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BACKGROUND AND AIMS Porto-sinusoidal vascular liver disorder (PSVD) is a rare disease that occasionally requires liver transplantation (LT), despite usually presenting preserved liver function. There remains a paucity of data pertaining to LT in PSVD. The aim was to identify features associated with post-LT outcomes in PSVD. METHODS Retrospective multicentre study of 79 patients who received LT for PSVD. RESULTS Median post-LT follow-up was 37 (range 1-261) mo. Refractory ascites 24 (30%), hepatic encephalopathy 16 (20%), and hepatopulmonary syndrome 13 (16.3%) were the most frequent indications for LT. Hepatocellular carcinoma was the indication in only 2 patients. Twenty-four patients died, 7 due to liver and 17 to non-liver related causes. Post-LT survival was 82.2%, 80.7%, and 68.6% at 1, 2, and 5 y, respectively. Post-LT survival was significantly better in patients without (n = 58) than in those with a persistent severe PSVD-associated condition (n = 21). Pre-LT hyperbilirubinemia levels and creatinine >100 µmol/L were also independently associated with poor survival. Six patients (7.6%) required a second LT. Recurrence of PSVD was confirmed by liver biopsy in only 1 patient and in 3 further patients it was likely. CONCLUSIONS LT in PSVD is associated with an acceptable outcome in the absence of associated severe conditions. However, persistence of a severe associated condition, pre-LT high bilirubin levels, or creatinine >100 µmol/L impact outcome, and these are features that should be considered when evaluating PSVD patients for LT. PSVD recurrence is possible after LT and needs to be explored, at least, in cases of posttransplant portal hypertension.

El género ofrece una atalaya para pensar y repensar el rol de las mujeres rurales durante la dictadura franquista. En esa convicción, el presente texto busca acercarse a las construcciones ideales sobre los sujetos femeninos que habitaban el medio rural que el poder puso en liza tras la guerra civil. Nuestra meta es aprehender los distintos modelos de mujer rural que se convirtieron en normativos en un periodo histórico definido por la imposición de una dictadura que marcó mudanzas en los modelos de mujer imperantes. Pretendemos acercarnos a su análisis y demostrar que se construyeron en consonancia con los distintos modelos de desarrollo económico que definieron la agricultura española durante la dictadura. Con este objetivo emplearemos fuentes de variadas naturalezas, incluida la prensa y las disposiciones legislativas, que emanaban de aquellas instituciones que fueron creadas para «moldear» a las mujeres rurales a imagen y semejanza del ideal construido. Prestaremos especial atención a la labor desarrollada por Sección Femenina, a través de la figura de las divulgadoras rurales y las Cátedras Ambulantes, así como por el Servicio de Extensión Agraria a partir de las figuras de las agentes de economía doméstica.

Head positioning in carotid surgery represents an often overlooked but sensitive period in the surgical plan. A 53-year-old male presented a significant decrement in median nerve somatosensory evoked potential (mSEP) following head and neck positioning for carotid pseudoaneurysm repair before skin incision.Neurophysiological monitoring was performed with mSEP and electroencephalography early during the patient's preparation and surgery. Within five minutes after rotation and extension of the head to properly expose the surgical field, the contralateral m-SEP significantly decreased in both cortical (N20/P25) and subcortical (P14/N18) components. Partial neck correction led to m-SEP improvement, allowing to proceed with the carotid repair. We discuss possible underlying pathophysiological mechanisms responsible for these changes and highlight the relevance of an early start on monitoring to avoid neurological deficits.

