Identification of seven types of pili in Mycobacterium tuberculosis: Using atomic force microscopy.

Background: Pili are polymeric, hydrophobic, proteinaceous structures generally composed of a major repeating subunit called pilin and, in some cases, a minor tip-associated adhesin subunit. Pili are involved in many virulence-associated functions, such as biofilm formation, adherence, and colonization of mucosal surfaces. Methods: Mycobacterium tuberculosis (MTB) strains were isolated from clinically and laboratory-confirmed cases of tuberculosis (TB). The TB isolates were subjected to the Xpert MTB/rifampicin test and then, further susceptibility testing was performed on them against first- and second-line drugs using proportional methods. Thereafter, the selected isolates were subculture in Dubos Tween-albumin liquid culture medium, and at their exponential growth phase (OD600 = 0.05 (5 × 106 colony-forming unit/mL), cells were observed under atomic force microscopy (AFM). For each isolate, 15-20 steel sample packs were prepared and observed under AFM. Here, the data presented are the result of average observation. Results: Under AFM, seven different types of pili were detected, out of which four types, i.e., Type III, Type IV secretion pili, and Type IV-like pili, curli-like pili (MTP) were similar to reported pili in Gram-negative and Gram-positive bacteria. Whereas the other three forms, i.e., Type V (relief funnel pili), Type VI (adhesion tapering), and Type VII (adhesion flap pili), were newly identified and named according to their appearance. Both Types of IV pili were detected in all clinical isolates irrespective of their susceptibility patterns, although significant differences were observed from the side of their protruding. Type Curli pili is similar in appearance in all clinical isolates. Types VI and VII were detected only in extensively drug-resistant and totally drug-resistant-TB isolates (100%). The Type III pili (secretion needle pili) was present in both susceptible- and drug-resistant bacilli, although in drug-resistant strains, we found a considerable difference in their length (50 µ ±10 nm in length) and sometimes, they also had tapering at end. The Type V pili was seen in susceptible isolates but it was at the resting stage (100%; lying aside of cell wall) whereas in drug-resistant isolates, they were getting apart from the cell wall of bacilli with a clear tapering or funnel shape structure. Conclusion: The results of this study highlight the importance of new types of pili expressions in respect of susceptibility patterns in TB. The identified new types of pili would be promising approaches for the treatment and prevention of drug-resistant TB, which needs further investigation.

Microbiome modulation in inflammatory diseases: Progress to microbiome genetic engineering.

Recent developments in sequencing technology and analytical approaches have allowed researchers to show that the healthy gut microbiome is very varied and capable of performing a wide range of tasks. The importance of gut microbiota in controlling immunological, neurological, and endocrine function is becoming well-recognized. Thereby, numerous inflammatory diseases, including those that impact the gastrointestinal system, as well as less obvious ones, including Rheumatoid arthritis (RA), cancer, gestational diabetes (GD), type 1 diabetes (T1D), and type 2 diabetes (T2D), have been linked to dysbiotic gut microbiota. Microbiome engineering is a rapidly evolving frontier for solutions to improve human health. Microbiome engineering seeks to improve the function of an ecosystem by manipulating the composition of microbes. Thereby, generating potential therapies against metabolic, inflammatory, and immunological diseases will be possible through microbiome engineering. This essay first provides an overview of the traditional technological instruments that might be used for microbiome engineering, such as Fecal Microbiota Transplantation (FMT), prebiotics, and probiotics. Moreover, we will also discuss experimental genetic methods such as Metagenomic Alteration of Gut microbiome by In situ Conjugation (MAGIC), Bacteriophage, and Conjugative plasmids in manipulating intestinal microbiota.

Prevalence of Anemia and its Relation with Shwachman Score in Children with Cystic Fibrosis.

