Publications by authors named "Talat Mokhtari Azad"

100 Publications

SARS-CoV-2 outbreak in Iran; the dynamics of the epidemic and evidence on two independent introductions.

Transbound Emerg Dis 2021 Apr 9. Epub 2021 Apr 9.

Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.

The SARS-CoV-2 virus has been rapidly spreading globally since December 2019, triggering a pandemic, soon after its emergence. While Iran was among the first countries confronted with rapid spread of virus in February 2020, no real-time SARS-CoV-2 whole-genome tracking in early phase of outbreak was performed in the country. To address this issue, we provided 50 whole-genome sequences of viral isolates ascertained from different geographical locations in Iran during March-July 2020. The corresponding analysis on origins, transmission dynamics and genetic diversity of SARS-CoV-2 virus, represented at least two introductions of the virus into the country, constructing two major clusters defined as B.4 and B.1*. The first entry of the virus might have occurred around 29 December 2019, as suggested by the time to the most recent common ancestor, followed by a rapid community transmission that led to dominancy of B.4 lineage in early epidemic till the end of June. Gradually, reduction in dominancy of B.4 occurred possibly as a result of other entries of the virus, followed by surge of B.1* lineages, as of mid-May. Remarkably, variation tracking of the virus indicated the increase in frequency of D614G mutation, along with B.1* lineages, which showed continuity till October 2020. The increase in frequency of D614G mutation and B.1* lineages from mid-May onward predicts a rapid viral transmission that may push the country into a critical health situation followed by a considerable change in composition of viral lineages circulating in the country.
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http://dx.doi.org/10.1111/tbed.14104DOI Listing
April 2021

Comparison of Snail1, ZEB1, E-Cadherin Expression Levels in HPV-Induced Cervical Cancer.

Iran J Public Health 2020 Nov;49(11):2179-2188

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: Molecular profiling techniques are the rapid detection of biomarkers in the human papillomavirus (HPV) infected cells. We aimed to measure the expression level of three cell factors including Snail1, ZEB-1, and E-cadherin in cervical cancer (CC), precancerous and healthy samples, simultaneously, to find potential biomarkers.

Methods: The expression level of the mentioned cell factors were investigated in 72 CC patients, precancerous patients, and healthy controls by using Real-Time PCR.

Results: The results demonstrated a significant reduction in the expression level of E-cadherin in cancer and precancerous cases than that in healthy cases; whereas the expression level of ZEB-1 and Snail1 were upregulated in cancer and precancerous samples. The receiver operating characteristic (ROC) analyses shows the highest AUC value emerged for Snail1: 1(95% CI: 1-1) in comparing CC and healthy groups with a sensitivity of 100.0 % and specificity of 100.0%.

Conclusion: The molecular biomarker Snail1 may be helpful to early diagnosis and prognosis of CC in the HPV-infected human populations. Considering the increased expression level of Snail1 in cancer and precancerous tissue compared to healthy tissue as well as the area under the ROC curve, Snail1 can be used for early detection of CC.
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http://dx.doi.org/10.18502/ijph.v49i11.4736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917501PMC
November 2020

The presence of SARS-CoV-2 in raw and treated wastewater in 3 cities of Iran: Tehran, Qom and Anzali during coronavirus disease 2019 (COVID-19) outbreak.

J Environ Health Sci Eng 2021 Feb 24:1-12. Epub 2021 Feb 24.

Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

This study aimed to identifying the presence of SARS-CoV-2 RNA in raw and treated wastewater during the COVID-19 outbreak in Tehran, Qom and Anzali cities (Iran). From three wastewater treatment plants (WWTPs), 28 treated and untreated wastewater composite samples were collected from April 4 to May 2, 2020. In this study, polyethylene glycol 6000 (PEG 6000) was used through one-step real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) for identification of RNA viruses. SARS-CoV-2 RNA was elicited from wastewater composite samples in all inlet samples taken from the three above mentioned cities. The results of outlet samples were as follows: 1) Results from Qom and East Anzali outlets showed no trace of SARS-CoV-2 RNA despite the difference in treatment disinfection method used (chlorine vs. ultraviolet (UV) disinfection). 2. In Tehran, SARS-CoV-2 RNA was not detected in any of the outlet samples taken from the modules disinfected by UV. Out of the four samples taken from the modules disinfected by chlorine, two were positive for the SARS-CoV-2 RNA which could have been caused by deficiencies in operation and maintenance. It can be concluded that meeting the standards of operation and maintenance (O&M) in WWTPs can considerably ensure that wastewater does not act as one of the roots of transmission for the disease.
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http://dx.doi.org/10.1007/s40201-021-00629-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903026PMC
February 2021

The dysregulation of microarray gene expression in cervical cancer is associated with overexpression of a unique messenger RNA signature.

Iran J Microbiol 2020 Dec;12(6):629-635

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background And Objectives: Human papillomavirus (HPV) is the fourth most common cause of cervical cancer (CC). The aim of the present study was to investigate gene expression levels of previously identified transcriptional signatures for malignant and non-malignant CC.

Materials And Methods: To validate of previously analyzed microarray gene expression data, we selected two hub genes (CDK1 and PLK1) and four differentially expressed mRNAs that were common in pre-malignant-normal and malignant-pre-malignant networks (SMS, NNT, UHMK1 and DEPDC1). To this purpose, the study included women diagnosed histologically with malignant CC (n=15), pre-malignant (n=15), and normal subjects (n=15). The expression of six host genes and viral E6/E7 genes were measured by quantitative Real-Time PCR.

