Evaluation of prevalence and risk factors of hepatitis G virus infection among hemodialysis patients referred to Iranian Army Hospitals in Tehran during 2012-2013

Background: GB virus C (GBV-C) or hepatitis G virus (HGV) is a newly discovered and enveloped RNA positive-stranded flavivirus-like particle, which has not yet been proven to have major negative effects on liver. Objectives: Increasing the risk of blood-borne infections in hemodialysis patients is a main health care concern in different countries. Therefore, it is important to estimate the prevalence and risk factors of hepatitis G virus infection in Iranian hemodialysis patients to design standard prevention and treatment plans. Patients and Methods: In this multicenter observational or epidemiologic study, 138 patients who underwent hemodialysis in Iranian Army hospitals in Tehran were included. Serum HIV antibody (Ab), HCV antibody and HBS antigen (Ag) were assessed. Demographic data such as gender, age, blood group, cause of renal failure, dialysis onset and duration were collected from medical files. GBV-C/HGV was evaluated by nested reverse transcription polymerase chain reaction (RT-PCR) method. Then, all data were analyzed by SPSS ver. 13. Results: In total, 81 males and 57 females were included. The mean age of patients was 62.16 ± 14.86 years. Six (4.3) had positive results for GBV-C/HGV by RT-PCR. Except gender (P = 0.045) and duration of dialysis in a week (P 0.05). All patients had negative results for HIV Ab, HCV Ab and HBS Ag. Conclusions: Overall, 4.3 of patients had positive results for GBV-C/HGV and all negative for HIV, HCV and HBV. Further studies are needed to elucidate real prevalence, risk factors and characteristics of HGV infection in Iranian hemodialysis patients. © 2015, Kowsar Corp

Hepatitis A virus and Hepatitis E virus seroprevalence among blood donors in Tehran, Iran

Background: Hepatitis A virus (HAV) and Hepatitis E virus (HEV) are both transmitted by the fecal-oral route and are known as the leading causes of acute viral hepatitis in the world, especially in developing countries. There is a lack of updated data on HAV and HEV seroprevalence in Iran. Objectives: The aim of this study was to determine the seroprevalence of HAV and HEV among a group of blood donors in Tehran, Iran. Materials and Methods: A cross-sectional study was performed from July 2014 to December 2014, on a total of 559 blood donors referred to the Tehran blood transfusion center. The serum samples were tested for antibodies to HAV and HEV, using the enzyme-linked immunosorbent assay. Results: In the present study, 536 (95.9) cases were male and 23 (4.1) female with mean age of 38 years. Out of 559 blood donors, 107 (19.1) were first-time donors, 163 (29.2) lapsed donors and 289 (51.7) regular donors. Anti-HAV was found in 395 (70.7) and anti-HEV in 45 (8.1) of the blood donors. The HAV and HEV seroprevalence increased by age. There was no significant difference between genders in terms of anti-HAV and anti-HEV status. The HAV and HEV seroprevalence was significantly related to the level of education, where the donors with higher level of education had lower rate of HAV and HEV seroprevalence. The HAV and HEV seroprevalence was significantly higher in regular and lapsed donors than in first-time donors. Conclusions: The present study showed that both HAV and HEV infections are still endemic in Iran. © 2016, Kowsar Corp

