Electronic equipment and appliances in special wards of hospitals as a source of azole-resistant Aspergillus fumigatus: a multi-centre study from Iran.

BACKGROUND: Azole-resistant Aspergillus fumigatus (ARAf), reported as a global public health concern, has been unexpectedly observed in different countries. AIM: To identify ARAf and detect azole resistance related to the CYP51A mutation in different hospital environmental samples. METHODS: In this multi-centre study from Iran, surfaces of electronic equipment and appliances from different hospitals in Iran were sampled using cotton swabs. All samples were cultured using azole-containing agar plates (ACAPs). Recovered Aspergillus isolates were identified at the species level using partial DNA sequencing of the ß-tubulin gene. The azole susceptibility testing of A. fumigatus isolates was performed using the Clinical and Laboratory Standards Institute M38-A3 guideline. The sequencing of the CYP51A gene was also performed to detect mutations related to resistance. FINDINGS: Out of the 693 collected samples, 89 (12.8%) Aspergillus species were recovered from ACAPs. Aspergillus fumigatus (41.6%) was the most prevalent, followed by A. tubingensis (23.6%) and A. niger (15.6%). Among 37 isolates of A. fumigatus, 19 (51.3%) showed high minimum inhibitory concentration (MIC) values to at least one of the three azoles, voriconazole, itraconazole, and posaconazole. CYP51A polymorphisms were detected in all 19 isolates, of which 52.6% showed the TR34/L98H mutation. Other detected mutations were G432C, G448S, G54E/G138C, F46Y, and Y121F/M220I/D255E. T289F and G432C were the first reported mutations in ARAf. CONCLUSION: There was a considerable level of azole resistance in hospital environmental samples, a serious warning for patients vulnerable to aspergillosis. Our findings have also revealed a different mutation pattern in the CYP51A gene.

Solution combustion synthesis (SCS) of theranostic ions doped biphasic calcium phosphates; kinetic of ions release in simulated body fluid (SBF) and reactive oxygen species (ROS) generation.

Theranostic ions offer suitable platforms for cancer theranostics; here, the effect of doping various amounts of theranostic ions (i.e., Sr2+, Fe2+, and Ti4+ ions) on the physicochemical properties and biological activities of calcium phosphates (CaPs) were investigated. The solution combustion synthesis (SCS) was conducted at different amounts of ions (i.e., = 0.1, 0.25, 0.5 mol). Desirable physicochemical properties were obtained in doped samples with 0.1 mol of ions. The particle size of the Sr, Fe, and Ti-doped samples was decreased from 68 to 39, 24, and 29 nm, respectively. The surface charge of the mentioned samples was changed from -20 to -24, -28, and -25 mV, respectively. Besides, the specific surface area of the mentioned samples was significantly increased from 38 to 79, 65, and 106 m2/g, respectively. It was found that bioactivity of doped CaPs improved ~95%, which relied on the high adsorption and desorption rate of Ca2+ ions in the simulated body fluid (SBF). The in vitro cell-based results demonstrate the potent effect of CaPs and theranostic ions doped CaPs on the reactive oxygen species (ROS) generation. In the presence of CaPs, the intracellular ROS generation is increased by about 60%. Besides, the intracellular ROS generation is improved in Sr2+, Fe2+, and Ti4+ ions doped CaPs by about 66, 64, and 68%. As a result of the high generation of ROS, the bone nodule formation of cell treated CaPs and theranostic ions doped CaPs is improved 25%-37%. Finally, it can be concluded that the use of the SCS approaches for doping of theranostic ions causes well-physicochemical properties and high biological activities.

Silicon-doped calcium phosphates; the critical effect of synthesis routes on the biological performance.

In this study, the effect of using different types of fuel and various amounts of Si4+ ions on the biological properties of silicon-doped calcium phosphates (CaPs), which were synthesized using solution combustion method were investigated. X-ray diffraction (XRD) patterns showed that hydroxyapatite/beta-tricalcium phosphate (HA/ßTCP) was crystallized in all synthesized samples. The synthesized sample using glycine as fuel, which doped with 0.1 mol Si4+ ions exhibited the most desirable properties. Consecutively, the zeta potential and specific surface area were enhanced from -20 to -27 mV and 38 to 146 m2/g, respectively, by increasing the amount of Si4+ ions from 0 to 0.1 mol. The bioactivity of the samples immersed in simulated body fluid (SBF) was innovatively determined by the joint analyses of the tensiometer, inductively coupled plasma (ICP), field emission scanning electron microscopy (FESEM), and XRD data. These findings plus theoretical calculations demonstrate, for the first time, that the Si4+ doping could improve the bioactivity of the powders up to ~155%. The results of in vitro cell-based experiments, including cell viability, alizarin red staining, and cell attachment, confirmed the positive effects of Si-doped powders in the biological systems. Furthermore, Si-doped powders were able to improve the migration ability of mammalian cells in vitro; they could be considered good candidates in angiogenesis-based therapeutic strategies.

