Preclinical and clinical studies suggest that inflammation and vascular dysfunction contribute to the pathogenesis of major depressive disorder (MDD). Chronic social stress alters blood–brain barrier ...(BBB) integrity through loss of tight junction protein claudin-5 (cldn5) in male mice, promoting passage of circulating proinflammatory cytokines and depression-like behaviors. This effect is prominent within the nucleus accumbens, a brain region associated with mood regulation; however, the mechanisms involved are unclear. Moreover, compensatory responses leading to proper behavioral strategies and active resilience are unknown. Here we identify active molecular changes within the BBB associated with stress resilience that might serve a protective role for the neurovasculature. We also confirm the relevance of such changes to human depression and antidepressant treatment. We show that permissive epigenetic regulation of cldn5 expression and low endothelium expression of repressive cldn5-related transcription factor foxo1 are associated with stress resilience. Regionand endothelial cell-specific whole transcriptomic analyses revealed molecular signatures associated with stress vulnerability vs. resilience. We identified proinflammatory TNFα/NFκB signaling and hdac1 as mediators of stress susceptibility. Pharmacological inhibition of stress-induced increase in hdac1 activity rescued cldn5 expression in the NAc and promoted resilience. Importantly, we confirmed changes in HDAC1 expression in the NAc of depressed patients without antidepressant treatment in line with CLDN5 loss. Conversely, many of these deleterious CLDN5-related molecular changes were reduced in postmortem NAc from antidepressanttreated subjects. These findings reinforce the importance of considering stress-induced neurovascular pathology in depression and provide therapeutic targets to treat this mood disorder and promote resilience.
Social interaction is known to be the main source of stress in human beings, which explains the translational importance of this research in animals. Evidence reported over the last decade has ...revealed that, when exposed to social defeat experiences (brief episodes of social confrontations during adolescence and adulthood), the rodent brain undergoes remodeling and functional modifications, which in turn lead to an increase in the rewarding and reinstating effects of different drugs of abuse. The mechanisms by which social stress cause changes in the brain and behavior are unknown, and so the objective of this review is to contemplate how social defeat stress induces long‐lasting consequences that modify the reward system. First of all, we will describe the most characteristic results of the short‐ and long‐term consequences of social defeat stress on the rewarding effects of drugs of abuse such as psychostimulants and alcohol. Secondly, and throughout the review, we will carefully assess the neurobiological mechanisms underlying these effects, including changes in the dopaminergic system, corticotrophin releasing factor signaling, epigenetic modifications and the neuroinflammatory response. To conclude, we will consider the advantages and disadvantages and the translational value of the social defeat stress model, and will discuss challenges and future directions.
The mechanisms by which social stress cause changes in the brain and behavior are not completely known. This review addresses the most important neurobiological mechanisms underlying the increase in the rewarding effects of psychostimulants and alcohol induced by social defeat.
The coronavirus disease (COVID-19) pandemic has caused a worldwide health and social crisis directly impacting the healthcare system. Hospitals had to rearrange its structure to meet clinical needs. ...Spain has been experiencing a shortage of working nurses. Student nurses in their last year at university were employed to help the National Health System respond to the COVID-19 crisis.
The aim of this study was to explore and understand the experience of nursing students' roles as healthcare aid in responding to the COVID-19 crisis.
A qualitative phenomenology design was used to explore undergraduate nursing students' perceptions of their experiences as HAs during the COVID-19 outbreak. Open face-to-face interviews were conducted to nursing students (n = 10) in May 2020. Data was analyzed using the hermeneutic interpretative approach.
All participants were women aged between 21 and 25 years. Seven main themes emerged: learning, ambivalent emotions and adaptation were classified at a personal level; teamwork, patient communication, and unclear care processes were categorized under hospital structure; and coping mechanisms were part of external factors.
Orientation, follow-up, and emotional support in crisis situations are key to unexperienced healthcare workers overcoming stressful emotions. Previous academic education and training may help novice future nurses feel more confident about their tasks and responsibilities as well as improve patient outcomes, resource management, and staff safety.
•Nurses are key in response to COVID-19 healthcare crisis.•Spain needs to invest in nursing, to reach the average OCDE nurse-population rate.•Nursing students working as healthcare aids need continuous support and follow-up.•Nursing students were very proud to actively contribute to the COVID-19 crisis.
