Iranian National Survey on Tinea Capitis: Antifungal Susceptibility Profile, Epidemiological Characteristics, and Report of Two Strains with a Novel Mutation in SQLE Gene with Homology Modeling.

BACKGROUND: The data on the epidemiological and antifungal susceptibility profile of tinea capitis (TC) in Iran has not been updated in recent decades. This report presents the Iranian epidemiological and drug susceptibility data regarding the distribution of dermatophytes species isolated by six national mycology centers for a period of one year (2020-2021). MATERIAL AND METHODS: A total of 2100 clinical samples from individuals suspeted to TC were subjected to mycological analysis of direct microscopy and culture. For definite species identification, the culture isolates were additionally subjected to PCR-RFLP and PCR-sequencing of the ITS ribosomal DNA (ITS-rDNA) region. Antifungal susceptibility profiles for eight common antifungal drugs were determined by CLSI M38-A3 guidelines. The SQLE gene was partially amplified and sequenced in two terbinafine-resistant and two susceptible T. mentagrophytes isolates to elucidate probable substitutions involved in resistance. RESULTS: TC (n = 94) was diagnosed in 75 children (79.8%) and 19 adults (20.2%) by direct microscopy and culture. Frequency of TC was significantly more among males (66 males = 70.2% vs 28 females = 29.8%). The prevalent age group affected was 5-9 years (39.36%). Thirty-two (34.04%) T. mentagrophytes, 27 (28.7%) T. tonsurans, 14 (14.9%) M. canis, 13 (13.8%) T. violaceum, 5 (5.32%) T. indotineae, 2 (2.1%) T. benhamiae, and 1 (1.1%) T. schoenleinii were identified as the causative agents. MIC values of isolates showed susceptibility to all antifungal agents, except for fluconazole and griseofulvin with GM MIC of 11.91 µg/ml and 2.01 µg/ml, respectively. Terbinafine exhibited more activity against isolates, with GM MIC 0.084 µg/ml followed by ketoconazole (0.100 µg/ml), econazole (0.107 µg/ml), itraconazole (0.133 µg/ml), butenafine (0.142 µg/ml), and miconazole (0.325 µg/ml). Two resistant T. mentagrophytes isolates harbored missense mutations in SQLE gene, corresponding to amino acid substitution F397L. Remarkably, one unique mutation, C1255T, in the SQLE sequence of two terbinafine-susceptible T. mentagrophytes strains leading to a change of leucine at the 419th position to phenylalanine (L419F) was detected. CONCLUSIONS: T. mentagrophytes, T. tonsurans, and M. canis remained the main agents of TC in Iran, however less known species such as T. indotinea and T. benhamiae are emerging as new ones. Terbinafine could still be the appropriate choice for the treatment of diverse forms of TC.

Evaluation of squamous cell carcinoma antigen 1 expression in oral squamous cell carcinoma (tumor cells and peritumoral T-lymphocytes) and verrucous carcinoma and comparison with normal oral mucosa.

BACKGROUND: Squamous cell carcinoma antigen (SCCA) is used as a prognostic marker for recurrence of squamous cell carcinoma in various sites, including head and neck. Studies suggest that its high serum levels are correlated to some clinical features, such as nodal metastasis. However, it is still unknown if high SCCA in patients with SCCA tissue expression in tumor cells are related to peripheral T-lymphocytes. Therefore, we did this study to evaluate SCCA expression in squamous cell carcinoma and verrucous carcinoma and to compare it with normal oral mucosa, also investigating the correlation between serum-based and tissue-based antigen levels. METHODOLOGY: In this study, the immunohistochemistry (IHC) technique was used to determine the SCCA1 expression pattern in 81 specimens divided into 3 groups, including oral squamous cell carcinoma, verrucous carcinoma, and normal oral mucosa. Serum-based and tissue-based antigen levels of 20 oral squamous cell carcinoma cases were compared by the western blot assay. SCCA expression was also evaluated and compared in both tumor cells and peripheral T-lymphocytes by the immunofluorescence assay. RESULTS: Our results showed that the SCCA levels in SCC specimens were significantly lower than in verrucous carcinoma and normal and hyperplastic oral mucosa specimens. We found no correlation between the IHC expression of SCCA and serum levels. SCCA was well expressed in both tumor cells and peripheral T-lymphocytes. CONCLUSION: Decreasing SCCA in SCC specimens suggested that SCC tumor cells may affect more than the serum levels of SCCA in some patients. In addition, expression of SCCA in peripheral T-lymphocytes showed that both tumor cells and T-lymphocytes may cause serum SCCA.

