First study of the detection of Human Herpes Virus-8 and major blood-borne viruses in iranian patients with SLE: A cross-sectional study.

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 < 0.0001), anti-HCMV (p = 0.014), and anti-EBV (p = 0.017) Abs was detected in SLE patients. HHV-8, HIV, HCV, and HBV genomic tests were negative in both groups, while only 1.1 %, 2.2 %, and 1.1 % of SLE patients were positive for anti-HIV, anti-HCV Abs, and HBsAg, respectively. The most frequent major complaint in patients was arthralgia (76.7 %). Conclusions: The increased prevalence of anti-HHV-8 Abs may not be related to the natural history of infection but to molecular mimicry. Increased anti-HCMV and anti-EBV Abs may also be associated with the development of SLE and may play direct or indirect roles in such infections or molecular mimicry. Since arthralgia is the most common symptom in SLE patients, the presence of these symptoms in any patient is a suggestive clue for the diagnosis of SLE. Defining the typical pattern of SLE in divergent nations with distinct environmental and geographical factors can be beneficial for obtaining a prompt diagnosis.

Transmitted Drug Resistance Against Integrase Strand Transfer Inhibitors in Iranian HIV-Infected Naïve Patients.

Background: Human Immunodeficiency Virus (HIV) has claimed the lives of millions of people during the past decades. While several antiretroviral drugs like Integrase Strand Transfer Inhibitors (INSTIs) have been introduced to control HIV, Transmitted Drug Resistance (TDR) in HIV genome caused failure in treatment. This study aimed to investigate TDR and natural occurring mutations (NOPs) in HIV integrase gene in Iranian HIV patients. Methods: In this cross-sectional study, blood samples of 30 HIV-positive patients who had never taken integrase inhibitors were considered for CD4 T cell count, RT real-time PCR, and, Nested PCR. The sequencing results were analyzed by CLC sequence viewer software and Stanford University HIV Drug Resistance Database. Results: In all samples, nine NOPs with a high prevalence were found; however, we did not find any drug resistance mutations, except for a mutation in one sample, which showed a low resistance level. Subtype A1 was dominant in all samples. Conclusion: Based on the findings and compared to our previous study, all patients were sustainable to main integrase inhibitors, including bictegravir, raltegravir, bictegravir, elvitegravir and dolutegravir. It seems the resistant mutation pattern attributed to integrase inhibitors was not diffent among studied patients; hence, the prescription of such inhibitors helps physicians to control HIV infection in Iranian HIV-infected patients.

First report on molecular docking analysis and drug resistance substitutions to approved HCV NS5A and NS5B inhibitors amongst Iranian patients.

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.

First report of HHV-8 viral load and seroprevalence of major blood-borne viruses in Iranian patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is characterized by autoimmune manifestations, and viral infections may have a key role in the development and progression of it. This study aimed to investigate the seroprevalence of major blood-borne viruses and HHV-8 viral load in Iranian SSc patients. METHODS: In this cross-sectional study, 90 patients with a confirmed history of SSc and 90 healthy blood donors were enrolled. The frequency of HHV-8, CMV, EBV, HIV, HBV, and HCV antibodies and HHV-8 viral load were evaluated by enzyme-linked immunosorbent assay and real-time PCR assay, respectively. RESULTS: HHV-8 IgG antibody was diagnosed in 61 (67.8%) patients and 3 (3.3%) healthy individuals (p<0.0001), but its genomic DNA was not detected in the patients or healthy blood donors. CMV and EBV antibodies were detected in 100% and 88.9% of SSc patients without any significant difference with healthy population (p>0.05). None of the patients or healthy population was positive for HBsAg and HIVAb; however, HCVAb was detected in two patients. CONCLUSION: According to the results, HHV-8 antibody was uniquely increased in SSc population while its frequency in healthy population was very low. Since none of the SSc patients were positive for HHV-8 genomic DNA, the high prevalence of HHV-8 antibody in this group was not related to the real history of infection. Therefore, antibody-mediated epitope mimicry can play a role to get the high rate of seropositivity and lead to pathogeneses of SSc. Besides, CMV and EBV viral load monitoring in SSc patients can help the physician to prescribe the viral drugs to suppress the viral replication and avoid the crucial effect of reactivation.

Evaluation of miR-122 Serum Level and IFN-λ3 Genotypes in Patients with Chronic HCV and HCV-Infected Liver Transplant Candidate.