Results: The results showed higher expression of CDK1/PLK1 hub genes and SMS, NNT and UHMK1 genes in malignant CC group than non-malignant CC group and normal group. A positive correlation was observed between gene expression of viral E6/E7 oncogenes and UHMK1 gene.

Conclusion: Dysregulation of several mRNA signatures are a common feature of CC and can be potentially used as diagnostic and prognostic biomarkers as well as can be applied to therapeutic targets for CC treatment.
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http://dx.doi.org/10.18502/ijm.v12i6.5039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884268PMC
December 2020

Prevalence and Type Distribution of Human Papillomavirus Recovered from the Uterine Cervix of Nigerian Women: A Systematic Review and Meta-Analysis

Asian Pac J Cancer Prev 2020 10 1;21(10):2837-2846. Epub 2020 Oct 1.

Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, UAE.

Background: Infection with an oncogenic type of human papillomavirus is a prerequisite for the development of precancerous cervical lesions and its subsequent progression to cervical cancer. With an alarming increase in the detection of other suspicious papillomavirus genotypes in both healthy and women with cervical lesions, there is a need for comprehensive data on cervical papillomavirus infection to address cervical cancer and other associated disease burden, especially in Sub-Sarahan Africa, where the bulk of the problem exists. The present study was conducted to develop comprehensive data on the prevalence and circulating genotypes of human papillomavirus in various risk categories in Nigeria. Methods: A systematic review and meta-analysis of peer-reviewed publications on cervical papillomavirus infection were performed. Relevant data were extracted from eligible studies published in PubMed, Web of Science, Embase, Scopus, and Google Scholar, from inception to July 31, 2019. The random-effect model was used to estimate the pooled prevalence. We identified 327 potential studies and pooled data from 18 studies, involving 5697 women aged 15-86 years. Results: The overall pooled prevalence of cervical papillomavirus infection was 42% (95%CI: 30-54%) in the general population and 37% (95%CI: 25-50%) among women living with HIV/AIDS, with the predominance of genotypes 16, 18, 31, 35, 52, 58 and 45. The highest prevalence was observed in teenagers and young adults and the second peak in women 50 years and above. Conclusion: The prevalence of cervical human papillomavirus infection is cumulatively high in Nigeria and HIV is a strong co-factor. We, therefore, strongly recommend the co-screening of human papillomavirus and cervical cancer and integration of the intervention strategy into the existing HIV-care guideline in Nigeria.
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http://dx.doi.org/10.31557/APJCP.2020.21.10.2837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798145PMC
October 2020

First Cases of SARS-CoV-2 in Iran, 2020: Case Series Report.

Iran J Public Health 2020 Aug;49(8):1564-1568

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

In Jan 2020, the outbreak of the 2019 novel coronavirus (SARS-CoV-2) in Wuhan, Hubei Province of China spread increasingly to other countries worldwide which WHO declared it as a public health emergency of international concern. Iran was included in the affected countries. Throat swab specimens were collected and tested by using real-time reverse transcription PCR (RT-PCR) kit targeting the E region for screening and RNA dependent RNA polymerase for confirmation. Conventional RT-PCR was conducted for the N region and the PCR products were sequenced by Sanger sequencing. The first seven cases of SARS-CoV-2 infections were identified in Qom, Iran. This report describes the clinical and epidemiological features of the first cases of SARS-CoV-2 confirmed in Iran. Future research should focus on finding the routes of transmission for this virus, including the possibility of transmission from foreign tourists to identify the possible origin of SARS-CoV-2 outbreak in Iran.
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http://dx.doi.org/10.18502/ijph.v49i8.3903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554384PMC
August 2020

Frequent detection of enterovirus D68 and rhinovirus type C in children with acute respiratory infections.

Eur J Clin Microbiol Infect Dis 2021 Mar 3;40(3):637-642. Epub 2020 Oct 3.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, 1471613151, Iran.

This study aimed to evaluate the prevalence of human rhinoviruses (HRVs) and the emergence of enterovirus D68 (EV-D68) in children. A total of 322 nasopharyngeal swab samples were provided from children with an initial diagnosis of upper and lower respiratory tract infections. A total of 34 and 70 cases were positive for EV-D68 and HRV, respectively. The phylogenetic analysis revealed that the clades A and B are the prevalent genotypes for EV-D68 and the HRV-positive samples belong to three types including HRV-A, HRV-B, and HRV-C. The results showed that EV-D68 and HRV-C are circulating in Iran especially in the winter.
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http://dx.doi.org/10.1007/s10096-020-04051-yDOI Listing
March 2021

Measles Outbreak in a Rural Population in Bahar District, Hamadan Province, West of Iran in 2018.

J Res Health Sci 2020 Feb 27;20(1):e00470. Epub 2020 Feb 27.

Department of Pediatrics, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Background: Measles is in elimination phase in Iran. Following occurrence of two cases of measles in two children under six years old with the history of measles immunization in one of the villages affiliated to Bahar District, west of Hamadan Province, northwest of Iran, this study was conducted to determine the immunity status of people living in the village affected by the measles outbreak in spring of 2018.

Study Design: A cross-sectional (descriptive-analytical) study.

Methods: Overall, 272 populations of 0-40 yr old in the village affected by outbreak were enrolled. Multistage sampling was used for choosing participants. The data collection tool was a researcher-made checklist used to collect epidemiological data including demographic characteristics and vaccination status. Blood samples were taken from them and sent to the measles reference laboratory for IgG testing. The amount of optical density (OD) greater than 0.2 was considered as positive and less than 0.1 negative, respectively.

