Julian Hospital

Ligand effects on the non-covalent interactions of phosphine gold(i) fluorothiolates were analysed using the QTAIM and NCI.

Stent deployment to treat coronary artery disease causes damage and loss of endothelial cells (EC). Repair of injured arteries by EC migration is co-ordinated by Rho family GTPases. It is also regulated by wall shear stress (WSS), a mechanical force exerted by flowing blood on the vessel wall, via mechanisms that are poorly understood. It was hypothesised that stent struts may impede repair of injured endothelium by inducing localised disturbances in WSS. To simulate a stented artery in vitro, chamber slides were fabricated with ridges (100 μm high) positioned perpendicularly to the flow direction. Confluent EC monolayers seeded on one side of either ridged or non-ridged (control) chambers were exposed to flowing culture medium (Ibidi® system). Flow patterns were determined by computational fluid dynamic (CFD) modelling and particle velocimetry. Live cell imaging and analysis using ImageJ® software enabled quantification of EC migration velocity and directional persistence (DP). EC on the non-ridged chamber slide were exposed to a uniform WSS of 13 dyn/cm2 and migrated relatively uniformly in parallel with the flow direction (average velocity 1.13 μm/min; DP 0.59). By contrast, CFD and particle velocimetry revealed spatial WSS differences over the ridged chamber, with significant spikes above physiological levels (>70 dyn/cm2) at the corners of the ridges and distinctive flow recirculation zone immediately downstream from ridges (-4 dyn/cm2). While EC were able to migrate over the ridges, cells that reached the recirculation zone displayed non-uniform directionality (DP 0.25) and reduced velocity (0.78 μm/min). Inhibition of the RhoA signalling pathway with ROCK inhibitors promoted EC forward migration within the recirculation zone by elevating DP (0.41) and velocity (1.16 μm/min). It was concluded that disturbed WSS downstream from stent strut-like ridges prevented the forward migration of EC. Inhibition of the RhoA/ROCK signaling pathway promoted EC migration and re-population of these sites. Our data suggest that treatment using a ROCK inhibitor may promote re-endothelialisation of stented arteries.

Abdominal aortic aneurysm (AAA) is a common cardiovascular disease among older people and demonstrates significant heritability. In contrast to similar complex diseases, relatively few genetic associations with AAA have been confirmed. We reanalyzed our genome-wide study and carried through to replication suggestive discovery associations at a lower level of significance. A genome-wide association study was conducted using 1830 cases from the United Kingdom, New Zealand, and Australia with infrarenal aorta diameter≥30 mm or ruptured AAA and 5435 unscreened controls from the 1958 Birth Cohort and National Blood Service cohort from the Wellcome Trust Case Control Consortium. Eight suggestive associations with P<1×10(-4) were carried through to in silico replication in 1292 AAA cases and 30,503 controls. One single-nucleotide polymorphism associated with P<0.05 after Bonferroni correction in the in silico study underwent further replication (706 AAA cases and 1063 controls from the United Kingdom, 507 AAA cases and 199 controls from Denmark, and 885 AAA cases and 1000 controls from New Zealand). Low-density lipoprotein receptor (LDLR) rs6511720 A was significantly associated overall and in 3 of 5 individual replication studies. The full study showed an association that reached genome-wide significance (odds ratio, 0.76; 95% confidence interval, 0.70-0.83; P=2.08×10(-10)). LDLR rs6511720 is associated with AAA. This finding is consistent with established effects of this variant on coronary artery disease. Shared causal pathways with other cardiovascular diseases may present novel opportunities for preventative and therapeutic strategies for AAA.

This survey investigates the role and views of NHS spiritual advisors across the United Kingdom on the provision of pastoral care for elderly people with mental health needs. The College of Health Care Chaplains provided a database, and questionnaires were sent to 405 registered NHS chaplains/spiritual advisors. The response rate was 59%. Quantitative and qualitative analyses were carried out. Spiritual advisors describe their working patterns and understanding of their roles within the modern NHS, and their observations of the level of NHS staff awareness of the importance of spiritual issues in the mental health care of older adults. They provide insights into possible negative and positive perceptions of their roles at a service level, and contribute suggestions of topics relevant to shared education between pastoral care and clinical services. This survey further highlights ethical and operational dimensions at the point of integration of the work of spiritual advisors and multidisciplinary teams.