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Treatment of chronic hepatitis C with direct-acting antivirals: The role of resistance

World Journal of Gastroenterology 2016年第29期22卷 6573-6581页

作者： Miguel Jiménez-Pérez Rocío González-Grande pilar espana contreras Isabel Pinazo Martínez Jesús de la Cruz Lombardo Raúl Olmedo Martín UGC de Aparato Digestivo Unidad de Hepatologia-Trasplante Hepatico Hospital Universitario Regional de Malaga 29010 Malaga Spain Liver transplantation and hepatology unit UGC de Aparato Digestivo Hospital Regional Universitario 29010 Malaga Spain

The use of direct-acting antivirals(DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response(around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants(RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These preexisting RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined.

关键词： Direct-acting antivirals Resistance Treatment Hepatitis C virus

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Remediation of amide pesticide-polluted soils by combined solarization and ozonation treatment

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Pedosphere 2024年第3期34卷 641-651页

作者： Isabel GARRIDO Carmen MMARTINEZ pilar FLORES pilar HELLIN Fulgencio contreras Jose FENOLL Department of Sustainability and Quality Group of Fruit and Vegetable Products Instituto Murciano de Investigacion y Desarrollo Agrario y MedioambientalLa Alberca 30150(Spain)

Agriculture has a close relationship with nature,but it can also be the source of negative and permanent environmental *** use of pesticides in modern agriculture is a common practice,but their side effects on the environment cannot be *** this study,we evaluated a combination of solarization and ozonation techniques for the elimination of six amide pesticides(boscalid,chlorantraniliprole,cyflufenamid,fluopyram,napropamide,and propyzamide)in *** experiments were performed with four different soils to assess the efficiency of this methodology at different soil temperatures and ozone dosages under laboratory conditions,and then a greenhouse pot experiment was conducted under controlled conditions during *** days after the onset of the experiments,higher degradation percentages of amide pesticides were observed in ozonized soils than in other treated soils,particularly when ozone was applied at 10 cm soil *** results show that the utilization of ozonation,along with solarization,represents a valid method for degrading residues of the studied pesticides and suggest that this combined technology may be a promising tool for remediating pesticide-polluted soils.

关键词： intermediate ozone pesticide degradation pesticide residue polyethylene film remediation technique

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Iatrogenic bile duct injury with loss of confluence

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World Journal of Gastrointestinal Surgery 2015年第10期7卷 254-260页

作者： Miguel-Angel Mercado Mario Vilatoba Alan contreras pilar Leal-Leyte Eduardo Cervantes-Alvarez Juan-Carlos Arriola Bruno-Adonai Gonzalez Surgery Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán PECEM Facultad de MedicinaUniversidad Nacional Autónoma de México

AIM: To describe our experience concerning the surgical treatment of Strasberg E-4(Bismuth Ⅳ) bile duct injuries. METHODS: In an 18-year period, among 603 patients referred to our hospital for surgical treatment of complex bile duct injuries, 53 presented involvement of the hilar confluence classified as Strasberg E4 injuries. Imagenological studies, mainly magnetic resonance imaging showed a loss of confluence. The files of these patients were analyzed and general data were recorded, including type of operation and postoperative outcome with emphasis on postoperative cholangitis, liver function test and quality of life. The mean time of follow-up was of 55.9 ± 52.9 mo(median = 38.5, minimum = 2, maximum = 181.2). All other patients with Strasberg A, B, C, D, E1, E2, E3, or E5 biliary injuries were excluded from this ***: Patients were divided in three groups: G1(n = 21): Construction of neoconfluence + Roux-en-Y hepatojejunostomy. G2(n = 26): Roux-en-Y portoenterostomy. G3(n = 6): Double(right and left) Rouxen-Y hepatojejunostomy. Cholangitis was recorded in two patients in group 1, in 14 patients in group 2, and in one patient in group 3. All of them required transhepatic instrumentation of the anastomosis and six patients needed live ***: Loss of confluence represents a surgicalchallenge. There are several treatment options at different stages. Roux-en-Y bilioenteric anastomosis(neoconfluence, double-barrel anastomosis, portoenterostomy) is the treatment of choice, and when it is technically possible, building of a neoconfluence has better outcomes. When liver cirrhosis is shown, liver transplantation is the best choice.

