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.

Molecular characterization of Staphylococcus aureus isolated from hospital-acquired infections in Ilam, Iran.

OBJECTIVE: This research study was undertaken to investigate antimicrobial resistance patterns and the prevalence of hospital-acquired infections (HAIs). The study focuses on common microorganisms responsible for HAIs and explores emerging challenges posed by antimicrobial drug-resistant isolates. METHODS: A comprehensive analysis of 123 patients with HAIs, hospitalized in surgical department and intensive care unit (ICU) at Imam Khomeini Hospital, Ilam, Iran, was conducted over a six-month period. Pathogenic bacterial isolates, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA), were isolated and subjected to antibiotic susceptibility testing. RESULTS: The study findings revealed a significant prevalence of multidrug-resistant (MDR) isolates, of which 73.3% were MRSA. Notably, 6.7% of S. aureus isolates exhibited resistance to vancomycin, indicating the emergence of VRSA. Respiratory infections were identified as the most prevalent HAI, constituting 34.67% of cases, often arising from extended ICU stays and invasive surgical procedures. Furthermore, patients aged 60 and above, particularly those associated with MDR, exhibited higher vulnerability to HAI. CONCLUSIONS: This research sheds light on the intricate interplay between drug resistance and HAI, highlighting the imperative role of rational antibiotic use and infection control in addressing this critical healthcare challenge.

The global prevalence of gastric cancer in Helicobacter pylori-infected individuals: a systematic review and meta-analysis.

BACKGROUND: Helicobacter pylori is a gastrointestinal pathogen that infects around half of the world's population. H. pylori infection is the most severe known risk factor for gastric cancer (GC), which is the second highest cause of cancer-related deaths globally. We conducted a systematic review and meta-analysis to assess the global prevalence of GC in H. pylori-infected individuals. METHODS: We performed a systematic search of the PubMed, Web of Science, and Embase databases for studies of the prevalence of GC in H. pylori-infected individuals published from 1 January 2011 to 20 April 2021. Metaprop package were used to calculate the pooled prevalence with 95% confidence interval. Random-effects model was applied to estimate the pooled prevalence. We also quantified it with the I2 index. Based on the Higgins classification approach, I2 values above 0.7 were determined as high heterogeneity. RESULTS: Among 17,438 reports screened, we assessed 1053 full-text articles for eligibility; 149 were included in the final analysis, comprising data from 32 countries. The highest and lowest prevalence was observed in America (pooled prevalence: 18.06%; 95% CI: 16.48 - 19.63; I2: 98.84%) and Africa (pooled prevalence: 9.52%; 95% CI: 5.92 - 13.12; I2: 88.39%). Among individual countries, Japan had the highest pooled prevalence of GC in H. pylori positive patients (Prevalence: 90.90%:95% CI: 83.61-95.14), whereas Sweden had the lowest prevalence (Prevalence: 0.07%; 95% CI: 0.06-0.09). The highest and lowest prevalence was observed in prospective case series (pooled prevalence: 23.13%; 95% CI: 20.41 - 25.85; I2: 97.70%) and retrospective cohort (pooled prevalence: 1.17%; 95% CI: 0.55 - 1.78; I 2: 0.10%). CONCLUSIONS: H. pylori infection in GC patients varied between regions in this systematic review and meta-analysis. We observed that large amounts of GCs in developed countries are associated with H. pylori. Using these data, regional initiatives can be taken to prevent and eradicate H. pylori worldwide, thus reducing its complications.

Nosocomial infections and antimicrobial susceptibility patterns among patients admitted to intensive care unit of Imam Khomeini hospital in Ilam, Iran.

