Identification of a Privileged Scaffold for Inhibition of Sterol Transport Proteins through the Synthesis and Ring Distortion of Diverse, Pseudo-Natural Products.

Sterol transport proteins mediate intracellular sterol transport, organelle contact sites, and lipid metabolism. Despite their importance, the similarities in their sterol-binding domains have made the identification of selective modulators difficult. Herein we report a combination of different compound library synthesis strategies to prepare a cholic acid-inspired compound collection for the identification of potent and selective inhibitors of sterol transport proteins.

Stochastic demethylation and redundant epigenetic suppressive mechanisms generate highly heterogeneous responses to pharmacological DNA methyltransferase inhibition.

Background: Despite promising preclinical studies, the application of DNA methyltransferase inhibitors in treating patients with solid cancers has thus far produced only modest outcomes. The presence of intratumoral heterogeneity in response to DNA methyltransferase inhibitors could significantly influence clinical efficacy, yet our understanding of the single-cell response to these drugs in solid tumors remains very limited.

Methods: In this study, we used cancer/testis antigen genes as a model for methylation-dependent gene expression to examine the activity of DNA methyltransferase inhibitors and their potential synergistic effect with histone deacetylase inhibitors at the single-cancer cell level.

PFAS concentrations in the blood of Danish surfers.

Background: Per- and poly-fluoroalkyl Substances (PFAS) have been used for decades in countless households and industrial products. Many PFAS do not degrade and are thus ubiquitous in the environment and within organisms. Humans are primarily exposed to PFAS through ingestion and inhalation, and such exposure has been associated with several health effects.

Prevalence and Temporal Trends of Attention Deficit Hyperactivity Disorder Medication Fills During Pregnancy and Breastfeeding in Denmark.

Background And Objectives: Females of reproductive age are increasingly using attention deficit hyperactivity disorder (ADHD) medication, but its use during pregnancy and breastfeeding is largely unknown. The aim of this study is to examine the prevalence of ADHD medication fills during pregnancy and breastfeeding, including characteristics of these females and cohort differences over time.

Methods: We conducted a descriptive study using Danish nationwide registers.

Anaesthesia teams´ perception of mental wellbeing, the psychosocial work environment and patient safety culture.

Background: Mental health issues among healthcare professionals (HCPs) are rising, impacting individual wellbeing, healthcare systems, and patient safety. This exploratory study aimed to analyse the association between anaesthesia teams' perception of their mental wellbeing, psychosocial work environment, and patient safety culture in a university hospital's anaesthesiology department. Second, to identify types of stressors and strategies to overcome them.