Evaluation of squamous cell carcinoma antigen 1 expression in oral squamous cell carcinoma (tumor cells and peritumoral T-lymphocytes) and verrucous carcinoma and comparison with normal oral mucosa

Abstract Background: Squamous cell carcinoma antigen (SCCA) is used as a prognostic marker for recurrence of squamous cell carcinoma in various sites, including head and neck. Studies suggest that its high serum levels are correlated to some clinical features, such as nodal metastasis. However, it is still unknown if high SCCA in patients with SCCA tissue expression in tumor cells are related to peripheral T-lymphocytes. Therefore, we did this study to evaluate SCCA expression in squamous cell carcinoma and verrucous carcinoma and to compare it with normal oral mucosa, also investigating the correlation between serum-based and tissue-based antigen levels. Methodology: In this study, the immunohistochemistry (IHC) technique was used to determine the SCCA1 expression pattern in 81 specimens divided into 3 groups, including oral squamous cell carcinoma, verrucous carcinoma, and normal oral mucosa. Serum-based and tissue-based antigen levels of 20 oral squamous cell carcinoma cases were compared by the western blot assay. SCCA expression was also evaluated and compared in both tumor cells and peripheral T-lymphocytes by the immunofluorescence assay. Results: Our results showed that the SCCA levels in SCC specimens were significantly lower than in verrucous carcinoma and normal and hyperplastic oral mucosa specimens. We found no correlation between the IHC expression of SCCA and serum levels. SCCA was well expressed in both tumor cells and peripheral T-lymphocytes. Conclusion: Decreasing SCCA in SCC specimens suggested that SCC tumor cells may affect more than the serum levels of SCCA in some patients. In addition, expression of SCCA in peripheral T-lymphocytes showed that both tumor cells and T-lymphocytes may cause serum SCCA.

Decreased Sox2 Messenger RNA Expression in Basal Cell Carcinoma.

BACKGROUND: Sox2, zeb1, and p21 have been implicated in aggressive behavior of squamous cell carcinoma (SCC) and melanoma. However, their expression level in basal cell carcinoma (BCC) has not been elucidated. We hypothesized BCC, contrary to SCC, and melanoma, could be a suitable model to study mechanisms which attenuate tumor metastasis. The aim of this study was to examine the messenger RNA (mRNA) expression levels of sox2, zeb1, and p21 in BCC. MATERIALS AND METHODS: Twenty-seven nonmetastatic BCC and twelve normal skin samples were evaluated using real-time reverse transcriptase polymerase chain reaction. RESULTS: The stemness marker sox2 demonstrated marked down-regulation, but zeb1 and p21 showed no significant change. CONCLUSIONS: Here, we report a negative association between sox2 mRNA expression level and nonmetastatic BCC, thus, providing a likely explanation for the fact that normal skin is more reliant on sox2 than BCC. BCC may be using decreased sox2 mRNA to remain incognito from metastatic potential.

Inherited Interleukin 2-Inducible T-Cell (ITK) Kinase Deficiency in Siblings With Epidermodysplasia Verruciformis and Hodgkin Lymphoma.

Biallelic mutations in the ITK gene cause a T-cell primary immunodeficiency with Epstein-Barr virus (EBV)-lymphoproliferative disorders. We describe a novel association of a homozygous ITK mutation with ß-human papillomavirus (HPV)-positive epidermodysplasia verruciformis. Thus, loss of function in ITK can result in broad dysregulation of T-cell responses to oncogenic viruses, including ß-HPV and EBV.

Autosomal recessive congenital ichthyosis: Genomic landscape and phenotypic spectrum in a cohort of 125 consanguineous families.

