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With the exception of foreign bodies, formerly food contact materials (FCM) were generally not considered a source of food safety concern. During the past decade several issues regarding FCM affected the food supply and caught the attention of industries, national bodies and of course consumers. But is it clear what an FCM is? The chapter presents different classifications of FCM depending on the type of contact, type of material and function. The potential hazards (physical, microbiological, chemical and allergen) associated with FCM and their risk factors are explained according to the type of material (e.g. wood, metal, plastic). The chapter also reviews the main standards used in the field (ISO 22000, BRCIoP and EN 15593) and gives an overview of the main regulations applicable. The chapter finishes with five case studies that bring the reader to reality in the management of FCM food safety.

Background and aims Transjugular intrahepatic portosystemic shunts (TIPS) are successfully used in the management of portal hypertension (PH)-related complications. Debate surrounds the diameter of the dilation. The aim was to analyse the outcomes of and complications deriving from TIPS in patients with cirrhosis and identify predictors of survival. Methods This was a retrospective single-centre study, which included patients with cirrhosis who had a TIPS procedure for PH from 2009 to October 2018. Demographic, clinical and radiological data were collected. The Kaplan–Meier method was used to measure survival and predictors of survival were identified with the Cox regression model. Results A total of 98 patients were included (78.6% male), mean age was 58.5 (SD±/−9.9) and the median MELD was 13.3 (IQR 9.5–16). The indications were refractory ascites (RA), variceal bleeding (VB) and hepatic hydrothorax (HH). Median survival was 72 months (RA 46.4, VB 68.5 and HH 64.7) and transplant-free survival was 26 months. Clinical and technical success rates were 70.5% and 92.9% respectively. Age (HR 1.05), clinical success (HR 0.33), sodium (HR 0.92), renal failure (HR 2.46) and albumin (HR 0.35) were predictors of survival. Hepatic encephalopathy occurred in 28.6% of patients and TIPS dysfunction occurred in 16.3%. Conclusions TIPS with 10-mm PTFE-covered stent is an effective and safe treatment for PH-related complications in patients with cirrhosis. Age, renal failure, sodium, albumin and clinical success are independent predictors of long-term survival.

Background Immunosuppressive calcineurin inhibitors have been associated with an increased risk of post-transplant malignancies. The mammalian target of rapamycin inhibitors (mTORi) is an alternative immunosuppressive regimen with an antineoplastic effect. The aim of the study was to determine the long-term survival of mTORi-treated recipients with de novo or recurring tumors after liver transplantation (LT). Methods This retrospective analysis included mTORi-treated LT recipients between March 2013 and March 2019. We analyzed long-term survival and mTORi indications in an oncology setting in patients with de novo and recurrent malignancies after LT. Overall survival (OS) rate was compared from the Spanish Liver Transplant Registry (SLTR) data using the Kaplan-Meier method. High-risk hepatocellular carcinoma (HCC) was defined as microvascular invasion or satellite lesions as described in the liver explant. Results A total of 237 patients underwent LT during the study period; 111 patients underwent mTORi-based immunosuppression (48%, cancer was the main indication): 24.5% high-risk HCC; 24.4% HCC recurrence; 14.3% cholangiocarcinoma; and 36.7% de novo malignancies. The 1- and 5-year OS rates after LT in the mTORi group were 83% and 65%, respectively (SLTR group, 85% and 72.6%, respectively); 30.6% patients received mTORi monotherapy, and 38.7% patients had an early switch to mTORi in the first 3 months after oncologic diagnosis. mTORi monotherapy or oncologic treatment strategies had a nonsignificant association with prognosis. The OS rate was higher when the mTORi switch occurred early, 83% and 67%, respectively. Conclusions mTORi-based immunosuppression may be a preferred option in patients transplanted with tumors. The OS rate was comparable to data from the SLTR. An mTORi early switch improves OS rate.

Objectives To develop and validate a specific protocol for SARS-CoV-2 detection in breast milk matrix and to determine the impact of maternal SARS-CoV-2 infection on the presence, concentration and persistence of specific SARS-CoV-2 antibodies. Design and patients This is a prospective, multicentre longitudinal study (April–December 2020) in 60 mothers with SARS-CoV-2 infection and/or who have recovered from COVID-19. A control group of 13 women before the pandemic were also included. Setting Seven health centres from different provinces in Spain. Main outcome measures Presence of SARS-CoV-2 RNA in breast milk, targeting the N1 region of the nucleocapsid gene and the envelope (E) gene; presence and levels of SARS-CoV-2-specific immunoglobulins (Igs)—IgA, IgG and IgM—in breast milk samples from patients with COVID-19. Results All breast milk samples showed negative results for presence of SARS-CoV-2 RNA. We observed high intraindividual and interindividual variability in the antibody response to the receptor-binding domain of the SARS-CoV-2 spike protein for each of the three isotypes IgA, IgM and IgG. Main Protease (MPro) domain antibodies were also detected in milk. 82.9% (58 of 70) of milk samples were positive for at least one of the three antibody isotypes, with 52.9% of these positive for all three Igs. Positivity rate for IgA was relatively stable over time (65.2%–87.5%), whereas it raised continuously for IgG (from 47.8% for the first 10 days to 87.5% from day 41 up to day 206 post-PCR confirmation). Conclusions Our study confirms the safety of breast feeding and highlights the relevance of virus-specific SARS-CoV-2 antibody transfer. This study provides crucial data to support official breastfeeding recommendations based on scientific evidence. Trial registration number NCT04768244., This study has been supported by a research grant from Fundación La Marató-TV3 (MilkCORONA, ref 202106).

This study evaluates a population-based screening of asymptomatic people, using a rapid antigen diagnostic test (RADT), in areas of high transmission. To detect sources of SARS-CoV-2 infection, nasopharyngeal samples were taken and were tested using RADT. Confirmatory RT-qPCR tests were performed in both positive and negative cases. The internal validity of the RADT, the prevalence of infection, and the positive and negative predictive values (PPV and NPV) were estimated, based on the percentages of confirmed cases with 95% confidence interval.. Of the 157,920 people registered, 50,492 participated in the screening, 50,052 were negative, and 440 were positive on the RADT (0.87%). A total of 221 positive RADT samples were reanalysed using RT-qPCR and 214 were confirmed as positive (96.8%, 95% CI: 93.5–98.7%), while 657 out of 660 negative RADT samples were confirmed as RT-qPCR negative (99.5%, 95% CI 98.7–99.9%). The sensitivity obtained was 65.1% (38.4–90.2%) and the specificity was 99.97% (99.94–99.99%). The prevalence of infection was 1.30% (0.95–2.13%). The PPVs were 95.4% (85.9–98.9%) and 97.9% (93.3–99.5%), respectively, while the NPVs were 99.7% (99.4–100%) and 99.2% (98.7–100%), respectively. The high specificity found allow us to report a high screening performance in asymptomatic patients, even in areas where the prevalence of infection was less than 2%.

Background A rare but life-threatening cause of pancytopenia after liver transplantation is hemophagocytic syndrome. We present a 48-year-old woman who underwent liver transplantation and developed a hemophagocytic syndrome secondary to Epstein-Barr virus with a fatal course, despite initial treatment with immunosuppressants. The diagnosis was made based on the bone marrow aspiration, in which macrophages with phagocytic activity were observed, and clinical findings. Due to the very poor outcomes and high mortality, in patients with severe pancytopenia hemophagocytic syndrome should be excluded, and a bone marrow aspiration should be considered.

