Evaluation Frequency of Human Papillomavirus and Its Related Genotypes in Women of the General Population Living in 11 Provinces of Iran.

Introduction: Persistent infection with one of the most high-risk genotypes of human papillomavirus causes all cases of cervical cancer and a significant proportion of other genital cancers. The HPV virus, unlike any other infection that leads to cancer, is transmitted only through sexual intercourse and is less affected by the general changes and development in lifestyle and medical standards, so only vaccination and screening can prevent the HPV virus and cancers caused by it. Therefore, determining the prevalence and distribution of HPV genotypes are of utmost importance in screening strategies regarding cervical cancer and vaccination decisions against HPV that vary based on the geographical and cultural characteristics of the study area. As a result, this study aimed to determine the frequency of human papillomavirus and the distribution of this virus's genotypes in the general population of women living in 11 provinces of Iran. Materials and Methods: This study is a community-based survey study. Sampling was done by the cluster sampling method. Women aged 15-59 years old from the general population living in 11 provinces of Iran were included in the study after considering the inclusion and exclusion criteria. Data were collected using a questionnaire and vaginal examination. The study was performed on 2562 vaginal specimens that were referred to the laboratory of the present study. HPV genome was detected by the nested MY-GP method and papillomavirus genotyping was performed using the PCR multiplex method to identify 19 papillomavirus genotypes. Results: The general prevalence of HPV in the 11 provinces was obtained at 2.4% (108 out of 2562 people). The highest prevalence of the virus was in the age group of 25-34 years. The prevalence of HPV was statistically significant among different provinces. Hormozgan province with 22 cases (5.9%) had the highest and Isfahan province with 6 cases (2.2%) had the lowest incidence of HPV. The prevalence of high-risk HPV and medium-risk HPV is 3%, and the prevalence of low-risk HPV was estimated to be 2.1% of the total female population. Also, the highest prevalence was related to genotype 16. Conclusion: According to the high prevalence of the HPV virus in young age groups in Iran, it is necessary to pay attention to screening programs to reduce the incidence of cervical cancer.

Genetic Diversity of HPV 16 and HPV 18 Based on Partial Long Control Region in Iranian Women.

BACKGROUND: Human papillomavirus (HPV) 16 and HPV 18 account for 75% of all cervical cancers. The L1 gene, encoding the major surface protein (MSP), is used to classify HPV types (lineages and sublineages), genotypes, and intratypic variants. Therefore, this study aimed to investigate the lineages, sublineages, genetic variabilities, and mutation effects on transcription factor binding sites by using partial sequences of the HPV 16 and HPV 18 long control regions (LCRs) in these samples. MATERIALS AND METHODS: After DNA isolation from 56 positive samples, the LCR of HPV 16 and HPV 18 were amplified using specific primers, and phylogenetic trees were drawn through MEGA X. Compared to the reference sequences, single nucleotide polymorphisms (SNPs) were identified. The transcription binding sites were also evaluated using the online PROMO database. RESULTS: The LCRs of 52 samples were successfully sequenced. Overall, 81.58% of all HPV 16 variants belonged to the D1 sublineage, followed by A4 (13.16%), A1 (2.63%), and C1 (2.63%) sublineages. All HPV 18 isolates belonged to A sublineage, 92.85% to A3 sublineage, and 7.15% to A4 sublineage. Out of 27 SNPs in the HPV 16 LCR, A7382T, T7384G, C7387T, C7393G, A7431G, T7448C, and C7783A were HPV 16-specific. Also, among 14 SNPs in the HPV 18 LCR, C7577A and A7943T were not previously reported. An insertion (C) between 7432 and 7433 positions was identified in all studied HPV 16 variants. Besides, most of the HPV 16 mutations were embedded in the YY1, TFIID, Oct-2, and NF-1 binding sites, while c-Fos and MBF1, as the most common binding sites, were affected by HPV 18 LCR mutations. CONCLUSION: The present results showed that D1 and A3 were the dominant sublineages of HPV 16 and HPV 18, respectively. Therefore, women infected with these variants need to be examined in further longitudinal studies to obtain more information about the oncogenic potential of these dominant variants in Iran. Besides, YY1, TFIID, Oct-2, NF-1, c-Fos, and MBF1 were the most frequent binding sites, which were influenced by the mutations.

Pulmonary manifestations in a cohort of patients with inborn errors of immunity: an 8-year follow-up study.

