An N-terminal extension to the hepatitis B virus core protein forms a poorly ordered trimeric spike in assembled virus-like particles.

Virus-like particles composed of the core antigen of hepatitis B virus (HBcAg) have been shown to be an effective platform for the display of foreign epitopes in vaccine development. Heterologous sequences have been successfully inserted at both amino and carboxy termini as well as internally at the major immunodominant epitope. We used cryogenic electron microscopy (CryoEM) and three-dimensional image reconstruction to investigate the structure of VLPs assembled from an N-terminal extended HBcAg that contained a polyhistidine tag. The insert was seen to form a trimeric spike on the capsid surface that was poorly resolved, most likely owing to it being flexible. We hypothesise that the capacity of N-terminal inserts to form trimers may have application in the development of multivalent vaccines to trimeric antigens. Our analysis also highlights the value of tools for local resolution assessment in studies of partially disordered macromolecular assemblies by cryoEM.

Successful rescue of severe hypernatraemia (196 mmol/L) by treatment with hypotonic fluid.

Hypernatraemia over 160 mmol/L is considered to be severe. This case reports a patient who developed extreme hypernatraemia with a serum sodium concentration of 196 mmol/L. The patient was known to have chronic renal impairment and was admitted with acute deterioration of renal function secondary to dehydration. This was considered to be secondary to poor oral fluid intake (related to depression) and lithium-induced nephrogenic diabetes insipidus with salt-losing nephropathy. The patient had a high urinary sodium excretion but was also in a pure water losing state as evidenced by an inappropriately low urine osmolality for the plasma osmolality and was successfully treated with hypotonic intravenous fluid and desmopressin.

A retrospective study of the prognostic impact of cytokine secretion in mixed lymphocyte culture on long-term graft function following allogeneic renal transplantation.

We have previously shown that in vitro measurement of cytokine production prior to renal transplantation can provide predictive information on the risk of acute rejection. Our earlier studies demonstrated that patients who secreted high levels of interferon-gamma (IFN-gamma) in OKT3-stimulated or mixed lymphocyte culture had a significantly increased risk of acute rejection compared with patients who secreted lower levels. In this study, we performed a retrospective analysis of the same cohort of patients in order to determine the prognostic value of cytokine profiles and other variables on long-term graft function. Our results show that high levels of IFN-gamma in pretransplant mixed lymphocyte culture are a highly significant predictor of poorer creatinine levels at 18, 24 and 36 months post-transplant.

Terminal right heart failure due to complex congenital cardiac disease successfully managed by home peritoneal drainage.

A man, aged 32, who had undergone surgical correction of complex congenital cardiac disease, had chronic severe right heart failure. Increasing reliance on diuretics led to deteriorating renal function, and he was rejected as a candidate for cardiac transplantation. By inserting a Tenckhoff catheter, and training him to drain his ascites at home, we achieved a dramatic improvement in both his cardiac and renal function. As far as we can ascertain, this is the first time this technique has been used for such a patient. We discuss the mechanisms of improvement, and suggest that other such patients with congenital cardiac disease might benefit from similar management.