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Sequencing of most Treponema pallidum (T. pallidum) genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein (arp). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical samples collected from ten countries on six continents. Both tp0470 and arp repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging. The number of tp0470 repeats is on average appears to be higher in Nichols-like clade strains than in SS14-like clade strains. Consistent with previous studies, we found that 14-repeat arp sequences predominate across both major clades, but the combination and order of repeat type varies among subclades, with many arp sequence variants limited to a single subclade. Although strains that were closely related by whole genome sequencing frequently had the same arp repeat length, this was not always the case. Structural modelling of TP0470 suggested that the eight residue repeats form an extended α-helix, predicted to be periplasmic. Modeling of the ARP revealed a C-terminal sporulation-related repeat (SPOR) domain, predicted to bind denuded peptidoglycan, with repeat regions possibly incorporated into a highly charged β- sheet. Outside of the repeats, all TP0470 and ARP amino acid sequences were identical. Together, our data, along with functional considerations, suggests that both TP0470 and ARP proteins may be involved in T. pallidum cell envelope remodeling and homeostasis, with their highly plastic repeat regions playing as-yet-undetermined roles.

The role of human oncoviruses in melanoma has been poorly investigated. The aim of this study was to investigate the association between oncoviruses and melanomas searching for human papillomavirus (HPV), Epstein Barr virus (EBV), and human herpesvirus 8DNA in melanoma specimens. Formalin-fixed and paraffin-embedded tissue specimens of cutaneous, mucosal, and ocular melanomas (OM) were selected from the Pathology Departments of the Galliera Hospital (Genoa) and the University Hospitals of Turin and Cagliari. Cutaneous and mucosal nevi have been collected as controls. The oncoviruses search has been performed with different polymerase chain reaction reagent kits. Fifty-four melanomas (25 mucosal, 12 ocular, and 17 cutaneous) and 26 nevi (15 cutaneous and 11 mucosal) specimens were selected. The detection rate for one of the investigated oncoviruses was 17% in mucosal, 20% in ocular, and 0% in cutaneous melanomas (CMs). Despite the differences between groups seeming remarkable, there was no statistical significance (p 0.5). Our data do not support a primary role of oncoviruses in melanoma carcinogenesis; however, the finding of HPV and EBV DNA in a considerable fraction of mucosal and OMs suggests that these viruses may act as cofactors in the development of extra-CMs.

Different therapeutic modalities for ano-genital warts (AGWs) are available but data on the efficacy of 5-fluorouracil 0.5%/salicylic acid 10% solution (5FU/SAsol) in the treatment of AGWs are scarse. We enrolled 17 patients with AGWs (14 males, 3 females with a mean age of 34.2 years) who gave written informed consent to the off-label use of topical 5FU/Sasol. Response to treatment was assessed based on the AGWs number: complete if there was complete clearance of the lesions; partial if there was50% decrease in the lesion number and none if there was50% decrease in the lesion number. Considering together partial and complete treatment response, 88% of the patients at 3 months and 94% at 6 months benefited from the 5FU/SAsol treatment. 5FU/SAsol was well tolerated by all the patients except one who experienced a burning sensation immediately after the application. The clearance rate that we found for 5-FU/SAsol after 3 months of treatment is comparable with that of the other commonly used therapeutic modalities (liquid nitrogen cryotherapy, imiquimod 5% cream). However, several patients on imiquimod and almost who underwent cryotherapy reported pain as adverse event while a mild pain was rarely reported with 5-FU/Sasol. In conclusion, although nowadays in Italy 5-FU/SAsol is marketed only for the treatment of actinic keratosis, our study described its effectiveness and tolerability also in the treatment of AGWs. Our data suggest that 5-FU/SAsol should be considered not only in case of resistant/recurrent AGWs but also as the first therapeutic option, especially when the number of lesions is small.

Pityriasis rosea (PR), PR-like eruptions (PR-LE), and herpes zoster have been frequently reported during the COVID-19 pandemic and following COVID-19 vaccination. PR is a self-limiting exanthematous disease and herpes zoster is a treatable condition; therefore, their occurrence does not require discontinuation of the vaccination schedule. PR-LE is a hypersensitivity reaction and is, therefore, less predictable in its course. In the case of a booster dose, the clinical manifestation may not recur, may be different from PR-LE, or may present with systemic symptoms; however, in the case of PR-LE, the possibility of mild and predominantly cutaneous adverse events should not discourage all eligible candidates from receiving and completing the COVID-19 vaccination program, as such adverse reactions represent a small risk considering the possible severe and fatal outcome of COVID-19. We emphasize the relevance of looking for any viral reactivation in patients infected with SARS-CoV-2 who have skin eruptions. The search for viral reactivations could be useful not only for distinguishing between PR and PR-LE but also because viral reactivations may contribute to a patient's systemic inflammation and influence the course of the disease.