Dermatologic adverse events (DAEs) are associated with a better outcome in patients with hepatocellular carcinoma (HCC) irrespective of the therapeutic agent received. The exact mechanisms associated with the development of DAEs are unknown although several studies point to direct toxicity of tyrosine kinase inhibitors (TKIs) to the skin or an immune-mediated reaction triggered by the oncologic treatment. As is the case in other conditions, individual genetic variants may partially explain a higher risk of DAEs.To evaluate the contribution of several gene variants to the risk of developing DAEs in HCC patients treated with TKIs.We first analyzed 27 single-nucleotide polymorphisms (SNPs) from 12 genes selected as potential predictors of adverse event (AE) development in HCC patients treated with sorafenib [Barcelona Clinic Liver Cancer 1 (BCLC1) cohort]. Three additional cohorts were analyzed forThe BCLC1 cohort showed that patients with arterial hypertension (AHT) (HR = 1.61;DAE development in HCC patients receiving TKIs could be explained by the

The Basque-Cantabrian Zone (BCZ) is a large, inverted Mesozoic basin (the Basque-Cantabrian basin or BCB) forming part of the Pyrenean-Cantabrian mountain belt, in the north of Iberian Peninsula. The Mesozoic basin developed in one of the most subsident regions between the European plate and the Iberian sub-plate during the stage of crustal hyperextension linked to the rifting of the Central-North Atlantic and the opening of the Bay of Biscay. The high subsidence rate led to the accumulation of more than 15 km of sediments according to some estimates, and the significant crustal extension caused the exhumation of the mantle in the easternmost sector of the BCB. The Alpine orogeny caused the closure and inversion of the BCB and its incorporation to the Pyrenean-Cantabrian orogen. In this work, we studied the crustal structure of the BCZ resulting from this long and complex tectonic evolution using five years of continuous seismic recordings gathered by a local network of broadband stations, most of them deployed in the framework of projects SISCAN and MISTERIOS. A total of 66 locations were used (not all of them simultaneously), with an average spacing of ~30 km between stations. From this dataset, we extracted the multi-mode phase velocities of surface waves and the ellipticity of Rayleigh waves from cross-correlations of the seismic ambient noise. This allowed us to retrieve the shear-wave velocity structure of the crust, especially at shallow to intermediate depths. To better constrain the deeper crustal structure, we also extracted teleseismic P-wave receiver functions for all suitable events. Each dataset was carefully analyzed before performing a nonlinear, joint inversion using the simulated annealing technique. The result is a set of 1D shear-wave velocity models that represent a compromise between all three datasets. These 1D models were then used in a linear interpolation to build a 3D model of the BCZ. The main feature of the 3D model is a thickened crust of up to 50 km beneath the Cantabrian Mountains. A discontinuous, intracrustal level of high-velocities is identified in the northern part of the model, coherently with previous geological and geophysical observations, suggesting that the thick crustal root would be caused by the indentation of the Cantabrian Margin lower crust into the Iberian crust, as has been already proposed. This new 3D model fills a gap in the knowledge of the study area, whose seismic characterization was primarily based on active source studies, which often only provide estimates of the P-wave velocities along 2D profiles.

A lyophilized preparation of an unspecific peroxygenase variant from Agrocybe aegerita (rAaeUPO-PaDa-I-H) is a highly effective catalyst for the oxygenation of a diverse range of N-heterocyclic compounds. Scalable biocatalytic oxygenations (27 preparative examples, ≈100 mgs scale) have been developed across a wide range of substrates, including alkyl pyridines, bicyclic N-heterocycles and indoles. H2O2 is the only stoichiometric oxidant needed, without auxiliary electron transport proteins, which is key to the practicality of the method. Reaction outcomes can be altered depending on whether hydrogen peroxide was delivered by syringe pump or through in situ generation using an alcohol oxidase from Pichia pastoris (PpAOX) and methanol as a co-substrate. Good synthetic yields (up to 84%), regioselectivity and enantioselectivity (up to 99% ee) were observed in some cases, highlighting the promise of UPOs as practical, versatile and scalable oxygenation biocatalysts.

