Global prevalence, mortality, and main characteristics of HIV-associated pneumocystosis: A systematic review and meta-analysis.

The epidemiology of Human Immunodeficiency Virus (HIV)-associated pneumocystosis (HAP) is poorly described on a worldwide scale. We searched related databases between January 2000 and December 2022 for studies reporting HAP. Meta-analysis was performed using StatsDirect (version 2.7.9) and STATA (version 17) according to the random-effects model for DerSimonian and Laird method and metan and metaprop commands, respectively. Twenty-nine studies with 38554 HIV-positive, 79893 HIV-negative, and 4044 HAP populations were included. The pooled prevalence of HAP was 35.4% (95% CI 23.8 to 47.9). In contrast, the pooled prevalence of PCP among HIV-negative patients was 10.16% (95% CI 2 to 25.3). HIV-positive patients are almost 12 times more susceptible to PCP than the HIV-negative population (OR: 11.710; 95% CI: 5.420 to 25.297). The mortality among HAP patients was 52% higher than non-PCP patients (OR 1.522; 95% CI 0.959 to 2.416). HIV-positive men had a 7% higher chance rate for PCP than women (OR 1.073; 95% CI 0.674 to 1.706). Prophylactic (OR: 6.191; 95% CI: 0.945 to 40.545) and antiretroviral therapy (OR 3.356; 95% CI 0.785 to 14.349) were used in HAP patients six and three times more than HIV-positive PCP-negatives, respectively. The control and management strategies should revise and updated by health policy-makers on a worldwide scale. Finally, for better management and understanding of the epidemiology and characteristics of this coinfection, designing further studies is recommended.

A comprehensive review on the role of T cell subsets and CAR-T cell therapy in Aspergillus fumigatus infection.

Understanding the immune response to Aspergillus fumigatus, a common cause of invasive fungal infections (IFIs) in immunocompromised individuals, is critical for developing effective treatments. Tcells play a critical role in the immune response to A. fumigatus, with different subsets having distinct functions. Th1 cells are important for controlling fungal growth, while Th2 cells can exacerbate infection. Th17 cells promote the clearance of fungi indirectly by stimulating the production of various antimicrobial peptides from epithelial cells and directly by recruiting and activating neutrophils. Regulatory T cells have varied functions in A.fumigatus infection. They expand after exposure to A. fumigatus conidia and prevent organ injury and fungal sepsis by downregulating inflammation and inhibiting neutrophils or suppressing Th17 cells. Regulatory T cells also block Th2 cells to stop aspergillosis allergies. Immunotherapy with CAR T cells is a promising treatment for fungal infections, including A. fumigatus infections, especially in immunocompromised individuals. However, further research is needed to fully understand the mechanisms underlying the immune response to A. fumigatus and to develop effective immunotherapies with CAR-T cells for this infection. This literature review explores the role of Tcell subsets in A.fumigatus infection, and the effects of CAR-T cell therapy on this fungal infection.

An Autochthonous Susceptible Candida auris Clade I Otomycosis Case in Iran.

Candida auris is a newly emerging multidrug-resistant fungal pathogen considered to be a serious global health threat. Due to diagnostic challenges, there is no precise estimate for the prevalence rate of this pathogen in Iran. Since 2019, only six culture-proven C. auris cases have been reported from Iran, of which, five belonged to clade V and one to clade I. Herein, we report a case of otomycosis due to C. auris from 2017 in a 78-year-old man with diabetes mellitus type II without an epidemiological link to other cases or travel history. Short tandem repeat genotyping and whole genome sequencing (WGS) analysis revealed that this isolate belonged to clade I of C. auris (South Asian Clade). The WGS single nucleotide polymorphism calling demonstrated that the C. auris isolate from 2017 is not related to a previously reported clade I isolate from Iran. The presence of this retrospectively recognized clade I isolate also suggests an early introduction from other regions or an autochthonous presence. Although the majority of reported C. auris isolates worldwide are resistant to fluconazole and, to a lesser extent, to echinocandins and amphotericin B, the reported clade I isolate from Iran was susceptible to all antifungal drugs.