INTRODUCTION: Nosocomial infections (NIs) are a major challenge worldwide. Identification of antibiotic resistance pattern extended spectrum beta-lactamases (ESBLs) and carbapenem-resistant Enterobacteriaceae (CRE) were the objectives of this study. METHODS: In this cross-sectional study, the antimicrobial susceptibility pattern of bacterial isolates collected from patients with NIs in ICU was determined. Overall, 42 Escherichia coli and Klebsiella pneumoniae isolates from different infection sites were used to determine phenotypic tests of ESBLs, Metallo-ß-lactamases (MBLs) and CRE. Detection of ESBLs, MBLs and CRE genes were performed by the polymerase chain reaction (PCR) method. RESULTS: From 71 patients with NIs, 103 different bacterial strains were isolated. The most frequently isolated bacteria were E. coli (n = 29; 28.16%), Acinetobacter baumannii (n = 15; 14.56%), and K. pneumoniae (n = 13; 12.26%). Also, the rate of multidrug-resistant (MDR) isolates was 58.25% (60/103). Based on phenotypic confirmation tests, 32 (76.19%) isolates of E. coli and K. pneumoniae produced ESBLs, and 6 (14.28%) isolates were identified as CRE producers. PCR showed the high prevalence of the blaCTX-M (n = 29; 90.62%) in ESBL genes. In addition, blaNDM was detected in 4 (66.66%), blaOXA-23 in 3 (50%), and blaOXA-48 gene in 1 (16.66%) isolates. The blaVIM, blaKPC, and blaIMP genes were not detected in any of the isolates. CONCLUSION: The Gram-negative bacteria E. coli, A. baumannii, and K. pneumoniae with high resistance levels were the most common bacteria causing NIs in the ICU. This study for the first time identified blaOXA-11, blaOXA-23, and blaNDM-1 genes in E. coli and K. pneumoniae in Ilam city of Iran.

Evaluating the incidence of ampC-ß-lactamase genes, biofilm formation, and antibiotic resistance among hypervirulent and classical Klebsiella pneumoniae strains.

AIM: Both immunocompetent and healthy individuals can become life-threateningly ill when exposed to the hypervirulent (hvKp) strains of Klebsiella pneumoniae (Kp). The main objectives of this study were to evaluate the presence of ampC-lactamase genes, biofilm formation, and antibiotic resistance in clinical strains of hvKp and cKp (classical K. pneumoniae). MATERIALS AND METHODS: Kp strains were collected from patients referred to Shahidzadeh Hospital in Behbahan City, Khuzestan Province, Iran. Several techniques were used to identify hvKp. The hypermucoviscosity phenotype was determined using the string test. Isolates that developed dark colonies on tellurite agar were assumed to be hvKp strains. If any of the iucA, iutA, or peg-344 genes were detected, the isolates were classified as hvKp. Phenotypic and genotypic detection of AmpC ß-lactamases of hvKp strains was performed by the combined disk method and polymerase chain reaction, respectively. In addition, crystal violet staining was used to determine the biofilm formation of these isolates. RESULTS: For this study, 76 non-duplicative isolates of Kp were collected. Overall, 22 (28.94%) strains had positive string test results, and 31 (40.78%) isolates were grown in tellurite-containing medium. The genes iucA and iutA or peg-344 were found in 23.68% of all Kp strains and in 50% of tellurite-resistant isolates, respectively. The most effective antibiotics against hvKp isolates were tetracycline (85.52%) and chloramphenicol (63.15%). Using the cefoxitin disc diffusion method, we observed that 56.57% (43/76) of the strains were AmpC producer. A total of 30.26% (n = 23/76) of the isolates tested positive for at least one ampC gene, including blaDHA (52.63%, n = 40), blaCIT (40.78%, n = 31), blaACC (19.76%, n = 15), blaMOX (25%, n = 19), and blaFOX (43.42%, n = 33). Biofilm formation analysis revealed that most hvKp isolates were weak (n = 6, 40%) and moderate (n = 5, 33.33%) biofilm producers. CONCLUSION: Healthcare practitioners should consider the possibility of the existence and acquisition of hvKp everywhere. The exact mechanisms of bacterial acquisition are also unknown, and it is unclear whether the occurrence of infections is related to healthcare or not. Thus, there are still many questions about hvKp that need to be investigated.

Evaluation of the Levels of Blood Cells, Vitamin D, and Inflammatory Factors in Children with PFAPA Syndrome.

