Obesidad y carcinoma hepatocelular

Blanca La obesidad es una enfermedad crónica de origen multifactorial prevenible, que se encuentra relacionada con más de 13 tumores diferentes, incluido el carcinoma hepatocelular (HCC). En la mayoría de los casos, la causa del cáncer hepático es el daño prolongado y la cicatrización del hígado [1]. Este hecho se conoce como cirrosis, y puede estar desencadenada por un consumo excesivo de alcohol, por enfermedades auto inmunitarias del hígado, por infecciones causadas por el virus de la hepatitis B o C o por una inflamación crónica del hígado. El desarrollo de la cirrosis relacionada con la inflamación prolongada del hígado engloba un amplio espectro de lesiones hepáticas, que se producen en ausencia de un consumo crónico de alcohol, entre las que se incluyen la esteatosis simple, la estetatosis asociada a cambios necro inflamatorios con grados variables de fibrosis y finalmente la aparición de cirrosis. Actualmente se considera a la enfermedad hepática grasa no alcohólica (NAFLD) como el principal componente hepático del ‘’síndrome metabólico’’, que engloba diferentes factores de riesgo vascular y metabólico como la obesidad visceral, la hiperglucemia, la resistencia a insulina, la dislipemia y la hipertensión arterial. La contribución de las citoquinas pro-inflamatorias secretadas por el tejido adiposo al desarrollo del HCC es de vital importancia y está siendo intensamente estudiada. Entre estas moléculas, destacamos la leptina, una hormona importante en el desarrollo de la obesidad dado que influye en la ingesta y en el gasto energético. Además, se ha postulado que la leptina contribuye al desarrollo de la resistencia a la insulina, la esteatosis, la inflamación y la fibrosis hepática. La leptina se une a su receptor en el hipotálamo y así se inicia una cascada de señalización celular que desencadena efectos fibrogénicos de forma sistémica. La afinidad rigurosa de la unión de la leptina y su receptor, así como la sobreexpresión de la leptina en las células cancerosas hepáticas con respecto a las células normales, hacen de la leptina una diana terapéutica ideal para la prevención y tratamiento del HCC, especialmente en pacientes obesos. Esta revisión proporciona un acercamiento a los efectos patológicos que ejerce la leptina, poniendo especial énfasis en los posibles mecanismos moleculares que desencadenan el daño hepático y el enfoque terapéutico de leptina, que podría ser utilizado en entornos clínicos futuros

Association with litter size of new polymorphisms on ESR1 and ESR2 genes in a Chinese-European pig line

The objective of this study was to search for polymorphisms in the coding region of the estrogen receptors 1 and 2 (ESR1 and ESR2 )and to analyze the effects of these variants and the well known intronic ESR1 Pvu II polymorphism on litter size in a Chinese-European pig line. We identified five silent single nucleotide polymorphisms (SNP) in the ESR1 cDNA: c.669T > C (exon 3), c.1227C > T (exon 5), c.1452C > T (exon 7), c.1665T > C and c.1755A > G (exon 8). One pair of these SNP (c.1665T > C and c.1755A > G) co-segregated in the analyzed line, and the SNP c.669T > C showed the same segregation pattern as the Pvu II polymorphism. These polymorphisms were tested in this study, although the c.1452C > T SNP within exon 7 was not analyzed due to its low informativeness. In the ESR2 cDNA, one missense SNP was found within exon 5, which caused an amino acid substitution in the coded protein: "c.949G > A (p.Val317Met)" and was tested on sow litter size. Information on 1622 litter records from 408 genotyped sows was analyzed to determine whether these SNP influenced the total number of piglets born (TNB) or the number of born alive (NBA). The polymorphisms ESR1: [Pvu II; c.669T > C], ESR1: [c.1665T > C; c.1755A > G] and ESR2: c.949G > A showed no statistically significant association with litter size. However, the ESR1: c.1227T allele was significantly associated with TNB. The additive substitution effect was estimated to be 0.40 piglets born per litter (P < 0.03), and no dominance effects were observed. This SNP could be useful in assisted selection for litter size in some pig lines, as a new genetic marker in linkage disequilibrium with the causative mutation

