ENCODE whole-genome data in the UCSC genome browser (2011 update)

The ENCODE project is an international consortium with a goal of cataloguing all the functional elements in the human genome. The ENCODE Data Coordination Center (DCC) at the University of California, Santa Cruz serves as the central repository for ENCODE data. In this role, the DCC offers a collection of high-throughput, genome-wide data generated with technologies such as ChIP-Seq, RNA-Seq, DNA digestion and others. This data helps illuminate transcription factor-binding sites, histone marks, chromatin accessibility, DNA methylation, RNA expression, RNA binding and other cell-state indicators. It includes sequences with quality scores, alignments, signals calculated from the alignments, and in most cases, element or peak calls calculated from the signal data. Each data set is available for visualization and download via the UCSC Genome Browser (http://genome.ucsc.edu/). ENCODE data can also be retrieved using a metadata system that captures the experimental parameters of each assay. The ENCODE web portal at UCSC (http://encodeproject.org/) provides information about the ENCODE data and links for access

Rapamycin/IL-2 combination therapy in patients with type 1 diabetes augments Tregs yet transiently impairs β-cell function.

Rapamycin/interleukin-2 (IL-2) combination treatment of NOD mice effectively treats autoimmune diabetes. We performed a phase 1 clinical trial to test the safety and immunologic effects of rapamycin/IL-2 combination therapy in type 1 diabetic (T1D) patients. Nine T1D subjects were treated with 2-4 mg/day rapamycin orally for 3 months and 4.5 × 10(6) IU IL-2 s.c. three times per week for 1 month. β-Cell function was monitored by measuring C-peptide. Immunologic changes were monitored using flow cytometry and serum analyses. Regulatory T cells (Tregs) increased within the first month of therapy, yet clinical and metabolic data demonstrated a transient worsening in all subjects. The increase in Tregs was transient, paralleling IL-2 treatment, whereas the response of Tregs to IL-2, as measured by STAT5 phosphorylation, increased and persisted after treatment. No differences were observed in effector T-cell subset frequencies, but an increase in natural killer cells and eosinophils occurred with IL-2 therapy. Rapamycin/IL-2 therapy, as given in this phase 1 study, resulted in transient β-cell dysfunction despite an increase in Tregs. Such results highlight the difficulties in translating therapies to the clinic and emphasize the importance of broadly interrogating the immune system to evaluate the effects of therapy

Rapamycin/IL-2 combination therapy in patients with type 1 diabetes augments Tregs yet transiently impairs β-cell function.

Rapamycin/interleukin-2 (IL-2) combination treatment of NOD mice effectively treats autoimmune diabetes. We performed a phase 1 clinical trial to test the safety and immunologic effects of rapamycin/IL-2 combination therapy in type 1 diabetic (T1D) patients. Nine T1D subjects were treated with 2-4 mg/day rapamycin orally for 3 months and 4.5 × 10(6) IU IL-2 s.c. three times per week for 1 month. β-Cell function was monitored by measuring C-peptide. Immunologic changes were monitored using flow cytometry and serum analyses. Regulatory T cells (Tregs) increased within the first month of therapy, yet clinical and metabolic data demonstrated a transient worsening in all subjects. The increase in Tregs was transient, paralleling IL-2 treatment, whereas the response of Tregs to IL-2, as measured by STAT5 phosphorylation, increased and persisted after treatment. No differences were observed in effector T-cell subset frequencies, but an increase in natural killer cells and eosinophils occurred with IL-2 therapy. Rapamycin/IL-2 therapy, as given in this phase 1 study, resulted in transient β-cell dysfunction despite an increase in Tregs. Such results highlight the difficulties in translating therapies to the clinic and emphasize the importance of broadly interrogating the immune system to evaluate the effects of therapy

Racial-ethnic differences in health-related quality of life among adults and children with glomerular disease

