Feasibility of a Randomized, Interventional Pilot Clinical Study of Oral Cannabinoids in People with HIV on Antiretroviral Therapy: CTNPT 028.

Cannabis-based medicines (CBMs) could help reduce systemic inflammation in people with HIV (PWH). In a prospective, randomized pilot study we enrolled participants from August 2021-April 2022 with HIV, aged ≥18 and on antiretroviral therapy and randomly assigned them to cannabidiol (CBD) ± Δ9-tetrahydrocannabinol (THC) capsules for 12 weeks with the primary objective being to assess safety and tolerability. Here we report on timeliness to study initiation, enrolment, compliance and retention rates. The target sample size was not reached. Two hundred and five individuals were approached, and 10 consented and were randomized; the rest refused (reasons: cannabis-related stigma/discomfort; too many study visits/insufficient time; unwillingness to undergo a "washout period" for three weeks) or were not eligible. The age of those randomized was 58 years (IQR 55-62); 80% were male. Only three met all criteria (30% enrolment compliance); seven were enrolled with minor protocol deviations. Compliance was excellent (100%). Eight (80%) participants completed the study; two (20%) were withdrawn for safety reasons (transaminitis and aggravation of pre-existing anemia). Time to study initiation and recruitment were the most challenging aspects. Ongoing work is required to reduce stigma related to CBMs. Future studies should find a balance between the requirements for safety monitoring and frequency of study visits.

The current status of interventional radiology in the undergraduate medical curriculum and the way forward.

Interventional radiology (IR) is underrepresented in undergraduate medical school curricula. Despite the introduction of a suggested undergraduate curriculum for IR by the British Society of Interventional Radiology (BSIR), current evidence suggests there is inadequate knowledge and awareness of IR amongst medical students. As a result of this, there is a lack of visibility of the subspeciality amongst medical students and junior doctors contributing to the shortage of IR trainees resulting in an IR workforce crisis in the UK. The uptake of the proposed undergraduate IR curriculum remains unclear, highlighting the need for a thorough audit and improvement of IR teaching in undergraduate medical education. In this commentary, we discuss the importance of including IR in the undergraduate curriculum, the evidence surrounding undergraduate IR education, the reasons for the potential lack of interest in IR from medical students and future steps to ensure optimal IR exposure in undergraduate medical school curricula.

Aspartic acid scanning mutation analysis of a goldfish growth hormone-releasing hormone (GHRH) receptor specific to the GHRHsalmon-like peptide.

Growth hormone-releasing hormone (GHRH) plays a pivotal role in the regulation of growth. The study of goldfish GHRH and its receptor is of particular interest as it is so far the only animal model in which two forms of GHRH-like (catfish-like and salmon-like) peptides coexist, and these peptides share only 30-40% of amino acid sequence identities with their mammalian counterparts. For these reasons, we have previously characterized a goldfish GHRH receptor, which is specific for a synthetic carp GHRH-like peptide. In this study, we investigated the structure-function relationships between the receptor and various ligands. Interestingly, among the two endogenous goldfish GHRH-like peptides, only the GHRHsalmon-like peptide was able to stimulate CHO cells transfected with the goldfish GHRH receptor. When the receptor was challenged by GHRHsalmon-like peptide either continuously for 45 min or periodically at 45-min intervals, mild homologous desensitization was observed. To determine whether the negatively charged residues of the receptor are responsible for discriminating GHRHsalmon-like from GHRHcatfish-like, 10 aspartic acid residues residing in the N-terminal ectodomain and the second exoloop were individually mutated to alanine by site-directed mutagenesis. Among these 10 mutants, four of them (D66A, D122A, D190A, and D196A) were defective as indicated by both cAMP assays and extracellular acidification rate measurements. Confocal microscopic studies showed that the D66A and D122A mutants, but not the D190A and D196A mutants, were expressed properly at the plasma membrane. Collectively, these results suggest that aspartic acid residues at positions 66 and 122 are critical for the interaction between the goldfish GHRH receptor and its endogenous ligands.