Predictors of cancer risk in the long-term solid-organ transplant recipient.

Malignancy is increasingly the leading cause of mortality in solid-organ recipients. Cancer incidence among the transplant population is overall threefold to fivefold higher than the general population with poorer outcomes for late-stage disease. Insights into the identification of patients at particular risk of developing a posttransplantation malignancy are imperative to ensure appropriate measures are instigated to reduce associated morbidity and mortality. This review focuses on potential clinical, immunologic, and genetic translational markers aimed at identifying long-term solid-organ transplant patients at high risk of developing cancer.

Optimal management of young adult transplant recipients: the role of integrated multidisciplinary care and peer support.

Young adults with chronic diseases do not fit easily into an aging adult patient population and are frequently isolated from peers. The result is a high rate of non-adherence with medical care and therapy, resulting in poor outcomes. This is an important clinical problem shared equally by young adults transitioning from pediatric care and those presenting directly to adult care. An integrated multidisciplinary pediatric-adult service can improve the transition process and preparation of the teenager for adult health care. A seamless transition into a dedicated young adult service results in reduced premature failure rates of kidney transplants and improved clinic and medication adherence.

Ybp1 and Gpx3 signaling in Candida albicans govern hydrogen peroxide-induced oxidation of the Cap1 transcription factor and macrophage escape.

AIMS: As Candida albicans is the major fungal pathogen of humans, there is an urgent need to understand how this pathogen evades toxic reactive oxygen species (ROS) generated by the host immune system. A key regulator of antioxidant gene expression, and thus ROS resistance, in C. albicans is the AP-1-like transcription factor Cap1. Despite this, little is known regarding the intracellular signaling mechanisms that underlie the oxidation and activation of Cap1. Therefore, the aims of this study were; (i) to identify the regulatory proteins that govern Cap1 oxidation, and (ii) to investigate the importance of Cap1 oxidation in C. albicans pathogenesis. RESULTS: In response to hydrogen peroxide (H2O2), but not glutathione-depleting/modifying oxidants, Cap1 oxidation, nuclear accumulation, phosphorylation, and Cap1-dependent gene expression, is mediated by a glutathione peroxidase-like enzyme, which we name Gpx3, and an orthologue of the Saccharomyces cerevisiae Yap1 binding protein, Ybp1. In addition, Ybp1 also functions to stabilise Cap1 and this novel function is conserved in S. cerevisiae. C. albicans cells lacking Cap1, Ybp1, or Gpx3, are unable to filament and thus, escape from murine macrophages after phagocytosis, and also display defective virulence in the Galleria mellonella infection model. INNOVATION: Ybp1 is required to promote the stability of fungal AP-1-like transcription factors, and Ybp1 and Gpx3 mediated Cap1-dependent oxidative stress responses are essential for the effective killing of macrophages by C. albicans. CONCLUSION: Activation of Cap1, specifically by H2O2, is a prerequisite for the subsequent filamentation and escape of this fungal pathogen from the macrophage.