Results: The mean age of the study population was 17.4 ±11.8 yr and the sex ratio was almost the same. Levels of antibodies against measles were positive in 63.24%, intermediate in 12.5% ​​and negative in 24.26%. There was no significant difference between the immunity status of the subjects with gender (P=0.236) and age group (P=0.113). Pearson correlation results showed that in males there was a significant positive correlation between the age of the participants and the serum IgG level (r = 0.26, P=0.003).

Conclusion: Measles immunity in communities is not sufficient to prevent outbreaks and small epidemics, and it is recommended that periodically, serological assessments carried out at community level and especially at high-risk groups.
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http://dx.doi.org/10.34172/jrhs.2020.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585754PMC
February 2020

Survey of WU and KI polyomaviruses, coronaviruses, respiratory syncytial virus and parechovirus in children under 5 years of age in Tehran, Iran.

Iran J Microbiol 2020 Apr;12(2):164-169

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background And Objectives: Severe acute respiratory infections (SARI) remain an important cause for childhood morbidity worldwide. We designed a research with the objective of finding the frequency of respiratory viruses, particularly WU and KI polyomaviruses (WUPyV & KIPyV), human coronaviruses (HCoVs), human respiratory syncytial virus (HRSV) and human parechovirus (HPeV) in hospitalized children who were influenza negative.

Materials And Methods: Throat swabs were collected from children younger than 5 years who have been hospitalized for SARI and screened for WUPyV, KIPyV, HCoVs, HRSV and HPeV using Real time PCR.

Results: A viral pathogen was identified in 23 (11.16%) of 206 hospitalized children with SARI. The rate of virus detection was considerably greater in infants <12 months (78.2%) than in older children (21.8%). The most frequently detected viruses were HCoVs with 7.76% of positive cases followed by KIPyV (2%) and WUPyV (1.5%). No HPeV and HRSV were detected in this study.

Conclusion: This research shown respiratory viruses as causes of childhood acute respiratory infections, while as most of mentioned viruses usually causes mild respiratory diseases, their frequency might be higher in outpatient children. Meanwhile as HRSV is really sensitive to inactivation due to environmental situations and its genome maybe degraded, then for future studies, we need to use fresh samples for HRSV detection. These findings addressed a need for more studies on viral respiratory tract infections to help public health.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244825PMC
April 2020

P16INK4A Immunohistochemistry as a Gold Standard for Cervical Cancer and Precursor Lesions Screening.

Iran J Public Health 2020 Feb;49(2):312-322

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: High-risk (HR) Human papillomaviruses (HPVs) are known as the main factors implicated in the pathogenesis of cervical preinvasive and invasive lesions. Therefore, the presence or absence of HR-HPV can be followed for the prognosis of low-grade and high-grade squamous intraepithelial lesions. Since the overexpression of p16INK4a protein depends on the presence of transcriptionally-active HPV, and due to its availability and simple interpretation, it may be considered as a proper marker to diagnose cervical cancer.

Methods: An immunohistochemical analysis of p16INK4a was performed in 72 cervical tissue specimens at Imam Khomeini Complex Hospital (Tehran, Iran) from 2016 to 2018. The performance parameters were calculated and compared using receiving operating characteristics curve (ROC) details.

Results: p16INK4a is significantly up-regulated in the cervical cancer samples in comparison with that in normal samples. Moreover, the ROC data showed the potential ability of p16INK4a under determined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. The molecular typing disclosed the attendance of HPV DNA in 44.4% of cases (32/72) with a predominance of HPV type 16.

Conclusion: The molecular biomarker p16INK4a can be a good candidate for the early diagnosis and prognosis of cervical cancer in HPV-infected patients. Considering the increase in the expression level of p16INK4a in cancer and precancer tissues, p16INK4a may be used for early detection of cervical cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231710PMC
February 2020

Potential of H1N1 influenza A virus as an air borne pathogen to induce infectivity in pancreas: a mouse model study.

J Environ Health Sci Eng 2020 Jun 17;18(1):303-310. Epub 2020 Mar 17.

1Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: H1N1 influenza virus, as an indoor/outdoor pathogen in air, can cause the flu-like illness and respiratory complication. The aim of this study was to evaluate the H1N1 influenza virus replication in pancreas and investigate the immune response against infected pancreas.

Material And Methods: First, mouse pancreas cell line was infected by H1N1 influenza A virus using intranasally and intravenously infection methods, and then the pancreas tissue was collected and pathology experiment was carried out. Next, the protein and genome of influenza virus were detected using immunocytochemistry and real-time PCR, respectively. In addition, serum cytokines and serum lipase were investigated using ELISA.

Result: The in-vitro results proved that the mouse pancreatic cell line can support influenza virus replication. The result also proved that influenza virus is capable to infect pancreas and induce pancreas damage. Further, the immune response in mice with infected pancreas exhibited a completely different pattern with that of mice infected through intranasal method.

Conclusion: It can be concluded that influenza virus can infect pancreas and change the influenza disease pathway, which might result in a pancreatic injury.
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http://dx.doi.org/10.1007/s40201-020-00468-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203352PMC
June 2020

Seroepidemiology of dengue and chikungunya fever in patients with rash and fever in Iran, 2017.

Epidemiol Infect 2020 02 26;148:e42. Epub 2020 Feb 26.

Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

After the mass campaign of Measles and Rubella vaccination in 2003 in Iran, the cases of measles and rubella infection decreased but still, the cases of rash and fever were reported. It is worth noting that some other viral infections show signs similar to measles and rubella such as some arboviruses. Considering the epidemic outbreak of arbovirus infections in countries neighbouring Iran, we performed this study to estimate the possibility of chikungunya and dengue fever among measles and rubella IgM negative patients presenting with rash and fever from December 2016 to November 2017 in the National Measles Laboratory at Tehran University of Medical Sciences. Serum samples were selected at random from patients from eight provinces. The presence of DENV IgM and CHIKV IgM was examined by enzyme-linked immunosorbent assay. Of the 1306 sera tested, 210 were CHIKV seropositive and 82 were dengue seropositive. Statistical analysis demonstrated a significant increase in the CHIKV IgM antibody seropositivity rate in Kerman (OR = 2.07, 95% CI: 1.10-3.92; P = 0.024) and Fars (OR = 1.77, 95% CI: 1.06-2.93; P = 0.027). The DENV and CHIKV seropositivity rate in summer is higher than in other seasons (P < 0.01). Our seropositive samples suggest possible CHIKV and DENV infection in Iran. It is likely that these viruses are circulating in Iran and there is a need to study vector carriage of these two viruses.
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http://dx.doi.org/10.1017/S0950268820000114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058646PMC
February 2020

Prevalence of Human Metapneumovirus Infections in Iran: A Systematic Review and Meta-Analysis.

Fetal Pediatr Pathol 2020 Feb 21:1-11. Epub 2020 Feb 21.

Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

We sought to systematically review the literature and perform a meta-analysis by assessing the prevalence of human metapneumovirus (hMPV) infections from a number of studies conducted in Iran. Entire studies addressing epidemiology of hMPV in Iran using data from PubMed, Scopus, Science Direct, Web of science, Google Scholar, Embase, and national Persian databases up to June 2019 were included. The estimated prevalence of hMPV was 8.9% (95% CI 5.4-14.2) in different regions in Iran. Compared to the global rate, in Iran hMPV infection presented an intermediate prevalence rate. The majority of hMPV positive patients were pediatric populations with pooled prevalence of 7.6% ( = 95%, 95% CI 3.5-15.6). This first comprehensive review covering researches over the last 11 years expanded our knowledge about hMPV circulating in Iran. Future large epidemiological studies are needed for the evaluation of hMPV prevalence and genotype distribution in different unanalyzed regions in Iran.
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http://dx.doi.org/10.1080/15513815.2020.1725939DOI Listing
February 2020

An insight to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis; evidence from high-throughput data integration and meta-analysis.

Retrovirology 2019 12 30;16(1):46. Epub 2019 Dec 30.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: Human T-lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the central nervous system that significantly affected spinal cord, nevertheless, the pathogenesis pathway and reliable biomarkers have not been well determined. This study aimed to employ high throughput meta-analysis to find major genes that are possibly involved in the pathogenesis of HAM/TSP.

Results: High-throughput statistical analyses identified 832, 49, and 22 differentially expressed genes for normal vs. ACs, normal vs. HAM/TSP, and ACs vs. HAM/TSP groups, respectively. The protein-protein interactions between DEGs were identified in STRING and further network analyses highlighted 24 and 6 hub genes for normal vs. HAM/TSP and ACs vs. HAM/TSP groups, respectively. Moreover, four biologically meaningful modules including 251 genes were identified for normal vs. ACs. Biological network analyses indicated the involvement of hub genes in many vital pathways like JAK-STAT signaling pathway, interferon, Interleukins, and immune pathways in the normal vs. HAM/TSP group and Metabolism of RNA, Viral mRNA Translation, Human T cell leukemia virus 1 infection, and Cell cycle in the normal vs. ACs group. Moreover, three major genes including STAT1, TAP1, and PSMB8 were identified by network analysis. Real-time PCR revealed the meaningful down-regulation of STAT1 in HAM/TSP samples than AC and normal samples (P = 0.01 and P = 0.02, respectively), up-regulation of PSMB8 in HAM/TSP samples than AC and normal samples (P = 0.04 and P = 0.01, respectively), and down-regulation of TAP1 in HAM/TSP samples than those in AC and normal samples (P = 0.008 and P = 0.02, respectively). No significant difference was found among three groups in terms of the percentage of T helper and cytotoxic T lymphocytes (P = 0.55 and P = 0.12).

Conclusions: High-throughput data integration disclosed novel hub genes involved in important pathways in virus infection and immune systems. The comprehensive studies are needed to improve our knowledge about the pathogenesis pathways and also biomarkers of complex diseases.
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http://dx.doi.org/10.1186/s12977-019-0508-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937958PMC
December 2019

Seroprevalence of anti-rubella and anti-measles antibodies in women at the verge of marriage in Iran.

Vaccine 2020 01 24;38(2):235-241. Epub 2019 Oct 24.

Focal Point for Measles and Rubella Surveillance, Centre for Communicable Diseases Control, Ministry of Health and Medical Education, Tehran, Iran.

Background: Measles and rubella as two highly contagious eruptive diseases are on the agenda to be eliminated in Iran by 2020. To evaluate the seroimmunity of the future mothers against rubella and measles, a nationwide serosurvey was implemented in 10 provinces, selected at random from 31 provinces in the country.

Methods: using a multistage sampling method, 1600 participants were interviewed and blood sampled in 40 'Pre-marriage Consultation Centers' across 40 districts. Using ELISA method, the sera were tested for anti-rubella and anti-measles IgG antibodies in the National Reference Laboratory for Measles and Rubella, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Results: Of the 1600 initial participants, the sera of 1573 participants were tested for rubella and 1569 for measles. The total seroprevalence of anti-rubella and anti-measles antibodies were 90.6% (95%CI: 89.1 to 92.0%) and 80.7% (95%CI: 78.7 to 82.6%) respectively. After 14 years, the effect of the immunization campaign of 2003 against rubella and measles on the age group of 5 to 25 years, was still apparent, i.e., there was a sharp difference between the seroprevalence of antibody (against both measles and rubella) of those who at the time of the present study were above 18 years with the younger age cohorts. For both diseases, higher seroprevalence of antibodies was detected in women above 18 years old.