Background: Cystic fibrosis is a chronic and progressive genetic disease with a worldwide prevalence. As the disease progresses, symptoms develop, and make its management more challenging. Accumulating evidence suggests that early diagnosis of CF can significantly contribute to preventing reported nutritional problems including anemia, vitamin deficiencies, and hypoalbuminemia. This cross-sectional study was conducted to assess disease severity in cystic fibrosis patients using the Shwachman-Kulczycki score, as well as to determine its relation with anemia and vitamin D deficiency. Materials and Methods: Clinical and CF-related laboratory data were collected from the medical records of 57 CF patients with a definitive diagnosis. At the time of diagnosis, physicians performed simultaneous, blood sampling and scoring of patients using the Shwachman scoring system. Results: The mean age of patients was 16.12±6.48 years. Total scores of 86-100, 71-85, 56-70, 41-55, and <40, were reported in 5.4%, 7.1%, 14.3%, 14.3%, and 58.9% of CF patients, respectively. A significant correlation was found between disease severity and patients' age (P=0.02). The analysis also showed that the disease severity was significantly higher in anemic patients when compared to non-anemics (p =0.006). Based on the results, 33 patients with normochromic, 11 patients with microcytic, and 6 patients with macrocytic anemia were diagnosed in this study. We did not find a significant difference between disease severity and vitamin D levels (P=0.150). Conclusion: The scoring system used in the current study could reflect properly the clinical status of CF patients. However, simultaneous use of various methods using a larger sample size for comparison of results is suggested to improve the accuracy of findings.

Non-coding RNAs/DNMT3B axis in human cancers: from pathogenesis to clinical significance.

Cancer is a complex disease with many contributing factors, and researchers have gained extensive knowledge that has helped them understand the diverse and varied nature of cancer. The altered patterns of DNA methylation found in numerous types of cancer imply that they may play a part in the disease's progression. The human cancer condition involves dysregulation of the DNA methyltransferase 3 beta (DNMT3B) gene, a prominent de novo DNA methyltransferase, and its abnormal behavior serves as an indicator for tumor prognosis and staging. The expression of non-coding RNAs (ncRNAs), which include microRNAs (miRNA), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), is critical in controlling targeted gene expression and protein translation and their dysregulation correlates with the onset of tumors. NcRNAs dysregulation of is a critical factor that influences the modulation of several cellular characteristics in cancerous cells. These characteristics include but are not limited to, drug responsiveness, angiogenesis, metastasis, apoptosis, proliferation, and properties of tumor stem cell. The reciprocal regulation of ncRNAs and DNMT3B can act in synergy to influence the destiny of tumor cells. Thus, a critical avenue for advancing cancer prevention and treatment is an inquiry into the interplay between DNMT3B and ncRNAs. In this review, we present a comprehensive overview of the ncRNAs/DNMT3B axis in cancer pathogenesis. This brings about valuable insights into the intricate mechanisms of tumorigenesis and provides a foundation for developing effective therapeutic interventions.

MicroRNA-122 in human cancers: from mechanistic to clinical perspectives.

MicroRNAs (miRNAs) are endogenous short non-coding RNAs that can regulate the expression of target genes post-transcriptionally and interact with mRNA-coding genes. MiRNAs play vital roles in many biological functions, and abnormal miRNA expression has been linked to various illnesses, including cancer. Among the miRNAs, miR-122, miR-206, miR-21, miR-210, miR-223, and miR-424 have been extensively studied in various cancers. Although research in miRNAs has grown considerably over the last decade, much is yet to be discovered, especially regarding their role in cancer therapies. Several kinds of cancer have been linked to dysregulation and abnormal expression of miR-122, indicating that miR-122 may serve as a diagnostic and/or prognostic biomarker for human cancer. Consequently, in this review literature, miR-122 has been analyzed in numerous cancer types to sort out the function of cancer cells miR-122 and enhance patient response to standard therapy.

MicroRNA-206 in human cancer: Mechanistic and clinical perspectives.

