Clinical infections by herpesviruses in patients treated with valproic acid: A nested case-control study in the Spanish Primary Care Database, BIFAP

The objective of this study is to evaluate the risk of clinical infections by herpesviruses in patients exposed to valproic acid (VPA).We performed a case-control study nested in a primary cohort selected from the Spanish primary care population-based research database BIFAP (Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria) over the period 2001–2015. The events of interest were those diseases caused by any herpesviruses known to infect humans. For each case, up to 10 controls per case matched by age, gender, and calendar date were randomly selected. A conditional logistic regression was used to compute adjusted odds ratios (OR) and their 95% confidence intervals (95% CI). Current use of VPA was associated with a trend towards a reduced risk of clinical infections by herpesviruses as compared with non-users (OR 0.84; CI 95% 0.7–1.0; p = 0.057). Among current users, a trend to a decreased risk with treatment durations longer than 90 days was also observed. The results show a trend to a reduced risk of clinical infection by herpesviruses in patients exposed to VPA. These results are consistent with those in vitro studies showing that, in cultured cells, VPA can inhibit the production of the infectious progeny of herpesviruses. This study also shows the efficient use of electronic healthcare records for clinical exploratory research studie

Role of the small GTPase Rab27a during Herpes simplex virus infection of oligodendrocytic cells

Abstract Background The morphogenesis of herpes simplex virus type 1 (HSV-1) comprises several events, of which some are not completely understood. It has been shown that HSV-1 glycoproteins accumulate in the trans-Golgi network (TGN) and in TGN-derived vesicles. It is also accepted that HSV-1 acquires its final morphology through a secondary envelopment by budding into TGN-derived vesicles coated with viral glycoproteins and tegument proteins. Nevertheless, several aspects of this process remain elusive. The small GTPase Rab27a has been implicated in regulated exocytosis, and it seems to play a key role in certain membrane trafficking events. Rab27a also seems to be required for human cytomegalovirus assembly. However, despite the involvement of various Rab GTPases in HSV-1 envelopment, there is, to date, no data reported on the role of Rab27a in HSV-1 infection. Results Herein, we show that Rab27a colocalized with GHSV-UL46, a tegument-tagged green fluorescent protein-HSV-1, in the TGN. In fact, this small GTPase colocalized with viral glycoproteins gH and gD in that compartment. Functional analysis through Rab27a depletion showed a significant decrease in the number of infected cells and viral production in Rab27a-silenced cells. Conclusions Altogether, our results indicate that Rab27a plays an important role in HSV-1 infection of oligodendrocytic cells.Peer Reviewe

Evidence of Muller's ratchet in herpes simplex virus type 1

Population bottlenecks can have major effects in the evolution of RNA viruses, but their possible influence in the evolution of DNA viruses is largely unknown. Genetic and biological variation of herpes simplex virus type 1 (HSV-1) has been studied by subjecting 23 biological clones of the virus to 10 plaque-to-plaque transfers. In contrast to large population passages, plaque transfers led to a decrease in replicative capacity of HSV-1. Two out of a total of 23 clones did not survive to the last transfer in 143 TK-cells. DNA from three genomic regions (DNA polymerase, glycoprotein gD and thymidine kinase) from the initial and passaged clones was sequenced. Nucleotide substitutions were detected in the TK and gD genes, but not in the DNA polymerase gene. Assuming a uniform distribution of mutations along the genome, the average rate of fixation of mutations was about five mutations per viral genome and plaque transfer. This value is comparable to the range of values calculated for RNA viruses. Four plaque-transferred populations lost neurovirulence for mice, as compared with the corresponding initial clones. LD50 values obtained with the populations subjected to serial bottlenecks were 4-to 67-fold higher than for their parental clones. These results equate HSV-1 with RNA viruses regarding fitness decrease as a result of plaque-to-plaque transfers, and show that population bottlenecks can modify the pathogenic potential of HSV-1. Implications for the evolution of complex DNA viruses are discussed. © 2013 SGM.Comunidad Autonoma de Madrid (GR/SAL/0413/2004); BFU2008-02816/BMC and MCINN from BFU2011-23604; Fundación Ramón Areces; (CIBERehd) in funded by the Instituto de Salud Calos IIIPeer Reviewe