Conclusion: Implementation of a Supplemental Immunization activity or revision of the national immunization schedule to add a third dose of measles and rubella containing vaccine during adolescence are/might be considered as possible options for bridging the gap in the seroimmunity of the younger age groups.
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http://dx.doi.org/10.1016/j.vaccine.2019.10.026DOI Listing
January 2020

Serum and tissue miRNAs: potential biomarkers for the diagnosis of cervical cancer.

Virol J 2019 10 7;16(1):116. Epub 2019 Oct 7.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, 1471613151, Iran.

Background: Finding new biomarkers for the early detection of cervical cancer is an essential requirement in this field. In this study, we aimed to evaluate the expression level of potential biomarkers in progression of cervical cancer in patients with cervical cancer compared to normal subjects.

Methods: The expression levels of tissue and serum miRNAs, including miR-9, miR-192 and miR-205, were investigated in 36 normal, 18 precancer, and 18 cervical cancer samples using real-time polymerase chain reaction.

Results: The results showed the higher significant expressions of miR-9, miR-192 and miR-205 in the tissue of cancer samples than those in the normal samples. Moreover, the miR-192 and miR-205 expression were significantly increased in the cancer group in comparison with the precancer group. Examination of serum samples revealed the increase in the expression level in the cancer groups than in the normal samples, for miR-9, miR-192 and miR-205 and the expressions of miR-9, miR-192 and miR-205 were significantly up-regulated in the precancer group in comparison with the normal group. Also the expression of miR-205 was remarkably increased in the cancer group in comparison with the precancer group. The receiver operating characteristic (ROC) analyses showed the highest area under the curve value for miR-192.

Conclusions: Given the increased expression level of miR-192 in cancer and in precancerous tissue and serum compared with the normal tissue and serum validated by analysing the ROC curve, miR-192 can be used as potential biomarker for the early detection of cervical cancer.
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http://dx.doi.org/10.1186/s12985-019-1220-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781360PMC
October 2019

Possible viral infections in flood disasters: a review considering 2019 spring floods in Iran.

Iran J Microbiol 2019 Apr;11(2):85-89

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Floods are one of the natural disasters occurring worldwide which have a massive range of health impacts. In addition to immediate dangers such as drowning, floods can increase the transmission of some communicable diseases. Up to now there was no report of viral infection outbreaks after 2019 spring floods in Iran. This review explains the possible viral infections which may occur during or after floods.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635310PMC
April 2019

Association of polymorphisms in inflammatory cytokines encoding genes with severe cases of influenza A/H1N1 and B in an Iranian population.

Virol J 2019 06 13;16(1):79. Epub 2019 Jun 13.

Department of Virology, School of Public Health, National Influenza Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: The increased levels of blood cytokines is the main immunopathological process that were attributed to severe clinical outcomes in cases of influenza A, influenza B and people with influenza-like illness (ILI). Functional genetic polymorphisms caused by single nucleotide polymorphisms (SNPs) in inflammatory cytokines genes can influence their functions either qualitatively or quantitatively, which is associated with the possibility of severe influenza infections. The aim of the present case-control study was to investigate the association of polymorphisms in inflammatory cytokines genes with influenza patients and ILI group in an Iranian population.

Methods: Total number of 30 influenza B, 50 influenza A (H1N1) and 96 ILI inpatient individuals were confirmed by Real-time RT-PCR and HI assays. The genotype determination was assessed for defined SNPs in IL-1β, IL-17, IL-10 and IL-28 genes.

Results: The frequencies of the IL-1β rs16944 (P = 0.007) and IL-17 rs2275913 (P = 0.006) genotypes were associated with severe influenza disease, while the frequencies of IL-10 rs1800872 and IL-28 rs8099917 were not associated with the disease (P > 0.05). Also, the absence of A allele in IL-17 rs2275913 SNP increased the risk of influenza A (H1N1) infection (P = 0.008).

Conclusions: This study demonstrated that influenza A- (H1N1) and B-infected patients and also ILI controls have different profiles of immune parameters, and individuals carrying the specific cytokine-derived polymorphisms may show different immune responses towards severe outcome.
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http://dx.doi.org/10.1186/s12985-019-1187-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567579PMC
June 2019

Molecular characterization of the glycoprotein and fusion protein in human respiratory syncytial virus subgroup A: Emergence of ON-1 genotype in Iran.

Infect Genet Evol 2019 07 1;71:166-178. Epub 2019 Apr 1.

Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

HRSV is a principle cause of infant hospitalization, childhood wheezing and a common pathogen in the elderly. Limited information exists regarding HRSV genotypes in Iran. In order to better understand HRSV strain diversity, we performed an in-depth evaluation of the genetic variability of the HRSV F protein detected in children under two years of age that, presented with acute respiratory symptoms during 2015-2016 in Tehran. A total of 180 nasopharyngeal swabs were evaluated. The HRSV positive samples were genotyped for G and F gene sequences using RT-PCR and sequencing methods. Phylogenetic analysis was performed using the neighbor-joining and maximum likelihood methods. Genetic and antigenic characteristics of the F gene, nucleotide and amino acids in significant positions and immune system binding regions, as well as the p-distance, positive/negative selection site, linear epitopes and glycosylation sites were investigated in all selected sequences. Among the 83 HRSV positive samples, the Fifty-five cases were successfully sequenced. All of them were classified as subgroup A and belonged to the ON-1 genotype, which possessed 72-nt duplication in the G gene. This study is the first report on the emergence of ON-1 in Iran. ON-1 Iranian sequences clustered in three lineages according to virus fusion (F) gene variations. F gene sequence analysis showed that all genetic changes in the isolates from Iran were base substitutions and no deletion/insertions were identified. The low dN/dS ratio and lack of positively selected sites showed that the fusion genes found in the strains from Iran are not under host selective pressure. Continuing and long-term molecular epidemiological surveys for early detection of circulating and newly emerging genotypes are necessary to gain a better understanding of their epidemic potential.
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http://dx.doi.org/10.1016/j.meegid.2019.03.026DOI Listing
July 2019

Induction of protective immune response to intranasal administration of influenza virus-like particles in a mouse model.

