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Background: Human Herpes Virus 8 (HHV-8) is involved in autoimmunity. However, its association with advanced liver disease has not been fully explained. Herein, the prevalence of HHV-8 viremia was assessed in Iranian liver transplant candidates with a confirmed diagnosis of cirrhosis. Methods: This cross-sectional study was conducted on 230 patients with cryptogenic cirrhosis, virus-related cirrhosis, and autoimmune hepatitis, as well as 140 healthy blood donors from April 2022 to September 2023. The HHV-8 IgG antibody concentration and viral load were evaluated via ELISA and RT‒PCR, respectively. Results: Anti-HHV-8 IgG antibodies were detected in 25 cirrhotic patients (10.8 %) and four healthy individuals (2.6 %) (p = 0.022). The majority of the seropositive patients had cryptogenic cirrhosis (20.4 %), followed by autoimmune hepatitis (13.1 %) and virus-related cirrhosis (4.7 %). The seropositivity of HHV-8 IgG antibody was significantly different among the etiologies of liver cirrhosis (p = 0.011). However, HHV-8 genomic DNA was not detected in the sera of the patients or healthy blood donors. Conclusion: The role of HHV-8 infection in the development of posttransplant diseases, together with the higher seroprevalence of HHV-8 antibodies in cirrhotic patients than in healthy individuals, highlights the importance of both primary and latent infections in liver transplantation. Therefore, serological and molecular screening of HHV-8 is highly suggested for liver transplant candidates and organ donors. The possibility of antibody-mediated epitope mimicry in cryptogenic and autoimmune groups with moderate HHV-8 antibody positivity and negative viral loads may account for the development of advanced liver diseases.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease caused by genetic and environmental factors such as viral infections. Genomic and serologic tests were applied to detect significant blood-borne viruses in SLE patients to determine whether there was a possible association between viral infections and SLE. Methods: Antibodies (Abs) against HHV-8, HCMV, EBV, HIV, HBV, and HCV in SLE patients suffering from SLE were assessed by ELISA. In addition, HHV-8 DNA and HIV-1 RNA were quantified by real-time PCR, and the HCV and HBV genomes were detected using nested PCR. Results: Compared to those in the control group, a high prevalence of anti-HHV-8 (p

Introduction: Various factors, including viruses, are involved in developing liver cirrhosis. Although the association of human herpesvirus-8 (HHV-8) with liver cirrhosis remains poorly understood, a significant increase in the titer of antibodies against this virus has been observed in cirrhotic patients. The present study aimed to evaluate the frequency of HHV-8-immunoglobulin G (HHV-8 IgG) in Iranian patients with liver cirrhosis. Material & Methods: In this cross-sectional study, 30 healthy blood donors and 30 patients with liver cirrhosis related to hepatitis B (n=20) and hepatitis C (n=10) viruses from those waiting for liver transplantation were included. The serum seropositivity of HHV-8 IgG antibody was evaluated using the enzyme-linked immunosorbent assay (ELISA) technique. Results: The seropositivity of HHV-8 IgG antibodies in patients and healthy groups was 6.7% (2 patients) and 3.3% (1 case), respectively, which did not show a significant difference between the two groups (P=0.554). In addition, the infection was not significantly related to the age and gender of the patients (P>0.05). Discussion & Conclusion: Considering the low prevalence of HHV-8 infection in Iranian patients with liver cirrhosis, it can be concluded that HHV-8 may not be associated with the incidence and progression of liver cirrhosis. Therefore, HHV-8 monitoring will not raise the concern about the development or worsening of liver disorders.

The operation of the electrical systems is a major problem for electrical companies’ subject to uncertainties threatening. In this study, the optimal management of the energy demand in the electrical distribution grid is done by interval optimization approach under electrical price uncertainty. The management of the energy demand is implemented via incentive-based modelling of the demand response programs (DRPs). The incentive-based modelling as reserve, and based on bid price for reduction of the electrical demand at peak hours is proposed. The interval optimization approach is used for the minimization of the electrical price uncertainty effects. The main objective in the proposed approach is minimizing operation cost; epsilon-constraint method is utilized to solve the problem. Finally, an electrical distribution grid has been used at various case studies to numerical simulation results and positive effects of the proposed modelling under uncertainties.

