Preventive nasal administration of flagellin restores antimicrobial effect of gentamicin and protects against a multidrug-resistant strain of Pseudomonas aeruginosa.

The increasing prevalence of multidrug-resistant Pseudomonas aeruginosa (PA) is a significant concern for chronic respiratory disease exacerbations. Host-directed drugs, such as flagellin, an agonist of toll-like receptor 5 (TLR5), have emerged as a promising solution. In this study, we evaluated the prophylactic intranasal administration of flagellin against a multidrug-resistant strain of PA (PAMDR) in mice and assessed the possible synergy with the antibiotic gentamicin (GNT). The results indicated that flagellin treatment before infection decreased bacterial load in the lungs, likely due to an increase in neutrophil recruitment, and reduced signs of inflammation, including proinflammatory cytokines. The combination of flagellin and GNT showed a synergistic effect, decreasing even more the bacterial load and increasing mice survival rates, in comparison to mice pre-treated only with flagellin. These findings suggest that preventive nasal administration of flagellin could restore the effect of GNT against MDR strains of PA, paving the way for the use of flagellin in vulnerable patients with chronic respiratory diseases.

Programa de gestão da dor crónica baseado em mindfulness: Uma scoping review / Chronic pain management program through mindfulness: A scoping review

Introdução: Um dos grandes desafios associados à dor crónica é o seu impacto negativo sobre os aspetos físicos e emocionais do indivíduo, frequentemente relacionados com depressão, ansiedade e incapacidade física. A literatura indica que o Mindfulness é relevante no controlo de dor crónica, existindo programas baseados neste conceito. Dessa forma, verifica-se a necessidade de mapear os seus conteúdos e a sua estrutura. Objetivo: Identificar, na literatura, os conteúdos e a estrutura de um programa com base na atenção plena (Mindfulness) para o alívio da dor crónica. Métodos: Realizou-se uma scoping review, orientada pelas guidelines do Instituto Joanna Briggs e pelo PRISMA-ScR. A pesquisa foi realizada em bases de dados: MEDLINE® with Full Text, CINAHL Complete, Academic Search Complete e Psychology and Behavioral Sciences Collection (acesso via EBSCOhost Web). Os artigos identificados abordam programas e intervenções de Mindfulness na gestão da dor crónica em adultos com idade superior a 18 anos, sem patologia psiquiátrica aguda diagnosticada. Incluíram-se estudos publicados até 2022, escritos em língua inglesa, portuguesa ou espanhola. Os dados foram extraídos a partir de um instrumento desenvolvido pela investigadora, alinhado com o objetivo e as questões de revisão. Foi realizada a síntese dos resultados sob a forma de representações visuais, em formato narrativo e através de quadros. Resultados: Foram incluídos 85 estudos a referir programas/intervenções de Gestão da Dor Crónica baseados em Mindfulness, nos quais foi possível identificar 54 programas e 29 intervenções. Da análise verificada foi possível verificar a existência de 37 diferentes estruturas, residindo esta diferença no número, na duração e no espaçamento entre sessões, entre outros e a presença de 27 conteúdos distintos. Verificou-se, ainda, que todos os programas e intervenções tiveram como referência o programa de Redução do Stresse baseado em Mindfulness. Conclusões: Com este estudo foi possível mapear os vários programas e as intervenções existentes para a Gestão da Dor Crónica baseados em Mindfulness. A caracterização efetuada permitiu perceber que todos os programas tiveram como referência o programa de Redução do Stresse baseado em Mindfulness. Como tal, a grande maioria dos conteúdos existentes são provenientes do referido programa. Ao nível da estrutura, verificou-se uma grande diversidade, a qual se reflete, sobretudo, ao nível da duração, da frequência e do espaçamento entre sessões. Conclui-se, assim, que o número de programas existentes no espaço internacional é reduzido. Esta evidência torna-se ainda mais relevante pelo facto de que todos os programas e intervenções existentes seguem o mesmo modelo de referência.

Introduction: One of the great challenges associated with chronic pain is its negative impact on the physical and emotional aspects of the individual, often related to depression, anxiety and physical disability. Literature points out that Mindfulness is relevant in chronic pain control, and there are programs based on this concept. So, the need to map its contents and structure becomes relevant. Aim: Identify, in literature, the contents and structure of programs based on Mindfulness for the relief of chronic pain. Methods: A scoping review was carried out, using the Joanna Briggs Institute and PRISMAScR guidelines. The research was developed using scientific databases. The selected articles identify Mindfulness programs and interventions in the management of chronic pain in adults with more than 18 years, without diagnosed acute psychiatric pathology. Studies published, until 2022, written in English, Portuguese or Spanish, were included. The data were extracted from an instrument developed by the researcher, aligned with the objective and the review questions. Results were synthesized in the form of visual representations, in narrative format and tables. Results: Eighty-five studies referring to chronic pain management programs and interventions based on Mindfulness were included in this scoping review. 54 programs and 29 interventions were identified. From the analysis carried out it was possible to verify the existence of 37 different structures. These differences relied on the number and duration of the sessions, and frequency the between sessions, among others. 27 different contents were identified. It was possible to verify that all the programs and interventions were based on the Mindfulness-Based Stress Reduction program. Conclusions: This study allowed to map the various existing programs and interventions for the management of chronic pain based on Mindfulness. The characterization carried out showed that all programs had the Mindfulness-Based Stress Reduction program as a reference. As such, most of the existing contents come from that program. In terms of structure, there was a great diversity, which is reflected, above all, in terms of duration and frequency between sessions. It is concluded, therefore, that the number of existing programs in the international space is reduced. This evidence is even more relevant because all existing programs and interventions follow the same reference model.