Molecular diagnosis, phylogenetic analysis, and antifungal susceptibility profiles of Candida species isolated from neutropenic oncological patients.

BACKGROUND: Neutropenia is the most important cause of life-threatening invasive fungal infections (IFIs). Here, we studied the frequency and antifungal susceptibility profiles of Candida species that colonized or caused infections among neutropenic patients with solid or hematological malignancies. METHODS: A total of 362 clinical samples were collected from 138 patients. After initial isolation using a mix of mycological methods, isolates were screened using chromogenic culture media. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied for molecular identification. Positive or suspected cases were confirmed using the reference method of sequencing. Antifungal susceptibility testing for voriconazole and caspofungin was carried out using the microbroth dilution method. An in-silico assay was applied for phylogenetic analysis. RESULTS: Thirty-four Candida strains were isolated. C. albicans (47.06%) and C. glabrata (29.41%) were the most frequent strains. Antifungal treatment reduced the chance of Candida colonization by almost 76% in neutropenic patients (OR: 1.759; 95% CI: 1.349 to 2.390; p value: 0.000). An unusual and non-resistant strain, C. lambica, was reported from the bloodstream of a 56-year-old man with hematologic malignancy (HM). Eight isolates were non-susceptible, and one isolate was resistant to voriconazole. Also, four isolates were non-susceptible to caspofungin. CONCLUSION: We can conclude that there is a cause-and-effect relationship between neutropenia, HM background, and Candida species separated from neutropenic patients, which can lead to possible infections. Further and repetitive studies are recommended using different molecular methods for better prediction and management of fungal infections in neutropenic patients.

In-vivo efficiency of the novel azole compounds (ATTAF-1 and ATTAF-2) against systemic candidiasis in a murine model.

BACKGROUND: Antifungal resistance is the main health concern in the control of invasive fungal infections. This research was designed to further assess the antifungal activity of aryl-1,2,4-triazole-3-ylthio analogs of fluconazole (ATTAFs) against Candida albicans systemic candidiasis in the murine model. MATERIALS & METHODS: The murine model of systemic candidiasis was designed via the inoculation of 1 × 106 CFU of Candida albicans. The treatment dosages of 3.5 and 35 mg/kg per day were selected for ATTAFs and fluconazole, respectively. The median survival time (MST) was assayed for 30 days post-infection. The quantitative and qualitative (via histopathology staining) fungal burden was also assessed. Furthermore, immunohistochemistry and biochemistry assays were performed to monitor anti-inflammatory activity using the Cyclooxygenase-2 (Cox-2) marker and changes in serum protein levels. RESULTS: ATTAFs considerably improved the survival of the murine model (P < 0.003). Compared with fluconazole, the antifungal activity of ATTAFs and their MST showed no difference (P > 0.05). However, these compounds decreased the fungal burden in the kidneys, spleen, and liver. CONCLUSION: Our research indicates that ATTAF-1 and ATTAF-2 are effective therapeutic agents due to their fungal clearing and increasing the MST in the murine model of systemic candidiasis. Although we concluded that these components are novel and promising candidates for the management of invasive candidiasis, further studies are warranted to correlate these findings with clinical outcomes.

A Comprehensive Review of Identification Methods for Pathogenic Yeasts: Challenges and Approaches.

Given the increasing incidence of yeast infections and the presence of drug-resistant isolates, accurate identification of the pathogenic yeasts is essential for the management of yeast infections. In this review, we tried to introduce the routine and novel techniques applied for yeast identification. Laboratory identification methods of pathogenic yeast are classified into three categories; I. conventional methods, including microscopical and culture-base methods II. biochemical/physiological-processes methods III. molecular methods. While conventional and biochemical methods require more precautions and are not specific in some cases, molecular diagnostic methods are the optimum tools for diagnosing pathogenic yeasts in a short time with high accuracy and specificity, and having various methods that cover different purposes, and affordable costs for researchers. Nucleotide sequencing is a reference or gold standard for identifying pathogenic yeasts. Since it is an expensive method, it is not widely used in developing countries. However, novel identification techniques are constantly updated, and we recommend further studies in this field. The results of this study will guide researchers in finding more accurate diagnostic method(s) for their studies in a short period of time.

