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Background: Iran is facing an epidemiological transition with the increasing burden of non-communicable diseases, such as obesity-related disorders and cardiovascular diseases (CVDs). We conducted a population-based prospective study to assess the prevalence and incidence rates of CVDs and obesity-related metabolic disorders and to evaluate the predictive ability of various CVD risk assessment tools in an Iranian population., Method: We enrolled 5,799 participants in Amol, a city in northern Iran, in 2009-2010 and carried out the first repeated measurement (RM) after seven years (2016-2017). For all participants, demographic, anthropometric, laboratory, hepatobiliary imaging, and electrocardiography data have been collected in the enrollment and the RM. After enrollment, all participants have been and will be followed up annually for 20 years, both actively and passively., Results: We adopted a multidisciplinary approach to overcome barriers to participation and achieved a 7-year follow-up success rate of 93.0% with an active follow-up of 5,394 participants aged 18-90 years. In the RM, about 64.0% of men and 81.2% of women were obese or overweight. In 2017, about 16.2% and 5.2% of men had moderate or severe non-alcoholic fatty liver disease, while women had a significantly higher prevalence of metabolic syndrome (35.9%), and type 2 diabetes mellitus (20.9%) than men. Of 160 deceased participants, 69 cases (43.1%) died due to CVDs over seven years., Conclusion: The most prevalent obesity-related chronic disease in the study was metabolic syndrome. Across the enrollment and RM phases, women exhibited a higher prevalence of obesity-related metabolic disorders. Focusing on obesity-related metabolic disorders in a population not represented previously and a multidisciplinary approach for enrolling and following up were the strengths of this study. The study outcomes offer an evidence base for future research and inform policies regarding non-communicable diseases in northern Iran., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Motamed, Zamani, Maadi, Ajdarkosh, Roozafzai, Keyvani, Poustchi, Shakeri, Ashrafi, Perumal, Rabiee, Moradi-Lakeh, Khoonsari, Kheyri, Sohrabi, Doustmohammadian, Amirkalali, Safarnezhad Tameshkel, Gholizadeh, Hosseini and Karbalaie Niya.)

Background: Sleep quality is a notable factor of well-being. It also may play a role in the development and progression of chronic diseases and cancers. Therefore, this study was performed to investigate poor sleep quality and its influencing factors among Iranian patients with esophageal and gastric cancer., Methods: In this cross-sectional study, a total of 312 Iranian adult patients who suffered from esophageal and gastric cancers were employed from a gastrointestinal cancer-based cohort study conducted in a referral hospital in Tehran between 2015 and 2018. Persian version of the Pittsburg Sleep Quality Index (PSQI) was used to measure poor sleep quality. Univariate and multiple logistic regression models were applied to determine the related factors to poor sleep quality., Results: Of the participants, 203 (65.06%) were men, and 75.96% had gastric cancer. The mean age was 63.13±12.10 years. The results demonstrated that more than 62% of the patients had poor sleep quality. 148 (62.44%) patients out of 237 patients with gastric cancer had poor-quality sleep. Also, 46 (64.38%) patients out of 237 patients with esophageal cancer had poor-quality sleep. Based on the results of multiple logistic regression models, marital status has a negative association with poor sleep quality (odds ratio [OR]=0.32, P =0.015). In addition, having chronic disease (OR=2.16; P =0.028) and wealth index (OR=3.11, P =0.013; OR=3.81, P =0.003; OR=3.29, P =0.009; OR=3.85, P =0.003 for rich, moderate, poor, and poorest subgroups, respectively) had a positive association with poor sleep quality., Conclusion: The findings showed that about two-thirds of the patients studied were poor sleepers. Also, it was observed that marital status, chronic disease, and wealth index were important factors associated with poor sleep quality., Competing Interests: Competing Interests The authors have no competing interests to declare that are relevant to the content of this article., (© 2024 Middle East Journal of Digestive Diseases.)

Background: As SARS-CoV-2 becomes a major global health, the authors aimed to predict the severity of the disease, the length of hospitalization, and the death rate of COVID-19 patients based on The Acute Physiology and Chronic Health Evaluation II (APACHE II) criteria, neutrophil-lymphocyte ratio (NLR), and C-reactive protein (CRP) levels to prioritize, and use them for special care facilities., Methods: In a retrospective study, 369 patients with COVID-19 hospitalized in the ICU from March 2021 to April 2022, were evaluated. In addition to the APACHE II score, several of laboratory factors, such as CRP and NLR, were measured., Results: The values of CRP, NLR, and APACHE II scores were significantly higher in hospitalized and intubated patients, as well as those who died 1 month and 3 months after hospital discharge than those in surviving patients. The baseline NLR levels were the strongest factor that adversely affected death in the hospital, death 1 month and 3 months after discharge, and it was able to predict death, significantly., Conclusion: CRP, NLR, and APACHE II were all linked to prognostic factors in COVID-19 patients. NLR was a better predictor of disease severity, the need for intubation, and death than the other two scoring tools., Competing Interests: The authors declare no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Mitogen-Activated Protein Kinase (MAPK) pathway and its downstream signaling pathways, play an important role in intracellular signaling. Mutations in KRAS (activating mutation) and BRAF proto-oncogenes are identified as key finding of colorectal cancer. The aim of this study was to examine mutation analysis of KRAS and BRAF in Iranian Colorectal cancer patients., Methods: We used fifty archived formalin fixed paraffin-embedded (FFPE) blocks of Iranian colorectal cancer patients. DNA was extracted from FFPE blocks for PCR assay. The quality of PCR products was determined using horizontal electrophoresis. Then, sequencing and analysis of the sequencing results were performed to investigate variation status in the sequences., Results: KRAS exons and BRAF genes exon 15 in 50 CRC patients were analyzed, among the 19 mutant KRAS samples, 18 (36%) patients had a single base substitution (synonymous mutation) in exon 5, p. Arg161Arg (c.483G>A) and 1 (2%) patient in exon 2 (codon 12), p. Gly12Cys (c.34G>T). Also, we observed two mutations p. Val600Glu (c.1799 T>A) and p. Ser616Thr (c.1846T>A) in exon 15 of BRAF gene., Conclusions: We found a novel variant in BRAF gene. The p. Ser616Thr (c.1846T>A) mutation was not previously reported and we conclude that other new mutations can be identified in KRAS and BRAF which may lead to colorectal cancer.

