Background. Olfactory dysfunction represents one of the most frequent symptoms of coronavirus disease 2019, affecting about 70 per cent of patients. However, the pathogenesis of the olfactory dysfunction in coronavirus disease 2019 has not yet been elucidated. Case report. This report presents the radiological and histopathological findings of a patient who presented with anosmia persisting for more than three months after infection with severe acute respiratory syndrome coronavirus-2. Conclusion. The biopsy demonstrated significant disruption of the olfactory epithelium. This shifts the focus away from invasion of the olfactory bulb and encourages further studies of treatments targeted at the surface epithelium.

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Game species are often manipulated by human beings, whose activities can deeply affect their genetic make-up and population structure. We focused on a geographically isolated wild boar population (Sardinia, Italy), which is classified, together with the Corsican population, as a separate subspecies (Sus scrofa meridionalis). Two hundred and ten wild boars collected across Sardinia were analysed with a set of 10 microsatellites and compared with 296 reference genotypes from continental wild populations and to a sample of domestic pigs. The Sardinian population showed remarkable diversity and a high proportion of private alleles, and strongly deviated from the equilibrium. A Bayesian cluster analysis of only the Sardinian sample revealed a partition into five subpopulations. However, two different Bayesian approaches to the assignment of individuals, accounting for different possible source populations, produced consistent results and proved the admixed nature of the Sardinian population. Indeed, introgressive hybridization with boars from multiple sources (Italian peninsula, central Europe, domestic stocks) was detected, although poor evidence of crossbreeding with free-ranging domestic pigs was unexpectedly found. After excluding individuals who carried exotic genes, the population re-entered HardyWeinberg proportions and a clear population structure with three subpopulations emerged. Therefore, the inclusion of introgressed animals in the Bayesian analysis implied an overestimation of the number of clusters. Nonetheless, two of them were consistent between analyses and corresponded to highly pure stocks, located, respectively, in northwest and south-west Sardinia. This work shows the critical importance of including adequate reference samples when studying the genetic structure of managed wild populations.

Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer type, lacking effective therapies and associated with a dismal prognosis. Palbociclib is a selective CDK4/6 inhibitor, which has been shown to suppress cell proliferation in many experimental cancer models. Recently, we demonstrated that pan-mTOR inhibitors, such as MLN0128, effectively induce apoptosis, although have limited efficacy in restraining proliferation of ICC cells. Here, we tested the hypothesis that palbociclib, due to its antproliferative properties in many cancer types, might synergize with MLN0128 to impair ICC growth. Human ICC cell lines and the AKT/YapS127A ICC mouse model were used to test the therapeutic efficacy of palbociclib and MLN0128, either alone or in combination. Administration of palbociclib suppressed ICC cell growth by inhibiting cell-cycle progression. Concomitant administration of palbociclib and MLN0128 led to a pronounced, synergistic growth constraint of ICC cell lines. Furthermore, while treatment with palbociclib or MLN0128 alone resulted in tumor growth reduction in AKT/YapS127A mice, a remarkable tumor regression was achieved when the two drugs were administered simultaneously. Mechanistically, palbociclib was found to potentiate MLN0128 mTOR inhibition activity, whereas MLN0128 prevented the upregulation of cyclin D1 induced by palbociclib treatment. Our study indicates the synergistic activity of palbociclib and MLN0128 in inhibiting ICC cell proliferation. Thus, combination of CDK4/6 and mTOR inhibitors might represent a novel, promising, and effective therapeutic approach against human ICC.

The aim of this study was to assess the role of a human papilloma virus (HPV) vaccine after loop electrosurgical excision procedure (LEEP) in reducing recurrent cervical dysplasia. A series of 503 women with cervical dysplasia received LEEP between January 2012 and October 2018. Of these patients, 379 were treated between January 2012 and June 2017, thus ensuring an adequate follow-up time. We made three attempts to establish telephone contact with each patient; 77 women did not respond and were excluded from the final study population, which consisted of 302 patients. One hundred eighty-two (60.7%) women were vaccinated with an HPV vaccine within 4 weeks of LEEP and 103 (34.3%) were followed up with but not vaccinated. Recurrence of cervical dysplasia requiring a further LEEP procedure occurred in 30 (10.5%) women, of whom 17 (16.5%) were not vaccinated and 13 (7.1%) were vaccinated (p-value = 0.010). At univariate analysis, HPV vaccination after LEEP (odds ratio (OR) = 0.4, p-value = 0.020) emerged as an independent protective factor. Choosing as an outcome of the analysis only recurrence as severe cervical lesions, the protective role of HPV vaccination after LEEP was found to be much more relevant with an odds ratio of 0.2 (95% CI = 0.1–0.6, p-value = 0.02). Administration of an HPV vaccine after LEEP seems to reduce the risk of recurrence, thus suggesting that HPV vaccination has a role as an adjuvant treatment after LEEP.