Mammalian circadian organization is governed by pacemaker neurons in the brain that communicate with oscillators in peripheral tissues. Adrenal glucocorticoids are important time-giving signals to peripheral circadian oscillators. We investigated the rhythm of Per1-luc expression in pineal, pituitary, salivary glands, liver, lung, kidney, cornea as well as suprachiasmatic nucleus from adrenalectomized and sham-operated rats kept under light-dark cycles, or exposed to single 6-h phase delays or advances of their light cycles. Adrenalectomy shifted the phases of Per1-luc in liver, kidney, and cornea and caused phase desynchrony and significant dampening in the rhythmicity of cornea. Treatment with hydrocortisone shifted the phases of Per1-luc in most of the tissues examined, even those that were not affected by adrenalectomy. The rhythm in cornea recovered in animals given hydrocortisone in vivo or when corneas were treated with dexamethasone in vitro. Adrenalectomy increased the rate of reentrainment after phase shifts in liver, kidney, cornea, pineal, lung, and suprachiasmatic nucleus but not in pituitary and salivary glands. Our data show that glucocorticoids act as strong entraining signals for peripheral circadian oscillators and may feed back on central oscillators as well.

Both bleeding and thrombosis are frequent in this population, but only thrombotic complications contributed to retransplantation and mortality. A standardized approach to coagulation testing and antithrombotic therapy may be useful in predicting and reducing adverse outcomes. Alternative approaches to monitoring hemostasis need to be prospectively investigated in this complex patient population.

Prolonged furosemide exposure was associated with a positive, but not statistically significant, difference in abnormal hearing screening in premature infants. Additional studies with post-hospital discharge audiology follow-up are needed to further evaluate the safety of furosemide in this population.

In the United States, the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act continue to promote clinical trials in pediatric populations across all age ranges. In 2014 and 2015, over 70 changes were made to drug labels with updates on information regarding pediatric populations. Additionally, multiple new therapies have received first-approvals for the treatment of pediatric indications ranging form rare genetic metabolic diseases to oncology. In the European Union, there have been more than 30 new authorizations for medicines used in children and 130 approved pediatric investigation plans. Despite the progress that has been made over the last two years, much work remains to further the development of safe and effective therapies for pediatric patients.