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Distinct bacteria are able to cope with highly diverse lifestyles; for instance, they can be free living or host-associated. Thus, these organisms must possess a large and varied genomic arsenal to withstand different environmental conditions. To facilitate the identification of genomic features that might influence bacterial adaptation to a specific niche, we introduce LifeStyle-Specific-Islands (LiSSI). LiSSI combines evolutionary sequence analysis with statistical learning (Random Forest with feature selection, model tuning and robustness analysis). In summary, our strategy aims to identify conserved consecutive homology sequences (islands) in genomes and to identify the most discriminant islands for each lifestyle.

Microbes are highly diverse and widely distributed organisms. They account for ~60% of Earth’s biomass and new predictions point for the existence of 1011 to 1012 species, which are constantly sharing genes through several different mechanisms. Genomic Islands (GI) are critical in this context, as they are large regions acquired through horizontal gene transfer. Also, they present common features like genomic signature deviation, transposase genes, flanking tRNAs and insertion sequences. GIs carry large numbers of genes related to specific lifestyle and are commonly classified in Pathogenicity, Resistance, Metabolic or Symbiotic Islands. With the advent of the next-generation sequencing technologies and the deluge of genomic data, many software tools have been developed that aim to tackle the problem of GI prediction and they are all based on the prediction of GI common features. However, there is still room for the development of new software tools that implements new approaches, such as, machine learning and pangenomics based analyses. Finally, GIs will always hold a potential application in every newly invented genomic approach as they are directly responsible for much of the genomic plasticity of bacteria.

Systems biology plays a central role for biological network analysis in the post-genomic era. Cytoscape is the standard bioinformatics tool offering the community an extensible platform for computational analysis of the emerging cellular network together with experimental omics data sets. However, only few apps/plugins/tools are available for simulating network dynamics in Cytoscape 3. Many approaches of varying complexity exist but none of them have been integrated into Cytoscape as app/plugin yet. Here, we introduce PetriScape, the first Petri net simulator for Cytoscape. Although discrete Petri nets are quite simplistic models, they are capable of modeling global network properties and simulating their behaviour. In addition, they are easily understood and well visualizable. PetriScape comes with the following main functionalities: (1) import of biological networks in SBML format, (2) conversion into a Petri net, (3) visualization as Petri net, and (4) simulation and visualization of the token flow in Cytoscape. PetriScape is the first Cytoscape plugin for Petri nets. It allows a straightforward Petri net model creation, simulation and visualization with Cytoscape, providing clues about the activity of key components in biological networks.

HTLV was initially described in association with a form of leukemia in Japan and a neurological disease in the Caribbean. It was soon shown that HTLV-II was endemic among Amerindians and particularly among Brazilian Indians. The Amazon Region of Brazil is presently the largest endemic area for this virus and has allowed several studies concerning virus biology, the search for overt disease, epidemiological data including detailed demographic data on infected individuals, clear-cut geographic distribution, definition of modes of transmission and maintenance within small, epidemiologically-closed groups, and advances in laboratory diagnosis of the infection. A new molecular subtype named HTLV-IIc was further described on the basis of genome sequencing and phylogenetic analysis. This subtype is present in other areas of Brazil, indicating that the virus is additionally both a valuable marker for tracing past human migration routes in the Americas and a probable marker for social habits of the present human population. HIV, the other human retrovirus, is still not prevalent among indigenous communities in the Brazilian Amazon, but these groups are also easy targets for the virus.

Blood samples from native Indians in the Kararao village (Kayapo), were analysed using serological and molecular methods to characterize infection and analyse transmission of HTLV-II. Specific reactivity was observed in 3/26 individuals, of which two samples were from a mother and child. RFLP analysis of the pX and env regions confirmed HTLV-II infection. Nucleotide sequence of the 5' LTR segment and phylogenetic analysis showed a high similarity (98%) between the three samples and prototype HTLV-IIa (Mot), and confirmed the occurrence of the HTLV-IIc subtype. There was a high genetic similarity (99.9%) between the mother and child samples and the only difference was a deletion of two nucleotides (TC) in the mother sequence. Previous epidemiological studies among native Indians from Brazil have provided evidence of intrafamilial and vertical transmission of HTLV-IIc. The present study now provides molecular evidence of mother-to-child transmission of HTLV-IIc, a mechanism that is in large part responsible for the endemicity of HTLV in these relatively closed populations. Although the actual route of transmission is unknown, breast feeding would appear to be most likely.

Abstract Background Singular value decomposition (SVD) is a powerful technique for information retrieval; it helps uncover relationships between elements that are not prima facie related. SVD was initially developed to reduce the time needed for information retrieval and analysis of very large data sets in the complex internet environment. Since information retrieval from large-scale genome and proteome data sets has a similar level of complexity, SVD-based methods could also facilitate data analysis in this research area. Results We found that SVD applied to amino acid sequences demonstrates relationships and provides a basis for producing clusters and cladograms, demonstrating evolutionary relatedness of species that correlates well with Linnaean taxonomy. The choice of a reasonable number of singular values is crucial for SVD-based studies. We found that fewer singular values are needed to produce biologically significant clusters when SVD is employed. Subsequently, we developed a method to determine the lowest number of singular values and fewest clusters needed to guarantee biological significance; this system was developed and validated by comparison with Linnaean taxonomic classification. Conclusions By using SVD, we can reduce uncertainty concerning the appropriate rank value necessary to perform accurate information retrieval analyses. In tests, clusters that we developed with SVD perfectly matched what was expected based on Linnaean taxonomy.

Abstract Background The use of food-grade Lactic Acid Bacteria (LAB) as DNA delivery vehicles represents an attractive strategy to deliver DNA vaccines at the mucosal surfaces as they are generally regarded as safe (GRAS). We previously showed that either native Lactococcus lactis (LL) or recombinant invasive LL expressing Fibronectin Binding Protein A of Staphylococcus aureus (LL-FnBPA+) or Internalin A of Listeria monocytogenes (LL-InlA+), were able to deliver and trigger DNA expression by epithelial cells, either in vitro or in vivo. InlA does not bind to its receptor, the murine E-cadherin, thus limiting the use of LL-InlA+ in in vivo murine models. Moreover, FnBPA binds to its receptors, integrins, via fibronectin introducing another limiting factor. In order to avoid the limitations of LL-InlA+ and LL-FnBPA+, a new L. lactis strain was engineered to produce a previously described mutated form of InlA (LL-mInlA+) allowing the binding of mInlA on murine E-cadherin. Results After showing the expression of mInLA at the surface of LL-mInlA+ strain, in vitro gentamycin survival assay in Caco-2 cells showed that LL-mInlA+ is 1000 times more invasive than LL. LL-mInlA+ invasivity was also validated by fluorescence microscopy. LL and LL-mInlA+ were transformed with pValacBLG, a plasmid containing the cDNA of bovine β-Lactoglobulin (BLG), resulting in strains LL-BLG and LL-mInlA+BLG. The plasmid transfer in vitro using LL-mInlA+BLG was increased 10 times compared to LL-BLG. Moreover, the number of mice producing BLG in isolated enterocytes after oral administration of LL-mInlA+BLG in vivo was slightly higher than after oral administration of LL-BLG. Conclusions We confirmed in this study that the production of mInlA at the surface of L. lactis is a promising strategy for plasmid transfer in vitro and in vivo.

