Recent advances in different interactions between toll-like receptors and hepatitis B infection: a review.

Hepatitis B virus (HBV) B infections remain a primary global health concern. The immunopathology of the infection, specifically the interactions between HBV and the host immune system, remains somewhat unknown. It has been discovered that innate immune reactions are vital in eliminating HBV. Toll-like receptors (TLRs) are an essential category of proteins that detect pathogen-associated molecular patterns (PAMPs). They begin pathways of intracellular signals to stimulate pro-inflammatory and anti-inflammatory cytokines, thus forming adaptive immune reactions. HBV TLRs include TLR2, TLR3, TLR4, TLR7 and TLR9. Each TLR has its particular molecule to recognize; various TLRs impact HBV and play distinct roles in the pathogenesis of the disease. TLR gene polymorphisms may have an advantageous or disadvantageous efficacy on HBV infection, and some single nucleotide polymorphisms (SNPs) can influence the progression or prognosis of infection. Additionally, it has been discovered that similar SNPs in TLR genes might have varied effects on distinct populations due to stress, diet, and external physical variables. In addition, activation of TLR-interceded signaling pathways could suppress HBV replication and increase HBV-particular T-cell and B-cell reactions. By identifying these associated polymorphisms, we can efficiently advance the immune efficacy of vaccines. Additionally, this will enhance our capability to forecast the danger of HBV infection or the threat of dependent liver disease development via several TLR SNPs, thus playing a role in the inhibition, monitoring, and even treatment guidance for HBV infection. This review will show TLR polymorphisms, their influence on TLR signaling, and their associations with HBV diseases.

Biofilm Formation in Mycobacterial Genus; Mechanism of Biofilm Formation and Anti-Mycobacterial Biofilm Agents.

Mycobacterium tuberculosis, Mycobacterium leprae, and non-tuberculous mycobacteria (NTM) are among the most significant human pathogens within the Mycobacterium genus. These pathogens can infect people who come into contact with biomaterials or have chronic illnesses. A characteristic pathogenic trait of mycobacteria is the development of biofilms, which involves several molecules, such as the GroEL1 chaperone, glycopeptidolipids, and shorter-chain mycolic acids. Bacterial behavior is influenced by nutrients, ions, and carbon sources, which also play a regulatory role in biofilm development. Compared to their planktonic phase, mycobacterial biofilms are more resilient to environmental stresses and disinfectants. Mycobacteria that produce biofilms have been found in several environmental studies, particularly in water systems. NTM can cause respiratory problems in individuals with underlying illnesses such as cystic fibrosis, bronchiectasis, and old tuberculosis scars. Mycobacteria that grow slowly, like those in the Mycobacterium avium complex (MAC), or rapidly, like Mycobacterium abscessus, can be pathogens. Infections related to biomaterials represent a significant category of biofilm-associated infections, with rapidly growing mycobacteria being the most frequently identified organisms. A biofilm produced by M. tuberculosis can contribute to caseous necrosis and cavity formation in lung tissue. Additionally, M. tuberculosis forms biofilms on clinical biomaterials. Biofilm formation is a major contributor to antimicrobial resistance, providing defense against drugs that would typically be effective against these bacteria in their planktonic state. The antibiotic resistance of biofilm-forming microbes may render therapy ineffective, necessitating the physical removal of biofilms to cure the infection. Recently, new approaches have been developed with potential anti-biofilm compounds to increase treatment effectiveness. Understanding biofilms is crucial for the appropriate treatment of various NTM diseases, and the recent discovery of M. tuberculosis biofilms has opened up a new field of study. This review focuses on the biofilm formation of the Mycobacterial genus, the mechanisms of biofilm formation, and anti-mycobacterial biofilm agents.

The effect of donepezil hydrochloride on post-COVID memory impairment: A randomized controlled trial.