BACKGROUND: Inborn errors of immunity (IEIs) are a group of congenital diseases caused by genetic defects in the development and function of the immune system. The involvement of the respiratory tract is one of the most common presentations in IEIs. METHODS: Overall, 117 patients with diagnosed IEIs were followed-up within 8 years at the National Research Institute of Tuberculosis and Lung Diseases (NRITLD). Demographic, clinical, and laboratory data were collected in a questionnaire. Pulmonary function test (PFT), chest X-ray (CXR), and high-resolution computed tomography (HRCT) scans were obtained where applicable. RESULTS: Our study population consisted of 48 (41%) patients with predominantly antibody deficiencies (PADs), 39 (32%) patients with congenital defects of phagocytes, 14 (11.9%) patients with combined immunodeficiency (CID), and 16 (14%) patients with Mendelian susceptibility to mycobacterial diseases (MSMD). . Recurrent pneumonia was the most common manifestation, while productive cough appeared to be the most common symptom in almost all diseases. PFT showed an obstructive pattern in patients with PAD, a restrictive pattern in patients with CID, and a mixed pattern in patients with CGD. HRCT findings were consistent with bronchiectasis in most PAD patients, whereas consolidation and mediastinal lesions were more common in the other groups. CONCLUSIONS: Pulmonary manifestations vary among different groups of IEIs. The screening for lung complications should be performed regularly to reveal respiratory pathologies in early stages and follow-up on already existing abnormalities.

Promising effects of tocilizumab in COVID-19: A non-controlled, prospective clinical trial.

BACKGROUND: The clinical presentation of SARS-CoV-2 infection ranges from mild symptoms to severe complications, including acute respiratory distress syndrome. In this syndrome, inflammatory cytokines are released after activation of the inflammatory cascade, with the predominant role of interleukin (IL)-6. The aim of this study was to evaluate the effects of tocilizumab, as an IL-6 antagonist, in patients with severe or critical SARS-CoV-2 infection. METHODS: In this prospective clinical trial, 76 patients with severe or critical SARS-CoV-2 infection were evaluated for eligibility, and ultimately, 42 patients were included. Tocilizumab was administered at a dose of 400 mg as a single dose via intravenous infusion. Primary outcomes included changes in oxygenation support, need for invasive mechanical ventilation, and death. Secondary outcomes included radiological changes in the lungs, IL-6 plasma levels, C-reactive protein levels, and adverse drug reactions. The data were analyzed using SPSS software. RESULTS: Of the 42 included patients, 20 (48%) patients presented the severe infection stage and 22 (52%) were in the critical stage. The median age of patients was 56 years, and the median IL-6 level was 28.55 pg/mL. After tocilizumab administration, only 6 patients (14%) required invasive ventilation. Additionally, 35 patients (83.33%) showed clinical improvement. By day 28, a total of 7 patients died (6 patients in the critical stage and 1 patient in the severe stage). Neurological adverse effects were observed in 3 patients. CONCLUSIONS: Based on the current results, tocilizumab may be a promising agent for patients with severe or critical SARS-CoV-2 infection, if promptly initiated during the severe stage.

Diffuse alveolar damage and thrombotic microangiopathy are the main histopathological findings in lung tissue biopsy samples of COVID-19 patients.

BACKGROUND: Since the outbreak of the novel coronavirus disease-2019 (COVID-19) in December 2019, limited studies have investigated the histopathologic findings of patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). MATERIAL AND METHODS: This study was conducted on 31 deceased patients who were hospitalized for COVID-19 in a tertiary hospital in Tehran, Iran. A total of 52 postmortem tissue biopsy samples were obtained from the lungs and liver of decedents. Clinical characteristics, laboratory data, and microscopic features were evaluated. Reverse transcription polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 was performed on specimens obtained from nasopharyngeal swabs and tissue biopsies. RESULTS: The median age of deceased patients was 66 years (range, 30-87 years) and 25 decedents (81 %) were male. The average interval from symptom onset to death was 13 days (range, 6-34 days). On histopathologic examination of the lung specimens, diffuse alveolar damage and thrombotic microangiopathy were the most common findings (80 % and 60 %, respectively). Liver specimens mainly showed macrovesicular steatosis, portal lymphoplasmacytic inflammation and passive congestion. No definitive viral inclusions were observed in any of the specimens. In addition, 92 % of lung tissue samples tested positive for SARS-CoV-2 by RT-PCR. CONCLUSIONS: Further studies are needed to investigate whether SARS-CoV-2 causes direct cytopathic changes in various organs of the human body.