The CYLD gene is a tumor suppressor, reduced in many cancers. Here, we aimed to investigate CYLD protein level and NF-κβ/TNF-α signaling pathway in rectal cancer patients with Lactobacillus acidophilus (L. acidophilus) consumption. One hundred ten patients with non-metastatic rectal cancer were randomly divided into L. acidophilus probiotic (500 mg, three times daily) and placebo groups for 13 weeks. The expression of CYLD, TNF-α, and NF-κB proteins and the genes involved in the NF-κβ/TNF-α pathway were evaluated using ELISA and qPCR techniques. The survival rate was measured after five years. Unlike the placebo group, the results showed a significant increase in the expression of CYLD protein and tumor suppressor genes, including FOXP3, ROR-γ, Caspase3, GATA3, T-bet, and a considerable decrease in the expression of NF-ҝβ and TNF-α proteins and oncogenes, including STAT3, 4, 5, 6, and SMAD 3, in the probiotic group. A higher overall survival rate was seen after L. acidophilus consumption compared to the placebo group (P < 0.05). L. acidophilus consumption can reduce inflammation factors by affecting CYLD protein and its downstream signaling pathways. A schematic plot of probiotic consumption Effects on the CYLD protein in regulating the NF-ĸβ signaling pathway in colorectal cancer. NF-ĸβ can be activated by canonical and noncanonical pathways, which rely on IκB degradation and p100 processing, respectively. In the canonical NF-κβ pathway, dimmers, such as p65/p50, are maintained in the cytoplasm by interacting with an IκBα protein. The binding of a ligand to a cell-surface receptor activates TRAF2, which triggers an IKK complex, containing -α, -β, -g, which phosphorylates IKK-β. It then phosphorylates IκB-α, leading to K48-ubiquitination and degradation of this protein. The p65/p50 protein freely enters the nucleus to turn on target genes. The non-canonical pathway is primarily involved in p100/RelB activation. It differs from the classical pathway in that only certain receptor signals activate this pathway. It proceeds through an IKK complex that contains two IKK-α subunits but not NEMO. Several materials including peptidoglycan, phorbol, myristate, acetate, and gram-positive bacteria such as probiotics inhibit NF-κB by inducing CYLD. This protein can block the canonical and noncanonical NF-κβ pathways by removing Lys-63 ubiquitinated chains from activated TRAFs, RIP, NEMO, and IKK (α, β, and γ). Moreover, TNF-α induces apoptosis by binding caspase-3 to FADD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Colon cancer is the most common type of gastrointestinal cancer. Genetic factors have been shown to have a role in the development of colorectal cancers. The aim of this study was to assess the expression of Cytochrome P2E1 (CYP2E1) gene polymorphism as a potential prognostic biomarker in the diagnosis, treatment, and prognosis evaluation of patients with colorectal cancer., Methods: in this cross-sectional study, all of our 100 patients with colorectal cancer who underwent surgical operation were included. DNA was extracted from the tumor specimens to assess Cytochrome P2E1 (CYP2E1) Gene polymorphism by Conventional-PCR. RFLP-PCR method was used for RsaI polymorphism evaluation. Patients' characteristics were also recorded and their associations with CYP2E1 were assessed., Results: One hundred tumor specimens were assessed. In total, 88 had wild-type, 8 had purely a 96 bp insertion in CYP2E1, and 4 were partially mutated by a single allele insertion. Generally, 10% of samples had positive results for the RsaI polymorphism. There were no statistically significant associations between CYP2E1 gene polymorphism and number of lymph nodes removed during the operation (P = 0.353), number of positive lymph nodes (P = 0.668), tumor specificity including mucinous or non-mucinous (P = 0.053), tumor invasion (P = 0.074), grading (P = 0.898), differentiation (P = 0.941), tumor location (P = 0.42) or staging (P = 0.182)., Conclusion: There was no association between RsaI type CYP2E1 polymorphism and colorectal cancer risk. Our study does not support the use of this biomarker to evaluate the prognosis of colon cancer.

Background: Household food insecurity (HFI) which has still been one of the major global public health issues is related to adverse health outcomes in individuals. Therefore, this study aimed to determine the prevalence of HFI and its associated factors in Iranian patients with esophageal and gastric cancers. Methods: The data of this cross-sectional study was obtained from 315 patients with esophageal and gastric cancers who were selected from a gastrointestinal cancer-based cohort study conducted in Firoozgar hospital, in Tehran. Food insecurity (FI) was measured using the Iranian version of the HFI questionnaire that was completed by a trained interviewer. The multivariable logistic regression model was used to determine the independent association of each factor with HFI. A P value lower than 0.05 was considered statistically significant. Results: The mean±SD of participants' age was 63.2±12.6 years and 65.4% were men. Most of the patients (75.8%) suffered from gastric cancer and 24.2% from esophageal cancer. The overall prevalence of FI among participants' households was 35.2%. There was an independent significant association between wealth index (WI) and HFI after the use of the multivariable logistic regression model, in such a way that the odds of FI in the poorest, poor, moderate, and rich patients' households were respectively, 6.41, 5.05, 2.74 and 2.04 times higher compared with the richest households. Conclusion: More than a third of participants' households struggled with FI, which was found to have a higher prevalence in loweconomic households. Therefore, health policymakers should intervene in food-insecure households by developing, establishing, and implementing strategies and control programs to improve affordable food access., Competing Interests: Competing Interests The authors declare no conflict of interest related to this work., (© 2023 Middle East Journal of Digestive Diseases.)

Background: Long-term safety and efficacy of BBIBP-CorV vaccine especially in individuals with chronic diseases, like cancer, is under investigation. In the present prospective study, we aimed to evaluate severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibody response with BBIBP-CorV vaccine in Iranian cancer patients., Methods: All the patients registered to receive BBIBP-CorV (Sinopharm) vaccine were divided into two groups of with (cases = 107) and without (controls = 45) history of cancer. Serum levels of SARS-CoV anti-spike recombinant receptor binding domain (anti-sRBD) and anti-nucleocapsid (anti-N) IgG serum levels were measured on days 0 (phase 0), 28-32 (phase I), and 56-64 (phase II) of vaccination. The data were analyzed using SPSS, version 22., Results: Totally, 152 individuals (67.1% females) with the mean age of 46.71 ± 15.36 years were included. Solid cancers included 87.8% of the cancer cases (46.7% gynecological and 31.8% gastrointestinal cancer). At Phases I and II, positive anti-sRBD IgG and anti-N IgG were significantly lower among the cases in total analysis. Side effects were not significantly different between the cases and controls. The lowest positive anti-sRBD IgG test was observed among the cancer patients who were simultaneously receiving chemotherapy (35.3%). Anti-sRBD IgG and anti-N IgG serum levels significantly increased at phases I and II in total analysis and in each group. In addition, serum anti-sRBD IgG increased during the three phases and it was significantly higher in the control group., Conclusion: Full vaccination of COVID-19 by BBIBP-CorV in immunocompromised patients such as cancer patients is safe and effective and could induce antibody response but in lower levels compared to healthy people. Probable causes to have minor antibody response found in males, older ages, individuals with BMI ≥ 25, those without past history of COVID-19 and with hematologic cancers. No significant side effects after vaccination were seen., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Safarnezhad Tameshkel, Abedin Dargoush, Amirkalali, Javadi, Ghiaseddin, Alimohamadi, Basi, Jamshidi Makiani, Zamani and Karbalaie Niya.)

Background: Treatment of Chronic Hepatitis C virus (HCV) infection in patients suffering from hereditary β-thalassemia major is a concern due to drug complications and liver malfunction. The aim of the present study was to evaluate treatment outcome of Direct-Acting Antiviral (DAA) therapy in thalassemia major patients infected with HCV in a three year follow-up., Methods: In a cohort study, long-term safety and efficacy of DAA therapy were evaluated in a group of thalassemia major patients suffering from chronic HCV infection. Hematologic and biochemical parameters as well as liver Fibroscan monitoring were assessed at the onset and three years after the treatment., Results: From among 84 patients enrolled in the study, 53.6% were males, 36.9% had cirrhosis, 96.4% had a history of Desferal usage, and 78.6% had a history of splenectomy. Unfortunately, 7 participants (8.3%) died prior to the end of follow-up with nearly half of them having Iron overload and heart failure complications. Fibroscan score, ALT, AST, and ferritin were significantly lower compared with baseline evaluation, while Hb, creatinine, and direct bilirubin increased significantly in the third year after the treatment., Conclusion: Safety and efficacy of Sofosbuvir and Daclatasvir in thalassemia patients assessed previously but our three year follow-up showed their mild complications and death into a long-term period after DAAs treatment and 91.7% three year survival rate, which may affected by other confounding factors, such as liver malfunction and Iron overload., (Copyright © 2022 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.)