[EN]: The Spanish Association for the Study of the Liver (AEEH) is convinced that the elimination of hepatitis C virus (HCV) in Spain is possible as long as we are able to use the resources and tools necessary for it. This document reflects the position of the AEEH regarding the elimination of HCV, establishing a wide range of recommendations that can be grouped into five categories: 1) Screening of HCV according to age, of the existence of classic acquisition risk factors of infection, active search of previously diagnosed patients and development of micro-elimination strategies in vulnerable populations; 2) Simplification of HCV diagnosis (one-step diagnosis and diagnosis at the point of patient care); 3) Simplification of patient treatment and improvement of care circuits; 4) Health policy measures, and, finally, 5) Establishment of HCV elimination indicators., [ES]: La Asociación Española para el Estudio del Hígado (AEEH) está convencida de que la eliminación de la hepatitis C en España es posible siempre y cuando seamos capaces de emplear los recursos y las herramientas necesarias para la misma. Este documento refleja la posición de la AEEH respecto a la eliminación del virus de la hepatitis C (VHC), estableciendo una amplia serie de recomendaciones que se pueden agrupar en cinco categorías: 1) cribado del VHC en función de la edad, de la existencia de factores de riesgo clásicos de adquisición de la infección, búsqueda activa de pacientes diagnosticados con anterioridad y desarrollo de estrategias de microeliminación en poblaciones vulnerables; 2) simplificación del diagnóstico del VHC (diagnóstico en un solo paso y diagnóstico en el punto de atención del paciente); 3) simplificación del tratamiento de los pacientes y mejora de los circuitos asistenciales; 4) medidas de política sanitaria, y, finalmente, 5) establecimiento de indicadores de eliminación del VHC.

Wastewater represents the main reusable water source after being adequately sanitized by wastewater treatment plants (WWTPs). In this sense, only bacterial quality indicators are usually checked to this end, and human pathogenic viruses usually escape from both sanitization procedures and controls, posing a health risk on the use of effluent waters. In this study, we evaluated a protocol based on aluminum adsorption–precipitation to concentrate several human enteric viruses, including norovirus genogroup I (NoV GI), NoV GII, hepatitis A virus (HAV), astrovirus (HAstV), and rotavirus (RV), with limits of detection of 4.08, 4.64, 5.46 log genomic copies (gc)/L, 3.31, and 5.41 log PCR units (PCRU)/L, respectively. Furthermore, the method was applied in two independent laboratories to monitor the presence of NoV GI, NoV GII, and HAV in effluent and influent waters collected from five WWTPs at two different sampling dates. Concomitantly, a viability PMAxx-RT-qPCR was applied to all the samples to get information on the potential infectivity of both influent and effluent waters. The ranges of the titers in influent waters for NoV GI, NoV GII, RV, and HAstV were 4.80–7.56, 5.19–7.31 log gc/L, 5.41–6.52, and 4.59–7.33 log PCRU/L, respectively. In effluent waters, the titers ranged between 4.08 and 6.27, 4.64 and 6.08 log gc/L, This study was supported by the “VIRIDIANA” Project AGL2017-82909 (AEI/FEDER, UE) funded by Spanish Ministry of Science, Innovation and Universities; the APOTI Grant (APOTIP/2018/007) from the Generalitat Valenciana; and the CSIC internal Project 201770I088. W. Randazzo was supported by a postdoctoral fellowship from Generalitat Valenciana (APOSTD/2018/150).

Background During the COVID-19 pandemic in 2020, breastfeeding in women positive for SARS-CoV-2 was compromised due to contradictory data regarding potential viral transmission. However, growing evidence confirms the relevant role of breast milk in providing passive immunity by generating and transmitting specific antibodies against the virus. Thus, our study aimed to develop and validate a specific protocol to detect SARS-CoV-2 in breast milk matrix as well as to determine the impact of maternal SARS-CoV-2 infection on presence, concentration, and persistence of specific SARS-CoV-2 antibodies. Study design/Methods A prospective multicenter longitudinal study in Spain was carried out from April to December 2020. A total of 60 mothers with SARS-CoV-2 infection and/or recovered from COVID-19 were included (n=52 PCR-diagnosed and n=8 seropositive). Data from maternal-infant clinical records and symptomatology were collected. A specific protocol was validated to detect SARS-CoV-2 RNA in breast milk, targeting the N1 region of the nucleocapsid gene and the envelope (E) gene. Presence and levels of SARS-CoV-2 specific immunoglobulins (Igs) -IgA, IgG, and IgM-in breast milk samples from COVID-19 patients and from 13 women before the pandemic were also evaluated. Results All breast milk samples showed negative results for SARS-CoV-2 RNA presence. We observed high intra- and inter-individual variability in the antibody response to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein for each of the three isotypes IgA, IgM and IgG. Protease domain (MPro) antibodies were also detected in milk. In general, 82.9 % of the milk samples were positive for at least one of the three antibody isotypes, being 52.86 % of those positive for all three Igs. Positivity rate for IgA was relatively stable over time (65.2 – 87.5 %), whereas it raised continuously for IgG (47.8 % the first ten days to 87.5 % from day 41 up to day 206 post-PCR confirmation). Conclusions Considering the lack of evidence for SARS-CoV-2 transmission through breast milk, our study confirms the safety of breastfeeding practices and highlights the relevance of virus-specific SARS-CoV-2 antibody transfer, that would provide passive immunity to breastfed infants and protect them against COVID-19 disease. This study provides crucial data to support official breastfeeding recommendations based on scientific evidence.

Water-based epidemiology (WBE) is a valuable early warning tool for tracking the circulation of the virus among the population, including not only symptomatic patients, but also asymptomatic, presymptomatic, and misdiagnosed carriers, which represent a high proportion of the infected population. In the specific case of Barcelona, wastewater surveillance anticipated by several weeks not only the original COVID-19 pandemic wave, but also the onset of the second wave., Two large wastewater treatment plants (WWTP), covering around 2.7 million inhabitants, which represents around 85% of the metropolitan area of Barcelona, were sampled before, during, and after the implementation of a complete lockdown. Five one-step reverse transcriptase quantitative PCR (RT-qPCR) assays, targeting the polymerase (IP2 and IP4), the envelope (E), and the nucleoprotein (N1 and N2) genome regions, were employed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detection in 24-h composite wastewater samples concentrated by polyethylene glycol (PEG) precipitation. SARS-CoV-2 was detected in a sewage sample collected 41 days ahead of the declaration of the first COVID-19 case. The evolution of SARS-CoV-2 genome copies in wastewater evidenced the validity of water-based epidemiology (WBE) to anticipate COVID-19 outbreaks, to evaluate the impact of control measures, and even to estimate the burden of shedders, including presymptomatic, asymptomatic, symptomatic, and undiagnosed cases. For the latter objective, a model was applied for the estimation of the total number of shedders, evidencing a high proportion of asymptomatic infected individuals. In this way, an infection prevalence of 2.0 to 6.5% was figured. On the other hand, proportions of around 0.12% and 0.09% of the total population were determined to be required for positive detection in the two WWTPs. At the end of the lockdown, SARS-CoV-2 RNA apparently disappeared in the WWTPs but could still be detected in grab samples from four urban sewers. Sewer monitoring allowed for location of specific hot spots of COVID-19, enabling the rapid adoption of appropriate mitigation measures. IMPORTANCE Water-based epidemiology (WBE) is a valuable early warning tool for tracking the circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among the population, including not only symptomatic patients but also asymptomatic, presymptomatic, and misdiagnosed carriers, which represent a high proportion of the infected population. In the specific case of Barcelona, wastewater surveillance anticipated by several weeks not only the original COVID-19 pandemic wave but also the onset of the second wave. In addition, SARS-CoV-2 occurrence in wastewater evidenced the efficacy of the adopted lockdown measures on the circulation of the virus. Health authorities profited from WBE to complement other inputs and adopt rapid and adequate measures to mitigate the effects of the pandemic. For example, sentinel surveillance of specific sewers helped to locate COVID-19 hot spots and to conduct massive numbers of RT-PCR tests among the population.