Background. Interest in electroencephalographic (EEG) coronavirus disease 2019 (COVID-19) findings has been growing, especially in the search for a specific-features EEG of encephalopathy. Methods. We made a retrospective analysis of 29 EEGs recorded in 15 patients with COVID-19 and neurological symptoms. We classified the EEGs as “Acute EEG” and “follow-up EEG.” We did a statistical analysis between voltage and respiratory status of the patient, stay or not in the intensive care unit (ICU), days of stay in the ICU, sedative drugs, pharmacological treatment, type of symptoms predominating, and outcome. Results. We found EEG abnormalities in all patients studied. We observed the amplitude of background

Background Persistent inflammation and immune activation are associated with lymph node fibrosis and end-organ diseases in treatment-suppressed people living with HIV (PLWH). We investigated the effect of switching to raltegravir and/or adding losartan on lymphoid tissue fibrosis and on the inflammatory/immune-activation mediators in treated HIV patients. Methods Chronic HIV-infected patients treated with two nucleoside reverse transcriptase inhibitors (2NRTI) and one non-NRTI (NNRTI) or protease inhibitor (PI) during at least 48 weeks were randomized to four groups (n = 48): 2NRTI + efavirenz (EFV), 2NRTI + EFV + losartan, 2NRTI + raltegravir and 2NRTI + raltegravir + losartan for 48 weeks. Tonsillar biopsy and peripheral blood markers of CD4 and CD8 T-lymphocyte activation and senescence, monocyte activation and soluble markers of inflammation were determined at baseline and at week 48 and compared between groups. Results No changes in lymphoid tissue architecture were observed. Adding losartan had no impact on lymphocyte subsets. Conversely, patients who switched to raltegravir showed a higher decrease in all activated [CD4+CD38+HLA-DR+, -0.3 vs. 0.48 (P = 0.033); CD8+CD38+ HLA-DR+, -1.6 vs. 1.3 (P = 0.02)] and senescent [CD4+CD28-CD57+, -0.3 vs. 0.26 (P = 0.04); CD8+CD28-CD57+, -6.1 vs. 3.8 (P = 0.002)] T lymphocytes. In addition, the median CD4/CD8 ratio increased by 0.35 in patients in the raltegravir group vs. 0.03 in the other arms (P = 0.002). Differences between groups in monocyte subpopulations or soluble inflammation markers were not observed. Conclusions Losartan had no effect on lymphoid fibrosis or immune activation/inflammation. Conversely, switching to a regimen with raltegravir significantly decreased activated and senescent T-lymphocyte subpopulations and increased CD4/CD8 ratio in successfully treated PLWH.

BACKGROUND AND AIMS Porto-sinusoidal vascular disease (PSVD) is a rare disease that requires excluding cirrhosis and other causes of portal hypertension for its diagnosis because it lacks a specific diagnostical test. Although it has been occasionally associated with autoimmune diseases, the pathophysiology of PSVD remains unknown. The aim of this study was to evaluate the potential role of autoimmunity in the pathophysiology and diagnosis of PSVD. METHODS Thirty-seven consecutive patients with PSVD and 39 with cirrhosis matched by gender, signs of portal hypertension and liver function were included (training set). By using Indirect Immunofluorescence, ELISA and slot-blot methods data 22 autoantibodies were identified in patients with PSVD and cirrhosis. Presence of anti-endothelial cells antibodies (AECA) was assayed by a cell-based ELISA. Thirty-one PSVD, 40 cirrhosis patients, 15 patients with splenomegaly associated with haematological disease and 14 healthy donors were included in a validation set. FINDINGS The proportion of patients with at least one positive antibody was statistically significantly higher in patients with PSVD compared with cirrhosis (92% vs 56%; P

