Glucocorticoid pharmacogenetics in pediatric idiopathic nephrotic syndrome

Idiopathic nephrotic syndrome represents the most common type of primary glomerular disease in children: glucocorticoids (GCs) are the first-line therapy, even if considerable interindividual differences in thepir efficacy and side effects have been reported. Immunosuppressive and anti-inflammatory effects of these drugs are mainly due to the GC-mediated transcription regulation of pro- and anti-inflammatory genes. This mechanism of action is the result of a complex multistep pathway that involves the glucocorticoid receptor and several other proteins, encoded by polymorphic genes. Aim of this review is to highlight the current knowledge on genetic variants that could affect GC response, particularly focusing on children with idiopathic nephrotic syndrome

Mesenchymal Stem Cell-Based Immunomodulation in Allogeneic Heterotopic Heart-Lung Transplantation

Mesenchymal stem cells are able to differentiate in various cell lineages and they have shown immunomodulatory properties in vitro, altering the cytokine secretion profile of T helper, T effector and dendritic cells and stimulating natural killer cells towards an anti-inflammatory and tolerant phenotype. In vivo they prolong skin allograft survival and may decrease graft-versus-host disease after hematopoietic stem cell transplants. In this work we studied the effects of mesenchymal stem cell treatment in an allogeneic heterotopic heart-lung transplant model. The following experimental groups were formed: A) Control B) Immunosuppressive therapy (Cyclosporine A) C) Mesenchymal stem-cell intravenous infusion D) Mesenchymal stem-cell infusion plus immunosuppressive treatment. The infusion of mesenchymal stem cells improved the mean graft survival up to 14.5±3.7 days with respect to the control group (3±0.6 days). Treatment with Cyclosporine A plus mesenchymal stem cells (group D) produced a mean survival time of 18.25±4.9 days, and was not significantly different to the results for group B (21.75±3.5 days). Furthermore, in the immunosuppressive treatment and the mesenchymal stem cell treatment, histological analysis revealed a reduction in the grade of rejection in heart and lung grafts. This decrease was most significant in group D. In conclusion, mesenchymal stem cells alone or in combination with Cyclosporine A were able to prolong graft survival time. These data suggest that, in vivo, mesenchymal stem cells retain their ability, already shown in vitro, to suppress lymphocyte activation and proliferation

Adverse Childhood Experiences and Resilience: Addressing the Unique Needs of Adolescents

Adolescents exposed to adverse childhood experiences (ACEs) have unique developmental needs that must be addressed by the health, education, and social welfare systems that serve them. Nationwide, over half of adolescents have reportedly been exposed to ACEs. This exposure can have detrimental effects, including increased risk for learning and behavioral issues and suicidal ideation. In response, clinical and community systems need to carefully plan and coordinate services to support adolescents who have been exposed to ACEs, with a particular focus on special populations. We discuss how adolescents' needs can be met, including considering confidentiality concerns and emerging independence; tailoring and testing screening tools for specific use with adolescents; identifying effective multipronged and cross-system trauma-informed interventions; and advocating for improved policies

Portals of Change: How Patient Portals Will Ultimately Work for Safety Net Populations

Despite the implementation of internet patient portals into the safety net after the introduction of the Affordable Care Act in the United States, little attention has been paid to the process of engaging vulnerable patients into these portals. The portal is a health technology tool that was developed with a mainstream, English-speaking audience in mind. Thus, there are valid concerns that such technologies will actually exacerbate health care disparities, conferring further advantages to the already advantaged. In this paper, we describe a framework for portal engagement (awareness, registration, and use) among safety net patients. We incorporate the experiences in the Los Angeles County Department of Health Services to illustrate important contextual factors for portal outreach in our safety net. Finally, we discuss considerations for moving forward with health technology in the safety net as the next version of patient portals are being developed

Salting the Charged Surface: pH and Salt Dependence of Protein G B1 Stability

This study shows significant effects of protein surface charges on stability and these effects are not eliminated by salt screening. The stability for a variant of protein G B1 domain was studied in the pH-range of 1.5–11 at low, 0.15 M, and 2 M salt. The variant has three mutations, T2Q, N8D, and N37D, to guarantee an intact covalent chain at all pH values. The stability of the protein shows distinct pH dependence with the highest stability close to the isoelectric point. The stability is pH-dependent at all three NaCl concentrations, indicating that interactions involving charged residues are important at all three conditions. We find that 2 M salt stabilizes the protein at low pH (protein net charge is +6 and total number of charges is 6) but not at high pH (net charge is ≤−6 and total number of charges is ≥18). Furthermore, 0.15 M salt slightly decreases the stability of the protein over the pH range. The results show that a net charge of the protein is destabilizing and indicate that proteins contain charges for reasons other than improved stability. Salt seems to reduce the electrostatic contributions to stability under conditions with few total charges, but cannot eliminate electrostatic effects in highly charged systems