Differential expression of biomarkers in saliva related to SARS-CoV-2 infection in patients with mild, moderate and severe COVID-19.

BACKGROUND: Severe COVID-19 is a disease characterized by profound dysregulation of the innate immune system. There is a need to identify highly reliable prognostic biomarkers that can be rapidly assessed in body fluids for early identification of patients at higher risk for hospitalization and/or death. This study aimed to assess whether differential gene expression of immune response molecules and cellular enzymes, detected in saliva samples of COVID-19 patients, occurs according to disease severity staging. METHODS: In this cross-sectional study, subjects with a COVID-19 diagnosis were classified as having mild, moderate, or severe disease based on clinical features. Transcripts of genes encoding 6 biomarkers, IL-1ß, IL-6, IL-10, C-reactive protein, IDO1 and ACE2, were measured by RT‒qPCR in saliva samples of patients and COVID-19-free individuals. RESULTS: The gene expression levels of all 6 biomarkers in saliva were significantly increased in severe disease patients compared to mild/moderate disease patients and healthy controls. A significant strong inverse relationship between oxemia and the level of expression of the 6 biomarkers (Spearman's correlation coefficient between -0.692 and -0.757; p < 0.001) was found. CONCLUSIONS: Biomarker gene expression determined in saliva samples still needs to be validated as a potentially valuable predictor of severe clinical outcomes early at the onset of COVID-19 symptoms.

Identification of peptides presented through the MHC-II of dendritic cells stimulated with Mycobacterium avium.

Mycobacterium avium (M. avium) represents a species of concern, because of its ability to modulate the host's innate immune response, and therefore influence trajectory of adaptative immunity. Since eradicative response against mycobacteria, and M. tuberculosis/M. avium, relies on peptides actively presented on a Major Histocompatibility complex-II (MHC-II) context, we assessed paradoxical stimulation of Dendritic Cell resulting on immature immunophenotype characterized by membrane minor increase of MHC-II and CD40 despite of high expression of the pro-inflammatory tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in supernatants. Identification of M. avium leucine rich peptides forming short α-helices shutting down Type 1T helper (Th1), contribute to the understanding of immune evasion of an increasingly prevalent pathogen, and may provide a basis for future immunotherapy to infectious and non-infectious disease.

Proteome Profile Changes Induced by Heterologous Overexpression of Mycobacterium tuberculosis-Derived Antigens PstS-1 (Rv0934) and Ag85B (Rv1886c) in Mycobacterium microti.

The development of new tuberculosis vaccines remains a global priority, and recombinant vaccines are a frequently investigated option. These vaccines follow a molecular strategy that may enhance protective efficacy. However, their functional differences, particularly with respect to glycosylation, remain unknown. Recent studies have shown that glycosylation plays a key role in the host-pathogen interactions during immune recognition. The aim of this study was to determine the differences in the glycosylation profiles of two recombinant strains of Mycobacterium microti, overexpressing Ag85B (Rv1886c) and PstS-1 (Rv0934) antigens of M. tuberculosis. For each strain, the glycosylation profile was determined by Western blotting with lectins. The results showed the presence of mannosylated proteins and evidence of linked sialic acid proteins. Interestingly, different proteome and glycoproteome profiles were observed between the two recombinant strains and the wild-type strain. We have shown here that the construction of the recombinant strains of M. microti has altered the proteome and glycosylation profiles of these strains, leading us to ask what impact these changes might have on the immune response.

Factors associated with delayed diagnosis among Filipino pediatric brain tumor patients: a retrospective review.

Aim: Determine delayed diagnosis measured by prediagnostic symptomatic interval (PSI) among Filipino pediatric brain tumor patients and identify associated factors. Methods: Data was collected retrospectively on Philippine General Hospital pediatric brain tumor patients from 2015 to 2019. PSI was calculated. Associated factors were determined. Results: 196 patients were included. Median PSI was 80.5 days. Longer PSI was significantly associated with older age, supratentorial and low-grade tumors, more physician consults prior to subspecialist referral, longer interval from neuroimaging request to facilitation, and those presenting with seizures (11-month delay), poor school performance (1-year delay), behavioral changes (1.3-year delay) and secondary amenorrhea (3-year delay). Conclusion: Delayed diagnosis among Filipino brain tumor patients is associated with age, tumor characteristics and symptoms that are uncommon in this condition. Awareness of these symptoms through physician education, close monitoring of patients, early subspecialist referral and better neuroimaging access may lead to earlier diagnosis.

Mucosal Microbiome Profiles Polygenic Irritable Bowel Syndrome in Mestizo Individuals.

Irritable bowel syndrome (IBS) is the most frequent functional gastrointestinal disorder, worldwide, with a high prevalence among Mestizo Latin Americans. Because several inflammatory disorders appear to affect this population, a further understanding of host genomic background variants, in conjunction with colonic mucosa dysbiosis, is necessary to determine IBS physiopathology and the effects of environmental pressures. Using a simple polygenic model, host single nucleotide polymorphisms (SNPs) and the taxonomic compositions of microbiota were compared between IBS patients and healthy subjects. As proof of concept, five IBS-Rome III patients and five healthy controls (HCs) were systematically studied. The human and bacterial intestinal metagenome of each subject was taxonomically annotated and screened for previously annotated IBS, ulcerative colitis, and Crohn's disease-associated SNPs or taxon abundance. Dietary data and fecal markers were collected and associated with the intestinal microbiome. However, more than 1,000 variants were found, and at least 76 SNPs differentiated IBS patients from HCs, as did associations with 4 phyla and 10 bacterial genera. In this study, we found elements supporting a polygenic background, with frequent variants, among the Mestizo population, and the colonic mucosal enrichment of Bacteroides, Alteromonas, Neisseria, Streptococcus, and Microbacterium, may serve as a hallmark for IBS.