Abstract Background Peanut (Arachis hypogaea L.) is a crop of economic and social importance, mainly in tropical areas, and developing countries. Its molecular breeding has been hindered by a shortage of polymorphic genetic markers due to a very narrow genetic base. Microsatellites (SSRs) are markers of choice in peanut because they are co-dominant, highly transferrable between species and easily applicable in the allotetraploid genome. In spite of substantial effort over the last few years by a number of research groups, the number of SSRs that are polymorphic for A. hypogaea is still limiting for routine application, creating the demand for the discovery of more markers polymorphic within cultivated germplasm. Findings A plasmid genomic library enriched for TC/AG repeats was constructed and 1401 clones sequenced. From the sequences obtained 146 primer pairs flanking mostly TC microsatellites were developed. The average number of repeat motifs amplified was 23. These 146 markers were characterized on 22 genotypes of cultivated peanut. In total 78 of the markers were polymorphic within cultivated germplasm. Most of those 78 markers were highly informative with an average of 5.4 alleles per locus being amplified. Average gene diversity index (GD) was 0.6, and 66 markers showed a GD of more than 0.5. Genetic relationship analysis was performed and corroborated the current taxonomical classification of A. hypogaea subspecies and varieties. Conclusions The microsatellite markers described here are a useful resource for genetics and genomics in Arachis. In particular, the 66 markers that are highly polymorphic in cultivated peanut are a significant step towards routine genetic mapping and marker-assisted selection for the crop.

Abstract Background Caseous lymphadenitis (CLA), caused by Corynebacterium pseudotuberculosis, is one of the most important diseases of sheep and goats, causing considerable economic losses for herd owners. Results We assessed the seroprevalence of infection with C. pseudotuberculosis in 805 sheep from 23 sheep farms that supply slaughterhouses in the state of Minas Gerais; we also analyzed management practices that could be associated with CLA occurrence, used on these and nearby farms that also supplied animals to the slaughterhouse (n = 60). The serum samples for assaying CLA infection were taken at the slaughterhouse. Frequency of infection with C. pseudotuberculosis was estimated at 43.7%, and farm frequency was estimated at 100%. Management practices were analyzed through a questionnaire. All farmers (60/60) had extensive/semi-extensive rearing system; 70.0% (42/60) identified sheep individually; 11.7% (7/60) had periodical technical assistance; 41.7% (25/60) disinfected the facilities; 86.7% (52/60) used barbed wire fences and did not implement adequate CLA control measures; only 11.7% (7/60) of breeders reported vaccination against C. pseudotuberculosis; 13.3% (8/60) took note of animals with clinical signs of CLA; 1.7% (1/60) opened and sanitized abscesses, and isolated the infected animals; 10.0% (6/60) knew the zoonotic potential of this disease and 1.7% (1/60) of the farmers culled animals in case of recurrence of abscesses. Conclusions It can be concluded that C. pseudotuberculosis infection is widely spread in sheep flocks in Minas Gerais state in Brazil and that there is a lack of good management measures and vaccination, allowing transmission of this infectious agent throughout the production network.

Abstract Background Corynebacterium ulcerans has been detected as a commensal in domestic and wild animals that may serve as reservoirs for zoonotic infections. During the last decade, the frequency and severity of human infections associated with C. ulcerans appear to be increasing in various countries. As the knowledge of genes contributing to the virulence of this bacterium was very limited, the complete genome sequences of two C. ulcerans strains detected in the metropolitan area of Rio de Janeiro were determined and characterized by comparative genomics: C. ulcerans 809 was initially isolated from an elderly woman with fatal pulmonary infection and C. ulcerans BR-AD22 was recovered from a nasal sample of an asymptomatic dog. Results The circular chromosome of C. ulcerans 809 has a total size of 2,502,095 bp and encodes 2,182 predicted proteins, whereas the genome of C. ulcerans BR-AD22 is 104,279 bp larger and comprises 2,338 protein-coding regions. The minor difference in size of the two genomes is mainly caused by additional prophage-like elements in the C. ulcerans BR-AD22 chromosome. Both genomes show a highly similar order of orthologous coding regions; and both strains share a common set of 2,076 genes, demonstrating their very close relationship. A screening for prominent virulence factors revealed the presence of phospholipase D (Pld), neuraminidase H (NanH), endoglycosidase E (EndoE), and subunits of adhesive pili of the SpaDEF type that are encoded in both C. ulcerans genomes. The rbp gene coding for a putative ribosome-binding protein with striking structural similarity to Shiga-like toxins was additionally detected in the genome of the human isolate C. ulcerans 809. Conclusions The molecular data deduced from the complete genome sequences provides considerable knowledge of virulence factors in C. ulcerans that is increasingly recognized as an emerging pathogen. This bacterium is apparently equipped with a broad and varying set of virulence factors, including a novel type of a ribosome-binding protein. Whether the respective protein contributes to the severity of human infections (and a fatal outcome) remains to be elucidated by genetic experiments with defined bacterial mutants and host model systems.

Abstract Background Heat shock proteins (HSPs) are important candidates for the development of vaccines because they are usually able to promote both humoral and cellular immune responses in mammals. We identified and characterized the hsp60-hsp10 bicistronic operon of the animal pathogen Corynebacterium pseudotuberculosis, a Gram-positive bacterium of the class Actinobacteria, which causes caseous lymphadenitis (CLA) in small ruminants. Findings To construct the DNA vaccine, the hsp60 gene of C. pseudotuberculosis was cloned in a mammalian expression vector. BALB/c mice were immunized by intramuscular injection with the recombinant plasmid (pVAX1/hsp60). Conclusion This vaccination induced significant anti-hsp60 IgG, IgG1 and IgG2a isotype production. However, immunization with this DNA vaccine did not confer protective immunity.

Abstract Background Second generation technologies have advantages over Sanger; however, they have resulted in new challenges for the genome construction process, especially because of the small size of the reads, despite the high degree of coverage. Independent of the program chosen for the construction process, DNA sequences are superimposed, based on identity, to extend the reads, generating contigs; mismatches indicate a lack of homology and are not included. This process improves our confidence in the sequences that are generated. Findings We developed Quality Assessment Software, with which one can review graphs showing the distribution of quality values from the sequencing reads. This software allow us to adopt more stringent quality standards for sequence data, based on quality-graph analysis and estimated coverage after applying the quality filter, providing acceptable sequence coverage for genome construction from short reads. Conclusions Quality filtering is a fundamental step in the process of constructing genomes, as it reduces the frequency of incorrect alignments that are caused by measuring errors, which can occur during the construction process due to the size of the reads, provoking misassemblies. Application of quality filters to sequence data, using the software Quality Assessment, along with graphing analyses, provided greater precision in the definition of cutoff parameters, which increased the accuracy of genome construction.