Molecular epidemiology of hepatitis C virus genotypes in Bushehr province, Iran

Background and Objectives: Molecular epidemiology of hepatitis C virus (HCV) is very important for the treatment of hepatitis C infection. The aim of this study was to determine the distribution of HCV genotypes in Bushehr province (South West of Iran). Materials and Methods: A total of 100 patients who were detected as positive for HCV antibody (by using ELISA method and RIBA test) referred to Arya Virology Laboratory between 2007-2009 in order to molecular diagnosis and furthermore virus genotyping. After detection of HCV, RNA genotyping of virus was done by using genotype specific primers. Results: Genotype 1a was found in 49% of the patients and genotype 3a was found in 40% of the patients and 1b in 5% of patients, while the genotype of the virus could not be identified in 5% of the patients. Finally, in 1% of patients coinfection due to 1a-3a genotypes was identified. Conclusion: The dominant genotype of HCV in Bushehr province, Iran, was determined as 1a.with acute hepatitis C ultimately develop chronic infection1. Only a minority of cases of acute HCV recover completely, with spontaneous virus eradication. In most cases the acute infection progresses to chronicity. Chronic HCV infection is defined as an infection that persists for more than 6 months, with or without clinical manifestations of hepatic or extrahepatic disease. Chronic type of this infection can cause cirrhosis, liver failure, and liver cancer. HCV infection is a global health problem and it is estimated that 200 million people of the world population are infected5. The global spread of chronic HCV infection coincided with the widespread use of transfused blood and blood products and with the expansion of intravenous drug use but decreased prior to the wide implementation of anti-HCV screening6. There are at least six major genotypes designated by Arabic numerals and more than 50 subtypes of HCV identified by lower case letters. The different genotypes have different geographic distributions1,4. Genotype determination of HCV is one of the most important factors in order to prediction of the viral persistency, pathogenicity and resistancy to antivirals7. The success and the treatment period of interferon and ribavirin seems to be related to the genotype of virus8. Furthermore, HCV genotyping is a useful tool to determine its molecular epidemiology, as they are indicative of transmission route of infection9,10. There is no published data about the distribution of HCV genotypes from Bushehr province (South West of Iran). Prevalence of HCV genotypes in Bushehr is an issue that is not sufficiently investigated and there is a need, therefore, to study this in detail

Assessment of indoor air pollution exposure in urban hospital microenvironments

Hospitals are microenvironments containing populations with potentially enhanced sensitivity to air pollution. The objectives of this study were to characterize the concentration of indoor and outdoor size-fractionated particulate matter (PM) at two urban hospital sites in Kashan, Iran, and to evaluate the relationship between indoor and outdoor PM levels. PM 1.0 , PM 2.5 , and PM 10 concentrations were measured over a 3-month period outside each hospital with parallel sampling at four indoor locations in patient wards. The results indicated that mean indoor concentrations at the sampling sites (PM 1.0 = 17.8 μg/m 3 , PM 2.5 = 45.5 μg/m 3 , and PM 10 = 162.7 μg/m 3 ) were found to be lower than outdoors levels (PM 1.0 = 20.6 μg/m 3 , PM 2.5 = 62.1 μg/m 3 , and PM 10 = 300.6 μg/m 3 ). Outdoor and indoor PM mass concentrations were associated with PM 1.0 , PM 2.5 , and PM 10.0 . Ambient wind speed also influenced the indoor/outdoor relationship for PM 1.0 and PM 2.5 but not for PM 10 . The average I/O ratios for PM 2.5 in the intensive care unit (ICU) and children�s ward at Shahid Beheshti Hospital were close to or above 1.00. Indoor PM 1.0 and PM 2.5 concentrations were found to be positively associated with outdoor PM 1.0 and PM 2.5 concentrations, but no relationship was observed with PM 10 . The present findings may inform policymakers in implementing evidence-based efforts for the aim of improving the indoor air quality in closed and confined spaces. © 2018, Springer Nature B.V

Molecular epidemiology of Kaposi�s sarcoma-associated herpes virus, and risk factors in HIV-infected patients in Tehran, 2014

Background: Kaposi�s sarcoma (KS) remains themostcommonmalignancyamongHIV-infected patients. Humanherpesvirus type- 8 (HHV-8) is regarded as the infectious etiological agent of Kaposi�s sarcoma (KSHV). Diagnostic procedures associated with KSHV are not routinely performed in HIV-infected subjects. Objectives: The main objective of this study is to obtain information on KSHV epidemiology in Iranian HIV-infected individuals. Patients and Methods: In the present cross-sectional study, 109 patients with established HIV infection, who visited a governmental and referral center for HIV screening in Tehran (Tehran west health center (TWHC)) between May 2014 and July 2015 were enrolled according to the convenience sample strategy. After peripheral blood collection, isolation of plasma and peripheral blood mononuclear cell (PBMC) compartments, DNA extraction was performed. KSHV DNA was analyzed by nested polymerase chain reaction (nested PCR) using primers from ORF-26 (virus minor capsid). Results: Among all 109 HIV-infected patients, 67 (61.5) were male, with an age range of 2 - 64 years (mean±standard deviation 35.8 ±13.3). KSHV DNA was found in PBMC and plasma samples of six (5.5) and four (3.6) patients, respectively. Conclusions: This study revealed a considerable prevalence of KSHV DNA, during latent and lytic phases, among HIV-infected patients. Risk factors for KSHV infection acquisition and concurrent. 0+infection with HIV were also evaluated. Diagnosis of KSHV in the group could be helpful for prognosis of Kaposi�s sarcoma and clinical management. © 2016, Iranian Red Crescent Medical Journal