BACKGROUND: The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA syndrome) is the most common type of recurrent fever in childhood. The aim of this study was evaluation of the levels of blood cells, vitamin D, and inflammatory factors in children with PFAPA syndrome. METHODS: This retrospective descriptive study was conducted on the recorded information of children with PFAPA syndrome referred to the children's specialty clinic of Imam Khomeini Hospital in Ilam city from March 2021 to February 2022. Complete demographic information, presence of underlying disease, changes in blood cells, vitamin D level and inflammatory factors were obtained from the patients' records. Diagnosis of PFAPA syndrome was performed according to Thomas' criteria. RESULTS: This study was conducted on 40 children with PFAPA syndrome. The majority of patients were male and in the age range of 3 - 4 years. The results show that the average percentage of neutrophil and lymphocyte cells in the blood of patients was 54.45% and 40.62%, respectively. Also, 6 (15%), 3 (7.5%), and 31 (77.5%) patients had normal neutrophil levels, neutropenia, and neutrophilia, respectively. Regarding lymphocyte cells, 26 (65%), 8 (20%), and 6 (15%) people had normal lymphocyte level, lymphocytosis and lymphopenia, respectively. ESR levels increased in all patients (average percentage: 16.72). CRP level was negative in 9 (22.5%) and +1 in 19 (47.5%) patients, respectively. The results showed that 33 (82.5%) patients were deficient in vitamin D level. CONCLUSIONS: The etiology and pathogenesis of PFAPA is still unknown; however, the rapid response to corticosteroid therapy is the indication of an immune deregulation. Treatment guidelines for PFAPA syndrome based on controlled studies are needed, as well as a better understanding of the disease itself.

Potential Role of Lactobacillus and Bifidobacterium for Preventing Kidney Stones.

BACKGROUND: A probiotic is a living microorganism that promotes host health when grown under appropriate conditions. Kidney stones are one of the universal agonizing diseases that have increased dramatically in recent years. One of the causes of this disease is hyperoxaluria (HOU), which is known to be an important factor in the formation of oxalate stones and is manifested by high levels of oxalate in the urine. In addition, about 80% of kidney stones contain oxalate, and decomposition of this material by microbes is one way to dispose of it. METHODS: Therefore, we examined a bacterial mixture containing Lactobacillus plantarum, Lactobacillus casei, Lactobacillus acidophilus, and Bifidobacterium longum to prevent of oxalate production in Wistar rats with kidney stones. We divided the rats into 6 groups defined in the method. RESULTS: The results of this study clearly show a decrease in urinary oxalate levels by exogenous means by L. plantarum, L. casei, L. acidophilus, and B. longum at the beginning of the experiment. Therefore, these bacteria can be used to control and prevent the formation of kidney stones. CONCLUSIONS: However, further studies should be conducted on the effects of these bacteria, and it is recommended to identify the gene responsible for the degradation of oxalate in order to develop a new probiotic.

Detection of qacΔE Efflux Pump Gene among the Clinical Isolates of Escherichia coli and its Correlation with Resistance to Disinfectants.

BACKGROUND: Disinfectants and antiseptics inhibit the dissemination of pathogenic organisms in hospitals but often cause disinfectant-resistant microorganisms, an important factor for nosocomial infection. This study aimed to evaluate the correlation between qacΔE efflux pump gene and its resistance to disinfectants among Escherichia coli clinical isolates. METHODS: A total of 97 E. coli isolates were isolated from patients with urinary tract infections. The minimum inhibition concentration (MIC) value of chlorhexidine and benzalkonium chloride was determined using broth microdilution method. Effect of efflux pumps was assessed by MIC test in the presence of phenylalanine-arginine ß-naphthylamide (PAßN), and then the qacΔE efflux pump gene was detected using polymerase chain reaction (PCR). RESULT: Of the isolates, 85.6% and 61.9% were resistant to chlorhexidine and benzalkonium chloride, respectively. Following the treatment of isolates with the efflux pump's inhibitor, PAßN, the MIC value of chlorhexidine and benzalkonium chloride decreased in 75.2% and 57.7% of the isolates, respectively. A significant correlation was found between PAßN treatment and the change in the resistant strains to susceptible strains (p = 0.021). The qacΔE gene was detected in 84.5% (n = 82) of the isolates, and the presence of the gene amongst disinfectant-resistant strains was also significant (p < 0.001). CONCLUSIONS: It is suggested to conduct other studies on other efflux pumps, as well as to periodically monitor the resistance to disinfectants. Substances inhibiting efflux pumps and neutral compounds are effective in the reduction of resistance to disinfectants. New disinfectants and drugs should be designed.

Global Estimate of Clarithromycin Resistance in Clinical Isolates of Helicobacter pylori: a Systematic Review and Meta-Analysis.