BACKGROUND AND AIMS Alcohol and metabolic syndrome (MS) coexist frequently as cofactors of liver disease. Previous studies suggest a deleterious effect of MS in advanced alcohol-related liver disease (ArLD). However, it is unknow whether MS can increase the risk of liver fibrosis in early stages of ArLD. The aim of this study was to investigate the effect of MS on liver fibrosis in subjects with alcohol consumption from a population-based cohort. METHODS The number of subjects include 1760(58%) of 3014 who were randomly selected from the community consumed alcohol and were classified as current drinkers, divided in moderate (n = 1222) or high-risk drinkers (n = 275) (>21 units/week men, >14 units/week women for high-risk drinkers), or former drinkers (n = 263). Liver fibrosis was estimated by measuring liver stiffness(LS) with transient elastography (TE). RESULTS Prevalence of significant LS using cutoff values of TE of 8 and 9.1kPa was increased in high-risk compared with moderate or former drinkers and lifetime abstainers. In subjects with alcohol consumption, LS was associated with male gender, AST, ALT, years of consumption, and MS. In high-risk drinkers, MS and intensity of consumption were the only factors associated with significant LS (OR 3.7 and 4.6 for LS ≥ 8 kPa and 3.9 and 9.2 kPa for LS ≥ 9.1 kPa, respectively). Presence of significant liver fibrosis in the liver biopsy was higher among high-risk as compared with moderate or former drinkers. CONCLUSION MS increases the risk of liver fibrosis in subjects with alcohol consumption. Among high-risk drinkers, only MS and consumption of high amount of alcohol are associated with risk of liver fibrosis.

Apresentação do Volume 8, Número 15, janeiro/junho de 2021De comunidades y campesinos.Cambio social y movilización colectiva en las sociedades rurales

Diagnosis of sinusoidal obstruction syndrome (SOS) after hematopoietic cell transplantation (HCT) is based on clinical criteria including weight gain, ascites, hepatomegaly, and jaundice.[1] However, clinical and histological features and prognosis of SOS after liver transplantation (LT) seem to differ from SOS after HCT.[2, 3] We aimed to determine the characteristics and outcomes of SOS after LT.

BOOK REVIEWS / CRÍTICA DE LIBROS / CRÍTICA DE LIVROS Paul Warde: The Invention of Sustainability: Nature and Destiny, c. 1500-1870 Simone Gingrich & Juan Infante Amate Jesús Fernández Fernández and Margarita Fernández Mier (Eds.): The Archaeology of Medieval Villages Currently Inhabited in Europe Christopher Dyer Giacomo Bonan: The State in the Forest: Contested Commons in the Nineteenth Century Venetian Alps Iñaki Iriarte Goñi Rosa Congost, Jorge Gelman and Rui Santos (Eds.): Property Rights in Land: Issues in Social, Economic and Global History Francisco J. Beltrán Tapia Alessandro Carassale, Claudio Littardi and Irma Naso (Ed.): Fichi: Storia, economia, tradizioni / Figs: History, Economy, Traditions Claudio Lorenzini Sandra Kuntz-Ficker (Ed.): The First Export Era Revisited: Reassessing its Contributions to Latin American Economies Vicente Pinilla Laurent Herment (Dir.): Histoire rurale de l’Europe, XVIe-XXe siècle Juan Pan-Montojo Édouard Lynch: Insurrections paysannes: De la terre à la rue. Usages de la violence au XXe siècle Alba Díaz-Geada Stéphane Le Bras: Le négoce des vins en Languedoc: L’emprise du marché, 1900-1970 Llorenç Ferrer-Alòs José Ignacio Cubero: Historia general de la agricultura: De los pueblos nómadas a la biotecnología Maria Antònia Martí Escayol Dale Tomich: Espacios de esclavitud: Tiempo/tiempos del capital Antonio Santamaría

Introduction Diagnosis of severe hepatitis C recurrence is based on analytical and histological criteria but there is little information about their correlation. Aim To assess the accuracy of laboratory criteria for the diagnosis of fibrosing cholestatic hepatitis (FCH). Patients and methods Retrospective analysis of prospectively collected data form HCV positive patients who underwent liver transplantation (LT) between 2000 and 2014 in two European university hospitals. Patients were classified according to laboratory criteria such as FCH, cholestatic hepatitis (CH) and non-cholestatic acute hepatitis (NCAH). Histological characteristics were also evaluated. Results Seventy patients with acute HCV recurrence within the first year after LT with an available liver biopsy were included in the study. Most patients were male (70%) with a median age of 58 years (50–64) and infected with genotype 1b (71.4%). Median time from LT to diagnosis of recurrence was 2.96 months (2.1–5.3). Thirty-nine patients were classified as FCH, 21 as CH and 10 as NCAH. Marked hepatocyte ballooning and ductular reaction were associated with the presence of FCH with an OR of 4.66 (p = 0.047) and 20.58 (p = 0.025), respectively. Considering liver biopsy as the gold standard, the sensitivity, specificity, positive and negative predictive values of the analytical criteria were 0.8, 0.5, 0.3 and 0.9, respectively. However, correlation between histological and analytical criteria was poor (k = 0.033). Discussion Analytical criteria may be used to rule out the presence of FCH, but a biopsy is mandatory to confirm the diagnosis. Ductular reaction and hepatocyte ballooning were independent predictors of FCH.