BACKGROUND: Post-Coronavirus Disease (COVID-19) condition, known as "post-COVID syndrome," is associated with a range of complications persisting even after recovery. Among these complications, cognitive dysfunction, including memory impairment, has been relatively common observed, impacting executive function and quality of life. To date, no approved treatment exists for this specific complication. Therefore, the present clinical trial aimed to investigate the impact of Donepezil Hydrochloride on post-COVID memory impairment. METHODS: A randomized, controlled trial (Approval ID: IRCT20210816052203N1) was conducted, enrolling 25 patients with post-COVID memory impairment. Participants with a history of hospitalization were randomly assigned to either the drug group (n = 10) or the control group (n = 15). Memory indices were assessed at baseline, one month, and three months later using the Wechsler Memory Scale-Revised test. SPSS software and appropriate statistical tests were employed for data analysis. RESULTS: The statistical analysis revealed no significant difference in WMS-R subtest and index scores between the drug and control groups at the 4-week and 12-week follow-up periods. However, within the drug group, there was a notable increase in the visual reproduction I and verbal paired associates II subtests during the specified time intervals. CONCLUSION: While donepezil 5 mg did not exhibit a significant overall increase in memory scales compared to the control group over time, our findings suggest that this medication may exert a positive effect on specific memory subtests. Further research and exploration are warranted to better understand the potential benefits of donepezil in managing post-COVID-related memory impairment. TRIAL REGISTRATION: The study was approved by the Research Ethics Committee of Aja University of Medical Sciences (Approval ID: IR.AJAUMS.REC.1400.125) and registered in the Iranian Registry of Clinical Trials (IRCT) (Approval ID: IRCT20210816052203N1).

Neuropathology of 30 deceased patients with COVID-19: a case series in Tehran, Iran.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect the nervous system and result in neurological symptoms. The most common feature of central nervous system involvement is hypoxia and congestion. This study aimed to evaluate the histopathology of cerebral tissue in deceased patients with coronavirus disease 2019 (COVID-19). Methods: In a case series study, we took cerebral samples of 30 deceased patients with COVID-19 through supraorbital bone from January to May 2021. The samples were fixed in a formalin solution, stained with haematoxylin-eosin dyes and studied by two expert pathologists. The Ethics Committee of AJA University of Medical Sciences approved this study with code IR.AJAUMS.REC.1399.030. Results: The mean age of the patients was 73.8 years, and the most common underlying disease was hypertension. Cerebral tissue samples showed hypoxic-ischaemic changes in 28 (93.3%), microhaemorrhage in six (20%), lymphocytic infiltration in five (16.7%) and thrombosis in three samples (10%). Conclusion: Hypoxic-ischaemic change was the most common neuropathology in our patient. Our study showed that many patients with severe COVID-19 may develop central nervous system involvement.

Cardio-Pulmonary Histopathology with Clinical Correlations of Deceased Patients with COVID-19: A Case Series in Tehran, Iran.

BACKGROUND: SARS-CoV-2 may affect vital organs. The present study investigated the histopathology of pulmonary and cardiac tissues with clinical correlation in deceased patients with COVID-19. METHODS: We obtained pulmonary and cardiac tissues from 30 deceased patients with COVID-19 in Tehran, Iran, from January to May 2021. Sampling was performed through a percutaneous needle biopsy. After slide preparation, two expert pathologists studied them. We assessed the correlation between clinical and pathological data by Fisher's exact test. RESULTS: The mean age of the patients was 73.8±13.4 years, and the male-to-female ratio was 23/7. The most common underlying disease was hypertension (HTN) in 25 patients (83%). Fifty-five tissue samples were achieved, including 28 pulmonary and 27 cardiac samples. Our results showed that all patients (100%) developed diffuse alveolar damage (DAD), and 26 (93%) developed hyaline membrane formation. The most common phase of DAD was the exudative-proliferative phase in 16 (57.1%). Three cardiac samples (11%) revealed myocarditis, and seven (26%) showed cardiomyocyte hypertrophy. In univariate analysis using Fischer's exact test, myocarditis had significant relationships with C-reactive protein (CRP) levels higher than 80 mg/dL (P=0.008) and elevated cardiac troponin levels higher than two-fold (P=0.01). CONCLUSION: COVID-19 can affect the major vital organs. However, only myocarditis had a significant relationship with the circulating levels of inflammatory factors.

Efficacy of a standardized herbal formulation from Glycyrrhiza glabra L. as an adjuvant treatment in hospitalized patients with COVID-19: A Randomized Controlled trial.