BACKGROUND: A high resistance rate to clarithromycin usually leads to failure to eradicate Helicobacter pylori. The aim of the present study was to review recent data on H. pylori resistance towards clarithromycin in clinical studies worldwide. METHODS: PubMed/Medline, Web of Science, and Embase were used for a systematic review from 1 January 2011 to 13 April 2021 to retrieve the clinical trial studies. Data were analyzed according to publication year, age, geographic area, and minimum inhibitory concentration (MIC). Statistical analysis was done by STATA version 14.0 (College Station, Texas). RESULTS: From a total of 4,304 articles, 89 articles related to clinical studies were selected for analysis. The overall H. pylori clarithromycin resistance rate was 34.95%. Based on continents, the highest and lowest pooled estimate of the bacterial resistance rates were observed in Asia (35.97%) and North America (7.02%), respectively. The highest and the lowest pooled estimate of H. pylori resistance rate to clarithromycin based on country were obtained in Australia (93.4%) and USA (7%), respectively. CONCLUSIONS: H. pylori resistance to clarithromycin in most parts of the world is more than 15%, so it is recommended that each country, after estimating the rate of resistance to clarithromycin, determine the treatment/eradication pattern for H. pylori infection.

Mixed oral biofilms are controlled by the interspecies interactions of Fusobacterium nucleatum.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) is an integral component of supra- and subgingival biofilms, especially more prevalent in subgingival areas during both periodontal health and disease. AIMS: In this review, we explore the physical, metabolic, and genetic interactions that influence the role of F. nucleatum in the formation of mixed oral biofilms. The role of F. nucleatum in antibiotic resistance in oral biofilms was discussed and some therapeutic strategies were proposed. METHODS: PubMed, Scopus, Google Scholar, and the Web of Science were extensively searched for English-language reports. RESULTS: F. nucleatum-derived proteins such as RadD, Fap2, FomA, and CmpA are involved in direct interactions contributing to biofilm formation, while autoinducer-2 and putrescine are involved in metabolic interactions. Both groups are essential for the formation and persistence of oral biofilms. This study highlights the clinical relevance of targeted interactions of F. nucleatum in supra- and subgingival oral biofilms. CONCLUSIONS: By focusing on these interactions, researchers and clinicians can develop more effective strategies to prevent biofilm-related disease and reduce the spread of antibiotic resistance. Further research in this area is warranted to explore the potential therapeutic interventions that can be derived from understanding the interactions of F. nucleatum in oral biofilm dynamics.

Antimicrobial resistance and biofilm formation capacity among Acinetobacter baumannii strains isolated from patients with burns and ventilator-associated pneumonia.

BACKGROUND: Acinetobacter baumannii is a pathogen responsible for nosocomial infections, especially in patients with burns and ventilator-associated pneumonia (VAP). The aims of this study was to compare the biofilm formation capacity, antimicrobial resistance patterns and molecular typing based on PFGE (Pulsed-Field Gel Electrophoresis) in A. baumannii isolated from burn and VAP patients. MATERIALS AND METHODS: A total of 50 A. baumannii isolates were obtained from burn and VAP patients. In this study, we assessed antimicrobial susceptibility, biofilm formation capacity, PFGE fingerprinting, and the distribution of biofilm-related genes (csuD, csuE, ptk, ataA, and ompA). RESULTS: Overall, 74% of the strains were multidrug resistant (MDR), and 26% were extensively drug-resistant (XDR). Regarding biofilm formation capacity, 52%, 36%, and 12% of the isolates were strong, moderate, and weak biofilm producers. Strong biofilm formation capacity significantly correlated with XDR phenotype (12/13, 92.3%). All the isolates harbored at least one biofilm-related gene. The most prevalent gene was csuD (98%), followed by ptk (90%), ataA (88%), ompA (86%), and csuE (86%). Harboring all the biofilm-related genes was significantly associated with XDR phenotype. Finally, PFGE clustering revealed 6 clusters, among which cluster No. 2 showed a significant correlation with strong biofilm formation and XDR phenotype. CONCLUSION: Our findings revealed the variable distribution of biofilm-related genes among MDR and XDR A. baumannii isolates from burn and VAP patients. A significant correlation was found between strong biofilm formation capacity and XDR phenotype. Finally, our results suggested that XDR phenotype was predominant among strong-biofilm producer A. baumannii in our region.

Molecular characterizations of antibiotic resistance, biofilm formation, and virulence determinants of Pseudomonas aeruginosa isolated from burn wound infection.

