos en documental: cuestión de etiqueta / Koldo Atxaga Arnedo (pp. 55-65). -- La creación del documental: archivo, recreaciones y entrevistas / Mónica del Sagrario Medina Cuevas y Alejandro Jiménez Arrazquito (pp. 67-76). -- Desterritorialización, modulación y puntos de inflexión en el documental contemporáneo español / Vanesa Fernández Guerra y Estibaliz Alonso Ruiz de Erentzun (pp. 79-103). -- La propuesta de vertebración del Novo Cine Galego: lo procesual y la marca documental / Fernando Redondo Neira y Xurxo González Rodríguez (pp. 105-126). -- Revisión de la etiqueta "Novo Cinema Galego". Testimonios de autor / Beli Martínez Martínez (pp. 127-152). -- El cine de no ficción en los cortometrajes de Kimuak: evoluación, tendencias y nuevas propuestas creativas / Ainhoa Fernández de Arroyabe Olaorut, Nekane E. Zubiaur Gorozika y Iñaki Lazkano Arrillaga (pp. 153-179). -- Cosas que hacen "crack". Emociones y cinefilia en Color perro que huye (Andrés Duque, 2011) / Miguel Fernández Labayen y Elena Oroz (pp. 181- 204). -- Estudio evolutivo del lenguaje narrativo, desde los primeros documentales a las transmedia / Begoña Gutiérrez San Miguel (pp. 207-244). -- La participación ciudadana en el documental colaborativo: hacia nuevas narrativas audiovisuales / Gloria Rosique Cedillo (pp. 245-263). -- Del documental lineal al webdocumental: enunciación y experiencia espectatorial en Gare du Nord de Claire Simon / Amanda Rueda (pp. 265-274). -- El documental multimedia interactivo. Un estudio de caso: En el reino del plomo (En Portada y Lab de RTVE.es, 2013) / Irene Liberia Vayá y Cristina Pérez de Algaba Chicano (pp. 275-299). -- Aproximación a la no ficción interactiva: panorámica del webdocumental español en la era digital / Robert Arnau Roselló (pp. 301-323)

A regulated deficit irrigation strategy for hedgerow olive orchards with high plant density

Background & Aims There is not a consensus on the best irrigation approach for super-high density (SHD) olive orchards. Our aim was to design and test a regulated deficit irrigation (RDI) strategy for a sustainable balance between water saving, tree vigour and oil production. Methods We tested our RDI strategy for 3 years in an ‘Arbequina’ orchard with 1,667 trees ha−1. Two levels of irrigation reduction were applied, 60RDI and 30RDI, scaled to replacing 60 % and 30 %, respectively, of the of irrigation needs (IN). We also had a full irrigation (FI) treatment as control, with IN totalling 4,701 m3 ha−1 Results The 30RDI treatment showed the best balance between water saving, tree vigour and oil production. With a yearly irrigation amount (IA) of 1,366 m3 ha−1, which meant 72 % water saving as compared to FI, the reduction in oil yield was 26 % only. Conclusions Our results, together with recent knowledge on the effect of water stress on fruit development, allowed us to suggest a potentially improved RDI strategy for which a total IA of ca. 2,100 m3 ha−1 was calculated. Both some management details and the benefits of this suggested RDI strategy are still to be tested

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

Land- and water-based exercise intervention in women with fibromyalgia: the al-andalus physical activity randomised controlled trial

Background The al-Andalus physical activity intervention study is a randomised control trial to investigate the effectiveness of a land- and water-based exercise intervention for reducing the overall impact of fibromyalgia (primary outcome), and for improving tenderness and pain-related measures, body composition, functional capacity, physical activity and sedentary behaviour, fatigue, sleep quality, health-related quality of life, and cognitive function (secondary outcomes) in women with fibromyalgia. Methods/Design One hundred eighty women with fibromyalgia (age range: 35-65 years) will be recruited from local associations of fibromyalgia patients in Andalucía (Southern Spain). Patients will be randomly assigned to a usual care (control) group (n = 60), a water-based exercise intervention group (n = 60) or a land-based exercise intervention group (n = 60). Participants in the usual care group will receive general physical activity guidelines and participants allocated in the intervention groups will attend three non-consecutive training sessions (60 min each) per week during 24 weeks. Both exercise interventions will consist of aerobic, muscular strength and flexibility exercises. We will also study the effect of a detraining period (i.e., 12 weeks with no exercise intervention) on the studied variables. Discussion Our study attempts to reduce the impact of fibromyalgia and improve patients' health status by implementing two types of exercise interventions. Results from this study will help to assess the efficacy of exercise interventions for the treatment of fibromyalgia. If the interventions would be effective, this study will provide low-cost and feasible alternatives for health professionals in the management of fibromyalgia. Results from the al-Andalus physical activity intervention will help to better understand the potential of regular physical activity for improving the well-being of women with fibromyalgia.This study was supported by the Consejeria de Turismo, Comercio y Deporte (CTCD-201000019242-TRA), the Spanish Ministry of Science and Innovation (I + D + I DEP2010-15639, grants: BES-2009-013442, BES-2011-047133, RYC-2010-05957, RYC-2011-09011), the Swedish Heart-Lung Foundation (20090635), the Spanish Ministry of Education (AP-2009-3173), Granada Research of Excelence Initiative on Biohealth (GREIB), Campus BioTic, University of Granada, Spain and European University of Madrid. Escuela de Estudios Universitarios Real Madrid. 2010/04RM

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Measurement of differential cross sections in the kinematic angular variable phi* for inclusive Z boson production in pp collisions at root s=8 TeV

Measurements of differential cross sections d sigma/d phi* and double-differential cross sections d(2)sigma/ld phi*d/y/ for inclusive Z boson production are presented using the dielectron and dimuon final states. The kinematic observable phi* correlates with the dilepton transverse momentum but has better resolution, and y is the dilepton rapidity. The analysis is based on data collected with the CMS experiment at a centre-of-mass energy of 8 TeV corresponding to an integrated luminosity of 19.7 fb(-1). The normalised cross section (1/sigma) d sigma/d phi*, within the fiducial kinematic region, is measured with a precision of better than 0.5% for phi* <1. The measurements are compared to theoretical predictions and they agree, typically, within few percent.Peer reviewe