Evaluating the Typing Power of Six Isoenzymatic Systems for Differentiation of Clinical and Standard Isolates of Candida Species.

Background: Due to the increasing prevalence of candidiasis, early detection of the causative agents may pave the way for the management of this infection. The present study aimed to assess the discriminative power of the six isoenzymatic systems for differentiating the Candida species. Materials and Methods: Sixteen standard Candida albicans and Candida dubliniensis strains and 30 fluconazole-sensitive and fluconazole-resistant clinical strains of Candida albicans were analyzed using a Multilocus Enzyme Electrophoresis (MLEE) method, including six enzymatic systems consisting of malate dehydrogenase (MDH), phosphoglucomutase (PGM), glucose-phosphate isomerase (GPI), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGD), and malic enzyme (ME). Results: Among the six enzymatic systems, ME showed no diagnostic activity, whereas MDH provided the best species-specific pattern for species discrimination. In addition, the MDH and G6PD systems provided a discriminatory pattern for differentiating C. dubliniensis from C. albicans isolates. The same isoenzymatic activity was detected in all 36 standard and clinical isolates. Moreover, the results showed no correlation between the isoenzymatic profiles and drug resistance. Conclusion: Among the investigated MLEE systems, MDH was able to differentiate between Candida albicans and Candida dubliniensis. Although no association was detected between isoenzyme patterns and fluconazole resistance in this investigation, isoenzyme patterns are likely correlated with virulence factors between species and even within species. To answer these questions, additional studies should be done on more strains.

A 3-year study of Candida infections among patients with malignancy: etiologic agents and antifungal susceptibility profile.

Objective: Opportunistic fungal infections by Candida species arise among cancer patients due to the weakened immune system following extensive chemotherapy. Prophylaxis with antifungal agents have developed the resistance of Candida spp. to antifungals. Accurate identification of yeasts and susceptibility patterns are main concerns that can directly effect on the treatment of patients. Methods: Over a period of three years, 325 cancer patients suspected to Candida infections were included in the current investigation. The clinical isolates were molecularly identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). All strains, were examined for in vitro susceptibility to the amphotericin B, itraconazole, fluconazole, and anidulafungin according to the CLSI M27 document. Results: Seventy-four cancer patients had Candida infections (22.7%). Candida albicans was the most common species (83.8%). Antifungal susceptibility results indicated that 100% of the Candida isolates were sensitive to amphotericin B; however, 17.6%, 9.4%, and 5.4% of clinical isolates were resistant to anidulafungin, fluconazole, and itraconazole, respectively. Conclusion: The findings of the present work shows a warning increase in resistance to echinocandins. Since all fluconazole resistance isolates were obtained from candidemia, we recommend amphotericin B as the first line therapy for this potentially fatal infection.

Molecular identification and antifungal susceptibility profiles of etiologic agents of oral candidiasis among HIV-positive patients: A multicenter study.

Background and Purpose: Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) is a serious risk factor for oral candidiasis (OC). In this regard, the present study aimed to investigate the frequency of Candida species collected from the oropharyngeal cavity of HIV-positive patients and the sensitivity of these isolates to antifungal drugs. Materials and Methods: Oral samples were collected from 169 HIV-positive patients. In addition to culture-based methods, a molecular assay via the polymerase chain reaction-restriction fragment length polymorphism method was applied to identify isolates using the MspI restriction enzyme. The disk diffusion method determined the susceptibility of isolated yeasts to common antifungal drugs according to the CLSI M44-A2 protocol. Results: In total, 81 participants (47.92%) were positive for OC, and Candida albicans was the most prevalent yeast (53.98%). The median age of patients was 36 years old (IQR=10.5; 17-59), and it was found that women are 27% more susceptible to HIV-associated OC (OR=1.268; 95% CI: 0.685-2.348). Patients who received antifungal therapy had a 97.3% reduced chance for OC (OR: 0.027; 95% CI: 0.008-0.091; P-value: 0.000). Antifungal therapy reduced the risk of OC by 97.3% (OR=0.027; 95% CI=0.008-0.091; P=0.000), and antiretroviral therapy decreased the chance of OC 4.42 times (OR=4.423; 95% CI=1.697-11.528; P=0.002). The resistance rates for antifungals, namely fluconazole, ketoconazole, itraconazole, amphotericin B, and nystatin were 15.93%, 8.85%, 7.96%, 5.31%, and 4.42%, respectively. Conclusion: Although several decades have passed since the emergence of HIV/AIDS, little information is available about fungal colonization and infections in this population. Further investigations are suggested using novel and reference molecular identification methods, such as matrix-assisted laser desorption ionization time-of-flight mass spectrometry and sequencing, respectively. In addition, more reliable methods for antifungal susceptibility testing are recommended.