BACKGROUND: Burn injuries result in disruption of the skin barrier against opportunistic infections. Pseudomonas aeruginosa is one of the main infectious agents colonizing burn wounds and making severe infections. Biofilm production and other virulence factors along with antibiotic resistance limit appropriate treatment options and time. MATERIALS AND METHODS: Wound samples were collected from hospitalized burn patients. P. aeruginosa isolates and related virulence factors identified by the standard biochemical and molecular methods. Antibiotic resistance patterns were determined by the disc diffusion method and ß-lactamase genes were detected by polymerase chain reaction (PCR) assay. To determine the genetic relatedness amongst the isolates, enterobacterial repetitive intergenic consensus (ERIC)-PCR was also performed. RESULTS: Forty P. aeruginosa isolates were identified. All of these isolates were biofilm producers. Carbapenem resistance was detected in 40% of the isolates, and blaTEM (37/5%), blaVIM (30%), and blaCTX-M (20%) were the most common ß-lactamase genes. The highest resistance was detected to cefotaxime, ceftazidime, meropenem, imipenem and piperacillin, and 16 (40%) isolates were resistant to these antibiotics. The minimum inhibitory concentrations (MIC) of colistin was lower than 2 µg/mL and no resistance was observed. Isolates were categorized to 17 MDR, 13 mono-drug resistance, and 10 susceptible isolates. High genetic diversity was also observed among the isolates (28 ERIC types) and most carbapenem-resistant isolates were classified into four main types. CONCLUSION: Antibiotic resistance, particularly carbapenem resistance was considerable among the P. aeruginosa isolates colonizing burn wounds. Combining carbapenem resistance with biofilm production and virulence factors would result in severe and difficult-to-treat infections.

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.

Antibacterial activity of recently approved antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) strains: A systematic review and meta-analysis.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections are considered an important public health problem, and treatment options are limited. Accordingly, in this meta-analysis, we analyzed published studies to survey in vitro activity of recently approved antibiotics against MRSA isolates. METHODS: We searched electronic databases; PubMed, Scopus, and Web of Science to identify relevant studies (until November 30, 2020) that have focused on the in vitro activity of telavancin, dalbavancin, oritavancin, and tedizolid against MRSA isolates. Statistical analyses were conducted using STATA software (version 14.0). RESULTS: Thirty-eight studies were included in this meta-analysis. Overall in vitro activity of tedizolid on 12,204 MRSA isolates was 0.250 and 0.5 µg/mL for MIC50 and MIC90, (minimum inhibitory concentration at which 50% and 90% of isolates were inhibited, respectively), respectively. The overall antibacterial activity of dalbavancin on 28539 MRSA isolates was 0.060 and 0.120 µg/mL for MIC50 and MIC90, respectively. The overall antibacterial activity of oritavancin on 420 MRSA isolates was 0.045 and 0.120 µg/mL for MIC50 and MIC90, respectively. The overall antibacterial activity of telavancin on 7353 MRSA isolates was 0.032 and 0.060 µg/mL for MIC50 and MIC90, respectively. The pooled prevalence of tedizolid, telavancin, and dalbavancin susceptibility was 100% (95% CI: 100-100). CONCLUSION: Telavancin, dalbavancin, oritavancin, and tedizolid had potent in vitro activity against MRSA isolates. The low MICs and high susceptibility rates of these antibiotics recommend a hopeful direction to introduce useful antibiotics in treating MRSA infections in the future.

An overview on inactivated and live-attenuated SARS-CoV-2 vaccines.

After about 2 years since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first infections were detected in Wuhan city of China in December 2019, which was followed by a worldwide pandemic with a record of 5.41 million deaths. Due to urgent need for the development of a safe and effective vaccine for coronavirus disease 2019 (COVID-19), attempts for producing efficient vaccines are inexhaustibly continuing. According to a report by the World Health Organization (WHO) on COVID-19 vaccine tracker and landscape, there are 149 vaccine candidates all over the world. Inactivated SARS-CoV-2 vaccines as a conventional vaccine platform consist of whole virus particles grown in cell culture and inactivated by chemicals. Because of benefits such as antigenic similarity to real virion inducing humoral and cellular immune responses and ease for transport and storage, these vaccines, including the vaccines produced by Bharat Biotech, Sinopharm, and Sinovac, are in use at large scales. In this study, we have a review on inactivated SARS-CoV-2 vaccines that are passing their phase 3 and 4 clinical trials, population which was included in the trials, vaccine producers, the efficiency, adverse effects, and components of vaccines, and other vaccine features.

Obesity and gut-microbiota-brain axis: A narrative review.

