The MAGIC trial: a pragmatic, multicentre, parallel, noninferiority, randomised trial of melatonin versus midazolam in the premedication of anxious children attending for elective surgery under general anaesthesia

\ua9 2023 The Author(s)Background: Child anxiety before general anaesthesia and surgery is common. Midazolam is a commonly used premedication to address this. Melatonin is an alternative anxiolytic, however trials evaluating its efficacy in children have delivered conflicting results. Methods: This multicentre, double-blind randomised trial was performed in 20 UK NHS Trusts. A sample size of 624 was required to declare noninferiority of melatonin. Anxious children, awaiting day case elective surgery under general anaesthesia, were randomly assigned 1:1 to midazolam or melatonin premedication (0.5 mg kg−1, maximum 20 mg) 30 min before transfer to the operating room. The primary outcome was the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF). Secondary outcomes included safety. Results are presented as n (%) and adjusted mean differences with 95% confidence intervals. Results: The trial was stopped prematurely (n=110; 55 per group) because of recruitment futility. Participants had a median age of 7 (6–10) yr, and 57 (52%) were female. Intention-to-treat and per-protocol modified Yale Preoperative Anxiety Scale-Short Form analyses showed adjusted mean differences of 13.1 (3.7–22.4) and 12.9 (3.1–22.6), respectively, in favour of midazolam. The upper 95% confidence interval limits exceeded the predefined margin of 4.3 in both cases, whereas the lower 95% confidence interval excluded zero, indicating that melatonin was inferior to midazolam, with a difference considered to be clinically relevant. No serious adverse events were seen in either arm. Conclusion: Melatonin was less effective than midazolam at reducing preoperative anxiety in children, although the early termination of the trial increases the likelihood of bias. Clinical trial registration: ISRCTN registry: ISRCTN18296119

Effect of Lipid Supplements on the Production and Glycosylation of Recombiant Interferon-Gamma Expressed in CHO Cells

The effects of lipids on the glycosylation of recombinant human interferon-gamma expressed in a Chinese Hamster Ovary cell line were investigated in batch culture. Lipids form an essential part of the N-grycosylation pathway, and have been shown to improve cell viability. In control (serum-free) medium the proportion of fully-glycosylated interferon-gamma deteriorated reproducibly with time in batch culture, but the lipoprotein supplement ExCyte was shown to minimise this trend. Partially substituting the bovine serum albumin content of the medium with a fatty-acid free preparation also improved interferon-gamma glycosylation, possibly indicating that oxidised lipids carried on Cohn fraction V albumin may damage the glycosylation process

Starch content and yield increase as a result of altering adenylate pools in transgenic plants

Starch represents the most important carbohydrate used for food and feed purposes. With the aim of increasing starch content, we decided to modulate the adenylate pool by changing the activity of the plastidial adenylate kinase in transgenic potato plants. As a result, we observed a substantial increase in the level of adenylates and, most importantly, an increase in the level of starch to 60% above that found in wild-type plants. In addition, concentrations of several amino acids were increased by a factor of 2–4. These results are particularly striking because this genetic manipulation also results in an increased tuber yield. The modulation of the plastidial adenylate kinase activity in transgenic plants therefore represents a potentially very useful strategy for increasing formation of major storage compounds in heterotrophic tissues of higher plants