Deletion of Fibroblast Growth Factor Receptor 2 from the Peri-Wolffian Duct Stroma Leads to Ureteric Induction Abnormalities and Vesicoureteral Reflux

Purpose: Pax3cre-mediated deletion of fibroblast growth factor receptor 2 (Fgfr2) broadly in renal and urinary tract mesenchyme led to ureteric bud (UB) induction defects and vesicoureteral reflux (VUR), although the mechanisms were unclear. Here, we investigated whether Fgfr2 acts specifically in peri-Wolffian duct stroma (ST) to regulate UB induction and development of VUR and the mechanisms of Fgfr2 activity. Methods: We conditionally deleted Fgfr2 in ST (Fgfr2 ST-/- ) using Tbx18cre mice. To look for ureteric bud induction defects in young embryos, we assessed length and apoptosis of common nephric ducts (CNDs). We performed 3D reconstructions and histological analyses of urinary tracts of embryos and postnatal mice and cystograms in postnatal mice to test for VUR. We performed in situ hybridization and real-time PCR in young embryos to determine mechanisms underlying UB induction defects. Results: We confirmed that Fgfr2 is expressed in ST and that Fgfr2 was efficiently deleted in this tissue in Fgfr2 ST-/- mice at embryonic day (E) 10.5. E11.5 Fgfr2 ST-/- mice had randomized UB induction sites with approximately 1/3 arising too high and 1/3 too low from the Wolffian duct; however, apoptosis was unaltered in E12.5 mutant CNDs. While ureters were histologically normal, E15.5 Fgfr2 ST-/- mice exhibit improper ureteral insertion sites into the bladder, consistent with the ureteric induction defects. While ureter and bladder histology appeared normal, postnatal day (P) 1 mutants had high rates of VUR versus controls (75% versus 3%, p = 0.001) and occasionally other defects including renal hypoplasia and duplex systems. P1 mutant mice also had improper ureteral bladder insertion sites and shortened intravesicular tunnel lengths that correlated with VUR. E10.5 Fgfr2 ST-/- mice had decreases in Bmp4 mRNA in stromal tissues, suggesting a mechanism underlying the ureteric induction and VUR phenotypes. Conclusion: Mutations in FGFR2 could possibly cause VUR in humans. © 2013 Walker et al

Dissemination of different sequence types lineages harboring blaCTX-M-15 among uropathogenic Escherichia coli in Kerman, Iran

Objective(s): Escherichia coli is one of the most important causes of urinary tract infections (UTIs). The aim of this study was to determine antimicrobial resistance, resistance and virulence genes; phylogenetic groups and identify the epidemiologic features of uropathogenic E. coli (UPEC) isolates by multilocus sequence typing (MLST). Materials and Methods: One hundred isolates of E. coli from inpatients with UTIs were collected in Kerman, Iran. Antimicrobial susceptibility testing, ESBLs, AmpC production and biofilm formation were performed by phenotypic methods. Phylogenetic groups, resistance and virulence genes were detected. Molecular typing of isolates was performed by MLST. Results: In this study, 76 of isolates were multidrug-resistant. The blaCTX-M-15 and blaTEM were the dominant ESBL-encoding gene. Among 63 ciprofloxacin-resistant isolates, the frequency of qnrS (15.8), qnrB (9.5), and aac (6')-Ib (25) genes was shown. Fifty-five present of isolates were classified as week biofilm, (14) moderate biofilm, and (5) strong. The predominant phylogenetic group was B2 (3). The prevalence of virulence genes ranged fimH (93), iutA (66), KpsmtII (59), sat (39), cnf (28) and hlyA (27). According to MLST results, 14 sequence types (ST) including ST-693, ST-90, ST-101, ST-1664, ST-2083, ST-131, ST-4443, ST-744, ST-361, ST-405, ST-922, ST-648, ST-5717and ST-410 were detected, indicating a high degree of genotypic diversity. Conclusion: We identified a high frequency of the ST131 clonal group among UTIs. These data show an important public health threat, and so further studies to control the dissemination and risk factors for acquisition of the ST131 clonal group and other STs are needed to make effective control. © 2020 Mashhad University of Medical Sciences. All rights reserved

Azole antifungal resistance in candida albicans and candida glabrata isolated from vulvovaginal candidiasis patients