Development of a high-resolution melt-based assay to rapidly detect the azole-resistant Candida auris isolates.

Background and Purpose: Candida auris is a multidrug-resistant yeast that rapidly spreads, making it the leading Candidate for the next pandemic. One main leading cause of emerging resistant C. auris isolates is nonsynonymous mutations. This study aimed to detect the Y132F mutation, one of the most important azole resistance-associated mutations in the ERG-11 gene of C. auris, by developing a reliable high-resolution melt (HRM)-based method. Materials and Methods: Five C. auris isolates from Iran, plus three control isolates from other Clades were used in the study. The antifungal susceptibility testing through micro broth dilution was performed to recheck their susceptibility to three azole antifungals, including fluconazole, itraconazole, and voriconazole. Moreover, the polymerase chain reaction (PCR) sequencing of the ERG-11 gene was performed. Following the bioinformatic analysis and HRM-specific primer design, an HRM-based assay was developed and evaluated to detect ERG-11 mutations. Results: The minimum inhibitory concentrations of fluconazole among Iranian C. auris isolates ranged from 8 to 64 µg/mL. The PCR-sequencing of the ERG-11 gene and bioinformatic analyses revealed the mutation of Y132F, a substitution consequence of A to T on codon 395 in one fluconazole-resistant isolate (IFRC4050). The developed HRM assay successfully differentiated the targeted single nucleotide polymorphism between mutant and wild types (temperature [Tm]: 81.79 ℃ - cycle threshold [CT]: 20.06 for suspected isolate). For both mutant and non-mutant isolates, the mean Tm range was 81.79-82.39 °C and the mean CT value was 20.06-22.93. These results were completely in accordance with the findings of DNA sequencing. Conclusion: The fast-track HRM-based method successfully detected one of the most common mechanisms of resistance in the ERG-11 gene of C. auris within 3 h. Finally, the development of more panels of HRM assays for the detection of all azole resistance mutations in C. auris ERG-11 is recommended to expand the scope of the field and facilitate the elaboration of rapid and accurate methods of antifungal resistance assessment.

Bacterial and fungal coinfections among patients with COVID-19 in Zanjan, Northwest of Iran; a single-center observational with meta-analysis of the literature.

Background and Objectives: There is a poor understanding about the prevalence and characteristics of secondary bacterial and fungal infections among Coronavirus diseases 2019 (COVID-19) superinfection in hospitalized patients. Materials and Methods: Four hundred COVID-19-proven patients were enrolled in this study. Nasal swabs for molecular assay (Real-time PCR) and sputum samples for further microbiological assays were collected. Following a broad-spectrum search, a meta-analysis was performed using StatsDirect software (version 2.7.9) according to the DerSimonian and Laird method applying the random-effects models. Results: Streptococcus spp. (21.5%) and Staphylococcus spp. (16.7%) had the highest prevalence of bacterial coinfection among the COVID-19 patients, while Acinetobacter spp. had the lowest prevalence (4.2%). Among fungal coinfections, Candida albicans was the most prevalent (6.7%), and Aspergillus spp. was the lowest (2%). Males, elderly patients, patients with a history of underlying diseases and drug use, patients who showed acute clinical symptoms, and patients with a prolonged hospital stay had a higher incidence of secondary infections (P-value <0.05). The pooled prevalence for bacterial and fungal coinfections was 33.52% (95% CI: 18.12 to 50.98; I2: 99.4%; P-value: <0.0001). Conclusion: We suggest designing additional research with a larger target population and diagnostic molecular analyses to depict a more realistic view of the coinfection status.