Declining trends in HIV and other sexually transmitted infections among female sex workers in Iran could be attributable to reduced drug injection: a cross-sectional study.

OBJECTIVE: The HIV trend among female sex workers (FSWs) is understudied. We assessed the prevalence and trend of HIV and five other STIs among FSWs in Iran. METHODS: We recruited FSWs (1337 in 2015, 1005 in 2010) from 21 sites in 13 cities in two cross-sectional biobehavioural surveys. Eligible FSWs were women aged ≥18 years who reported selling sex to more than one male client in the past 12 months. Consenting FSWs were interviewed using a behavioural questionnaire and tested for HIV and five other STIs. We considered study sites as clusters in the analysis and two-sided Fisher's exact test to compare the HIV prevalence between the two survey rounds. RESULTS: HIV prevalence was 2.1% in 2015 (vs 4.0% in 2010, p=0.007). Lifetime drug injection was reported by 6.1% of participants in 2015 (vs 14.6% in 2010, p=0.003). In 2015, among FSWs with history of lifetime drug injection, HIV prevalence was 8.6% (vs 9.8% in 2010, p=0.425). The prevalence of other STIs in 2015 was 0.4% (95% CI 0.2 to 1.0) for syphilis, 1.3% (95% CI 0.8 to 2.1) for gonorrhoea, 6.0% (95% CI 4.8 to 7.4) for chlamydia, 11.9% (95% CI 8.5 to 16.5) for trichomoniasis and 41.8% (95% CI 39.2 to 44.5) for human papillomavirus. CONCLUSIONS: HIV prevalence among FSWs in Iran decreased, but remains considerably high. The decrease in HIV prevalence compared with 2010 might be explained by a decrease in drug injection. Other STIs are also high in this population. Harm reduction programmes need to be continued and scaled up among this underserved population in Iran.

Absence of Human Papillomavirus in Benign and Malignant Breast Tissue.

BACKGROUND & OBJECTIVE: Malignant breast tumors, which are one of the most important deadly cancers in women, like many other cancers, are proposed to be related to viruses etiologically. Proper management of breast carcinoma necessitates an identification of the etiological factors. Human Papillomavirus is considered to have an etiological role in breast carcinoma. We carried out this study to find out if Human Papillomavirus-DNA is present in the malignant and benign breast tissue in our patients. METHODS: Seventy-five paraffin-embedded breast cancer tissues and 75 normal breast tissues and benign breast lesions were examined in this study (case-control) to look for Human Papillomavirus-DNA employing Nested Polymerase Chain reaction. The tissues were examined over a period of ten years in the pathology department of the Pathobiology Laboratory Center of Tehran. RESULTS: No Human Papillomavirus-DNA was found in any of the malignant or control group specimens. CONCLUSION: Our results showed no evidence of Human Papillomavirus in cancerous and benign tissues, which is consistent with some other studies in English medical literature. More investigations using more specimens from different parts of the country are required to confirm the presence or absence of any connection between Human Papillomavirus and development of breast carcinoma in Iran.

Association of specific viral infections with childhood asthma exacerbations.

INTRODUCTION: Asthma exacerbations may occur due to a variety of triggers including respiratory viruses. The aim of this study was to determine the role of particular viral infections in asthma exacerbations in children. MATERIALS AND METHODS: The study was performed at Dr. Daneshvari Hospital Pediatric Emergency Department, Shahid Beheshti University of Medical Sciences, Tehran, Iran between 2014 and 2015. A nasopharyngeal aspirate or swab was obtained from each patient during admission. All samples were maintained at 4 °C until submission to the virology laboratory and were tested for respiratory viruses by nucleic acid testing. RESULTS: A total of 60 patients with asthma exacerbations were recruited for this study. Of the 60 samples collected from the patients with acute asthma exacerbations, rhinovirus was detected in 12 patients (20%), respiratory syncytial virus in 5 (8%), adenovirus in 5 (8%), and influenza virus in 1 (1.6%). Respiratory pathogens were not detected in 37 (61%) samples. All the samples investigated showed single viral infection. CONCLUSIONS: To conclude, the most common viruses detected were rhinovirus followed by respiratory syncytial virus (RSV) and adenovirus. RSV was more commonly associated with more severe attacks. Both the study design (e.g., time of sampling, age of the patients, etc.) and also the method used for viral detection influence the frequency of detection of the respiratory viruses.