J Cell Physiol 2019 Feb 19. Epub 2019 Feb 19.

Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Human influenza A viruses (IAVs) cause global pandemics and epidemics, which remains a nonignorable serious concern for public health worldwide. To combat the surge of viral outbreaks, new treatments are urgently needed. Here, we design a new vaccine based on virus-like particles (VLPs) and show how intranasal administration of this vaccine triggers protective immunity, which can be exploited for the development of new therapies. H1N1 VLPs were produced in baculovirus vectors and were injected into BALB/c mice by the intramuscular (IM) or intranasal (IN) route. We found that there were significantly higher inflammatory cell and lymphocyte concentrations in bronchoalveolar lavage samples and the lungs of IN immunized mice; however, the IM group had little signs of inflammatory responses. On the basis of our results, immunization with H1N1 influenza VLP elicited a strong T cell immunity in BALB/c mice. Despite T cell immunity amplification after both IN and IM vaccination methods in mice, IN-induced T cell responses were significantly more intense than IM-induced responses, and this was likely related to an increased number of both CD11b and CD103 dendritic cells in mice lungs after IN administration of VLP. Furthermore, evaluation of interleukin-4 and interferon gamma cytokines along with several chemokine receptors showed that VLP vaccination via IN and IM routes leads to a greater CD4 Th1 and Th2 response, respectively. Our findings indicated that VLPs represent a potential strategy for the development of an effective influenza vaccine; however, employing relevant routes for vaccination can be another important part of the universal influenza vaccine puzzle.
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http://dx.doi.org/10.1002/jcp.28339DOI Listing
February 2019

Influenza vaccine: Where are we and where do we go?

Rev Med Virol 2019 01 8;29(1):e2014. Epub 2018 Nov 8.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

The alarming rise of morbidity and mortality caused by influenza pandemics and epidemics has drawn attention worldwide since the last few decades. This life-threatening problem necessitates the development of a safe and effective vaccine to protect against incoming pandemics. The currently available flu vaccines rely on inactivated viral particles, M2e-based vaccine, live attenuated influenza vaccine (LAIV) and virus like particle (VLP). While inactivated vaccines can only induce systemic humoral responses, LAIV and VLP vaccines stimulate both humoral and cellular immune responses. Yet, these vaccines have limited protection against newly emerging viral strains. These strains, however, can be targeted by universal vaccines consisting of conserved viral proteins such as M2e and capable of inducing cross-reactive immune response. The lack of viral genome in VLP and M2e-based vaccines addresses safety concern associated with existing attenuated vaccines. With the emergence of new recombinant viral strains each year, additional effort towards developing improved universal vaccine is warranted. Besides various types of vaccines, microRNA and exosome-based vaccines have been emerged as new types of influenza vaccines which are associated with new and effective properties. Hence, development of a new generation of vaccines could contribute to better treatment of influenza.
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http://dx.doi.org/10.1002/rmv.2014DOI Listing
January 2019

Correction to: Blocking of opioid receptors in experimental formaline-inactivated respiratory syncytial virus (FI-RSV) immunopathogenesis: from beneficial to harmful impacts.

Med Microbiol Immunol 2018 11;207(5-6):345

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

In the original publication, seventh author's name was incorrectly published as 'Maryam Golaram'.
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http://dx.doi.org/10.1007/s00430-018-0562-1DOI Listing
November 2018

Sero-epidemiological evaluation of rubella immunity among pre-marriage women in Iran.

Hum Vaccin Immunother 2019 11;15(9):2117-2120. Epub 2019 Jul 11.

Social Determinants of Health Research Center, Hamadan University of Medical Sciences , Hamadan , Iran.

Few studies have addressed the seroepidemiological profile of rubella among a representative population of young adult women. This study aims to determine the immunity and susceptibility rate against rubella in a representative population of women in reproductive age in Iran through serological evaluation. This cross-sectional study was conducted in 2012 on 804 pre-marriage women in Iran. Multi-stage random sampling was used for choosing study sample. Serologic test were used to assess subjects' immunity to rubella and their titers of IgG antibody against rubella with ELISA method was measured. In total, 98.4% (95% CI: 97.5% -99.2%) of study participants were immune against rubella. Five women (0.6%) were in borderline category and 1% (8 women) was susceptible to rubella. The proportion of immune people in low and high incidence regions was 99.3% (95% CI: 97.8-99.9%), and 97.5% (95% CI: 96.4-98.5%), respectively (= 0.05). Our data indicated that level of immunity to rubella in women of reproductive age in Iran is satisfactory. This finding indicates the achievement of Iran to the goal of high level of serum immunity against rubella among young women.
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http://dx.doi.org/10.1080/21645515.2018.1504527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773378PMC
March 2020

Molecular detection of HHV1-5, AAV and HPV in semen specimens and their impact on male fertility.

Hum Fertil (Camb) 2019 Jun 24;22(2):133-138. Epub 2018 Apr 24.

a Virology Department, School of Public Health , Tehran University of Medical Sciences , Tehran , Iran.