MicroRNAs (miRNAs), small non-coding RNAs approximately 20-25 nt in length, play important roles via directly binding to the corresponding 3' UTR of target mRNAs. Recent research has shown that miRNAs cover a wide range of diseases, including several types of cancer. It is interesting to note that miR-206 operates as a tumor suppressor and is downregulated in abundant cancer types, such as breast cancer, lung cancer, colorectal cancer, and so forth. Interestingly, a growing number of studies have also reported that miR-206 could function as an oncogene and promote tumor cell proliferation. Thereby, miR-206 may act as either oncogenes or tumor suppressors under certain conditions. In addition, it was widely acknowledged that restoring tumor-suppressor miR-206 has emerged as an unconventional cancer therapy strategy. Therefore, miR-206 might be a newfangled procedure for achieving a more significant treatment outcome for cancer patients. This review summarizes the role of miR-206 in several cancer types and the contributions made between miR-206 and the diagnosis, treatment, and drug resistance of solid tumors.

Effect of COVID-19 pandemic on incidence of mycobacterial diseases among suspected tuberculosis pulmonary patients in Tehran, Iran.

Background: Recent pandemic of coronavirus SARS-CoV-2 (COVID-19) caused limitations in the country's strategies to fight against mycobacterial infections. The aim of this study was to compare the suspected tuberculosis (TB) pulmonary patients before and during the COVID-19 pandemic (January 2018-December 2021) who were referred to the National Reference TB Laboratory (NRL TB), Tehran, Iran. The mycobacterial isolated strains were identified and compared with previous data. Methods: A total of 16,899 clinical samples collected from 7041 suspected pulmonary TB patients were received from 2018 to 2021. Primary isolation of Mycobacterium isolates was done on Löwenstein-Jensen medium. Then, the DNA was extracted from acid-fast bacillus culture-positive samples and identification was performed by IS6110, Hsp65, and 16S-23S rRNA genes using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, and nested PCR methods. Results: A total of 11679 specimens (69.1%) from 4866 suspected TB patients were collected in 2018-2019 and 5220 specimens (30.8%; from 2175 patients) in 2020-2021. Out of 11679 specimens, 2046 samples that belong to 852 patients were infected with Mycobacterium tuberculosis, and the remaining were non-TB Mycobacterium (NTM) species (n = 244) isolated from 102 patients. The cultures for 12894 specimens were either negative (76.3%) or contaminated (845/16899; 5%). A comparison of the total number of patients who were referred for diagnosis and treatment (954/666 patients, P > 0.05) showed a 30.1% reduction during the COVID-19 pandemic. Although, with these low number of patients, the significant increases of NTM species (P < 0.05) among suspected TB pulmonary patients were observed. Besides, new species of NTM, for example, Mycobacterium peregrinum and Mycobacterium montefiorense, were detected. For the past 20 years, these two species were not reported from pulmonary patients in Iran. Conclusions: During the pandemic of COVID-19, the TB diagnosis network became irregular, as a consequence, many patients could not reach the treatment center, and this could increase the circulation of mycobacterial diseases (TB and NTM). The study shows the emergence of new opportunistic NTM species also.

Correlation of single-nucleotide polymorphism at interferon-gamma R1 (at Position - 56) in positive purified protein derivative health workers with COVID-19 infection.