Abstract Background Bacterial exported proteins represent key components of the host-pathogen interplay. Hence, we sought to implement a combined approach for characterizing the entire exoproteome of the pathogenic bacterium Corynebacterium pseudotuberculosis, the etiological agent of caseous lymphadenitis (CLA) in sheep and goats. Results An optimized protocol of three-phase partitioning (TPP) was used to obtain the C. pseudotuberculosis exoproteins, and a newly introduced method of data-independent MS acquisition (LC-MSE) was employed for protein identification and label-free quantification. Additionally, the recently developed tool SurfG+ was used for in silico prediction of sub-cellular localization of the identified proteins. In total, 93 different extracellular proteins of C. pseudotuberculosis were identified with high confidence by this strategy; 44 proteins were commonly identified in two different strains, isolated from distinct hosts, then composing a core C. pseudotuberculosis exoproteome. Analysis with the SurfG+ tool showed that more than 75% (70/93) of the identified proteins could be predicted as containing signals for active exportation. Moreover, evidence could be found for probable non-classical export of most of the remaining proteins. Conclusions Comparative analyses of the exoproteomes of two C. pseudotuberculosis strains, in addition to comparison with other experimentally determined corynebacterial exoproteomes, were helpful to gain novel insights into the contribution of the exported proteins in the virulence of this bacterium. The results presented here compose the most comprehensive coverage of the exoproteome of a corynebacterial species so far.

Abstract Background Corynebacterium pseudotuberculosis is generally regarded as an important animal pathogen that rarely infects humans. Clinical strains are occasionally recovered from human cases of lymphadenitis, such as C. pseudotuberculosis FRC41 that was isolated from the inguinal lymph node of a 12-year-old girl with necrotizing lymphadenitis. To detect potential virulence factors and corresponding gene-regulatory networks in this human isolate, the genome sequence of C. pseudotuberculosis FCR41 was determined by pyrosequencing and functionally annotated. Results Sequencing and assembly of the C. pseudotuberculosis FRC41 genome yielded a circular chromosome with a size of 2,337,913 bp and a mean G+C content of 52.2%. Specific gene sets associated with iron and zinc homeostasis were detected among the 2,110 predicted protein-coding regions and integrated into a gene-regulatory network that is linked with both the central metabolism and the oxidative stress response of FRC41. Two gene clusters encode proteins involved in the sortase-mediated polymerization of adhesive pili that can probably mediate the adherence to host tissue to facilitate additional ligand-receptor interactions and the delivery of virulence factors. The prominent virulence factors phospholipase D (Pld) and corynebacterial protease CP40 are encoded in the genome of this human isolate. The genome annotation revealed additional serine proteases, neuraminidase H, nitric oxide reductase, an invasion-associated protein, and acyl-CoA carboxylase subunits involved in mycolic acid biosynthesis as potential virulence factors. The cAMP-sensing transcription regulator GlxR plays a key role in controlling the expression of several genes contributing to virulence. Conclusion The functional data deduced from the genome sequencing and the extended knowledge of virulence factors indicate that the human isolate C. pseudotuberculosis FRC41 is equipped with a distinct gene set promoting its survival under unfavorable environmental conditions encountered in the mammalian host.

Abstract Background Bacteria may compete with yeast for nutrients during bioethanol production process, potentially causing economic losses. This is the first study aiming at the quantification and identification of Lactic Acid Bacteria (LAB) present in the bioethanol industrial processes in different distilleries of Brazil. Results A total of 489 LAB isolates were obtained from four distilleries in 2007 and 2008. The abundance of LAB in the fermentation tanks varied between 6.0 × 105 and 8.9 × 108 CFUs/mL. Crude sugar cane juice contained 7.4 × 107 to 6.0 × 108 LAB CFUs. Most of the LAB isolates belonged to the genus Lactobacillus according to rRNA operon enzyme restriction profiles. A variety of Lactobacillus species occurred throughout the bioethanol process, but the most frequently found species towards the end of the harvest season were L. fermentum and L. vini. The different rep-PCR patterns indicate the co-occurrence of distinct populations of the species L. fermentum and L. vini, suggesting a great intraspecific diversity. Representative isolates of both species had the ability to grow in medium containing up to 10% ethanol, suggesting selection of ethanol tolerant bacteria throughout the process. Conclusions This study served as a first survey of the LAB diversity in the bioethanol process in Brazil. The abundance and diversity of LAB suggest that they have a significant impact in the bioethanol process.

Abstract Background Lactic acid bacteria (LAB) are attractive tools to deliver therapeutic molecules at the mucosal level. The model LAB Lactococcus lactis has been intensively used to produce and deliver such heterologous proteins. However, compared to recombinant lactococci, lactobacilli offer some advantages such as better survival in the digestive tract and immunomodulatory properties. Here, we compared different strategies to optimize the production of bovine β-lactoglobulin (BLG), a major cow's milk allergen, in the probiotic strain Lactobacillus casei BL23. Results Using a nisin-inducible plasmid system, we first showed that L. casei BL23 strain could efficiently secrete a reporter protein, the staphylococcal nuclease (Nuc), with the lactococcal signal peptide SPUsp45 fused to its N-terminus. The fusion of SPUsp45 failed to drive BLG secretion but led to a 10-fold increase of intracellular BLG production. Secretion was significantly improved when the synthetic propeptide LEISSTCDA (hereafter called LEISS) was added to the N-terminus of the mature moiety of BLG. Secretion rate of LEISS-BLG was 6-fold higher than that of BLG alone while intracellular production reached then about 1 mg/L of culture. The highest yield of secretion was obtained by using Nuc as carrier protein. Insertion of Nuc between LEISS and BLG resulted in a 20-fold increase in BLG secretion, up to 27 μg/L of culture. Furthermore, the lactococcal nisRK regulatory genes were integrated into the BL23 chromosome. The nisRK insertion allowed a decrease of BLG synthesis in uninduced cultures while BLG production increased by 50% after nisin induction. Moreover, modification of the induction protocol led to increase the proportion of soluble BLG to around 74% of the total BLG production. Conclusion BLG production and secretion in L. casei were significantly improved by fusions to a propeptide enhancer and a carrier protein. The resulting recombinant strains will be further tested for their ability to modulate the immune response against BLG via mucosal delivery in a cow's milk allergy model in mice.

Abstract Brucella spp. are facultative intracellular pathogens that have the ability to survive and multiply in professional and non-professional phagocytes, and cause abortion in domestic animals and undulant fever in humans. Several species are recognized within the genus Brucella and this classification is mainly based on the difference in pathogenicity and in host preference. Brucella strains may occur as either smooth or rough, expressing smooth LPS (S-LPS) or rough LPS (R-LPS) as major surface antigen. This bacterium possesses an unconventional non-endotoxic lipopolysaccharide that confers resistance to anti-microbial attacks and modulates the host immune response. The strains that are pathogenic for humans (B. abortus, B. suis, B. melitensis) carry a smooth LPS involved in the virulence of these bacteria. The LPS O-chain protects the bacteria from cellular cationic peptides, oxygen metabolites and complement-mediated lysis and it is a key molecule for Brucella survival and replication in the host. Here, we review i) Brucella LPS structure; ii) Brucella genome, iii) genes involved in LPS biosynthesis; iv) the interaction between LPS and innate immunity.

