Unexpected Exacerbation of Neuroinflammatory Response After a Combined Therapy in Old Parkinsonian Mice

The design of therapeutic strategies that focus on the repositioning of anti-inflammatory and antioxidant drugs are a great bet to slow down the progression of neurodegenerative disorders. Despite the fact that Parkinson’s disease (PD) is an age-related pathology, almost all experimental studies are carried out in young animals. Here, we evaluated the possible neuroprotective effect of the combination of the antioxidant N-acetylcysteine (NAC) and the anti-inflammatory HA-1077 in aged 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice (C57BL/6 mice, 20 months old), whose individual treatment has been shown to have neuroprotective effects in this Parkinsonism model. Interestingly, NAC+HA-1077-based treatment produced a significant increase in dopaminergic neuronal death accompanied by an increase in microglial and astroglial activation in the Substantia Nigra pars compacta (SNpc) and striatum of old-Parkinsonian mice compared to their control group. The astroglial response was also explored by co-immunostaining for GFAP and S100b together with p-JNK and it was found to be particularly exacerbated in the MPTP+NAC+HA-1077 group. The unexpected toxic effects found in the combined use of NAC and HA-1077 in old-Parkinsonian mice highlight the importance of taking into account that in elderly Parkinsonian patients the combination of some drugs (most of them used for other different age-related alterations) can have side effects that may result in the exacerbation of the neurodegenerative process

Recommendation system to determine suitable and viable hiking routes: a prototype application in Sierra de las Nieves Nature Reserve (southern Spain)

This paper describes a system for recommending hiking routes to help manage hiking activities in a protected area. The system proposes various routes, based on five criteria that maximize some aspects of hikers’ requirements (by analyzing the viability and difficulty of the trails) and also those of protected areas managers (by proposals to relieve congestion in areas already used for hiking and to promote awareness of new ones, as a contribution to environmental education). The recommendation system uses network analysis, multi-criteria decision analysis and geographic information system by free software tools: PgRouting, PostgreSQL and PostGIS. This system has been tested in Sierra de las Nieves Nature Reserve (Andalusia, Spain). Of the 182 routes obtained by the system, 62 (34%) are considered viable for hikers in Sierra de las Nieves, taking into account the type of user most likely to visit this protected area. Most routes have a high difficulty level, which is coherent with the mountainous character of the protected area.This study is a contribution to the Research Projects SEJ2007-67690, funded by the Spanish Ministry of Science and Innovation, and P07HUM-03049, funded by the Ministry of Innovation, Science and Enterprise of the Andalusian Regional Government. This work was carried out within the framework of research group HUM 776 (Geographic Analysis) of the Andalusian Regional Government

IntroVerse: a comprehensive database of introns across human tissues

Dysregulation of RNA splicing contributes to both rare and complex diseases. RNA-sequencing data from human tissues has shown that this process can be inaccurate, resulting in the presence of novel introns detected at low frequency across samples and within an individual. To enable the full spectrum of intron use to be explored, we have developed IntroVerse, which offers an extensive catalogue on the splicing of 332,571 annotated introns and a linked set of 4,679,474 novel junctions covering 32,669 different genes. This dataset has been generated through the analysis of 17,510 human control RNA samples from 54 tissues provided by the Genotype-Tissue Expression Consortium. IntroVerse has two unique features: (i) it provides a complete catalogue of novel junctions and (ii) each novel junction has been assigned to a specific annotated intron. This unique, hierarchical structure offers multiple uses, including the identification of novel transcripts from known genes and their tissue-specific usage, and the assessment of background splicing noise for introns thought to be mis-spliced in disease states. IntroVerse provides a user-friendly web interface and is freely available at https://rytenlab.com/browser/app/introverse

Material docente con un enfoque práctico dirigido a la caracterización de compuestos inorgánicos

Se han elaborado una coleccón de ejercicios utilizando las técnicas de caracterizacion de materiales inorgánicos Además se incluyen un tutorial en el que se dirige al estudiante como es la manera de identificar las bandas caracteristicas de los compuestos, y tambien hay conocimientos generales de EDS. Los ejercicios propuestos tambien se presentan resueltos paso a paso para que se puedan seguir de manera sencilla su desarrollo

