New immunosuppressive agents in pediatric transplantation

Immunosuppressive therapy in pediatrics continues to evolve. Over the past decade, newer immunosuppressive agents have been introduced into adult and pediatric transplant patients with the goal of improving patient and allograft survival. Unfortunately, large-scale randomized clinical trials are not commonly performed in children. The purpose of this review is to discuss the newer immunosuppressive agents available for induction therapy, maintenance immunosuppression, and the treatment of rejection

Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomized controlled trials

Objective Previous studies have suggested that niacin treatment raises glucose levels in patients with diabetes and may increase the risk of developing diabetes. We undertook a meta-analysis of published and unpublished data from randomised trials to confirm whether an association exists between niacin and new-onset diabetes. Methods We searched Medline, EMBASE and the Cochrane Central Register of Controlled Trials, from 1975 to 2014, for randomised controlled trials of niacin primarily designed to assess its effects on cardiovascular endpoints and cardiovascular surrogate markers. We included trials with ≥50 non-diabetic participants and average follow-up of ≥24 weeks. Published data were tabulated and unpublished data sought from investigators. We calculated risk ratios (RR) for new-onset diabetes with random-effects meta-analysis. Heterogeneity between trials was assessed using the I2 statistic. Results In 11 trials with 26 340 non-diabetic participants, 1371 (725/13 121 assigned niacin; 646/13 219 assigned control) were diagnosed with diabetes during a weighted mean follow-up of 3.6 years. Niacin therapy was associated with a RR of 1.34 (95% CIs 1.21 to 1.49) for new-onset diabetes, with limited heterogeneity between trials (I2=0.0%, p=0.87). This equates to one additional case of diabetes per 43 (95% CI 30 to 70) initially non-diabetic individuals who are treated with niacin for 5 years. Results were consistent regardless of whether participants received background statin therapy (p for interaction=0.88) or combined therapy with laropiprant (p for interaction=0.52). Conclusions Niacin therapy is associated with a moderately increased risk of developing diabetes regardless of background statin or combination laropiprant therapy

High calcium bioglass enhances differentiation and survival of endothelial progenitor cells, inducing early vascularization in critical size bone defects

Early vascularization is a prerequisite for successful bone healing and endothelial progenitor cells (EPC), seeded on appropriate biomaterials, can improve vascularization. The type of biomaterial influences EPC function with bioglass evoking a vascularizing response. In this study the influence of a composite biomaterial based on polylactic acid (PLA) and either 20 or 40% bioglass, BG20 and BG40, respectively, on the differentiation and survival of EPCs in vitro was investigated. Subsequently, the effect of the composite material on early vascularization in a rat calvarial critical size defect model with or without EPCs was evaluated. Human EPCs were cultured with β-TCP, PLA, BG20 or BG40, and seeding efficacy, cell viability, cell morphology and apoptosis were analysed in vitro. BG40 released the most calcium, and improved endothelial differentiation and vitality best. This effect was mimicked by adding an equivalent amount of calcium to the medium and was diminished in the presence of the calcium chelator, EGTA. To analyze the effect of BG40 and EPCs in vivo, a 6-mm diameter critical size calvarial defect was created in rats (n = 12). Controls (n = 6) received BG40 and the treatment group (n = 6) received BG40 seeded with 5×105 rat EPCs. Vascularization after 1 week was significantly improved when EPCs were seeded onto BG40, compared to implanting BG40 alone. This indicates that Ca2+ release improves EPC differentiation and is useful for enhanced early vascularization in critical size bone defects

Rectification properties of conically shaped nanopores: consequences of miniaturization

