Genetic and Molecular Factors in Drug-Induced Liver Injury: A Review

The diagnosis of drug-induced liver injury (DILI) is challenging and based on complex diagnostic criteria. DILI falls into two main categories i) intrinsic 'dose-dependent' Type A reactions ii) 'idiosyncratic' or Type B reactions (which are usually not predictable). Idiosyncratic reactions can be immunoallergic (hypersensitivity), or metabolic, although overlap between categories can occur. The aim of this review is to summarise the general view of underlying mechanisms in DILI and to highlight individual risk factors for developing hepatotoxicity. Polymorphisms of bioactivation/ toxification pathways through CYP450 enzymes (Phase I), detoxification reactions (Phase II) and excretion/transport (Phase III) are explored together with immunological factors that might determine DILI. The importance of establishing a multidisciplinary and multi-centric network to promote the understanding and research in hepatotoxicity is underlined. Challenges such as genetic analyses for association studies and whole genome studies, pharmacogenetic testing and future approaches to study DILI are considered. Knowledge regarding these operational mechanisms could provide further insight for the prospective identification of susceptible patients at risk of developing drug-induced hepatotoxicity.

Carpal tunnel syndrome associated with oral bisphosphonates. A population-based cohort study

© 2016 Carvajal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Bisphosphonates are widely used to prevent osteoporotic fractures. Some severe musculoskeletal reactions have been described with this medication; among them, some cases of carpal tunnel syndrome. Thus, the aim of this study was to explore whether bisphosphonates may be associated with this syndrome. Methods: A cohort study was conducted to compare exposed to unexposed women; the exposed group was that composed of women having received at least one prescription of an oral bisphosphonate. For the purpose, we used information from The Health Improvement Network (THIN) database. The outcome of interest was defined as those women diagnosed with carpal tunnel syndrome. A survival analysis was performed; the Cox proportional hazard model was used to calculate hazard ratios and 95% confidence intervals, and to adjust for identified confounding variables. Results: Out of a sample of 59,475 women older than 51 years, 19,825 were treated with bisphosphonates during the period studied. No differences in age distribution or mean follow-up time were observed between the two groups in comparison. Overall, there were 572 women diagnosed with carpal tunnel syndrome, 242 (1.2%) in the group exposed to bisphosphonates, and 330 (0.8%) in the unexposed. An adjusted hazard ratio of developing carpal tunnel syndrome of 1.38 (95%CI, 1.15-1.64) was found for women exposed to bisphosphonates; no significant changes in the hazard ratios were found when considering different levels of bisphosphonate exposure

Distintas narrativas para un mismo contenido : la tabla periódica en los libros de texto

Se analizan las ‘narrativas’ implícitas en una muestra amplia de libros de texto para establecer una tipologia que tiene implicaciones en la selección de los contenidos de los temas que se tratan en el libro. Se ha centrado el estudio en la Tabla periódica de los elementos, siguiendo las investigaciones de Linares (2004) y Izquierdo y Adúriz (2007). Los resultados del análisis que se ha realizado en una muestra amplia de libros de texto a partir de los años cincuenta muestran que la manera de presentar a la Tabla Periódica en el libro intenta ser coherente con el enfoque global de la química en él. Ahora bien, se detectan incoherencias que nos llevan a proponer un foro de discusión sobre el diseño de los contenidos de química a la luz de las propuestas didácticas actuales y sobre la función actual de los libros de texto en la enseñanza de la Química

The Cross-Cultural Invariance of the Servant Leadership Survey: A Comparative Study across Eight Countries

This paper tests and confirms the cross-cultural equivalence of the Servant Leadership Survey (SLS) in eight countries and languages: The Netherlands, Portugal, Germany, Iceland, Italy, Spain, Turkey and Finland. A composite sample consisting of 5201 respondents from eight countries that all filled out the SLS was used. A three-step approach was adopted to test configural invariance, measurement equivalence, and structural equivalence. For the full 30-item version of the SLS, configural invariance and partial measurement equivalence were confirmed. Implications of these results for the use of the SLS within cross-cultural studies are discussed

The influence of roads on the fine-scale population genetic structure of the dengue vector Aedes aegypti (Linnaeus)

Dengue is endemic in tropical and subtropical countries and is transmitted mainly by Aedes aegypti. Mosquito movement can be affected by human-made structures such as roads that can act as a barrier. Roads can influence the population genetic structure of Ae. aegypti. We investigated the genetic structure and gene flow of Ae. aegypti as influenced by a primary road, Espana Boulevard (EB) with 2000-meter-long stretch and 24-meters-wide in a very fine spatial scale. We hypothesized that Ae. aegypti populations separated by EB will be different due to the limited gene flow as caused by the barrier effect of the road. A total of 359 adults and 17 larvae Ae. aegypti were collected from June to September 2017 in 13 sites across EB. North (N1-N8) and South (S1-S5) comprised of 211 and 165 individuals, respectively. All mosquitoes were genotyped at 11 microsatellite loci. AMOVA FST indicated significant genetic differentiation across the road. The constructed UPGMA dendrogram found 3 genetic groups revealing the clear separation between North and South sites across the road. On the other hand, Bayesian cluster analysis showed four genetic clusters (K = 4) wherein each individual samples have no distinct genetic cluster thus genetic admixture. Our results suggest that human-made landscape features such as primary roads are potential barriers to mosquito movement thereby limiting its gene flow across the road. This information is valuable in designing an effective mosquito control program in a very fine spatial scale

Evaluation of cleaning and disinfection procedures against Samonella enterica at swine farms, transport and lairage facilities

Evaluation of the cleaning and disinfection protocols effectiveness against Salmonella in three points of the pork production chain: finishing farm, transport and lairage. A 22.2% of the farms, 62.5% of the slaughter trucks and 63.6% of the holding pens tested were positive to Salmonella after cleaning and disinfection procedures

TERC polymorphisms are associated both with susceptibility to colorectal cancer and with longer telomeres.

Shorter telomeres have been associated with increased risk of malignancy, including colorectal cancer (CRC). Telomere length is heritable and may be an intermediate phenotype linked to genetic susceptibility to CRC