Background: Globally, most people die from cardiovascular diseases. We aimed to compare predictive ability of six obesity indices, including body mass index, waist circumference, waist-to-hip ratio, waist-to-height ratio, conicity index, and abdominal volume index, to identify people at risk of fatal and non-fatal cardiovascular events, in a cohort study., Methods: We studied 5147 participants in a baseline population-based cohort study conducted in northern Iran. The obesity measures were calculated in enrollment phase (2009-2010), and the cardiovascular events were recorded during a 7-year follow-up phase (2010-2017). Receiver operating characteristic (ROC) analyses and Cox hazard regression models were applied, considering the obesity measures as predictors, and the 7-year cardiovascular events as outcomes. Multiple Cox models were adjusted by age, prior history of cardiovascular diseases, chronic kidney diseases, insulin resistance, diabetes mellitus, dyslipidemia, hypertension, and smoking status., Results: Conicity index showed the highest performance in predicting 7-year fatal and non-fatal cardiovascular events with areas under the ROC curve of 0.77 [95% confidence interval: 0.71-0.82], and 0.63 [0.59-0.68] in men, and 0.80 [0.74-0.87], and 0.65 [0.60-0.71] in women, respectively. In multiple Cox models, the obesity measures had no significant associations with cardiovascular events in women. In men, only waist-to-height ratio was independently associated with 7-year non-fatal cardiovascular events (hazard ratio: 1.19 [95% confidence interval: 1.01-1.38])., Conclusions: Although waist-to-height ratio had an independent association with 7-year non-fatal cardiovascular events in men, conicity index showed the best ability to predict 7-year fatal and non-fatal cardiovascular events in our study., Competing Interests: None., (© 2022 Published by Elsevier B.V.)

Background and Aims: Continuous scoring systems were developed versus traditional dichotomous approaches to define metabolic syndrome. The current study was carried out to evaluate the ability of scoring systems to predict fatal and nonfatal cardiovascular events., Materials and Methods: The data of 5147 individuals aged 18 years or more obtained from a population-based cohort study were analyzed. The occurrence of atherosclerotic cardiovascular disease (ASCVD) in the period of 7 years follow-up was considered as the associated outcome. Joint Interim Statement (JIS) definition, as a traditional definition of metabolic syndrome (MetS), and two versions of MetS scoring systems, based on standardized regression weights from structural equation modeling (SEM) and simple method for quantifying metabolic syndrome (siMS) were considered as potential predictors., Results: The scoring systems, particularly, based on SEM, were observed to have a significant association with composite cardiovascular events (HR = 1.388 [95% CI = 1.153-1.670], p = .001 in men and HR = 1.307 [0.95% CI = 1.120-1.526] in women) in multiple Cox proportional hazard regression analyses, whereas the traditional definition of MetS did not show any significant association. While both two scoring systems showed acceptable predictive abilities for cardiovascular events in women (MetS score based on SEM: area of under curve [AUC] = 0.7438 [95% CI = 0.6195-0.7903] and siMS: AUC = 0.7207 [95% CI = 0.6676-0.7738]), the two systems were not acceptable for identifying risk in men., Conclusion: Unlike the dichotomous definition of MetS, the scoring systems showed an independent association with cardiovascular events. Scoring systems, particularly those based on SEM, may be useful for the prediction of cardiovascular events in women., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: During community-wide outbreaks, patients and their families may suffer from anxiety after making behavioral changes. This study aimed to investigate the anxiety, knowledge, and lived experiences of families with COVID-19 patients admitted to medical centers., Methods: The present multi-center study was conducted by a mixed method using convenient sampling in hospitalized COVID-19 patients in Firoozgar and Rajaie Hospitals between May and July 2020. Anxiety was measured using a short form of the State-Trait Anxiety Inventory. The participants' level of knowledge was assessed by an online questionnaire. The lived experiences of the families were explained through semi-structured interviews. Data were analyzed by Chi square, ANOVA, independent-samples t test, Kruskal Wallis, and Mann-Whitney tests in SPSS 16. P values≤0.05 were considered statistically significant., Results: The mean age of the 324 family members, who participated in the study was 45.1±13.3 years. The mean anxiety score of the subjects was 13.5±4.1, and 63.6% of the participants had moderate to severe anxiety. The subjects' mean score for knowledge on COVID-19 was 7.15±1.32. The highest mean percentage of data received by the subjects on COVID-19 (42.7%) was obtained through radio and television broadcasting. A total of 251 important phrases were obtained from interview analysis and code extraction, out of which five main themes and 17 sub-themes were extracted., Conclusion: Our findings showed that anxiety was relatively high in families with COVID patients during the pandemic, and it was associated with age, sex, income, and familial relationships. The level of knowledge on the COVID-19 disease in families was moderate. Therefore, relevant interventions and raising people's awareness are recommended., (Copyright: © Iranian Journal of Medical Sciences.)

BACKGROUND : Hepatitis C virus (HCV) genotype distribution is different in various regions. A variety of strategies could be used to detect HCV genotypes and subtypes. The aim of the present study was to introduce a genotyping method by an in-house protocol that could be used to determine HCV drug-resistant variants and phylogeny studies. METHODS : Samples from 91 patients with thalassemia were used for HCV genotyping by Cobas 4800 platform, and 50 cases of 1a, 1b, and 3a genotypes underwent amplification and sequencing of NS5A and NS5B by using consensus primers via conventional reverse transcription-polymerase chain reaction (RT-PCR) method. An ABI 3730xl system used for direct sequencing. Raw sequences were analyzed by popular bioinformatics software MEGA6 and CLC workbench 5. Phylogenetic construction was drawn using 1000 replicates bootstrap by the neighbor-joining method. Multiple sequence alignment (MSA) was performed for mutation detection. RESULTS : Sequencing results of 50 HCV isolates subtypes 1a (31/45), 3a (15/22) and 1b (4/8) NS5A and NS5B genes showed there were 72 NS5A and 105 NS5B mutations. Moreover, 8 resistant associated substitutions (RASs) were identified in nine thalassemia cases by multiple sequence alignment (MSA) protein analysis. The phylogenetic tree construct drew confirmed by the Cobas HCV genotyping results. CONCLUSION : The phylogenetic analysis could be a useful tool for HCV genotyping in case of determining the drug-resistant substitutions; however, it is time-consuming and needs expert analysis and interpretation. This preliminary study in Iranian patients with thalassemia introduces specific conventional RT-PCR to find RASs to direct acting antivirals (DAAs) and subtype determination at the same time., Competing Interests: CONFLICT OF INTEREST All authors declare that they have no financial interests related to the material in the manuscript., (© 2022 Middle East Journal of Digestive Diseases.)

