Potent in vitro activity of curcumin and quercetin co-encapsulated in nanovesicles without hyaluronan against Aspergillus and Candida isolates.

The rapid emergence of resistance to classical antifungals has increased the interest in novel antifungal compounds. Curcumin and quercetin are two natural plant-derived bioactive molecules shown to promote wound healing in injured tissues. In this study, we investigated the in vitro susceptibility of several Aspergillus and Candida isolates to curcumin and quercetin encapsulated in nanovesicles with and without hyaluronan and elucidated the efficacy of these nanovesicles as topical drug delivery systems. Antifungal susceptibility testing performed according to the CLSI guidelines indicated that curcumin-quercetin co-encapsulated in nanovesicles without hyaluronan (CUR-QUE-NV-WH) had stronger activity against Candida isolates than fluconazole. Furthermore, CUR-QUE-NV-WH showed efficacy against fluconazole-resistant Candida isolates as evidenced by MICs at least two times lower than those of fluconazole. Examination of skin permeation profiles using an in vitro Franz diffusion cell system revealed that curcumin and quercetin delivered by nanovesicles were released and accumulated in the skin; however, only quercetin could penetrate through the skin layers. Collectively, our results demonstrate that CUR-QUE-NV-WH has potent antifungal activity against Candida isolates and might be a topical treatment, which warrants its further investigation as a novel antifungal agent.

Candida africana vulvovaginitis: Prevalence and geographical distribution.

Candida africana has been recovered principally as a causative agent of vulvovaginal candidiasis (VVC) from different countries, which is likely to be misidentified as the typical Candida albicans or Candida dubliniensis. The current study aimed to characterize C. albicans species complex obtained from VVC based on conventional and molecular assays. Furthermore, in vitro antifungal susceptibility testing was performed based on CLSI documents. Additionally, due to low knowledge concerning C. africana infections, we reviewed all published papers from 1991 to 2019. One hundred forty-four out of 287 patients were identified with Candida infection, among whom 151 isolates of Candida were obtained. Candida albicans 109 (72.1%), Candida glabrata 21 (13.9%), Candida krusei 8 (5.2%), Candida tropicalis 5 (3.3%), Candida africana 3 (1.9%), Candida parapsilosis 3 (1.9%) and C. dubliniensis 2 (1.3%) were isolated from patients. MIC results showed that C. africana isolates were susceptible to all tested antifungal drugs. Candida africana infections were more prevalent in Africa. One hundred fifteen (40.6%) of patients with C. africana candidiasis were from seven African countries, and Madagascar and Angola had the majority of cases. The epidemiological data, phenotypic, clinical features, ecologic similarity, and antifungal susceptibility profiles for better understanding of the pathogenic mechanisms and optimal treatment underlying non-CandidaalbicansCandida vulvovaginitis are highly recommended.

Molecular epidemiology of environmental Cryptococcus species isolates based on amplified fragment length polymorphism.

OBJECTIVE: Cryptococcosis is a major opportunistic fungal infection caused by members of the genus Cryptococcus, mainly those belonging to the Cryptococcus neoformans/Cryptococcus gattii species complexes. Here, we report a comprehensive molecular epidemiological study of the environmental distribution of Cryptococcus isolates in Shiraz, Iran with review of litreature. METHOD: A total of 406 samples were obtained from Eucalyptus trees and 139 samples from pigeon droppings. Cryptococcus species identification and genotyping were performed by amplified fragment length polymorphism (AFLP) fingerprinting sequencing and sequencing of the ITS rDNA region. RESULTS: Majority of the isolates belonged to the Naganishia taxon (n=69) including N. albida (formerly C. albidus, n=62), N. globosa (formerly C. saitoi, n=4), N. adeliensis (formerly C. adeliensis, n=2), N. diffluens (formerly C. diffluens, n=1), and the identified C. neoformans isolates (n=25) belonged to genotype AFLP1/VNI (n=22) and AFLP1B/VNII (n=3). CONCLUSION: More research efforts should be employed to isolate C. gattii species complex from environmental niches in Iran and provide additional evidence related to novel molecular types.

Pesticide behavior in paddy fields and development of azole-resistant Aspergillus fumigatus: Should we be concerned?

Tricyclazole as a common fungicide wildly used to control rice blast disease in the Asian country may induce azole resistance in Aspergillus fumigatus isolates. The main reason of the acquired azole resistance is probably environmental exposure through wide fungicide use in agriculture. The present study was conducted with the aim of investigating the current status of the azole-resistant A. fumigatus obtained from the paddy fields with exposure to tricyclazole. A total of 108 soil samples were collected from four different locations of paddy fields in Mazandaran Province, Iran. Pure fungal colonies were initially identified based on the conventional tools, and then reconfirmed by using DNA sequencing of the partial ß-tubulin gene. In addition, the in vitro antifungal susceptibility was determined using the Clinical and Laboratory Standards Institute document (CLSI) M38-A2. The identification of the mutations in the CYP51A gene was accomplished by the implementation of the polymerase chain reaction amplification assay on the selected isolates. Overall, 31 of 108 (28.7%) isolates were identified as A. fumigatus, four (3.7%) of which were recognized as azole-resistant with MICs of itraconazole ≥8µg/ml and voriconazole ≥4µg/ml. Only two out of the four azole-resistant A. fumigatus isolates harboured TR34/L98H variant and the other two isolates were identified as azole-resistant without any CYP51A gene mutations. However, other point mutations (TR46/Y121F/T289A) were not detected in the CYP51A gene. The high molecular structure similarity between environmental and medical triazoles may result in the selection of resistance mechanisms. Nonetheless, one might conclude that tricyclazole with different molecular structures against medical azoles induces azole-resistance in A. fumigatus isolates. The behavior of such pesticides as tricyclazole in the rice paddy fields would have an effective role in the development of azole-resistance that requires detailed information.