There is no doubt that the use of Internet for purchasing products and services has constituted a crucial change in how people go about buying them. In the era of digital transformation, the possibility of accessing information provided by other users about their personal experiences has taken on more weight in the selection and buying processes. On these lines, traditional word-of-mouth (WOM) has given way to electronic word-of-mouth (eWOM), which constitutes a major social change. This behavior is particularly relevant in the services area, where potential users cannot in advance assess what is on offer. There is an abundant literature analyzing the effects of eWOM on different variables of interest in this sector. However, little is known about the factors that determine eWOM. Thus, the main objective of the present paper is to analyze the impact of two variables (objective quality and perceived quality) on eWOM. Both of them are crucial for potential customers in the process of finding hotel accommodations and they can motivate people to make such comments. The results demonstrate that these variables truly have a significant impact on whether or not users make comments on line. Moreover, it proved possible to observe certain differences according to the profile of the tourist involved and the destination where the hotel is located. In the current changing environment, this information is of great use for hotel managers in order to design strategies according to the type of guest they wish to attract.

[Abstract] A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) α-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions. Ministerio de Economía y Empresa; IDI-20151125 Ministerio de Ciencia, Innovación y Universidades; SAF SAF 2017-87846-R

The COVID-19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a rapidly emerging pandemic which has enforced extreme containment measures worldwide. In the absence of a vaccine or efficient treatment, cost-effective epidemiological surveillance strategies are urgently needed. Here, we have used RT-qPCR for SARS-CoV-2 detection in a series of longitudinal metropolitan wastewaters samples collected from February to April 2020, during the earliest stages of the epidemic in the Region of Valencia, Spain. We were able to consistently detect SARS-CoV-2 RNA in samples taken in late February, when communicated cases in that region were only incipient. We also find that the wastewater viral RNA context increased rapidly and anticipated the subsequent ascent in the number of declared cases. Our results strongly suggest that the virus was undergoing community transmission earlier than previously believed, and suggest that wastewater analysis could be sensitive and cost-effective strategy for COVID-19 epidemiological surveillance. Routine implementation of this surveillance tool would significantly improve our preparedness against new or re-occurring viral outbreaks., This research was funded by CSIC 202070E101 grant, 210152 project of Valencian Innovation Agency/GV, and AGL2017-82909 (AEI/FEDER, UE) funded by Spanish Ministry of Science, Innovation and Universities to G.S., ERC Consolidator Grant 724519-Vis-à-Vis to R.S. and FONDO-COVID19 COV20/00210 funded by Instituto de Salud Carlos III to P.D-C. W.R. was supported by APOSTD/2018/150 postdoctoral fellowship, and E.C–F. was supported by a predoctoral contract from the MICINN, Call 2018.

SARS-CoV-2 was detected in Barcelona sewage long before the declaration of the first COVID-19 case, indicating that the infection was present in the population before the first imported case was reported. Sentinel surveillance of SARS-CoV-2 in wastewater would enable adoption of immediate measures in the event of future COVID-19 waves.Article Summary LineSARS-CoV-2 genomes occur in sewage long before the declaration of COVID-19 cases among the population.

BACKGROUND AND AIMS Nonalcoholic fatty liver disease (NAFLD) is a long-term complication after liver transplantation. Our aims were to determine de-novo-NAFLD at 5-year post-liver transplantation and identify predictive risk factors. METHODS This was a retrospective analysis of de-novo-NAFLD at 5-year post-liver transplantation. NAFLD was defined as the radiological evidence of steatosis. Data from transplanted patients between November 2001 and May 2014 were collected. Noninvasive fibrosis scores were calculated. Predictors of de-novo NAFLD and survival were assessed by multivariate analyses and Kaplan-Meier method. RESULTS A total of 252 liver transplantations were evaluated after applying exclusion criteria, (78.6% men) with 54.9 years old (SD ± 9.5). Prevalence of de-novo NAFLD at 5-year post-liver transplantation was 36.1%. Cardiovascular events were presented in 19.88% and 23.08% of non-NAFLD and NAFLD patients, (P = 0.58). On multivariate analysis, male sex (OR, 5.40; P = 0.001), obesity (OR, 3.72; P = 0.017), metabolic syndrome (OR, 4.69; P

Food contaminated by hepatitis A virus (HAV) is responsible of the 2–7% of all HAV outbreaks worldwide. This review provides a description of the HAV characteristics, its infectivity and epidemiological features. In addition, this review compiles existing original papers reporting HAV prevalence, viral titres in foodstuffs and the risk associated with food contamination. The purpose of this revision is to conduct a structured and systematic review of the published molecular procedures for HAV detection in food, including the assessment of its infectivity.

Background Cirrhosis as a result of alcohol-related liver disease is one of the most common indications for liver transplantation (LT) in Spain. Patients presenting for LT should be checked for alcohol abuse in clinical interviews and use of laboratory tests to confirm abstinence. The ethyl-glucuronide (EtG) test is very sensitive and can be positive in urine up to 5 days after consumption. Our main objective is to know the rate of alcohol abstinence by using the urine EtG test in patients evaluated for LT and to assess its correlation with the clinical interviews and laboratory test. Methods We conducted a prospective analysis of the results of the EtG in urine of patients evaluated for LT from January 2017 to March 2019 and its correlation with the medical and psychiatric interviews and with the laboratory test. Results We included 160 patients who were referred to LT evaluation. Among all cases, 84.1% were men, with an average age of 57.8 years. Alcohol-related liver disease was the most frequent cause (64.1%). Urine-EtG was positive in 10 patients (6.2%), 9 of them in patients with ALD and 1 in a patient with hepatitis C virus. The alcohol consumption was recognized by 80% of the patients in the clinical interview. Cases with positive EtG had higher levels of analytical parameters than those with a negative test. Conclusions In our series, 6.2% of patients referred for LT evaluation had recently consumed alcohol. The determination of EtG in urine is probably an effective and objective technique in the detection of alcohol consumption to ensure abstinence in the LT candidates.

Este trabajo se centra en el estudio de la oferta de precios a través de canales online (Booking.com) en un destino turístico. Los hoteles se han seleccionado mediante muestreo aleatorio simple estratificado con afijación proporcional. Se trabaja con un conjunto de datos de grandes dimensiones (big data, con un total de 1.353.751 registros). Se considera una antelación de estancia de aproximadamente un año, lo que supone una gran novedad respecto a estudios previos. En el trabajo se presentan los valores de precios considerando los datos habitualmente publicados por los hoteles en estos canales, lo que permite ofrecer una panorámica de la operativa relativa a la oferta de precios a través de la distribución online a nivel de destino turístico. This work focuses on the study of prices offered through an online distribution channel (Booking.com) on a concrete tourism destination. Hotels were selected by a stratified simple random sampling method with proportional allocation. Research is done over an extensive dataset (1,353,751 of records, big data). The advance booking period considered covers approximately a whole year, and this represents a great novelty with respect to previous studies. Average prices are calculated from the values ordinarily published by hotels on this type of channels, which allows providing the outline of the operational management of prices implemented on the destination, through the online distribution and from the supply perspective.