Background: Considering the affecting role of environmental factors including trace elements and heavy metals on the upper gastrointestinal (GI) cancers, there is paucity of empirical research in tissue evaluations., Objectives: The present study aimed to measure the tissue content of some trace elements and heavy metals such as zinc (Zn), chromium (Cr), manganese (Mn), tin (Sn), copper (Cu), aluminum (Al), lead (Pb), and iron (Fe) in esophagus and gastric cancerous tissues compared to the adjacent healthy tissues., Methods: In a cross-sectional study, the aforementioned trace elements and heavy metals were evaluated among patients with esophagus and gastric cancers. During endoscopy, multiple samples were taken from cancerous lesions and the adjacent healthy tissues. The classic flame atomic absorption spectroscopy (FAAS) method was employed as the study framework., Results: Fifty patients with the mean age of 53.92 ± 8.73 were enrolled in the current study. Thirteen patients suffered from esophageal cancer and thirty-seven patients were afflicted with gastric cancer. The results revealed significant differences in the median concentrations of Zn, Cr, Sn and, Cu (P < 0.05) between the two groups. Although there were no significant changes in the tissue content in the esophageal samples, in the median concentrations of Zn, Cr and, Sn (P < 0.05) in gastric tissues, significant differences were observed. Further, the results indicated that gender enacted an affecting role in the level of some trace elements and heavy metals., Conclusion: The tissue contents of some elements were altered in gastric and esophageal cancers; this difference may reflect the underlying mechanism of cellular changing during the tumorigenesis or direct exposure of these elements. It seems that under the shade of other coexisting risk factors, larger cohort studies are suggested to be conducted to investigate other probable aspects in this area of interest., (Copyright © 2021. Published by Elsevier GmbH.)

Background: The utilization of indexes for the diagnosis of non-alcoholic fatty liver disease (NAFLD) can be valuable. This study was conducted to determine the ability of the Framingham steatosis index (FSI) to distinguish between people with NAFLD and those without and to predict people at risk of NAFLD to establish the need for lifestyle modifications in such individuals., Methods: Our study was conducted in two phases from 2009-2010 (phase I) to 2016-2017 (phase II). A total of 4670 people in northern Iran were included. NAFLD was diagnosed by ultrasound. The FSI was calculated based on age, sex, hypertension, diabetes mellitus status, liver enzyme levels and triglyceride levels. Receiver operating characteristic (ROC) analysis was conducted to determine the discriminatory and predictive abilities of the FSI. To remove the confounding effects of potential mediators, logistic regression was performed in which NAFLD was considered the outcome and the FSI as the predictor., Results: The odds ratios of the FSI when the outcome was the prevalence of NAFLD in phase I and when the outcome was new cases of NAFLD from 2009-2010 to 2016-2017 were 4.909 (4.243-5.681) and 2.453 (2.024-2.972), respectively (P<0.001). The areas under the curve (AUCs) for the discriminatory and predictive abilities of the FSI were 0.8421 (95% CI: 0.8314-0.8527) and 0.7093 (95% CI: 0.6863-0.7322), respectively., Conclusion: The FSI has a strong ability to diagnose NAFLD while it has an acceptable ability to predict the occurrence of new cases of NAFLD., (Copyright © 2021. Published by Elsevier Masson SAS.)

Background: COVID-19 was introduced by the World Health Organization (WHO) as a global pandemic. The disease manifestations ranges from a mild common cold to severe disease and death. It has a higher mortality rate in people with a history of comorbidities, including cardiovascular disease (CVD) and can also contribute to cardiac injury. This study was conducted to evaluate the relationship between troponin levels as a cardiac marker and adverse outcomes in this disease., Methods: The study sample included 438 patients hospitalized with COVID-19; however, the troponin data of 6 patients were not available. The need to be admitted to the intensive care unit (ICU), and death were considered the adverse outcome in patients with COVID-19. Troponin levels were checked in all patients on day 1 and day 3 of hospitalization. Multiple logistic regression analysis was performed to determine whether there was an independent association between the adverse outcomes and troponin enzyme in hospitalized patients with COVID-19., Results: The mean age of patients was 61.29 ± 15.84 years. Among the 432 patients tested on day 1 of hospitalization, 24 patients (5.6%) tested positive (Troponin 1), and among the 303 patients tested on day 3, 13 patients (4.3%) tested positive (Troponin 2). Based on our results, Troponin 1 showed an independent association with both death (3.008 [95%CI = 1.091-8.290]; P = 0.033) and need for ICU admission (8.499 [95%CI = 3.316-21.788]; P < 0.001) in multiple logistic regression analysis. Moreover, the status of Troponin 2 had an independent significant association with both death (4.159 [95%CI = 1.156-14.961]; P = 0.029) and ICU admission (7.796 [95%CI = 1.954-31.097]; P = 0.004)., Conclusion: Troponin showed a significant association with adverse outcomes in people who were hospitalized with COVID-19. The periodical assessment of this enzyme from the time of hospitalization may improve the clinical decision making of clinicians., (© 2021 Isfahan Cardiovascular Research Center & Isfahan University of Medical Sciences.)

Since emerging coronaviruses have always become a human health concern globally especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV) and Middle East respiratory syndrome coronavirus and a novel coronavirus was introduced in Wuhan, China, in December 2019 (called SARS-CoV-2), many researchers focused on its epidemics, virological and clinical features. SARS-CoV-2 is classified as Betacoronaviruses genus and Sarbecovirus subgenus (lineage B). The virus shows a great similarity with SARS-CoV and bat SARS-like coronaviruses. In this study, we evaluate SARS-CoV-2 virus phylogeny and evolution by using current virus and related sequences., (© 2020 The Authors Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

BACKGROUND Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection showed the presence of resistant-associated substitutions (RASs). The aim of the present study was to carry out a follow-up of patients with baseline RASs to report the impact of RASs on DAA therapy outcome. METHODS In a cohort study, we analyzed NS5A and NS5B RASs among nine thalassemia cases by baseline RASs. In a 2-year follow-up, we analyzed viral markers and biochemical and hematological parameters of the participants and their sustained virologic response (SVR). Statistical analyses were performed using SPSS software version 22. RESULTS RASs for HCV subtype 1a included M28V, L31M, and H58P. For subtype 1b: L28M, R30Q, S24F, and C316N. And for subtype 3a: C316S, and S24F. In patients with cirrhosis (n = 5), ALT ( p = 0.001) and AST ( p = 0.007) levels were significantly reduced after treatment, and creatinine level slightly increased ( p = 0.025). However, no significant data was observed in non-cirrhotic patients following the treatment. CONCLUSION The present study did not show any adverse effects of DAA therapy among patients with thalassemia suffering from chronic HCV infection with baseline RASs. Furthermore, reduction in ferritin and liver stiffness levels after DAA therapy could show the efficacy of DAA in such patients., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest related to this work., (© 2021 The Author(s).)