Epidemiological and mycological characteristics of candidemia in Iran: A systematic review and meta-analysis.

To date, there has been no comprehensive review of the epidemiology, risk factors, species distribution, and outcomes of candidemia in Iran. This study aimed to perform a systematic review and meta-analysis of all reported candidemia cases in Iran until December 2015. The review process occurred in three steps, namely a literature search, data extraction and statistical analyses. After a comprehensive literature search, we identified 55 cases. The mean age of patients was 46.80±24.30 years (range 1-81 years). The main risk factors for candidemia were surgery and burns (23.6%), followed by malignancies (20%), use of broad-spectrum antibiotics (18.2%), and diabetes (7.3%). Candida parapsilosis (n=17, 30.8%) was the leading agent, followed by Candida albicans (n=15, 27.3%), Candida glabrata (n=10, 18.2%), and Candida tropicalis (n=8, 14.5%). The frequencies of candidemia cases due to C. glabrata, C. parapsilosis, and C. albicans were significantly higher among patients aged>60, 21-40, and 41-60 years, respectively. Comparison of risk factors for candidemia by multiple logistic regression showed that one of the most important risk factors was surgery (OR: 4.245; 95% CI: 1.141-15.789; P=0.031). The outcome was recorded in only 19 cases and 13 of those patients (68.4%) expired. This study confirms that knowledge of the local epidemiology is important when conducting surveillance studies to prevent and control candidemia and will be of interest for antifungal stewardship.

Successful treatment with caspofungin of candiduria in a child with Wilms tumor; review of literature.

Symptomatic candiduria often occurs in patients with indwelling bladder catheters or immunocompromised host. Isolation of Candida in urine in high-risk patients should primarily be considered as a marker for candidemia. Hematological and genitourinary malignancies are one of the main risk factors associated with Candida urinary tract infections (CUTI). Fluconazole is a choice for initial treatment of CUTI, but it is fluctuate depending on the patient's condition including renal failure, site of urinary infection and Candida species. Poor glomerular filtration is the main disadvantage echinocandins resulting in very low urinary concentrations. Therefore, echinocandins have prohibited their use in CUTI. Up to now, there are only 10 cases reported in the literatures with highly effective echinocandins in CUTI because of high concentrations in the tissue are needed to control invasive fungal disease. Herein, we report a candiduria followed by renal candidiasis caused by Candida albicans in a 6-year-old Iranian male with a history of Wilms tumor in left kidney. Direct examination of urine specimen revealed an infection due to budding yeast cells with numerous pseudohyphae and growths of C. albicans was reconfirmed by sequencing of ITS rDNA region. MICs in increasing order were as follows: caspofungin (0.016µg/ml), voriconazole (0.125µg/ml), amphotericin B (0.25µg/ml), itraconazole (0.5µg/ml) and fluconazole (2µg/ml). It seems that successful treatment with caspofungin owes achieved high renal tissue concentrations that are unrelated to glomerular filtration. In conclusion, predisposing factors for better outcome are more important than treatment of CUTI, therefore, management of UTI is essential for critically patients.

Assessing the trace metal pollution in the sediments of Mahshahr Bay, Persian Gulf, via a novel pollution index.

Sediment samples were collected from the Petrochemical Special Economic Zone of Mahshahr Bay, Persian Gulf, and analyzed for possible trace metal contamination by means of a chemical partitioning method. The heavy metal contents in the sediments follow the order of Al > Sr > Mn > Zn > Ni > Ba > Cr > Cu > As > Co. The degree of sediment contamination was evaluated using pollution load index (PLI), modified degree of contamination (mC d), geo-accumulation index (I geo), and enrichment factor (EF). All these indices compare present concentrations of metals to their background levels in crust and shale. In a specific area with high geological background like Mahshahr Bay, such a comparison may lead to erroneous conclusions. Due to the remarkable contribution of lithogenous fraction, as the natural component, to the bulk concentration of trace metals in the sediments of such an area, assessment of chemical hazard to the surrounding aquatic environment should not be carried out through traditional approaches. In the present study, anthropogenic portion of the metals was determined through one-step chemical sequential extraction and lithogenous portion substituted for the mean crust and shale levels in the new pollution index (RIAquatic). PLI, mC d, and I geo revealed overall low values, but EF, pollution index (I POLL), and newly developed pollution index were relatively high for all samples.

Spin-transfer torque generated by a topological insulator.

