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Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with no therapeutic consensus. Oxidation and inflammation are hallmarks in the progression of this complex disease, which also involves interactions between the genetic background and the environment. Mastiha is a natural nutritional supplement known to possess antioxidant and anti-inflammatory properties. This study investigated how a 6-month Mastiha supplementation (2.1 g/day) could impact the antioxidant and inflammatory status of patients with NAFLD, and whether genetic variants significantly mediate these effects. We recruited 98 patients with obesity (BMI ≥ 30 kg/m2) and NAFLD and randomly allocated them to either the Mastiha or the placebo group for 6 months. The anti-oxidative and inflammatory status was assessed at baseline and post-treatment. Genome-wide genetic data was also obtained from all participants, to investigate gene-by-Mastiha interactions. NAFLD patients with severe obesity (BMI > 35kg/m2) taking the Mastiha had significantly higher total antioxidant status (TAS) compared to the corresponding placebo group (P value=0.008). We did not observe any other significant change in the investigated biomarkers as a result of Mastiha supplementation alone. We identified several novel gene-by-Mastiha interaction associations with levels of cytokines and antioxidant biomarkers. Some of the identified genetic loci are implicated in the pathological pathways of NAFLD, including the lanosterol synthase gene (LSS)associated with glutathione peroxidase activity (Gpx) levels, the mitochondrial pyruvate carrier-1 gene (MPC1)and the sphingolipid transporter-1 gene (SPNS1) associated with hemoglobin levels, the transforming growth factor‐beta‐induced gene (TGFBI) and the micro-RNA 129-1 (MIR129-1)associated with IL-6 and the granzyme B gene (GZMB) associated with IL-10 levels. Within the MAST4HEALTH randomized clinical trial (NCT03135873,www.clinicaltrials.gov) Mastiha supplementation improved the TAS levels among NAFLD patients with severe obesity. We identified several novel genome-wide significant nutrigenetic interactions, influencing the antioxidant and inflammatory status in NAFLD.

OBJECTIVES: Oral microbiome plays an important role in oral diseases. Among them, proliferative verrucous leucoplakia (PVL) is an uncommon form of progressive multifocal leukoplakia with a worryingly rate of malignant transformation. Here, we aimed to characterize the oral microbiome of PVL patients and compare it with those of healthy controls. MATERIAL AND METHODS: Oral biopsies from ten PVL patients and five healthy individuals were obtained and used to compare their microbial communities. The sequence of the V3-V4 region of 16S rRNA gene was used as the taxonomic basis to estimate and analyze the composition and diversity of bacterial populations present in the samples. RESULTS: Our results show that the oral microbial composition and diversity are significantly different among PVL patients and healthy donors. The average number of observed operational taxonomic units (OTUs) was higher for healthy donors than for PVL, proving a loss of diversity in PVL. Several OTUs were found to be more abundant in either group. Among those that were significantly enriched in PVL patients, potential protumorigenic pathogens like Oribacterium sp. oral taxon 108, Campylobacter jejuni, uncultured Eubacterium sp., Tannerella, and Porphyromonas were identified. CONCLUSION: Oral microbiome dysbiosis was found in patients suffering from PVL. To the best of our knowledge, this is the first study investigating the oral microbiome alterations in PVL and, due to the limited number of participants, additional studies are needed. Oral microbiota-based biomarkers may be helpful in predicting the risks for the development of PVL.

Scope: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease with poor therapeutic strategies. Mastiha possesses antioxidant/anti-inflammatory and lipid-lowering properties. The authors investigate the effectiveness of Mastiha as a nonpharmacological intervention in NAFLD. Methods and Results: Ninety-eight patients with NAFLD in three countries (Greece, Italy, Serbia) are randomly allocated to either Mastiha or Placebo for 6 months, as part of a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The authors assess NAFLD severity via magnetic resonance imaging (MRI) scanning and LiverMultiScan technique and evaluate the effectiveness of Mastiha through medical, anthropometric, biochemical, metabolomic, and microbiota assessment. Mastiha is not superior to Placebo on changes in iron-corrected T1 (cT1) and Liver Inflammation Fibrosis score (LIF) in entire patient population; however, after BMI stratification (BMI ≤ 35 kg m-2 and BMI > 35 kg m-2), severely obese patients show an improvement in cT1 and LIF in Mastiha versus Placebo. Mastiha increases dissimilarity of gut microbiota, as shown by the Bray-Curtis index, downregulates Flavonifractor, a known inflammatory taxon and decreases Lysophosphatidylcholines-(LysoPC) 18:1, Lysophosphatidylethanolamines-(LysoPE) 18:1, and cholic acid compared to Placebo. Conclusion: Mastiha supplementation improves microbiota dysbiosis and lipid metabolite levels in patients with NAFLD, although it reduces parameters of liver inflammation/fibrosis only in severely obese patients. © 2021 Wiley-VCH GmbH