Aim
There is a need to explore new alternatives for root canal disinfection in regenerative endodontics, since the current strategies are far from ideal. Currently, the potential use of diclofenac ...(DC) is being investigated for controlling root canal infections. The objective was to evaluate the antimicrobial efficacy of novel DC‐based hydrogels (DCHs) against polymicrobial biofilms grown in radicular dentine and root canals and to compare results with triantibiotic (TAH) and diantibiotic (DAH) hydrogels, and calcium hydroxide (CaOH2).
Methodology
The in vitro antimicrobial activity of intracanal medicaments was evaluated against 3‐week‐old polymicrobial root canal biofilms grown on human radicular dentine. Dentine samples were obtained and randomly divided into the study groups (n = 4/group): (1) 1 mg/ml TAH; (2) 1 mg/ml DAH; (3) 5% diclofenac (DCH); (4) 2.5% DCH; (5) 1.25% DCH; (6) 1 mg/ml DAH + 5% DCH; (7) Ca(OH)2 paste; (8) positive control. The microbial viability, in terms of percentage of intact cell membranes, was assessed after 7 days by confocal scanning laser microscopy (CSLM). The ex vivo efficacy of intracanal medications was evaluated in root canals infected with a polymicrobial suspension. Intracanal microbiological samples at baseline (S1) and 7 days post‐treatment (S2) were taken; microbial quantification and cell viability were assessed by quantitative polymerase chain reaction (qPCR) and flow cytometry (FC). The mean Log10 of bacterial DNA copies in root canal samples before (S1) and the Log10 reduction of DNA copies S1–S2 in qPCR were recorded. The absolute value of total cells stained, and the percentage reduction of intact membrane cells after treatment (S1–S2), were analysed by FC. Global comparison was done using the Kruskal–Wallis test, whilst the Mann–Whitney U test was used for pair‐by‐pair comparison.
Results
Confocal scanning laser microscopy analysis indicated that the greatest effectiveness was obtained with 5% DCH, showing significant differences with respect to the other groups (p < .001). In root canals, the highest Log10 DNA reduction S1–S2 was obtained with 5% DCH and TAH, with no differences between them. The results of FC showed that only 5% DCH proved significantly superior to the other treatments.
Conclusions
Sodium DC hydrogels demonstrate antimicrobial efficacy against endodontic biofilms.
•Three different extraction protocols were tested for extraction pesticides from high oil commodities.•Four different clean-ups for QuEChERS were tested.•Sorbent containing ZrO2 provided the best ...results.•Correlation between recoveries and evaporation/reconstitution step was found.
Several extraction methods were evaluated in terms of recoveries and extraction precision for 113 pesticides in avocado: QuEChERS with various d-SPE clean-ups (Z-Sep, Z-Sep+, PSA+C18 and silica), miniLuke and ethyl acetate. Extracts were analysed using liquid chromatography coupled with triple quadrupole mass spectrometer working in multi-reaction monitoring mode. Z-Sep and Z-Sep+ are new types of material for high lipid matrices – these two sorbents contain ZrO2, which improves fat removal from the extracts. The QuEChERS protocol with Z-Sep provided the highest number of pesticides with recoveries in the 70–120% range along with the lowest amount of coextracted matrix compounds. Subsequently, this method was validated in two matrices – avocado and almonds. In the validation recoveries at two levels – 10 and 50μg/kg – limit of quantitation, linearity, matrix effects, as well as the inter- and intraday precision were studied. In the avocado samples, 107 analytes had LOQs equal to 10μg/kg (signal to noise of quantitative transition was equal 20 or more). In the almond samples, 92 pesticides had LOQs equal to 10μg/kg (S/N≥20) and 2 pesticides at 50μg/kg. The validated method was employed in the analysis of real avocado and almond samples.
During recent years matrix effects in liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) have quickly become a major concern in food analysis. The phenomenon of ion suppression can ...lead to errors in the quantification of the analytes of interest, as well as can affect detection capability, precision, and accuracy of the method. Sample dilution is an easy and effective method to reduce interfering compounds, and so, to diminish matrix effects. In this work, matrix effects of 53 pesticides in three different matrices (orange, tomato and leek) were evaluated. Several dilutions of the matrix were tested in order to study the evolution of signal suppression. Dilution of the extracts led to a reduction of the signal suppression in most of the cases. A dilution factor of 15 demonstrated to be enough to eliminate most of the matrix effects, opening the possibility to perform quantification with solvent based standards in the majority of the cases. In those cases where signal suppression could not be reduced, a possible solution would be to use stable isotope-labelled internal standards for quantification of the problematic pesticides.