Small Heat Shock Proteins B1 and B6: Which One is the Most Effective Adjuvant in Therapeutic HPV Vaccine?

Therapeutic human papillomaviruse (HPV) vaccines have the potential to inhibit the tumor growth by targeting HPV E6 and E7 oncoproteins. Among different vaccine strategies, DNA and protein-based approaches are the most effective candidates for stimulation of the immune responses against HPV infections. Our study was designed to assess the efficacy of small heat shock proteins B1 (Hsp27) and B6 (Hsp20) as an adjuvant accompanied by HPV16 E7 and hPP10-E7 antigens in tumor mouse model. A major key for successful DNA and protein transfer into cells is the development of delivery systems with high efficiency and low cytotoxicity. Herein, we used hPP10 and MPG cell penetrating peptides (CPPs) for protein and DNA delivery in vivo, respectively. Our data indicated that the combination of Hsp27 with the recombinant hPP10-E7 protein in homologous protein/protein (hPP10-E7 + Hsp27) and heterologous DNA/protein (pcDNA-E7 + MPG/ hPP10-E7 + Hsp27) significantly enhanced the E7-specific T cell responses. Indeed, these regimens induced high levels of IgG2a, IFN-γ and IL-2 directed toward Th1 responses and also Granzyme B secretion as compared to other immunization strategies, and also displayed complete protection more than 60 days after treatment. These data suggest that the use of Hsp27 as an adjuvant and MPG and hPP10 as a gene and protein carrier would represent promising applications for improvement of HPV therapeutic vaccines. © 2018 IUBMB Life, 70(10):1002-1011, 2018.

Symptom-Based Versus Laboratory-Based Diagnosis of Five Sexually Transmitted Infections in Female Sex Workers in Iran.

Among 1337 Iranian adult female sex workers in 2015, we assessed the diagnostic value of 4 self-reported sexually transmitted infection (STIs) symptoms for detecting laboratory-confirmed gonorrhea, chlamydia, trichomoniasis, human papillomavirus (HPV), and syphilis. While 37.7% reported vaginal discharge (VD), 25.9% reported pain or burning (P/B), 3.0% reported genital ulcers (GU), and 1.4% reported genital warts (GW), the prevalence of laboratory-confirmed syphilis, gonorrhea, chlamydia, trichomoniasis, and HPV was 0.4, 1.3, 6.0, 11.9, and 41.9%, respectively. The sensitivity of VD was 40.3% for detecting tricomoniasis, 37.5% for chlamydia, and 37.5% for gonorrhea. The sensitivity of P/B ranged from 12.5% for gonorrhea to 25.2% for trichomoniasis. The sensitivity of GU and GW was very low for 5 STIs. The sensitivity of all symptoms combined was also lower than 50%. Among asymptomatic participants, 41.2% tested positive for HPV, 11.8% for trichomoniasis, and less than 6.6% for other STIs. Symptom-based case management and surveillance of STIs can lead to misclassification of a large proportion of cases.

Delivery of molecular cargoes in normal and cancer cell lines using non-viral delivery systems.

OBJECTIVE: In this study, transfection efficiency of human papillomavirus (HPV) E7 DNA and protein constructs into HEK-293T normal cell line, and A549 and TC-1 tumor cell lines was evaluated by four delivery systems including supercharge GFP, hPP10 cell penetrating peptide, TurboFect and Lipofectamine using fluorescence microscopy and flow cytometry. RESULTS: The results indicated that Lipofectamine 2000 and TurboFect produced more effective transfection for GFP and E7-GFP DNA constructs in HEK-293T cells compared to in A549 and TC-1 cells (p < 0.05). In contrast, the supercharge GFP was efficient for E7 DNA and E7 protein delivery in both normal cell (~ 83.94 and ~ 77.01% for HEK-293T), and cancer cells (~ 71.69 and ~ 67.19% for TC-1, and ~ 73.86 and ~ 67.49% for A549), respectively. Indeed, in these cell lines, transfection efficiency by +36 GFP reached ~ 60-80%. Moreover, the hPP10 produced the best transfection result for E7-GFP protein in HEK-293T cells (~ 63.66%) compared to TurboFect (~ 32.95%); however, the efficiency level of hPP10 was only ~ 17.51 and ~ 16.36% in TC-1 and A549 cells. CONCLUSIONS: Our data suggested that the supercharge GFP is the most suitable transfection vehicle for DNA and protein delivery into TC-1 and A549 tumor cell lines compared to other carriers.