Objectives To explore the pathophysiology of proliferative verrucous leukoplakia, a rare oral disorder that exhibits high rates of recurrence and malignant transformation, through a RNAseq case-control study. Material and methods We obtained oral biopsies from 10 patients with verrucous leukoplakia lesions and from the mucosa of 5 healthy individuals for sequencing using RNAseq technology. Using bioinformatic methods, we investigated gene expression and enrichment differences between patients both with and without the disorder. We applied network biology methods to investigate functional relations among those genes that were differentially deregulated. Results We detected 140 differentially expressed genes with distinct roles in immune surveillance, tissue and organ morphogenesis, development, and organization. Of these 140 genes, 111 have been previously described as cancer expression biomarkers, being oral squamous cell carcinoma the most represented type of cancer among them. Of these 140 genes, 26 were prioritized for further investigation as biomarkers using larger sample sizes. Conclusions The gene expression patterns of healthy and unhealthy patients differed in 140 genes whose deregulation has a functional impact on normal functioning of the immune system. This immune expression profile provides a plausible hypothesis to explain the transformation to oral squamous cell carcinoma observed in 6 of the 10 assayed cases.

Trabajo presentado al: 37th International Society for Animal Genetics Conference (ISAG). Abstract book, P216, pp.121.Lleida, Spain, 7-12 Julio 2019.

The incidence of opportunistic yeast infections in humans has been increasing over recent years. These infections are difficult to treat and diagnose, in part due to the large number and broad diversity of species that can underlie the infection. In addition, resistance to one or several antifungal drugs in infecting strains is increasingly being reported, severely limiting therapeutic options and showcasing the need for rapid detection of the infecting agent and its drug susceptibility profile. Current methods for species and resistance identification lack satisfactory sensitivity and specificity, and often require prior culturing of the infecting agent, which delays diagnosis. Recently developed high-throughput technologies such as next generation sequencing or proteomics are opening completely new avenues for more sensitive, accurate and fast diagnosis of yeast pathogens. These approaches are the focus of intensive research, but translation into the clinics requires overcoming important challenges. In this review, we provide an overview of existing and recently emerged approaches that can be used in the identification of yeast pathogens and their drug resistance profiles. Throughout the text we highlight the advantages and disadvantages of each methodology and discuss the most promising developments in their path from bench to bedside., The authors discuss the current status of the use of high-throughput (-omics) technologies on the diagnostics of yeast infections.

Background There has been an increasing interest in studying sickness presenteeism (SP). An ever-increasing amount of scientific literature is published using this term, yet there appears to be considerable heterogeneity in how it is assessed, which could result in substantial differences in the definition and interpretation of the phenomenon really being studied. We aim to discuss what really is being studied, depending on how the phenomenon is operationalized, measured, and analyzed. Methods A study based on a literature review and an empirical illustration using data of the third Spanish Psychosocial Risks Survey (2016). Results Differences are observed based on the population in which SP is measured, the cut-off points used to define a worker as presenteeist, the reasons for an SP episode and even an analysis of the phenomenon treated as a count or as a dichotomous. Conclusions Without being completely exclusive, it seems that restricting the population of analysis to only those workers who consider that they should not have gone to work due to their health, and/or establishing low cut-off points to define someone as presenteeist, would more clearly delimit the study of SP to the exercise of a right to sick leave. In contrast, working with the entire population or using high cut-off points appears to relate the study of SP more with health status and less with the exercise of rights. On the other hand, taking the reasons for SP into account would probably help to improve interpretation of the phenomenon.

The innate immune system provides a primary line of defense against pathogens. Stimulator of IFN genes (STING), encoded by the TMEM173 gene, is a critical protein involved in IFN-b induction in response to infection by different pathogens. In this study, we describe the expression of three different alternative-spliced human (h) TMEM173 mRNAs producing STING truncated isoforms 1, 2, and 3 in addition to the full-length wild-type (wt) hSTING. All of the truncated isoforms lack exon 7 and share the N-terminal transmembrane region with wt hSTING. Overexpression of the three STING truncated isoforms failed to induce IFN-b, and they acted as selective pathway inhibitors of wt hSTING even in combination with upstream inducer cyclic-di-GMP-AMP synthase. Truncated isoforms alter the stability of wt hSTING, reducing protein t1/2 to some extent by the induction of proteasome-dependent degradation. Knocking down expression of truncated isoforms increased production of IFN-b by THP1 monocytes in response to intracellular cytosolic DNA or HSV-1 infection. At early stages of infection, viruses like HSV-1 or vesicular stomatitis virus reduced the ratio of full-length wt hSTING/truncated STING isoforms, suggesting the skewing of alternative splicing of STING toward truncated forms as a tactic to evade antiviral responses. Finally, in silico analysis revealed that the human intron–exon gene architecture of TMEM173 (splice sites included) is preserved in other mammal species, predominantly primates, stressing the relevance of alternative splicing in regulating STING antiviral biology.

