Una nueva estela funeraria de época romana descubierta en Malpartida de Cáceres

We present one of the most important findings of the archaeological developments in 2007 on the site of the «Dehesa de Los Estantes», in the municipality of Malpartida de Cáceres: A tall granite stele with a triangular pediment containing the epitaph of a woman, dedicated to her by her husband, both of indigenous origin. In addition, the inscribed message is surrounded by a rich set of iconographic elements. The chronology proposed for this monumentum is the third century AD.Presentamos aquí uno de los hallazgos más relevantes de la intervención arqueológica desarrollada durante el año 2007 en el paraje de la «Dehesa de Los Estantes», dentro del término municipal de Malpartida de Cáceres: una «esbelta» estela granítica de cabecera triangular que contiene el epitafio de una mujer y la dedicatoria de su esposo, ambos de extracción indígena. Además, el mensaje textual va reforzado por un rico conjunto de elementos iconográficos. La cronología que proponemos para el monumentum es el siglo III d.C.We present one of the most important findings of the archaeological developments in 2007 on the site of the «Dehesa de Los Estantes», in the municipality of Malpartida de Cáceres: A tall granite stele with a triangular pediment containing the epitaph of a woman, dedicated to her by her husband, both of indigenous origin. In addition, the inscribed message is surrounded by a rich set of iconographic elements. The chronology proposed for this monumentum is the third century AD

Mediterranean diet and olive oil, microbiota, and obesity-related cancers. From mechanisms to prevention

Olive oil (OO) is the main source of added fat in the Mediterranean diet (MD). It is a mix of bioactive compounds, including monounsaturated fatty acids, phytosterols, simple phenols, secoiridoids, flavonoids, and terpenoids. There is a growing body of evidence that MD and OO improve obesity-related factors. In addition, obesity has been associated with an increased risk for several cancers: endometrial, oesophageal adenocarcinoma, renal, pancreatic, hepatocellular, gastric cardia, meningioma, multiple myeloma, colorectal, postmenopausal breast, ovarian, gallbladder, and thyroid cancer. However, the epidemiological evidence linking MD and OO with these obesity-related cancers, and their potential mechanisms of action, especially those involving the gut microbiota, are not clearly described or understood. The goals of this review are 1) to update the current epidemiological knowledge on the associations between MD and OO consumption and obesity-related cancers, 2) to identify the gut microbiota mechanisms involved in obesity-related cancers, and 3) to report the effects of MD and OO on these mechanisms

E-cadherin expression is associated with somatostatin analogue response in acromegaly

Acromegaly is a rare disease resulting from hypersecretion of growth hormone (GH) and insulin‐like growth factor 1 (IGF1) typically caused by pituitary adenomas, which is associated with increased mortality and morbidity. Somatostatin analogues (SSAs) represent the primary medical therapy for acromegaly and are currently used as first‐line treatment or as second‐line therapy after unsuccessful pituitary surgery. However, a considerable proportion of patients do not adequately respond to SSAs treatment, and therefore, there is an urgent need to identify biomarkers predictors of response to SSAs. The aim of this study was to examine E‐cadherin expression by immunohistochemistry in fifty‐five GH‐producing pituitary tumours and determine the potential association with response to SSAs as well as other clinical and histopathological features. Acromegaly patients with tumours expressing low E‐cadherin levels exhibit a worse response to SSAs. E‐cadherin levels are associated with GH‐producing tumour histological subtypes. Our results indicate that the immunohistochemical detection of E‐cadherin might be useful in categorizing acromegaly patients based on the response to SSAs.ISCIII‐Subdirección General de Evaluación y Fomento de la Investigación PI13/02043 PI16/00175FEDER PI13/02043 PI16/00175Junta de Andalucía A‐0023‐2015 A‐0003‐2016 CTS‐1406 BIO‐0139Andalusian Ministry of Health C‐0015‐2014CIBERobn PI13/ 02043 PI16/0017

A Slow-Digesting Carbohydrate Diet during Rat Pregnancy Protects O spring from Non-Alcoholic Fatty Liver Disease Risk through the Modulation of the Carbohydrate-Response Element and Sterol Regulatory Element Binding Proteins

