Using the FVB strain of mice for the evaluation of clinical and experimental ketamine (IP) associated with phenothiazines, benzodiazepines and α2-agonists

El objetivo de este trabajo ha consistido en evaluar el estado fisiológico de los animales mediante el control de las frecuencias respiratoria y cardiaca así como la tasa de saturación de oxígeno durante la anestesia con ketamina asociada a otros fármacos. Para ello hemos utilizado 40 ratones FVB consanguíneos (20 machos y 20 hembras) de 11 semanas de edad, a los que se les administró por vía intraperitoneal ketamina asociada a un depresor del sistema nervioso central: acepromazina, diazepam, medetomidina, midazolam o xilazina. Obtuvimos resultados que difirieron mucho entre sexos, concluyendo que en machos los mejores resultados obtenidos fueron con la asociación a los α2-agonistas, mientras que en las hembras, al menos a las dosis empleadas, no pudimos afirmar que ninguna de las asociaciones fuese óptima.The aim of this work has been to evaluate the physiological status of animals by controlling the respiratory rate and heart rate and oxygen saturation during anesthesia with ketamine in combination with other drugs. We have used 40 consanguine FVB mice (20 males and 20 females) from 11 weeks of age, who were administered intraperitoneally with a ketamine-associated central nervous system depressant:acepromazina, diazepam, medetomidine, midazolam or xylazine. We obtained results that differed greatly between the sexes, in males, concluding that the best results were obtained with the association of α2- agonists, while in females, at least at the doses employed, did not say that none of the associations were optima

Evaluation of toxicological endpoints in female zebrafish after bisphenol A exposure

Given the importance of bisphenol A (BPA) as a xenoestrogen and its potential effects on human and animal, we evaluated BPA exposure's short-term effects on follicular development, yolk protein vitellogenin (VTG) production and aromatase expression in female zebrafish. Histological modifications were observed along with increased presence of atretic follicles. Whole-body VTG concentration increased with the dose of BPA exposure. In contrast, expression of Cyp19a mRNA in the ovaries of BPA-exposed fish exhibited an apparent non- monotonic response curve, marked by downregulation at 1 μg/L BPA, upregulation at 10 μg/L BPA, and a return to downregulation at 100 μg/L BPA and higher doses. Ovaries only exhibited significant increases in follicular atresia and VTG concentration after exposure to 100 μg/L BPA and higher doses. Ovarian histopathology, ar- omatase Cyp19a transcript levels and whole-body VTG protein abundance may be good biomarkers for early detection of environmental BPA exposur

Barriers to Accessing and Using Web Archives in Latin America

Presentation for the IIPC General Assembly and Web Archiving Conference held on May 10-12, 2023 in Hilversum, Netherlands. This presentation discusses linguistic, economic, social, and technical barriers to accessing and using web archives in Latin American countries and possible solutions to lower these barriers

Mycorrhiza induced resistance against pests: from the lab to the field

1 página - Conferencia invitada presentada en Iberian Plant Biology 2023. XVIII Portuguese-Spanish Congress on Plant Biology and the XXV Meeting of the Spanish Society of Plant Biology. 9-12 Julio 2023, Braga, PortugalArbuscular mycorrhizal fungi (AMF) can prime plant defences increasing their resistance against pathogens and insect herbivores. Using tomato as a model, we have shown that inoculation with different AMF reduces the performance of the chewing herbivore Spodoptera exigua and the leaf miner Tuta absoluta. Transcriptomic and metabolomics analyses revealed that this Mycorrhiza Induced Resistance (MIR) is associated to boosted activation of plant direct and indirect defences in response to the attackers. We found primed accumulation in attacked leaves of antiherbivore metabolites, including alkaloids and polyamine conjugates, and functional analyses demonstrated that some of the identified compounds significantly inhibit herbivore development. In addition, the symbiosis altered the volatile blends released by the plant, and enhanced the attraction of natural enemies of the pests (Nesidiocoris tenuis, commonly used in biocontrol programs). Finally, networks analyses allowed the identification of key regulators of the primed response within the jasmonic acid and ethylene signalling pathways. Despite the many studies showing induced resistance by microorganisms in different plant‐pest systems, the variability in the protection achieved under agronomic settings is hindering the application of this strategy in agriculture. Plant‐microbe‐herbivore interactions are highly context dependent, with multiple biotic and abiotic factors influencing the final output. Identifying such factors is essential to optimize the application of microbial inoculants for crop protection in agriculture. We found that the plant genotype and nutrient availability are important drivers of the context dependency of MIR in tomato. Despite of the variability, comparisons across different experimental scales, from controlled lab set‐ups to commercial production conditions, confirmed that MIR can be achieved under crop production conditions and is compatible with other biocontrol methods. Accordingly, MIR can be a relevant addition to current Integrated Pest Management Programs