Abstract Background Brucella abortus is a facultative intracellular pathogen that mainly infects cattle and humans. Current vaccines rely on live attenuated strains of B. abortus, which can revert to their pathogenic status and thus are not totally safe for use in humans. Therefore, the development of mucosal live vaccines using the food-grade lactic acid bacterium, Lactococcus lactis, as an antigen delivery vector, is an attractive alternative and a safer vaccination strategy against B. abortus. Here, we report the construction of L. lactis strains genetically modified to produce B. abortus GroEL heat-shock protein, a candidate antigen, in two cellular locations, intracellular or secreted. Results Only the secreted form of GroEL was stably produced in L. lactis, suggesting a detrimental effect of GroEL protein when intracellularly produced in this bacterium. Only trace amounts of mature GroEL were detected in the supernatant fraction of induced lactococcal cultures, and the GroEL precursor remained stacked in the cell fraction. Attempts to raise the secretion yields were made, but even when GroEL was fused to a synthetic propeptide, secretion of this antigen was not improved. Conclusion We found that L. lactis is able to produce, and to secrete, a stable form of GroEL into the extracellular medium. Despite the low secretion efficiency of GroEL, which suggest that this antigen interacts with the cell envelope of L. lactis, secretion seems to be the best way to achieve both production and protein yields, regardless of cellular location. The L. lactis strain secreting GroEL has potential for in vivo immunization.

Abstract Lactococcus lactis, the model lactic acid bacterium (LAB), is a food grade and well-characterized Gram positive bacterium. It is a good candidate for heterologous protein delivery in foodstuff or in the digestive tract. L. lactis can also be used as a protein producer in fermentor. Many heterologous proteins have already been produced in L. lactis but only few reports allow comparing production yields for a given protein either produced intracellularly or secreted in the medium. Here, we review several works evaluating the influence of the localization on the production yields of several heterologous proteins produced in L. lactis. The questions of size limits, conformation, and proteolysis are addressed and discussed with regard to protein yields. These data show that i) secretion is preferable to cytoplasmic production; ii) secretion enhancement (by signal peptide and propeptide optimization) results in increased production yield; iii) protein conformation rather than protein size can impair secretion and thus alter production yields; and iv) fusion of a stable protein can stabilize labile proteins. The role of intracellular proteolysis on heterologous cytoplasmic proteins and precursors is discussed. The new challenges now are the development of food grade systems and the identification and optimization of host factors affecting heterologous protein production not only in L. lactis, but also in other LAB species.

Background: Riverine communities face various health problems, which involve geographical and cultural barriers to accessing care, in addition to a lack of financial investments in services aimed at these communities, resulting in a process of invisibility for the population living in these regions. In this scenario, the significant burden of snakebite envenoming (SBE) highlights the need for participatory research to address ways to minimize this situation. Thus, this study aimed to describe the priority health problems identified by this population and the ranking of SBEs in that context, mapping solutions according to the local reality., Methodology/principal Findings: This study was conducted in Limeira, a riverine community located in Tabatinga, in the extreme Western Brazilian Amazonia, on the borders with Peru and Colombia. The research lasted approximately one year, from 2021 to 2022.It is a participatory study that followed three steps: baseline assessment of the community, community assembly, and final data analysis. The study included a total of 42 participants in the sociodemographic survey, which served as the basis for the subsequent stages of data collection. Of these 42 individuals, 32 participated in the qualitative interviews, and 20 took part in the community assembly. Participants emphasized snakebite envenoming as a significant health issue, though not the only one, and reported frequent encounters with snakes, underscoring its severity as a concern. The qualitative analysis identified three main themes: Snakebites in the Community, which focused on personal experiences with snakes; Common Health Problems, which addressed other health issues faced by community members; and Community Defining Solutions, which discussed strategies and solutions proposed by the community to address these challenges., Conclusions/significance: Improvements in health care delivery to populations living in Amazonian communities are possible with the judicious use of tested integrated interventions, particularly when the community identifies various concurrent health problems. SBE control programs in remote areas of the Brazilian Amazon should be planned with a multidisciplinary and intercultural approach, preferably integrated with broader interventions that address the population's needs for a range of health issues., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Santos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: High sodium intake is a major risk factor for hypertension and renal diseases. Previous studies have shown that a suspension of ethanolic extract of Psidium guajava (guava) leaves (PsE) has antihypertensive effects in rats on a high-sodium diet (HSD), but some mechanisms to that remain unexplored. This study explored whether oral PsE treatment affects sodium handling by the intestine and alters the gut microbiome in HSD-fed rats., Methods: Male Wistar rats were divided into two groups: standard salt diet (SSD) and HSD (0.9% Na+), from weaning. After 12 weeks, both groups received PsE (200 mg/kg) or a vehicle for an additional 4 weeks., Key Findings: Sodium excretion was measured using flame photometry, and sodium absorption was assessed by intestinal perfusion technique. The gut microbiome was analysed through 16S ribosomal gene sequencing. HSD increased faecal sodium, further elevated by PsE, which inhibited intestinal sodium absorption in HSD rats. HSD altered the abundance of specific bacterial families, which PsE partially reversed. No changes in alpha diversity were noted among groups., Conclusions: These findings suggest that PsE inhibited intestinal sodium handling and that PsE, combined with increased faecal sodium, may reshape the gut microbiome of HSD rats to resemble that of SSD rats., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This study presents the development of a procedure based on copper preconcentration at the cloud point of commercial spirulina dietary supplements, with determination by digital image colorimetry. A fractional factorial design 2 4-1 and Doehlert matrix were applied in the method optimization. The developed method presented 0.062 and 0.20 mg kg -1 Cu as limits of detection and quantification, respectively. The main advantages of this procedure come from the pre-concentration and the speed resulting from its direct determination in the surfactant-rich phase, eliminating the stage of discarding the original bulky aqueous phase. The found precision values, expressed as repeatability, were 2.8 % (5.0 μg L -1 ) and 2.2 % (20 μg L -1 ). Trueness was assessed using spike test and analysis of certified reference materials (Apple leaves and Oyster tissue), demonstrating that the method presents adequate trueness. Copper concentrations in the analyzed samples ranged from 19.92 to 55.32 mg kg -1 , representing a low nutritional contribution of 0.66-1.54 %, considering this supplement's recommended intake of 3 g day -1 ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Microbial biofilms constitute a significant virulence factor and a substantial challenge in clinical environments due to their role in promoting antimicrobial resistance and their resilience to eradication efforts. Methicillin-resistant Staphylococcus aureus (MRSA) infections substantially increase healthcare costs, extend hospitalizations, and elevate morbidity and mortality rates. Therefore, developing innovative strategies to target and eliminate these bacteria and their biofilms effectively is imperative for robust epidemiological control. In this study, we evaluated the antibacterial and antibiofilm activities of cell-free supernatant (CFS) obtained from the Bacillus velezensis 1273 strain culture. Our data showed that CFS inhibited the growth of S. aureus ATCC 29213 and MRSA (clinical strain), with greater efficacy observed against S. aureus (1:16 dilution). Furthermore, CFS showed substantial potential in reducing biofilm formation in both strains (∼30 %) at subinhibitory concentrations. Additionally, the antibacterial activity against biofilm-formed cells showed that pure CFS treatment decreased the viability of S. aureus (60 %) and MRSA (45 %) sessile cells. We further demonstrated that CFS treatment induces the production of reactive oxygen species (ROS) and damages the membranes and cell walls of the pathogen cells. Genome analysis revealed the presence of genes encoding bacteriocins and secondary metabolites with antibacterial activity in the B. velezensis 1273 genome. These findings highlight the potential of probiotic bacterial metabolites as antibiofilm and anti-multidrug-resistant pathogens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: The traditional communities of the Brazilian Amazon possess significant knowledge regarding the huge therapeutic arsenal available from natural sources that can be used to care for their health problems. This study aimed to identify, map and synthesize the scientific evidence on the use of traditional medicine as a therapeutic resource when used by traditional communities of the Brazilian Amazon., Methods: This is a scoping review, which is a method used to map the main concepts of a research area, the available evidence and its sources. It is developed in five steps: (1) identification of the research question; (2) identification of relevant studies; (3) selection of studies; (4) data analysis; and (5) grouping, synthesis and presentation of data., Results: Medicinal plants, vertebrates and invertebrates, among other medicinal products, are elements that are widely used by traditional populations. Plant stems, bark, leaves, flowers, fruits, seeds, roots, tubers and even the whole plant are prepared in various forms, such as teas, infusions, smoke for rituals, baths, macerations, oils, ointments, concoctions, dressings, incenses and exfoliants, among others. The main structures and forms used from animals are lards, fats, viscera, horns, cocoons, nests, feathers and beaks of birds, eggs and roes. These therapeutic practices are often carried out using endogenous, wild and domesticated natural resources present in the biodiverse environments of traditional populations. They involve magical-religious beliefs to treat all types of illnesses, including cultural syndromes that affect children, young people, adults and the elderly., Conclusion: This scoping review has an important role to disseminate and expand the discussion of traditional medicine practices, inviting readers - whether they are health professionals, community members, managers or decision-makers - to a continuing debate using an intercultural dialogue necessary to improve approaches. From this perspective, it is essential to consider the comprehensive legal and legal framework that guides the public policies of national health systems.

