Corticotrophin-Releasing Factor (CRF) through CRF1 Receptor Facilitates the Expression of Morphine-Related Positive and Aversive Memory in Mice

Different studies have elucidated the mechanisms underlying the formation and expression of drug-related cue memories; corticotrophin-releasing factor (CRF) plays a critical role in reward- and aversion-driven associative learning. In the present chapter, we have evaluated whether CP-154,526, a selective CRF1 receptor (CRF1R) antagonist, or genetic deletion of CRF1R (KO mice) have comparable effects on conditioned place preference (CPP) and conditioned place aversion (CPA) learning. We also investigated CP-154,526 effects on morphine-induced CPP activation of CRF, CREB phosphorylation, and thioredoxin (Trx1) expression in dentate gyrus (DG), a brain region involved in memory consolidation, and the role of hypothalamic-pituitary-adrenocortical (HPA) axis in CPA expression and extinction. The CRF1R antagonist abolished the acquisition of morphine CPP, Trx-1 and BDNF increased expression, and pCREB/Trx-1 co-localization in the DG. The increase in adrenocorticotropic hormone (ACTH) plasma levels observed after CPA expression was attenuated in CRF1R KO mice, suggesting a role of HPA axis in aversive memories. Altogether, these results suggest a critical role of CRF, through CRF1R, in molecular changes involved in memory formation and consolidation and may facilitate the development of effective treatments for opioid addiction

Antimicrobial residue assessment in 5, 357 commercialized meat samples from the Spain-France cross-border area: A new approach for effective monitoring

Although antimicrobials are valuable allies in animal production, their extended use has led to unexpected threats associated with the emergence and propagation of antimicrobial resistance. Moreover, when withdrawal periods in food-producing animals are not observed, antimicrobial residues can access the food chain, causing direct toxicity, allergies, and/or intestinal microbiota dysbiosis in consumers. Given that Spain and France are the largest meat producers in the EU and also count among the top consumers of meat, our study''s aim was to investigate the presence of antimicrobials in commercialized meat purchased in the Spain-France cross-border area (POCTEFA region). 5, 357 meat samples were collected from different animal species and a variety of different retailer types in Spain (Zaragoza, Bilbao, and Logroño) as well as in France (Toulouse and Perpignan). Meat samples were analysed by a screening method (Explorer®+QuinoScan®), yielding 194 positive samples, which were further evaluated by UPLC-QTOF (Ultra Performance Liquid Chromatography-Quadrupole Time of Flight) for confirmation. Chromatographic analyses found antimicrobial residues in 30 samples, although only 5 of them (0.093% of initial samples) were non-compliant according to the current legislation. Further studies suggested that this mismatch between screening and confirmatory analyses might be due to the presence of biologically active metabolites derived from degradation of antimicrobials that were not identified by the targeted UPLC-QTOF method, but which might play a decisive role in the inhibition of the biological Explorer® test. Although chromatographic techniques detect the marker compounds determined by European and national regulations, and although they are the methods selected for official control of antimicrobials in food, certain unknown metabolites might escape their monitoring. This thus suggests that biological tests are the most adequate ones in terms of ideal consumer health protection

Evolution of the use of corticosteroids for the treatment of hospitalised COVID-19 patients in Spain between March and November 2020: SEMI-COVID national registry

Objectives: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. Material and methods: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID- 19 Registry from March to November 2020. Results: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236- 996) µg/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%. Conclusions: Patients with greater comorbidity, severity, and inflammatory markers were those treated with CTs. In severe patients, there is a trend towards the use of higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Poblaciones de estafilococos coagulasa positivos en carne de pollo

En el presente trabajo se evalúa la calidad microbiológica de la carne de pollo. Se han determinado las poblaciones de estafilococos coagulasa positivos en distintos productos de pollo. En el 5,56% de las muestras analizadas se encontraron poblaciones comprendidas entre 1 y 2,3 log ufc/g

Evaluación de la eficacia del tratamiento con ácido málico para reducir las poblaciones de Salmonella presente en carne de pollo

En el presente trabajo se evalúa la calidad eficacia del ácido málico en el contro de Salmonella en carne de pollo. Los resultados obtenidos ponen de manifiesto la eficacia del ácido málico para reducir las poblaciones de Salmonella sin afectar negativamente a la calidad sensoria

Sporadic melanoma in South-Eastern Italy: the impact of melanocortin 1 receptor (MC1R) polymorphism analysis in low-risk people and report of three novel variants

Environmental and genetic risk factors are involved in the development of melanoma. The role of the melanocortin 1 receptor (MC1R) gene has been investigated and differences according to geographic areas have been described. To evaluate the role of some clinical and genetic risk factors in melanoma development, we performed a case–control study involving 101 melanoma patients and 103 controls coming from South-Eastern Italy (Puglia), after achieving informed consent. We confirmed the role of known clinical risk factors for melanoma. Furthermore, 42 MC1R polymorphisms were observed. Three of these variants (L26V, H232L, D294Y) were not previously reported in the literature. Their predicted impact on receptor function was evaluated using bioinformatic tools. We report an overall frequency of MC1R variants in our population higher than in Northern or Central Italy. The most common polymorphism found was V60L, that has been recently reported to spread among South Mediterranean population. This variant influenced phenotypic characteristics of our population while it did not impinge on melanoma risk. An increased risk of melanoma was associated with two or more MC1R variants, when at least one was RHC, compared to people carrying the MC1R consensus sequence or a single MC1R polymorphism. Interestingly, we observed an increased risk of melanoma in subjects with darker skin and lower nevus count, usually considered at low risk, when carrying MC1R polymorphisms