Introduction: As no specific pharmacological intervention has been known for COVID-19, medicinal plants may be a suitable candidate for management of this disease. The aim of this study was to investigate the efficacy of a herbal syrup from licorice as an adjuvant treatment in hospitalized patients with COVID-19. Materials and methods: 213 hospitalized patients diagnosed with COVID-19 were assigned to receive either standardized licorice syrup as an adjuvant treatment plus standard care [Syrup Group (SYRUP), N = 91], or standard care alone [Standard Group (STANDARD), N = 104], for 7 days. The primary endpoint was duration of hospitalization in survivors. The secondary endpoints included 25% increase in oxygen saturation, C-reactive protein (CRP) difference and lymphocyte difference from baseline, number of death and number of patients transferred to ICU. Results: Mean duration of admission was 5.24 days in SYRUP and 7.14 days in STANDARD (p < 0.001). Oxygen saturation increased in 86 of 91 patients (94.5%) in the licorice group, compared to 83 of 104 patients (79.8%) in the control group (p = 0.002). There was no significant difference between the two groups in the number of patients died during hospitalization (p = 0.837). Five patients in SYRUP and 16 patients in STANDARD were transferred to ICU (p < 0.026). Mean reduction in CRP (p < 0.001) and mean increase in the number of lymphocytes (p = 0.008) in SYRUP were significantly higher than STANDARD. Discussion: Licorice syrup as an adjuvant treatment demonstrated promising results on duration of hospital admission, O2 saturation as well as inflammatory markers in COVID-19 patients; however, further clinical studies with larger sample size are suggested to achieve more conclusive results.

Efficacy of Red Blood Cell Exchange as Adjunctive Treatment for Hypoxemia and Survival Rate of Patients With Severe Coronavirus-2 Disease: An Open-Labeled Phase 2 Randomized Clinical Trial.

Background: Severe acute respiratory syndrome (SARS) coronavirus-2 may infect red blood cells (RBCs) and impact oxygenation. We aimed to evaluate the efficacy of RBC exchange as an adjunctive treatment for hypoxemia and the survival rate of patients with severe coronavirus disease 2019 (COVID-19). Methods: In a randomized clinical trial, we divided sixty patients with severe COVID-19 into two groups. The intervention group received the standard treatment of severe COVID-19 with RBC exchange three to four times in 2 days. The control group only received the standard treatment. Our primary outcomes were improving hypoxemia in 7 days, recovery or discharge, and death in 28 days. We conducted Chi-square test, independent samples t-test, and Fisher's exact test to analyze the results. The ethical committee of Aja University of Medical Sciences approved the study (IR.AJAUMS.REC.1399.054), and the Iranian clinical trial registration organization registered it (IRCT20160316027081N2). Results: Twenty-nine men and thirty-one women with a mean age of 67.5 years entered the study. The frequency of hypertension and diabetes mellitus was 86.7 and 68.3%, respectively. The most common symptoms of severe COVID-19 were dyspnea (91.6%), cough (75%), and fever (66.6%). Our results showed that hypoxemia improved in 21 of the 30 patients (70%) in the intervention group and 10 of the 30 patients (33.3%) in the control group (P < 0.004). The recovery and discharge rates were 19 of 30 patients (63.3%) in the intervention group and 2 of 30 patients (6.7%) in the control group (P < 0.001). Conclusion: The RBC exchange improved the oxygenation and survival rate in patients with severe COVID-19.

Donepezil Beyond Alzheimer's Disease? A Narrative Review of Therapeutic Potentials of Donepezil in Different Diseases.

Donepezil hydrochloride is an acetylcholine esterase inhibitor studied and approved to treat Alzheimer's disease (AD). However, this drug can have positive therapeutic potential in treating different conditions, including various neurodegenerative disorders such as other types of dementia, multiple sclerosis, Parkinson's disease, psychiatric and mood disorders, and even infectious diseases. Hence, this study reviewed the therapeutic potential of this drug in treating Alzheimer's and other diseases by reviewing the articles from databases including Web of Science, Scopus, PubMed, Cochrane, and Science Direct. It was shown that donepezil could affect the pathophysiology of these diseases via mechanisms such as increasing the concentration of acetylcholine, modulating local and systemic inflammatory processes, affecting acetylcholine receptors like nicotinic and muscarinic receptors, and activating various cellular signaling via receptors like sigma-1 receptors. Despite many therapeutic potentials, this drug has not yet been approved for treating non-Alzheimer's diseases, and more comprehensive studies are needed.