The emergence of resistance to antiretroviral drugs is the main problem in their long-term efficacy and by considering the wide use of protease inhibitors (PIs), monitoring drug resistance mutations is necessary. Therefore, this study aimed to investigate the PIs drug resistance mutations in Iranian patients as well as subtyping using bioinformatics analysis. Fifteen Iranian patients living with Human Immunodeficiency Virus (HIV) (PLWH) were examined. RNA was used to amplify and sequence the HIV protease gene; also, HIV viral load was determined for all samples. The sequencing results were analyzed by several strong bioinformatics tools to determine the drug-resistance mutations and HIV subtypes. Some polymorphisms in the protease gene were recognized; however, there was no significant rate of major or minor drug resistance mutations in our studied patients. Subtyping analysis revealed the new subtype (D) and the previously reported ones, A and CRF-AD 35, in patients. This study confirmed that the resistance mutations and genetic polymorphisms of the protease region are rare in Iranian-infected patients that can be concluded that prescribing protease inhibitor class in HIV-infected patients is promising in controlling HIV in Iran. In addition, conducting periodic studies to determine the new mutations and the rate of drug resistance to PIs in Iranian individuals highlights the importance of WHO guidelines that recommends monitoring of genotypic-resistance testing and investigation of mutations in HIV-related genes.

Abstract Background NS5A and NS5B proteins of hepatitis C virus (HCV) are the main targets of compounds that directly inhibit HCV infections. However, the emergence of resistance-associated substitutions (RASs) may cause substantial reductions in susceptibility to inhibitors. Methods Viral load and genotyping were determined in eighty-seven naïve HCV-infected patients, and the amplified NS5A and NS5B regions were sequenced by Sanger sequencing. In addition, physicochemical properties, structural features, immune epitopes, and inhibitors-protein interactions of sequences were analyzed using several bioinformatics tools. Results Several amino acid residue changes were found in NS5A and NS5B proteins; however, we did not find any mutations related to resistance to the treatment in NS5B. Different phosphorylation and few glycosylation sites were assessed. Disulfide bonds were identified in both proteins that had a significant effect on the function and structure of HCV proteins. Applying reliable software to predict B-cell epitopes, 3 and 5 regions were found for NS5A and NS5B, respectively, representing a considerable potential to induce the humoral immune system. Docking analysis determined amino acids involved in the interaction of inhibitors and mentioned proteins may not decrease the drug efficiency. Conclusions Strong interactions between inhibitors, NS5A and NS5B proteins and the lack of efficient drug resistance mutations in the analyzed sequences may confirm the remarkable ability of NS5A and NS5B inhibitors to control HCV infection amongst Iranian patients. The results of bioinformatics analysis could unveil all features of both proteins, which can be beneficial for further investigations on HCV drug resistance and designing novel vaccines.

Background: Systemic lupus erythematosus is a systemic autoimmune disease that affects almost all organs of the body, and viral infections are involved in its development and progression. The present study aimed to evaluate the serological status of some viral infections in patients with systemic lupus erythematosus and a healthy population. Methods: This descriptive study conducted from May 2017 to April 2018 at Shiraz HIV/AIDS Research Center, Shiraz University of Medical Sciences, Shiraz, Iran on 70 patients with systemic lupus erythematosus and 70 healthy individuals who had no autoimmune diseases and were matched with the patient group for age and sex. All patients had active records and were routinely visited in rheumatology clinic of Hafez hospital, affiliated with Shiraz University of Medical Sciences. The evidence of active disease was assessed by the physicians of this practice according to the American College of Rheumatology criteria. Peripheral blood samples were collected in tubes containing EDTA and centrifuged at 3000 rpm for 5 min. The plasma of study participants was evaluated for HBsAg, HCVAb, HIVAb, EBV-VCA-IgG, and CMV-IgG using a commercially available ELISA kit. Results: The seropositivity of CMV-IgG and EBV-VCA-IgG in the systemic lupus erythematosus group was 70 (100%) and 65 (92.9%), and in healthy individuals was 68 (97.1%) and 57 (81.4%), respectively. The prevalence of EBV-VCA-IgG in the systemic lupus erythematosus group was significantly higher than healthy ones (P=0.043). The optical density (OD) of CMV-IgG and EBV-VCA-IgG in patients with systemic lupus erythematosus was significantly higher than in healthy individuals (P