Pulmonary function and radiologic features in survivors of critical COVID-19: a 3-month prospective cohort

© 2021 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/BACKGROUND: More than 20% of hospitalized patients with COVID-19 demonstrate ARDS requiring ICU admission. The long-term respiratory sequelae in such patients remain unclear. RESEARCH QUESTION: What are the major long-term pulmonary sequelae in critical patients who survive COVID-19? STUDY DESIGN AND METHODS: Consecutive patients with COVID-19 requiring ICU admission were recruited and evaluated 3 months after hospitalization discharge. The follow-up comprised symptom and quality of life, anxiety and depression questionnaires, pulmonary function tests, exercise test (6-min walking test [6MWT]), and chest CT imaging. RESULTS: One hundred twenty-five patients admitted to the ICU with ARDS secondary to COVID- 19 were recruited between March and June 2020. At the 3-month follow-up, 62 patients were available for pulmonary evaluation. The most frequent symptoms were dyspnea (46.7%) and cough (34.4%). Eighty-two percent of patients showed a lung diffusing capacity of less than 80%. The median distance in the 6MWT was 400 m (interquartile range, 362-440 m). CT scans showed abnormal results in 70.2% of patients, demonstrating reticular lesions in 49.1% and fibrotic patterns in 21.1%. Patients with more severe alterations on chest CT scan showed worse pulmonary function and presented more degrees of desaturation in the 6MWT. Factors associated with the severity of lung damage on chest CT scan were age and length of invasive mechanical ventilation during the ICU stay. INTERPRETATION: Three months after hospital discharge, pulmonary structural abnormalities and functional impairment are highly prevalent in patients with ARDS secondary to COVID- 19 who required an ICU stay. Pulmonary evaluation should be considered for all critical COVID-19 survivors 3 months after discharge.This study was supported in part by the Instituto de Salud Carlos III [Grant CIBERESUCICOVID, COV20/00110] and was cofunded by European Regional Development Funds, “Una manera de hacer Europa.” D. d. G.-C. has received financial support from the Instituto de Salud Carlos III [Grant Miguel Servet 2020: CP20/00041], co-funded by the European Social Fund “Investing in Your Future.” L. P. acknowledges receiving financial support from the Ministry of Science, Innovation and Universities for the Training of University Lecturers (FPU19 / 03526).Peer ReviewedPostprint (author's final draft

Development of a prediction model for short-term remission of patients with Crohn’s disease treated with anti-TNF drugs

Therapy with anti-tumor necrosis factor (TNF) has dramatically changed the natural history of Crohn’s disease (CD). However, these drugs are not without adverse events, and up to 40% of patients could lose efficacy in the long term. We aimed to identify reliable markers of response to anti-TNF drugs in patients with CD. A consecutive cohort of 113 anti-TNF naive patients with CD was stratified according to clinical response as short-term remission (STR) or non-STR (NSTR) at 12 weeks of treatment. We compared the protein expression profiles of plasma samples in a subset of patients from both groups prior to anti-TNF therapy by SWATH proteomics. We identified 18 differentially expressed proteins (p ≤ 0.01, fold change ≥ 2.4) involved in the organization of the cytoskeleton and cell junction, hemostasis/platelet function, carbohydrate metabolism, and immune response as candidate biomarkers of STR. Among them, vinculin was one of the most deregulated proteins (p < 0.001), whose differential expression was confirmed by ELISA (p = 0.054). In the multivariate analysis, plasma vinculin levels along with basal CD Activity Index, corticosteroids induction, and bowel resection were factors predicting NSTR

Photoprotective effect of verbascoside from Buddleja cordata in SKH-1 mice exposed to acute and chronic UV-B radiation

Ultraviolet radiation (UVR) is involved in both sunburn and the development of skin cancer, which has a high incidence worldwide. Strategies to reduce these effects include the use of photoprotective substances. The aim of this work was to investigate the photoprotective effect of verbascoside isolated from the methanolic extract of Buddleja cordata (BCME) in SKH-1 mice exposed to acute and chronic UV-B radiation. The mouse dorsal area was evaluated macroscopically and microscopically for diagnosis; verbascoside penetration into mouse skin was investigated in vivo by the tape stripping method. After acute UV-B exposure, 100% of irradiated mice that had been protected with verbascoside showed no signs of sunburn or of inflammatory processes. After chronic exposure, 100% of unprotected mice showed skin carcinomas; in contrast, in mice topically treated with either BCME or verbascoside, the presence of lesions was decreased by 90%. These results prove that verbascoside penetrates through the skin of mice and suggest that verbascoside and BCME may potentially prevent photodamage on mice’s skin after acute and chronic UVR exposure