Introduction: Diabetes mellitus and hypertension are described as the most common comorbidities among COVID-19 patients. We investigated the adverse effect of ACEIs in diabetic and nondiabetic patients with COVID-19., Methods: This prospective study consisted of 617 RT-PCR-confirmed COVID-19 inpatients. Demographic and baseline characteristics, underlying comorbid diseases, and antihypertensive drugs were evaluated. Study outcome (in-hospital death) was evaluated with the Kaplan-Meyer method and Cox regression model. Statistical analyses were performed with SPSS software for Windows. P values < .05 were considered significant., Results: Mean ± SD age was 58.49 ± 15.80 (range: 18 to 94) years old. Cox regression analysis revealed that age (adjusted hazard ratio [HR] = 1.04, 95% CI: 1.03 to 1.06), diabetes mellitus (adjusted HR = 2.07, 95% CI: 1.32 to 3.26), immunocompromised patients (adjusted HR = 2.33, 95% CI: 1.29 to 4.21), acute kidney injury (AKI) (adjusted HR = 3.23, 95% CI: 2.01 to 5.19), ICU admission (adjusted HR = 2.48, 95% CI: 1.46 to 4.21), Asthma and COPD (adjusted HR = 2.13, CI:1.6 to 4.28) and ACEI (adjusted HR = 3.08, 95% CI: 1.56 to 6.06), respectively were associated with in-hospital death. Among diabetic patients, ACEI (adjusted HR = 3.51, 95% CI: 1.59 to 7.75), AKI (adjusted HR = 3.32, 95% CI: 1.76 to 6.45) and ICU admission (adjusted HR = 3.64, 95% CI: 1.530 to 8.65) were associated with increased mortality. The Kaplan-Meier survival curve showed a lower survival rate in diabetic patients with ACE inhibitor (adjusted HR = 3.36, 95% CI: 2.25 to 7.71)., Conclusion: ACEIs may harm the diabetic patient's outcome with COVID-19. Further studies can confirm if ACE inhibitors have an adverse effect on COVID-19 diabetic patient's mortality.

Epstein-Barr virus (EBV) is known as one of the most widespread oncogenic viruses. Head and neck squamous cell carcinoma (HNSCC) is triggered by various risk factors. The aim of the present study was to determine the EBV infection rate, genotyping and variants frequency in HNSCC patients. In this cross-sectional study, 156 patients with HNSCC were enrolled. Formalin fixed paraffin embedded (FFPE) tissue samples were selected from hospitals affiliated to Iran University of Medical Sciences, Tehran, Iran. The EBV EBNA-3C, EBNA-1 and LMP-1 genes were amplified by PCR and then analyzed and confirmed by nucleotide sequencing. CLC work bench 5, MEGA6 and SPSS v.21 software were used for analysis the raw data. The mean age ± SD (years) of the all patients (n = 156) was 60.5 ± 12.6, in which of 121(77.6%) males it was 60.7 ± 11.9 and of 35 (22.4%) females it was 59.7 ± 14.9. Totally, 20 samples (12.8%) were found to be infected with EBV genome. The EBV genotypes 1 and 2 were calculated 90% (18/20) and 10% (2/20), respectively. vLMP-1 found in 40% (4/10) of all LMP-1 tested samples. Furthermore, the EBNA-1 predominant variants were P-ala followed by P-thr and also there were three P-ala-v2 sub variants. Statistics could not find any significant associations although there were some potentials. By our preliminary study in Iran, it revealed that EBV-1 is the predominant Epstein-Barr virus genotype in head and neck squamous cell carcinoma patients. vLMP-1 isolates showed lower survival rate than others. EBNA-1 variants had no significant association with any specific disease complication.

Background: The aim of the current study was to investigate and track the SARS-CoV-2 in Iranian Coronavirus Disease 2019 (COVID-19) patients using molecular and phylogenetic methods., Methods: We enrolled seven confirmed cases of COVID-19 patients for the phylogenetic assessment of the SARS-CoV-2 in Iran. The nsp-2, nsp-12, and S genes were amplified using one-step RT-PCR and sequenced using Sanger sequencing method. Popular bioinformatics software were used for sequences alignment and analysis as well as phylogenetic construction., Results: The mean age of the patients in the present study was 60.42 ± 9.94 years and 57.1% (4/7) were male. The results indicated high similarity between Iranian and Chinese strains. We could not find any particular polymorphisms in the assessed regions of the three genes. Phylogenetic trees by neighbor-joining and maximum likelihood method of nsp-2, nsp-12, and S genes showed that there are not any differences between Iranian isolates and those of other countries., Conclusion: As a preliminary phylogenetic study in Iranian SARS-CoV-2 isolates, we found that these isolates are closely related to the Chinese and reference sequences. Also, no sensible differences were observed between Iranian isolates and those of other countries. Further investigations are recommended using more comprehensive methods and larger sample sizes., Competing Interests: Declaration of Competing Interest There is no conflict of interests between authors in the present study., (Copyright © 2020. Published by Elsevier B.V.)

Patients with thalassemia major are at high risk of hepatitis C through blood transfusion from donors infected by hepatitis C virus (HCV). The use of direct-acting antiviral (DAA) therapy against such HCV infections has increased in different populations. However, resistant viral variants can affect treatment outcomes, and therefore improved surveillance strategies are needed. Accordingly, we aimed to evaluate resistance-associated substitutions (RASs) to HCV DAAs at the baseline of treatment in thalassemia patients in a referral center. Out of 89 thalassemia patients who suffered from HCV infection and were referred to our center between 2016 and 2017, 43 underwent further analysis of the HCV nonstructural proteins NS5A and NS5B using polymerase chain reaction (PCR) sequencing methods. Unique primers were designed using bioinformatics software for separate detection of HCV subtypes 1a, 3a, and 1b. Detection of RASs was performed based on previously published literature. Statistical analysis was carried out using SPSS version 19. The participants, 60.4% (26/43) of whom were male, had a mean age ± standard deviation (SD) of 33.0 ± 5.0 years. HCV subtype 1a was found in 27 cases, 3a in 13, and 1b in three. In HCV subtype 1a there were 163 mutations in NS5A and 212 mutations in NS5B. The frequency of RASs was 20.9% (8 RASs in 9 patients), including M28V and H58P in subtype 1a, L28M, R30Q, C316N, and C316S in subtype 1b, and S24F in subtype 3a. Statistically, the subtype 1b and a higher mutation rate in NS5A were associated with RASs (p-value < 0.05). The emergence of natural RASs to HCV DAAs serves as a warning of the risk of drug resistance in response to the broad usage of antivirals. However, relapses in these DAA-treated HCV-infected thalassemia patients are rarely reported. Our findings indicate that the prevalence of RASs prevalence at baseline was 20.9% in these patients, and this calls for extrapolation to a larger population study, as highlighted in other studies, with larger sample sizes, high-throughput methods, and follow-up in order to fully evaluate treatment outcomes in RASs-detected individuals. Optimized therapeutic strategies, particularly in complex, difficult-to-cure patients, can effectively prevent DAA treatment failure as a result of selection for RASs.

Since the 1970 the replication and pathogenesis mechanism of different coronaviruses have been studded.. In 2002-2003, SARS (Severe Acute Respiratory Syndrome coronavirus) in China emerged which resulted in 8098 cases and 774 deaths. About 10 years later in 2012, the MERS (Middle East Respiratory Syndrome coronavirus) spread in Middle Eastern countries and leads to infection in 2465 cases. In Dec 2019, another acute respiratory disease caused by a novel coronavirus named SARS-2 emerged in Wuhan, China. The virus is assumed to be mainly transmitted by respiratory droplets. Travels and communications leads to high prevalence of COVID-19 (Coronavirus Disease 2019) in the world, and currently in Iran. The current review was conducted to compare the virus structure, genome organization, virus life cycle, pathogenesis and prediction the future of COVID-19., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest., (Copyright © 2020 Taherizadeh et al. Published by Tehran University of Medical Sciences.)