Median nerve somatosensory evoked potentials (SEPs) may present changes during cavernous malformation (CM) resection unrelated to new post-operative sensory deficits. We performed intraoperative neurophysiological monitoring of median SEPs (m-SEPs) in three patients who underwent CM resection (surgery) near the sensory-motor cortex. The only preoperative clinical manifestations in all patients were seizures. All patients presented m-SEPs alterations on the side of the lesion during the procedure. Two patients presented permanent changes in the cortical potentials. In the third patient, the cortical and subcortical components suffered temporal fluctuations to return to baselines at the end of the surgery. None of these patients developed new post-operative clinical deficits. During brain cavernous malformation resection, significant fluctuations in the amplitude of different components of m-SEPs may occur. These changes may be due to excitability variations on m-SEP generators and do not translate into new post-operative neurological deficits.

[Background & Aims] Porto-sinusoidal vascular disease (PSVD) is a rare vascular liver disease of unknown etiology that causes portal hypertension. It usually affects young individuals and shortens live expectancy. The deregulated pathways involved in PSVD development are unknown and therefore we lack curative treatments. The purpose of this study was to integrate transcriptomic and clinical data by comprehensive network-based modeling in order to uncover altered biological processes in patients with PSVD., [Methods] We obtained liver tissue samples from 20 consecutive patients with PSVD and 21 sex- and age-matched patients with cirrhosis and 13 histologically normal livers (HNL) (initial cohort) and performed transcriptomic analysis. Microarray data were analyzed using weighted gene correlation network analysis to identify clusters of highly correlated genes differently expressed in patients with PSVD. We next evaluated the molecular pathways enriched in patients with PSVD and the core-related genes from the most significantly enriched pathways in patients with PSVD. Our main findings were validated using RNA sequencing in a different cohort of PSVD, cirrhosis and HNL (n = 8 for each group)., [Results] Patients with PSVD have a distinctive genetic profile enriched mainly in canonical pathways involving hemostasis and coagulation but also lipid metabolism and oxidative phosphorylation. Serpin family (SERPINC1), the apolipoproteins (APOA, APOB, APOC), ATP synthases (ATP5G1, ATP5B), fibrinogen genes (FGB, FGA) and alpha-2-macroglobulin were identified as highly connective genes that may have an important role in PSVD pathogenesis., [Conclusion] PSVD has a unique transcriptomic profile and we have identified deregulation of pathways involved in vascular homeostasis as the main pathogenic event of disease development. [Lay summary] Porto-sinusoidal vascular disease is a rare but life-shortening disease that affects mainly young people. Knowledge of the disrupted pathways involved in its development will help to identify novel therapeutic targets and new treatments. Using a systems biology approach, we identify that pathways regulating endothelial function and tone may act as drivers of porto-sinusoidal vascular disease., This study was supported by the Instituto de Salud Carlos III FIS PI17/00398, the Ministry of Education and Science, Spain (SAF-2016-75767-R); Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR-SGR2017-517) a grant from Generalitat de Catalunya, Fondo Europeo de Desarrollo Regional (FEDER) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), funded by Instituto de Salud Carlos III. Marta Magaz is a recipient of a Río Hortega grant from Instituto de Salud Carlos III. Pol Olivas has been funded by Contractes Clínic de Recerca ”Emili Letang-Josep Font’’ 2020, granted by Hospital Clínic de Barcelona.