Corrigendum: A Survey Using the Social Networks Revealed Poor Knowledge on Fecal Microbiota Transplantation.

This article was initially published on the Journal of Neurogastroenterology and Motility with omission of a funding source. The funding source should be added as the following: "Financial support: This work was supported by DGAPA PAPPIT UNAM (IV200315)."

Specific Proteins in Nontuberculous Mycobacteria: New Potential Tools.

Nontuberculous mycobacteria (NTM) have been isolated from water, soil, air, food, protozoa, plants, animals, and humans. Although most NTM are saprophytes, approximately one-third of NTM have been associated with human diseases. In this study, we did a comparative proteomic analysis among five NTM strains isolated from several sources. There were different numbers of protein spots from M. gordonae (1,264), M. nonchromogenicum type I (894), M. nonchromogenicum type II (935), M. peregrinum (806), and M. scrofulaceum/Mycobacterium mantenii (1,486) strains, respectively. We identified 141 proteins common to all strains and specific proteins to each NTM strain. A total of 23 proteins were selected for its identification. Two of the common proteins identified (short-chain dehydrogenase/reductase SDR and diguanylate cyclase) did not align with M. tuberculosis complex protein sequences, which suggest that these proteins are found only in the NTM strains. Some of the proteins identified as common to all strains can be used as markers of NTM exposure and for the development of new diagnostic tools. Additionally, the specific proteins to NTM strains identified may represent potential candidates for the diagnosis of diseases caused by these mycobacteria.

A cross-sectional triangulation analysis of the knowledge, attitudes and practices of patients from the endocrinology clinic of the Philippine General Hospital on the use of herbal dietary supplements

OBJECTIVE: This study aimed to determine the knowledge, attitudes and practices (KAP) of a selected population of patients on herbal dietary supplements (HDS).METHOD: Methodological triangulation was used to generate a conceptual framework on HDS KAP. A survey of 175 patients was performed to measure knowledge and attitudes regarding HDS and SPSS was used for data analysis. Inverviews and focus group discussions (FGDs) were conducted to further explore the attitudes and practices, and constant comparison method was used for analysis of responses.RESULTS: Respondents were generally aware of HDS. Majority of survey respondents believed that HDS are different from conventional drugs (52.0%, pThe attitude toward HDS was generally positive. Majority (64.0%, pAmong the survey respondents, only 22% were HDS users. Family was shown to promote use while cost deterred their use.CONCLUSION: Individual knowledge and attitudes on HDS exert significant influence toward HDS practices. Factors that promote use are poor knowledge and positive attitudes toward HDS. Good knowledge seems to lead to judicious use or non-use.

Genomic and proteomic analyses of Mycobacterium bovis BCG Mexico 1931 reveal a diverse immunogenic repertoire against tuberculosis infection.

BACKGROUND: Studies of Mycobacterium bovis BCG strains used in different countries and vaccination programs show clear variations in the genomes and immune protective properties of BCG strains. The aim of this study was to characterise the genomic and immune proteomic profile of the BCG 1931 strain used in Mexico. RESULTS: BCG Mexico 1931 has a circular chromosome of 4,350,386 bp with a G+C content and numbers of genes and pseudogenes similar to those of BCG Tokyo and BCG Pasteur. BCG Mexico 1931 lacks Region of Difference 1 (RD1), RD2 and N-RD18 and one copy of IS6110, indicating that BCG Mexico 1931 belongs to DU2 group IV within the BCG vaccine genealogy. In addition, this strain contains three new RDs, which are 53 (RDMex01), 655 (RDMex02) and 2,847 bp (REDMex03) long, and 55 single-nucleotide polymorphisms representing non-synonymous mutations compared to BCG Pasteur and BCG Tokyo. In a comparative proteomic analysis, the BCG Mexico 1931, Danish, Phipps and Tokyo strains showed 812, 794, 791 and 701 protein spots, respectively. The same analysis showed that BCG Mexico 1931 shares 62% of its protein spots with the BCG Danish strain, 61% with the BCG Phipps strain and only 48% with the BCG Tokyo strain. Thirty-nine reactive spots were detected in BCG Mexico 1931 using sera from subjects with active tuberculosis infections and positive tuberculin skin tests. CONCLUSIONS: BCG Mexico 1931 has a smaller genome than the BCG Pasteur and BCG Tokyo strains. Two specific deletions in BCG Mexico 1931 are described (RDMex02 and RDMex03). The loss of RDMex02 (fadD23) is associated with enhanced macrophage binding and RDMex03 contains genes that may be involved in regulatory pathways. We also describe new antigenic proteins for the first time.