© 2020 by the authors., The aim of the present study was to perform the molecular epidemiology of rotaviruses and noroviruses detected in sewage samples from a large wastewater facility from the city of Valencia, Spain. A total of 46 sewage samples were collected over a one-year period (September 2016 to September 2017). Norovirus and rotavirus were detected and quantified by RT-qPCR, genotyped by semi-nested RT-PCR and further characterized by sequencing and phylogenetic analyses. Noroviruses and rotaviruses were widely distributed in sewage samples (69.6% for norovirus GI, 76.0% norovirus GII, and 71.7% rotaviruses) and viral loads varied from 4.33 to 5.75 log PCRU/L for norovirus GI, 4.69 to 6.95 log PCRU/L for norovirus GII, and 4.08 to 6.92 log PCRU/L for rotavirus. Overall, 87.5% (28/32) of GI noroviruses could not be genotyped, 6.25% (2/32) of the samples contained GI.2 genotype, and another 6.25% (2/32) were positive for GI.4 genotype. The most common genotype of GII noroviruses was GII.2 (40%, 14/35), followed by GII.6 (8.6%, 3/35) and GII.17 (5.7%, 2/35) while the remaining GII strains could not be typed (45.7%, 16/35). Rotavirus VP4 genotype P[8] was the only one found in 19 out of 33 rotavirus-positive samples (57.7%). G2 was the most prevalent rotavirus VP7 genotype (15.2%, 5/33) followed by G3, G9, and G12, with two positive samples for each genotype (6.1%, 2/33). In one sample both G1 and G2 genotypes were detected simultaneously (3%). The results presented here show that the surveillance of noroviruses and rotaviruses in sewage is useful for the study of their transmission in the population and their molecular epidemiology., This work was supported by Spanish Government (Ministerio de Economía y Competitividad) grants AGL2017-84165-C2-2-R, RYC-2013-12442, and AGL2017-82909-R (AEI/FEDER, UE) funded by Spanish Ministry of Science, Innovation and Universities. This work was also founded by the Generalitat Valenciana and the UE FEDER program IDIFER/2018/056. CSB is the recipient of a predoctoral grant FPI from the Spanish Government RE2018-083315. RGR and WR are supported by postdoctoral fellowships from Valencian Government (APOST/2017/037 and APOSTD/2018/150).

Gastroenteritis and hepatitis, caused by human noroviruses (HuNoVs) and hepatitis A virus (HAV), respectively, are the most common illnesses resulting from the consumption of food contaminated with human enteric viruses. Food-grade polymers can be tailor designed to improve food safety, either as novel food-packaging materials imparting active antimicrobial properties, applied in food contact surfaces to avoid cross-contamination, or as edible coatings to increase fresh produce's shelf life. The incorporation of antimicrobial agents into food-grade polymers can be used to control the food microbiota and even target specific foodborne pathogens to improve microbiological food safety and to enhance food quality. Enteric viruses are responsible for one fifth of acute gastroenteritis cases worldwide and the development of food-grade polymers and biopolymers with antiviral activity for food applications is a topic of increased interest, both for academia and the food industry, even though developments are still limited. This review compiles existing studies in this widely unexplored area and highlights the potential of these developments to improve viral food safety.

OBJECTIVES: Interferon-free therapies have an improved safety and efficacy profile. However, data in elderly patients, who have frequently advanced liver disease, associated comorbidities, and use concomitant medications are scarce. The im of this study was to assess the effectiveness and tolerability of all-oral regimens in elderly patients in real-life clinical practice. METHODS: Retrospective analysis of hepatitis C virus (HCV) patients aged >= 65 years receiving interferon-free regimens within the Spanish National Registry (Hepa-C). RESULTS: Data of 1,252 patients were recorded. Of these, 955 (76%) were aged 65-74 years, 211 (17%) were aged 75-79 years, and 86 (7%) were aged >= 80 years at the start of antiviral therapy. HCV genotype-1b was predominant (88%) and 48% were previous non-responders. A significant proportion of patients had cirrhosis (922; 74%), of whom 11% presented decompensated liver disease. The most used regimens were SOF/LDV (33%), 3D (28%), and SOF/SMV (26%). Ribavirin was added in 49% of patients. Overall, the sustained virological response (SVR12) rate was 94% without differences among the three age categories. Albumin = 75 years (2.59 (1.16-5.83); P = 0.02) and albumin = 75 years) or those with advanced liver disease (albumin

El artículo explora las particularidades en la gestión de la provisión de agua en México, mediante el examen de los arreglos de gobernanza en los que intervienen actores gubernamentales, privados y sociales. El análisis se sustenta en investigación documental y de campo en dos casos de estudio de municipios en la región del alto Lerma: Xalatlaco y Santiago Tianguistenco. Parte de la idea de que los procesos de inclusión y exclusión al derecho al agua están condicionados por la forma en que se asumen los arreglos de gobernanza con las organizaciones comunitarias que participan en la gestión del recurso. La exploración muestra que las organizaciones comunitarias son actores que determinan el acceso al agua en las poblaciones.

Summary Background Cytotoxic chemotherapy is generally ineffective in patients with hepatocellular carcinoma. We assessed the intravenous perfusion of doxorubicin-loaded nanoparticles in patients with hepatocellular carcinoma in whom previous sorafenib therapy had failed. Methods We did a multicentre, open-label, randomised, controlled phase 3 trial at 70 sites in 11 countries. Patients with hepatocellular carcinoma with one or more previous systemic therapies, including sorafenib, were randomly assigned to receive 30 mg/m2 doxorubicin-loaded nanoparticles (30 mg/m2 group), 20 mg/m2 doxorubicin-loaded nanoparticles (20 mg/m2 group), or standard care using a computer-generated randomisation list prepared by the funder and stratified by geographic region. Patients in the experimental groups received perfusion of the drug every 4 weeks and those in the control group received any systemic anticancer therapy (except sorafenib) as per investigator decision. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the population of patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov , number NCT01655693 . Findings Between June 15, 2012, and Jan 27, 2017, 541 patients were screened, of whom 144 were excluded and 397 were randomly assigned to one of the groups (133 to the 30 mg/m2 group; 130 to the 20 mg/m2 group; and 134 to the control group). Median follow-up was 22·7 months (IQR 11·2–34·9). After pooling the doxorubicin groups for the efficacy analysis, median overall survival was 9·1 months (95% CI 8·1–10·4) in the pooled doxorubicin-loaded nanoparticles group and 9·0 months (7·1–11·8) in the control group (HR 1·00 [95% CI 0·78–1·28], two-sided p=0·99). 227 (94%) of 242 patients who received doxorubicin-loaded nanoparticles and 100 (75%) of 134 patients in the control group had at least one treatment-emergent adverse event. The most common drug-related grade 3 or 4 treatment-emergent adverse events were neutropenia (25 [10%] of 242 treated with doxorubicin-loaded nanoparticles and eight [6%] of 134 in the control group), asthenia (six [2%] and four [3%]), and thrombocytopenia (three [1%] and ten [7%]). Six (2%) patients treated with doxorubicin-loaded nanoparticles and one (1%) of those in the control group were deemed by investigators to have had a drug-related death. Serious adverse events occurred in 74 (31%) patients who received doxorubicin-loaded nanoparticles and 48 (36%) in the control group. Interpretation Doxorubicin-loaded nanoparticles did not improve overall survival for patients with hepatocellular carcinoma in whom previous sorafenib treatment had failed. Funding Onxeo.