Vibrio vulnificus (Vv) is a multi-host pathogenic species currently subdivided into three biotypes (Bts). The three Bts are human-pathogens, but only Bt2 is also a fish-pathogen, an ability that is conferred by a transferable virulence-plasmid (pVvbt2). Here we present a phylogenomic analysis from the core genome of 80 Vv strains belonging to the three Bts recovered from a wide range of geographical and ecological sources. We have identified five well-supported phylogenetic groups or lineages (L). L1 comprises a mixture of clinical and environmental Bt1 strains, most of them involved in human clinical cases related to raw seafood ingestion. L2 is formed by a mixture of Bt1 and Bt2 strains from various sources, including diseased fish, and is related to the aquaculture industry. L3 is also linked to the aquaculture industry and includes Bt3 strains exclusively, mostly related to wound infections or secondary septicemia after farmed-fish handling. Lastly, L4 and L5 include a few strains of Bt1 associated with specific geographical areas. The phylogenetic trees for ChrI and II are not congruent to one another, which suggests that inter-and/or intra-chromosomal rearrangements have been produced along Vv evolution. Further, the phylogenetic trees for each chromosome and the virulence plasmid were also not congruent, which also suggests that pVvbt2 has been acquired independently by different clones, probably in fish farms. From all these clones, the one with zoonotic capabilities (Bt2-Serovar E) has successfully spread worldwide. Based on these results, we propose a new updated classification of the species based on phylogenetic lineages rather than on Bts, as well as the inclusion of all Bt2 strains in a pathovar with the particular ability to cause fish vibriosis, for which we suggest the name "piscis."

Background: Antibiotic resistance is a major biomedical problem upon which public health systems demand solutions to construe the dynamics and epidemiological risk of resistant bacteria in anthropogenically-altered environments. The implementation of computable models with reciprocity within and between levels of biological organization (i.e. essential nesting) is central for studying antibiotic resistances. Antibiotic resistance is not just the result of antibiotic-driven selection but more properly the consequence of a complex hierarchy of processes shaping the ecology and evolution of the distinct subcellular, cellular and supra-cellular vehicles involved in the dissemination of resistance genes. Such a complex background motivated us to explore the P-system standards of membrane computing an innovative natural computing formalism that abstracts the notion of movement across membranes to simulate antibiotic resistance evolution processes across nested levels of micro- and macro-environmental organization in a given ecosystem. Results: In this article, we introduce ARES (Antibiotic Resistance Evolution Simulator) a software device that simulates P-system model scenarios with five types of nested computing membranes oriented to emulate a hierarchy of eco-biological compartments, i.e. a) peripheral ecosystem; b) local environment; c) reservoir of supplies; d) animal host; and e) host's associated bacterial organisms (microbiome). Computational objects emulating molecular entities such as plasmids, antibiotic resistance genes, antimicrobials, and/or other substances can be introduced into this framework and may interact and evolve together with the membranes, according to a set of pre-established rules and specifications. ARES has been implemented as an online server and offers additional tools for storage and model editing and downstream analysis. Conclusions: The stochastic nature of the P-system model implemented in ARES explicitly links within and between host dynamics into a simulation, with feedback reciprocity among the different units of selection influenced by antibiotic exposure at various ecological levels. ARES offers the possibility of modeling predictive multilevel scenarios of antibiotic resistance evolution that can be interrogated, edited and re-simulated if necessary, with different parameters, until a correct model description of the process in the real world is convincingly approached. ARES can be accessed at http://gydb.org/ares.

While the model of public service television that focuses on audiences has been traditionally criticised for being more akin to the commercial television model than to the public service broadcasting model, contemporary literature points out that in the age of digitisation and convergence audience participation is precisely a key element of public television (Castro, 2012; Doyle, 2010; Kjus, 2009; Bardoel, 2007). This article examines audience participation in Spanish regional public service television and, particularly, tries to determine two questions: 1) whether the variety of participation channels provided by crossmedia productions –a TV show’s website, discussion forums and Twitter and Facebook accounts– increases effective audience participation; and 2) whether this participation can be said to contribute to the fulfilment of the mission of public service television, especially proximity television. Method. The study first provides a review of the literature on audience participation and the forms of participation promoted by European, national and regional policies. The TV show La noche de…, broadcast by the Spanish network ETB 2, is subsequently analysed based on the results of the literature review. Results: The increasing attention paid to audience participation in the European and Spanish literature and legislations is not proportionally reflected on the reality of public service television, and particularly of regional public service television corporations.