关键词： Bile duct injury Hepatojejunostomy Biliary repair

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Candidate genes underlying QTL for flowering time and their interactions in a wide spring barley(Hordeum vulgare L.) cross

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The Crop Journal 2021年第4期9卷 862-872页

作者： Ana M.Casas Carlota R.Gazulla Arantxa Monteagudo Carlos P.Cantalapiedra Marian Moralejo Mpilar Gracia Francisco J.Ciudad William T.B.Thomas Jose L.Molina-Cano Scott Boden Bruno contreras-Moreira Ernesto Igartua Department of Genetics and Plant Production Aula Dei Experimental Station(EEAD-CSIC)Avda Montanana 1005E-50059 ZaragozaSpain University of Lleida-AGROTECNIO Center Avda.Rovira Roure 19125198 LleidaSpain Instituto de Tecnologia Agraria Junta de Castilla y LeonITACyLP.O.Box 17247071 ValladolidSpain The James Hutton Institute InvergowrieDundee DD25DAUK Institut de Recerca i Tecnologia Agroalimentaries(UdL-IRTA) Avda Rovira Roure 19125198 LleidaSpain John Innes Centre Norwich Research ParkNorwich NR47UHUK Fundacion ARAID calle Maria de Luna 1150018 ZaragozaSpain Present address:Centro de Biotecnologia y Genomica de Plantas Universidad Politecnica de Madrid(UPM)and Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria(INIA)Madrid 28223Spain Present address:School of Agriculture Food and WineWaite Research InstituteUniversity of AdelaideGlen OsmondSA 5064Australia Present address:The European Bioinformatics Institute(EMBL-EBI) Wellcome Trust Genome CampusHinxtonUK

Response to vernalization and photoperiod are the main determinants controlling the time to flowering in temperate cereals. While the individual genes that determine a plant's response to these environmental signals are well characterized, the combinatorial effect on flowering time of allelic variants for multiple genes remains unresolved. This study investigated the genetic control of flowering-time in a biparental population of spring barley, derived from a wide cross between a late-flowering European and an early-flowering North-American cultivar. While the major flowering time genes are not segregating in the Beka ×Logan cross, large variation in flowering was observed. We identified five QTL, with both parents found to contribute early alleles. The catalog of QTL discovered aligns with several candidate genes affecting flowering time in barley. The combination of particular alleles at HvCEN, HvELF3 and HvFT1 in Logan are responsible for the earliness of this cultivar. Interestingly, earliness for flowering could be further enhanced, with Beka found to contribute three early alleles, including a QTL colocating with a HvFD-like gene, suggesting that there are diverse aspects of the flowering-time pathway that have been manipulated in these two cultivars. Epistatic interactions between flowering-time QTL or candidate genes were observed in field data and confirmed under controlled conditions. The results of this study link photoperiod-dependent flowering-time genes with earliness per se genes into a single model, thus providing a unique framework that can be used by geneticists and breeders to optimize flowering time in barley.

关键词： Barley Flowering HvELF3 HvCEN HvFT1

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Arrhythmogenic cardiomyopathy with left ventricular involvement versus ischemic heart disease: lessons learned from the family study and the reviewed autopsy of a young male

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Forensic Sciences Research 2019年第3期4卷 274-279页

作者： pilar Molina Jorge Sanz-Sánchez Manuel Fenollosa Marina Martínez-Matilla Juan Giner Esther Zorio Servicio de Patología Instituto de Medicina Legal y Ciencias Forenses de ValenciaValenciaEspana Unidad de Valoración del Riesgo de Muerte Súbita Familiar and Unidad de Cardiopatías Familiares Muerte Súbita y Mecanismos de Enfermedad(CaFaMuSMe)Instituto de Investigación Sanitaria La FeValenciaEspana Servicio de Cardiología Hospital Universitario y Politécnico La FeValenciaEspana Unidad Genómica Instituto de Investigación Sanitaria La FeValenciaEspana