Cryptococcus and cryptococcosis in Iran during 1969-2019: A systematic review and meta-analysis.

OBJECTIVE: Limited data are available on the epidemiology and etiology of cryptococcal infections in the Middle East. We aimed to conduct the systematic review and meta-analysis to summarize the epidemiological data on prevalence of Cryptococcus species complexes in trees and their surroundings, bird guano and secretions, animals, and highlight the reported episodes of cryptococcosis in Iran. MATERIALS AND METHODS: Twelve databases, including PubMed, Science Direct, Scopus, Proquest, Google Scholar, Embase, and the ISI Web of Science, as well as the national databases, from January 1969 to October 2019 were searched. Furthermore, gray literature (e.g., thesis, congress abstracts) was evaluated using Iran Doc and www.thesis. RESEARCH: ac.ir. Search process was accomplished on English or Persian language articles using the following keywords: "Cryptococcus", "Cryptococcosis", "invasive fungal infection", "Humans", "Birds", "Pigeon", "Animals", "Tree", "Eucalyptus", and "Iran", both alone and in combination. RESULTS: Overall 36 studies were eligible regarding Cryptococcus and cryptococcosis in Iran. The total prevalence rates of Cryptococcus species in the tree was 4.7% (95% CI: 2.3-7.8), and in bird guano was 20.4% (95% CI: 10.7-32.2). Cryptococcosis in animal, and human were 1.7% (95% CI: 0.01-5.1), and 2.8% (95% CI: 0.7v6.1), respectively. The highest prevalence of Cryptococcus in the trees (14.6%), and bird guano (89.4%) in Khorasan, animals (8.9%) in Chaharmahal and Bakhtiari, and human (4.4%) in Mazandaran provinces were reported. CONCLUSIONS: Given the significant risk of Cryptococcus species for susceptible humans, mainly HIV-infected patients, it seems quite necessary to adopt concrete preventive strategies to pinpoint the environmental habitats of this yeast.

Vertebroplasty in the treatment of osteoporotic vertebral fractures: results and functional outcome in a series of 175 consecutive patients.

Osteoporosis is the most common cause of vertebral collapse, which significantly impairs mobility and quality of life. Primary management consists of conservative therapeutic measures such as analgesics, bed rest, external bracing and rehabilitation. Percutaneous vertebroplasty for the treatment of osteoporotic compressive fractures has gained popularity during the last decade. The limited invasiveness and encouraging results of vertebroplasty obtained in the treatment of patients with symptomatic osteoporotic compression fractures have favored an extensive use of the procedure for the management of patients with disabling pain refractory to conservative therapy. In the present paper, the authors provide procedure results and functional outcomes in a series of 175 consecutive patients with 242 symptomatic osteoporotic vertebral compression fractures treated by means of percutaneous polymethylmethacrylate vertebroplasty.

Induction and localization of cutaneous interleukin-1 beta mRNA during contact sensitization.

Chemical allergens that induce contact sensitivity cause changes in levels of epidermal cytokines. In mice one of the earliest epidermal cytokines to be upregulated following sensitization is interleukin-1 beta (Iota L-1 beta). The present study investigated the kinetics and in situ localization of induced IL-1 beta expression in mouse skin following topical exposure to the contact allergen oxazolone. Mice were exposed topically to 1% oxazolone, with control mice exposed to vehicle (acetone:olive oil 4:1) alone, and at various times thereafter skin was excised for IL-1 beta mRNA and protein determination by in situ hybridization and enzyme-linked immunosorbant assay (ELISA), respectively. IL-1 beta mRNA was found to be expressed constitutively at low levels in skin from naïve (untreated) and vehicle-treated mice, with mRNA localized in some hair follicles and sebaceous glands; no IL-1 beta mRNA was detected in the epidermis of control animals. Following topical exposure of mice to oxazolone for 5-15 min, upregulation of IL-1 beta mRNA was observed in the epidermis, dermis, hair follicles, and sebaceous glands; at 90 min and beyond the pattern of IL-1 beta mRNA expression declined toward control. Analysis of whole skin homogenates by ELISA demonstrated cutaneous IL-1 beta protein to be present constitutively in both vehicle-treated and naïve mice. Following exposure to oxazolone, cutaneous IL-1 beta protein expression was elevated at 30 min, decreased at 1 h, and fell below the limit of detection of the assay at 2 h before returning to constitutive levels at 4 and 24 h. IL-1 beta protein levels in vehicle-treated mice, naïve mice, and mice treated with the respiratory allergen trimellitic anhydride were unchanged over this time period. The present study demonstrated that IL-1 beta mRNA expression was upregulated rapidly and transiently in well-defined regions of mouse epidermis and dermis during contact sensitization, and was succeeded by an elevation in IL-1 beta protein. This early highly localized upregulation of IL-1 beta lends further support to the hypothesis that this cytokine plays a key role in the initial stages of skin sensitization. Such information will enhance our understanding of the molecular processes involved in allergic contact dermatitis and may provide a mechanistic basis for designing refined animal and in vitro alternatives to existing models of skin sensitization.