Magnetic devices are a leading contender for the implementation of memory and logic technologies that are non-volatile, that can scale to high density and high speed, and that do not wear out. However, widespread application of magnetic memory and logic devices will require the development of efficient mechanisms for reorienting their magnetization using the least possible current and power. There has been considerable recent progress in this effort; in particular, it has been discovered that spin-orbit interactions in heavy-metal/ferromagnet bilayers can produce strong current-driven torques on the magnetic layer, via the spin Hall effect in the heavy metal or the Rashba-Edelstein effect in the ferromagnet. In the search for materials to provide even more efficient spin-orbit-induced torques, some proposals have suggested topological insulators, which possess a surface state in which the effects of spin-orbit coupling are maximal in the sense that an electron's spin orientation is fixed relative to its propagation direction. Here we report experiments showing that charge current flowing in-plane in a thin film of the topological insulator bismuth selenide (Bi2Se3) at room temperature can indeed exert a strong spin-transfer torque on an adjacent ferromagnetic permalloy (Ni81Fe19) thin film, with a direction consistent with that expected from the topological surface state. We find that the strength of the torque per unit charge current density in Bi2Se3 is greater than for any source of spin-transfer torque measured so far, even for non-ideal topological insulator films in which the surface states coexist with bulk conduction. Our data suggest that topological insulators could enable very efficient electrical manipulation of magnetic materials at room temperature, for memory and logic applications.

ERCC1 is a prognostic biomarker in locally advanced head and neck cancer: results from a randomised, phase II trial.

BACKGROUND: Cisplatin-radiotherapy is a preferred standard for locally advanced, head and neck squamous cell carcinoma (HNSCC). However, the cisplatin-attributable survival benefit is small and toxicity substantial. A biomarker of cisplatin resistance could guide treatment selection and spare morbidity. The ERCC1-XPF nuclease is critical to DNA repair pathways resolving cisplatin-induced lesions. METHODS: In a phase II trial, patients with untreated Stage III-IVb HNSCC were randomised to cisplatin-radiotherapy with/without erlotinib. Archived primary tumours were available from 90 of 204 patients for this planned substudy. Semi-quantitative ERCC1 protein expression (H-score) was determined using the FL297, 4F9, and 8F1 antibodies. The primary analysis evaluated the relationship between continuous ERCC1 protein expression and progression-free survival (PFS). Secondary analyses included two pre-specified ERCC1 cutpoints and performance in HPV-associated disease. RESULTS: Higher ERCC1 expression was associated with inferior PFS, as measured by the specific antibodies FL297 (HR=2.5, 95% CI=1.1-5.9, P=0.03) and 4F9 (HR=3.0, 95% CI=1.2-7.8, P=0.02). Patients with increased vs decreased/normal ERCC1 expression experienced inferior PFS (HR=4.8 for FL297, P=0.003; HR=5.5 for 4F9, P=0.007). This threshold remained prognostic in HPV-associated disease. CONCLUSION: ERCC1-XPF protein expression by the specific FL297 and 4F9 antibodies is prognostic in patients undergoing definitive cisplatin-radiotherapy for HNSCC, irrespective of HPV status.

Endoscopic neck dissection in an animal model: comparison of nodal yield with open-neck dissection.

OBJECTIVE: To evaluate the possibility, complications, and efficacy of endoscopic neck dissection (END) in a porcine model. DESIGN: Experimental self-controlled study. SUBJECTS: Minipigs. INTERVENTION: Endoscopic neck dissection was performed using general anesthesia with techniques adapted from laparoscopic surgery. The tissue specimens removed were divided according to porcine equivalents of human neck groups. After the completion of END, open-neck dissection was performed using standard surgical techniques, and the remaining tissue within each neck group was retrieved. A pathologist evaluated each specimen without knowing its exact origin in terms of neck group or side and the type of surgical technique used. For each specimen, the number of retrieved lymph nodes and their anatomical integrity were analyzed. RESULTS: Ten neck dissections were performed in 8 minipigs without any major complications. The number of retrieved lymph nodes by END was 18.4 +/- 7.4 (mean +/- SD). Completed open-neck dissection retrieved an additional 3.3 +/- 1.8 lymph nodes. The efficacy rate of END was 88% +/- 10% (+/ -SD). The majority of retrieved lymph nodes were intact, with less than 5% of nodes exhibiting crushing artifacts. CONCLUSIONS: Endoscopic neck dissection in a porcine model seems to be free of major complications and able to retrieve the majority of neck lymph nodes. A larger number of animals and their survival need to be studied before human studies can begin.

New objective and quantitative tests for gustatory sweating.

Two newly developed tests for gustatory sweating, providing both quantitative and topographic information, are presented. In both tests a paper stencil shaped to fit the complex anatomy of the parotid region is used. The blotting paper technique uses the difference in weight before and after gustatory stimulation to measure the amount of sweating. The iodine-sublimated paper histogram (ISPH) uses iodine sublimated office paper that changes colour when wet. The paper stencil is than digitized and a histogram algorithm applied to measure the area of sweating. A calibration of these tests with known and appropriate quantities of saline is presented.