Ischemic heart disease (IHD) is the leading cause of sudden cardiac death (SCD) and often non-thrombosed severe coronary stenoses with or without myocardial scars are *** dominant arrhythmogenic cardiomyopathy (LDAC) is a life-threating rare disease which has been more thoroughly studied in the last *** macroscopic study of an SCD victim was conducted and re-evaluated 9years *** cardiological work-up in his firstdegree relatives initially comprised an electrocardiogram (ECG) and an *** they were re-evaluted 9years later,a cardiac magnetic resonance,an ECG-monitoring,an exercise testing and a genetic study were performed and the pedigree was extended *** 2008,an IHD was suspected in the sports-triggered SCD of a 37-year-old man upon the postmortem (75% stenosis of the left main and circumflex coronary arteries;the subepicardial left ventricular fibrofatty infiltration with mild myocardial degeneration was assumed to be a past myocardial infarction).No cardiomyopathy was identified in any of the two proband's *** years thereafter,distant relatives were diagnosed with LDAC due to a pathogenic desmoplakin *** reanalysis of the two sisters showed ventricular arrhythmias in one of them without structural heart involvement and the reviewed postmortem of the proband was reclassified as LDAC based on the fibrofatty infiltration;both were mutation *** completion of the family study on 19 family members yielded one SCD due to LDAC (the proband),three living patients diagnosed with LDAC (two with a defibrillator),one mutation carrier without structural ventricular involvement,and 14 healthy relatives (who were discharged) with a very good co-segregation of the *** rare,LDAC exists and sometimes its differential diagnosis with iHD has to be *** previous postmortem misdiagnoses can help family screening to further prevent SCDs.

关键词： Forensic sciences forensic pathology ischemic heart disease arrhythmogenic cardiomyopathy family study

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The Deaf Literacy （DEAFLI）： A European Project for Young and Adult Deaf People E-learning

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Journal of Health Science 2017年第2期5卷 73-80页

作者： Natalia Perez Aguado Maria del pilar Femandez-Viader Departament de Psicologia Evolutiva i de I'Educacio Universitat de Barcelona Barcelona Espana

DEAFLI is a GRUNDTVIG project （538750-LLP-1-2013-1-ES） thought to help deaf people improve their language skills and their chances to access employment. DEAFLI is a 10-lesson course designed to enhance the acquisition of key competences in written language by young deaf people and deaf adults. DEAFLI aims to improve their education and to facilitate their access to the labour market in the countries taking part in the project （Spain, Austria, Italy and the UK）, therefore, materials and resources will be developed for this purpose. DEAFLI uses multimedia technology for teaching and learning activities, incorporating a learning platform with an open forum and a DVD. Each partner develops their share of the lessons which are then adapted to the different languages of the consortium （Catalan, Italian, English and German）, and the four sign languages of the countries belonging to the partnership： LSC （Catalan Sign Language）, LIS （Italian Sign Language）, BSL （British Sign Language） and 13GS （Austrian Sign Language）. So far, the first four lessons have been developed （the topics are：＂formal and informal Letter＂, ＂CV and cover letter＂, ＂press articles＂ and ＂how to read a job advert＂）. DEAFLI includes videos with grammar explanations in the Sign Languages of each of thecountries taking part in the project in order to support the deaf students＇ comprehension of the contents, as well as interactive exercises （***）. Currently, 80% of deaf people are fimctional illiterate, in other words, they complete a basic education, but do not reach suitable language proficiency, neither in its oral form nor in its written one, leading to a handicap in social situations due to the fact that written language proficiency is considered an essential tool in advanced societies, since it guarantees fundamental access to information and knowledge and, therefore, helps to develop a better identity and personal autonomy, while it affects social and work integration. Nowadays, accessibili

关键词： Deafness and Education E-Learning.

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