Background: There are no consistent results between previous studies for an independent association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) events., Aim: To determine if there is an independent association between NAFLD and CVD events., Methods: In the present study, valid outcome data of 4808 subjects were available for phase 2 of our cohort study. These subjects had been followed up for seven years from phase 1, beginning in 2009-2010 to phase 2 during 2016-2017. Simple and multiple Cox proportional models were used to determine the association between NAFLD in the primary phase of the cohort and subsequent fatal and non-fatal CVD events during follow-up., Results: The incidence of non-fatal CVD events in males with NAFLD was significantly higher ( P = 0.004) than in males without NAFLD. A positive association was demonstrated between NAFLD and non-fatal CVD events in males (Hazard ratio = 1.606; 95%CI: 1.166-2.212; P = 0.004) by the simple Cox proportional hazard model, but no independent association was detected between these in the multiple Cox models., Conclusion: No independent association was detected between NAFLD and CVD. It is likely that diabetes mellitus and age may be the principle mediators in this regard., Competing Interests: Conflict-of-interest statement: There is not any potential conflict of interest that might constitute an embarrassment to any of the authors., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Hepatitis B virus (HBV), along with Hepatitis C virus chronic infection, represents a major risk factor for hepatocellular carcinoma (HCC) development. However, molecular mechanisms involved in the development of HCC are not yet completely understood. Recent studies have indicated that mutations in CTNNB1 gene encoding for β-catenin protein lead to aberrant activation of the Wnt/ β-catenin pathway. The mutations in turn activate several downstream genes, including c-Myc , promoting the neoplastic process. The present study evaluated the mutational profile of the CTNNB1 gene and expression levels of CTNNB1 and c-Myc genes in HBV-related HCC, as well as in cirrhotic and control tissues. Mutational analysis of the β-catenin gene and HBV genotyping were conducted by direct sequencing. Expression of β-catenin and c-Myc genes was assessed using real-time PCR. Among the HCC cases, 18.1% showed missense point mutation in exon 3 of CTNNB1 , more frequently in codons 32, 33, 38 and 45. The frequency of mutation in the hotspots of exon 3 was significantly higher in non-viral HCCs (29.4%) rather than HBV-related cases (12.7%, P  = 0.021). The expression of β-catenin and c-Myc genes was found upregulated in cirrhotic tissues in association with HBV infection. Mutations at both phosphorylation and neighboring sites were associated with increased activity of the Wnt pathway. The results demonstrated that mutated β-catenin caused activation of the Wnt pathway, but the rate of CTNNB1 gene mutations was not related to HBV infection. HBV factors may deregulate the Wnt pathway by causing epigenetic alterations in the HBV-related HCC., Competing Interests: Competing interestsAll the authors have stated to have no conflict of interest for declaration., (© The Author(s) 2020.)

Background: Some recent studies reported an inverse association between obesity and risk of cardiovascular diseases (CVD), heart failure related mortality rate, outcomes of myocardial infarction (MI), and the consequences of cardiovascular events interventions; this inverse association was named the obesity paradox. The present study was conducted with the aim to determine whether the obesity paradox will be detectable when the 10-year risk of CVD is estimated using CVD risk assessment tools., Methods: The related data of 2910 subjects aged 40-74 years obtained in our cohort study that was carried out among 6140 subjects in Amol, in northern Iran, was included in this study. CVD risk assessment tools were used to estimate the 10-year risk of CVD. Obesity was evaluated using 4 indices, including waist circumference (WC), waist to height ratio (WHtR), waist to hip ratio (WHR), and body mass index (BMI). The receiver operating characteristic (ROC) curve analysis was utilized to evaluate the discriminatory power of obesity indices for 10-year risk of CVD., Results: Categorizing the participants to with and without obesity according to BMI showed that a significantly higher proportion of men with obesity had a 10-year risk of CVD ≥ 7.5% and ≥ 10% according to American College of Cardiology/American Heart Association (ACC/AHA) and the Framingham approaches, respectively. A higher proportion of women without obesity had a 10-year risk of CVD ≥ 7.5% than women with obesity based on the ACC/AHA equation (28.54% vs. 24.15%; P = 0.0707). BMI had a non-significant AUC (< 0.5) according to the the ACC/AHA equation., Conclusion: BMI showed a weak and non-significant inverse association with 10-year risk of CVD estimated using pooled cohort equations of ACC/AHA in women. However, this result cannot directly provide enough evidence for the obesity paradox., (© 2020 Isfahan Cardiovascular Research Center & Isfahan University of Medical Sciences.)

Back ground and Aim: Heavy metals are considered as risk factors in the development of some types of cancers. In this context, the lead (Pb) along with its biological impacts on the human body has raised significant concerns in public health. The aim of this study was to compare the plasma levels of the lead element in patients with gastrointestinal (GI) cancer and healthy subjects to examine whether this element has a role in the susceptibility of cancer. Methods: In a case-control study conducted between March 2016 to February 2017, the plasma levels of the lead were assessed. One-hundred patients with upper and lower GI cancers, as well as one-hundered healthy subjects who were age- and sex-matched participated in our study. A classic flame atomic absorption spectroscopy (FAAS) method was employed for the determination of the lead element in plasma levels of all subjects. Results: The mean age of patients was 53.8±10.6 years old. The patient group consisted of 51 male and 49 female patients. The results showed that the concentrations of Pb were lower than the defined toxic levels. The comparison of the mean levels of Pb between the case and control groups revealed that there was no statistically significant difference even when the gender, age, and history of smoking were included in the statistical analysis. Our findings showed that the concentration of Pb is significantly associated with the type of cancer (p<0.003) and the location of the tumor (whether upper or lower tract was affected) (p<0.003). Conclusion: Lead may contributes to the pathology and progression of GI cancers but we can not conclude that it involved in the causation or susceptibility of healthy individuals to develop GI cancer.

Background and Objectives: Iran, as a developing country, is experiencing high burdens of Helicobacter pylori (Hp)-associated non-communicable diseases. Hp stool antigen test (HpSA) is widely used as an inexpensive and feasible noninvasive method to diagnose Hp infection, instead of invasive approaches. The current study aimed at evaluating the diagnostic and predictive values of HpSA test for Hp infection in Iranian patients with dyspepsia., Methods: The current cross sectional study was performed on 100 patients with dyspepsia. Gastric mucosal specimens were taken, processed, and examined according to the standard protocols. Simultaneously, stool samples were obtained and sent to laboratory for further analyses. Hp stool antigen titers were assessed using enzyme-linked immunosorbent assay (ELISA) technique., Results: Stool antigen titers were not associated with gender ( P -value=0.284), but correlated to age (r=0.213, P -value=0.034). Considering 0.385 as a cutoff point, the HpSA test had 80.4% sensitivity and 85.7% specificity., Conclusion: Based on cost-effectiveness of HpSA test, the current study findings corroborated the use of HpSA test to detect and follow-up patients with Hp infection, as an alternative method to detect Hp rather than invasive procedures.