Active learning and generic competences in an operating systems course

The Bologna Declaration and the implementation of the European Higher Education Area are promoting the use of active learning methodologies. The aim of this study is to evaluate the effects obtained after applying active learning methodologies to the achievement of generic competences as well as to the academic performance. This study has been carried out at the Universidad Politécnica de Madrid, where these methodologies have been applied to the Operating Systems I subject of the degree in Technical Engineering in Computer Systems. The fundamental hypothesis tested was whether the implementation of active learning methodologies (cooperative learning and problem based learning) favours the achievement of certain generic competences (‘teamwork’ and ‘planning and time management’) and also whether this fact improved the academic performance of our students. The original approach of this work consists in using psychometric tests to measure the degree of acquired student’s generic competences instead of using opinion surveys, as usual. Results indicated that active learning methodologies improve the academic performance when compared to the traditional lecture/discussion method, according to the success rate obtained. These methods seem to have as well an effect on the teamwork competence (the perception of the behaviour of the other members in the group) but not on the perception of each students’ behaviour. Active learning does not produce any significant change in the generic competence ‘planning and time management’

Inflamación y neuropatogenia asociada al VIH

Brain HIV-1-infection may result in a syndrome of profound cognitive, behavioural and motor impairment known as AIDS dementia complex (ADC) in adults and HIV-related encephalopathy in children. Although the introduction of HAART has prolonged and improved the lives of infected individuals, it is clear that HAART does not provide complete protection against neurological damage in HIV/AIDS. HIV-1associated dementia is a complex phenomenon, which could be the result of several mechanisms caused by those players using different intracellular signalling pathways. Since HIV-1 does not easily infect neuronal cells, neuronal damage is likely to be induced by soluble factors including viral proteins, proinflammatory cytokines, chemokines or prostaglandins released by HIV-1-infected macrophages or microglial cells. These soluble factors are also responsible for activation of uninfected cells and, thus, for spreading and perpetuation of brain damage.Thus, it is necessary an antiretroviral therapy that not only inhibit microglia infection, but also diminish pro-inflammatory factors and astrocytic activation to reduce neuronal damage.Key Words: Central Nervous System, Inflammation, HIV, Cytokines, Neurodegeneration.La infección cerebral por el VIH puede resultar en una profunda afectación del conocimiento, comportamiento y capacidades motoras, todo ello conocido como complejo demencia sida (CDS) en adultos y encefalopatía en niños (EP). Aunque la introducción de la TARGA ha prolongado y mejorado la vida de los individuos infectados, parece claro que la terapia antirretroviral no proporcional una protección completa frente al daño neurológico observado en esta enfermedad. La demencia-VIH es un complejo fenómeno que aparece como resultado de varios mecanismos causados por múltiples mediadores utilizando diferentes vías de señalización intracelular. Ya que el VIH no parece infectar masivamente a las neuronas, el daño neuronal es probablemente inducido por factores solubles entre los que se incluyen proteínas virales (gp120 y Tat principalmente), citocinas proinflamatorias, quimiocinas y prostaglandinas liberadas por macrófagos cerebrales infectados y células de la microglía activadas y/o infectadas. Estos factores solubles son además los responsables de la activación de células no infectadas aumentando y perpetuando de este modo el daño cerebral. Es pues necesario que la terapia esté dirigida no solo a limitar la infección de la microglía sino también la producción de estos mediadores inflamatorios y la activación de los astrocitos, para poder disminuir el daño neuronal observado en esta enfermedad.Palabras clave: Sistema Nervioso, Inflamación, VIH, Citocinas, Neurodegeneración

Microprocessor error diagnosis by trace monitoring under laser testing

This work explores the diagnosis capabilities of the enriched information provided by microprocessors trace subsystem combined with laser fault injection. Laser fault injection campaigns with delimited architectural regions have been accomplished on an ARM Cortex-A9 device. Experimental results demonstrate the capability of the presented technique to provide additional information of the various error mechanisms that can happen in a microprocessor. A comparison with radiation campaigns presented in previous work is also discussed, showing that laser fault injection results are in good agreement with neutron and proton radiation results

Application of directly brewed compost extract improves yield and quality in baby leaf lettuce grown hydroponically