In the Brazilian Amazon, snakebite envenomations (SBEs) disproportionately affect Indigenous populations, and have a significantly higher incidence and lethality than in non-Indigenous populations. This qualitative study describes the Indigenous and biomedical healthcare domains for SBE care from the perspective of the Indigenous medical and nursing students in Manaus, Western Brazilian Amazon. In-depth interviews were conducted with five Indigenous students from the Amazonas State University, between January and December 2021. The interviews were analyzed using inductive content analysis. We organized an explanatory model with five themes: (1) participants' identities; (2) causality levels in Indigenous and biomedical systems; (3) therapeutic itineraries in Indigenous and biomedical systems; (4) ideological implications of adding biomedical devices to Indigenous healing systems; and (5) therapeutic failure in and efficacy of Indigenous and biomedical systems. From a noncolonial perspective and seeking to increase the quality and acceptability of health care for the Indigenous populations of the Brazilian Amazon, the training of Indigenous health professionals presents itself as a promising strategy. For this goal, universities should serve as empowering settings for Indigenous health students that support them in their growth and development, raise their awareness of injustice, and catalyze change toward a culturally adapted and effective service for the users., (© 2024 John Wiley & Sons Ltd.)

This scoping review mapped the academic literature focused on the therapeutic itinerary of children who seek care in health services and proposed an explanatory model to expand the concept and classification of these health itineraries. A total of 789 articles were reviewed, of which 28 were eligible for inclusion. In these 28 it was possible to observe that the child's therapeutic itinerary is more than a physical path, but also encompasses all choices within a specific social and cultural environment in which the child is inserted. Our proposal is to expand the concept beyond the therapeutic, classifying the itinerary also according to the objective, the decision-making agent, respect for the presence of company, the health subsystem used, according to the physical continuity of the itinerary, the perception of efficacy of the patient, the nature of the illness, the administration of healthcare, the means of transport used, the person providing information about the itinerary, the planning of the itinerary and its completeness. Knowing the child's itineraries toward healthcare allows the development of innovative discourses and practices for future public policies, through which the principles of comprehensiveness and resoluteness in children's health would be strengthened. There is still a need to deepen knowledge about the meanings and feelings regarding their interpretations of the events suffered in childhood., (© 2024 John Wiley & Sons Ltd.)

Objectives: to comprehend men's perception of paternal parenthood while caring for infants to promote child development., Methods: this qualitative study adopts an exploratory approach and was conducted with undergraduate and graduate students, faculty, and staff who are fathers of infants up to 6 months old from a higher education institution, excluding fathers from mononuclear families. Data collection occurred through semi-structured interviews and was analyzed using thematic categorical analysis., Results: fifteen men participated in the study. From the analysis, two empirical categories emerged: "Perception of being a father: challenges and novelties" and "Promotion of child development: actions carried out by fathers". Fathers revealed feeling unprepared, the need for emotional support, and recognized activities aimed at their children's development., Final Considerations: the relevance of the paternal figure for child development is highlighted, as well as the need for public policies to encourage paternal parenthood.