The aim of this work was to identify and characterize the levels of development of derivative schema. In order to do so, a questionnaire to 103 university students with previous instruction in Differential Calculus was applied. The questionnaire was composed of three tasks. For the identification of the levels of development of schema and their subsequent characterization, we consider the framework proposed by the APOS theory. In particular, this framework was operationalized through the establishment of 27 variables that allowed for the breakdown of the resolution protocols from the questionnaire into discrete elements. In this way, we obtained a vector associated with each of these variables. The identification of students assigned to each level of development of schema was carried out by a cluster analysis. Subsequently, we performed a statistical analysis of frequencies and implicative, with the 27 variables, which allowed to characterize the levels of development identified.

La Asociación Española para el Estudio del Hígado (AEEH) está convencida de que la eliminación de la hepatitis C en España es posible siempre y cuando seamos capaces de emplear los recursos y las herramientas necesarias para la misma. Este documento refleja la posición de la AEEH respecto a la eliminación del virus de la hepatitis C (VHC), estableciendo una amplia serie de recomendaciones que se pueden agrupar en cinco categorías: 1) cribado del VHC en función de la edad, de la existencia de factores de riesgo clásicos de adquisición de la infección, búsqueda activa de pacientes diagnosticados con anterioridad y desarrollo de estrategias de microeliminación en poblaciones vulnerables; 2) simplificación del diagnóstico del VHC (diagnóstico en un solo paso y diagnóstico en el punto de atención del paciente); 3) simplificación del tratamiento de los pacientes y mejora de los circuitos asistenciales; 4) medidas de política sanitaria, y, finalmente, 5) establecimiento de indicadores de eliminación del VHC. The Spanish Association for the Study of the Liver (AEEH) is convinced that the elimination of hepatitis C virus (HCV) in Spain is possible as long as we are able to use the resources and tools necessary for it. This document reflects the position of the AEEH regarding the elimination of HCV, establishing a wide range of recommendations that can be grouped into five categories: 1) Screening of HCV according to age, of the existence of classic acquisition risk factors of infection, active search of previously diagnosed patients and development of microelimination strategies in vulnerable populations; 2) Simplification of HCV diagnosis (one-step diagnosis and diagnosis at the point of patient care); 3) Simplification of patient treatment and improvement of care circuits; 4) Health policy measures, and, finally, 5) Establishment of HCV elimination indicators.

[ES] Los principales patógenos víricos que podemos adquirir ingiriendo alimentos contaminados son los norovirus, el virus de la hepatitis A y el virus de la hepatitis E que se propagan principalmente a través de la vía fecal oral. En los últimos años, la incidencia de brotes de transmisión alimentaria causados por estos patógenos ha experimentado un aumento considerable, en parte debido al comercio globalizado y a los cambios en los hábitos de consumo. Las matrices alimentarias que mayor riesgo representan para el consumidor son los moluscos bivalvos, vegetales de IV gama, frutas tipo baya y platos listos para comer. Actualmente las técnicas moleculares son las más habituales para la detección de estos patógenos en alimentos, aunque todavía existen dudas acerca del significado de la presencia de estos genomas víricos en términos de seguridad alimentaria. La infectividad de estos patógenos en alimentos viene también determinada por su elevada persistencia ambiental y por su resistencia a los tratamientos aplicados para la conservación de los alimentos., [EN]The main viral pathogens that can be acquired by ingesting contaminated food are norovirus, and hepatitis A and E viruses that are spread mainly through the oral-faecal route. In recent years, the incidence of foodborne outbreaks caused by these pathogens has increased considerably, partly due to globalised trade and changes in consumption habits. Foodborne outbreaks caused by enteric viruses are mainly associated with bivalve molluscs, fresh-cut vegetables, berries and ready-to-eat meals. Molecular-based techniques are currently used for the detection of these pathogens in food, although there are still doubts about the significance of the presence of viral genomes in terms of food safety. The infectivity of these pathogens in food is also driven by their high persistence in the environment and to their resistance to treatments commonly applied by the food industry.

Foodborne illnesses caused by the consumption of berries contaminated with human enteric viruses, namely human noroviruses (NoVs) and the hepatitis A virus (HAV), remain a significant food safety concern. The objective of this research was to investigate a food-grade edible coating composed of alginate/oleic and containing green tea extract (GTE) as an antiviral agent for the preservation of fresh strawberries and raspberries. Berries were stored at ambient (25 °C) temperature and refrigerated (10 °C) conditions. Initially, the effect of the pH of the film-forming dispersions (FFD) on their antioxidant and antiviral activity was analysed. Then, the physicochemical properties of edible alginate-oleic acid coatings containing GTE were studied, and finally, their antiviral efficacy when applied onto strawberries and raspberries at 10 and 25 °C was evaluated. The results showed that the antioxidant properties of the films were not pH-dependent, but the antiviral activity was higher at a pH 5.5. The infectivity of the murine norovirus (MNV), a human norovirus surrogate, and HAV in fresh strawberries after the coating treatments was reduced by approximately 1.5–2 log during the 4-days storage period at 10 °C as compared to the controls and a complete inactivation of both viruses was observed after overnight storage at 25 °C. However, the efficacy of the GTE-coatings was slightly reduced on the raspberries, probably due to the difference in the amount of coating that adhered to their surface (4.64 ± 0.23 g and 1.54 ± 0.15 g⋅cm−2 for strawberries or raspberries, respectively). Therefore, this paper reports, for the first time, the potential of antiviral edible coatings to improve the safety of berries against foodborne pathogens., P. L. Flores-Meraz thanks CONACYT from the grant. M.J. Fabra is recipient of a Ramon y Cajal (RYC-2014-158) contract from the Spanish Ministry of Economy, Industry and Competitiveness.

The hepatitis E virus (HEV) is an emerging pathogen showing a considerable increase in the number of reported cases in Europe mainly related to the ingestion of contaminated food. As with other relevant viral foodborne pathogens, real-time reverse transcriptase polymerase chain reaction (RT-qPCR) is the gold standard for HEV detection in clinical, food, and environmental samples, but these procedures cannot discriminate between inactivated and potentially infectious viruses. Thus, the aim of this study was to develop a viability PCR method to discriminate between native, heat-, and high-pressure processing (HPP)-treated HEV using the hepatitis A virus (HAV) as a cultivable surrogate. To this end, different concentrations of viability markers (PMAxx and platinum chloride, PtCl) were screened firstly on purified viral RNA using different RT-qPCR assays. Reductions of HEV RNA signals of > 17.5, > 15.0, and > 15.5 quantification cycles (Cq) were reported for PtCl and 1.6, 2.9, and 8.4 Cq for PMAxx, clearly indicating a better performance of PtCl than PMAxx irrespective of the RT-qPCR assay used. The most efficient viability pretreatment (500 μM PtCl incubated at 5°C for 30 min) was then assessed on native, heat-, and HPP-treated HEV suspension. The optimized viability RT-qPCR discriminated successfully between native, heat-, and HPP-treated HEV, to different extents depending on the experimental conditions. In particular, approximately 2-log10 reduction was reported by PtCl-RT-qPCR at both 72 and 95°C compared to the control. Additionally, both viability pretreatments were tested for HPP-treated HAV without success, while PtCl-RT-qPCR completely eliminated (> 5.6-log10 reduction) the RT-qPCR signals of HPP-treated HEV. Although this viability procedure may still overestimate infectivity, the PtCl pretreatment represents progress to better interpreting the quantification of intact HEV, and it could be included in molecular procedures used to quantify enteric viruses in food and environmental samples., This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO) (AGL2017-82909) and the Spanish National Institute for Agriculture and Food Research and Technology (INIA) co-financed by the European Social Fund (Project RTA2014-00024-C03). Financial support has been co-sponsored by the European Regional Development Fund (FEDER). This work was carried out during a scholarship supported by the Doctoral Program Sandwich Exterior (PDSE), process number 88881.132189/2016-01, financed by CAPES - Brazilian Federal Agency for Postgraduate Support and Evaluation at the Brazilian Ministry of Education.