Analysis of 239 ordinary and severe cases of COVID-19: Clinical features and treatment.

This study retrospectively analyzed the clinical characteristics of patients with new coronavirus infection (COVID-19) and summarizes the treatment experience. A total of 239 COVID-19 patients admitted to the Hajar Hospital, Aja University of Medical Science, Tehran, Iran from March 22, 2020 to May 18, 2020 were selected, including 176 cases in the ordinary group and 63 cases in the severe/critical group. We collected and compared the clinical data of the two groups of patients, including general conditions, clinical symptoms, signs, laboratory tests, lung CT imaging and prognosis, and analyzed the treatment plans of the two groups. The mean age of 239 COVID-19 patients was 48.1±17.6 years, including 132 males. Patients in the severe and critically ill groups were older than the normal group, with more males and more underlying diseases. The difference was statistically significant (p < 0.05). The lymphocyte (LYM) counts and albumin (ALB) counts of the severe and critically ill groups were more significantly lower than those of the normal group; while the percentage of neutrophils (NEU), C-reactive protein (CRP), D-dimer, and lactate The increase of lactate dehydrogenase (LDH) and urea nitrogen (BUN) was more significant, and the difference was statistically significant (p < 0.05). Patients in the severe and critically ill groups received more antiviral drugs, glucocorticoids, and nasal catheters than those in the normal group, and the difference was statistically significant (p < 0.05). Also, we observed that the most radiological finding was bilateral ground-glass opacity in both groups, however, the rate of typical abnormalities in both chest CT scan and chest x-ray was significantly higher in sever/critical group except air-bronchogram. Taken together, we showed that combination of oseltamivir and glucocorticosteroid such as dexamethasone was very effective in severe patients.

Expression of RND efflux pumps mediated antibiotic resistance in Pseudomonas aeruginosa clinical strains.

Resistance-Nodulation-Division (RND) efflux pumps are responsible for multidrug resistance in Pseudomonas aeruginosa. The present study aimed to evaluate the overexpression of RND efflux pumps and its role in the antibiotic resistance of P. aeruginosa clinical isolates. A number of 122 isolates were obtained from three military hospitals in Tehran, Iran. In order to determine the antibiotic resistance, the isolates were identified and assessed by the disk diffusion and agar dilution methods. This study investigated the gene expression of four multi-drug efflux pump systems (MexAB-OprM, MexCD-OprJ, MexEF-OprN and MexXY (-OprA)) and its correlation with antibiotic resistance. The isolates indicated that the highest resistance rate was against ticarcillin (80%), followed by ciprofloxacin (74%) and meropenem (71%). Most of them expressed mexB (69%), mexC (28.7%), mexE (43.4%), and mexY (74.6%), suggesting that mexB and mexY were highly expressed in the studied strains. The overexpression of mexB and mexY was significantly more prevalent in the ICU wards (p = 0.033). Furthermore, there was a significant correlation between the expression of RND-type efflux pumps and the resistance to most anti-pseudomonal antibiotics.

Cardiac Complications in COVID-19: A Systematic Review and Meta-analysis.

BACKGROUND: The newly emerged coronavirus disease 2019 (COVID-19) seems to involve different organs, including the cardiovascular system. We systematically reviewed COVID-19 cardiac complications and calculated their pooled incidences. Secondarily, we compared the cardiac troponin I (cTnI) level between the surviving and expired patients. METHODS: A systematic search was conducted for manuscripts published from December 1, 2019 to April 16, 2020. Cardiovascular complications, along with the levels of cTnI, creatine kinase (CK), and creatine kinase MB (CK-MB) in hospitalized PCR-confirmed COVID-19 patients were extracted. The pooled incidences of the extracted data were calculated, and the unadjusted cTnI level was compared between the surviving and expired patients. RESULTS: Out of 1094 obtained records, 22 studies on a total of 4,157 patients were included. The pooled incidence rate of arrhythmia was 10.11%. Furthermore, myocardial injury had a pooled incidence of 17.85%, and finally, the pooled incidence for heart failure was 22.34%. The pooled incidence rates of cTnI, CK-MB, and CK elevations were also reported at 15.16%, 10.92%, and 12.99%, respectively. Moreover, the pooled level of unadjusted cTnI was significantly higher in expired cases compared with the surviving (mean difference = 31.818, 95% CI = 17.923-45.713, P value <0.001). CONCLUSION: COVID-19 can affect different parts of the heart; however, the myocardium is more involved.