Background: Scleroderma is a chronic systemic disorder that affects the connective tissues. It is characterized by several immune manifestations, inflammation, vascular damage, and fibrosis. Some of the viral infections with complex mechanisms are involved in the development and progression of many autoimmune diseases, such as scleroderma. The present study aimed to investigate the serological prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) infections in Iranian patients with scleroderma. Methods: In this descriptive study 65 patients with scleroderma and 65 healthy individuals who had no autoimmune diseases and matched for age and sex, from May 2017 to April 2018 at Shiraz HIV/AIDS Research Center, Shiraz University of Medical Sciences, Shiraz, Iran, were included. The serum of study participants were evaluated for cytomegalovirus specific immunoglobulin G (CMV-IgG), Epstein-Barr virus viral capsid antigen immunoglobulin G (EBV-VCA-IgG), hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVAb), and human immunodeficiency virus antibody (HIVAb) using commercially available the enzyme-linked immunosorbent assay (ELISA) kit. Results: CMV-IgG was diagnosed in serum of all patients with scleroderma, while 49 (98%) healthy subjects had positive results for this test. In addition, EBV-VCA-IgG was diagnosed in 58 (89.2%) sclerodermic patients and 40 (80%) healthy subjects. The prevalence of CMV-IgG and EBV-VCA-IgG was not significantly different between patients and healthy subjects and had no significant relationship with age and sex. However, the titer of antibodies against CMV and EBV infections in the scleroderma group was higher than that in the control group (P

We aimed to investigate the association of pretreatment host and/or viral related factors with sustained virological response (SVR) rate in chronic hepatitis C (CHC) infected patients. This cohort study was performed on 200 IFN-naïve Iranian CHC patients who were treated with pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV). Pretreatment levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting blood sugar (FBS), HCV load and genotype were determined, and the pattern of changes was monitored throughout the course of treatment. The baseline FBS value in the non-responder group was significantly higher than that of the SVR group. The SVR group showed a rapid and continuous decline of ALT/AST activity from the beginning of the treatment, while the ALT level was fluctuating in non-responder and relapse groups. Persistent normalization of transaminases during combination antiviral therapy was significantly associated with SVR rate. Besides, age and FBS levels had the greatest impact on SVR. Minocycline seems to be a safe and effective adjuvant in the management of patients with schizophrenia.

Introduction: Combination of interferon-alpha (IFN-α) and Ribavirin (RBV) drugs is used for treatment of hepatitis C virus (HCV) chronic infection. Various factors play role in the response rate of HCV infected patients to treatment. HCV genotype along with viral load, age, race, obesity, insulin resistance, fibrosis and interleukin 28B gene (IL-28B) polymorphisms are considered the most important ones. In recent years, it has been claimed that some polymorphisms close to IL-28B gene play a significant role in response to combined therapy among which IL-28B polymorphisms have a more important role in sustained virological response (SVR). In this study, frequency of genotypes of rs8099917 polymorphism of interleukin 28B gene in 2 groups of Iranian healthy individuals and HCV infected patients living in Tehran was compared. Materials & Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to compare the frequency of genotypes of rs8099917 polymorphism between 105 healthy individuals and 105 chronic HCV infected patients. The results were analyzed with SPSS version 15 using χ2 test. Findings: The genotype frequency of this polymorphism in the healthy individuals was demonstrated as GG: 1%, GT: 25.7% and TT: 73.3%, while in HCV infected patients, it was shown as GT: 58.1% and TT: 41.9%.. No GG genotype was detected in the patients infected with HCV. Discussion & Conclusion: Our investigation came to the conclusion that a significant difference existed between the 2 groups of Iranian healthy and HCV infected individuals regarding the frequency of rs8099917 genotypes and frequency of favorable TT genotype, because it was higher among the healthy individuals than that of the patients infected with HCV