Therapeutic effect of perinatal exogenous melatonin on behavioral and histopathological changes and antioxidative enzymes in neonate mouse model of cortical malformation.

BACKGROUND: Melatonin, which is an antioxidant and neuroprotective agent, can be an effective treatment for neurological disorders. We assessed the effect of melatonin administration on histological changes, antioxidant enzyme levels, and behavioral changes in a neonate mouse model of cortical malformation. MATERIALS AND METHODS: Cortical malformation was induced by two injections of 15 mg/kg methylazoxymethanol (MAM) on gestational day 15 (E15). Pregnant Balb/c mice were randomly divided into the following six groups: Control (CO), Melatonin (MEL), Luzindole (LUZ), MAM, MEL + MAM1 (co-treatment), and MEL + MAM2 (pretreatment). Melatonin was intraperitoneally injected at a dose of 10 mg/kg daily (from E15 until delivery of from E6 for 20 days after delivery). On postnatal day 31, the activity and anxiety of mice were assessed by open field and elevated plus maze tests, respectively. Histopathological changes in the neonate cortex were studied using hematoxylin and eosin staining and neurofilament immunohistochemistry. Enzyme-linked immunosorbent assays were used to measure the activity of nitric oxide (NO), malondialdehyde (MDA), and antioxidant enzymes, including catalase (CAT), super oxide dismutase (SOD), and glutathione peroxidase (GPX). RESULTS: In the behavioral assessment of neonate mice, a significant increase in the crossing activity and decrease in anxiety were recorded in groups treated with MAM plus melatonin. In histological examination, heterotopic, dysmorphic, and ectopic cells, as well as dyslamination, were seen in the MAM and LUZ groups. However, these defects were attenuated in the MAM plus melatonin groups. Significant reductions were recorded in the SOD and GPX levels in the MAM and LUZ groups compared to the control, while the NO level was increased in these groups. Groups that received MAM plus melatonin showed significant increases in the levels of SOD and GPX and a significant decrease in the level of NO, compared to the MAM group. CONCLUSION: Melatonin increased the crossing activity and decreased the anxiety in the treated mice of the neonate mouse model of cortical malformation. Histologically, the administration of exogenous melatonin in pregnant mice and their neonates had a protective effect on the cerebral cortex of neonates. Also, this effect is elicited by decreasing NO and increasing antioxidative enzymes.

Lack of HPV in Benign and Malignant Epithelial Ovarian Tumors in Iran

Background: Ovarian epithelial tumors one of the most common gynecological neoplasms; we here evaluated the presence of HPV in benign and malignant examples. Methods: In this cross-sectional study the records of 105 patients with epithelial ovarian tumors (benign and malignant) referred to Imam Hossein University Hospital from 2012 to 2015 were evaluated along with assessment of the presence of the HPV infection using PCR. Results: Among 105 patients, comprising 26 (24.8%) with malignant and 79 (75.2%) with benign lesions, the factors found to impact on malignancy were age at diagnosis, age at first pregnancy, number of pregnancies and hormonal status. However, malignancies was not related to abortion, late menopause, and early menarche. In none of the ovarian tissues (benign and malignant) was HPV DNA found. Conclusion: In this study HPV DNA could not be found in any epithelial ovarian tumors (benign and malignant) removed from 105 women; more studies with larger sample size are needed for a definite conclusion.

Herpes Simplex Virus and Langerhans Cell Histiocytosis.

BACKGROUND AND OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare histiocytic proliferative disorder of unknown etiology and mainly affects young children. The histological feature is granuloma-like proliferation of langerhans-type dendritic cells. Although the possible role of viruses such as Epstein-Barr virus (EBV, Human Herpes virus -4), Human Herpes virus-6 (HHV-6), Herpes Simplex virus (HSV) types 1 and 2 and Cytomegalovirus (CMV, Human Herpes virus-5) is suggested in the pathogenesis of LCH by some investigators, its exact pathophysiology has not been cleared yet. In this study, we investigated the presence of HSV types 1 and 2 in Iranian children with LCH. METHODS: In this retrospective study, we investigated the prevalence of presence of HSV types 1 and 2 (in 30 patients with LCH), using paraffin-embedded tissue samples and 30 age and tissue-matched controls (operated for reasons other than infectious diseases) from the Department of Pediatric Pathology, Tehran, Iran, by nested Polymerase Chain reaction method. No ethical issues arose in the study, because only the pathology reports were reviewed and patients were anonymous. RESULTS: We failed to find HSV types 1 and 2 DNA in any of the 30 patients with LCH or the control group. CONCLUSION: According to our findings, HSV types 1 and 2 do not appear to have any etiologic role in the pathogenesis of LCH in Iranian children. These results are in accordance with previous investigations with negative findings.

