Development of innovative multi-epitope mRNA vaccine against Pseudomonas aeruginosa using in silico approaches.

The rising issue of antibiotic resistance has made treating Pseudomonas aeruginosa infections increasingly challenging. Therefore, vaccines have emerged as a viable alternative to antibiotics for preventing P. aeruginosa infections in susceptible individuals. With its superior accuracy, high efficiency in stimulating cellular and humoral immune responses, and low cost, mRNA vaccine technology is quickly replacing traditional methods. This study aimed to design a novel mRNA vaccine by using in silico approaches against P. aeruginosa. The research team identified five surface and antigenic proteins and selected their appropriate epitopes with immunoinformatic tools. These epitopes were then examined for toxicity, allergenicity and homology. The researchers also checked their presentation and identification by major histocompatibility complex cells and other immune cells through valuable tools like molecular docking. They subsequently modeled a multi-epitope protein and optimized it. The mRNA was analyzed in terms of structure and stability, after which the immune system's response against the new vaccine was simulated. The results indicated that the designed mRNA construct could be an effective and promising vaccine that requires laboratory and clinical trials.

Effect of alcohol consumption on breast cancer: probabilistic bias analysis for adjustment of exposure misclassification bias and confounders.

PURPOSE: This study was conducted to evaluate the effect of alcohol consumption on breast cancer, adjusting for alcohol consumption misclassification bias and confounders. METHODS: This was a case-control study of 932 women with breast cancer and 1000 healthy control. Using probabilistic bias analysis method, the association between alcohol consumption and breast cancer was adjusted for the misclassification bias of alcohol consumption as well as a minimally sufficient set of adjustment of confounders derived from a causal directed acyclic graph. Population attributable fraction was estimated using the Miettinen's Formula. RESULTS: Based on the conventional logistic regression model, the odds ratio estimate between alcohol consumption and breast cancer was 1.05 (95% CI: 0.57, 1.91). However, the adjusted estimates of odds ratio based on the probabilistic bias analysis ranged from 1.82 to 2.29 for non-differential and from 1.93 to 5.67 for differential misclassification. Population attributable fraction ranged from 1.51 to 2.57% using non-differential bias analysis and 1.54-3.56% based on differential bias analysis. CONCLUSION: A marked measurement error was in self-reported alcohol consumption so after correcting misclassification bias, no evidence against independence between alcohol consumption and breast cancer changed to a substantial positive association.

Worldwide Prevalence of Colistin Resistance among Enterobacteriaceae: a Systematic Review and Meta-Analysis.

BACKGROUND: The aim of the present meta-analysis is to estimate the prevalence of colistin resistance among the Enterobacteriaceae family. METHODS: Articles from various databases (Medline, Scopus, Web of Science, and Embase) examining colistin resistance among Enterobacteriaceae in human, animal, and environmental specimens were searched from 2016 to 2021 using related keywords. The Cochran's Q-test and I2 were applied to evaluate heterogeneity and a random-effects model was used to assess the pooled prevalence. The meta-regression method was applied to determine heterogeneity among the studies. RESULTS: Of 5,145 articles, 60 articles with a sample size of 404,856 was included. The pooled estimate for prevalence of bacterial resistance were 9.13% (95% CI: 6.96 to 11.56; I-squared = 99.4%) in total, 8.34% (95% CI: 5.87 to 11.16; I-squared = 99.3%) for Klebsiella spp. subgroup and 3.44% (95% CI: 2.46 to 4.57; I-squared = 98.4%) for E. coli subgroup. The pooled prevalence for human and animal settings were 9.07% (95% CI: 6.77 to 11.67; I-squared = 99.3%) and 9.73% (95% CI: 484 to 16.02; I-squared = 99.4%), respectively. The continent (coefficient: 3.51; 95% CI: 0.08 to 6.94, p: 0.045) and bacterial type (coefficient: 0.03; 95% CI: 0.01 to 0.05 p: 0.042) had significant effects on heterogeneity among studies. CONCLUSION: The results of this study showed that the prevalence of colistin resistance in Enterobacteriaceae was similar between animals and humans, with the highest colistin resistance found in Klebsiella strains.