Background: Colorectal cancer (CRC) as a worldwide human health concern is identified being a multifactorial subject that infection with specific viral particles such as oncogenic viruses is research interest. Human bocavirus (HBoV) as a recent isolated virus has been investigated in many respiratory and enteric diseases but rare studies evaluates it in tissue specimens especially in cancerous sections. The aim of this study was to detect the presence of HBoV genome and its genotyping in CRC patient’s tissue and compare the result with matched healthy control group tissue. Method: in this retrospective case-control study, CRC cases were sporadic and non-familial cancerous while control subjects had healthy or non-malignant lesions in colon tissue. A conventional-PCR performed by specific primers for HBoV VP1 gene. After sequencing of positive PCR products, raw data used for trimming and alignment by bioinformatics software CLC Main Workbench 5 and MEGA5. SPSS v.22 used for statistical calculations. Result: a total of 157 subjects were participated that 66 were diagnosed as CRC cases and 91 were non-CRC colon tissue as control group that matched by the cases. The mean age (y) ± standard deviation of each case and control groups were 59.35±14.48 and 57.21±14.66, respectively. PCR results showed there were 1.3% (2/157) HBoV positive (of each groups one was positive). Sequencing analysis showed all were HBoV-1 genotype. Conclusion: our study showed there are low rate of HBoV genome in Iranian CRC and non-CRC colon tissue. Furthermore, the predominant genotype in our studied subsets were HBoV-1 according to phylogenetic analysis., (Creative Commons Attribution License)

Human papillomavirus (HPV) is a common viral infection worldwide associated with a variety of cancers. The integration of the HPV genome in these patients causes chromosomal instability and triggers carcinogenesis. The aim of this study was to investigate the HPV-16 genome physical status in four major cancers related to HPV infection. Formalin-fixed paraffin-embedded blocks from our previous projects on head and neck, colorectal, penile, and cervical cancers were collected, and HPV-16-positive specimens were used for further analysis. The DNA extraction copy number of E2 and E7 genes was calculated by qualitative real-time PCR method. Serially diluted standards that were cloned in PUC57 plasmid were used. Standard curve and melting curve analysis was used for quantification. Of the 672 specimens studied, 76 (11.3%) were HPV-16 positive. We found that 35.6% (16/45) were integrated. Statistical analysis showed that there were significant correlations between integration of HPV-16 and cervical cancer end-stage carcinogenesis (P < .0001), episomal form, and ASCUS lesions (P = .045). Significant correlation in penile cancer patients was seen between the episomal form and high-grade cancer stage (P = .037). Integration is a major factor in the carcinogenesis mechanism of HPV and has different prevalence in various cancers with a higher rate in progression except in penile cancer., (Copyright © 2018. Published by Elsevier Inc.)

Context: Patients with thalassaemia are at risk of infections such as hepatitis C virus (HCV) due to their repeated blood transfusions; meanwhile, the treatment of thalassaemia patients who had developed HCV infection is a controversial issue., Aims: Although the effectiveness of direct-acting antivirals on HCV infection has been confirmed, their side-effects as well as effects on haematological factors due to the resultant need for blood transfusion remain to be further understood., Materials and Methods: In this study, 61 patients with major beta thalassaemia and HCV infection, and who had a history of interferon treatment failure were examined. The patients underwent a 24-week treatment with sofosbuvir (SOF) and daclatasvir (DAC). Sustained virological response 12 was used to assess response to treatment. At the end of the study, the need for blood transfusion and serum ferritin was evaluated., Results: About 98.4% of the patients responded to the treatment, and only one patient with genotype 1b did not respond positively. No significant complications necessitating treatment cessation were observed, and all the patients tolerated the treatment well. The level of liver enzymes showed a significant reduction 12 weeks after the treatment. The need for blood transfusions in patients before treatment was averagely 1.595 ± 0.65 bag per month, in which 1.593 ± 0.64 bags were received after treatment (P = 0.9). This regimen did not affect the amount of anaemia in patients and did not differentiate the need for blood transfusions. The rate of haemoglobin before treatment was 9.5 ± 1.42 g/dl, which reached 9.6 ± 1.6 g/dl after treatment (P = 0.54). Ferritin levels decreased significantly (from 1948.08 ± 1539.54 to 1315.73 ± 1207.67 ng/ml) (P = 0.001) in the patients after the treatment., Conclusion: Combination of SOF and DAC is an effective and tolerable treatment regimen without affect on the amount of anaemia in patients and did not differentiate the need for blood transfusions., Competing Interests: There are no conflicts of interest

Background: Head and neck squamous cell carcinomas (HNSCC) are a major health issue in many parts of the world. Recently, attention has focused on the human papilloma virus (HPV) as a potential causative agent for HNSCC. This study aimed to survey HPV occurrence in HNSCCs as part of a comprehensive molecular epidemiology approach. Methods: In this retrospective study, patients were recruited from hospitals affiliated to the Iran University of Medical Sciences, Tehran, Iran. Formalin-fixed paraffin-embedded (FFPE) blocks were subjected to DNA isolation by QIAamp® DNA FFPE Tissue Kit and nested PCR, HPV-16 specific conventional PCR, and extra INNO-LiPA HPV genotyping assays were subsequently performed. PCR products were purified with a High Pure PCR Product Purification Kit and sequenced with an ABI 3730 XL sequencer. CLC Main Workbench 5 and MEGA5 bioinformatics software was used to analyze the raw data and to create the phylogenetic tree. SPSS v.20 was applied for statistical analysis. Results: A total of 156 FFPE blocks were collected from 2011 to 2017. Total mean age (y) of participants was 60.5 ± 12.6; 77.6 % (121/156) being men and 22.4% (35/156) e women. Overall, 5/156 (3.2%) patients (3 females and 2 males) were found to be HPV positive using the three methods. HPV genotyping revealed HPV types 16, 2, 27, and 43 in these malignancies. Tumor location and lymph node involvement indicated significant differences between the sexes. Conclusion: Although high risk HPV genotypes have been associated with HNSCCs, our findings indicate a potential of low risk HPV types to also contribute to such malignancies., (Creative Commons Attribution License)

Background & Objective: Nonalcoholic fatty liver diseases (NAFLD) is the major cause of hepatocellular carcinoma and increases the risk of mortality. Understanding the trends of its clinical and biochemical changes is essential to identify patients with NAFLD that are at the greatest risk of nonalcoholic steatohepatitis (NASH) and cirrhosis in Iran., Methods: Patients with NAFLD confirmed by ultrasonography were enrolled into the current study. They had negative serologic markers of viral or autoimmune hepatitis, no findings in favor of metabolic liver disease, and had not received medications that affect liver, such as silymarin and Ursobil. Biochemical and clinical symptoms and histological variables were evaluated for each patient. Descriptive statistics were used to compute all variables., Results: A total of 206 patients, including 109 male and 97 female, with the mean age of 41.2 years were enrolled. The number of patients without obesity and diabetes were 34 (16.4%) and 48 (23.1%), respectively. Sleep disorder, delayed sleep, daytime sleepiness, and late dinner were noticeably common in patients with NAFLD. Furthermore, anxiety, thirst sensation, bloating, warming sensation, defecation disturbances, and upper abdominal pain were common among patients with NAFLD., Conclusion: NAFLD is a heterogeneous disorder with vast clinical presentations. It seems that anxiety and gastrointestinal problem are common among such patients. Moreover, inadvertent sleep could have a considerable effect on developing NAFLD. Patients with diabetes have more severe NAFLD, based on clinical and histological findings., Competing Interests: The authors declared no conflict of interest exists.