Escherichia coli (E. coli) are widely related to pyometra and cystitis in dogs, and these infections can occur simultaneously. The goal of this study was to determine genetic and pathogenic insights of 14 E. coli isolated simultaneously from pyometra content and bladder urine of seven bitches. To achieve this, in silico and in vitro comparative analyses were conducted. Whole-genome comparisons demonstrated that E. coli isolated from pyometra and urine of the same animal were predominantly genetic extraintestinal E. coli clones belonging to the same Sequence Type and phylogroup. The E. coli clones identified in this study included ST372, ST457, ST12, ST127, ST646, and ST961. Five isolates (35.7%) belonged to the ST12 complex. Except for two E. coli, all other isolates belonged to the B2 Clermont phylogroup. Interestingly, some genomes of E. coli from urine carried more virulence genes than those E. coli from pyometra. Both pyometra and urine E. coli isolates demonstrated a strong affinity for adhering to HeLa and T24 cells, with a low affinity for invading them. However, certain isolates from urine exhibited a greater tendency to adhere to T24 cells in qualitative and quantitative assays compared to isolates from pyometra. In conclusion, this study revealed the high genomic similarity between pyometra and urine E. coli isolates, as well as the virulent capacity of both to colonize endometrial and urothelial cells. The findings of this study underscore the importance of concurrently managing both infections clinically and could potentially contribute to future resources for the prevention of cystitis and pyometra., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Serratia marcescens is an opportunistic pathogen found ubiquitously in the environment and associated with a wide range of nosocomial infections. This multidrug-resistant bacterium has been a cause of concern for hospitals and healthcare facilities due to its ability to spread rapidly and cause outbreaks. Next generation sequencing genotyping of bacterial isolates has proven to be a valuable tool for tracking the spread and transmission of nosocomial infections. This has allowed for the identification of outbreaks and transmission chains, as well as determining whether cases are due to endogenous or exogenous sources. Evidence of nosocomial transmission has been gathered through genotyping methods. The aim of this study was to investigate the genetic diversity of carbapenemase-producing S. marcescens in an outbreak at a public hospital in Cuiaba, MT, Brazil., Methodology: Ten isolates of S. marcenses were sequenced and antibiotic resistance profiles analyzed over 12 days., Results: The isolates were clonal and multidrug resistant. Gentamycin and tigecycline had sensitivity in 90% and 80% isolates, respectively. Genomic analysis identified several genes that encode β-lactamases, aminoglycoside-modifying enzymes, efflux pumps, and other virulence factors., Conclusions: Systematic surveillance is crucial in monitoring the evolution of S. marcescens genotypes, as it can lead to early detection and prevention of outbreaks., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Thalita PPS Cruz, Francisco KSF Azevedo, Marco A Pepato, Paula S Rizzo, Francisco JD Souto, Bertram Brenig, Aristóteles Góes-Neto, Siomar C Soares, Rommel TJ Ramos, Vasco AC Azevedo, Mateus M Costa, Leonardo Broetto, Luciano Nakazato, Valéria Dutra.)

Aerobic exercise training (AET) has emerged as a strategy to reduce cancer mortality, however, the mechanisms explaining AET on tumor development remain unclear. Tumors escape immune detection by generating immunosuppressive microenvironments and impaired T cell function, which is associated with T cell mitochondrial loss. AET improves mitochondrial content and function, thus we tested whether AET would modulate mitochondrial metabolism in tumor-infiltrating lymphocytes (TIL). Balb/c mice were subjected to a treadmill AET protocol prior to CT26 colon carcinoma cells injection and until tumor harvest. Tissue hypoxia, TIL infiltration and effector function, and mitochondrial content, morphology and function were evaluated. AET reduced tumor growth, improved survival, and decreased tumor hypoxia. An increased CD8 + TIL infiltration, IFN-γ and ATP production promoted by AET was correlated with reduced mitochondrial loss in these cells. Collectively, AET decreases tumor growth partially by increasing CD8 + TIL effector function through an improvement in their mitochondrial content and function., Competing Interests: The authors declare no competing interest., (© 2024 The Authors.)

Chemotherapy-induced intestinal mucositis is a major side effect of cancer treatment. Statins are 3-hydroxy-3-methyl glutaryl coenzyme reductase inhibitors used to treat hypercholesterolemia and atherosclerotic diseases. Recent studies have demonstrated that atorvastatin (ATV) has antioxidant, anti-inflammatory, and resulting from the regulation of different molecular pathways. In the present study, we investigated the effects of ATV on intestinal homeostasis in 5-fluorouracil (5-FU)-induced mucositis. Our results showed that ATV protected the intestinal mucosa from epithelial damage caused by 5-FU mainly due to inflammatory infiltrate and intestinal permeability reduction, downregulation of inflammatory markers, such as Tlr4, MyD88, NF-κB, Tnf-a, Il1β, and Il6 dose-dependent. ATV also improved epithelial barrier function by upregulating the mRNA transcript levels of mucin 2 (MUC2), and ZO-1 and occludin tight junction proteins. The results suggest that the ATV anti-inflammatory and protective effects on 5-FU-induced mice mucositis involve the inhibition of the TLR4/MYD88/NPRL3/NF-κB, iNos, and caspase 3.

The exogenous application of bioregulators, such as salicylic acid (SA), has exhibited promising outcomes in alleviating drought stress. Nevertheless, its impact on culantro ( Eryngium foetidum L.) remains unexplored. Thus, the aim of this study was to assess how SA impacts the growth, morphophysiology, and essential oil composition of culantro when subjected to drought. To achieve this, culantro plants were grown under three different watering regimes: well-watered, drought-stressed, and re-watered. Additionally, they were either treated with SA (100 µM) or left untreated, with water serving as the control. SA application did not mitigate the effects of drought in biomass production but increased biomass, leaf number, leaf area, and photosynthetic pigments under well-irrigated and re-watered conditions. After a drought period followed by re-watering, plants recovered membrane integrity independently of SA application. Water stress and the exogenous application of SA also modulated the profile of essential oils. This is the first report about SA and drought affecting growth and essential oil composition in culantro.

Trametes villosa is a remarkable white-rot fungus (WRF) with the potential to be applied in lignocellulose conversion to obtain chemical compounds and biofuels. Lignocellulose breakdown by WRF is carried out through the secretion of oxidative and hydrolytic enzymes. Despite the existing knowledge about this process, the complete molecular mechanisms involved in the regulation of this metabolic system have not yet been elucidated. Therefore, in order to understand the genes and metabolic pathways regulated during lignocellulose degradation, the strain T. villosa CCMB561 was cultured in media with different carbon sources (lignin, sugarcane bagasse, and malt extract). Subsequently, biochemical assays and differential gene expression analysis by qPCR and high-throughput RNA sequencing were carried out. Our results revealed the ability of T. villosa CCMB561 to grow on lignin (AL medium) as the unique carbon source. An overexpression of Cytochrome P450 was detected in this medium, which may be associated with the lignin O-demethylation pathway. Clusters of up-regulated CAZymes-encoding genes were identified in lignin and sugarcane bagasse, revealing that T. villosa CCMB561 acts simultaneously in the depolymerization of lignin, cellulose, hemicellulose, and pectin. Furthermore, genes encoding nitroreductases and homogentisate-1,2-dioxygenase that act in the degradation of organic pollutants were up-regulated in the lignin medium. Altogether, these findings provide new insights into the mechanisms of lignocellulose degradation by T . villosa and confirm the ability of this fungal species to be applied in biorefineries and in the bioremediation of organic pollutants., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2024 The Authors.)

