Approximately 90% of patients with advanced breast cancer develop bone metastases; an event that results in severe decrease of quality of life and a drastic deterioration in prognosis. Therefore, to increase the survival of breast cancer patients, the development of new therapeutic strategies to impair metastatic process and skeletal complications is critical. Previous studies on the role of cathepsin K (CTSK) in metastatic spreading led to several strategies for inhibition of this molecule such as MIV-711 (Medivir), balicatib and odanacatib (ODN) which were on trial in the past. The present study intended to assess the anti-metastatic efficacy of ODN in breast cancer cells. Human breast cancer cell lines MDA-MB-231 were treated with different concentrations of ODN and performed invasion, adhesion and migration assays and, RT-PCR and western blot to evaluate the effect of ODN on the metastatic potential of breast cancer cells. ODN markedly decreased wound healing cell migration, invasion and adhesion at a dose dependent manner. ODN inhibits cell invasion by decreasing the matrix metalloproteinase (MMP-9) with the upregulation of TIMP-1 expression. ODN effectively inhibited the phosphorylation of extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal Kinase (JNK), and blocked the expression of β-integrins and FAK proteins. ODN also significantly inhibited PI3K downstream targets Rac1, Cdc42, paxillin and Src which are critical for cell adhesion, migration and cytoskeletal reorganization. ODN exerts anti-metastatic action through inhibition of signaling pathway for MMP-9, PI3K and MAPK. This indicates potential therapeutic effects of ODN in the treatment of metastatic breast cancer.The Covid-19 pandemic affected large part of Italy since February 2020; we, therefore, aimed to assess the impact of 2020 SARS-CoV-2 outbreak on telemedicine management of cardiovascular disease (CVD) in Italy. We analyzed data from three telemedicine dispatch centers, one located in Genoa, serving private clients (pharmacies, general practitioners), one in Brescia, serving pharmacies, and one in Bari, serving regional public STEMI network and emergency medical service in Apulia (4 million inhabitants). Demographic data and principal electrocardiogram diagnosis were collected and analyzed. Records from the time interval March 1, 2020 and April 1, 2020 were compared with the corresponding period in 2019. The comparative analysis of data shows a 54% reduction of telemedicine electrocardiogram transmission in Genoa telemedicine center (from 364 to 166), 68% in Brescia (from 5.745 to 1.905), 24% in Bari (from 15.825 to 11.716); relative reduction according to electrocardiogram diagnosis was 38% for acute coronary syndrome, 40% for other acute CVD in Genoa center, 24% for acute coronary syndrome, and 38% for other acute CVD in Bari. Male/female ratio remained substantially unchanged. A dramatic reduction of telemedicine access for CVD was observed during Covid-19 outbreak in March 2020 in Italy. The reduction was substantially consistent for all electrocardiogram findings, ACS, other acute CVD and normal.Acid rain and acidification research are indeed a multidisciplinary field. This field evolved from the first attempts to mitigate acid freshwater in the 1920s, then linking acid rain to the acidification in late 1950s, to the broad project-concepts on cause and effect from the late 1960s. Three papers from 1974, 1976 and 1988 demonstrate a broad approach and comprise scientific areas from analytical chemistry, biochemistry, limnology, ecology, physiology and genetics. Few, if any, environmental problems have led to a public awareness, political decisions and binding limitations as the story of acid rain. Acid precipitation and acidification problems still exist, but at a lower pressure, and liming has been reduced accordingly. However, the biological responses in the process of recovery are slow and delayed. The need for basic science, multidisciplinary studies, long time series of high-quality data, is a legacy from the acid rain era, and must form the platform for all future environmental projects.Early studies published in Ambio showed large-scale acidification of lakes in southern Sweden and Norway from acid rain. These studies were important for delimiting various scientific issues and thus for eventually contributing to legislation, which reduced emissions of sulfur dioxide and nitrogen oxides and helped to mitigate this major environmental problem. Long-term studies and monitoring in Sweden and Norway and at Hubbard Brook Experimental Forest in New Hampshire helped guide this legislation in Europe and in the USA.Shingrix is a recombinant adjuvant subunit vaccine. HRO761 The vaccine is approved in Germany for prevention of zoster manifestation and postherpetic neuralgia in adults aged ≥60 years. In the case of bullous skin lesions after vaccination with Shingrix a zoster disease should be considered. Unexpected side effects associated with the vaccination should be reported to the Drug Commission of the German Medical Association. No consensus exists regarding the most appropriate staging system to predict overall survival (OS) for hepatocellular carcinoma (HCC) in surgical candidates. Thus, we aimed to determine the prognostic ability of eight different staging systems in a European cohort of patients undergoing liver resection for HCC. Patients resected for HCC between 2010 and 2019 at our institution were analyzed with Kaplan-Meier and Cox regression analyses. Likelihood ratio (LR) χ (homogeneity), linear trend (LT) χ (discriminatory ability), and Akaike Information Criterion (AIC, explanatory ability) were used to determine the staging system with the best overall prognostic performance. Liver resection for HCC was performed in 160 patients. Median OS was 39months (95% confidence interval (CI) 32-46months) and median RFS was 26months (95% CI 16-34months). All staging systems (BCLC, HKLC, Okuda, CLIP, ITA.LI.CA staging and score, MESH, and GRETCH) showed significant discriminatory ability regarding OS, with ITA.LI.CA score (LR χ 30.08, LT χ 13.90, AIC 455.27) and CLIP (LR χ 28.65, LT χ 18.95, AIC 460.07) being the best performing staging systems. ITA.LI.CA and CLIP are the most suitable staging system to predict OS in European HCC patients scheduled for curative-intent surgery.ITA.LI.CA and CLIP are the most suitable staging system to predict OS in European HCC patients scheduled for curative-intent surgery.