Survey on phenotypic resistance in Enterococcus faecalis: comparison between the expression of biofilm-associated genes in Enterococcus faecalis persister and non-persister cells.

BACKGROUND: Phenotypic resistance is considered as a serious therapeutic challenge for which a definitive remedy has not been discovered yet. Biofilm and persister cell formation are two well-studied phenotypic resistance phenomena, leading to the recalcitrance and relapse of different types of chronic infections. The presence of persister cells in biofilm structures seems to be one of the main factors contributing to the relapse of infections and treatment failure. Given the dormant and inert nature of persister cells, they can be easy targets for the immune system factors. Biofilm formation can be a survival strategy for the defenseless persister cells. Thus, this study was aimed to evaluate the expression of biofilm-associated genes in Enterococcus faecalis persister and non-persister cells. METHODS: Vancomycin susceptibility and biofilm formation ability were investigated among 95 E. faecalis clinical isolates using microtiter broth dilution and microtiter plate assays, respectively. PCR was used to determine the presence of biofilm-related genes (gelE, esp, and agg) among the vancomycin-susceptible, biofilm producer E. faecalis isolates (91 isolates). Minimum bactericidal concentration for biofilms (MBCB) were determined for vancomycin using the MTP assay. Bacterial persister assay was performed using an enzymatic lysis assay. Finally, the expression of biofilm-related genes was compared between the persister and non-persister isolates of E. faecalis using real-time qPCR. RESULTS: E. faecalis isolates showed a high level of susceptibility (95.8%) to vancomycin (MIC < 1 µg/mL). The gelE, esp, and agg genes were found in 91 (100%), 72 (79.12), and 74 (81.32) of the isolates, respectively. All the E. faecalis isolates were tolerant to vancomycin in the biofilm condition, showing a MBCB of > 2500 µg/mL. Based on the enzymatic lysis assay, only 3 isolates, out of the 91, had the ability to form persister cells. The expression of biofilm-associated genes was higher among the persister compared to non-persister E. faecalis isolates. CONCLUSIONS: Biofilm-associated persister cells indicated a high vancomycin tolerance compared to non-persister cells. Moreover, persister isolates showed a higher tendency for biofilm formation and a higher expression level of the biofilm-associated genes, compared to non-persister isolates.

Effect of Chlorhexidine (CHX) and Hydrogen Peroxide (H2O2) on the Biofilm Formation of Enterococcus faecalis.

BACKGROUND: Biofilm makes bacteria resistant to antimicrobial agents and facilitates the transmission of infectious diseases in hospitals. Disinfectant compounds are frequently used to control surface contamination. This study was designed to investigate the effect of chlorhexidine (CHX) and hydrogen peroxide (H2O2) on biofilm formation of Enterococcus faecalis. METHODS: This study was performed on 40 E. faecalis clinical isolates. After the determination of MIC, the effect of different concentrations of CHX and H2O2 on the biofilm formation was evaluated. Also, the relative expression level of the studied biofilm genes, following exposure to sublethal concentration of CHX and H2O2, was assessed using quantitative reverse transcription PCR (qRT-PCR). RESULTS: The frequency of the asa1, efaA, epaI, and esp biofilm genes were 80%, 92.5%, 100%, and 75%, respectively. Various concentrations of CHX increased the biofilm mass in E. faecalis. Also, the combination of CHX and H2O2 at sub-minimal inhibitory concentrations, significantly elevated the expression of asa1, epaI, and esp genes. CONCLUSIONS: The results of this study showed that the improper use of disinfectants can increase the ability of biofilm formation in E. faecalis and may cause selective pressure leading to the emergence of biocide-resistant microorganisms.

Inhibitory Effects of Carvacrol on Biofilm Formation and Expression of Biofilm Related Genes in Clinical Isolates of Enterococcus faecalis.

