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An association between climatic conditions and asthma mortality has been widely assumed. However, it is unclear whether climatic variations have a fingerprint on asthma dynamics over long time intervals. The aim of this study is to detect a possible correlation between climatic indices, namely the Atlantic Multidecadal Oscillation and Pacific Decadal Oscillation, and asthma mortality rates over the period from 1950 to 2015 in the contiguous US. To this aim, an analysis of non-stationary and non-linear signals was performed on time series of US annual asthma mortality rates, AMO and PDO indices to search for characteristic periodicities. Results revealed that asthma death rates evaluated for four different age groups (5-14 yr; 15-24 yr; 25-34 yr; 35-44 yr) share the same pattern of fluctuation throughout the 1950-2015 time interval, but different trends, i.e. a positive (negative) trend for the two youngest (oldest) categories. Annual asthma death rates turned out to be correlated with the dynamics of the AMO, and also modulated by the PDO, sharing the same averaged ∼44 year-periodicity. The results of the current study suggest that, since climate patterns have proved to influence asthma mortality rates, they could be advisable in future studies aimed at elucidating the complex relationships between climate and asthma mortality.

Cytochrome P450 17A1 (CYP17A1) is an important target in the treatment of prostate cancer because it produces androgens required for tumour growth. The FDA has approved only one CYP17A1 inhibitor, abiraterone, which contains a steroidal scaffold similar to the endogenous CYP17A1 substrates. Abiraterone is structurally similar to the substrates of other cytochrome P450 enzymes involved in steroidogenesis, and interference can pose a liability in terms of side effects. Using non-steroidal scaffolds is expected to enable the design of compounds that interact more selectively with CYP17A1. Therefore, we combined a structure-based virtual screening approach with density functional theory (DFT) calculations to suggest non-steroidal compounds selective for CYP17A1. In vitro assays demonstrated that two such compounds selectively inhibited CYP17A1 17α-hydroxylase and 17,20-lyase activities with IC50 values in the nanomolar range, without affinity for the major drug-metabolizing CYP2D6 and CYP3A4 enzymes and CYP21A2, with the latter result confirmed in human H295R cells.