Background: The aim of the present study was to investigate the susceptibility of purified protein derivative (PPD) plus health-care workers to SARS-CoV-2 (COVID-19). For this reason, single-nucleotide polymorphism (SNP) of interferon-gamma (IFN-γ) gene at position +2109 and IFN-γ receptor 1 (R1) at position -56 was assessed in PPD plus group before and after COVID-19 infection (2017-2018; 2020-2021). Methods: The selected study cases (n = 100) that were working in tuberculosis (TB) unite (5-10 years) with PPD positivity >15 mm (16-20 mm) were included in this investigation. Sampling was done twice, once before and after the COVID-19 pandemic. Group A contains 50 samples collected from the GenBank TB laboratory that belong to TB staff before the pandemic (2017-2018). The other sample (Group B; 2021) was collected from the same unite during the COVID-19 pandemic. The SNP in the IFN-γ gene (+2109; 670 bp) and IFN-γ R 1 (-56; 366 bp) was performed using a specific primer and the polymerase chain reaction products were digested using restriction enzyme Fau I and Bts I, respectively. Statistical analyses were used to obtain the frequency of alleles among all studied cases. The confidence intervals (CIs) and t-test were calculated using the SPSS and GraphPad Prism software. Results: In overall, the most frequent genotype in Group A was AA (41/50; 82%) and Group B was 76% (38/50) in position + 2109 (odds ratio [OR] = 0.69, 95% CI, 0.26-1.83, and P = 0.46). Although in position -56, the most frequent genotype in Group A was TT (35/50; 70%) which significantly was than Group B TT (15/50; 30%) (OR = 0.184, 95% CI, 0.78-0.43, and P = 0.00). The frequency of allele A was more in both groups at position + 2109 (OR = 0.815, 95% CI, 0.23-2.86, and P = 0.75), whereas the dominate allele at position -56 was T in Group A (OR = 1.37, 95% CI, 0.62-3.02, and P = 0.42). Conclusion: No significant differences were observed in + 2109 in genotype among Group A and B. The main differences were seen in IFN-γ R1 at position (-56) between Group A and B. Hence, the IFN-γ R1 may play important role in COVID-19 infection. However, more study is needed to clear the IFN-γ correlation to COVID-19 infection.

Assessment of Cystic Fibrosis Distribution Based on Air Pollution by Geographical Information System (GIS).

Background: It is widely accepted that concerns have been recently raised regarding the impact of air pollution on the health of children with cystic fibrosis (CF). Air pollution probably affects the exacerbation of CF and its laboratory findings. On the other hand, the World Health Organization (WHO) has asked all countries to update their data and reports on the distribution and prevalence of CF in different areas. The purpose of the present study was to investigate the distribution and prevalence of CF based on the levels of atmospheric pollutants, such as PM10, PM2.5, SO2, NO2, CO, and O3 in 22 zones of Tehran, and to report the abnormal laboratory findings that might indicate the exacerbation of CF. Materials and Methods: The studied statistical population included children with CF referred to Masih Daneshvari Hospital from 2003 to 2020. Demographic data, location of living area, and laboratory findings were extracted from patient records. The geographic information system (GIS) was applied to indicate the distribution and dispersion of the disease. The information related to air pollutants was collected from all stations in Tehran during the studied period by the Department of Environment of Tehran Province, and the average levels were used for final reporting. Results: The analysis results on 287 CF patients demonstrated that the risk of disease exacerbation significantly increased by the presence of air pollutants. In areas with multiple air pollutants, more laboratory findings were observed to be abnormal, and the lower survival rate for patients with CF was recorded. Investigating the CF distribution pattern based on climatic layers and above mean sea level (AMSL) indicated that distribution of the disease was higher in dry areas with lower AMSL and the higher volume of the atmospheric pollutants, which were primarily centralized in southern and central Tehran. Conclusion: Environmental factors, such as air pollution, can be considered vital parameters, along with high-risk factors, such as pure and integrated race, migration, and mutation, influencing the prevalence and exacerbation of CF symptoms. Considering the higher prevalence of CF in deprived areas of Tehran, households' cultural and economic level appears to be a factor in the lack of diagnostic screening and prevention of CF in these areas. On the other hand, continuous monitoring of the air pollution caused by traffic and giving warnings to CF patients and their parents is particularly important.

Molecular Dynamic Simulations and Molecular Docking as a Potential Way for Designed New Inhibitor Drug without Resistance.