Introduction: The socioeconomic burden of irritable bowel syndrome with constipation (IBS-C) has never been formally assessed in Spain. Patients and methods: This 12-month (6-month retrospective and prospective periods) observational, multicentre study assessed the burden of moderate-to-severe IBS-C in Spain. Patients were included if they had been diagnosed with IBS-C (Rome III criteria) within the last 5 years and had moderate-to-severe IBS-C (IBS Symptom Severity Scale score [IBS-SSS] >= 175) at inclusion. The primary objective was to assess the direct cost to the Spanish healthcare system (HS). Results: A total of 112 patients were included, 64 (57%) of which had severe IBS-C at inclusion. At baseline, 89 (80%) patients reported abdominal pain and distention. Patient quality of life (QoL), measured by the IBS-C QoL and EQ-5D instruments, was found to be impaired with a mean score of 59 and 57 (0100, worst-best), respectively. Over the 6-month prospective period the mean IBS-C severity, measured using the IBS-SSS showed some improvement (315234 [0500, bestworst]). During the year, 89 (80%) patients used prescription drugs for IBS-C, with laxatives being the most frequently prescribed (n = 70; 63%). The direct cost to the HS was (sci)1067, and to the patient was (sci)568 per year. The total direct cost for moderate-to-severe IBS-C was (sic)1635. Discussion: The majority of patients reported continuous IBS-C symptoms despite that 80% were taking medication to treat their IBS-C. Overall healthcare resource use and direct costs were asymmetric, with a small group of patients consuming the majority of resources. (C) 2018 Elsevier Espana, S.L.U. All rights reserved.

The hepatitis E virus (HEV), which is an increasing cause of acute viral hepatitis in Europe, is a zoonotic virus that is mainly transmitted through contaminated water, consumption of raw or undercooked meat from pigs or wild boar, blood transfusion, and organ transplantation. Although the role of HEV transmission through contaminated produce has not been confirmed, the presence of HEV has been reported in irrigation waters and in vegetables. The present study used a World Health Organization (WHO) international standard and clinical samples to evaluate the performance characteristics of three RT-qPCR assays for detection and quantification of HEV. Two of the evaluated assays provided good analytical sensitivity, as 250 international units (IU) per ml could be detected. Then, experiments focused on evaluating the elution conditions suitable for HEV release from vegetables, with the method proposed by the ISO 15216:2017 selected for evaluation in three types of fresh vegetables. The concentration method proposed by the ISO 15216:2017 combined with the RT-qPCR described by Schlosser et al. (2014) resulted in average HEV recoveries of 1.29%, 0.46%, and 3.95% in lettuce, spinach, and pepper, respectively, with an average detection limit of 1.47 × 105 IU/25 g. In naturally contaminated samples, HEV was detected in sewage only (10/14), while no detection was reported in lettuce (0/36) or in irrigation water samples (0/24)., This work was supported by the Spanish National Institute for Agriculture and Food Research and Technology (INIA) co-financed by the European Social Fund (Project RTA2014-00024-C03). Financial support has been co-sponsored by the European Regional Development Fund (FEDER). This work was carried out during a scholarship supported by the Doctoral Program Sandwich Exterior (PDSE), process number 88881.132189/2016-01, Financed by CAPES - Brazilian Federal Agency for Postgraduate Support and Evaluation at the Brazilian Ministry of Education.

Chemical sanitizers continue to be widely used by the food industry to disinfect food contact surfaces. However, as some chemical disinfectants have been reported to produce unhealthy by-products, alternative and natural compounds need to be investigated. To this end, nine essential oils (EOs) were screened to develop a natural sanitizing solution (SAN) for disinfecting food contact surfaces. Once extracted, their antimicrobial activity and chemical composition were determined. An exploratory multivariate approach was used to investigate the relationships between the chemical and microbiological data sets. Among the tested EOs, Thymbra capitata EO, containing up to 93.31% oxygenated monoterpenes (mainly carvacrol), showed the strongest antimicrobial activity and thus was assayed as a potential SAN for food contact surfaces. To this end, a SAN consisting of 1% T. capitata EO was first validated according to the AOAC standard, which showed about 8 log reduction for Escherichia coli and Salmonella enterica after 30 and 60 s of contact time, respectively. Then, the SAN was evaluated at various concentrations, cleanliness conditions, and contact times on stainless steel, glass, and polypropylene surfaces for sanitizing purposes. The results showed that the SAN containing 2.5% of T. capitata EO applied for 10 min, reduced the levels of E. coli by >3 log and S. enterica by 1 log under clean working conditions on the three tested surfaces. These findings indicate that EOs can be used as natural disinfectants to decontaminate food contact surfaces, thus lowering the risk of the indirect transfer of bacterial pathogens to food or persons., This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO) (RYC-2012-09950) and the Spanish National Institute for Agricultural and Food Research and Technology (INIA) co-financed by the European Social Fund (Project RTA2014-00024-C03). GS was supported by the “Ramon y Cajal” Young Investigator.

Shellfish contamination by human noroviruses (HuNoVs) is a serious health and economic problem. Recently an ISO procedure based on RT-qPCR for the quantitative detection of HuNoVs in shellfish has been issued, but these procedures cannot discriminate between inactivated and potentially infectious viruses. The aim of the present study was to optimize a pretreatment using PMAxx to better discriminate between intact and heat-treated HuNoVs in shellfish and sewage. To this end, the optimal conditions (30 min incubation with 100 μM of PMAxx and 0.5% of Triton, and double photoactivation) were applied to mussels, oysters and cockles artificially inoculated with thermally-inactivated (99 °C for 5 min) HuNoV GI and GII. This pretreatment reduced the signal of thermally-inactivated HuNoV GI in cockles and HuNoV GII in mussels by > 3 log. Additionally, this pretreatment reduced the signal of thermally-inactivated HuNoV GI and GII between 1 and 1.5 log in oysters. Thermal inactivation of HuNoV GI and GII in PBS, sewage and bioaccumulated oysters was also evaluated by the PMAxx-Triton pretreatment. Results showed significant differences between reductions observed in the control and PMAxx-treated samples in PBS following treatment at 72 and 95 °C for 15 min. In sewage, the RT-qPCR signal of HuNoV GI was completely removed by the PMAxx pretreatment after heating at 72 and 95 °C, while the RT-qPCR signal for HuNoV GII was completely eliminated only at 95 °C. Finally, the PMAxx-Triton pretreatment was applied to naturally contaminated sewage and oysters, resulting in most of the HuNoV genomes quantified in sewage and oyster samples (12 out of 17) corresponding to undamaged capsids. Although this procedure may still overestimate infectivity, the PMAxx-Triton pretreatment represents a step forward to better interpret the quantification of intact HuNoVs in complex matrices, such as sewage and shellfish, and it could certainly be included in the procedures based on RT-qPCR., This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO) (RYC-2012-09950 and RYC-2013-12442) and the Spanish National Institute for Agriculture and Food Research and Technology (INIA) co-financed by the European Social Fund (Project RTA2014-00024-C03). Financial support has been co-sponsored by the European Regional Development Fund (FEDER). GS and JRD were supported by the “Ramón y Cajal” Young Investigator.