Autosomal recessive congenital ichthyosis (ARCI), a phenotypically heterogeneous group of non-syndromic Mendelian disorders of keratinization, is caused by mutations in as many as 13 distinct genes. We examined a cohort of 125 consanguineous families with ARCI for underlying genetic mutations. The patients' DNA was analyzed with a gene-targeted next generation sequencing panel comprising 38 ichthyosis associated genes. The interpretations of results of genomic data were assisted by genome-wide homozygosity mapping and transcriptome sequencing. Sequence data analysis identified biallelic mutations in 106 families out of a total of 125 (85%), most of them (102, 96.2%) being homozygous, reflecting consanguinity in these families. Among the 85 distinct mutations in 10 different genes, 45 (53%) were previously unreported. Phenotype-genotype correlations allowed assignment of specific genes in the majority of the families to a specific subtype of ARCI, lamellar ichthyosis (LI) versus congenital ichthyosiform erythroderma (CIE). Interestingly, mutations in several genes could give rise to an overlapping phenotype consistent with either LI or CIE. Also, this is the third report for SDR9C7 and SULT2B1, and fourth report for CERS3 mutations. Direct comparison of our results with previously published regional cohorts highlights the global mutation landscape of ARCI, however, population specific differences were noted.

Combination of Fractional Radiofrequency and Thermo-Contraction Systems for Facial Skin Rejuvenation: A Clinical and Histological Study.

BACKGROUND: Radiofrequency energy systems are popular options in the treatment of skin laxity and wrinkles. Fractional radiofrequency devices (FRFs) have increased the efficacy and safety. The thermo-contraction (TC) system is also a novel technology that can promote a marked lifting effect. OBJECTIVES: This trial was done to assess the safety and efficacy of a combination treatment using the FRF system and TC for facial skin rejuvenation. METHODS: Fifteen female volunteers (mean age, 47.07 ± 8.83 years) received 3 FRF and 6 TC bipolar treatments in 3 weeks. Assessment methods included wrinkle grading by independent investigator using Glogau wrinkle scoring, objective measurement of depth, area, and volume of right nasolabial fold (using the VisioFace CSI software), thickness and echo-density of the dermis (using high-frequency ultrasound), and measurement of the skin biophysical parameters before and 3 months after last treatment. Histological assessment was also performed on 5 volunteer participants. RESULTS: The clinical evaluation showed a significant improvement in Glogau wrinkle scoring after 3 months (P value, 0.041). The area and volume of nasolabial folds were also significantly reduced (P values, 0.026 and 0.031, respectively). Skin ultrasound showed a significant increase in echo-density of the dermis, which was confirmed by histological findings of an increase in dermal collagen content. Adverse reactions were all transient and mild in severity, and subjects were "moderately satisfied" with the treatment (Likert scale, 3.6 out of 5). CONCLUSIONS: The results of this trial showed that a combination therapy by FRF and TC bipolar systems is efficient and safe for facial skin rejuvenation.

BMI1 and TWIST1 downregulated mRNA expression in basal cell carcinoma.

BACKGROUND: BMI1, TWIST1 and SNAI2/SLUG have been implicated in aggressive behavior of squamous cell carcinoma (SCC) and melanoma and BMI1 expression could identify subtypes of Merkel cell carcinoma (MCC). However, BMI1, TWIST1 and SNAI2 expression levels in basal cell carcinomas (BCCs) have not been elucidated. We hypothesized BCC could be a good model system to decipher mechanisms which inhibit processes that drive tumor metastasis. The aim of this study was to examine the mRNA expression level of BMI1, TWIST1, and SNAI2 in BCCs. MATERIALS AND METHODS: Thirty-five fresh non-metastatic BCC tissue samples and seven fresh normal skin tissue samples were evaluated by real-time RT-PCR. RESULTS: BMI1 and TWIST1 demonstrated marked down-regulation (p<0.00l, p=0.00l respectively), but SNAI2 showed no significant change (p=0.12). CONCLUSIONS: Previous literature has clearly demonstrated a positive association between BMI1 and TWIST1 expression and metastatic BCC, aggressive SCC and melanoma. Here, we demonstrated a negative association between BMI1 and TWIST1 mRNA expression level and BCC.

Synthesis of a phenylalanine imprinted polymer for attenuation of phenylalanine absorption via the gut in a murine hyperphenylalaninemia model.