High-fat (HF) and rapid digestive (RD) carbohydrate diets during pregnancy promote excessive adipogenesis in o spring. This e ect can be corrected by diets with similar glycemic loads, but low rates of carbohydrate digestion. However, the e ects of these diets on metabolic programming in the livers of o spring, and the liver metabolism contributions to adipogenesis, remain to be addressed. In this study, pregnant insulin-resistant rats were fed high-fat diets with similar glycemic loads but di erent rates of carbohydrate digestion, High Fat-Rapid Digestive (HF–RD) diet or High Fat-Slow Digestive (HF–SD) diet. O spring were fed a standard diet for 10 weeks, and the impact of these diets on the metabolic and signaling pathways involved in liver fat synthesis and storage of o spring were analyzed, including liver lipidomics, glycogen and carbohydrate and lipid metabolism key enzymes and signaling pathways. Livers from animals whose mothers were fed an HF–RD diet showed higher saturated triacylglycerol deposits with lower carbon numbers and double bond contents compared with the HF–SD group. Moreover, the HF–RD group exhibited enhanced glucose transporter 2, pyruvate kinase (PK), acetyl coenzyme A carboxylase (ACC) and fatty acid (FA) synthase expression, and a decrease in pyruvate carboxylase (PyC) expression leading to an altered liver lipid profile. These parameters were normalized in the HF–SD group. The changes in lipogenic enzyme expression were parallel to changes in AktPKB phosphorylation status and nuclear expression in carbohydrate-response element and sterol regulatory element binding proteins. In conclusion, an HF–RD diet during pregnancy translates to changes in liver signaling and metabolic pathways in o spring, enhancing liver lipid storage and synthesis, and therefore non-alcoholic fatty liver disease (NAFLD) risk. These changes can be corrected by feeding an HF–SD diet during pregnancy.This research was funded by the European Union’s Seventh Framework Programme (FP7/2007–2013): project EarlyNutrition, under grant agreement no. 289346

Neurocognitive Function in Acromegaly after Surgical Resection of GH-Secreting Adenoma versus Naïve Acromegaly

Patients with active untreated acromegaly show mild to moderate neurocognitive disorders that are associated to chronic exposure to growth hormone (GH) and insulin-like growth factor (IGF-I) hypersecretion. However, it is unknown whether these disorders improve after controlling GH/IGF-I hypersecretion. The aim of this study was to compare neurocognitive functions of patients who successfully underwent GH-secreting adenoma transsphenoidal surgery (cured patients) with patients with naive acromegaly. In addition, we wanted to determine the impact of different clinical and biochemical variables on neurocognitive status in patients with active disease and after long-term cure. A battery of six standardized neuropsychological tests assessed attention, memory and executive functioning. In addition, a quantitative electroencephalography with Low-Resolution Electromagnetic Tomography (LORETA) solution was performed to obtain information about the neurophysiological state of the patients. Neurocognitive data was compared to that of a healthy control group. Multiple linear regression analysis was also conducted using clinical and hormonal parameters to obtain a set of independent predictors of neurocognitive state before and after cure. Both groups of patients scored significantly poorer than the healthy controls on memory tests, especially those assessing visual and verbal recall. Patients with cured acromegaly did not obtain better cognitive measures than naïve patients. Furthermore memory deficits were associated with decreased beta activity in left medial temporal cortex in both groups of patients. Regression analysis showed longer duration of untreated acromegaly was associated with more severe neurocognitive complications, regardless of the diagnostic group, whereas GH levels at the time of assessment was related to neurocognitive outcome only in naïve patients. Longer duration of post-operative biochemical remission of acromegaly was associated with better neurocognitive state. Overall, this data suggests that the effects of chronic exposure to GH/IGF-I hypersecretion could have long-term effects on brain functions. © 2013 Martín-Rodríguez et al.Funding for this project was provided by an R&D grant from Novartis Oncology and the Plan Andaluz de Investigación (CTS-444). DAC was supported by the “Ramón y Cajal” program (RYC-2006-001071) of the Spanish Ministry of Science and Innovation.Peer Reviewe

Urine Phenylacetylglutamine Determination in Patients with Hyperphenylalaninemia

Phenylketonuria (PKU), an autosomal-recessive inborn error of phenylalanine (Phe) metabolism is the most prevalent disorder of amino acid metabolism. Currently, clinical follow-up relies on frequent monitoring of Phe levels in blood. We hypothesize that the urine level of phenylacetylglutamine (PAG), a phenyl-group marker, could be used as a non-invasive biomarker. In this cross-sectional study, a validated liquid chromatography coupled to tandem mass spectrometry (LC-MS) method was used for urinary PAG quantification in 35 participants with hyperphenylalaninemia (HPA) and 33 age- and sex-matched healthy controls. We have found that (a) PKU patients present higher urine PAG levels than healthy control subjects, and that (b) there is a significant correlation between urine PAG and circulating Phe levels in patients with HPA. In addition, we show a significant strong correlation between Phe levels from venous blood samples and from capillary finger-prick dried blood spot (DBS) samples collected at the same time in patients with HPA. Further research in order to assess the potential role of urine PAG as a non-invasive biomarker in PKU is warranted.Funding: J.d.l.H. acknowledges the Biocruces Bizkaia Health Research Institute contract for Intensification of Research Activities. This work was partially funded by the Basque Department of Education (IT1281-19). The chemical analysis and the preparation of the manuscript were partially financed by Biocruces Bizkaia Health Research Institute and Carlos III Health Research Institutes. Acknowledgments: The authors thank the patients with hyperphenylalaninemia and healthy volunteers for their kind participation. We thank the Association for those affected by phenylketonuria of the Basque Country (Euskadi PKU-OTM Elkartea) for their collaboration. J.d.l.H., L.C., N.L.-O., G.F., A.A. and M.U. are members of the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN)—Project ID No. 739543

A Metabolomics Signature Linked To Liver Fibrosis In The Serum Of Transplanted Hepatitis C Patients

Liver fibrosis must be evaluated in patients with hepatitis C virus (HCV) after liver transplantation because its severity affects their prognosis and the recurrence of HCV. Since invasive biopsy is still the gold standard to identify patients at risk of graft loss from rapid fibrosis progression, it becomes crucial the development of new accurate, non-invasive methods that allow repetitive examination of the patients. Therefore, we have developed a non-invasive, accurate model to distinguish those patients with different liver fibrosis stages. Two hundred and three patients with HCV were histologically classified (METAVIR) into five categories of fibrosis one year after liver transplantation. In this cross-sectional study, patients at fibrosis stages F0-F1 (n = 134) were categorised as "slow fibrosers" and F2-F4 (n = 69) as "rapid fibrosers". Chloroform/methanol serum extracts were analysed by reverse ultra-high performance liquid chromatography coupled to mass spectrometry. A diagnostic model was built through linear discriminant analyses. An algorithm consisting of two sphingomyelins and two phosphatidylcholines accurately classifies rapid and slow fibrosers after transplantation. The proposed model yielded an AUROC of 0.92, 71% sensitivity, 85% specificity, and 84% accuracy. Moreover, specific bile acids and sphingomyelins increased notably along with liver fibrosis severity, differentiating between rapid and slow fibrosers

Stabilization of LKB1 and Akt by neddylation regulates energy metabolism in liver cancer

The current view of cancer progression highlights that cancer cells must undergo through a post-translational regulation and metabolic reprogramming to progress in an unfriendly environment. In here, the importance of neddylation modification in liver cancer was investigated. We found that hepatic neddylation was specifically enriched in liver cancer patients with bad prognosis. In addition, the treatment with the neddylation inhibitor MLN4924 in Phb1-KO mice, an animal model of hepatocellular carcinoma showing elevated neddylation, reverted the malignant phenotype. Tumor cell death in vivo translating into liver tumor regression was associated with augmented phosphatidylcholine synthesis by the PEMT pathway, known as a liver-specific tumor suppressor, and restored mitochondrial function and TCA cycle flux. Otherwise, in protumoral hepatocytes, neddylation inhibition resulted in metabolic reprogramming rendering a decrease in oxidative phosphorylation and concomitant tumor cell apoptosis. Moreover, Akt and LKB1, hallmarks of proliferative metabolism, were altered in liver cancer being new targets of neddylation. Importantly, we show that neddylation-induced metabolic reprogramming and apoptosis were dependent on LKB1 and Akt stabilization. Overall, our results implicate neddylation/signaling/metabolism, partly mediated by LKB1 and Akt, in the development of liver cancer, paving the way for novel therapeutic approaches targeting neddylation in hepatocellular carcinoma

Stabilization of LKB1 and Akt by neddylation regulates energy metabolism in liver cancer

The current view of cancer progression highlights that cancer cells must undergo through a post-translational regulation and metabolic reprogramming to progress in an unfriendly environment. In here, the importance of neddylation modification in liver cancer was investigated. We found that hepatic neddylation was specifically enriched in liver cancer patients with bad prognosis. In addition, the treatment with the neddylation inhibitor MLN4924 in Phb1-KO mice, an animal model of hepatocellular carcinoma showing elevated neddylation, reverted the malignant phenotype. Tumor cell death in vivo translating into liver tumor regression was associated with augmented phosphatidylcholine synthesis by the PEMT pathway, known as a liver-specific tumor suppressor, and restored mitochondrial function and TCA cycle flux. Otherwise, in protumoral hepatocytes, neddylation inhibition resulted in metabolic reprogramming rendering a decrease in oxidative phosphorylation and concomitant tumor cell apoptosis. Moreover, Akt and LKB1, hallmarks of proliferative metabolism, were altered in liver cancer being new targets of neddylation. Importantly, we show that neddylation-induced metabolic reprogramming and apoptosis were dependent on LKB1 and Akt stabilization. Overall, our results implicate neddylation/signaling/metabolism, partly mediated by LKB1 and Akt, in the development of liver cancer, paving the way for novel therapeutic approaches targeting neddylation in hepatocellular carcinoma

Plataformes digitals BigTech del sistema educatiu català i drets de la infància: amenaces i reptes

L'informe és el resultat de l'execució del projecte EdDiT “Corporacions tecnològiques, plataformes educatives digitals i garantia dels drets de la infància amb enfocament de gènere (ACCD, 2022-23)”, per part del grup de recerca consolidat Esbrina (2021 SGR 686 -UB) de la Universitat de Barcelona.Podeu consultar la versió en castellà a recurs relacionat[cat] L'actual procés de digitalització de l'educació està marcat per la presència de plataformes digitals de corporacions tecnològiques o BigTech en un nombre creixent de centres educatius. Aquest procés de plataformizació, intensificat durant la pandèmia de la COVID-19, genera múltiples desafiaments per a l'Administració pública i, en particular, per als sistemes educatius, principalment vinculats a la seva capacitat de garantir l'alfabetització digital, l'accés al coneixement, la protecció dels drets de la infància, l'equitat de gènere i, en general, el benestar de la comunitat educativa. En aquest escenari sorgeix el projecte edDIT (Corporacions tecnològiques, plataformes educatives digitals i garantia dels drets de la infància amb enfocament de gènere), l'objectiu principal del qual ha estat explorar i analitzar les percepcions i opinions de persones expertes, dels diversos agents de la comunitat educativa (professionals de l'educació, famílies i alumnat) en relació amb l'ús de plataformes digitals als centres educatius i amb els seus potencials efectes sobre els drets de la infància. Amb aquesta finalitat, s’ha desenvolupat una recerca basada en un disseny mixt que ha inclòs la realització de 20 entrevistes (14 amb persones expertes en l'àmbit de l'educació i la tecnologia digital i 6 amb representants d'equips directius de centres educatius), de 16 grups de discussió (8 amb docents i 8 amb alumnat), de l'aplicació d'una enquesta a 2.330 famílies d'alumnat matriculat en centres educatius públics de Catalunya, i de l'anàlisi de les condicions d'ús de les principals plataformes digitals corporatives presents als centres educatius catalans. Per a l'anàlisi de les evidències recollides s’han identificat sis dimensions de dret i protecció de la infància en entorns digitals. Aquestes dimensions s'han desenvolupat discursivament articulant l'evidència generada en cadascuna de les fases de la recerca. Els resultats mostren que els drets de la infància estan sent potencialment afectats per la presència de les plataformes digitals corporatives als centres educatius. Davant això, es proposa una major implicació de l'Administració pública a l'hora de garantir un ús més segur d'aquests recursos en educació, que asseguri i promogui els drets de la infància.Financiado por la Agència Catalana de Cooperació al Desenvolupament (ACCD) (subvenciones a proyectos de desarrollo y educación para el desarrollo, convocatoria 2021 ACC145/21/000103)