A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study

Background: The identification of critically ill COVID-19 patients at risk of fatal outcomes remains a challenge. Here, we first validated candidate microRNAs (miRNAs) as biomarkers for clinical decision-making in critically ill patients. Second, we constructed a blood miRNA classifier for the early prediction of adverse outcomes in the ICU. Methods: This was a multicenter, observational and retrospective/prospective study including 503 critically ill patients admitted to the ICU from 19 hospitals. qPCR assays were performed in plasma samples collected within the first 48 h upon admission. A 16-miRNA panel was designed based on recently published data from our group. Results: Nine miRNAs were validated as biomarkers of all-cause in-ICU mortality in the independent cohort of critically ill patients (FDR < 0.05). Cox regression analysis revealed that low expression levels of eight miRNAs were associated with a higher risk of death (HR from 1.56 to 2.61). LASSO regression for variable selection was used to construct a miRNA classifier. A 4-blood miRNA signature composed of miR-16-5p, miR-192-5p, miR-323a-3p and miR-451a predicts the risk of all-cause in-ICU mortality (HR 2.5). Kaplan‒Meier analysis confirmed these findings. The miRNA signature provides a significant increase in the prognostic capacity of conventional scores, APACHE-II (C-index 0.71, DeLong test p-value 0.055) and SOFA (C-index 0.67, DeLong test p-value 0.001), and a risk model based on clinical predictors (C-index 0.74, DeLong test-p-value 0.035). For 28-day and 90-day mortality, the classifier also improved the prognostic value of APACHE-II, SOFA and the clinical model. The association between the classifier and mortality persisted even after multivariable adjustment. The functional analysis reported biological pathways involved in SARS-CoV infection and inflammatory, fibrotic and transcriptional pathways. Conclusions: A blood miRNA classifier improves the early prediction of fatal outcomes in critically ill COVID-19 patients.11 página

Identification of circulating microRNA profiles associated with pulmonary function and radiologic features in survivors of SARS-CoV-2-induced ARDS

There is a limited understanding of the pathophysiology of postacute pulmonary sequelae in severe COVID-19. The aim of current study was to define the circulating microRNA (miRNA) profiles associated with pulmonary function and radiologic features in survivors of SARS-CoV-2-induced ARDS. The study included patients who developed ARDS secondary to SARS-CoV-2 infection (n = 167) and a group of infected patients who did not develop ARDS (n = 33). Patients were evaluated 3 months after hospital discharge. The follow-up included a complete pulmonary evaluation and chest computed tomography. Plasma miRNA profiling was performed using RT-qPCR. Random forest was used to construct miRNA signatures associated with lung diffusing capacity for carbon monoxide (DLCO) and total severity score (TSS). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were conducted. DLCO < 80% predicted was observed in 81.8% of the patients. TSS showed a median [P25;P75] of 5 [2;8]. The miRNA model associated with DLCO comprised miR-17-5p, miR-27a-3p, miR-126-3p, miR-146a-5p and miR-495-3p. Concerning radiologic features, a miRNA signature composed by miR-9-5p, miR-21-5p, miR-24-3p and miR-221-3p correlated with TSS values. These associations were not observed in the non-ARDS group. KEGG pathway and GO enrichment analyses provided evidence of molecular mechanisms related not only to profibrotic or anti-inflammatory states but also to cell death, immune response, hypoxia, vascularization, coagulation and viral infection. In conclusion, diffusing capacity and radiological features in survivors from SARS-CoV-2-induced ARDS are associated with specific miRNA profiles. These findings provide novel insights into the possible molecular pathways underlying the pathogenesis of pulmonary sequelae.This work is supported by Instituto de Salud Carlos III (COV20/00110), co-funded by European Regional Development Fund (ERDF)/“A way to make Europe”. CIBERES is an initiative of the Instituto de Salud Carlos III. Suported by: Programa de donaciones “estar preparados” UNESPA (Madrid, Spain) and Fundación Francisco Soria Melguizo (Madrid, Spain). Supported by La Fundació La Marató de TV3, projecte amb codi 202108-30/-31. COVIDPONENT is funded by Institut Català de la Salut and Gestió de Serveis Sanitaris. MM is the recipient of a predoctoral fellowship (PFIS: FI21/00187) from Instituto de Salud Carlos III. MCGH is the recipient of a predoctoral fellowship from “University of Lleida”. DdGC has received financial support from Instituto de Salud Carlos III (Miguel Servet 2020: CP20/00041), co-funded by the European Social Fund (ESF)/“Investing in your future”. AC acknowledges receiving financial support from Instituto de Salud Carlos III (ISCIII; Sara Borrell 2021: CD21/00087). ENL and GL were funded by COVID1005 and ACT210085 from National Agency of Investigation & Development & Development (ANID), Chil