Transporter Expressions as Part of Required Scaling Factor to Support In vitro In vivo Extrapolation for Blood-Brain Barrier Drug Permeability.

Access of drugs to the central nervous system is limited by the blood-brain barrier, and this in turn affects drug efficacy/toxicity. To date, most drug discovery optimization paradigms have relied heavily on in vitro transporter assays and preclinical species pharmacokinetic evaluation to provide a qualitative assessment of human brain penetration. Because of the lack of human brain pharmacokinetic data, mechanistic models for preclinical species, combined with in vitro and in silico data, are useful for translation to human.

Effectiveness of a Dedicated Rural General Surgery Residency Track: A 13-Year Analysis of the First ACGME Designated Rural Track.

Background: The shortage of general surgeons in rural America is well documented. The North Dakota community-based general surgery residency program initiated a unique approach to training for rural practice through a dedicated rural track. The rural track included 9 months of rotations in specialty rotations beneficial for rural practice.

Natural and Semisynthetic Immunomodulatory Luakuliide Labdane Diterpenoids.

Spectroscopy-guided isolation of extracts of the Tongan marine sponge cf. (Lamarck, 1814) has resulted in the reisolation of the labdane diterpenoid luakuliide A () and one new congener, luakulialactam A (). In addition to establishing the absolute configuration of , synthetic modifications to the luakuliide framework at key positions has created a set of six derivatives (-) which were used to interrogate a structure-activity relationship relating to the immunomodulatory effects of luakuliide A.

Artificial intelligence (AI) for paediatric fracture detection: a multireader multicase (MRMC) study protocol.

Introduction: Paediatric fractures are common but can be easily missed on radiography leading to potentially serious implications including long-term pain, disability and missed opportunities for safeguarding in cases of inflicted injury. Artificial intelligence (AI) tools to assist fracture detection in adult patients exist, although their efficacy in children is less well known. This study aims to evaluate whether a commercially available AI tool (certified for paediatric use) improves healthcare professionals (HCPs) detection of fractures, and how this may impact patient care in a retrospective simulated study design.