The Omicron variant of concern (VOC) has a peculiar spectrum of mutations characterized by the acquisition of mutations or deletions rarely detected in previously identified variants, particularly in the spike glycoprotein. Such mutations, mostly residing in the receptor-binding domain, could play a pivotal role in enhancing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity (by increasing binding affinity for ACE2), jeopardizing spike recognition by therapeutic and vaccine-induced antibodies and causing diagnostic assay failure.
Chronic infection with Hepatitis B Virus (HBV) is a major cause of liver-related morbidity and mortality worldwide. HBV-DNA integration into the human genome is recognized as a frequent event occurring during the early phases of HBV infection and characterizing the entire course of HBV natural history. The development of refined molecular biology technologies sheds new light on the functional implications of HBV-DNA integration into the human genome, including its role in the progression of HBV-related pathogenesis and in triggering the establishment of pro-oncogenic mechanisms, promoting the development of hepatocellular carcinoma. The present review provides an updated and comprehensive overview of the current body of knowledge on HBV-DNA integration, focusing on the molecular mechanisms underlying HBV-DNA integration and its occurrence throughout the different phases characterizing the natural history of HBV infection. Furthermore, here we discuss the main clinical implications of HBV integration as a biomarker of HBV-related pathogenesis, particularly in reference to hepatocarcinogenesis, and how integration may act as a barrier to the achievement of HBV cure with current and novel antiviral therapies. Overall, a more refined insight into the mechanisms and functionality of HBV integration is paramount, since it can potentially inform the design of ad hoc diagnostic tools with the ability to reveal HBV integration events perturbating relevant intracellular pathways and for identifying novel therapeutic strategies targeting alterations directly related to HBV integration.
Vitamin D3 reported in Italy in 2017 the net expenditure of almost €180 million, reaching the first place for consumption and the third place for conventional pharmaceutical spending. The aim of the study was to evaluate whether a shift of vitamin D3 prescriptions toward 100 000 IU formulation, less costly, could allow savings from the health-care perspective. An approach promoting the prescription of this formulation has been applied in a local health authority (ASL CN2) in Piedmont Region (Italy) starting from 2015. The retail pharmaceutical market and the consumption of vitamin D3 has been analyzed from year 2014 to 2017 in order to evaluate differences in expenditures. Despite an increase in consumption, the introduction of the new formulation enabled ASL CN2 to save about €280 000 in 2017 considering the regional average expenditure per 1000 inhabitants as a reference. If Piedmont Region had presented an average expenditure in line with that of ASL CN2, the annual regional savings would have exceeded €7 million in 2017 alone. A shift of vitamin D3 prescriptions toward 100 000 IU formulations would allow reducing costs from the payer perspective. Savings may be used to contain public pharmaceutical expenditure or can be allocated to fund other health-care technologies and services.
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