INTRODUCTION: Obesity is a major health problem that is associated with many physiological and mental disorders, such as diabetes, stroke, and depression. Gut microbiota has been affirmed to interact with various organs, including the brain. Intestinal microbiota and their metabolites might target the brain directly via vagal stimulation or indirectly through immune-neuroendocrine mechanisms, and they can regulate metabolism, adiposity, homoeostasis and energy balance, and central appetite and food reward signaling, which together have crucial roles in obesity. Studies support the concept of bidirectional signaling within the gut-brain axis (GBA) in the pathophysiology of obesity, mediated by metabolic, endocrine, neural, and immune system mechanisms. MATERIALS AND METHODS: Scopus, PubMed, Google Scholar, and Web of Science databases were searched to find relevant studies. RESULTS: The gut-brain axis (GBA), a bidirectional connection between the gut microbiota and brain, influences physiological function and behavior through three different pathways. Neural pathway mainly consists of the enteric nervous system (ENS) and vagus nerve. Endocrine pathway, however, affects the neuroendocrine system of the brain, particularly the hypothalamus-pituitary-adrenal (HPA) axis and immunological pathway. Several alterations in the gut microbiome can lead to obesity, by modulating metabolic pathways and eating behaviors of the host through GBA. Therefore, novel therapies targeting the gut microbiome, i.e., fecal microbiota transplantation and supplementation with probiotics and prebiotics, can be a potential treatment for obesity. CONCLUSION: This study corroborates the effect of gut microbiome on physiological function and body weight. The results show that the gut microbiota is becoming a target for new antiobesity therapies.

Clinical manifestations, treatment options, and comorbidities in COVID-19 relapse patients: A systematic review.

INTRODUCTION: Interest revolving around coronavirus disease 2019 (COVID-19) reinfection is escalating rapidly. By definition, reinfection denotes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), PCR redetection, and COVID-19 recurrence within three months of the initial symptoms. The main aim of the current systematic review was to evaluate the features of COVID-19 relapse patients. MATERIALS AND METHODS: For this study, we used a string of terms developed by a skilled librarian and through a systematical search in PubMed, Web of Science, and Embase for eligible studies. Clinical surveys of any type were included from January 2019 to March 2021. Eligible studies consisted of two positive assessments separated by a negative result via RT-PCR. RESULTS: Fifty-four studies included 207 cases of COVID-19 reinfection. Children were less likely to have COVID-19 relapse. However, the most patients were in the age group of 20-40 years. Asthenia (66.6%), headache (66.6%), and cough (54.7%) were prevalent symptoms in the first SARS-CoV-2 infection. Asthenia (62.9%), myalgia (62.9%), and headache (61.1%) were most frequent in the second one. The most common treatment options used in first COVID-19 infection were lopinavir/ritonavir (80%), oxygen support (69.2%), and oseltamivir (66.6). However, for the treatment of second infection, mostly antibiotics (100%), dexamethasone (100%), and remdesivir (80%) were used. In addition, obesity (32.5%), kidney failure (30.7%), and hypertension (30.1%) were the most common comorbidities. Unfortunately, approximately 4.5% of patients died. CONCLUSION: We found the potency of COVID-19 recurrence as an outstanding issue. This feature should be regarded in the COVID-19 management. Furthermore, the first and second COVID-19 are similar in clinical features. For clinically practical comparison of the symptoms severity between two epochs of infection, uniform data of both are required. We suggest that future studies undertake a homogenous approach to establish the clinical patterns of the reinfection phenomena.

Neurological manifestations in patients with COVID-19: A systematic review and meta-analysis.

