Fragmented day-night cycle induces reduced light avoidance, excessive weight gain during early development, and binge-like eating during adulthood in mice.

Fragmented day-night (FDN) cycles are environments in which multiple periods of light and dark alternate across a 24 h period. Exposure to FDN cycles disrupts circadian rhythms, resulting in period lengthening and alterations to mood in mice. A constant light environment, which also induces period lengthening, is linked to mood and metabolic disturbances and disruption to the development of the circadian clock.

Design and synthesis of long acting inhaled corticosteroids for the treatment of asthma.

In this Letter we present data for a novel series of ICS for the treatment of asthma. 'Inhalation by design' principles have been applied to a series of highly potent steroidal GR agonists, with a focus on optimising the potential therapeutic index in human. Pharmacokinetic properties were tuned with high intrinsic clearance and low oral bioavailability in mind, to minimise systemic exposure and reduce systemically driven adverse events.