Accompanying a semi-nested PCR assay to support histopathology findings of fungal keratitis in formalin-fixed paraffin-embedded corneal samples.

BACKGROUND: Fungal species are responsible for 40%-50% of all microbial keratitis cases. Due to the low amount of extracted DNA in ocular Formalin-fixed Paraffin-embedded (FFPE) samples, selecting a reliable molecular method is a substantial issue in this field. METHODS: Sixty-six samples were collected via the penetrating keratoplasty (PK) technique. Histopathology assays were performed using hematoxylin-eosin (H&E) and periodic acid Schiff (PAS) staining methods. The ITS1/ITS4 and ITS1/ITS2 primer pairs were used in a semi-nested polymerase chain reaction (PCR) to target the universal internal transcribed spacer (ITS) region. Some PCR results were validated through sequencing. RESULTS: Fungal DNA was detected in 44 of 66 samples (66.7%), and histopathology was positive for 41 of 66 samples (62.1%). Of 41 histopathologically proven fungal-positive cases, 39 were PCR-positive (95%). Moreover, of 44 PCR-positive samples, 39 (88.6%) were histopathology-positive, and 5 (11.3%) were histopathology-negative. Totally in 39 cases (59%), both histopathology and PCR yielded positive results. The Kappa agreement rate between the two diagnostic methods, including histopathology and PCR, was 0.77. Sensitivity, specificity, positive predictive value, and false predictive value were reported as 88.64%, 90.9%, 95.12%, and 80%, respectively. CONCLUSION: As we reached the acceptable Kappa agreement rate, we concluded that applying the semi-nested PCR assay is a promising method for supporting the evidence by histopathology. Finally, we suggest targeting more specific gene regions using primer pairs that amplify smaller amplicon sizes and surveying novel molecular methods such as NGS to achieve higher sensitivity and Kappa agreement rates.

Fusarium proliferatum-induced chronic lip ulcer: successful treatment with itraconazole: a case report.

BACKGROUND: Fusarium species are saprophytic fungi with a worldwide distribution. These fungi cause various infections among immunocompromised patients; however, they can also involve immunocompetent individuals. CASE PRESENTATION: We report a case of a 41-year-old Iranian woman who presented with ulcerative lesions on her lips 10 months ago. She had a long history of anxiety but had no history of classical risk factors such as trauma, cosmetic lip tattoo, burning in her lips, smoking or use of alcohol and opium. A skin biopsy from the lower lip was performed and sent for microbiological examinations. Hyaline septate hyphae were seen on direct microscopy with potassium hydroxide. The clinical specimen was subcultured on sabouraud dextrose agar with chloramphenicol and prepared for antifungal susceptibility testing and molecular identification. Considering the minimum inhibitory concentrations (MIC) for antifungals, itraconazole (100 mg orally twice a day) was started for her, and after 2 months, the lesions were treated. She followed up for 3 months, and no signs of disease recurrence were observed. CONCLUSIONS: Selecting an appropriate treatment strategy according to the laboratory assessments is essential in clinical practice and the management of rare infections to prevent related mortality and morbidity of opportunistic fungal infections.

Global prevalence and subgroup analyses of coronavirus disease (COVID-19) associated Candida auris infections (CACa): A systematic review and meta-analysis.