Mycobacterium tuberculosis is the cause of tuberculosis in humans and is responsible for more than 2 million deaths per year. Despite the development of anti-tuberculosis drugs (Isoniazid, Rifampicin, Ethambutol, pyrazinamide, streptomycin, etc.) and the TB vaccine, this disease has claimed the lives of many people around the world. Drug resistance in this disease is increasing day by day. Conventional methods for discovering and developing drugs are usually time-consuming and expensive. Therefore, a better method is needed to identify, design, and manufacture TB drugs without drug resistance. Bioinformatics applications in obtaining new drugs at the structural level include studies of the mechanism of drug resistance, detection of drug interactions, and prediction of mutant protein structure. In the present study, computer-based approaches including molecular dynamics simulation and molecular docking as a novel and efficient method for the identification and investigation of new cases as well as the investigation of mutated proteins and compounds will be examined .

Non-coding RNA in SARS-CoV-2: Progress toward therapeutic significance.

The recently developed pathogenic virus, SARS-CoV-2, was found in the Hubei Province, China. Giving rise to a broad spectrum of symptoms, SARS-CoV-2 rapidly spread across the globe, causing multi-systemic and dangerous complications, with death in extreme cases. Thereby, the number of research cases increases every day on preventing infection and treating its resulting damage. Accumulating evidence suggests noncoding RNAs (ncRNAs) are necessary for modifying virus infection and antiviral immune reaction, along with biological processes regulating SARS-CoV-2 and subsequent disease states. Therefore, understanding these mechanisms might provide a further understanding of the pathogenesis and feasible therapy alternatives against SARS-CoV2. Consequently, the molecular biology of SARS-CoV-2, ncRNA's role in its infection, and various RNA therapy tactics against the virus have been presented in this review section.

The role of interferon-gamma and interferon-gamma receptor in tuberculosis and nontuberculous mycobacterial infections.

Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM) remain the leading causes of lung disease and mortality worldwide. Interferon-gamma (IFN-γ) and its receptor (IFN-γR) play a key role in mediating immunity against Mtb and NTM. This study was conducted as a systematic review; all information was collected from databases such as: PubMed, Scopus, Medline, SID, and medical databases. Finally, all the collected data were reviewed, and all content was categorized briefly. There is growing evidence that IFN-γ plays an important role in host defense against these two intracellular pathogens by activating macrophages. In addition, IFN-γ has been shown to be an integral part of various antibacterial methods such as granuloma formation and phagosome-lysosome fusion, both of which lead to the death of intracellular Mycobacterium. As a result, its absence is associated with overgrowth of intracellular pathogens and disease caused by Mtb or Mycobacterium nontuberculosis. We also look at the role of IFN-γR in Mtb or NTM because IFN-γ acts through IFN-γR. Finally, we introduce new approaches to the treatment of M. tuberculosis complex (MTC) and NTM disease, such as cell and gene-based therapies that work by modulating IFN-γ and IFN-γR.

Characterization of Clinical Isolates of Mycobacterium simiae Using Drug Susceptibility Tests and Molecular Analyses.

Mycobacterium simiae is an emerging nontuberculous mycobacterium (NTM) and an opportunistic pathogen which is described mainly in Asia and presents in the environment that can cause pulmonary infection. The objective of this study is to characterize M. simiae clinical isolates using mycobacterial interspersed repetitive unit variable-number tandem repeats (MIRU-VNTR) typing for the differentiation of the strains. A total of 169 clinical isolates of NTM were recovered from patients suspected of having tuberculosis (TB)-like and related infections. After isolation and identification of mycobacterial strains by conventional biochemical and PCR-based tests, M. simiae strains were confirmed using restriction fragment length polymorphism (RFLP)-based identification assay. Furthermore, drug susceptibility and MIRU-VNTR typing was performed using on the clinical isolates of M. simiae. Out of 169 NTM strains, 92 (54.4%) isolates were identified as M. simiae. Antibiotic susceptibility experiments indicated that all 92 M. simiae isolates were resistant to first line antimycobacterial agents. Moreover, 8 (8.6%) M. simiae isolates were resistant to ciprofloxacin; and 6 (6.5%) were resistant to both amikacin and kanamycin, while the remaining were susceptible to second line antimycobacterial agents. MIRU-VNTR analysis showed that the M. simiae isolates were classified in four distinct M. simiae clusters and two single types. The minimum spanning analysis revealed that the isolates were grouped in three complexes. The data suggested that MIRI-VNTR typing is useful for typing of M. simiae isolates, however, MIRU-16 locus was absolutely absent in M. simiae.

