BackgroundLiving grafts produced by combining autologous heart-resident stem/progenitor cells and tissue engineering could provide a new therapeutic option for definitive correction of congenital heart disease. The aim of the study was to investigate the antigenic profile, expansion/differentiation capacity, paracrine activity, and pro-angiogenic potential of cardiac pericytes and to assess their engrafting capacity in clinically certified prosthetic grafts.Methods and ResultsCD34pos cells, negative for the endothelial markers CD31 and CD146, were identified by immunohistochemistry in cardiac leftovers from infants and children undergoing palliative repair of congenital cardiac defects. Following isolation by immunomagnetic bead-sorting and culture on plastic in EGM-2 medium supplemented with growth factors and serum, CD34pos/CD31neg cells gave rise to a clonogenic, highly proliferative (>20 million at P5), spindle-shape cell population. The following populations were shown to expresses pericyte/mesenchymal and stemness markers. After exposure to differentiation media, the expanded cardiac pericytes acquired markers of vascular smooth muscle cells, but failed to differentiate into endothelial cells or cardiomyocytes. However, in Matrigel, cardiac pericytes form networks and enhance the network capacity of endothelial cells. Moreover, they produce collagen-1 and release chemo-attractants that stimulate the migration of c-Kitpos cardiac stem cells. Cardiac pericytes were then seeded onto clinically approved xenograft scaffolds and cultured in a bioreactor. After 3 weeks, fluorescent microscopy showed that cardiac pericytes had penetrated into and colonized the graft.ConclusionsThese findings open new avenues for cellular functionalization of prosthetic grafts to be applied in reconstructive surgery of congenital heart disease.

Background Benzodiazepines and Z-drugs (such as zopiclone) are widely prescribed in primary care. Given their association with addiction and dependence, understanding where and for whom these medications are being prescribed is a necessary step in addressing potentially harmful prescribing. Objective To determine whether there is an association between primary care practice benzodiazepine and Z-drug prescribing and practice population socioeconomic status in England. Methods This was a cross-sectional study. An aggregated data set was created to include primary care prescribing data for 2017, practice age and sex profiles and practice Index of Multiple Deprivation (IMD) scores—a marker of socioeconomic status. Drug doses were converted to their milligram-equivalent of diazepam to allow comparison. Multiple linear regression was used to examine the association between IMD and prescribing (for all benzodiazepines and Z-drugs in total, and individually), adjusting for practice sex (% male) and older age (>65 years) distribution (%). Results Benzodiazepine and Z-drug prescribing overall was positively associated with practice-level IMD score, with more prescribing in practices with more underserved patients, after adjusting for age and sex (P < 0.001), although the strength of the association varied by individual drug. Overall, however, IMD score, age and sex only explained a small proportion of the overall variation in prescribing across GP practices. Conclusion Our findings may, in part, be a reflection of an underlying association between the indications for benzodiazepine and Z-drug prescribing and socioeconomic status. Further work is required to more accurately define the major contributors of prescribing variation.

BackgroundBenzodiazepines and Z-drugs (such as zopiclone) are widely prescribed in primary care in England. Prescribed for various indications, such as anxiolysis and insomnia, it has been previously reported that an association may exist with deprivation.AimTo determine whether there was an association between benzodiazepine/Z-drug prescribing (overall, and by individual drug) and practice-level socioeconomic deprivation in England.MethodMonthly primary care prescribing data for 2017, as well as practice age and sex profile, were downloaded from NHS Digital. Prescribing was aggregated by year. Drug doses were converted to their milligram-equivalent of diazepam to allow comparison. Practice-level Index of Multiple Deprivation (IMD 2015) scores were obtained from Public Health England. Multiple linear regression was used to examine the association between IMD and prescribing (for all benzodiazepines/Z-drugs, and individually), after adjusting for practice sex (% male) and older age (% >65 years) distribution. Practice-level prescribing was defined as milligrams of diazepam-equivalent per 1000 registered patients in 2017.ResultsOn univariate analysis, overall benzodiazepine prescribing was positively associated with practice-level IMD score, with more prescribing in more deprived practices (P<0.001). After adjusting for practice age and sex profile, IMD score remained an independent predictor of prescribing levels (P<0.001). These associations were consistent for all benzodiazepines/Z-drugs when analysed separately.ConclusionHigher practice-level socioeconomic deprivation, as described by IMD score, was associated with increased benzodiazepine/Z-drug prescribing. This may, in part, be a reflection of an underlying association of the indications for prescribing and socioeconomic deprivation. Further work is required to more accurately define the underlying reasons for these associations.