BACKGROUND: Nowadays, novel antimicrobial strategies are being developed which focus on debilitating, rather than killing the microorganisms. In this regard, anti-biofilm therapy is one of the important ways to combat bacterial infections. Therefore, the aim of the current study was to evaluate the anti-biofilm activity of Carvacrol against E. faecalis by means of its effects on biofilm formation as well as on the gene expression levels of the two biofilm related genes, Epa and Esp. METHODS: A total of 40 clinical strains of E. faecalis were collected from three hospitals in Tehran, Iran during 2020. These isolates were confirmed by biochemical and genotypic methods. Antibacterial and anti-biofilm activity of Carvacrol essence were determined according the standard protocol. Finally, expression level of the biofilm related genes (Epa and Esp) were evaluated before and after the treatment with Carvacrol. RESULTS: A total of 14 isolates were considered as strong biofilm producers and were used for analysis. Carvacrol essence showed the best antibacterial activity at 2,500 µg/mL concentration against all the isolates, the biofilm formation capacity was decreased by Carvacrol essence, and it was statistically significant (p < 0.05). Expression levels of the Esp gene were decreased in 5 isolates while increased in 3 isolates following the Carvacrol treatment. Ex-pression levels of the EpaI gene was significantly decreased (p < 0.05) in 4 isolates following the Carvacrol treatment. CONCLUSIONS: In conclusion, the results presented in this study suggest that carvacrol extract exhibits significant antimicrobial and anti-biofilm properties against E. faecalis, even against vancomycin resistant isolates.

In Vitro and In Silico Investigation of some Type II TA Genes in H. Pylori.

BACKGROUND: In addition to antibiotic resistance, the entry of Helicobacter pylori into the persistence phase leads to recurrent and chronic infections, as well as the development of antibiotic resistance in persister cells. METHODS: In this study, after genetic confirmation of H. pylori in 20 biopsy specimens, the prevalence of the type II TA systems mazEF, relEB, yafQ/dinJ was investigated. Also, the most common system observed in the study in terms of structure, evolution, and molecular interaction was evaluated by bioinformatics tools. RESULTS: The results of the PCR test on 20 biopsy samples were positive for ureA and glmM genes. Moreover, yafQ/ dinJ was the only module positive in half of the samples (10 samples) in the PCR technique. The toxin residues and their interactions with the cognate antitoxin residues are revealed by docking analysis results. Furthermore, the multiple sequence alignment (MSA) of the YafQ toxin showed that this toxin has a low polymorphism among H. pylori species. The evolutionary study showed that the yafQ toxin had the highest sequence similarity among the bacteria Helicobacter cetorm (60% similarity) and Muricauda olearia (57.35 % similarity). CONCLUSIONS: Collectively, the data of the present study indicate that the YafQ/DinJ is the dominant type II TA system and has the highest frequency among the studied systems in H. pylori, and further studies are required to elucidate its exact role in this bacterium.

Worldwide prevalence of microbial agents' coinfection among COVID-19 patients: A comprehensive updated systematic review and meta-analysis.

BACKGROUND: To provide information about pathogens' coinfection prevalence with SARS-CoV-2 could be a real help to save patients' lives. This study aims to evaluate the pathogens' coinfection prevalence among COVID-19 patients. METHOD: In order to find all of the relevant articles, we used systematic search approach. Research-based databases including PubMed, Web of Science, Embase, and Scopus, without language restrictions, were searched to identify the relevant bacterial, fungal, and viral coinfections among COVID-19 cases from December 1, 2019, to August 23, 2021. In order to dig deeper, other scientific repositories such as Medrxiv were probed. RESULTS: A total of 13,023 studies were found through systematic search. After thorough analysis, only 64 studies with 61,547 patients were included in the study. The most common causative agents of coinfection among COVID-19 patients were bacteria (pooled prevalence: 20.97%; 95% CI: 15.95-26.46; I2 : 99.9%) and less frequent were virus coinfections (pooled prevalence: 12.58%; 95% CI: 7.31-18.96; I2 : 98.7%). The pooled prevalence of fungal coinfections was also 12.60% (95% CI: 7.84-17.36; I2 : 98.3%). Meta-regression analysis showed that the age sample size and WHO geographic region did not influenced heterogeneity. CONCLUSION: We identified a high prevalence of pathogenic microorganism coinfection among COVID-19 patients. Because of this rate of coinfection empirical use of antibacterial, antifungal, and antiviral treatment are advisable specifically at the early stage of COVID-19 infection. We also suggest running simultaneously diagnostic tests to identify other microbiological agents' coinfection with SARS-CoV-2.