Innocampus Explora: Nuevas formas de comunicar ciencia

[EN] Innocampus Explora aims to show the students of the Burjassot-Paterna campus of the Universitat de València how the different scientific degrees are interrelated. To do this we propose activities in which students and teachers work together to cover the interdisciplinary nature of science, both in everyday and professional issues. Throughout this course the activities developed relate to new ways to communicate science. With the development of this project we contribute to a transversal quality education for all the participating students.[ES] Innocampus Explora tiene por objetivo mostrar a los estudiantes del campus de Burjassot-Paterna de la Universitat de València cómo los diferentes grados científicos están interrelacionados. Para ello proponemos actividades en las que estudiantes y profesores trabajen conjuntamente para abarcar la interdisciplinariedad de la ciencia, tanto en temas cotidianos como profesionales. A lo largo de este curso las actividades desarrolladas se relacionan con las nuevas formas de comunicar ciencia. Con el desarrollo de este proyecto contribuimos a una formación transversal de calidad para todos los estudiantes participantes.Moros Gregorio, J.; Rodrigo Martínez, P.; Torres Piedras, C.; Montoya Martínez, L.; Peña Peña, J.; Pla Díaz, M.; Galarza Jiménez, P.... (2019). Innocampus Explora: Nuevas formas de comunicar ciencia. En IN-RED 2019. V Congreso de Innovación Educativa y Docencia en Red. Editorial Universitat Politècnica de València. 814-823. https://doi.org/10.4995/INRED2019.2019.10449OCS81482

Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections

IMPORTANCE The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. OBJECTIVE To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. INTERVENTIONS Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or pa renteral ertapenem for the comparator group after 4 days. MAIN OUTCOMES AND MEASURES The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. RESULTS Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to infinity percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI. -infinity to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). CONCLUSIONS AND RELEVANCE This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections

Plan de comunicación interna y externa de la Facultad de Ciencias Sociales. Programa de Actividades Complementarias y de Difusión Cultural de la Facultad II

Memoria ID-0258. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2014-2015

Discourse Analysis and Terminology in Languages for Specific Purposes

Aquest importantíssim recull conté estudis i reflexions sobre temes rellevants en la recerca sobre LSP: anglès mèdic, el llenguatge de la publicitat i periodístic, telecomunicacions i terminologia informàtica, llenguatge comercial i jurídic... Malgrat que gran part dels treballs aplegats es refereixen a l'anglès, també hi ha que tracten l'alemany, francès i altres llengües. Conté textos en anglès, francés, portuguès i castellà

A randomized, double-blind study on the efficacy of oral domperidone versus placebo for reducing SARS-CoV-2 viral load in mild-to-moderate COVID-19 patients in primary health care

15 p.-3 fig.-3 tab.Introduction:The clinical effect of domperidone against COVID-19 has been investigated in a double-blind phase III clinical trial (EudraCT number 2021-001228-17). Domperidone has shown in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential immudolatory properties through the stimulation of prolactin secretion.Patients and methods:The efficacy of oral domperidone plus standard of care (SOC; n = 87) versus placebo plus SOC (n = 86) was evaluated in a 28-day randomized double-blind multicentre study in primary health care centres. A total of 173 outpatients with mild-to-moderate COVID-19 were included. Three daily doses of 10 mg (30 mg/day) of domperidone or placebo were administered for 7 days. Reduction of viral load on day 4 was the primary efficay endpoint. It was estimated in saliva samples by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), as the cycle thresholds detected ORF1ab, N Protein and S Protein genes.Results:A significant reduction in the viral load was observed (p < 0.001) from baseline to days 4, 7 and 14 of the three genes studied with non-significant differences between domperidone and placebo groups. Twenty-three patients (13.3%) experienced adverse events, 14 patients in the domperidone group (16.1%) and 9 patients in the placebo group (10.5%). No patients needed to be hospitalized.Conclusion: Results do not prove the use of domperidone as antiviral in patients with COVID-19.This research was funded by CSIC (grant no. PIE 201980E024) and by the European Commission: NextGeneration EU (Regulation EU 2020/2094) through CSIC’s Global Health Platform (PTI Salud Global). The study sponsor was Agencia Estatal Consejo Superior de Investigaciones Científicas, M.P. (CSIC), Madrid, Spain. The sponsor was involved in the design, data interpretation, manuscript review and the decision to submit the article for publication.Peer reviewe