The clinical aspects and lineages involved in Extraintestinal pathogenic Escherichia coli (ExPEC) infections in dogs remain largely unknown. In this study, we investigated the antimicrobial resistance and molecular structures of ExPECs isolated from infected dogs in Brazil. Samples were obtained from dogs (n = 42) with suspected extraintestinal bacterial infections. Phylogroup B2 was predominant (65.1%). No association was observed between the site of infection, phylogroups, or virulence factors. Almost half of the isolates (44.2%) were MDR, and 20.9% were extended-spectrum β-lactamase (ESBL)-positive. E. coli isolates that were resistant to fluoroquinolones (27.9%) were more likely to be MDR. The CTX-M-15 enzyme was predominant among the ESBL-producing strains, and seven sequence types were identified, including the high-risk clones ST44 and ST131. Single SNPs analysis confirmed the presence of two clonal transmissions. The present study showed a high frequency of ExPECs from phylogroup B2 infecting various sites and a high frequency of ESBL-producing strains that included STs frequently associated with human infection. This study also confirmed the nosocomial transmission of ESBL-producing E. coli, highlighting the need for further studies on the prevention and diagnosis of nosocomial infections in veterinary settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective . To track the BP (blood pressure) trajectory of healthy infants during the first year of life of healthy infants born in Northeast Brazil. Methods . In this cohort study, BP was assessed by oscillometry at the first 24 hours of life and 12 months of age. Results . Systolic blood pressure (SBP) and diastolic blood pressure (DBP) increased with age ( P  < .001) and were not influenced by gender (SBP: P  = .178 and DBP: P  = .623) or type of delivery (SBP: P  = .827 and DBP: P  = .106), when compared between the first 24 hours of life and 12 months of age. Conclusion . The data from the present study increased knowledge about the trajectory of BP during the first year of life. The increase in BP between the first month and the first year of life was not influenced by gender or type of delivery., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

The poultry sector demands alternative additives to antibiotics that can be used as performance enhancers. Therefore, this experiment was conducted to evaluate the probiotics effects on performance, intestinal health, and redox status of 720 broilers exposed to heat stress from 15 days of age. Eight dietary treatments were evaluated: basal diet (BD) without antibiotic and probiotic (T1); BD supplemented with antibiotic zinc bacitracin (T2), BD supplemented with commercial probiotic of Bacillus subtilis DSM 17,299 (T3), BD supplemented with non-commercial probiotic of Lactococcus lactis NCDO 2118, Lactobacillus delbrueckii CNRZ 327, Escherichia coli CEC15, or Saccharomyces boulardii (T4 to T7), and BD simultaneously supplemented with the four non-commercial probiotics (T8). Feed intake, weight gain, and feed conversion were determined in the period from 1 to 42 days of age. Carcass and cuts yield, abdominal fat deposition, cloacal temperature, weight and length of intestine, activity of myeloperoxidase and eosinophilic peroxidase enzymes in the jejunum, jejunal histomorphometry, relative gene expression in the jejunum (occludin, zonulin, interleukin-8, cholecystokinin, ghrelin, and heat shock protein-70), and liver (heat shock protein-70), in addition to malondialdehyde level and superoxide dismutase activity in the intestine, liver, and blood, were measured in broilers at 42 days old. As main results, broilers fed T1 diet exhibited lower weight gain (3.222 kg) and worse feed conversion (1.70 kg/kg). However, diets containing non-commercial probiotics resulted in up to 3.584 kg of weight gain and improved feed conversion by up to 10%, similar to that observed for broilers of the T2 and T3 groups., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study of multiple cases aimed to analyze the social support network of young mothers of children diagnosed with congenital syphilis in a municipality in Ceará with six participants. Information was collected through semi-structured interviews and analyzed using the cross-case synthesis analytical technique. The young women's social network comprised family members, people outside the family, and social facilities. We identified heterogeneous bonds and social support as essential in the gestational and postpartum periods after the diagnosis of syphilis. The vertical transmission of syphilis is permeated by subjectivities identified from understanding the context involving social networks, interpersonal relationships, and support for mothers and their children.

Antimicrobial resistance is increasing despite new treatments being employed, so novel strategies are required to ensure that bacterial infections remain treatable. Bacteriophages (phages; bacteria viruses) have the potential to be used as natural antimicrobial methods to control bacterial pathogens such as Salmonella spp. A Salmonella phage, Wara, was isolated from environmental water samples at the Subaé River Basin, Salvador de Bahia, Brazil. The basin has environmental impacts in its main watercourses arising from the dumping of domestic and industrial effluents and agricultural and anthropological activities. The phage genome sequence was determined by Oxford Nanopore Technologies (ONT) MinION and Illumina HiSeq sequencing, and assembly was carried out by Racon (MinION) and Unicycler (Illumina, Illumina + MinION). The genome was annotated and compared to other Salmonella phages using various bioinformatics approaches. MinION DNA sequencing combined with Racon assembly gave the best complete genome sequence. Phylogenetic analysis revealed that Wara is a member of the Tequintavirus genus. A lack of lysogeny genes, antimicrobial resistance, and virulence genes indicated that Wara has therapeutic and biocontrol potential against Salmonella species in healthcare and agriculture.