Cytomegalovirus and Langerhans Cell Histiocytosis: Is There a Link?

BACKGROUND: Langerhans cell histiocytosis is a rare proliferative histiocytic disease of unknown etiology. Histologically, it is characterized by granuloma-like proliferation of Langerhans-type dendritic cells derived from bone marrow. Many investigators have suggested the possible role of viruses such as Epstein-Barr virus, human herpesvirus-6 (HHV-6), herpes simplex virus (HSV) types 1 and 2, and Cytomegalovirus in the pathogenesis of Langerhans cell histiocytosis. OBJECTIVES: In this study, we have investigated the presence of Cytomegalovirus in Langerhans cell histiocytosis in Iranian children. PATIENTS AND METHODS: In this retrospective study, we have investigated the presence of Cytomegalovirus DNA expression, using paraffin-embedded tissue samples of 30 patients with Langerhans cell histiocytosis and 30 age and site-matched controls by qualitative Polymerase Chain Reaction (PCR) method. RESULTS: No significant difference in prevalence of Cytomegalovirus presence between patients and controls was found. Cytomegalovirus was found by qualitative PCR in only 2 (6.66%) out of 30 patients and in 1 (3.3%) of 30 control samples with a P value of 1 (1.00 > 0.05) using chi-square test with OR: 2.07; 95% CI of OR: 0.18 - 24.15. CONCLUSIONS: Our findings do not support the hypothesis of a possible role for Cytomegalovirus in the pathogenesis of Langerhans cell histiocytosis.

Telomere Shortening in Blood Leukocytes of Patients with Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation that is not completely reversible by administration of inhaled bronchodilators. Many studies propose that telomere length shortening might have occurred in COPD patients. We aimed to determine the telomere length in COPD patients and compare the results of non-smoking and smoking control subjects. MATERIALS AND METHODS: In our case-control study, 84 clinically stable COPD patients were recruited on admission to Masih Daneshvari Hospital. Eighty-five healthy controls were also selected including 45 non-smokers and 40 smokers admitted for diseases other than COPD. Spirometry was done for all subjects. Telomere length was measured by quantitative real time PCR as described by Cawthon. The telomere repeat copy number (T) to single-gene copy number (S) ratio was calculated using the comparative Ct method. RESULTS: The mean ±SD of age was 64.33±10.04 years in patients and 65.06 ±10.02 years in controls (P=0.693). The mean ±SD of FEV1 was 1.62±0.75 L in patients, 2.84±0.54 L in smoker controls and 2.83±0.56 L in non-smoker controls; significant differences were detected in this regard between cases and controls (P<0.001). T/S ratio was significantly lower in COPD patients (0.61±0.08) than in the control subjects (0.69±0.09) (P<0.001). However, telomere length was shorter in the patients than in controls in each age group (P<0.001). Additionally, there were no statistically significant differences in telomere length between the smoker and non-smoker control subjects. Regarding the correlation between BMI and telomere length, there were no significant differences among the patients and control groups. CONCLUSION: In conclusion, we found that telomere length in COPD patients was shorter than that in smoker and non-smoker controls, irrespective of age, sex, spirometric variables, BMI and history of cigarette smoking.

Disseminated Kaposi's Sarcoma with the Involvement of Penis in the Setting of HIV Infection.

Kaposi's sarcoma (KS) is a malignant proliferation of the endothelial cells. It typically presents with several vascular nodules on the skin and other organs. The penile localization of KS, particularly on the shaft area, is exceptional. We report an HIV-positive 34-year-old man who had multiple purplish-black plaques on his extremities and several small violaceous macules on the glans and shaft of the penis. Kaposi's sarcoma was diagnosed by histopathology.

Expression of two basic mRNA biomarkers in peripheral blood of patients with non-small cell lung cancer detected by real-time rt-PCR, individually and simultaneously.

