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This study aimed to investigate azole resistance mechanisms in Aspergillus flavus, which involve cyp51A and cyp51B genes. Real-time Reverse Transcriptase qPCR method was applied to determine the overexpression of cyp51A and cyp51B genes for 34 A. flavus isolates. PCR sequencing of these two genes was used to detect the presence of gene mutations. Susceptibility test found sensitivity to voriconazole (VOR) in all strains. 14.7% and 8.8% of isolates were resistant to itraconazole (IT) and posaconazole (POS), respectively, with a cross-resistance in 5.8%. For the double resistant isolates (IT/POS), the expression of cyp51A was up to 17-fold higher. PCR sequencing showed the presence of 2 mutations in cyp51A: a synonymous point mutation (P61P) in eight isolates, which did not affect the structure of CYP51A protein, and another non synonymous mutation (G206L) for only the TN-33 strain (cross IT/POS resistance) causing an amino acid change in the protein sequence. However, we noted in cyp51B the presence of the only non-synonymous mutation (L177G) causing a change in amino acids in the protein sequence for the TN-31 strain, which exhibits IT/POS cross-resistance. A short single intron of 67 bp was identified in the cyp51A gene, whereas three short introns of 54, 53, and 160 bp were identified in the cyp51B gene. According to the models provided by PatchDock software, the presence of non-synonymous mutations did not affect the interaction of CYP51A and CYP51B proteins with antifungals. In our study, the overexpression of the cyp51A and cyp51B genes is the primary mechanism responsible for resistance in A. flavus collection. Nevertheless, other resistance mechanisms can be involved.

Seventy-seven strains of Malassezia were included in this study. Biofilm and hydrolytic enzyme production were studied by using specific solid media. The Real-Time reverse transcriptase qPCR method was applied to determine the overexpression of genes encoding the extracellular enzymes. All included Malassezia species produced biofilms. No statistically significant difference was observed between Malassezia species in biofilm formation (p = 0.567). All Malassezia species produced lipase, and 95% of Malassezia globosa showed a strong enzymatic activity (Pz = 0.55 ± 0.02). A statistically significant difference was observed between the mean keratinase indices of Malassezia slooffiae and the other Malassezia species (p = 0.005). The overexpression of one or more genes was observed in 100% of strains isolated from patients with folliculitis, 87.5% – with pityriasis versicolor, and 57.14% of the control group isolates. A statistically significant difference in the lipase gene expression (p = 0.042) was between the strains from patients with folliculitis and the control group. This investigation provides more information about the frequency of the production of the major enzymes considered virulence factors of Malassezia species. Interestingly, the overexpression of one or more genes was observed in strains isolated from patients with Malassezia disorders.

Trichoblastic carcinoma is a sporadic malignant tumor. It usually arises in the scalp, trunk, and extremities. However, its occurrence in the base of the penis is highly uncommon. To our knowledge, there were no similar cases reported in the literature. Case Presentation. A 65-year-old Tunisian man with no significant medical history consulted our department with a 10 cm ulcerative lesion on the base of the penis. The lesion biopsy was concordant with the diagnosis of basal cell carcinoma. The patient underwent a wide local excision. The tissue defect was reconstructed by an anterolateral pedicled flap of the thigh. The final histopathology report was concordant with the diagnosis of a trichoblastic carcinoma. Conclusion. There is no treatment consensus due to the few reported cases of trichoblastic carcinoma in the literature. Surgical excision with free margins remains the cornerstone of the treatment.

This article presents an hybrid and hierarchical model in which two modeling and simulation approaches, discrete event system specification simulation (DEVS) and semantic technologies, were used together in order to help in the analysis of a major healthcare problem, the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Indeed, the complexity of the SARS-CoV-2 replication process, and the range of hierarchical scales over which it interacts with cellular components (extending from genomic and transcriptomic to proteomic and metabolomic scales), and the intricate way in which they are interwoven, make its understanding very challenging. It is therefore crucial to model the different scales of the replication process, by taking into account all interactions with the infected cell. By combining the advantages of both DEVS simulation and ontological modeling, we propose a hierarchical ontology-based DEVS simulation model of the SARS-CoV-2 viral replication at both the micro-molecular (proteomic and metabolomic) and macro-molecular (genomic and transcriptomic) scales. First, we demonstrate the usefulness of combining DEVS simulation and semantic technologies in a common modeling framework to face the complexity of the SARS-CoV-2 viral replication at different scales. Second, the modeling and simulation of the SARS-CoV-2 replication process on different levels provide valuable information on the different stages of the virus's life cycle and lays the foundation for a system to anticipate future mutations selected by the virus. [ABSTRACT FROM AUTHOR]