An Overview of Genetic Information of Latent Mycobacterium tuberculosis.

Mycobacterium tuberculosis has infected more than two billion individuals worldwide, of whom 5%-10% have clinically active disease and 90%-95% remain in the latent stage with a reservoir of viable bacteria in the macrophages for extended periods of time. The tubercle bacilli at this stage are usually called dormant, non-viable, and/or non-culturable microorganisms. The patients with latent bacilli will not have clinical pictures and are not infectious. The infections in about 2%-23% of the patients with latent status become reactivated for various reasons such as cancer, human immunodeficiency virus infection, diabetes, and/or aging. Many studies have examined the mechanisms involved in the latent state of Mycobacterium and showed that latency modified the expression of many genes. Therefore, several mechanisms will change in this bacterium. Hence, this study aimed to briefly examine the genes involved in the latent state as well as the changes that are caused by Mycobacterium tuberculosis. The study also evaluated the relationship between the functions of these genes.

A Homozygous Truncating Mutation in NALCN Causing IHPRF1: Detailed Clinical Manifestations and a Review of Literature.

Infantile hypotonia, with psychomotor retardation and characteristic facies 1 (IHPRF1), is a rare disorder characterized by global developmental delay and dysmorphic features. This syndrome is caused by genetic anomalies within the NALCN gene. The current report examines a 9-year-old female IHPRF1 patient. Our objective was to contribute to the delineation of the underlying factors influencing this rare condition. Whole exome sequencing (WES) was utilized to identify the disease-causing mutation in the affected individual. Subsequently, Sanger sequencing was performed for the patient, her parents, and two close relatives in order to confirm the detected mutation. Moreover, detailed clinical examinations including EEG, echocardiography, and biochemical/physical tests were carried out to elucidate the effects of the mutation. WES identified a homozygous nonsense mutation in the NALCN gene (c.2563C>T p.R855X). This mutation was confirmed by Sanger sequencing in the patient and her family members and segregated with the autosomal recessive inheritance pattern of IHPRF1. Moreover, genotype-phenotype correlation analysis confirmed the disease-causing nature of this mutation. The current report provides the first detailed description of a patient with this homozygous nonsense mutation (c.2563C>T p.R855X) and expands the clinical spectrum of IHPRF1 disease. Possible influences of sex and other factors on this disease are discussed and a review of the literature is also provided.

Human genetic background in susceptibility to tuberculosis.

Tuberculosis (TB), especially in developing countries, is a major threat to human health. The pathogenesis of TB remains poorly understood, and <5%-10% of individuals infected with Mycobacterium tuberculosis (MTB) will develop clinical disease. The human genetic factors contributing to susceptibility or resistance to TB pathogenesis have been investigated by high-throughput and low-throughput association studies. Genetic polymorphisms of several genes including TLR, IGRM, VDR, ASAP1, AGMO, FOXP1, and UBLCP1 effect on the disease phenotype and also the outcome of TB treatment. Recently, microRNAs (miRNAs), which negatively regulated gene expression at the posttranscriptionally level, have gained increasing attention due to their altered expression in various human diseases, including some infections. They are crucial posttranscriptional regulators of immune response in both innate and adaptive immunity. It has been established in recent studies that the host immune response against MTB is regulated by many miRNAs, most of which are induced by MTB infection. Moreover, differential expression of miRNAs in TB patients may help distinguish between TB patients and healthy individuals or latent TB. In this review, we summarize and discuss the literature and highlight the role of selected single nucleotide polymorphisms and miRNAs that have been associated with TB infection.