The conformational state of the activation loop (A-loop) is pivotal for the activity of most protein kinases. Hence, the characterization of the conformational dynamics of the A-loop is important to increase our understanding of the molecular processes related to diseases and to support the discovery of small molecule kinase inhibitors. Here, we carry out a combination of molecular dynamics (MD) and essential dynamics (ED) analyses to fully map the effects of phosphorylation, ADP, and conformation disrupting (CD) inhibitors (i.e., CD532 and MLN8054) on the dynamics of the A-loop of Aurora-A. MD revealed that the stability of the A-loop in an open conformation is enhanced by single phospho-Thr-288, while paradoxically, the presence of a second phosphorylation at Thr-287 decreases such stability and renders the A-loop more fluctuant in time and space. Moreover, we found that this post-translational modification has a significant effect on the direction of the A-loop motions. ED analysis suggests that the presence of the phosphate moiety induces the dynamics of Aurora-A to sample two distinct energy minima, instead of a single large minimum, as in unphosphorylated Aurora-A states. This observation indicates that the conformational distributions of Aurora-A with both single and double phospho-threonine modifications are remarkably different from the unphosphorylated state. In the closed states, binding of CD532 and MLN8054 inhibitors has the effect of increasing the distance of the N- and C-lobes of the kinase domain of Aurora-A, and the angle analysis between those two lobes during MD simulations showed that the N- and C-lobes are kept more open in presence of CD532, compared to MLN8054. As the A-loop is a common feature of Aurora protein kinases, our studies provide a general description of the conformational dynamics of this structure upon phosphorylation and different ligands binding.

Background: Various factors threaten the health and recovery of hospitalized elderly, including stressors in medical service centers. Therefore, the aim of the present study was to develop and preliminary validate a measurement tool to assess hospitalization-related stressors (HRS) among the elderly. Materials and Methods: This methodological research was conducted in 2015. The study was performed in two main phases. In the first phase, which was to develop the questionnaire, the data were collected through literature review, interview with few elderly patients, and calculating content validity index with the participation of 16 experts. The second phase included preliminary validation of the questionnaire in which a convenient sample of 200 hospitalized elderly patients recruited from 4 educational medical centers of the Isfahan University of Medical Sciences were studied. Principal component analysis method was used to identify the factorial structure of the questionnaire. In order to evaluate validity, Cronbach′s alpha coefficient was calculated. Results: After evaluating the results and relocating and merging some of the items, a version of 26 items in 7 categories was prepared with acceptable internal consistency (Cronbach′s alpha coefficient from 0.67 to 0.78 for the components and 0.83 for the tool). Conclusions: In this study, we were able to identify a set of important components and indicators of HRS in elderly; so it can be used as a useful instrument. Future studies are recommended in order to develop and validate this tool in other communities.

Background & Objective: Hepatitis C Virus (HCV) is one of the important risk factors for liver cirrhosis and hepatocellular carcinoma. Some of the host genetic factors such as interleukin 28B (IL-28B) may influence the response to the antiviral therapy. IL28B is a member of the interferon (IFN) family which causes an antiviral response. Previous studies indicated that rs12979860 polymorphisms of the IL-28B gene can influence persistent antiviral response. Therefore, in this study, the frequency of genotypes of rs12979860 polymorphisms in two groups of healthy and HCV infected Iranian individuals were evaluated. Materials & Methods: In this cross sectional study, PCR-RFLP method was used to evaluate the frequency of genotypes of rs12979860 polymorphisms in 105 healthy individuals and 105 chronic HCV infected patients. Results: The frequency of rs12979860 genotypes in healthy individuals was CC: 50.5%, CT: 45.7%, and TT: 3.8%. In HCV infected patients it was CC: 22.9%, CT: 63.8%, and TT: 13.3%. The frequency of rs12979860 genotypes had significant difference between two groups however it is not associated with sex. Conclusion: A significant difference was observed between healthy individuals and HCV infected patients in the frequency of rs12979860 genotypes. The favorable CC genotypes and unfavorable TT genotypes was more detected in healthy individuals and HCV infected patients, respectively.

Abstract INTRODUCTION: Prevalence of influenza A virus (Flu-A), respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) was assessed in children with acute respiratory infections (ARIs). METHODS: Nasopharyngeal aspirates and throat swabs were subjected to real-time polymerase chain reaction (PCR) to detect RSV and Flu-A and to conventional PCR to detect hMPV. RESULTS: Of the 156 children assessed, 93 (59.6%) carried at least one virus, with 35.9% positive for RSV, 14.1% for hMPV, and 9.6% for Flu-A. The prevalence of co-infections was 2.6%. CONCLUSIONS: The high detection rate may reflect increased sensitivity of real-time PCR compared to traditional PCR and viral culture.