Incidence and Risk Factors of Brucellosis in Kermanshah Province, Iran During 2010-2014.

INTRODUCTION: Incidence of brucellosis was growing up in Iran during the past years. Kermanshah province-west of Iran is one of the endemic regions of the disease. The aim of this study was to evaluate the incidence and risk factors of brucellosis in Kermanshah province during a recent five-year period. METHODS: This study was an observational cross-sectional study performed on registries of the patients with brucellosis at the center for the zoonotic disease of Kermanshah University of medical sciences during 2010-2014. The data was collected using a questionnaire containing demographic data and the risk factor of brucellosis. Collected data were analyzed by SPSS-22 software using descriptive statistic, Chi-square, and student t-test. RESULTS: The five-years mean incidence of brucellosis in our study was 46.5 in one hundred thousand, and male to female ratio was 1.37/1. The most common risk factors of brucellosis in our patients were unpasteurized dairy products' consumption (47%) and occupational contact with livestock (14.4%). 84% of the patients were rural. The most common diagnostic method was the standard agglutination test within 1/160 and 1/320 titers. CONCLUSION: Risk factors of brucellosis in our study were like other studies, but in more than onethird of the patients, no risk factor was identified. Lack of livestock vaccination history and incomplete registered data about other possible transmission routes of transmission were the limitations of the study.

Tuberculous ventriculitis: A rare complication of central nervous system tuberculosis.

Tuberculous ventriculitis is an inflammatory infection of the ventricular system of the brain, and is caused by Mycobacterium tuberculosis. We herein present the case of an immunocompromised patient with brain tuberculomas who developed ventriculitis during treatment. The patient was successfully treated with a high dose of steroid, long-term antituberculosis drugs, and aggressive supportive care.

Brain Hydatid Cyst with Atypical Symptoms in an Adult: A Case Report.

Brain hydatid cyst constitutes one of the leading causes of cranial mass in the endemic region, especially among the children. Symptoms of the disease are associated with rising of intracranial pressure and focal neurological deficit. Surgical excision of the cyst is essential to treatment. Here we present a 19 yr-old male livings in Ardabil, northwest of Iran, referred to Neurosurgery Clinic in Khanevadeh University Hospital, Tehran, Iran with a large brain hydatid cyst and atypical symptoms. He was treated by surgical excision of the cyst without any complication. There were not any clinical or radiological signs of recurrence after one-year follow-up.

Association between Hepatitis G and Unknown Chronic Hepatitis.

BACKGROUND: Hepatitis G virus (HGV) is a hepatotrope virus with unknown importance. The genome of the virus has been detected in patients with acute or chronic non-A-E hepatitis, cirrhosis, and hepatocellular carcinoma. The aim of this study was to determine the association between hepatitis G and unknown chronic hepatitis. METHODS: This case-control study was performed in Ebne-Sina military hospital in Hamadan, Iran. The cases were 35 military staff with unknown chronic hepatitis. The control group consisted of 59 healthy subjects who had normal levels of serum alanine aminoteransferase (ALT). The data were analyzed by SPSS, version18, using Fisher's exact test, the Student's t-test, and multivariate logistic regression analysis. RESULTS: Only one patient in the case group (2.9%) tested positive for HGV antibodies, and no one was infected in the control group. There was no association between HGV infection and unknown chronic hepatitis in our study (P=0.37). A significant association was found between the male gender and unknown chronic hepatitis (OR=14.9, P=0.01). CONCLUSION: No association between HGV infection and unknown chronic hepatitis was found in our study, so it was not necessary to evaluate these patients for HGV infection.