Computerised tomography scan in multi-drug-resistant versus extensively drug-resistant tuberculosis.

PURPOSE: Multi-drug-resistant tuberculosis (MDR-TB) is simultaneously resistant to isoniazid and rifampin. Of course, this germ may also be resistant to other anti-tuberculosis drugs. Patients with extensively drug-resistant tuberculosis (XDR-TB) are also resistant to all types of fluoroquinolone and at least one of the three injectable medications: amikacin, clarithromycin, or kanamycin, in addition to isoniazid and rifampin. Therefore, the main objective of the current study was to evaluate and compare the computed tomography (CT) scan findings of MDR-TB and XDR-TB patients. MATERIAL AND METHODS: In this comparative descriptive cross-sectional study 45 consecutive TB patients who referred to Masih Daneshvari Hospital, Tehran, Iran from 2013 to 2019 were enrolled. TB was diagnosed based on sputum smear and sensitive molecular and microbial tests. Patients were divided into two groups (MDR-TB and XDR-TB) based on two types of drug resistance. CT scan findings were compared for cavitary, parenchymal, and non-parenchymal disorders. The early diagnostic values of these factors were also calculated. RESULTS: Findings related to cavitary lesions including the pattern, number, size of the largest cavity, maximum thickness of the cavity, lung involvement, number of lobes involved, and the air-fluid levels in the two patient groups were similar (p > 0.05). Parenchymal findings of the lung also included fewer and more nodules of 10 mm in the MDR-TB and XDR-TB groups, respectively. Tree-in-bud, ground-glass-opacity, bronchiectasis, cicatricial emphysema, and lobar atelectasis were similar in the two patient groups (p > 0.05). Findings outside the parenchymal lung, including mediastinal lymphadenopathy and pericardial effusion, showed no statistically significant difference between the MDR-TB and XDR-TB groups (p > 0.05). Parenchymal calcification was more common in the XDR group than in the MDR group (64.7% and 28.6%, respectively) with a significant difference (p = 0.01). CONCLUSIONS: CT scan findings in patients with XDR-TB are similar to those of patients with MDR-TB for cavitary, parenchymal, and non-parenchymal lung characteristics. However, patients with XDR-TB tend to have more parenchymal calcification and left-sided plural effusion. CT characteristics overlap between XDR-TB and those with MDR-TB. It can be concluded that CT scan features are not sensitive to the diagnosis.

Prevalence of Mycobacterium abscessus among the Patients with Nontuberculous Mycobacteria.

BACKGROUND: Considering the importance of the increasing incidence of non-tuberculous mycobacteria, especially Mycobacterium abscessus worldwide, we conducted a study to evaluate the incidence of these diseases in our area. The aim of this study was to evaluate the prevalence of M. abscessus in patients with non-tuberculous mycobacteria. METHODS: This descriptive study was performed on 18,083 samples isolated from patients with non-tuberculous mycobacteria during 2011-2017 at the Mycobacteriology Research Center (MRC), Tehran, Iran. To identify the Mycobacterium species, a 439 bp fragment of the IS6110 gene was first amplified using primers TB1 and TB2. Samples with a negative polymerase chain reaction (PCR) result were analyzed to investigate non-tuberculosis mycobacteria (NTM), especially M. abscessus using the RFLP method. RESULTS: Of the 18,083 samples, 5513 (30.49%, 95% CI, 12.95) strains of Complex Tuberculosis and 236 (1.31%, 95% CI, 1.84) strains of NTM were identified. The mean age of the patients with NTM was 18 years, and most of them were male. The most commonly identified species in this study were M. abscessus type Ι 32 (13.56%, 95% CI, 18.36) and M. abscessus type II 13 (5.51%, 95%CI, 20.04). CONCLUSION: In this study, we observed a high prevalence of Mycobacterium abscessus type 1 in patients. As the treatment protocol for non-TB mycobacteria is different from M. abscessus complex, the diagnosis of these species as soon as possible will be significant for physicians.