The aim of this work was to study whether the application of a directly brewed compost extract (added in the nutrient solution or by microsprinkler) could be used to improve the yield and quality of baby leaf red lettuce growing in a floating system, and to control the incidence of Pythium irregulare. Its e_ect on the quality of fresh-cut red lettuce was also studied. For this, two experiments were carried out over two growing cycles (winter–spring and autumn). The results showed that the use of compost extract added to the nutrient solution improved baby leaf lettuce growth and quality, reducing the nitrate content and enhancing the content of potentially health-promoting compounds such as phenols and flavonoids and the antioxidant capacity. Microbial quality was maintained during storage and the compost extract had no negative e_ect on the microbial load of the final product. In addition, application of the compost decreased the population of P. irregulare in the water. It is concluded that the application of directly brewed compost extract is of potential use in a sustainable soilless production system for baby leaf red lettuce, since it improves the yield and quality of the product and is able to control the incidence of P. irregulare.This work was supported by projects AGL2017-84085-C3-3-R and AGL2017-84085-C3-1-R from the Ministerio de Economía y Competitividad of Spain

Cooperative Learning vs. Project Base Learning.

The Bologna Declaration and the implementation of the European Higher Education Area are promoting the use of active learning methodologies such as cooperative learning and project based learning. This study was motivated by the comparison of the results obtained after applying Cooperative Learning (CL) and Project Based Learning (PBL) to a subject of Computer Engineering. The fundamental hypothesis tested was whether the academic success achieved by the students of the first years was higher when CL was applied than in those cases to which PBL was applied. A practical case, by means of which the effectiveness of CL and PBL are compared, is presented in this work. This study has been carried out at the Universidad Politécnica de Madrid, where these mechanisms have been applied to the Operating Systems I subject from the Technical Engineering in Computer Systems degree (OSIS) and to the same subject from the Technical Engineering in Computer Management degree (OSIM). Both subjects have the same syllabus, are taught in the same year and semester and share also formative objectives. From this study we can conclude that students¿ academic performance (regarding the grades given) is greater with PBL than with CL. To be more specific, the difference is between 0.5 and 1 point for the individual tests. For the group tests, this difference is between 2.5 and 3 points. Therefore, this study refutes the fundamental hypothesis formulated at the beginning. Some of the possible interpretations of these results are referred to in this study

Using genome wide association studies to identify common QTL regions in three different genetic backgrounds based on Iberian pig breed

One of the major limitation for the application of QTL results in pig breeding and QTN identification has been the limited number of QTL effects validated in different animal material. The aim of the current work was to validate QTL regions through joint and specific genome wide association and haplotype analyses for growth, fatness and premier cut weights in three different genetic backgrounds, backcrosses based on Iberian pigs, which has a major role in the analysis due to its high productive relevance. The results revealed nine common QTL regions, three segregating in all three backcrosses on SSC1, 0–3 Mb, for body weight, on SSC2, 3–9 Mb, for loin bone-in weight, and on SSC7, 3 Mb, for shoulder weight, and six segregating in two of the three backcrosses, on SSC2, SSC4, SSC6 and SSC10 for backfat thickness, shoulder and ham weights. Besides, 18 QTL regions were specifically identified in one of the three backcrosses, five identified only in BC_LD, seven in BC_DU and six in BC_PI. Beyond identifying and validating QTL, candidate genes and gene variants within the most interesting regions have been explored using functional annotation, gene expression data and SNP identification from RNASeq data. The results allowed us to propose a promising list of candidate mutations, those identified in PDE10A, DHCR7, MFN2 and CCNY genes located within the common QTL regions and those identified near ssc-mir-103-1 considered PANK3 regulators to be further analysed.info:eu-repo/semantics/publishedVersio

Identification of genomic regions regulating sex determination in Atlantic salmon using high density SNP data