Viral infections have been considered as possible destructive factors that influence male fertility. The aim of this study was to determine the prevalence of human herpes viruses 1-5 (HHV1-5), adeno associated virus (AAV) and human papilloma virus (HPV) in semen and whether these influence semen quality. DNA extraction was performed using phenol-chloroform protocol, then three different nested-PCRs were done to detect HHV1-5, AAV and HPV DNAs in the semen samples. Of 145 samples, 66 (45.5%) were positive at least for one of the viruses. The genome detection rate of HSV1/2, VZV, EBV, HCMV, AAV and HPV were zero, 2.8%, zero, 1.4%, 27.6% and 19.3%, respectively. Of 66 positive samples for these viruses, 6 (4.1% of all samples) were positive for two viruses simultaneously. Here no association was found between variations in semen parameters related to fertility and detection of VZV, HCMV, AAV and HPV DNA in semen samples. It should be noted that the prevalence of different viruses in semen, and their relevance to male infertility, differs significantly due to the genome extraction and amplification methods or due to a real variation between study populations and geographical regions.
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http://dx.doi.org/10.1080/14647273.2018.1463570DOI Listing
June 2019

Seroprevalence of antibodies to measles and rubella eight months after a vaccination campaign in the southeast of Iran.

Hum Vaccin Immunother 2018 06 26;14(6):1412-1416. Epub 2018 Feb 26.

c National Reference Laboratory for Measles and Rubella, School of Public Health, Tehran University of Medical Sciences , Tehran , Iran.

Eight months after the mass immunization campaign of November 2015 against measles and rubella in the southeast of Iran, in order to evaluate the sero-immunity level of the people living in the mentioned region, a serosurvey study was performed. Using a multi-stage probability proportional to size cluster sampling, the sera of 1,056 participants, ranging from 15 months to 20 years old, were tested for measles and rubella IgG antibodies in the National Reference Laboratory at Tehran University of Medical Sciences, Tehran, Iran. The seroprevalence rates of antibodies against measles and rubella in the age groups below 16 years were respectively 98.4 and 93.2%. In the age group of 16 to 20 years, who was not the target of the mass immunization campaign, the said rates were respectively 91.7% and 87.4%. The herd immunity of the age groups below 16 years, who were the target of the campaign, is favourably high and reassuring both for measles and for rubella. Campaigns of supplementary vaccination play a substantial role for filling the gaps in the herd immunity.
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http://dx.doi.org/10.1080/21645515.2018.1436920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6037465PMC
June 2018

Head-to-head immunogenicity comparison of Edmonston-Zagreb vs. AIK-C measles vaccine strains in infants aged 8-12 months: A randomized clinical trial.

Vaccine 2018 01 27;36(5):631-636. Epub 2017 Dec 27.

National Reference Laboratory for Measles and Rubella, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: A non-inferiority multi-centre parallel randomized double-blind trial was implemented in Zahedan district, Sistan-va-Baluchestan province, Iran, to compare the performance of the two measles vaccines which are in use in the National Immunization Programme of Iran and are of two different measles virus vaccine strains: Edmonston-Zagreb (EZ) strain vs. AIK-C strain. The main outcome measure was appearance of anti-measles antibody in sera.

Methods: 200 infants, 8-12 months old, whose parents consented for their children to be included in the study, were randomized in permutation blocks of size 4-8 in four Urban Health Clinics. Having given a pre-vaccination blood sample, they received measles-rubella vaccine containing one of the vaccine strains mentioned before. After 60 days, the second blood sample was taken. The sera of the pre- and post-vaccination blood samples were tested for anti-measles antibodies in the National Reference Measles Laboratory. Parents, laboratory technicians and statistician were blind to groupings.

Results: Of the 200 children equally randomized in the two arms, 185 who were seronegative before vaccination (88 in the EZ arm and 97 in the AIK-C arm) were entered in the final analysis. The seroconversion rate in the EZ arm was 76.1% (95% CI: 60.2-85.2%), and that in the AIK-C arm was 58.7%; (95% CI: 48.8-68.7%). The absolute rate difference was 17. 4% (4.1-30.9%; P-value: .012), and the relative seroconversion rate of EZ to AIK-C was 1.3 (95% CI: 1.1-1.6; P-value: .012). No adverse events were reported during the study period.

Conclusion: A considerable difference in the seropositivity of different measles containing vaccines could be demonstrated in the first year of life.

Trial Registration: Iranian Registry of Clinical Trials Registration Number: IRCT2016032827144N1; May 10, 2016 (www.who.int/ictrp/network/irct/en/).
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http://dx.doi.org/10.1016/j.vaccine.2017.12.048DOI Listing
January 2018

The Comparison of Sensitivity and Specificity of ELISA-based Microneutralization Test with Hemagglutination Inhibition Test to Evaluate Neutralizing Antibody against Influenza Virus (H1N1).

Iran J Public Health 2017 Dec;46(12):1690-1696

Dept. of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: The most common serological assay to measure anti-influenza antibodies is hemagglutination inhibition (HI) assay. Recently, neutralizing antibodies against influenza virus infection or vaccination can also be detected using microneutralization assays and occasionally, have greater sensitivity than the standard HI assays. The study aimed to compare the sensitivity and specificity of ELISA-based microneutralization (microNT-ELISA) and conventional HI assays in order to detect influenza H1N1 virus antibodies.

Methods: MicroNT-ELISA was set up according to the WHO Manual on Influenza Diagnosis and Surveillance in Virology Department of Tehran University of Medical Sciences for the detection of neutralizing antibodies against H1N1 influenza virus in 2013. Fifty serum samples were analyzed with both HI and microNT-ELISA assays. Correlation between methods was calculated by linear regression analysis.