Simultaneous Molecular Detection of Common Bacterial Enteropathogens in Children with Diarrhea by Multiplex-PCR Assay.

BACKGROUND: Diarrhea remains a major threat to children in low- and middle-income countries, which is the second cause of death among children in the world. The aim of the present study was to develop and evaluate a multiplex-PCR assay for direct detection of common bacterial enteropathogens in fecal specimens. METHODS: One hundred and three stool specimens were collected from children under 5 years of age with gastroenteritis during a six-month period in Ilam, Iran. The multiplex PCR assay simultaneously detected Shigella spp., Campylobacter jejuni, Enteropathogenic Escherichia coli (EPEC), Enterotoxigenic Escherichia coli (ETEC), and Salmonella enterica in stool samples. RESULTS: Our results demonstrated that the prevalence of Shigella spp. Campylobacter jejuni, EPEC, ETEC, and Salmonella enterica were 21.35%, 10.67%, 1.94%, 0.97% and 0%, respectively. In addition, Shigella spp. with Campylobacter jejuni and EPEC with Campylobacter jejuni coinfection were observed in sample 11 (10.67%). The analytical sensitivity of the multiplex PCR assay was estimated to be 0.01 ng/µL of genomic DNA from culture. The analytical specificity was determined to be 100% by using common and standard enteropathogenic bacterial strains. CONCLUSIONS: The molecular method developed in the study was rapid, sensitive, and specific for detection of common bacterial enteropathogens.

The characterization of bacterial communities of oropharynx microbiota in healthy children by combining culture techniques and sequencing of the 16S rRNA gene.

The high incidence of bacterial respiratory infections has led to a focus on evaluating the human respiratory microbiome. Studies based on culture-based and molecular methods have shown an increase in the bacterial community that includes the bacterial phyla Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria in the oropharynx of healthy individuals. Therefore, recognizing this microbial compound and subsequently identifying those carriers of specific pathogens can be of great help in predicting future infections and their control. In this prospective study, we sought to characterize the bacterial communities of the respiratory microbiome in healthy children aged between 3 and 6 years old by combining both cultural techniques and sequencing of the 16S rRNA gene. Seventy-seven oropharynx samples using Dacron swabs were collected from 77 healthy children in the kindergartens of Ilam, Iran. Bacterial identification was performed by phenotypic methods and in house developed PCR-based sequencing (the V1-V9 hypervariable region of the bacterial 16S ribosomal RNA gene). In total, 346 bacterial isolates were characterized based on phenotypic and sequencing-based molecular methods. The 3 most predominant phyla were Firmicutes (74%), Proteobacteria (22%), and Actinobacteria (4%). At the level of the genus, Staphylococci (coagulase-positive and coagulase-negative) and Streptococci were dominant. Also, the most commonly identified potentially pathogenic colonisers were S. aureus (75%), Enterobacteriaceae spp. (40.1%), and A. baumannii (15.6%). The present study identified 3 phyla and 9 family of bacteria in the oropharyngeal microbiome. Remarkably, the presence of potential pathogenic bacteria in the nasopharynx of healthy children can predispose them to infectious diseases, and also frequent exposure to human respiratory bacterial pathogens are further risk factors.

Multiple-Locus Variable-Number Tandem-Repeat Analysis Genotyping of Brucella Isolates from Iran.

