GP training in affluent practices in Scotland: the experiences of GP trainees and implications for their future practice.

UK general practice faces workforce challenges. The pandemic, and cost-of-living crisis are felt hardest by our most deprived communities. The Scottish Government is keen to tackle Scotland's high drugs-related deaths. The perceptions and experiences of GP specialist trainees who have trained in deprived communities are already known. This qualitative study explored the perceptions and experiences of trainees from affluent practices and how this training may affect their future career. One-to-one in-depth interviews were conducted and analysed using grounded theory methods. Seven participants were interviewed. Five themes were constructed: training practice choices, perceptions of working in deprived areas, unmet learning needs for working in deprived areas, other sources of deprivation exposure and future working intentions. Most did not choose their training practice because of its affluence. They perceived that working in a deprived area would have challenges: less staff, higher rates of pathology, communication challenges, poorer patient health literacy. Addiction care was a significant unmet learning need. Most lacked confidence to work in deprived areas, and were likely to work in their training practice or similar, upon completion of training. This research has implications for ensuring equity of GP workforce provision and whether GP Specialty Training fulfils its intention of producing 'a GP who is capable of working independently in a variety of primary care settings'. Those training in highly-affluent settings may not feel able to meet this aim. Training providers should consider this limited experience and whether rotations, involving affluent and deprived area practices, would prepare future GPs to work with a range of socioeconomic populations.

Biophysical and structural characterisation of nucleic acid complexes with modified cyclodextrins using circular dichroism.

Modified cyclodextrins (CDs) have shown great promise as non-viral gene and siRNA delivery vectors in a range of in vitro and in vivo studies. In the current study, structural and biophysical characterisation of selected CDs was carried out to enhance our understanding of their interaction with nucleic acids. The methods used for such characterisation were dynamic light scattering, zeta potential measurements and circular dichroism. Variations in the chemistries of individual CDs and in the type of formulation were shown to affect key properties of complexes such as size, surface charge and nucleic acid conformation. Furthermore, the effects of temperature and pH on the conformation of nucleic acids were investigated. pH studies were intended to mimic the conditions encountered by cationic complexes during endocytosis. Circular dichroism studies revealed that changes occurred in DNA and siRNA conformation upon complexation with CDs and when exposed to increasing temperature and decreasing pH. Overall, siRNA appeared to be more susceptible to conformational changes although complexation of siRNA with CDs tended to have a stabilising effect.

Targeted gene delivery to hepatocytes with galactosylated amphiphilic cyclodextrins.

OBJECTIVES: Achieving targeted delivery of gene medicines is desirable to maximise activity. Here, galactosylated amphiphilic cyclodextrins (CDs) are examined in terms of their ability to transfect asialoglycoprotein receptor-bearing HepG2 cells. METHODS: Cationic amphiphilic CDs were synthesised as well as amphiphilic CDs bearing galactose-targeting ligands with different linker lengths. Binding of galactosylated CDs to a galactose-specific lectin was examined by surface plasmon resonance. CDs were formulated with and without the helper lipid DOPE and complexed with plasmid DNA. Transfection was evaluated by luciferase assay. Intracellular trafficking was assessed by confocal microscopy. KEY FINDINGS: Binding of targeted CDs to a galactose-specific lectin was achieved. Binding decreased with linker length between the galactosyl group and the CD core. Contrary to the lectin binding results, transfection levels increased with an increase in linker length from 7 atoms to 15. Compared to non-targeted formulations, a significant increase in transfection was observed only in the presence of the helper lipid DOPE. Confocal microscopy revealed that DOPE caused a pronounced effect on cellular distribution. CONCLUSIONS: The galactose-targeting ligand induced substantial increases in transfection over non-targeted formulations when DOPE was included, indicating the potential for targeted gene delivery using CD-based delivery systems.