Human noroviruses (HNoVs) are primarily transmitted by the fecal-oral route, either by person-to-person contact, or by ingestion of contaminated food or water as well as by aerosolization. Moreover, HNoVs significantly contribute to foodborne diseases being the causative agent of one-fifth of acute gastroenteritis worldwide. As a consequence of globalization, transnational outbreaks of foodborne infections are reported with increasing frequency. Therefore, in this review, state-of-the-art information regarding molecular procedures for human norovirus detection in food as well common food processing technologies have been summarized. Besides, the purpose of this chapter is to consolidate basic information on various aspects of HNoVs and to summarize food processing technologies that can potentially be applied in the food industry.

Advances in immunotherapy have changed the therapeutic landscape of non-small cell lung cancer (NSCLC), extending overall survival over standard chemotherapy. However, by removing the protection against autoimmunity, immunotherapy can increase immune-related adverse events (irAEs). In addition, new patterns of radiological response have been observed in patients treated with immune checkpoint inhibitors (ICIs). We report the case of a 77 year-old patient with advanced lung adenocarcinoma, who presented three consecutive different irAEs (nephritis, hepatitis, and pneumonitis) and an atypical radiological response (partial response, dissociated response, and "disease flare") in relation to treatment with the PD-1 inhibitor nivolumab. The role of ICIs in elderly patients, the incidence of consecutive irAEs, and the new patterns of radiological response, are also reviewed.

Introduction: chronic kidney disease is a frequent complication after liver transplantation. The use of calcineurin inhibitors is one of the causes of this complication. Current immunsuppression regimens that reduce the use of calcineurin inhibitors may be associated with an improved preservation of renal function. Objective: the study aimed to assess the evolution of renal function after liver transplantation in the current routine clinical practice. Methods: an observational, prospective, multicenter study in adult liver transplant recipients was performed. Two hundred and thirty patients with a good renal function before transplantation were assessed six months post-transplantation (baseline) and every six months until month 30. Results: at baseline, 32% of the patients had a reduction in the glomerular filtration rate below 60 ml/min/1.73 m2. The mean glomerular filtration rate increased from 72.3 to 75.6 ml/min/1.73 m2 at baseline and month 30 respectively (p < 0.01). The mean serum creatinine levels (mg/dl) decreased from 1.13 to 1.09 (p < 0.01). The percentage of patients with stage 3 chronic kidney disease decreased from 31.7% to 26.4%, whereas the percentage of patients with stage 4 remained unchanged (0.4% at baseline and 0.5% at month 30). No patients progressed to end-stage kidney disease that required dialysis or renal transplantation. Conclusion: in the routine clinical practice, a moderate deterioration of renal function is frequent after liver transplantation. However, advanced chronic kidney disease is infrequent in patients with a good pre-transplant renal function.

Hepatitis A infection, caused by hepatitis A virus (HAV), is the leading cause of human viral hepatitis throughout the world and is mainly propagated via the fecal–oral route. Transnational outbreaks of food-borne infections are reported with increasing frequency as a consequence of international food trade. Food-borne outbreaks caused by HAV are mainly associated with bivalve molluscs, produce (soft fruits and leafy greens), and ready-to-eat meals. The purpose of this paper was to conduct a structured and systematic review of the published literature on the current state of knowledge regarding the stability of HAV in foods as well as the efficacy of food processing strategies and to identify and prioritize research gaps regarding practical and effective mechanisms to reduce HAV contamination of foods. In particular, processing and disinfection strategies for the 3 food categories have been compiled in this review, including common and emerging food technologies. Overall, most of these processes can improve food safety; however, from a commercial point of view, none of the methods can guarantee total HAV inactivation without affecting the organoleptic qualities of the food product.

The goal of the present research work was to assess the management of sewage sludge (SS) by composting using fermented water hyacinth (WHferm) as an amendment. The water hyacinth was fermented, and a higher production of volatile fatty acids (VFAs) (782.67 mg L(-1)) and soluble organic carbon (CSOL) (4788.34 mg L(-1)) was obtained using a particle size of 7 mm compared to 50 mm. For composting, four treatments (10 kg fresh weight each) were evaluated: treatment A (100 % SS + 0 % WHferm), treatment B (75 % SS + 25 % WHferm), treatment C (50 % SS + 50 % WHferm), and treatment D (25 % SS + 75 % WHferm). The WHferm added to SS, especially in treatments C (50 %) and D (75 %), increased the initial contents of organic matter (OM), organic carbon (CORG), CSOL, the C/N ratio, and the germination index (GI). The heavy metal content (HMC) (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) at the beginning was below the maximum allowed by USEPA regulations. All of the samples were free of Salmonella sp. from the beginning. The reduction of the CORG, CSOL, total Kjeldahl nitrogen (TKN), and C/N ratio indicated the degradation of the OM by day 198. The treatments with WHferm (B, C, and D) yielded higher values of electrical conductivity, cation exchange capacity, and GI than SS at day 198. No significant differences were observed in GI among the treatments with WHferm. The fecal coliforms were eliminated (

Survival after orthotopic liver transplantation (OLT) has increased over the last decades, focusing on the metabolic complications that contribute to patient morbidity and mortality. The aim of our study was to describe the prevalence of metabolic syndrome (MS), its components, and its associated factors in patients who underwent OLT in a hospital in Spain. From November 2001 to January 2014, we performed 415 transplantations in 386 patients. We analyzed 204 patients with a minimum follow-up of 1 year (77.6% were male and the mean age was 54.2+/-9.5 years). The most frequent etiology was alcohol (41%), followed by hepatitis C virus (29.1%). The indication was decompensated cirrhosis in 51.8% and hepatocellular carcinoma in 34%. According to modified National Cholesterol Education Program-Adult Treatment Panel-III (NCEP-ATP III) criteria, 5 years post-transplantation MS was diagnosed in 38.2% of patients. Significant independent predictors of post-transplantation MS on logistic regression analysis were as follows: pretransplantation obesity (odds ratio [OR], 3.09; P = .056), 1-year post-transplantation obesity (OR, 3.95; P = .009), pretransplantation diabetes (OR, 4.63; P = .001), 1-year post-transplantation diabetes (OR, 3.01; P = .015), 1-year post-transplantation hypertension (OR, 1.85; P = .176), and hypertriglyceridemia at the first year after transplantation (OR, 2.32; P = .063). In our center the prevalence of MS at 5 years after OLT is slightly lower than published. The most important risk factors were obesity and diabetes (both pretransplantation and the first year post-transplantation).