Results: The linear correlation coefficient squares, R2, of microNT-ELISA and HI test was 0.61 (<0.0001) and we observed a high index of coincidence between the two tests. According to McNemar's test, there was no statistically significant difference between these two assays (>0.05).

Conclusion: The sensitivity and specificity of microNT-ELISA assay were high (87% and 73%, respectively) and closely related to gold standard test results. Therefore, microNT-ELISA is recommended as an alternative or complementary test to conventional HI assay for serological and epidemiological purposes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734969PMC
December 2017

Blocking of opioid receptors in experimental formaline-inactivated respiratory syncytial virus (FI-RSV) immunopathogenesis: from beneficial to harmful impacts.

Med Microbiol Immunol 2018 04 18;207(2):105-115. Epub 2017 Dec 18.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Opioid system plays a significant role in pathophysiological processes, such as immune response and impacts on disease severity. Here, we investigated the effect of opioid system on the immunopathogenesis of respiratory syncytial virus (RSV) vaccine (FI-RSV)-mediated illness in a widely used mouse model. Female Balb/c mice were immunized at days 0 and 21 with FI-RSV (2 × 10 pfu, i.m.) and challenged with RSV-A2 (3 × 10 pfu, i.n.) at day 42. Nalmefene as a universal opioid receptors blocker administered at a dose of 1 mg/kg in combination with FI-RSV (FI-RSV + NL), and daily after live virus challenge (RSV + NL). Mice were sacrificed at day 5 after challenge and bronchoalveolar lavage (BAL) fluid and lungs were harvested to measure airway immune cells influx, T lymphocyte subtypes, cytokines/chemokines secretion, lung histopathology, and viral load. Administration of nalmefene in combination with FI-RSV (FI-RSV + NL-RSV) resulted in the reduction of the immune cells infiltration to the BAL fluid, the ratio of CD4/CD8 T lymphocyte, the level of IL-5, IL-10, MIP-1α, lung pathology, and restored weight loss after RSV infection. Blocking of opioid receptors during RSV infection in vaccinated mice (FI-RSV-RSV + NL) had no significant effects on RSV immunopathogenesis. Moreover, administration of nalmefene in combination with FI-RSV and blocking opioid receptors during RSV infection (FI-RSV + NL-RSV + NL) resulted in an increased influx of the immune cells to the BAL fluid, increases the level of IFN-γ, lung pathology, and weight loss in compared to control condition. Although nalmefene administration within FI-RSV vaccine decreases vaccine-enhanced infection during subsequent exposure to the virus, opioid receptor blocking during RSV infection aggravates the host inflammatory response to RSV infection. Thus, caution is required due to beneficial/harmful functions of opioid systems while targeting as potentially therapies.
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http://dx.doi.org/10.1007/s00430-017-0531-0DOI Listing
April 2018

Evaluation of Antibody and Cytokines Responses in Intranasally and Intramuscularly Administrated BALB/C Mice With Influenza Virus-Like Particle.

Acta Med Iran 2017 Oct;55(10):604-611

Department of Virology, School of Public Health, National Influenza Center, Tehran University of Medical Sciences, Tehran, Iran.

We previously developed an influenza virus like particle with HA, M, and NA proteins using Bac-to-Bac expression system and SF9 cell line. To evaluate the immunogenicity of our construct, we assessed the humoral, cytokine induced by H1N1-VLP in BALB/c mice immunized intranasally and intramuscularly. Enzyme-linked immunosorbent assay and Relative quantitative real-time PCR were used to evaluate the antibody (IgG and IgA) and mRNA levels of IL-6, IL-4, IL-10 and IFN-g in PBMCs. Our results showed that VLP was capable of intranasal (I.N.) and intramuscular (I.M.) induction of serum IgG and IgA responses. Interestingly, I.N. route induced higher IgG and IgA titer than I.M. route, which was statistically significant. Moreover, mRNA levels of IL-6 (4.2-4.5 folds), IFN-g (5.5-5.7 folds), and the anti-inflammatory cytokine IL-10 (2.5-3 folds) and IL-4 (2.4-2.8 folds) were significantly elevated in mice immunized I.N. and I.M. with H1N1-VLP compared to the control group. Our findings indicated that a non-infectious genome-less VLP approach mimics parenteral virus with multiple viral antigens and epitopes that stimulate a diverse set of immune responses such as innate immunity, specific serum IgG antibody, cell-mediated immunity, and local antibodies.
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October 2017

Human T-lymphotropic virus 1 (HTLV-1) pathogenesis: A systems virology study.

J Cell Biochem 2018 05 19;119(5):3968-3979. Epub 2018 Jan 19.

Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

The main mechanisms of interaction between Human T-lymphotropic virus type 1 (HTLV-1) and its hosts in the manifestation of the related disease including HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and Adult T-cell leukemia/lymphoma (ATLL) are yet to be determined. It is pivotal to find out the changes in the genes expression toward an asymptomatic or symptomatic states. To this end, the systems virology analysis was performed. Firstly, the differentially expressed genes (DEGs) were taken pairwise among the four sample sets of Normal, Asymptomatic Carriers (ACs), ATLL, and HAM/TSP. Afterwards, the protein-protein interaction networks were reconstructed utilizing the hub genes. In conclusion, the pathways of cells proliferation and transformation were identified in the ACs state. In addition to immune pathways in ATLL, the inflammation and cancer pathways were discened in both diseases of ATLL and HAM/TSP. The outcomes can specify the genes involved in the pathogenesis and help to design the drugs in the future.
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http://dx.doi.org/10.1002/jcb.26546DOI Listing
May 2018