BACKGROUND: Brucellosis is considered a main health concern in humans and animals. Neither familiar molecular methods nor the classical biotyping techniques are acceptable for subtyping Brucella spp. Loci containing variable number tandem repeats (VNTRs) have recently demonstrated their practicality in typing isolates from human and animal origin despite the excessive genetic homogeneity in the genus Brucella. METHODS: The genotypic characteristics of sixty-six Brucella melitensis and thirty-four Brucella abortus isolates from veterinary samples and human brucellosis cases in Iran during 2014 - 2018. They were analyzed using multiple-locus variable-number tandem-repeat analysis (MLVA) which consisted of sixteen primer pairs and designed and classified as belonging to one of the three panels: panel 1 (MLVA-8: eight loci including Bruce06, Bruce08, Bruce11, Bruce12, Bruce42, Bruce43, Bruce45, and Bruce55), panel 2A (three loci including Bruce18, Bruce19, and Bruce21), and panel 2B (five loci including Bruce04, Bruce07, Bruce09, Bruce16, and Bruce30); MLVA-11 (panels 1 and 2A), and MLVA-16 (panels 1, 2A, and 2B) using BioNumerics software (Version 7.6). RESULTS: Using panel 1, 2A, and 2B (MLVA-16), 59 genotypes with a genetic similarity coefficient ranging from 91 to 100% were obtained from the 100 Brucella spp. isolates. For all isolates, only genotype 36 and genotype 26 were obtained using panels 1 and 2A, respectively. The B. abortus isolates showed variations at 9 different genotypes, while B. melitensis isolates have been dispersed in 50 different genotypes. Bruce16 and Bruce4 showed the highest discriminatory power. CONCLUSIONS: The MLVA-16 assay appeared to be a useful and important molecular genotyping tool that is capable of proving epidemiological linkages in outbreak and trace-back investigations and is helpful in improving the effectiveness of brucellosis control programs.

A potential marker in brucellosis, long non coding RNA IFNG-AS1.

Brucellosis is the most common bacterial zoonotic infection. This pathogen may survive and sustain in host. The aim of this study is to define relationship between long noncoding (lnc) RNA-IFNG-AS1 and interferon gamma (IFN-γ) in different groups of patients with brucellosis compared to control group. In this study, associations of lncRNA IFNG-AS1 expression with secretion of IFN-γ level in Sixty patients with brucellosis, which were divided into 3 groups (acute, chronic and relapse groups), as a case group were compared with 20 subjects with negative serological tests and brucellosis clinical manifestation as a control group. In this regard, RNA were extracted from isolated peripheral blood mononuclear cells (PBMCs). LncRNA IFNG-AS1, T-box transcription factor (T-bet) and IFN-γ expressions were detected using quantitative polymerase chain reaction (qPCR). Serum level IFN-γ was assessed using enzyme linked immunosorbent assay (ELISA). The results showed that expression level of LncRNA IFNG-AS1, T-bet and IFN-γ increased significantly in all patient groups in compared to healthy subjects (P < 0.0001, P < 0.01, P < 0.001). However, there was no significant difference in T-bet expression between chronic and healthy groups (P = 0.98). Additionally, further analysis revealed that the serum level of IFN-γ in acute and relapsed groups were higher than control group (P < 0.0001, P < 0.001). The effective role of IFNG-AS1 in many protective actions, including enhancing the expression of INF-γ in the immune response of brucellosis patients, revealed new potential marker, LncRNA IFNG-AS1 in screening, diagnosis or treatment of brucellosis.

Phenotypic and Genotypic Characterization of ESBL-, AmpC-, and Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli Isolates.

OBJECTIVES: Drug resistance among gram-negative bacteria is a worldwide challenge. Due to the importance of drug-resistant Klebsiella pneumoniae and Escherichia coli strains in hospital-acquired infections, we aimed to determine the phenotypic and genotypic characteristics of ESBL-, AmpC-, and carbapenemase-producing isolates obtained from hospitalized patients in Tehran and Ilam (Iran). MATERIALS AND METHODS: In total, 90 K. pneumoniae isolates and 65 E. coli isolates were collected from various infections. Phenotypic identification of bacterial isolates was performed using standard methods. Phenotypic screening of ESBL, AmpC, and carbapenemase enzymes was carried out. Detection of ESBL, AmpC, and carbapenemase genes was also performed by the PCR method. RESULTS: Phenotypic detection tests showed that 36 (40%) K. pneumoniae and 23 (35.4%) E. coli isolates were ESBL producers. Moreover, 18 (20%) and 6 (9.2%) K. pneumoniae and E. coli isolates were AmpC producers, respectively. Modified Hodge test results indicated that 39 (43.3%) K. pneumoniae and 18 (27.7%) E. coli isolates produced carbapenemase. Molecular tests showed that 40% of K. pneumoniae and 36.9% of E. coli isolates were ESBL positive. AmpC was detected in 24.4 and 13.8% of K. pneumoniae and E. coli isolates. Carbapenemase was detected in 34 (37.8%) K. pneumoniae and 13 (20%) E. coli isolates. -Conclusion: In this study, 3 K. pneumoniae isolates simultaneously carried ESBL, AmpC, and carbapenemase genes. Up-to-date strategies such as combination therapy or utilization of new antimicrobial agents might help to combat such drug-resistant organisms.