Drug-related mutational patterns in hepatitis B virus (HBV) reverse transcriptase proteins from Iranian treatment-Naïve chronic HBV patients

Background: Immunomodulators and Nucleotide analogues have been used globally for the dealing of chronic hepatitis B virus (HBV) infection. However, the development of drug resistance is a major limitation to their long-term effectiveness. Objectives: The aim of this study was to characterize the hepatitis B virus reverse transcriptase (RT) protein variations among Iranian chronic HBV carriers who did not receive any antiviral treatments. Materials and Methods: Hepatitis B virus partial RT genes from 325 chronic in active carrier patients were amplified and directly sequenced. Nucleotide/amino acid substitutions were identified compared to the sequences obtained from the database. Results: All strains belonging to genotype D.365 amino-acid substitutions were found. Mutations related to lamivudine, adefovir, telbivudine, and entecavir occurred in (YMDD) 4% (n = 13), (SVQ) 17.23% (n = 56), (M204I/V + L180M) 2.45% (n = 8) and (M204I) 2.76% (n = 9) of patients, respectively. Conclusions: RT mutants do occur naturally and could be found in HBV carriers who have never received antiviral therapy. However, mutations related to drug resistance in Iranian treatment-naïve chronic HBV patients were found to be higher than other studies published formerly. Chronic HBV patients should be monitored closely prior the commencement of therapy to achieve the best regimen option. © 2013, KOWSAR Corp

Compromised Hippocampal Neuroplasticity in the Interferon-α and Toll-like Receptor-3 Activation-Induced Mouse Depression Model.

Disrupted neuronal plasticity due to subtle inflammation is considered to play a fundamental role in the pathogenesis of major depressive disorder. Interferon-α (IFN-α) potentiates immune responses against viral pathogens that induce toll-like receptor-3 (TLR3) activation but evokes severe major depressive disorder in humans by mechanisms that remain insufficiently described. By using a previously established mouse model of depression induced by combined delivery of IFN-α and polyinosinic:polycytidylic acid (poly(I:C)), a TLR3 agonist, we provide evidence that IFN-α and poly(I:C) reduce apical dendritic spine density in the hippocampal CA1 area ex vivo via mechanisms involving decreased TrkB signaling. In vitro, IFN-α and poly(I:C) treatments required neuronal activity to reduce dendritic spine density and TrkB signaling. The levels of presynaptic protein vesicular glutamate transporter (VGLUT)-1 and postsynaptic protein postsynaptic density-95 (PSD95) were specifically decreased, whereas the expression of both synaptic and extrasynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor 1 (AMPAR1) was increased by IFN-α and poly(I:C) delivery. Patch clamp recordings in primary hippocampal neurons revealed that morphological changes at the synapse induced by IFN-α and poly(I:C) costimulation were accompanied by an increased action potential threshold and action potential frequency, indicative of impaired neuronal excitability. Taken together, IFN-α and poly(I:C) delivery leads to structural and functional alterations at the synapse indicating that compromised neuroplasticity may play an integral role in the pathogenesis of immune response-induced depression

A Sequential Targeting Strategy Interrupts AKT-Driven Subclone-Mediated Progression in Glioblastoma

Purpose: Therapy resistance and fatal disease progression in glioblastoma are thought to result from the dynamics of intra-tumor heterogeneity. This study aimed at identifying and molecularly targeting tumor cells that can survive, adapt, and subclonally expand under primary therapy. Experimental design: To identify candidate markers and to experimentally access dynamics of subclonal progression in glioblastoma, we established a discovery cohort of paired vital cell samples obtained before and after primary therapy. We further used two independent validation cohorts of paired clinical tissues to test our findings. Follow-up preclinical treatment strategies were evaluated in patient-derived xenografts. Results: We describe, in clinical samples, an archetype of rare ALDH1A1+ tumor cells that enrich and acquire AKT-mediated drug resistance in response to standard-of-care temozolomide (TMZ). Importantly, we observe that drug resistance of ALDH1A1+ cells is not intrinsic, but rather an adaptive mechanism emerging exclusively after TMZ treatment. In patient cells and xenograft models of disease, we recapitulate the enrichment of ALDH1A1+ cells under the influence of TMZ. We demonstrate that their subclonal progression is AKT-driven and can be interfered with by well-timed sequential rather than simultaneous antitumor combination strategy. Conclusions: Drug-resistant ALDH1A1+/pAKT+ subclones accumulate in patient tissues upon adaptation to TMZ therapy. These subclones may therefore represent a dynamic target in glioblastoma. Our study proposes the combination of TMZ and AKT inhibitors in a sequential treatment schedule as a rationale for future clinical investigation