INTRODUCTION: The intensification of coronavirus disease 2019 (COVID-19) complications, severe symptoms, and high mortality rate has led researchers to focus on this significant issue. While respiratory and cardiac complications have been described as high-risk manifestations in patients with COVID-19, neurological complications can also enhance mortality. This study aimed to evaluate the prevalence of neurological complications arises from SARS-CoV-2 and assess the mortality rate from neurological complications. MATERIAL AND METHODS: Literature review was conducted by searching in PubMed/Medline, Web of Sciences, and Embase. After performing search strategies with relevant terms, a number of articles were excluded, including review articles, systematic review or meta-analysis, duplicate publication of same researchers, congress abstracts, animal studies, case reports, case series, and articles reporting a history of neurological features prior to COVID-19 infection. After retrieving the data, statistical analysis was performed using the STATA Version 14 software. RESULTS: From 4455 retrieved publications, 20 articles were selected for further analysis. Among 18,258 included patients, 2791 showed neurological symptoms, which were classified into different groups. Headache, confusion, and fatigue were reported as the most non-specific neurological features in confirmed COVID-19 patients. Psychiatric symptoms, CNS disorders, cerebrovascular disorders, CNS inflammatory disorders, PNS disorders, neuromuscular disorders, etc., were defined as specific neurological manifestations. The pooled prevalence of neurological manifestations and mortality rate of COVID-19 patients with neurological features were estimated to be 23.0% (95% CI: 17.8-29.2) and 29.1% (95% CI: 20.3-39.8), respectively. CONCLUSION: Neurological manifestations may commonly happen in patients with COVID-19. This study reported a high prevalence of neurological complications and mortality rates in COVID-19 patients. Therefore, patients with COVID-19 who indicated neurological symptoms should be taken seriously and should receive early treatment to prevent undesirable events.

Mechanism of action, resistance, synergism, and clinical implications of azithromycin.

BACKGROUND: Azithromycin (AZM), sold under the name Zithromax, is classified as a macrolide. It has many benefits due to its immunomodulatory, anti-inflammatory, and antibacterial effects. This review aims to study different clinical and biochemisterial aspects and properties of this drug which has a priority based on literature published worldwide. METHODS: Several databases including Web of Science, Google Scholar, PubMed, and Scopus were searched to obtain the relevant studies. RESULTS: AZM mechanism of action including the inhibition of bacterial protein synthesis, inhibition of proinflammatory cytokine production, inhibition of neutrophil infestation, and macrophage polarization alteration, gives it the ability to act against a wide range of microorganisms. Resistant organisms are spreading and being developed because of the irrational use of the drug in the case of dose and duration. AZM shows synergistic effects with other drugs against a variety of organisms. This macrolide is considered a valuable antimicrobial agent because of its use as a treatment for a vast range of diseases such as asthma, bronchiolitis, COPD, cystic fibrosis, enteric infections, STIs, and periodontal infections. CONCLUSIONS: Our study shows an increasing global prevalence of AZM resistance. Thus, synergistic combinations are recommended to treat different pathogens. Moreover, continuous monitoring of AZM resistance by registry centers and the development of more rapid diagnostic assays are urgently needed.

Identification of metallo-ß-lactamases and AmpC production among Escherichia coli strains isolated from hemodialysis patients with urinary tract infection.

BACKGROUND: This study aimed to identify metallo-ß-lactamases (MBLs) and AmpC ß-lactamases-producing Escherichia coli isolates obtained from hemodialysis (HD) patients with urinary tract infections (UTI). METHODS AND RESULTS: A total of 257 HD patients with UTI were included in this study, from which 47 E. coli isolates were collected. Antibiotic susceptibility was tested by disc diffusion method. MBLs and AmpC production were phenotypically detected by imipenem-ethylenediaminetetracetate and cefoxitin/boronic acid assays, respectively. The presence of MBLs and AmpC genes was examined by polymerase chain reaction (PCR). Fosfomycin and ampicillin were the most and the least effective antibiotics against E. coli isolates, respectively. Moreover, 61.7% (29/47) of E. coli isolates were multidrug-resistant with seven different antibiotypes. Antibiotype V (AMP-CIP-IMP-MEM-CPD-CRO-CTX-GEN-LEV-SXT-TOB) was the most prevalent profile. Besides, 24 (51.1%) isolates were simultaneously resistant to imipenem and meropenem. Phenotypic assay showed MBL production in 16 (66.7%) of the 24 carbapenem-resistant E. coli isolates. The distribution of MBL genes in carbapenem-resistant E. coli was as follows: blaIMP 18 (72%), blaVIM 7 (28%), and blaNDM 1 (4%). AmpC was detected in 61.7% (29/47) of the isolates using the phenotypic method. The presence of AmpC genes was confirmed by PCR in only 26 of 29 (86.7%) AmpC producers. The frequencies of blaDHA-1, blaACC, and blaCMY-2 were 6 (20.7%), 11 (37.9%), and 21 (72.4%), respectively. CONCLUSIONS: The emergence of MBL and AmpC coproducing E. coli isolates calls for an urgent surveillance program for timely diagnosis and screening of these genes in our healthcare systems.