BACKGROUND: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are the most common markers of liver damage, but serum level interpretation can be complicated. In hepatocytes, microRNA-122 (miR-122) is the most abundant miRs and its high expression in the serum is a characteristic of liver disease. OBJECTIVE: We aimed to compare the circulatory level of miR-122 in patients with Chronic Hepatitis C (CHC), Hepatitis C Virus (HCV) infected Liver Transplant Candidates (LTC) and healthy controls to determine if miR-122 can be considered as an indicator of chronic and advanced stage of liver disease. METHODS: MiR-122 serum level was measured in 170 Interferon-naïve (IFN-naïve) CHC patients, 62 LTC patients, and 132 healthy individuals via TaqMan real-time PCR. Serum levels of miR-122 were normalized to the serum level of Let-7a and miR-221. Also, the ALT and AST levels were measured. RESULTS: ALT and AST activities and the expression of circulatory miR-122 were similar in the CHC and LTC groups, but it had significantly increased compared to healthy individuals (P<0.001 and P<0.001, respectively). Up-regulation of miR-122 in the sample of patients with normal ALT and AST activities was also observed, indicating that miR-122 is a good marker with high sensitivity and specificity for diagnosing liver damage. CONCLUSION: miR-122 seemed to be more specific for liver diseases in comparison with the routine ALT and AST liver enzymes. Since the lower levels of circulating miR-122 were observed in the LTC group compared to the CHC group, advanced liver damages might reduce the release of miR-122 from the hepatocytes, as a sign of liver function deficiency.

Impact of IL28 Genotypes and Modeling the Interactions of HCV Core Protein on Treatment of Hepatitis C.

BACKGROUND: Mutations in the core CVR region of hepatitis C virus (HCV) and polymorphisms of interleukin 28B (IL28B) are associated with progression toward liver disease and in response to therapy. In addition, interactions of the core protein with some cell interactors can be related to HCV liver damage. AIM: This study aimed to evaluate the effect of core mutations as well as IL28B polymorphism on clinical features, sustained virological response (SVR) in 1a and 3a HCV genotypes amongst Iranian HCV infected patients, and the impact of mutations on core protein properties, antigenic properties, and interactions with HCV inhibitors, using several bioinformatics tools. METHODS: Seventy-nine Iranian patients infected with HCV genotypes 1a and 3a and diagnosed with chronic active hepatitis were examined. Plasma viral RNA was used to amplify and sequence the HCV Core gene; also, HCV viral load, molecular genotyping, and the liver enzymes were determined for all samples. The sequencing results were analyzed by several reliable bioinformatics tools to determine the physicochemical properties, B cell epitopes, post-modification changes, and secondary/tertiary structures; and evaluate the interactions with 4 drugs by docking method. RESULT: There were some substitutions in core CVR related to ALT and AST enzymes that can lead to HCV advanced liver disease. The most prevalent mutation for 3a genotypes was a substitution in aa 162 (I to V) while we did not find any mutation in 1a responder group. Polymorphism of the rs8099917 showed that the majority of patients had TG heterozygous and carried CT genotype at the rs12979860. Analysis indicated several phosphorylation sits for core protein as well as two important disulfide bonds. Immunogenic prediction showed that core protein can strongly induce the immune system. Interaction analysis, using the docking method revealed two potential interactors (Vitronectin and SETD2). CONCLUSION: Generally, mutations in all core CVR regions in all patients showed a relationship between such substitutions and higher liver enzymes that can result in advanced liver disease progression in HCV infected patients. Furthermore, immunoinformatics analysis determined the possible immunodominant regions to be considered in HCV vaccine designs. Furthermore, no association between SVR and IL28B polymorphism was shown. In silico analysis determined modification sites, structures, B-cell epitopes of core protein and interactions with several interactors can lead to persistent HCV infection in the cell and the progress of liver diseases.

Viral etiology of acute respiratory infections in children in Southern Iran.

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.

Glutathione S-Transferase Gene Polymorphisms and the Development of New-Onset Diabetes After Liver Transplant.