[Abstract] Background and Aims. Hepatitis C (HCV) therapy with Sofosbuvir (SOF)/Simeprevir (SMV) in clinical trials and real‐world clinical practice, showed high rates of sustained virological response (SVR) in non‐cirrhotic genotype (GT)‐1 and GT‐4 patients. These results were slightly lower in cirrhotic patients. We investigated real‐life effectiveness and safety of SOF/SMV with or without ribavirin (RBV) in a large cohort of cirrhotic patients. Methods. This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV‐GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January‐2014 and December‐2015. Demographic, clinical, virological and safety data were analysed. Results. Overall SVR was 92.3%; the majority of patients were treated with RBV (62%) for 12 weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100×109/L, transient elastography≥21 Kpa) showed significantly lower SVR rates (84.4%‐91.9%) than patients with less advanced liver disease (93.8%‐95.9%, P

Background & Aims Antiviral therapy for the treatment of hepatitis C (HCV) infection has proved to be safe and efficacious in patients with cirrhosis awaiting liver transplantation (LT). However, the information regarding the clinical impact of viral eradication in patients on the waiting list is still limited. The aim of the study was to investigate the probability of delisting in patients who underwent antiviral therapy, and the clinical outcomes of these delisted patients. Methods Observational, multicenter and retrospective analysis was carried out on prospectively collected data from patients positive for HCV, treated with an interferon-free regimen, while awaiting LT in 18 hospitals in Spain. Results In total, 238 patients were enrolled in the study. The indication for LT was decompensated cirrhosis (with or without hepatocellular carcinoma [HCC]) in 171 (72%) patients, and HCC in 67 (28%) patients. Sustained virologic response (SVR) rate was significantly higher in patients with compensated cirrhosis and HCC (92% vs. 83% in patients with decompensated cirrhosis with or without HCC, p =0.042). Among 122 patients with decompensated cirrhosis without HCC, 29 (24%) were delisted due to improvement. No patient with baseline MELD score >20 was delisted. After delisting (median follow-up of 88weeks), three patients had clinical decompensations and three had de novo HCC. Only two of the patients with HCC had to be re-admitted onto the waiting list. The remaining 23 patients remained stable, with no indication for LT. Conclusions Antiviral therapy is safe and efficacious in patients awaiting LT. A quarter of patients with decompensated cirrhosis can be delisted asa result of clinical improvement, which appears to be remain stable in most patients. Thus, delisting is a safe strategy that could spare organs and benefit other patients with a more urgent need. Lay summary Antiviral therapy in patients awaiting liver transplantation is safe and efficacious. Viral eradication allows removal from the waiting list of a quarter of treated patients. Delisting because of clinical improvement is a safe strategy that can spare organs for patients in urgent need.

Background & Aims Direct-acting antiviral agents (DAA) combining daclatasvir (DCV) have reported good outcomes in the recurrence of hepatitis C virus (HCV) infection after liver transplant (LT). However, its effect on the severe recurrence and the risk of death remains controversial. We evaluated the efficacy, predictors of survival, and safety of DAC-based regimens in a large real-world cohort. Methods A total of 331 patients received DCV-based therapy. Duration of therapy and ribavirin use were at the investigator's discretion. The primary endpoint was sustained virological response (SVR) at week 12. A multivariate analysis of predictive factors of mortality was performed. Results Intention-to-treat (ITT) and per-protocol SVR were 93.05% and 96.9%. ITT-SVR was lower in cirrhosis (n=163) (96.4% vs. 89.6% p=0.017); the SVR in genotype 3 (n=91) was similar, even in advanced fibrosis (96.7% vs. 88%, p=0.2). Ten patients (3%) experienced virological failure. Therapy was stopped in 18 patients (5.44%), and ten died during treatment. A total of 22 patients (6.6%) died. Albumin (HR= 0.376; 95%CI 0.155-0.910) and baseline MELD (HR=1.137; 95%CI: 1.061-1.218) were predictors of death. Conclusion DCV-based DAA treatment is efficacious and safe in patients with HCV infection after LT. Baseline MELD score and serum albumin are predictors of survival irrespective of viral response. This article is protected by copyright. All rights reserved.

Background & Aims (i) To describe the demographic, clinical, virological and histological characteristics of the patients undergoing evaluation for indication of triple therapy against hepatitis C virus genotype 1, and to identify the reasons why candidate patients are excluded; and (ii) to evaluate the characteristics of the healthcare environment related to treatment. Methods Observational, prospective and multi-centred study involving 16 hospitals of Spain. Data were collected on 1122 patients receiving attention in the outpatient clinics between June and December 2012. Results Of the 1122 patients evaluated, 769 were finally included in this study; 27% (211/769) had contraindications to the therapy. Of those without contraindications, 54% (301/558) did not receive the treatment, and so, only about a third of the patients (33%–257/769) underwent therapy. The reasons for not initiating therapy were as follows: patient refusal (30%), mild disease/awaiting new treatments (34%), restrictions by the health service (30%), other reasons (6%). In univariate analyses, the probability of receiving treatment was related to: age

Cytomegalovirus (CMV) is the most common viral pathogen that negatively affects the outcome of liver transplantation. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases it invades tissues, including the transplanted allograft. In addition, CMV has been significantly associated with an increased predisposition to allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survivals. We carried out a study on a Spanish adult liver transplant recipient who rapidly presented anemia and was diagnosed as having Coomb negative (nonimmune) hemolytic anemia, gastric ulcer, pneumonitis, and cholangitis associated with a CMV infection.

Essential oils (EOs) have long been applied as flavoring agents in foods, and due to their content in antimicrobial compounds, they have potential as natural agents for food preservation. In this study the effect of three EOs, clove, oregano and zataria, was evaluated on the infectivity of norovirus surrogates, i.e. feline calicivirus (FCV) and murine norovirus (MNV). Different concentrations of EOs were individually mixed with each virus at titers of ca. 7–8 log TCID 50 /ml and incubated for 2 h at 4 °C and 37 °C. The infectivity of the recovered viruses after triplicate treatments was evaluated by cell-culture assays. 2% of oregano EO at 37 °C decreased the FCV titers by 3.75 log TCID 50 /ml, with decreasing effects at lower concentrations, and also decreased MNV titers by 1.04–1.62 log TCID 50 /ml, with respect to the concentration used. Clove and zataria EO effects on FCV showed similar trends in titer reductions to those obtained with oregano EO, achieving the maximum titer reduction when FCV was treated at 37 °C with 0.1% of zataria EO. These results represent a step forward in the understanding of EOs as antimicrobials and their possible application in the food industry as alternative natural compounds to reduce viral contamination and, therefore enhancing food safety.

XVIII Jornades de Foment de la Investigació de la Facultat de Ciències Humanes i Socials (Any 2013) The use of Information and Communication Technologies (ICTs) in language learning and teaching has greatly increased in the last decade. Among the different technological tools used in the learning process, virtual worlds have gained popularity among educators and students (e.g. Warburton, 2009; Wang & Burton, 2012; Zhang, 2012; Duncan et al., 2012). This article explores the different possibilities the virtual world Second Life (SL) offers in the language learning process. SL is an online virtual world where residents all over the globe can interact through their avatars by which they can collaborate and learn in an experimental way. This paper offers a theoretical approach about the potential of SL in foreign language education. Firstly, it explores the use of this platform in education, explaining its origins, evolution and current changes. Secondly, it will focus on the advantages and disadvantages of the use of this virtual world for learning languages, paying special attention to the different learning environments, the students’ motivation, and the educational activities amongst others. This paper will conclude with a section of pedagogical implications in which an activity will be proposed to show the different implications of SL in a foreign language classroom. Students will have to work on four different activities that will be based on one of the main four language skills that are established by the Common European Framework of Reference (CEFR): writing, speaking, listening and reading. After explaining the activity, special attention will be paid to the strengths and weaknesses of this specific task.