Effects of corticotrophin releasing hormone on contractile activity of myometrium from pregnant women.

OBJECTIVE: To determine whether corticotrophin releasing hormone plays a role in the regulation of tone in term nonlabouring human myometrium. SETTING: A teaching hospital research laboratory. SAMPLE: Thirty-seven women undergoing elective nonlabour caesarean section under regional anaesthesia. METHODS: Human corticotrophin releasing hormone (1, 10, 100 nmol/L) was added to strips of term, nonlabouring myometrium mounted in an organ bath, and the effect on spontaneous, oxytocin (1 nmol/L) or prostaglandin F2alpha (100 nmol/L) stimulated contractions determined. Cyclic adenosine monophosphate (cAMP) content of the tissue was also determined by enzyme immunoassay. RESULTS: Corticotrophin releasing hormone did not affect myometrial tension development in any of the experimental protocols. cAMP increased transiently after addition of corticotrophin releasing hormone (166.7 +/- 12.7% at 1 minute) but this was not reflected by any change in tension. CONCLUSIONS: This study suggests that despite high maternal plasma concentrations of corticotrophin releasing hormone in pregnancy at term, this peptide is unlikely to play a direct role in the control of myometrial contractility in nonlabouring myometrium.

Intravenous immunoglobulin in autoimmune chronic urticaria.

Histamine releasing autoantibodies play a central role in the pathogenesis of chronic urticaria (CU) in approximately 30% of affected patients. We investigated the therapeutic effect of high-dose intravenous immunoglobulin (IVIG) on disease activity in patients with severe CU of autoimmune aetiology. Autoimmune urticaria was diagnosed by the development of a weal-and-flare reaction to the intradermal injection of autologous serum and by serum-induced histamine release from the basophil leucocytes of healthy donors in vitro. Ten patients with severe, autoimmune CU, poorly responsive to conventional treatment, were treated with IVIG 0.4 g/kg per day for 5 days. The outcome on cutaneous wealing and itch was monitored using urticaria activity scores, visual analogue scales and autologous intradermal serum tests. Clinical benefit was noted in nine of 10 patients: three patients continue in prolonged complete remissions (3 years follow-up), two had temporary complete remissions, and symptoms in four patients improved subsequent to treatment. There was significant improvement in the urticaria activity scores and visual analogue scores at 2 (P < 0.01) and 6 weeks (P < 0.01) post-IVIG compared with the baseline values (Wilcoxon matched pairs). The diminution in urticarial activity in the majority of patients corresponded with a reduced weal-and-flare response to the intradermal injection of autologous post-treatment serum compared with the pretreatment serum. Minor side-effects were common, but there were no serious or long-term adverse effects. IVIG represents a novel therapeutic option in selected patients with recalcitrant CU associated with histamine releasing autoantibodies.

Dermal mast cell activation by autoantibodies against the high affinity IgE receptor in chronic urticaria.

Previous studies identified autoantibodies against the IgE high affinity receptor alpha-chain, Fc epsilon RI alpha, in sera of selected patients with severe chronic idiopathic urticaria. We have now determined the incidence of anti-Fc epsilon RI alpha autoantibodies in a group of 163 patients. Intradermal injection of autologous serum caused skin reactions indicative of mast cell degranulation in 98 (60%) patients. Based on histamine release from IgE-sensitized and nonsensitized basophil leukocytes of healthy donors, we detected anti-Fc epsilon RI alpha autoantibodies in sera from 38 (23%) urticaria patients and evidence for anti-IgE antibodies in a further nine patients. The sera that released histamine from basophils induced histamine release (4-34%, n = 12) from mast cells in incubated skin slices. Protein-G affinity chromatography of sera demonstrated that mast cell histamine release was IgG-mediated. Preincubation of sera or the IgG fraction with a recombinant alpha-chain of Fc epsilon RI inhibited histamine release from mast cells and basophils. Further studies with the mouse anti-human Fc epsilon RI alpha antibody 29C6 showed that mast cells and basophils were similarly sensitive to IgG-mediated direct cross-linking of Fc epsilon RI, with 0.01-1.0 micrograms/ml 29C6 evoking histamine release in each case. These studies demonstrate that circulating levels of anti-Fc epsilon RI alpha autoantibodies mediate histamine release from skin mast cells in vitro and, taken together with in vivo evidence of mast cell degranulation following intradermal injection of autologous serum, support the concept that anti-Fc epsilon RI alpha autoantibodies are relevant to the pathogenesis of severe chronic urticaria in about 25% of patients.