Angiogenesis: From Chronic Liver Inflammation to Hepatocellular Carcinoma

Recently, new information relating to the potential relevance of chronic hepatic inflammation to the development and progression of hepatocellular carcinoma (HCC) has been generated. Persistent hepatocellular injury alters the homeostatic balance within the liver; deregulation of the expression of factors involved in wound healing may lead to the evolution of dysplastic lesions into transformed nodules. Progression of such nodules depends directly on the development and organization of a vascular network, which provides the nutritional and oxygen requirements to an expanding nodular mass. Angiogenic stimulation promotes intense structural and functional changes in liver architecture and physiology, in particular, it facilitates transformation of dysplasia to nodular lesions with carcinogenic potential. HCC depends on the growth and spreading of vessels throughout the tumor. Because these vascular phenomena correlate with disease progression and prognosis, therapeutic strategies are being developed that focus on precluding vascular expansion in these tumors. Accordingly, an in-depth study of factors that promote and support pathological angiogenesis in chronic hepatic diseases may provide insights into methods of preventing the development of HCC and/or stimulating the regression of established HCC

Aplicación de las tecnologías de la información geográfica en el diseño de itinerarios para la educación en paisaje en el ámbito de los Parques Nacionales

El proyecto pretende acercar los distintos tipos de paisajes a los estudiantes a partir de un itinerario y realizar una explicación a través de diversas actividades, que estarán disponibles online, de forma que se puedan trabajar los parques tanto de forma virtual como real. Los medios con los que contamos se basan en el trabajo realizado en el PIMCD anterior (PIMCD 224/2015 La potencialidad de la nube para el trabajo de campo en Geografía: El Parque Nacional de la Sierra de Guadarrama), centrado sobre el PN Sierra de Guadarrama, cuya metodología y recursos pedagógicos empleados serán enriquecidos y reutilizados en este proyecto en el que se continuará empleando las tecnologías de la información geográfica para el diseño de itinerarios geográficos que pongan al alcance de los docentes los paisajes de los Parques Nacionales, en el primer centenario de la Ley que crea su figura (primera Ley de Parques Nacionales se promulga en 1916). Tomando como punto de partida el concepto de paisaje que acuerda el Convenio Europeo del Paisaje (CEP) y las premisas didácticas que el mismo expone relativas a la inscripción de los aprendizajes necesarios, somos conscientes de la multiplicidad de recursos de que hoy disponemos para contribuir positivamente a desarrollar la sensibilidad y el sentido ético de los estudiantes y el profesorado hacia los paisajes en general y los espacios naturales protegidos en particular. Multiplicidad que responde tanto a la creciente disponibilidad de recursos web e información geográfica que ofrece la nube, como a la accesibilidad a nuevos dispositivos como GPS, tabletas o smartphones, que han supuesto una generalización en el acceso a información georreferenciada. Partiendo de esta realidad, nuestro proyecto se vertebra en dos líneas preferentes. Por un lado, acercar esta diversidad de nuevas tecnologías y la información geográfica o geoinformación al profesorado y alumnado, ofreciendo recursos que sirvan para el aprendizaje de su manejo dentro y fuera del aula y, por otro, mejorar el conocimiento de los valores naturales y culturales de distintos espacios singulares y sus paisajes, fomentando una conciencia social conservacionista tal y como contempla entre sus objetivos principales la Red de Parques Nacionales de España

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Withdrawal Is Associated with Higher Mortality in Hospitalized Patients with COVID-19

Our main aim was to describe the effect on the severity of ACEI (angiotensin-converting enzyme inhibitor) and ARB (angiotensin II receptor blocker) during COVID-19 hospitalization. A retrospective, observational, multicenter study evaluating hospitalized patients with COVID-19 treated with ACEI/ARB. The primary endpoint was the incidence of the composite outcome of prognosis (IMV (invasive mechanical ventilation), NIMV (non-invasive mechanical ventilation), ICU admission (intensive care unit), and/or all-cause mortality). We evaluated both outcomes in patients whose treatment with ACEI/ARB was continued or withdrawn. Between February and June 2020, 11,205 patients were included, mean age 67 years (SD = 16.3) and 43.1% female; 2162 patients received ACEI/ARB treatment. ACEI/ARB treatment showed lower all-cause mortality (p < 0.0001). Hypertensive patients in the ACEI/ARB group had better results in IMV, ICU admission, and the composite outcome of prognosis (p < 0.0001 for all). No differences were found in the incidence of major adverse cardiovascular events. Patients previously treated with ACEI/ARB continuing treatment during hospitalization had a lower incidence of the composite outcome of prognosis than those whose treatment was withdrawn (RR 0.67, 95%CI 0.63-0.76). ARB was associated with better survival than ACEI (HR 0.77, 95%CI 0.62-0.96). ACEI/ARB treatment during COVID-19 hospitalization was associated with protection on mortality. The benefits were greater in hypertensive, those who continue

High-resolution hepatitis C virus subtyping using NS5B deep sequencing and phylogeny, an alternative to current methods