Nasal Immunization with the C-Terminal Domain of Bcla3 Induced Specific IgG Production and Attenuated Disease Symptoms in Mice Infected with Clostridioides difficile Spores.

Clostridioides difficile is a Gram-positive, spore-forming bacterium that causes a severe intestinal infection. Spores of this pathogen enter in the human body through the oral route, interact with intestinal epithelial cells and persist in the gut. Once germinated, the vegetative cells colonize the intestine and produce toxins that enhance an immune response that perpetuate the disease. Therefore, spores are major players of the infection and ideal targets for new therapies. In this context, spore surface proteins of C. difficile, are potential antigens for the development of vaccines targeting C. difficile spores. Here, we report that the C-terminal domain of the spore surface protein BclA3, BclA3CTD, was identified as an antigenic epitope, over-produced in Escherichia coli and tested as an immunogen in mice. To increase antigen stability and efficiency, BclA3CTD was also exposed on the surface of B. subtilis spores, a mucosal vaccine delivery system. In the experimental conditions used in this study, free BclA3CTD induced antibody production in mice and attenuated some C. difficile infection symptoms after a challenge with the pathogen, while the spore-displayed antigen resulted less effective. Although dose regimen and immunization routes need to be optimized, our results suggest BclA3CTD as a potentially effective antigen to develop a new vaccination strategy targeting C. difficile spores.

A probiotic treatment increases the immune response induced by the nasal delivery of spore-adsorbed TTFC.

BACKGROUND: Spore-forming bacteria of the Bacillus genus are widely used probiotics known to exert their beneficial effects also through the stimulation of the host immune response. The oral delivery of B. toyonensis spores has been shown to improve the immune response to a parenterally administered viral antigen in mice, suggesting that probiotics may increase the efficiency of systemic vaccines. We used the C fragment of the tetanus toxin (TTFC) as a model antigen to evaluate whether a treatment with B. toyonensis spores affected the immune response to a mucosal antigen. RESULTS: Purified TTFC was given to mice by the nasal route either as a free protein or adsorbed to B. subtilis spores, a mucosal vaccine delivery system proved effective with several antigens, including TTFC. Spore adsorption was extremely efficient and TTFC was shown to be exposed on the spore surface. Spore-adsorbed TTFC was more efficient than the free antigen in inducing an immune response and the probiotic treatment improved the response, increasing the production of TTFC-specific secretory immunoglobin A (sIgA) and causing a faster production of serum IgG. The analysis of the induced cytokines indicated that also the cellular immune response was increased by the probiotic treatment. A 16S RNA-based analysis of the gut microbial composition did not show dramatic differences due to the probiotic treatment. However, the abundance of members of the Ruminiclostridium 6 genus was found to correlate with the increased immune response of animals immunized with the spore-adsorbed antigen and treated with the probiotic. CONCLUSION: Our results indicate that B. toyonensis spores significantly contribute to the humoral and cellular responses elicited by a mucosal immunization with spore-adsorbed TTFC, pointing to the probiotic treatment as an alternative to the use of adjuvants for mucosal vaccinations.

Induction of a Specific Humoral Immune Response by Nasal Delivery of Bcla2ctd of Clostridioides difficile.

Clostridioides difficile, formerly known as Clostridium difficile, is a spore-forming bacterium considered as the most common cause of nosocomial infections in developed countries. The spore of C. difficile is involved in the transmission of the pathogen and in its first interaction with the host; therefore, a therapeutic approach able to control C. difficile spores would improve the clearance of the infection. The C-terminal (CTD) end of BclA2, a spore surface protein of C. difficile responsible of the interaction with the host intestinal cells, was selected as a putative mucosal antigen. The BclA2 fragment, BclA2CTD, was purified and used to nasally immunize mice both as a free protein and after adsorption to the spore of Bacillus subtilis, a well-established mucosal delivery vehicle. While the adsorption to spores increased the in vitro stability of BclA2CTD, in vivo both free and spore-adsorbed BclA2CTD were able to induce a similar, specific humoral immune response in a murine model. Although in the experimental conditions utilized the immune response was not protective, the induction of specific IgG indicates that free or spore-bound BclA2CTD could act as a putative mucosal antigen targeting C. difficile spores.

Concentration of 12 Metals and Metalloids in the Blood of White Stork (Ciconia ciconia): Basal Values and Influence of Age and Gender.

The white stork (Ciconia ciconia) is being increasingly used in biomonitoring programmes of environmental contaminants due to its growing population in Europe; however, studies on inorganic elements are scarce. The blood of 70 white storks was collected and analysed by inductively coupled plasma mass spectroscopy (ICP-MS) to determine the presence of the following elements: lead (Pb), mercury (Hg), arsenic (As), nickel (Ni), iron (Fe), zinc (Zn), copper (Cu), selenium (Se), manganese (Mn), chromium (Cr), cobalt (Co), and cadmium (Cd). Our main goals were to determine the mean concentrations of these elements in the blood and to study its association with age and gender. Mean concentrations were highest for Fe, followed by Zn, and lowest for Co and Cd. The metal levels were similar to the values referred in the literature for the same species from different locations. No statistically significant differences were found between males and females. Regarding age, statistically significant differences were observed for Ni, Cu, Se, Hg, and Pb between young and adult animals (except for Pb, values in adults were higher than in fledglings). Many element concentrations were correlated, with the strongest correlations between the pairs Hg-Se, Hg-As, and Fe-Zn, mainly in adults. This study provides the baseline data for a monitoring program based on white stork blood as a nondestructive sample.