Background: Vulvovaginal candidiasis (VVC) is the most frequent fungal disorder in healthy and normal women. Objectives: The aim of this study was to evaluate the in vitro antifungal susceptibility of clinical isolates Candida albicans and Candida glabrata, the two most common candida species in Iranian patients with VVC. Methods: One hundred and eight clinical isolates of candida, including; C. albicans (n = 77) and C. glabrata: (n = 31) were isolated from the 108 patients with VVC. The in vitro activity of caspofungin (CAS), amphotericin B (AMB), voriconazole (VRC), itraconazole (ITC), fluconazole (FLC), and nystatin (NYS) were determined according to the CLSI M27-A3 and CLSI M27-S4. Results: Our results were shown 8 (25.8 %) and 6 (7.8 %) C. glabrata and C. albicans isolates resistance to FLU, respectively. Furthermore, resistance to VRC and ITC were observed in 8.4%, and 3.7% of all isolates, and six isolates (5.6%) had intermediate MIC to CAS. Conclusions: We reported 8 (25.8 %) and 6 (7.8 %) C. glabrata and C. albicans isolates resistance to FLU, respectively. Furthermore, resistance to VRC and ITC were observed in 8.4% and 3.7% of all isolates, respectively. © 2021, Author(s)

Evaluation of chromosomally and acquired mechanisms of resistance to carbapenem antibiotics among clinical isolates of Pseudomonas aeruginosa in Kerman, Iran

Introduction: Multidrug-resistant (MDR) of Pseudomonas aeruginosa isolates are increasing around the world which can cause serious problems for antimicrobial therapy in hospital settings. Our aim in present study was to evaluation of intrinsic and acquired mechanisms of resistance to carbapenem antibiotics among 170 clinical isolates of P. aeruginosa in Kerman, Iran. Material and methods: CLSI recommendations were used for determination of antimicrobial susceptibility testing of isolates. Metallo-β-lactamase (MBL) producing isolates were detected by the double-disc synergy test (DDST) using the 2-mercaptopropionic acid and efflux pump over-activity were determined by the microdilution method using PabN. PCR-sequencing technique was used for to detection and sequencing of carbapenemase, blaCTX-M and oprD genes. Transcriptional levels of the mexA gene in carbapenem-resistant isolates was evaluated by qReal-time PCR (qPCR) and ERIC-PCR technique was used for molecular typing of carbapenem-resistant isolates. Results: According to our findings, colistin was the most active agent against P. aeruginosa isolates. All carbapenem-resistant P. aeruginosa were efflux pumps overproducers and 4.92 isolates were MBL producing. The MBL genes including: blaNDM, blaVIM, blaIMP and blaSIM were detected in (2, 3.3), (1, 1.6), (1, 1.6), (1, 1.6), of the isolates, respectively. The oprD gene was disrupted in 9 isolates by insertion sequences (ISs). The qPCR experiment showed that transcriptional levels of mexA gene in 26 (42.6) carbapenem-resistant P. aeruginosa have more than 2-7-fold change with comparison to P. aeruginosa PAO1 strain. ERIC-PCR results was showed 10 clusters and 6 singletons in carbapenem-resistant isolates. Conclusions: In this study, we reported blaNDM-1 and blaSIM positive P. aeruginosa isolates for the first time in Kerman, Iran. Furthermore, our results were showed that intrinsic resistance mechanisms including overexpression of efflux pump and inactivation of oprD have an important role in resistance to carbapenem antibiotics in clinical isolates of P. aeruginosa in Kerman, Iran. © 2020 Elsevier Inc

Determination of antibiotic resistance genes, immune evasion cluster and agr types among Staphylococcus aureus strains isolated from children with adenoiditis

Adenoiditis is the most common infection in childhood and different microorganism such as viruses and bacteria cause this infection. Staphylococcus aureus (S. aureus) is the main Gram-positive bacterium that can involve in adenoiditis. The aim of this study was to determination of antibiotic resistance, immune evasion cluster genes and agr types among S. aureus isolates were collected from children with adenoiditis. Totally 36 clinical isolates of S. aureus were obtained from 112 children suffering from adenoiditis. Susceptibility of the isolates to different antimicrobial agents were determined using standard disk diffusion method. PCR technique was used for detection of resistance and virulence genes. SCCmec and agr typing were used for molecular typing of the isolates. All isolates were sensitive to vancomycin and 47.2 of isolates were resistant to penicillin. Twenty-two present of isolates were considered as MRSA and SCCmec type IV was detected in 5 MRSA isolates. Only, agr types I and II were identified among the isolates. ermC was the predominant macrolide resistance gene and ant(4�)-Ia was the most common aminoglycoside resistance gene. Virulence genes including sak, chp and sea were identified in 47.2 (n = 17), 30.5 (n = 11) and 13.8 (n = 5). This study was the first report in Iran, Kerman, about determination of antibiotic resistance, virulence genes, agr groups and SCCmec types among the clinical S. aureus isolates were collected from children with adenoiditis. Also, our results can be helpful in empirical therapy and increase our knowledge about genetic characteristics of S. aureus isolates are involved to adenoiditis. © 202