INTRODUCTION: Although extensive research has been conducted on lung cancer markers, a singular clinically applicable marker has not been found yet. The objective of this study was to evaluate the sensitivity and the specificity of carcinoembryonic antigen (CEA) mRNA and lung-specific X protein (LUNX) mRNA biomarkers in peripheral blood to detect lung cancer individually and simultaneously. METHODS: Thirty patients affected by lung cancer and 30 healthy individuals were studied in this research. Three vials of cDNA were made from each sample after taking peripheral blood samples and extracting total RNA. Each sample was examined by the real-time RT-PCR technique. The result from each vial was then compared with the sensitivity of overall marker. RESULTS: The CEA mRNA was positive in 24 out of 30 lung cancer patients. Hence, its sensitivity was determined at 80%, differing significantly from that observed in healthy individuals, where 11 positive cases were seen. The overall sensitivity of this marker was significantly associated with positivity in vials 2 and 3 but not in vial 1. The LUNX mRNA was positive in 21 out of 30 patients, indicating 70% sensitivity. This finding significantly differed from that in healthy individuals. The overall sensitivity of this marker was significantly associated with positivity in vials 1 and 3, but not in vial 2. In 93.3% of the patients, at least one positive marker was observed. CONCLUSION: The mentioned mRNA could be suggested as sensitive and specific markers in peripheral blood for primary diagnosis of lung cancer.

Detection of Epstein-Barr Virus DNA in Langerhans Cell Histiocytosis.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare histiocytic proliferation of unknown etiology. It is characterized by granuloma-like proliferation of Langerhans-type dendritic cells and mainly affects young children. Although multiple investigators have suggested the possible role of viruses, such as Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), Herpes simplex virus (HSV) types 1 and 2, and Cytomegalovirus (CMV) in the pathogenesis of LCH, it remains, however, debated. OBJECTIVES: The EBV infection is reported to be associated with LCH. Nevertheless, no report could be found about involved Iranian children in English medical literature. In this study, we investigated the presence of EBV in Iranian children with LCH. PATIENTS AND METHODS: In this retrospective study, in which we investigated the prevalence of presence of EBV DNA in LCH, using paraffin-embedded tissue samples of 30 patients with LCH and 30 age and tissue-matched controls, who were operated for reasons other than infectious diseases (between the years 2002 and 2012), by real-time polymerase chain reaction (RT-PCR) method, in the department of pediatric pathology. No ethical issues arose in the study, because only the pathology reports were reviewed, retrospectively, and the patients were anonymous. RESULTS: There was a significant difference in prevalence of EBV presence between patients and controls. The EBV was found by RT-PCR in 19 (63.33%) out of 30 patients and only in eight (26.7%) of 30 control samples. The P = 0.004, was calculated using chi-square test (OR: 4.75; 95% CI: 1.58 ‒ 14.25). CONCLUSIONS: Our study is the first investigation performed on patients with LCH and its possible association with EBV in Iran. Considering the P = 0.004, which is statistically significant, the findings do support the hypothesis of a possible role for EBV in the pathogenesis of LCH. These results are in accordance with several previous investigations, with positive findings.

No evidence for a role of Merkel cell polyomavirus in small cell lung cancer among Iranian subjects.

Merkel cell polyomavirus (MCPyV), as a new member of polyomaviruses, has recently been discovered as a possible etiologic factor for human cancer. It was first detected in Merkel cell carcinoma (MCC). Small cell lung cancer (SCLC) is a malignant lung tumor which shares histopathological and genetic features with MCC, as both are of neuroendocrine origin. In this study, we investigated the presence of MCPyV DNA in SCLC specimens by real-time PCR. Our null hypothesis was that MCPyV is an etiologic factor in SCLC, as previously seen in MCC. Formalin-fixed and paraffin-embedded (FFPE) specimens were obtained from 50 patients, who underwent bronchoscopic biopsy and were diagnosed with SCLC between March 2010 and March 2012. Similarly, we obtained bronchoscopic biopsy specimens from 29 patients, who were diagnosed with non-small cell lung cancer (NSCLC). All samples were obtained at a single center (Masih Daneshvari Hospital, Tehran, Iran). Real-time PCR was done to detect the presence of MCPyV DNA. After excluding one specimen from the SCLC group due to loss of tumor tissue, we did not detect MCPyV DNA in samples from patients with either SCLC (the mean age 58.9 years, male/female ratio: 7.3/1) or NSCLC. Our results suggest that MCPyV does not play a role in the pathogenesis of SCLC, which is in accord with the results from other prior investigations.