Background: The indigenous populations of Brazil present poor health indicators and a disproportionate prevalence and case-fatality rate of neglected tropical diseases, including snakebite envenomations (SBEs). This study aims to estimate access to medical care for SBEs and analyze the barriers that prevent victims from accessing healthcare in indigenous communities in two health districts located in the Western Brazilian Amazon., Methodology/principal Findings: This cross-sectional study used semi-structured interviews to collect data from individuals who experienced SBEs in the Upper Rio Solimões and Upper Rio Negro indigenous health districts. Of the 187 participants, 164 (87.7%) reported that they had access to healthcare and received assistance in a hospital in the urban area of the municipalities. Frequency was 95.4% in the Upper Rio Solimões SIHD, and 69.6% in the Upper Rio Negro SIHD (P<0.0001). The study found that the availability of indigenous medicine as the only choice in the village was the main reason for not accessing healthcare (75%), followed by a lack of financial resources and means of transportation (28.1%). Four deaths were reported from SBEs, resulting in a case-fatality rate of 2.1%., Conclusions/significance: In the study areas, there are records of SBE patients who did not receive medical attention. Availability of pre-hospital emergency transport using motorboats, a greater number of hospitals and better navigability of the Solimões River and its tributaries would make access easier for indigenous people living in the region of the Upper Solimões River. The implementation of cross-cultural hospital care needs to be considered in order to reduce the resistance of indigenous populations in relation to seeking treatment for SBEs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 de Farias et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Inflammatory bowel diseases (IBD) are gastrointestinal disorders characterized by a breakdown in intestinal homeostasis by inflammatory immune responses to luminal antigens. Novel strategies for ameliorating IBD have been proposed in many studies using animal models. Our group has demonstrated that administration of Lactococcus lactis NCDO 2118 can improve clinical parameters of colitis induced by oral administration of dextran sulphate sodium (DSS). However, it is not clear whether other strains of L. lactis can yield the same effect. The objective of present study was to analyze the effects of three different L. lactis strains (NCDO2118, IL1403 and MG1363) in the development of DSS-induced colitis in C57BL/6 mice. Acute colitis was induced in C57/BL6 mice by the administration of 2% DSS during 7 consecutive days. Body weight loss and shortening of colon length were observed in DSS-treated mice, and none of L. lactis strains had an impact in these clinical signs of colitis. On the other hand, all strains improved the global macroscopical disease index and prevented goblet cells depletion as well as the increase of intestinal permeability. TNF-α production was reduced in gut mucosa of L. lactis DSS-treated mice indicating a modulation of a critical pro-inflammatory response by all strains tested. However, only L. lactis NCDO2118 and MG1363 induced a higher frequency of CD11c + CD11b - CD103 + tolerogenic dendritic cells in lymphoid organs of mice at steady state. We conclude that all tested strains of L. lactis improved the clinical scores and parameters of colitis, which confirm their anti-inflammatory properties in this model of colitis., (© 2023. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Rotavirus (RV) and Norovirus (NV) are the main viral etiologic agents of acute gastroenteritis (AG), a serious pediatric condition associated with significant death rates and long-term complications. Anti-RV vaccination has been proved efficient in the reduction of severe AG worldwide, however, the available vaccines are all attenuated and have suboptimal efficiencies in developing countries, where AG leads to substantial disease burden. On the other hand, no NV vaccine has been licensed so far. Therefore, we used immunoinformatics tools to develop a multi-epitope vaccine (ChRNV22) to prevent severe AG by RV and NV. Epitopes were predicted against 17 prevalent genotypes of four structural proteins (NV's VP1, RV's VP4, VP6 and VP7), and then assembled in a chimeric protein, with two small adjuvant sequences (tetanus toxin P2 epitope and a conserved sequence of RV's enterotoxin, NSP4). Simulations of the immune response and interactions with immune receptors indicated the immunogenic properties of ChRNV22, including a Th1-biased response. In silico search for putative host-homologous, allergenic and toxic regions also indicated the vaccine safety. In summary, we developed a multi-epitope vaccine against different NV and RV genotypes that seems promising for the prevention of severe AG, which will be further assessed by in vivo tests., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Helioswilton Sales-Campos reports financial support was provided by Fundação de Amparo à Pesquisa (FUNAPE). Amanda de Oliveira Matos reports financial support was provided by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Pedro Henrique dos Santos Dantas reports financial support was provided by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Heme is an iron-protoporphyrin complex with an essential physiologic function for all cells, especially for those in which heme is a key prosthetic group of proteins such as hemoglobin, myoglobin, and cytochromes of the mitochondria. However, it is also known that heme can participate in pro-oxidant and pro-inflammatory responses, leading to cytotoxicity in various tissues and organs such as the kidney, brain, heart, liver, and in immune cells. Indeed, heme, released as a result of tissue damage, can stimulate local and remote inflammatory reactions. These can initiate innate immune responses that, if left uncontrolled, can compound primary injuries and promote organ failure. In contrast, a cadre of heme receptors are arrayed on the plasma membrane that is designed either for heme import into the cell, or for the purpose of activating specific signaling pathways. Thus, free heme can serve either as a deleterious molecule, or one that can traffic and initiate highly specific cellular responses that are teleologically important for survival. Herein, we review heme metabolism and signaling pathways, including heme synthesis, degradation, and scavenging. We will focus on trauma and inflammatory diseases, including traumatic brain injury, trauma-related sepsis, cancer, and cardiovascular diseases where current work suggests that heme may be most important.

Background and Objectives: Lean management is a strategy for improving health care experiences of patients. While best practices for engaging patients in quality improvement have solidified in recent years, few reports specifically address patient engagement in Lean activities. This study examines the benefits and challenges of incorporating patient engagement strategies into the Veterans Health Administration's (VA) Lean transformation., Methods: We conducted a multisite, mixed-methods evaluation of Lean deployment at 10 VA medical facilities, including 227 semistructured interviews with stakeholders, including patients., Results: Interviewees noted that a patient-engaged Lean approach is mutually beneficial to patients and health care employees. Benefits included understanding the veteran's point of view, uncovering inefficient aspects of care processes, improved employee participation in Lean events, increased transparency, and improved reputation for the organization. Challenges included a need for focused time and resources to optimize veteran participation, difficulty recruiting a diverse group of veteran stakeholders, and a lack of specific instructions to encourage meaningful participation of veterans., Conclusions/implications: As the first study to focus on patient engagement in Lean transformation efforts at the VA, this study highlights ways to effectively partner with patients in Lean-based improvement efforts. Lessons learned may also help optimize patient input into quality improvement more generally., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Mucositis is defined as inflammatory and ulcerative lesions along of the gastrointestinal tract that leads to the imbalance of the intestinal microbiota. The use of compounds with action on the integrity of the intestinal epithelium and their microbiota may be a beneficial alternative for the prevention and/or treatment of mucositis. So, the aim of this study was to evaluate the effectiveness of the association of fructo-oligosaccharides (FOS) and arginine on intestinal damage in experimental mucositis. BALB/c mice were randomized into five groups: CTL (without mucositis + saline), MUC (mucositis + saline), MUC + FOS (mucositis + supplementation with FOS-1st until 10th day), MUC + ARG (mucositis + supplementation with arginine-1st until 10th day), and MUC + FOS + ARG (mucositis + supplementation with FOS and arginine-1st until 10th day). On the 7th day, mucositis was induced with an intraperitoneal injection of 300 mg/kg 5-fluorouracil (5-FU), and after 72 h, the animals were euthanized. The results showed that association of FOS and arginine reduced weight loss and oxidative stress (P < 0.05) and maintained intestinal permeability and histological score at physiological levels. The supplementation with FOS and arginine also increased the number of goblet cells, collagen area, and GPR41 and GPR43 gene expression (P < 0.05). Besides these, the association of FOS and arginine modulated intestinal microbiota, leading to an increase in the abundance of the genera Bacteroides, Anaerostipes, and Lactobacillus (P < 0.05) in relation to increased concentration of propionate and acetate. In conclusion, the present results show that the association of FOS and arginine could be important adjuvants in the prevention of intestinal mucositis probably due to modulated intestinal microbiota., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Intestinal mucositis (IM) is a common side effect resulting from cancer treatment. However, the management so far has not been very effective. In the last years, the role of the gut microbiota in the development and severity of mucositis has been studied. Therefore, the use of probiotics and paraprobiotics could have a potential therapeutic effect on IM. The aim of our study was to investigate the impact of the administration of Lacticaseibacillus rhamnosus (L. rhamnosus) CGMCC1.3724 and the paraprobiotic on IM in mice. For 13 days, male Balb/c mice were divided into six groups: control (CTL) and mucositis (MUC)/0.1 mL of saline; CTL LrV and MUC LrV/0.1 mL of 10 8  CFU of viable Lr; CTL LrI and MUC LrI/0.1 mL of 10 8  CFU of inactivated Lr. On the 10th day, mice from the MUC, MUC LrV, and MUC LrI groups received an intraperitoneal injection (300 mg/kg) of 5-fluorouracil to induce mucositis. The results showed that the administration of the chemotherapeutic agent increased the weight loss and intestinal permeability of the animals in the MUC and MUC LrV groups. However, administration of paraprobiotic reduced weight loss and maintained PI at physiological levels. The paraprobiotic also preserved the villi and intestinal crypts, reduced the inflammatory infiltrate, and increased the mucus secretion, Muc2 gene expression, and Treg cells frequency., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)