Prenatal exposures and cell type proportions are main drivers of DNA methylation in maltreated and non-maltreated children.

DNA methylation in peripheral tissues may be a relevant biomarker of risk for developing mental disorders after exposure to early life adversity. Genes involved in HPA axis regulation, such as , might play a key role. In this study, we aimed to identify the main drivers of salivary methylation in a cohort of 162 maltreated and non-maltreated children aged 3-5 years at two measurement timepoints.

Best practices in the African Medicines Regulatory Harmonization initiative: Perspectives of regulators and medicines manufacturers.

In the African Medicines Regulatory Harmonization initiative, national regulatory authorities (NRAs) within each of Africa's regional economic communities coordinate their activities, rely on the work of one another and other trusted regulatory authorities, and apply other principles of smart regulation. The first regional medicines regulatory harmonization (MRH) initiative in Africa was launched in 2012, with the goal of accelerating access to quality, safe, effective medical products, and now five MRH initiatives are active on the continent. Thus, a wealth of knowledge regarding best practices and approaches to dealing with common challenges has accumulated.

Reliance: a smarter way of regulating medical products - The IPRP survey.

: A survey was conducted among national regulatory authorities' members of the International Pharmaceutical Regulators Programme (IPRP) to collect and share experiences of reliance approaches. Reliance allows formally, or informally, one regulatory authority to use assessments made by other regulatory authorities while remaining responsible for the final decision. Reliance is an essential concept to increase the efficiency of the global regulatory oversight of medical products by national regulatory authorities.

The T-type calcium channel isoform Ca3.1 is a target for the hypnotic effect of the anaesthetic neurosteroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile.

Background: The mechanisms underlying the role of T-type calcium channels (T-channels) in thalamocortical excitability and oscillations in vivo during neurosteroid-induced hypnosis are largely unknown.

Methods: We used patch-clamp electrophysiological recordings from acute brain slices ex vivo, recordings of local field potentials (LFPs) from the central medial thalamic nucleus in vivo, and wild-type (WT) and Ca3.1 knock-out mice to investigate the molecular mechanisms of hypnosis induced by the neurosteroid analogue (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH).