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Diana Llopiz, Marta Ruiz, Lorea Villanueva, Tamara Iglesias, Leyre Silva, Josune Egea, Juan J Lasarte, Perrine Pivette, Véronique Trochon-Joseph, Bérangère Vasseur, Graham Dixon, Bruno Sangro, Pablo Sarobe
Immune checkpoint inhibitors are currently tested in different combinations in patients with advanced hepatocellular carcinoma (HCC). Nivolumab, an anti-PD-1 agent, has gained approval in the second-line setting in the USA. Epigenetic drugs have immune-mediated antitumor effects that may improve the activity of immunotherapy agents. Our aim was to study the therapeutic efficacy of checkpoint inhibitors (anti-CTLA-4 and anti-PD-1 antibodies) in combination with the histone deacetylase inhibitor (HDACi) Belinostat...
December 13, 2018: Cancer Immunology, Immunotherapy: CII
Pablo Burraco, Maider Iglesias-Carrasco, Carlos Cabido, Ivan Gomez-Mestre
Consequences of human actions like global warming, spread of exotic species or resource consumption are pushing species to extinction. Even species considered to be at low extinction risk often show signs of local declines. Here, we evaluate the impact of eucalypt plantations, the best-known exotic tree species worldwide and its interaction with temperature and predators on amphibian development, growth, antipredator responses and physiology. For this purpose, we applied a fully factorial experiment crossing two types of leaf litter (native oak or eucalypt), two temperatures (15 and 20°C) and presence/absence of native predators...
2018: Conservation Physiology
Mark Z Kos, Jubao Duan, Alan R Sanders, Lucy Blondell, Eugene I Drigalenko, Melanie A Carless, Pablo V Gejman, Harald H H Göring
The dopaminergic hypothesis of schizophrenia (SZ) postulates that positive symptoms of SZ, in particular psychosis, are due to disturbed neurotransmission via the dopamine (DA) receptor D2 (DRD2). However, DA is a reactive molecule that yields various oxidative species, and thus has important non-receptor-mediated effects, with empirical evidence of cellular toxicity and neurodegeneration. Here we examine non-receptor-mediated effects of DA on gene co-expression networks and its potential role in SZ pathology...
December 13, 2018: Translational Psychiatry
Naveed Akhtar, Saadat Kamran, Rajvir Singh, Rayaz A Malik, Dirk Deleu, Paula J Bourke, Sujatha Joseph, Mark D Santos, Deborah M Morgan, Faisal M Wadiwala, Reny Francis, Blessy M Babu, Pooja George, Rumissa Ibrahim, Pablo Garcia-Bermejo, Ashfaq Shuaib
BACKGROUND: Stroke in diabetics may delay recovery and increases the risk of early recurrence of stroke. We compared the outcomes of patients (with and without diabetes) admitted with an acute ischemic stroke (AIS) in the state of Qatar. PATIENTS AND METHODS: We prospectively compared the clinical presentation, complications, discharge outcome, and stroke recurrence at 90 days in patients with and without diabetes. RESULTS: Five thousand two hundred twenty-eight stroke patients were admitted between January 2014 and December 2017...
December 10, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Estrella Gómez-Tortosa, Yalda Baradaran-Heravi, Valentina González Alvarez, María José Sainz, Cristina Prieto-Jurczynska, Rosa Guerrero-López, Pablo Agüero Rabes, Christine Van Broeckhoven, Julie van der Zee, Alberto Rábano Gutiérrez
Frontotemporal lobar degeneration caused by GRN mutations is mainly associated with a TDP-43 type A proteinopathy. We present a family with autosomal dominant frontotemporal lobar degeneration caused by a novel GRN nonsense mutation (c.5G>A: p.Trp2*) in which the proband's brain also showed prominent glial tauopathy consistent with an aging-related tau astrogliopathy. Astrocytic tauopathy, 4R(+) and 3R(-) immunoreactive, was characterized by thorn-shaped astrocytes present in subpial, subependymal, and perivascular areas, and in gray matter; plus granular or fuzzy tau immunoreactivity in astrocytic processes in gray matter, either solitary or clustered in different regions...
November 20, 2018: Neurobiology of Aging
Antonio Scarano, Francesco Carinci, Felice Lorusso, Felice Festa, Lorenzo Bevilacqua, Pablo Santos de Oliveira, Michele Maglione
Background : Piezosurgery is a surgical procedure that is able to perform osteotomies by a micrometric and selective cut of the bone tissue. The objective of this investigation was to evaluate two different techniques; an ultrasonic device, and a drill approach for implant site preparation. Methods : A total of fifty patients were recruited for the randomized clinical trial to receive dental implants for fixed prosthetic restoration in the posterior mandible and were allotted to two groups. In Group A the implant site was prepared following a drilling technique, while in Group B the implant site was prepared using an ultrasonic device; moreover, the operative duration was recorded...
December 11, 2018: Materials
Tarra L Penney, Thomas Burgoine, Pablo Monsivais
Eating away from home is a risk factor for poor diet quality and obesity. With an ever-increasing proportion of household food spend directed toward eating out, the proliferation of these food establishments may contribute to their use, a potential precursor to less healthy food choices and low overall diet quality. However few studies are conducted at the national level and across a range of away from home food sources. The purpose of this study was to examine the association between the density of away from home food establishments (e...
December 11, 2018: International Journal of Environmental Research and Public Health
Lucas A Defelipe, Juan Pablo Arcon, Carlos P Modenutti, Marcelo A Marti, Adrián G Turjanski, Xavier Barril
Simulations of molecular dynamics (MD) are playing an increasingly important role in structure-based drug discovery (SBDD). Here we review the use of MD for proteins in aqueous solvation, organic/aqueous mixed solvents (MDmix) and with small ligands, to the classic SBDD problems: Binding mode and binding free energy predictions. The simulation of proteins in their condensed state reveals solvent structures and preferential interaction sites (hot spots) on the protein surface. The information provided by water and its cosolvents can be used very effectively to understand protein ligand recognition and to improve the predictive capability of well-established methods such as molecular docking...
December 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Pedro Reis Costa, Pablo Estevez, David Castro, Lucía Soliño, Neide Gouveia, Carolina Santos, Susana Margarida Rodrigues, José Manuel Leao, Ana Gago-Martínez
Ciguatoxins (CTXs), endemic from tropical and subtropical regions of the Pacific and Indian Ocean and the Caribbean Sea, have caused several human poisonings during the last decade in Europe. Ciguatera fish poisonings (CFP) in Madeira and Canary Islands appear to be particularly related with consumption of fish caught close to Selvagens Islands, a Portuguese natural reserve composed of three small islands that harbor high fish biomass. In this study, fish specimens considered as potential vectors of CTXs were caught in Madeira and Selvagens archipelagos for toxins determination via sensitive liquid chromatography with tandem mass spectrometry detection (LC⁻MS/MS)...
December 7, 2018: Toxins
Pablo Luis B Figueiredo, Laine C Pinto, Jamile S da Costa, Alberto Ray C da Silva, Rosa Helena V Mourão, Raquel C Montenegro, Joyce Kelly R da Silva, José Guilherme S Maia
ETHNOPHARMACOLOGICAL RELEVANCE: Oils and extracts of Eugenia uniflora have been reported as antimicrobial, antifungal, antinociceptive, antiprotozoal, antioxidant and cytotoxic. AIM OF THE STUDY: The oils of five specimens (E1 to E5) that occur in the Brazilian Amazon were extracted, analyzed for their chemical composition, and submitted to antioxidant and cytotoxic assays. MATERIAL AND METHODS: Oils were hydrodistilled, analyzed by GC and GC-MS, and submitted to PCA and HCA analyses...
December 10, 2018: Journal of Ethnopharmacology
Viola Schmelter, Lena Antonaci, Susanne Fröhlich, Diran Herebian, Pablo Verde, Martin Heil, Thomas Hoehn
This study assesses the impact of prenatal stress and intrauterine growth restriction (IUGR) on the dehydroepiandrosterone (DHEA) and dehydroepiandrosteronesulfate (DHEAS) concentrations in nails of newborns. Nail samples were gained from 56 newborn infants. The concentration of DHEA and DHEAS was measured by liquid chromatography/tandem mass spectrometry. Prenatal stress was assessed by the Prenatal Distress Questionnaire and by the Life Experience Survey. Prenatal stress was not associated with infant nail DHEA or DHEAS concentrations...
December 10, 2018: Biological Psychology
A V L Freitas, R R Ramos, K L Silva-Brandão, N Coutouné, L M Magaldi, J L Pablos, N Rosser, K S Brown
The present paper describes Heliconius hermathena curua Freitas & Ramos ssp. nov. This subspecies exhibits a non-mimetic phenotype typical of H. hermathena, but is characterized by the merging of the yellow streak over the forewing cubitus with the red postmedian band in the dorsal forewing. The subspecies is known from two localities in the south of Altamira, Pará State, Brazil, where it inhabits an isolated patch of "campina" vegetation more than 600 km from the nearest known H. hermathena populations...
December 12, 2018: Neotropical Entomology
Pablo Ferreira-Chamorro, Alejandro Redondo, Gabriela Riego, Sergi Leánez, Olga Pol
Chronic neuropathic pain is associated with anxiety- and depressive-like disorders. Its treatment remains a serious clinical problem due to the lack of efficacy of the available therapeutic modalities. We investigated if the activation of the transcription factor Nrf2 could modulate the nociceptive and emotional disorders associated with persistent neuropathic pain and potentiated the analgesic activity of morphine. The possible mechanisms implicated in these effects have been also evaluated. Therefore, in C57BL/6 mice with neuropathic pain induced by the chronic constriction of the sciatic nerve (CCI), we assessed the antinociceptive, anxiolytic, and anti-depressant effects of the repeated intraperitoneal administration of a Nrf2 inducer, sulforaphane (SFN), and the effects of this treatment on the local antinociceptive actions of morphine...
2018: Frontiers in Pharmacology
Lara Valiño-Rivas, Leticia Cuarental, Mateo Agustin, Holger Husi, Pablo Cannata-Ortiz, Ana B Sanz, Harald Mischak, Alberto Ortiz, Maria Dolores Sanchez-Niño
Background: Mutations in Melanoma Antigen-encoding Gene D2 (MAGED2) promote tubular dysfunction, suggesting that MAGE proteins may play a role in kidney pathophysiology. We have characterized the expression and regulation of MAGE genes in normal kidneys and during kidney disease. Methods: The expression of MAGE genes and their encoded proteins was explored by systems biology multi-omics (kidney transcriptomics and proteomics) in healthy adult murine kidneys and following induction of experimental acute kidney injury (AKI) by a folic acid overdose...
December 11, 2018: Nephrology, Dialysis, Transplantation
Juan Pablo Gomez, Dawn M Nekorchuk, Liang Mao, Sadie J Ryan, José Miguel Ponciano, Jason K Blackburn
Quantitative models describing environmentally-mediated disease transmission rarely focus on the independent contribution of recruitment and the environment on the force of infection driving outbreaks. In this study we attempt to investigate the interaction between external factors and host's population dynamics in determining the outbreaks of some indirectly transmitted diseases. We first built deterministic and stochastic compartmental models based on anthrax which were parameterized using information from literature and complemented with field observations...
2018: PloS One
Lourdes Vicent, Alberto Esteban-Fernández, Manuel Gómez-Bueno, Javier De-Juan, Pablo Díez-Villanueva, Ángel Manuel Iniesta, Ana Ayesta, Hugo González-Saldívar, Antonio Rojas-González, Ramón Bover-Freire, Diego Iglesias, Marcos García-Aguado, Jesús A Perea-Egido, Manuel Martínez-Sellés
Sacubitril/valsartan (SV) is a new therapy in heart failure with reduced ejection fraction. Our aim was to determine the efficacy and safety of this drug daily clinical practice.We performed a multicenter registry in 10 hospitals. All patients who started SV from October 2016 to March 2017 on an outpatient basis were included.A total of 427 patients started treatment with SV. Mean follow-up was 7.0±0.1 months. Forty-nine patients (11.5%) discontinued SV, and 12 (2.8%) died. SV discontinuation was associated with higher cardiovascular (hazard ratio [HR] 13...
December 10, 2018: Journal of Cardiovascular Pharmacology
Rosa Martin-Mateos, Thiago M De Assuncao, Juan Pablo Arab, Nidhi Jalan-Sakrikar, Usman Yaqoob, Thomas Greuter, Vikas K Verma, Angela J Mathison, Sheng Cao, Gwen Lomberk, Philippe Mathurin, Raul Urrutia, Robert C Huebert, Vijay H Shah
BACKGROUND & AIMS: Transdifferentiation of hepatic stellate cells (HSCs) into myofibroblasts is a key event in the pathogenesis of liver fibrosis. Transforming growth factor β (TGF-β) and platelet-derived growth factor (PDGF) are canonical HSC activators after liver injury. The aim of this study was to analyze the epigenetic modulators that differentially control TGF-β and PDGF signaling pathways. METHODS: We performed a transcriptomic comparison of HSCs treated with TGF-β or PDGF-BB using RNA sequencing...
September 15, 2018: Cellular and Molecular Gastroenterology and Hepatology
Renata L Markman, Liana P Webber, Carlos H V Nascimento Filho, Leonardo A Reis, Pablo A Vargas, Marcio A Lopes, Virgilio Zanella, Manoela D Martins, Cristiane H Squarize, Rogerio M Castilho
PURPOSE: Emerging evidence indicates that bromodomains comprise a conserved class of epigenome readers involved in cancer development and inflammation. Bromodomains are associated with epigenetic modifications of gene transcription through interactions with lysine residues of histone tails. Particularly, the bromodomain and extra-terminal domain (BET) family member BRD4 has been found to be involved in the control over oncogenes, including c-MYC, and in the maintenance of downstream inflammatory processes...
December 11, 2018: Cellular Oncology (Dordrecht)
Marcos Jordan, Xavier Aguilera, José Carlos González, Pablo Castillón, Mónica Salomó, José Antonio Hernández, Leonardo Ruiz, José Maria Mora, Pilar Camacho-Carrasco, Salvi Prat-Fabregat, Alba Bosch, Ainhoa Rodriguez-Arias, María José Martínez-Zapata
INTRODUCTION: We assessed the efficacy of fibrin sealant (FS) and tranexamic acid (TXA) administered topically in patients with a hip fracture treated with prosthetic replacement. MATERIALS AND METHODS: Parallel, multicentre, open label, randomised, clinical trial. We compared three interventions to reduce blood loss: (1) 10 ml of FS, (2) 1 g of topical TXA, both administered at the end of the surgery, and (3) usual haemostasis (control group). The main outcome was blood loss collected in drains...
December 11, 2018: Archives of Orthopaedic and Trauma Surgery
Elena Garcia-Martin, Laura Jarauta, Elisa Vilades, Jose Ramon Ara, Jesus Martin, Vicente Polo, Jose Manuel Larrosa, Luis Emilio Pablo, Maria Satue
Purpose: To evaluate the ability of new swept-source (SS) optical coherence tomography (OCT) technology to detect changes in retinal and choroidal thickness in patients with multiple sclerosis (MS). Methods: A total of 101 healthy and 97 MS eyes underwent retinal and choroidal assessment using SS Triton OCT (Topcon). Macular thickness and peripapillary data (retinal, ganglion cell layer (GCL+, GCL++) and retinal nerve fiber layer (RNFL) thickness) were analyzed, including choroidal thickness evaluation...
2018: Journal of Ophthalmology
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