[The physical activity paradox.] / Il paradosso dell'attività fisica.

Recent discoveries have shown that the effects of physical activity on health are not the same in all its domains. In particular, the health effects of physical activity differ not only in terms of modality and intensity, but also based on the context in which it is carried out. Several studies have observed that those who do a lot of physical activity at work tend to have worse health outcomes than those who do less physical activity at work but more exercise in their free time. This phenomenon has been defined as the "physical activity paradox". However, it is worth reporting that differences in health outcomes have been observed for different socioeconomic positions and that more favorable socioeconomic positions tend to have healthier lifestyles.

The impact of COVID-19 pandemic on gambling: A systematic review.

BACKGROUND AND AIMS: Since the COVID-19 outbreak, people's habits changed radically. In fact, to limit the spread of SARS-CoV-2, governments implemented restrictive measures that influenced the lives of individuals. The aim of this systematic review is to analyze the impact of COVID-19 on gambling by examining three different outcomes: frequency, expenditure, and transition among possible types of gambling. METHODS: All studies assessing the impact of restrictive measures implemented to limit the spread of SARS-CoV-2 on gambling were included. For the search, two different databases were used: Pubmed and CINAHL. Moreover, two different populations were analyzed: the general population, and subjects who used to gamble before SARS-CoV-2 pandemic. All qualitative studies, reports not based on peer-review, and papers in which the statistical unit was not the subject but the gambling or wagering operators were excluded. RESULTS: From the search, 408 reports were identified. Of these, 28 were included in the systematic review. From the studies, a strong reduction in the frequency and expenditure of land-based gambling emerged, while the results about online gambling were different among the studies. However, a reduction was observed assessing sports betting, and an increase emerged considering online casino and skill games. Finally, a significant migration from land-based gambling to online platforms was identified. The main reasons for these findings were the physical closures of land-based gambling venues and the more time spent at home, the suspension or cancelation of sporting events on which subjects used to bet, and more mental health issues during this challenging period. CONCLUSIONS: The COVID-19 pandemic greatly affected subjects' habits, including gambling, by reducing land-based gambling and sports betting, and increasing gambling on online platforms. This shift poses significant challenges, requiring a comprehensive approach to monitor and mitigate the negative consequences of this increase in online gambling caused by the pandemic.

Vector integration and fate in the hemophilia dog liver multiple years after AAV-FVIII gene transfer.

ABSTRACT: Gene therapy using adeno-associated virus (AAV) vectors is a promising approach for the treatment of monogenic disorders. Long-term multiyear transgene expression has been demonstrated in animal models and clinical studies. Nevertheless, uncertainties remain concerning the nature of AAV vector persistence and whether there is a potential for genotoxicity. Here, we describe the mechanisms of AAV vector persistence in the liver of a severe hemophilia A dog model (male = 4, hemizygous; and female = 4, homozygous), more than a decade after portal vein delivery. The predominant vector form was nonintegrated episomal structures with levels correlating with long-term transgene expression. Random integration was seen in all samples (median frequency, 9.3e-4 sites per cell), with small numbers of nonrandom common integration sites associated with open chromatin. No full-length integrated vectors were found, supporting predominant episomal vector-mediated long-term transgene expression. Despite integration, this was not associated with oncogene upregulation or histopathological evidence of tumorigenesis. These findings support the long-term safety of this therapeutic modality.

HIV- 1 lentivirus tethering to the genome is associated with transcription factor binding sites found in genes that favour virus survival.

Lentiviral vectors (LV) are attractive for permanent and effective gene therapy. However, integration into the host genome can cause insertional mutagenesis highlighting the importance of understanding of LV integration. Insertion site (IS) tethering is believed to involve cellular proteins such as PSIP1/LEDGF/p75, which binds to the virus pre-integration complexes (PICs) helping to target the virus genome. Transcription factors (TF) that bind both the vector LTR and host genome are also suspected influential to this. To determine the role of TF in the tethering process, we mapped predicted transcription factor binding sites (pTFBS) near to IS chosen by HIV-1 LV using a narrow 20 bp window in infected human induced pluripotent stem cells (iPSCs) and their hepatocyte-like cell (HLC) derivatives. We then aligned the pTFBS with these sequences found in the LTRs of native and self-inactivated LTRs. We found significant enrichment of these sequences for pTFBS essential to HIV-1 life cycle and virus survival. These same sites also appear in HIV-1 patient IS and in mice infected with HIV-1 based LV. This in silco data analysis suggests pTFBS present in the virus LTR and IS sites selected by HIV-1 LV are important to virus survival and propagation.