BACKGROUND: Increased hospitalisation rates in the Coronavirus disease 19 (COVID-19) era lead to a new wave of hospital-acquired infections such as emerging multidrug-resistant Candida auris. We aimed to evaluate and estimate the global prevalence of coronavirus-associated C. auris infection (CACa). METHODS: We searched related databases between December 2019 and April 2022 for studies that reported data about CACa. Meta-analysis was performed using MedCalc software version 20.104 according to the DerSimonian and Laird method applying the random-effects model. We evaluated heterogeneity using the χ2 -based Q statistic (significant for p-value < .1) and the I2 statistic (>75% indicative of 'notable' heterogeneity). Moreover, if possible, an odds ratio (OR) analysis was performed for eligible data. RESULTS: Our meta-analysis includes ten eligible studies, including 1942 patients hospitalised with COVID-19; 129 were C. auris cases. The overall pooled prevalence of CACa was estimated at 5.7%. The mortality rate of CACa was estimated at 67.849%. Hypertension was the most prevalent comorbidity (59.374%), followed by diabetes mellitus (52.898%) and cardiovascular diseases (31.392%). Men with a prevalence rate of 80.012% were 3.27 (OR) times more prone to getting infected by C. auris. CONCLUSION: We concluded that the prevalence of C. auris infections decreased during the COVID-19 pandemic and the prevalence gradient changed from Asia to America. Unfortunately, there are many descriptive studies with duplicate content in the field of epidemiology of C. auris infections which are increasing every day. We suggest further non-descriptive studies to accurately establish the cause-and-effect relationships between C. auris and COVID-19 infections.

Evaluating a semi-nested PCR to support histopathology reports of fungal rhinosinusitis in formalin-fixed paraffin-embedded tissue samples.

BACKGROUND: Fungal rhinosinusitis (FRS) encompasses a various spectrum of diseases. Histopathology is the "reference method" for diagnosing FRS, but it cannot determine the genus and species. Moreover, in more than 50% of the histopathologically proven cases, the culture elicited no reliable results. This study was an attempt to evaluate the diagnostic efficiency of semi-nested polymerase chain reaction (PCR) from formalin-fixed paraffin-embedded (FFPE) functional endoscopic sinus surgery (FESS) in FRS patients. METHODS: One hundred ten specimens were subjected to DNA extraction and histopathology examination. The amplification of the ß-globin gene by conventional PCR was used to confirm the quality of extracted DNA. The semi-nested PCR was performed using ITS1, ITS2, and ITS4 primers during two steps. Sequencing the internal transcribed spacer region (ITS1-5.8S-ITS2) to identify causative agents was performed on PCR products. RESULTS: Sixty-four out of 110 samples were positive by histopathology evidence, of which 56 samples (87.5%) were positive by PCR. Out of 46 negative samples by histopathological methods, five samples (10.9%) yielded positive results by PCR. Sensitivity, specificity, positive predictive value, and negative predictive value of the semi-nested PCR method were reported 87.5%, 89.2%, 92.7%, and 85.2%, respectively. The kappa factor between PCR and histopathological methods was 0.76, indicating substantial agreements between these two tests. CONCLUSION: Due to the acceptable sensitivity and specificity of the present method, it might be used to diagnose fungal sinusitis infections along with microscopic techniques. This method is recommended to confirm the diagnose of suspected fungal sinusitis with negative histopathology results.

Emerging of Fatal Colitis with Multidrug-Resistant Candida glabrata after Small Bowel Transplantation.

BACKGROUND: Small bowel transplantation is a potential option for patients with intestinal-failure, and the incidences of infections caused by Candida species that are more resistant to antifungal drugs are increasing in these patients. In this manuscript, we reported a case of fatal colitis after small bowel transplantation induces by multidrug-resistant (MDR) Candida glabrata. Case Presentation. A 52-year-old man has undergone an extensive small bowel resection with the length of the remaining bowel which was less than 40 cm who became a candidate for transplantation. Four months after transplantation, the patient experienced severe bloody diarrhea with abdominal distension. Ileoscopy and colonoscopy did not show neither pathological change and rejection nor cytomegalovirus (CMV) infection posttransplantation. Abdomen computed tomography showed diffuse moderate small bowel wall thickening. After detection of budding yeast in the stool samples, stool culture was positive for Candida, DNA was extracted, and ITS1-5.8s-ITS2 region of the fungal agent was amplified. Sequencing analysis of PCR and antifungal susceptibility testing revealed that this isolate was multidrug-resistant C. glabrata. Besides, there was no evidence for other pathogens known to cause infection in various laboratory tests. Immediate antifungal treatments with caspofungin remained unsuccessful, and on the eighteenth day of admission, the patient expires with septic shock. CONCLUSION: These findings highlight the challenging management of candidiasis in patients with small bowel transplantation. Infectious diseases due to MDR organisms have emerged as a vital clinical problem in this patient population.