To describe the view of faculty who train health and safety professionals on the roles and competencies needed to promote the integration of preventive actions at the company level.We used a Delphi method, in three rounds, on an intentional sample of experts, and asked them to rate the appropriateness, relevance and acceptability of 8 professional roles, on a scale of 1 to 9 points. We also asked them to formulate and rank order the corresponding competencies, in order of importance.Participant responses (n=76, 58% of the initially identified faculty) show a broad consensus when assessing professional roles (over 85% of participants rated two of these roles highly, with scores between 7 and 9) and general agreement on the three most important competencies in terms of knowledge, skills and attitudes to promote the integration of preventive actions.The experts participating in this study agreed that the main roles to be performed by health and safety professionals to promote prevention integration are as advisors and trainers. The competencies considered most important are knowledge about the company activity, its risks and the problems linked to the activity (to know), ability to work in multidisciplinary teams (to know how), and to perform professional duties ethically, with independence and impartiality (to know how to be).Conocer el punto de vista de docentes que forman prevencionistas acerca de cuáles son los roles y competencias necesarios en los profesionales de la salud laboral para promover la integración de la prevención en la empresa. MÉTODO: Se utiliza la técnica Delphi en triple vuelta sobre una muestra intencional de expertos a los que se pidió que puntuaran en una escala de 1 a 9 la pertinencia, relevancia y aceptabilidad de un listado de ocho roles, y que enunciaran y ordenaran según su importancia las correspondientes competencias.Las respuestas obtenidas de los participantes (n=76, 58% de los docentes en el listado inicial) muestran amplio consenso en la valoración de los roles (más del 85% de los participantes coinciden en otorgar puntuaciones altas –entre 7 y 9– para dos de los ocho roles listados) así como un acuerdo generalizado sobre las tres competencias más importantes en relación con los conocimientos, habilidades y actitudes adecuadas para promover la integración de la prevención en la empresa.En opinión de los expertos participantes los principales roles que debe ejercer el profesional de salud laboral para promover la integración de la prevención son el de asesor y el de formador. Las competencias consideradas como más importantes son el conocimiento de la actividad de la empresa así como los riesgos y los problemas derivados de dicha actividad (saber), la capacidad de trabajar en equipos multidisciplinares (saber hacer), y el poseer ética profesional, independencia e imparcialidad (saber ser, estar).

This article describes and analyses the regulatory frameworks and the current pluralism protection policies in the United States and several countries of the European Union (Germany, France, the United Kingdom, the Netherlands, Italy and Spain). The data obtained allowed a qualitative assessment to be carried out, through a comparative analysis, in order to identify certain similarities and some significant differences. Thus, it was found that pluralism protection is a common denominator in the communication policies of these countries. However, regulatory and legislative differences depend on social, geographical and media contexts, and time variations in the application of policies depend on audiovisual media market liberalisation processes.

Along this paper we study how a small and regional public television channel has used public funding to improve its service and to enlarge its scope to new technologies. The case we have selected is CCRTV Interactiva (CCRTV Interactive), a sister company of the Corporaci6 Catalana de Mitjans Audiovisuals (Catalan Audiovisual Media Corporation), a public regional corporation depending on the Catalonian Government. After reviewing the legal and market framework, we analyse the strategy of the corporation, its services and its results. A reasonable funding, a good coordination between old and new media and between creative and technological personnel, an effective leadership and the creation of a separated company seems to be key factors to understand the success of CCRTV Interactiva on new media markets.

The genome of the pea aphid shows remarkable levels of gene duplication and equally remarkable gene absences that shed light on aspects of aphid biology, most especially its symbiosis with Buchnera., Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems., Author Summary Aphids are common pests of crops and ornamental plants. Facilitated by their ancient association with intracellular symbiotic bacteria that synthesize essential amino acids, aphids feed on phloem (sap). Exploitation of a diversity of long-lived woody and short-lived herbaceous hosts by many aphid species is a result of specializations that allow aphids to discover and exploit suitable host plants. Such specializations include production by a single genotype of multiple alternative phenotypes including asexual, sexual, winged, and unwinged forms. We have generated a draft genome sequence of the pea aphid, an aphid that is a model for the study of symbiosis, development, and host plant specialization. Some of the many highlights of our genome analysis include an expanded total gene set with remarkable levels of gene duplication, as well as aphid-lineage-specific gene losses. We find that the pea aphid genome contains all genes required for epigenetic regulation by methylation, that genes encoding the synthesis of a number of essential amino acids are distributed between the genomes of the pea aphid and its symbiont, Buchnera aphidicola, and that many genes encoding immune system components are absent. These genome data will form the basis for future aphid research and have already underpinned a variety of genome-wide approaches to understanding aphid biology.