Polymer technology plays an influential role in biomedical sciences. Molecular imprinting is a technique for preparation of polymers with structure-selective adsorptive properties. High selectivities of these materials have nowadays advanced to the point that they are being utilized for several biomedical applications such as drug delivery. Phenylketonuria is a genetic disease characterized by accumulation of phenylalanine (Phe) in blood with toxic consequences. The aim of the present study is to synthesize a phenylalanine imprinted polymer for attenuation of phenylalanine absorption in the gut in a murine hyperphenylalaninemia model. A molecularly imprinted polymer (MIP) against Phe and a non-imprinted polymer (NIP) were synthesized and their Phe binding properties were studied in Simulated Intestinal Fluid (SIF). Two classes of binding sites were then found in the MIP: high affinity (KD = 62.5 µM) and low affinity (KD = 1 mM). Histological toxicity and LD50 of the MIP, after oral administration to murine hyperphenylalaninemia, were examined prior to investigation of the effects of the imprinted polymer on blood Phe concentrations in animal models. Our findings suggest that the MIP against Phe can decrease the blood Phe concentration in an animal model of hyperphenylalaninemia.

The prevalence of Epstein-Barr virus infection in head and neck non-Hodgkin's lymphomas in Khorasan, northeast of Iran.

OBJECTIVES: To investigate the frequency and possible role of Epstein-Barr virus infection in non-Hodgkin's lymphomas of the oral cavity and maxillofacial region in Khorasan (Northeast of Iran). METHODS: The cross-sectional retrospective study assessed the frequency of Epstein-Barr virus infection in non-immunosuppressed non-Hodgkin's lymphoma cases of the oral cavity and maxillofacial region. Formalin-fixed, paraffin-embedded tissue sections from 34 cases of head and neck non-Hodgkin's lymphoma (17 low-grade B-cell lymphoma, 14 diffuse large B-cell lymphoma, and 3 peripheral T cell lymphoma) were selected as a case group, and 10 normal lymph node sections were considered as a control group. Polymerase chain reaction was used to detect the EBV-DNA in tissue specimens. SPSS 16 was used for statistical analysis of the data. RESULTS: EBV-DNA was detected in 26.5% of NHL samples. Among NHLs, Epstein-Barr virus was found to be positive in 50% cases with diffuse large B-cell lymphoma and 11.8% of low grade B-cell lymphomas. Epstein-Barr virus was not detected in any cases of peripheral T-cell lymphoma. CONCLUSION: Although it seems that Epstein-Barr virus appears to be an etiological factor in some subtypes of non-Hodgkin's lymphomas, especially in diffuse large B-cell lymphoma, more researches should be done to investigate the relationship between Epstein-Barr virus infection and head and neck non-Hodgkin's lymphomas.

Accelerated epidermal regeneration and improved dermal reconstruction achieved by polyethersulfone nanofibers.

INTRODUCTION: In this study, thick polyethersulfone (PES) nanofibrous scaffolds were prepared by fine tuning of electrospinning parameters and was evaluated for wound dressing applications. MATERIALS AND METHODS: Scanning electron microscopy and Brunauer-Emmett-Teller methods were used for PES nanofibers characterization. The interaction between fibroblasts and nanofibers was studied in vitro. Further, a mouse model was used to evaluate the effectiveness of the PES scaffold in wound healing. Vaseline gauze dressing and a conventional gas permeable bandage were used as a control. The wound repair process was evaluated by histological examination and immunohistochemistry staining using antibodies to cytokeratin 10 (CK10), proliferating cell nuclear antigen (PCNA), and alpha-smooth muscle actin (alpha-SMA). RESULTS AND CONCLUSION: The characterization of nanofibers showed that the PES membrane has nanoscale, porous, high surface area structure. These properties conferred higher exudate absorption capacity for the PES scaffold which is essential for effective wound healing. In vitro results indicated that the PES scaffold can support fibroblast proliferation similar to that with tissue culture polystyrene. Epithelial regeneration was expeditiously accelerated under PES as compared with Vaseline gauze. Greater fibroblast maturation, improved collagen deposition and faster edema resolution were the superior properties of PES over the commercial dressing. Based on these results we conclude that the biocompatible PES nanofibers can effectively be used as a dressing to accelerate wound healing.