Nanopores attracted a great deal of scientific interest as templates for biological sensors as well as model systems to understand transport phenomena at the nanoscale. The experimental and theoretical analysis of nanopores has been so far focused on understanding the effect of the pore opening diameter on ionic transport. In this article we present systematic studies on the dependence of ion transport properties on the pore length. Particular attention was given to the effect of ion current rectification exhibited for conically shaped nanopores with homogeneous surface charges. We found that reducing the length of conically shaped nanopores significantly lowered their ability to rectify ion current. However, rectification properties of short pores can be enhanced by tailoring the surface charge and the shape of the narrow opening. Furthermore we analyze the relationship of the rectification behavior and ion selectivity for different pore lengths. All simulations were performed using MsSimPore, a software package for solving the Poisson-Nernst-Planck (PNP) equations. It is based on a novel finite element solver and allows for simulations up to surface charge densities of -2 e/nm^2. MsSimPore is based on 1D reduction of the PNP model, but allows for a direct treatment of the pore with bulk electrolyte reservoirs, a feature which was previously used in higher dimensional models only. MsSimPore includes these reservoirs in the calculations; a property especially important for short pores, where the ionic concentrations and the electric potential vary strongly inside the pore as well as in the regions next to pore entrance

SUMOylation Status and Effects of SUMylation on DAX-1

DAX-1 (Dosage Sensitive Sex Reversal Adrenal Hypoplasia Congenita on the X Chromosome gene 1) is a Nuclear Hormone Receptor, which acts as a transcriptional repressor in the nucleus. DAX-1 plays an important role in development and also appears to have some influence on the progression of cancer. In an effort to better understand DAX-1 function both in normal and disease states we are examining one type of posttranslational modification, SUMOylation. SUMOylation involves the addition of the small polypeptide conjugate SUMO (Small Ubiquitin-like Modifier) to proteins, this can have a variety of effects on protein activity. To study the effects of SUMOylation on DAX-1, the overall SUMOylation status of DAX-1 in mammalian cell lines was determined. It was found that DAX-1 is SUMOylated in several cell lines, both normal and carcinoma cells. Mutations were made in putative SUMOylation sites within the DAX-1 gene and assayed for changes in gene expression and activity

Suicide attempt in a rural area of Vietnam: Incidence, methods used and access to mental health care

OBJECTIVES: The study aims to determine the incidence of suicide attempt, describe the methods used, and assess use of health care services including mental health care after suicide attempt in a rural area of Vietnam. METHODS: All suicide attempters (104) during 2003-2007 were listed, diagnosed and re-evaluated by trained physicians according to the research criteria of the WHO Multicentre Study of Attempted Suicide. All attempters were interviewed by trained medical staff to investigate methods used, socio-demographic characteristics and use of health services. RESULTS: The yearly incidence was 10.2 per 100000 person-years, 10.6 per 100000 in males and 9.8 per 100000 in females. 99% of cases committed suicide attempt by poisoning, 62.6% by pesticides and 36.3% by pharmaceutical drugs. 34.3% reported having been in contact with somatic care and 13.2% had received mental health care. Among those who reported some treatment received, 47.5% had been in contact with official health care services, 8.1% had pharmacy keepers' consultation or were treated by traditional healers and 4% reported self treatment. CONCLUSION: The incidence of suicide attempt was lower in this population compared to other settings. While the majority of attempters use pesticides, many had used psychotropic drugs. Contact with mental health services following the attempt was very limited in this setting. Suicide prevention for this high risk group should focus on reducing access to pesticides and psychotropic drugs. Mental health services should be made more accessible in rural areas

Rationale and practical techniques for mouse models of early vein graft adaptations

Mouse models serve as relatively new yet powerful research tools to study intimal hyperplasia and wall remodeling of vein bypass graft failure. Several model variations have been reported in the past decade. However, the approach demands thoughtful preparation, selected sophisticated equipment, microsurgical technical expertise, advanced tissue processing, and data acquisition. This review compares several described models and aims (building on our personal experiences) to practically aid the investigators who want to utilize mouse models of vein graft failure.Clinical RelevanceSurgical revascularization via vein grafting offers immediate and often dramatic end organ benefit. However, substantial percentages of vein conduits placed develop stenosis or fail, often early. Mechanistic studies of the complex interplay between the biologic and physical forces that drive failure have been hampered by limited quantity and quality of clinical specimens, and the inability of systems such as computer models and cell culture to mimic the clinical circumstance. This review summarizes the power and limitations of mouse vein graft models, and it includes practical experience-based advice for researchers aiming to utilize this tool