Background: A complete understanding of the genetic basis for sexual determination and differentiation is necessary in order to implement efficient breeding schemes at early stages of development. Atlantic salmon belongs to the family Salmonidae of fishes and represents a species of great commercial value. Although the species is assumed to be male heterogametic with XY sex determination, the precise genetic basis of sexual development remains unclear. The complexity is likely associated to the relatively recent salmonid specific whole genome duplication that may be responsible for certain genome instability. This instability together with the capacity of the sex-determining gene to move across the genome as reported by previous studies, may explain that sexual development genes are not circumscribed to the same chromosomes in all members of the species. In this study, we have used a 220 K SNP panel developed for Atlantic salmon to identify the chromosomes explaining the highest proportion of the genetic variance for sex as well as candidate regions and genes associated to sexual development in this species. Results: Results from regional heritability analysis showed that the chromosomes explaining the highest proportion of variance in these populations were Ssa02 (heritability = 0.42, SE = 0.12) and Ssa21 (heritability = 0.26, SE = 0.11). After pruning by linkage disequilibrium, genome-wide association analyses revealed 114 SNPs that were significantly associated with sex, being Ssa02 the chromosome containing a greatest number of regions. Close examination of the candidate regions evidenced important genes related to sex in other species of Class Actinopterygii, including SDY, genes from family SOX, RSPO1, ESR1, U2AF2A, LMO7, GNRH-R, DND and FIGLA. Conclusions: The combined results from regional heritability analysis and genome-wide association have provided new advances in the knowledge of the genetic regulation of sex determination in Atlantic salmon, supporting that Ssa02 is the candidate chromosome for sex in this species and suggesting an alternative population lineage in Spanish wild populations according to the results from Ssa21.Ministerio de Economía y Competitividad | Ref. RZ2012–00011-C02–00Ministerio de Ciencia e Innovación | Ref. JCI-2011-1089

Pseudomonas aeruginosa antibiotic susceptibility profiles, genomic epidemiology and resistance mechanisms: a nation-wide five-year time lapse analysis

COVID-19; SARS-CoV-2; Electronic health recordsCOVID-19; SARS-CoV-2; Registros médicos electrónicosCOVID 19; SARS-CoV-2; Registres mèdics electrònicsBackground Pseudomonas aeruginosa healthcare-associated infections are one of the top antimicrobial resistance threats world-wide. In order to analyze the current trends, we performed a Spanish nation-wide high-resolution analysis of the susceptibility profiles, the genomic epidemiology and the resistome of P. aeruginosa over a five-year time lapse. Methods A total of 3.180 nonduplicated P. aeruginosa clinical isolates from two Spanish nation-wide surveys performed in October 2017 and 2022 were analyzed. MICs of 13 antipseudomonals were determined by ISO-EUCAST. Multidrug resistance (MDR)/extensively drug resistance (XDR)/difficult to treat resistance (DTR)/pandrug resistance (PDR) profiles were defined following established criteria. All XDR/DTR isolates were subjected to whole genome sequencing (WGS). Findings A decrease in resistance to all tested antibiotics, including older and newer antimicrobials, was observed in 2022 vs 2017. Likewise, a major reduction of XDR (15.2% vs 5.9%) and DTR (4.2 vs 2.1%) profiles was evidenced, and even more patent among ICU isolates [XDR (26.0% vs 6.0%) and DTR (8.9% vs 2.6%)] (p < 0.001). The prevalence of Extended-spectrum β-lactamase/carbapenemase production was slightly lower in 2022 (2.1%. vs 3.1%, p = 0.064). However, there was a significant increase in the proportion of carbapenemase production among carbapenem-resistant strains (29.4% vs 18.1%, p = 0.0246). While ST175 was still the most frequent clone among XDR, a slight reduction in its prevalence was noted (35.9% vs 45.5%, p = 0.106) as opposed to ST235 which increased significantly (24.3% vs 12.3%, p = 0.0062). Interpretation While the generalized decrease in P. aeruginosa resistance, linked to a major reduction in the prevalence of XDR strains, is encouraging, the negative counterpart is the increase in the proportion of XDR strains producing carbapenemases, associated to the significant advance of the concerning world-wide disseminated hypervirulent high-risk clone ST235. Continued high-resolution surveillance, integrating phenotypic and genomic data, is necessary for understanding resistance trends and analyzing the impact of national plans on antimicrobial resistance.This work was supported by MSD and by the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea—NextGenerationEU through grants PI21/00017 and Personalized and precision medicine grant (MePRAM Project, PMP22/00092)