Immunosuppression strategies that selectively inhibit effector T cells while preserving and even enhancing CD4+FOXP3+ regulatory T cells (Treg) permit immune self-regulation and may allow minimization of immunosuppression and associated toxicities. Many immunosuppressive drugs were developed before the identity and function of Treg were appreciated. A good understanding of the interactions between Treg and immunosuppressive agents will be valuable to the effective design of more tolerable immunosuppression regimens. This review will discuss preclinical and clinical evidence regarding the influence of current and emerging immunosuppressive drugs on Treg homeostasis, stability, and function as a guideline for the selection and development of Treg-friendly immunosuppressive regimens.

In addition to the differences between populations in transcriptional and translational regulation of genes, alternative pre-mRNA splicing (AS) is also likely to play an important role in regulating gene expression and generating variation in mRNA and protein isoforms. Recently, the genetic contribution to transcript isoform variation has been reported in individuals of recent European descent. We report here results of an investigation of the differences in AS patterns between human populations. AS patterns in 176 HapMap lymphoblastoid cell lines derived from individuals of European and African ancestry were evaluated using the Affymetrix GeneChip® Human Exon 1.0 ST Array. A variety of biological processes such as response to stimulus and transcription were found to be enriched among the differentially spliced genes. The differentially spliced genes also include some involved in human diseases that have different prevalence or susceptibility between populations. The genetic contribution to the population differences in transcript isoform variation was then evaluated by a genome-wide association using the HapMap genotypic data on single nucleotide polymorphisms (SNPs). The results suggest that local and distant genetic variants account for a substantial fraction of the observed transcript isoform variation between human populations. Our findings provide new insights into the complexity of the human genome as well as the health disparities between the two populations.

SummaryThe advent of large-scale in vitro differentiation of human stem cell-derived insulin-producing cells (SCIPC) has brought us closer to treating diabetes using stem cell technology. However, decades of experiences from islet transplantation show that ischemia-induced islet cell death after transplant severely limits the efficacy of the therapy. It is unclear to what extent human SCIPC are susceptible to ischemia. In this study, we show that more than half of SCIPC die shortly after transplantation. Nutrient deprivation and hypoxia acted synergistically to kill SCIPC in vitro. Amino acid supplementation rescued SCIPC from nutrient deprivation, likely by providing cellular energy. Generating SCIPC under physiological oxygen tension of 5% conferred hypoxia resistance without affecting their differentiation or function. A two-pronged strategy of physiological oxygen acclimatization during differentiation and amino acid supplementation during transplantation significantly improved SCIPC survival after transplant.

Background The superomedial pedicle with vertical scar (SMP) breast reduction (BR) is gaining popularity for its round, projecting breast and shorter incision when compared to the traditional Wise-pattern reduction using an inferior pedicle (IFP). However, there is a paucity of large volume institutional outcomes studies identifying how SMP/BR fares against more traditional methods of reduction. The purpose of this study is to compare outcomes after SMP/BR and IFP/BR in the only large volume, matched cohort study-to-date. Methods A retrospective review of a prospectively-maintained database of all bilateral BRs over the three-year period was performed. 100 SMP/BR breasts (50 patients) were matched to 100 IFP/BR breasts (50 patients). Matching was implemented based on age (+/− 3 years) and size of reduction (+/− 200 grams). Patient demographics including age, BMI, and ethnicity, size of reduction, NAC sensitivity, minor and major postoperative complications, and symptomatic relief were assessed. Statistical analysis was performed with SAS v9.2 (Cary, NC). Results 212 patients underwent 424 bilateral BR between 1/2009 – 6/2012 at a single institution; IFP/BR was used in 76% of cases. Mean age and BMI was 31.4 (+/−9.9) and 30.8 (+/− 3.5) in the SMP/BR cohort and 31.6 (+/− 9.9) and 31.8 (+/− 3.6) in the IFP/BR cohort. Mean volume of tissue reduced was 815 grams per breast (range 200–2068g) and 840 grams per breast (range 250–2014g), respectively. All patients achieved symptomatic relief. No statistical difference in major or minor complications was seen between two cohorts; SMP: major 4% (Return to OR 2%; wound infection 2%) and minor complications 25% versus IFP: major 3% (NAC necrosis 1%; hematoma 1%; would infection 1%) and minor complications 24%. No significant difference in complications was seen between small and large volume reductions. Conclusion SMP/BR is a novel, alternative mammaplasty technique with low complication rates and excellent functional and aesthetic outcomes. This is the first matched cohort study to demonstrate that SMP/BR can be used for a wide range of macromastia without a significant difference in complication rates when compared with the traditional Wise-pattern IFP reduction mammaplasty. Level of Evidence Prognostic/Risk, Level III