Circulating levels of the miRNAs, miR-194, and miR-29b, as clinically useful biomarkers for colorectal cancer.

The microRNAs (miRNAs), miR-194 and miR-29b, have been shown to downregulate in colorectal cancer (CRC) and may identify and classify CRC patients as compared with those in control subjects. In the current study, we aimed to explore whether the serum levels of the miRNAs could be potential biomarkers for diagnosis and prognosis of CRC. A quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assay was utilized to determine and compare serum levels of miR-194 and miR-29b in 55 patients with CRC and 55 control subjects. The correlations between levels of the miRNAs and clinicopathological stages of cancer were analyzed in patients. Receiver operating characteristic (ROC) curve and survival analyses were carried out, respectively, to determine diagnostic and prognostic values of the miRNAs. Serum levels of miR-194 and miR-29b were found to be significantly lower in CRC patients than those in control subjects (P < 0.0001). Moreover, serum levels of the miRNAs in patients were inversely correlated with the advanced TNM stages (P = 0.01). ROC curve and survival analyses revealed that reduced levels of the miRNAs could serve as diagnostic and prognostic biomarkers for patients with CRC (P = 0.0001). Serum levels of miR-194 and miR-29b may serve as potential biomarkers for diagnosis and prognosis of CRC.

Sewage as a rich source of phage study against Pseudomonas aeruginosa PAO.

Pseudomonas aeruginosa is a ubiquitous organism which has emerged as a major public health threat in hospital environments. Overuse of antibiotics has significantly exacerbated the emergence of multi-drug resistant bacteria such as P. aeruginosa. Phages are currently being utilized successfully for aquaculture, agriculture and veterinary applications. The aim of this study was to isolate and characterize of lytic P. aeruginosa phage from sewage of Ilam, Iran. Phage was isolated from sewage that was added to the enrichment along with the host and subsequently filtered. Plaque assay was done by using an overlay method (also called the double agar layer method). Purified plaques were then amplified for characterization. Finally, RAPD-PCR method was conducted for genotyping and Transition electron micrograph (TEM) recruited to determine the morphology and phage family. The phage had high concentration and tremendous effects against a variety of clinical and general laboratory strains (ATCC15693) of P. aeruginosa. Among a set of primers in RAPD panel, only P2 and RAPD5 primers, were useful in differentiating the phages. TEM images revealed that the isolated phages were members of the Siphoviridae family. The phage effectiveness and specificity towards target bacteria and potential to control biofilm formations will be investigate in our further studies.

Inhibitory Effects of Carvacrol on Biofilm Formation in Colistin Heteroresistant Acinetobacter baumannii Clinical Isolates.

BACKGROUND: The ability of bacteria to form biofilm is an essential strategy for creating stable infections. This issue is more critical in Acinetobacter bauamannii as a hospital pathogen. Today, the control of biofilm formation and solutions to prevent or remove biofilm is being developed. Carvacrol has been considered an anti-biofilm compound in significant bacteria. This study investigated the anti-biofilm effect of Carvacrol on biofilm formation in clinical colistin heteroresistant isolates of A. baumannii. METHODS: 22 clinical strains of A. baumannii were collected from Motahari Hospital in Tehran, Iran, in 2019. Biochemical and genotypic methods confirmed these isolates. Colistin heteroresistance was determined by the Standard PAP method. Carvacrol's antibacterial and anti-biofilm activity was determined according to the standard protocol. RESULTS: About 12 isolates were considered strong biofilm producers and were used for analysis. Six isolates had hetero-resistance to colistin. Carvacrol at a 512 g/ml concentration showed the best antibacterial activity against all isolates. The sub-MIC of Carvacrol (256 g/ml) reduced the biofilm formation capacity, which was statistically significant (p < 0.05). CONCLUSION: The results of this study showed that sub-MIC of Carvacrol has anti-biofilm effects in clinical A.baumannii colistin hetero-resistance isolates.