The molecular mechanisms driving the progression from early-chronic liver disease (CLD) to cirrhosis and, finally, acute-on-chronic liver failure (ACLF) are largely unknown. Our aim was to develop a protein network-based approach to investigate molecular pathways driving progression from early-CLD to ACLF.Transcriptome analysis was performed on liver biopsies from patients at different liver disease stages, including fibrosis, compensated cirrhosis, decompensated cirrhosis and ACLF, and control healthy livers. We created 9 liver-specific disease-related protein-protein interaction networks capturing key pathophysiological processes potentially related to CLD. We used these networks as a framework and performed gene set-enrichment analysis (GSEA) to identify dynamic gene profiles of disease progression.Principal component analyses revealed that samples clustered according to the disease stage. GSEA of the defined processes showed an upregulation of inflammation, fibrosis and apoptosis networks throughout disease progression. Interestingly, we did not find significant gene expression differences between compensated and decompensated cirrhosis, while ACLF showed acute expression changes in all the defined liver disease-related networks. The analyses of disease progression patterns identified ascending and descending expression profiles associated with ACLF onset. Functional analyses showed that ascending profiles were associated with inflammation, fibrosis, apoptosis, senescence and carcinogenesis networks, while descending profiles were mainly related to oxidative stress and genetic factors. We confirmed by qPCR the upregulation of genes of the ascending profile and validated our findings in an independent patient cohort.ACLF is characterized by a specific hepatic gene expression pattern related to inflammation, fibrosis, apoptosis, senescence and carcinogenesis. Moreover, the observed profile is significantly different from that of compensated and decompensated cirrhosis, supporting the hypothesis that ACLF should be considered a distinct entity.By using transjugular biopsies obtained from patients at different stages of chronic liver disease, we unveil the molecular pathogenic mechanisms implicated in the progression of chronic liver disease to cirrhosis and acute-on-chronic liver failure. The most relevant finding in this study is that patients with acute-on-chronic liver failure present a specific hepatic gene expression pattern distinct from that of patients at earlier disease stages. This gene expression pattern is mostly related to inflammation, fibrosis, angiogenesis, and senescence and apoptosis pathways in the liver.

La Aplasia Medular pura de Celulas Rojas es un trastorno que se caracteriza por anemia con ausencia casi completa de precursores de celulas rojas en la medula osea, con contaje de leucocitos y plaquetas normales. La anemia de Diamond-Blackfan es un sindrome de insuficiencia de la medula osea caracterizada por anemia, reticulocitopenia y disminucion de precursores eritroides en la medula osea. Se presenta el caso de un lactante menor masculino de 2 meses de edad, sin antecedentes familiares ni perinatales de importancia, cuya madre evidencia palidez cutaneo mucosa progresiva asociado a hiporexia; acude a centro de salud donde realizan paraclinicos que reportan hemoglobina en 1,7g/dL. Se realiza frotis de sangre periferica donde se muestra serie eritroide francamente afectada con contaje granulocitico y megacariocitico normales; se realiza biopsia y aspirado de medula osea concluyendose aplasia medular de serie roja y en vista de otros hallazgos clinicos, se plantea posible anemia de Diamond-Blackfan. Se indica tratamiento con glucocorticoides, sin embargo por respuesta insuficiente, se inicia eritropoyetina aumentando dosis de forma progresiva, a pesar de la administracion de la misma, amerita transfusiones sanguineas de forma regular; se realizan estudios de compatibilidad con familiares de primer grado resultando positivos, actualmente es candidato a trasplante alogenico de medula osea. Se concluye que a pesar de corresponder a un sindrome poco frecuente, debe sospecharse ante la presencia de anemia severa, sin perdida sanguinea aguda y descarte previo de otras etiologias, ademas se plantea que el inicio oportuno del tratamiento es fundamental para la supervivencia de estos pacientes.

The aim of this article is to historize the transformations of the agrarian complex and of rural society in Galiza during Francoism, through the study of state policies regarding the agrarian spher...