OBJECTIVES: The association between the glutathione S-transferase polymorphisms and the development of new-onset diabetes mellitus after liver transplant was studied. MATERIALS AND METHODS: Peripheral blood samples were collected from 106 liver transplant patients divided into 2 groups: 52 with new-onset diabetes mellitus and 54 without new-onset diabetes mellitus; 169 healthy individuals with no clinical evidence of diabetes mellitus were selected as a control group. The multiplex polymerase chain reaction technique was used for genotyping GSTM1 and GSTT1 genes, using the cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) gene as an internal control. The genotype of GSTP1 was determined using the restriction fragment length polymorphism-polymerase chain reaction technique. RESULTS: The frequency of both GSTM1 null and GSTT1 null genotypes was not significantly different in liver transplant patients with new-onset diabetes mellitus compared with the control group (P = .11 for GSTM1; P = .71 for GSTT1). Also, there was no statistically significant association between the frequency of the GSTP1 genotypes in the liver transplant patients with new-onset diabetes mellitus compared with controls. Neither GSTM1 nor GSTT1 null genotypes were associated with the risk of developing new-onset diabetes mellitus (P = .22 for GSTM1; P = .56 for GSTT1). However, the frequency of the heterozygous mutation (AG) in the A313G GSTP1 polymorphism in patients with new-onset diabetes mellitus was significantly higher than in patients without new-onset diabetes mellitus (55.8% vs 7.4%; P = .00). Thus, the risk of developing new-onset diabetes mellitus was significantly higher in patients presenting with heterozygous GSTP1 genotypes (odds ratio = 15.76; 95% confidence interval = 4.53-60.28; P = .00). CONCLUSIONS: The GSTP1 AG genotype was associated with an increased susceptibility to the development of new-onset diabetes mellitus after liver transplant.

Viral etiology of acute respiratory infections in children in Southern Iran

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.

Role of serum level and genetic variation of IL-28B in interferon responsiveness and advanced liver disease in chronic hepatitis C patients.

Interleukin-28B (IL-28B) is suspected to be associated with response to treatment and one of the basic immunological backgrounds in liver transplant candidate (LTC). We aimed to assess whether genotypes of IL-28B can play a role in therapeutic response or advanced stages of liver disease. A total of 364 subjects were genotyped for IL-28B rs12979860 and rs8099917 SNPs using PCR-RFLP assay. Moreover, IL-28 serum level, HCV loads, and genotype were performed. A significant increase was observed in the frequencies of unfavorable rs12979860 genotypes/CT + TT in the chronic hepatitis C (CHC) and LTC groups. In the case of rs8099917, CHC group had a significantly higher frequency of unfavorable genotypes/GT + GG compared to the healthy group. IL-28B serum level was also significantly higher in healthy group compared with the CHC and LTC groups. There were no differences in the distribution of the IL-28B genotypes and haplotypes between responder and non-responder patients. Our results suggest, for the first time, that unfavorable rs12979860 genotypes can be considered one of the important immunological backgrounds in the Iranian LTC population that was confirmed with the lower IL-28 serum level compared to healthy group. Besides, there was a possible association of favorable IL-28B genotypes with lower odds of susceptibility to CHC infection but no support for a positive association between analyzed SNPs and an outcome of therapy. Moreover, non-CT haplotypes may be regarded as a genetic risk factor that can increase the chance of infection with HCV and progression toward end-stage HCV-related liver disease.

Development and initial psychometric evaluation of the hospitalization-related stressors questionnaire for elderly patients.

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.

SEROLOGICAL RESPONSE TO VACCINES IN CHILDREN WITH DIABETES.

OBJECTIVE: Patients with diabetes mellitus (DM) are more susceptible to infections. Deficiency in some domains of immune system could be one of the main reasons, which increases the risk of infections. The aim of this study was to assess antibody responses to vaccines in a group of children with diabetes and in the controls. METHODS: A cross-sectional study was performed among 90 children under 15 years of age with a history of type 1 DM, referred to endocrinology clinics of university hospitals; Mofid Children Hospital and Loghman Hospital. Also, we enrolled ninety healthy children as the control group. Antibody levels against diphtheria, tetanus, pertussis, measles, mumps, rubella and hepatitis B (HB) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Among 90 patients with diabetes, 48% were male and 52% were female and in the control group 49% were male and 51% were female. Regarding IgG antibody levels against measles, there was not any significant difference between the two groups, but according to the applied kit, IgG levels against measles vaccine were positive in 62% of the diabetic and 84% of the controls. Also, there was a significant difference between the two groups in terms of IgG antibody level against rubella, but consistent with the applied kit, there was not any significant difference between the two the groups. CONCLUSION: Given the results of the study, no difference was found between patients with diabetes and controls who were vaccinated with pertussis, diphtheria, tetanus, mumps and HB vaccines. But there are some concerns about measles and rubella vaccinations that need further investigation.