Proteomics Exploration of Brucella melitensis to Design an Innovative Multi-Epitope mRNA Vaccine.

Brucellosis is a chronic and debilitating disease in humans, causing great economic losses in the livestock industry. Making an effective vaccine is one of the most important concerns for this disease. The new mRNA vaccine technology due to its accuracy and high efficiency has given promising results in various diseases. The objective of this research was to create a novel mRNA vaccine with multiple epitopes targeting Brucella melitensis. Seventeen antigenic proteins and their appropriate epitopes were selected with immunoinformatic tools and surveyed in terms of toxicity, allergenicity, and homology. Then, their presentation and identification by MHC cells and other immune cells were checked with valid tools such as molecular docking, and a multi-epitope protein was modeled, and after optimization, mRNA was analyzed in terms of structure and stability. Ultimately, the immune system's reaction to this novel vaccine was evaluated and the results disclosed that the designed mRNA construct can be an effective and promising vaccine that requires laboratory and clinical trials.

COVID-19 Mass Vaccination and Flu Season: Concern for Decreased Public Health Measures and Worsening the Influenza Situation.

Reports show that other ordinary childhood infections like measles or influenza are likely to reemerge. The re-emergence of infectious diseases may happen due to the direct impact of the pandemic on the community because of decreased access to health and medical services, interrupted transport systems, weaknesses in the supply chain, flight restrictions, closings of the border, and international trade problems. The most prevalent cause (60.9%) for low vaccine uptake and coverage during the current pandemic was fear of exposure to the COVID-19 virus outside the home. The expectation and hope that the pattern of reduction in transmission and number of influenza cases will continue over the next flu season depend on continued adherence to nonpharmaceutical interventions and their long-term application. But there is always the fear and threat of increasing the spread of influenza by reducing the movement restrictions and low adherence to protective health measures due to vaccination. So far, not much information has been published about the interaction between different infectious diseases in the background of the coronavirus pandemic and related interventions. The purpose of this article is to examine the general effects of the COVID-19 vaccination on the spread of influenza in the coming seasons.

In silico Study of the Proteins Involved in the Persistence of Brucella spp.

BACKGROUND: One of the major problems with Brucella infections is its tendency to become chronic and recurrent, providing a hindrance to the management of this infection. It has been proposed that chronicity is greatly affected by a phenomenon called persistence in bacteria. Several mechanisms are involved in bacterial persistence, including the type II toxin-antitoxin system, the SOS and oxidative and stringent responses. METHODS: In this in silico study, these persistence mechanisms in Brucella spp. were investigated. RESULTS: The structure and the interactions between modules involved in these systems were designed, and novel peptides that can interfere with some of these important mechanisms were developed. CONCLUSION: Since peptide-based therapeutics are a new and evolving field due to their ease of production, we hope that peptides developed in this study, as well as the information about the structure and interactions of modules of persistence mechanisms, can further be used to design drugs against Brucella persister cells in the hope of restraining the chronic nature of Brucellosis.

Environmental Surface Contamination with SARS-CoV-2: Toilets as the Most Contaminated Surfaces in COVID-19 Referral Hospital.

INTRODUCTION: The possibility of surface transmission in hospitals with high density of COVID- 19 patients is unneglectable. The aim of this study is to determine the extent of surface contamination in coronavirus central hospital of Ilam province in western Iran. MATERIALS AND METHODS: In this experimental study, 205 samples were taken from environmental surfaces in hospital. SARS-CoV-2 RNA detected by Real-time RT-PCR. RESULTS: 121 out of 205 (50.02%) samples were positive. The most contaminated objects were toilet sites (5/5,100% ICU; 5/5, 100% isolation wards). CONCLUSION: High surface contamination with SARS-CoV-2 proposes the surface as a potential route of transmission.