The neuropeptide oxytocin (OXT) plays a critical role in the regulation of social and emotional behaviors. OXT plays a role in stress response and in drug reward, but to date no studies have ...evaluated its implication in the long-lasting increase of the motivational effects of cocaine induced by repeated social defeat (RSD). During the social defeat procedure, 1 mg/kg of OXT was administered 30 min before each episode of RSD. Three weeks after the last defeat, the effects of cocaine on the conditioned place preference (CPP), locomotor sensitization and the self-administration (SA) paradigms were evaluated. The influence of OXT on the levels of BDNF in the prefrontal cortex (PFC), striatum and hippocampus was also measured. Our results confirm that raising the levels of OXT during social defeat stress can block the long-lasting effects of this type of stress. OXT counteracts the anxiety induced by social defeat and modifies BDNF levels in all the structures we have studied. Moreover, OXT prevents RSD-induced increases in the motivational effects of cocaine. Administration of OXT before each social defeat blocked the social defeat-induced increment in the conditioned rewarding effects of cocaine in the CPP, favored the extinction of cocaine-associated memories in both the CPP and SA, and decreased reinstatement of cocaine-seeking behavior in the SA. In conclusion, the long-lasting effects of RSD are counteracted by administering OXT prior to stress, and changes in BDNF expression may underlie these protective effects.
•Social defeat stress induces a long-lasting increase in anxiety like behavior.•Social defeat stress enhances rewarding properties of cocaine.•Social defeat stress increase BDNF levels in prefrontal cortex.•Oxytocin treatment favors the extinction of cocaine-associated memories.•Oxytocin administration counteracts stress effect in anxiety and in BDNF levels.
Between June 22 and 24, 2020, the Appeals Chamber of the International Criminal Court held the appeal hearings in the Laurent Gbagbo and Charles Blé Goudé case. In them, the parties made their ...observations regarding the alleged error made by the Trial Chamber I in the acquittal pronouncement in failing to apply a clearly defined standard of proof or to sufficiently assess the available evidence, including the reports from non-governmental organizations. In the light of the debate originated in this case, this paper analyse the probative value assigned to these reports in the jurisprudence of the ICC. Also, it is analysed whether the admission of these reports goes against the rights of the accused.
Entre los días 22 y 24 de junio de 2020, la Sala de Apelaciones de la Corte Penal Internacional celebró las audiencias del caso “Gbagbo y Charles Blé Goudé”. En ellas, las partes formularon sus observaciones respecto al supuesto error en el que incurrió la Sala de Primera Instancia en su sentencia de absolución al no aplicar un estándar de prueba claramente definido ni valorar suficientemente las pruebas disponibles, incluyendo los informes de organizaciones no gubernamentales . Al hilo del debate originado en este caso, el presente trabajo analiza el valor probatorio asignado en la jurisprudencia de la CPI a dichos informes y estudia si su admisión como prueba en los procedimientos contravendría los derechos del acusado.
Abstract Introduction The aim of this study was to evaluate the antimicrobial activity of a 2.5% sodium hypochlorite (NaOCl)/9% etidronic acid (HEBP) irrigant solution on Enterococcus faecalis ...growing in biofilms and a dentinal tubule infection model. Methods The antimicrobial activity of the solutions 2.5% NaOCl and 9% HEBP alone and associated was evaluated on E. faecalis biofilms grown in the Calgary biofilm model (minimum biofilm eradication concentration high-throughput device). For the dentinal tubule infection test, the percentage of dead cells in E. faecalis –infected dentinal tubules treated with the solutions for 10 minutes was measured using confocal laser scanning microscopy and the live/dead technique. Available chlorine and pH of the solutions were also measured. Distilled water was used as the control. Nonparametric tests were used to determine statistical differences. Results The highest viability was found in the distilled water group and the lowest in the NaOCl-treated dentin ( P < .05). Both NaOCl solutions killed 100% of the E. faecalis biofilms and showed the highest antimicrobial activity inside dentinal tubules, without statistical differences between the 2 ( P < .05). The HEBP isolated solution killed bacteria inside dentinal tubules but did not present any significant effect against E. faecalis biofilms. The incorporation of HEBP to NaOCl did not cause any loss of available chlorine within 60 minutes. Conclusions HEBP did not interfere with the ability of NaOCl to kill E. faecalis grown in biofilms and inside dentinal tubules.
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