Familial Cases of Trichophyton benhamiae Infection Transmitted from a Guinea Pig in Iran

Trichophyton benhamiae is a zoophilic dermatophyte mainly transmitted to humans from guinea pigs. This zoophilic species can also cause dermatophytosis as reported by human contact with other animals, such as rabbit, cat, and fox. Here, we report the tinea faciei and tinea corporis cases: a 12-year-old girl and her 53-year-old father, with no history of immunodeficiency and underlying disease, caused by T. benhamiae transmitted from a guinea pig in Iran. Dermatological examination revealed several erythematous, round, scaly, and approximately 1–4-cm-diameter lesions in both patients. The girl had seven skin lesions, and her father presented two skin lesions on the front side of his neck. The girl’s lesions had started 3 weeks before and her father’s lesions appeared 7 days after the first clinical appearance of the lesions in the daughter. The girl had daily close contact with a guinea pig, while her father did not have any direct exposure to the pet. Examination of the lesions scraping with 10% potassium hydroxide (KOH 10%) revealed hyaline septate hyphae and arthroconidia. The dermatophyte isolated in culture was identified as T. benhamiae using molecular analysis. The patients were successfully treated using topical sertaconazole nitrate 2% cream twice a day for 4 weeks

In vitro antifungal activity of luliconazole, efinaconazole, and nine comparators against aspergillus and candida strains isolated from otomycosis

Background: Aspergillus and Candida species are the most commonly identified fungal pathogens in otomycosis. However, we usually encounter some difficulties in its treatment because many patients show resistance to antifungal agents and present a high recurrence rate. Objectives: The current research was conducted to compare the in vitro activities of luliconazole (LUL), and efinaconazole (EFN) and the nine comparators on Aspergillus and Candida strains isolated from otomycosis. Methods: The in vitro activities of nine common antifungal drugs (amphotericin B (AMB), voriconazole (VRC), fluconazole (FLU), itraconazole (ITC), ketoconazole (KTO), clotrimazole (CLO), nystatin (NYS), terbinafine (TRB), and caspofungin (CAS)) and two novel new azoles (LUL and EFN) against of 108 clinical isolates of Aspergillus and Candida species obtained from otomycosis were assessed according to the CLSI broth microdilution document. Results: The LUL and EFN had the geometric mean minimum inhibitory concentrations (GM MICs) of 0.098 and 0.109 µg/mL against all Aspergillus strains, respectively. Furthermore, the GM MICs of all Candida isolates for LUL, EFN, CAS, CLO, VRC, AMB, ITC, KTO, FLU, NYS, and TRB were calculated to be 0.133, 0.144, 0.194, 0.219, 0.475, 0.537, 0.655, 1.277, 4.905, 9.372, and 13.592 µg/mL, respectively. Additionally, 6 (35.29%), 2 (11.7%), and 1 (5.88%) Candida isolates were resistant to FLU, CAS, and VRC, respectively. Conclusions: As the findings indicated, LUL and EFN showed the lowest GM MIC values against the examined species. Accordingly, these novel imidazole and triazole antifungal agents can be regarded as proper candidates for the treatment of otomycosis caused by Aspergillus and Candida strain

Oral Coenzyme Q10 supplementation leads to better preservation of kidney function in steroid-resistant nephrotic syndrome due to primary Coenzyme Q10 deficiency.

Primary Coenzyme Q10 (CoQ10) deficiency is an ultra-rare disorder caused by defects in genes involved in CoQ10 biosynthesis leading to multidrug-resistant nephrotic syndrome as the hallmark kidney manifestation. Promising early results have been reported anecdotally with oral CoQ10 supplementation. However, the long-term efficacy and optimal prescription remain to be established. In a global effort, we collected and analyzed information from 116 patients who received CoQ10 supplements for primary CoQ10 deficiency due to biallelic pathogenic variants in either the COQ2, COQ6 or COQ8B genes. Median duration of follow up on treatment was two years. The effect of treatment on proteinuria was assessed, and kidney survival was analyzed in 41 patients younger than 18 years with chronic kidney disease stage 1-4 at the start of treatment compared with that of an untreated cohort matched by genotype, age, kidney function, and proteinuria. CoQ10 supplementation was associated with a substantial and significant sustained reduction of proteinuria by 88% at 12 months. Complete remission of proteinuria was more frequently observed in COQ6 disease. CoQ10 supplementation led to significantly better preservation of kidney function (5-year kidney failure-free survival 62% vs. 19%) with an improvement in general condition and neurological manifestations. Side effects of treatment were uncommon and mild. Thus, our findings indicate that all patients diagnosed with primary CoQ10 deficiency should receive early and life-long CoQ10 supplementation to decelerate the progression of kidney disease and prevent further damage to other organs