Background: Varicella zoster virus (VZV) causes chickenpox in children and zoster (zona) in the elderly. Using RFLP-PCR method for detection of VZV specific SNPs ORF38, 54 and 62 could distinguish the profile of VZV isolates. The aim of this study was to investigate enzymatic digestion pattern of VZV ORF38 and ORF54 in chickenpox patients using RFLP technique., Methods: Thirty-eight chickenpox patients, who referred to the hospitals of Iran University of Medical Sciences in Tehran from May 2010 to June 2015 were enrolled in this cross sectional study. After the DNA extraction, PCR amplification of 38 VZV isolates performed by specific primers of ORFs 38 and 54, then RFLP assay and digestion carried out by PstI (for ORF38) and BglI (for ORF54) restriction enzymes., Results: Of 38 positive VZV DNA, the mean age (yr)±SD was 34.4±23.3 (range: 7-89). 22 (57.9%) were female and 16 (42.1%) were male. The predominant VZV profile of BglI(+) PstI(+) were 89.5% (34/38) followed by 10.5% (4/38) PstI(+) BglI‾. Statistical analysis showed that there was no significant relationship between genotype, age, sex, and year of infection variables (P value> 0.05). The common VZV genotype among Iranian patients with chickenpox and zona infection is genotype BglI(+) PstI(+) followed by PstI(+) BglI‾., Conclusion: There are different VZV circulating genotypes that call for for more research on this field by widely population and other methods such as nucleotide sequencing to justify the accurate VZV genotype prevalence in Iran.

Background: Investigations of methods for detection of mutations have uncovered major weaknesses of direct sequencing and pyrosequencing, with their high costs and low sensitivity in screening for both known and unknown mutations. High resolution melting (HRM) analysis is an alternative tool for the rapid detection of mutations. Here we describe the accuracy of HRM in screening for KRAS and BRAF mutations in metastatic colorectal cancer (mCRCs) samples. Materials and Methods: A total of 1000 mCRC patients in Mehr Hospital, Tehran, Iran, from Feb 2008 to May 2012 were examined for KRAS mutations and 242 of them were selected for further assessment of BRAF mutations by HRM analysis. In order to calculate the sensitivity and specificity, HRM results were checked by pyrosequencing as the golden standard and Dxs Therascreen as a further method. Results: In the total of 1,000 participants, there were 664 (66.4%) with wild type and 336 (33.6%) with mutant codons 12 and/or 13 of the KRAS gene. Among 242 samples randomly checked for the BRAF gene, all were wild type by HRM. Pyrosequencing and Dxs Therascreen results were in line with those of the HRM. In this regard, the sensitivity and specificity of HRM were evaluated as 100%. Conclusion: The findings suggest that the HRM, in comparison with DNA sequencing, is a more appropriate method for precise scanning of KRAS and BRAF mutations. It is also possible to state that HRM may be an attractive technique for the detection of known or unknown somatic mutations in other genes., (Creative Commons Attribution License)

Background: Hirschsprung disease is a complex genetic disorder of the enteric nervous system (ENS), often called congenital aganglionic megacolon and characterized by the absence of enteric neurons along a variable length of the intestine. The definitive diagnosis of Hirschsprung disease relies on histologic and/or histochemical staining of sections from suction rectal biopsies. Calretinin immunohistochemistry (IHC) may be a useful in its diagnosis. This study aimed to proof the usefulness of immunohistochemical staining for calretinin in rule out of Hirschsprung disease., Methods: Paraffin blocks and slides were retrieved from the pathology archives of Ali Asghar Hospital, Tehran, Iran from 2007 to 2011 with pathology report based on the presence (14 patients) or absence (70 patients) of ganglion cells and transitional zone anatomical region (10 patients). Slides were stained with hematoxylin and eosin method to confirm the initial diagnosis was verification again. After preparing the slides, they were stained by IHC for calretinin. Then, the results were analyzed using SPSS software., Results: In most patients, IHC for calretinin provided highly compatible results with hematoxylin-eosin findings in diagnosis of Hirschsprung disease. The values of specificity and accuracy between calretinin and standard histology (H&E) compared by the Fisher exact test declared calretinin presented significantly higher specificity and accuracy values than H&E staining ( P <0.0001)., Conclusion: Calretinin IHC overcomes most of the difficulties encountered using the histology hematoxylin-eosin. Then, IHC for calretinin is a good ancillary method used by pathologists in diagnosis of Hirschsprung disease., Competing Interests: The authors declare that there is no Conflict of Interests.

Background: Nowadays, the immune response to hepatitis C (HCV) treatment has become a crucial issue mostly due to the interleukin 28B (IL-28B) polymorphism effects in chronic HCV patients. The aim of this study was to detect the polymorphism of IL-28B gene (rs12979860) in HCV genotype 1 patients treated with pegylated Interferon and Ribavirin., Methods: From the 2010 to 2012, a total of 115 peripheral blood mononuclear cells (PBMCs) of HCV patients who presented to Gastrointestinal & Liver Disease Research Center (GILDRC), Firoozgar Hospital, Tehran, Iran were enrolled in this retrospective cross sectional study. Samples were then categorized based on the presence of sustained virologic response (SVR and no-SVR). Variables including age, gender, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of the two groups were investigated based on different IL-28B genotypes., Results: Analysis by the variables of age and gender showed a mean age ± SD of 42.1±14.0 and gender variability of 44 females (38.2%) and 71 males (61.8%). Adding up these results, the analysis of ALT levels revealed that there was between 293 and 14 mg/ml; AST levels ranged between 217 and 17 mg/ml; the viral load (HCV RNA) ranged between 7,822,000 and 50 IU/ml; the prevalence of CC, CT and TT genotypes were 90.9%, 54% and 25.0%., Conclusion: IL-28B polymorphism has an effective impact on the therapeutic response to ribavirin and peginterferon combination therapy in chronic HCV patients infected by different genotypes. This polymorphism is crucial in natural clearance.

Background and Objectives: Hepatitis C virus (HCV) chronically infects around 200 million people worldwide and frequently causes liver cirrhosis and hepatocellular carcinoma. Rapid detection of this virus results in decreasing the distance between infection and initiation the anti-viral treatment, and may prevent most of the undesirable consequences. The new detected HCV protein "Core+1" made from the ribosomal frame shift in Core region is an important candidate for diagnostic tools. This study was conducted to design a recombinant Bacmid plasmid expressing the HCV 1a Core+1 sequence in the Baculovirus expression system for further diagnostic applications., Materials and Methods: The HCV Core +1 gene was amplified by PCR using the pcDNA-HAF recombinant vector that contained the Core+1 sequence from HCV genotype 1a as a template, and the specific primers with 2 restriction sites for Nco I and Xba I restriction enzymes. The PCR product was cloned in XbaI/NcoI restriction sites of the linearized pFastBac-HTB vector and evaluated by using those restriction enzymes and sequencing. Then the recombinant pFastBac-HTB vector was transformed in DH10Bac and the result was screened and confirmed by X-Gal discrimination and PCR., Results: The HCV 1a Core+1 was successfully amplified and the PCR product was confirmed by using the related restriction enzymes and sequencing. Cloning of pFastBac vector with the purified PCR product of HCV Core+1 was confirmed. Finally, the recombinant Bacmid was successfully transformed in DH10Bac., Conclusion: The recombinant Bac-Core+1 expression vector is considered as an important tool to transfect the sf9 cell line and expression the Core+1 protein.