Interactions between immune response to fungal infection and microRNAs: The pioneer tuners.

Due to their physiological and biological characteristics, numerous fungi are potentially emerging pathogens. Active dynamicity of fungal pathogens causes life-threatening infections annually impose high costs to the health systems. Although immune responses play crucial roles in controlling the fate of fungal infections, immunocompromised patients are at high risk with high mortality. Tuning the immune response against fungal infections might be an effective strategy for controlling and reducing the pathological damages. MicroRNAs (miRNAs) are known as the master regulators of immune response. These single-stranded tuners (18-23 bp non-coding RNAs) are endogenously expressed by all metazoan eukaryotes and have emerged as the master gene expression controllers of at least 30% human genes. In this review article, following the review of biology and physiology (biogenesis and mechanism of actions) of miRNAs and immune response against fungal infections, the interactions between them were scrutinised. In conclusion, miRNAs might be considered as one of the potential goals in immunotherapy for fungal infections. Undoubtedly, advanced studies in this field, further identifying of miRNA roles in governing the immune response, pave the way for inclusion of miRNA-related immunotherapeutic in the treatment of life-threatening fungal infections.

MicroRNAs and response to therapy in leukemia.

A variety of epigenetic factors involved in leukemia pathogenesis. Among various epigenetic factors, microRNAs (miRNAs) have emerged as important players, which affect a sequence of cellular and molecular signaling pathways. Leukemia is known as progressive cancer, which is related to many health problems in the world. It has been shown that the destruction of the blood-forming organs could lead to abnormal effects on the proliferation and development of leukocytes and their precursors. Despite many attempts for approved effective and powerful therapies for patients with leukemia, finding and developing new therapeutic approaches are required. One of the important aspects of leukemia therapy, identification of underlying cellular and molecular mechanisms involved in the pathogenesis of leukemia. Several miRNAs (ie, miR-103, miR-101, mit-7, let-7i, miR-424, miR-27a, and miR-29c) and play major roles in response to therapy in patients with leukemia. miRNAs exert their effects by targeting a variety of targets, which are associated with response to therapy in patients with leukemia. It seems that more understanding about the roles of miRNAs in response to therapy in patients with leukemia could contribute to better treatment of patients with leukemia. Here, for the first time, we summarized various miRNAs, which are involved in response to therapy in the treatment patients with leukemia.

Determine the prevalence of gestational diabetes in Ardakan and its related factors.

Gestational Diabetes (GD) is amongst the most common metabolic disorders. Due to the important complications of GD on maternal and fetal health and in order to identify the prevalence of GD in various climate and cultures, the present studies aimed to determine the prevalence of GD in Ardakan and its related factors in 2014-2015. This cross-sectional study was conducted in 3808 pregnant women referring to rural and urban health centers in Ardakan city in 2013-14. Demographic, clinical, and obstetrics history of the subjects was gathered. GD was defined based on Glucose Tolerance Test (GTT). Descriptive and Logistic regression models were applied. The prevalence of GD was estimated to be 7.5% (286) which was higher in 35-39 age group, urban residents, obese mothers, and pregnancies ended with macrosome babies. The odds of GD was higher in obese mothers by 1.62 times (95%CI: 1.18-2.24), in mothers above ages of 40 by 10.53 (95%CI: 3.8-29.3), in mothers with a history of GD by 3.86 (95%CI:1.65-8.93), and in pregnancies ended with a macro some baby by 2.2 (95%CI: 0.97-5.1). The prevalence of GD in Ardakan was similar to other studies in the area. It seems that improvement of GD screening in older mothers and those with a history of GD could be a priority of surveillance system in Yazd Province.