Project based learning: Application to a research master subject of thermal engineering

The European Higher Education Area (EHEA) requires the student a more autonomous work. This autonomy is related to the outcome of the self-regulated learning process. The self-regulation involves a self-management skill set coping with any adverse contingency and entails the knowledge of the available abilities and the personal control to put in action those skills. The learning self-regulation serves as a critical process to develop learning to learn competences that enable to transform the mental aptitudes into academic competences. However, it is necessary to make modifications of the learning conditions to achieve it in an adequate way. Thus, the academic authorities should empower skills that facilitate autonomous learning as well as contribute with tools to the student proactivity. In this sense, the problem-based learning is an effective method to facilitate the acquisition of transversal competences. This didactic methodology may be performed in terms of individual or team-based-learning (TBL) that is necessary linked to a teaching-learning open system. An adaptation of the PBL to the thermal engineering studies, the project based learning model, was designed to the ‘Building Energetic Efficiency’ subject of the Research Master

Project based learning: Application to a research master subject of thermal engineering

The European Higher Education Area (EHEA) requires the student a more autonomous work. This autonomy is related to the outcome of the self-regulated learning process. The self-regulation involves a self-management skill set coping with any adverse contingency and entails the knowledge of the available abilities and the personal control to put in action those skills. The learning self-regulation serves as a critical process to develop learning to learn competences that enable to transform the mental aptitudes into academic competences. However, it is necessary to make modifications of the learning conditions to achieve it in an adequate way. Thus, the academic authorities should empower skills that facilitate autonomous learning as well as contribute with tools to the student proactivity. In this sense, the problem-based learning is an effective method to facilitate the acquisition of transversal competences. This didactic methodology may be performed in terms of individual or team-based-learning (TBL) that is necessary linked to a teaching-learning open system. An adaptation of the PBL to the thermal engineering studies, the project based learning model, was designed to the ‘Building Energetic Efficiency’ subject of the Research Master

Development of Luminescent Nd-Doped LaNbO Compound Thin Film Growth by Magnetron Sputtering for the Improvement of Solar Cells

Nd3+-doped LaNbO phosphor thin films were prepared by radio-frequency magnetron sputtering on Si substrates. The effects of a 1% Nd-doping concentration, after annealing at 1200 °C for 12 h, on the light-emitting properties of the sputtered thin films were characterized via several experimental techniques and deeply discussed. Photoluminescence characterization showed strong emission peaks typical of Nd3+ centers at 880 nm and 1060 nm when a 325 nm wavelength laser source was applied. Similar responses were detected in Nd3+-doped La3NbO7 powder samples fabricated by the solid-state reaction method. The coexistence of two phases (LaNbO4 and La3NbO7) in the thin films with higher nominal thickness was clearly identified based on different structural analyses. The promising results open the possibility for developing phosphor substrates as a preliminary step for the improvement of solar cells based on photon recycling mechanisms

Development of Luminescent Nd-Doped LaNbO Compound Thin Film Growth by Magnetron Sputtering for the Improvement of Solar Cells

Nd3+-doped LaNbO phosphor thin films were prepared by radio-frequency magnetron sputtering on Si substrates. The effects of a 1% Nd-doping concentration, after annealing at 1200 °C for 12 h, on the light-emitting properties of the sputtered thin films were characterized via several experimental techniques and deeply discussed. Photoluminescence characterization showed strong emission peaks typical of Nd3+ centers at 880 nm and 1060 nm when a 325 nm wavelength laser source was applied. Similar responses were detected in Nd3+-doped La3NbO7 powder samples fabricated by the solid-state reaction method. The coexistence of two phases (LaNbO4 and La3NbO7) in the thin films with higher nominal thickness was clearly identified based on different structural analyses. The promising results open the possibility for developing phosphor substrates as a preliminary step for the improvement of solar cells based on photon recycling mechanisms