Association of IL-10 gene promoter polymorphisms with susceptibility to pseudoexfoliation syndrome, pseudoexfoliative and primary open-angle glaucoma.

BACKGROUND: The involvement of cytokines in pathogenesis of pseudoexfoliation syndrome and glaucoma has been demonstrated in several studies. The aim of the present study was to explore the association between three promoter polymorphisms -592C/A (rs1800872), - 819C/T (rs1800871) and -1082A/G (rs1800896) of interleukin 10 (IL-10) gene with susceptibility to pseudoexfoliation syndrome (PEX), pseudoexfoliative glaucoma (PEXG), and primary open-angle glaucoma (POAG). METHODS: In this study, 114 PEX, 118 PEXG, 114 POAG patients and 126 healthy individuals from Iranian population were participated. Detailed ophthalmic examinations by an ophthalmologist including slit-lamp bio-microscopic examination, dilated examination of the lens, gonioscopy, and funduscopy were carried out on patients and controls. Genomic DNA was extracted from the blood samples and ARMS-PCR was performed to detect promoter polymorphisms of IL-10. RESULTS: In all three SNPs studied, there was a significant difference in the genotype distribution between patients and control subjects. Results revealed that the AA genotype of IL-10 -592C/A SNP is associated with PEX. However, TT genotype of -819C/T and AA genotype of -1082A/G SNP are significantly associated with susceptibility to either PEX or PEXG and POAG disorders. Furthermore, the ACC haplotype containing the IL-10 -1082A allele was associated with PEX (P = 0.02, OR = 5.76, 95% CI = 5.17-24.49), PEXG (P = 0.006, OR = 7.54, 95% CI = 6.62-30.76) and POAG (P = 0.003, OR = 8.11, 95% CI = 7.13-33.15). CONCLUSIONS: Our results demonstrated that IL-10 gene promoter polymorphisms are associated with susceptibility to PEX, PEXG and POAG in Iranian population. Considering the fact that IL-10 polymorphisms are associated with various IL-10 expressions, further research is needed to explain its involvement in these disorders and the formation of extracellular fibrillar amyloid deposits in PEX and PEXG.

TNFα -857 C/T and TNFR2 +587 T/G polymorphisms are associated with cystic fibrosis in Iranian patients.

Identification of modifier genes influencing phenotype of cystic fibrosis (CF) patients has become a challenge in CF pathophysiology, prognostic estimations and development of new therapeutic strategies. The aim of this study was to explore the association between four genetic polymorphisms of three modifier genes with CF, by comparing their alleles, genotypes and haplotype frequencies in patients and controls. In this favor, two regulatory polymorphic loci in TNFα promoter (-857C/T, rs1799724 and -238A/G, rs361525) and two functional polymorphic loci in TNFR1 (+36A/G, rs767455) and TNFR2 (+587T/G, rs1061622) were genotyped in 70 patients and 79 controls, using PCR-RFLP. Clinical pulmonary data were also recorded from all studied patients. Results indicated that an association was observed between both T allele and CT/TT genotypes of TNFα (P = 0.0005, OR = 7.06, 95% CI = 3.71-13.45) with CF under dominant model of inheritance. GG genotype of TNFR2 +587 (P = 0.0005, OR = 4.92, 95%CI = 2.34-10.34) was significantly associated with CF using recessive model. Consistently, more severe pulmonary disorder was found for patients carrying either T dominant allele of TNFα -857 or GG genotype of TNFR2 +587 polymorphic sites. Despite an association of A-T and G-T haplotypes with CF, no significant association was found between these haplotypes and clinical parameters of CF. Overall, TNFα -857 T allele and GG genotype of TNFR2 +587 were more frequent in CF patients compared to healthy controls and hence, they showed an association with CF and severe pulmonary phenotype in Iranian patients.