HepatitisCvirus(HCV)is classified into seven major genotypesand67 subtypes. Recent studies haveshownthat inHCVgenotype 1-infected patients, response rates to regimens containingdirect-acting antivirals(DAAs)are subtype dependent. Currently available genotypingmethods have limited subtyping accuracy.Wehave evaluated theperformanceof adeep-sequencing-basedHCVsubtyping assay, developed for the 454/GS-Junior platform, in comparisonwith thoseof two commercial assays (VersantHCVgenotype 2.0andAbbott Real-timeHCVGenotype II)andusingdirectNS5Bsequencing as a gold standard (direct sequencing), in 114 clinical specimenspreviously tested by first-generation hybridization assay (82 genotype 1and32 with uninterpretable results). Phylogenetic analysis of deep-sequencing reads matched subtype 1 callingbypopulation Sanger sequencing(69%1b,31%1a) in 81 specimensandidentified amixed-subtype infection (1b/3a/1a) in one sample. Similarly,amongthe 32previously indeterminate specimens, identical genotypeandsubtype results were obtained by directanddeep sequencing in all but four samples with dual infection. In contrast, both VersantHCVGenotype 2.0andAbbott Real-timeHCVGenotype II failed subtype 1 calling in 13 (16%) samples eachandwere unable to identify theHCVgenotype and/or subtype inmore than half of the nongenotype 1 samples.Weconcluded that deep sequencing ismore efficient forHCVsubtyping than currently available methodsandallows qualitative identificationofmixed infectionsandmay bemorehelpfulwith respect to informing treatment strategies withnewDAA-containing regimens across allHCVsubtypesThis study has been supported by CDTI (Centro para el Desarrollo Tecnológico Industrial), Spanish Ministry of Economics and Competitiveness (MINECO), IDI-20110115; MINECO projects SAF 2009-10403; and also by the Spanish Ministry of Health, Instituto de Salud Carlos III (FIS) projects PI10/01505, PI12/01893, and PI13/00456. CIBERehd is funded by the Instituto de Salud Carlos III, Madrid, Spain. Work at CBMSO was supported by grant MINECO-BFU2011-23604, FIPSE, and Fundación Ramón Areces. X. Forns received unrestricted grant support from Roche and has acted as advisor for MSD, Gilead, and Abbvie. M. Alvarez-Tejado, J. Gregori, and J. M. Muñoz work in Roche Diagnostic

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Diseño de una guía didáctica para la interpretación del paisaje a partir de recursos cartográficos online

El presente proyecto tiene por objetivo diseñar una guía didáctica para la interpretación del paisaje basada en cartografía digital online, adaptable a diferentes niveles académicos, cuyo fin será promover la educación en paisaje, de acuerdo con la necesidad que el Convenio Europeo del Paisaje (CEP) plantea acerca de contribuir a la formación de una sociedad que valore y demande paisajes de calidad, pues estos desempeñan un importante papel de interés general en los campos cultural, ecológico, medioambiental y social. El concepto de paisaje del que partimos es el acordado en el CEP y en las diferentes leyes del paisaje autonómicas españolas, entendiendo por paisaje no sólo aquellos espacios con altos valores naturales y/o estéticos, sino todo territorio tal y como lo percibe la sociedad. La guía supone el fruto de los resultados de numerosos trabajos llevados a cabo por el grupo en relación con la didáctica del paisaje. Entre ellos los PIMCD: 133/2011, 165/2013, 98/2014, 224/2015, 52/2016 y, principalmente del anterior 113/2017, en los que se han diseñado y aplicado recursos didácticos como comentario de imágenes, desarrollo de cartografía digital o diseño de itinerarios didácticos para la interpretación del paisaje en el ámbito de los Parques Nacionales españoles. Así, el proyecto se vertebra en dos líneas preferentes. Por un lado, acercar la diversidad de nuevas tecnologías y la información geográfica o geoinformación a través de una guía que compendia un variado elenco de recursos cartográficos digitales para el profesorado y alumnado, ofreciendo recursos que sirvan para el aprendizaje dentro y fuera del aula y, por otro, mejorar el conocimiento acerca de los valores naturales y culturales de los paisajes, fomentando una conciencia social que contribuya con su puesta en valor y mejora. La guía resultante podrá ser consultada en abierto y en el Atlas Digital Escolar por nuestros alumnos, tanto del Grado de Geografía y Ordenación del Territorio, los Grados de Maestro en Educación Infantil y Primaria así como de los másteres en Formación del Profesorado de ESO y Bachillerato, FP y Enseñanza de Idiomas, de Tecnologías de la Información y de Dinámicas Territoriales

Diseño de un modelo didáctico para la educación en paisaje utilizando Sigweb

A través del PIMCD 113, se ha diseñado e implementado un modelo didáctico para la educación en paisaje enfocado a alumnos del Grado de Maestro de Educación Primaria

Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: A nationwide study in Spain

Objective To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. Settings The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. Participants This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. Interventions An exploratory factorial analysis was performed to select the most relevant variables of the sample. Primary and secondary outcome measures Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. Results Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/10 5 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade =3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/10 5 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. Conclusions Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/10 5 people/week) was a statistically independent predictor of mortality. Trial registration number CEIM 20/217