ATRT–SHH comprises three molecular subgroups with characteristic clinical and histopathological features and prognostic significance

Atypical teratoid/rhabdoid tumor (ATRT) is an aggressive central nervous system tumor characterized by loss of SMARCB1/INI1 protein expression and comprises three distinct molecular groups, ATRT–TYR, ATRT–MYC and ATRT–SHH. ATRT–SHH represents the largest molecular group and is heterogeneous with regard to age, tumor location and epigenetic profile. We, therefore, aimed to investigate if heterogeneity within ATRT–SHH might also have biological and clinical importance. Consensus clustering of DNA methylation profiles and confirmatory t-SNE analysis of 65 ATRT–SHH yielded three robust molecular subgroups, i.e., SHH-1A, SHH-1B and SHH-2. These subgroups differed by median age of onset (SHH-1A: 18 months, SHH-1B: 107 months, SHH-2: 13 months) and tumor location (SHH-1A: 88% supratentorial; SHH-1B: 85% supratentorial; SHH-2: 93% infratentorial, often extending to the pineal region). Subgroups showed comparable SMARCB1 mutational profiles, but pathogenic/likely pathogenic SMARCB1 germline variants were over-represented in SHH-2 (63%) as compared to SHH-1A (20%) and SHH-1B (0%). Protein expression of proneural marker ASCL1 (enriched in SHH-1B) and glial markers OLIG2 and GFAP (absent in SHH-2) as well as global mRNA expression patterns differed, but all subgroups were characterized by overexpression of SHH as well as Notch pathway members. In a Drosophila model, knockdown of Snr1 (the fly homologue of SMARCB1) in hedgehog activated cells not only altered hedgehog signaling, but also caused aberrant Notch signaling and formation of tumor-like structures. Finally, on survival analysis, molecular subgroup and age of onset (but not ASCL1 staining status) were independently associated with overall survival, older patients (> 3 years) harboring SHH-1B experiencing relatively favorable outcome. In conclusion, ATRT–SHH comprises three subgroups characterized by SHH and Notch pathway activation, but divergent molecular and clinical features. Our data suggest that molecular subgrouping of ATRT–SHH has prognostic relevance and might aid to stratify patients within future clinical trials. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00401-022-02424-5

Identification of Ischemic Regions in a Rat Model of Stroke

Investigations following stroke first of all require information about the spatio-temporal dimension of the ischemic core as well as of perilesional and remote affected tissue. Here we systematically evaluated regions differently impaired by focal ischemia.Wistar rats underwent a transient 30 or 120 min suture-occlusion of the middle cerebral artery (MCAO) followed by various reperfusion times (2 h, 1 d, 7 d, 30 d) or a permanent MCAO (1 d survival). Brains were characterized by TTC, thionine, and immunohistochemistry using MAP2, HSP72, and HSP27. TTC staining reliably identifies the infarct core at 1 d of reperfusion after 30 min MCAO and at all investigated times following 120 min and permanent MCAO. Nissl histology denotes the infarct core from 2 h up to 30 d after transient as well as permanent MCAO. Absent and attenuated MAP2 staining clearly identifies the infarct core and perilesional affected regions at all investigated times, respectively. HSP72 denotes perilesional areas in a limited post-ischemic time (1 d). HSP27 detects perilesional and remote impaired tissue from post-ischemic day 1 on. Furthermore a simultaneous expression of HSP72 and HSP27 in perilesional neurons was revealed.TTC and Nissl staining can be applied to designate the infarct core. MAP2, HSP72, and HSP27 are excellent markers not only to identify perilesional and remote areas but also to discriminate affected neuronal and glial populations. Moreover markers vary in their confinement to different reperfusion times. The extent and consistency of infarcts increase with prolonged occlusion of the MCA. Therefore interindividual infarct dimension should be precisely assessed by the combined use of different markers as described in this study