The final, published version of this article is available at https://doi.org/10.1159/000516832Introduction: Disparities in health-related quality of life (HRQOL) have been inadequately studied in patients with glomerular disease. The aim of this study was to identify relationships among race/ethnicity, socioeconomic status, disease severity, and HRQOL in an ethnically and racially diverse cohort of patients with glomerular disease. Methods: Cure Glomerulonephropathy (CureGN) is a multinational cohort study of patients with biopsy-proven glomerular disease. Associations between race/ethnicity and HRQOL were determined by the following: (1) missed school or work due to kidney disease and (2) responses to Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires. We adjusted for demographics, socioeconomic status, and disease characteristics using multivariable logistic and linear regression. Results: Black and Hispanic participants had worse socioeconomic status and more severe glomerular disease than white or Asian participants. Black adults missed work or school most frequently due to kidney disease (30 vs. 16–23% in the other 3 groups, p = 0.04), and had the worst self-reported global physical health (median score 44.1 vs. 48.0–48.2, p < 0.001) and fatigue (53.8 vs. 48.5–51.1, p = 0.002), compared to other racial/ethnic groups. However, these findings were not statistically significant with adjustment for socioeconomic status and disease severity, both of which were strongly associated with HRQOL in adults. Among children, disease severity but not race/ethnicity or socioeconomic status was associated with HRQOL. Conclusions: Among patients with glomerular disease enrolled in CureGN, the worse HRQOL reported by black adults was attributable to lower socioeconomic status and more severe glomerular disease. No racial/ethnic differences in HRQOL were observed in children.Funding for the CureGN consortium is provided by U24DK100845 (formerly UM1DK100845), U01DK100846 (formerly UM1DK100846), U01DK100876 (formerly UM1DK100876), U01DK100866 (formerly UM1DK100866), and U01DK100867 (formerly UM1DK100867) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Patient recruitment is supported by NephCure Kidney International. Dates of funding for the first phase of CureGN were from September 16, 2013 to May 31, 2019. Dr. Krissberg is a Tashia and John Morgridge Endowed Postdoctoral Fellow of the Stanford Maternal and Child Health Research Institute. Dr. Nestor reports support by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant No. TL1TR001875. Dr. Kopp is supported by the Intramural Research Program, NIDDK, NIH

Methylaminolaevulinic acid photodynamic therapy in the treatment of erythroplasia of Queyrat

BACKGROUND: Erythroplasia of Queyrat (EQ) is an intra-epithelial carcinoma of the penis. Progression to invasive carcinoma may occur. Its cause is unknown but some evidence suggests infection with human papillomavirus in the pathogenesis of EQ; however, recent data do not confirm this. Therapy is difficult and associated with important recurrence rates. Photodynamic therapy (PDT) employs a photosensitizer excited by visible light. The resulting photodynamic reaction selectively destroys atypical cells. Only few reports exist on the use of topical PDT in the treatment of EQ. OBJECTIVE: We report 11 cases of EQ treated by topical methylaminolaevulinic acid (MAL) PDT. RESULTS: Out of 11 male patients with EQ treated by topical MAL-PDT, 3 achieved complete remission sustained for 24 and 51 months and 4 a partial remission sustained for 2-45 months with a follow-up period of 4-45 months (1 patient lost to follow-up); surprisingly, 2 of the 4 patients with partial remission presented a complete remission after 20 and 45 months of follow-up, respectively, without further therapy. Four patients showed progression of the disease. CONCLUSION: Whereas topical MAL-PDT offers the advantages of tumour specificity, preservation of function and a good cosmetic result, side effects may cause treatment discontinuation in some cases. Treatment of EQ with PDT may represent a valuable option in selected cases, but our data do not allow considering it as a first-line therapeutic option

Examining the social porosity of environmental features on neighborhood sociability and attachment

The local neighborhood forms an integral part of our lives. It provides the context through which social networks are nurtured and the foundation from which a sense of attachment and cohesion with fellow residents can be established. Whereas much of the previous research has examined the role of social and demographic characteristic in relation to the level of neighboring and cohesion, this paper explores whether particular environmental features in the neighborhood affect social porosity. We define social porosity as the degree to which social ties flow over the surface of a neighborhood. The focus of our paper is to examine the extent to which a neighborhood's environmental features impede the level of social porosity present among residents. To do this, we integrate data from the census, topographic databases and a 2010 survey of 4,351 residents from 146 neighborhoods in Australia. The study introduces the concepts of wedges and social holes. The presence of two sources of wedges is measured: rivers and highways. The presence of two sources of social holes is measured: parks and industrial areas. Borrowing from the geography literature, several measures are constructed to capture how these features collectively carve up the physical environment of neighborhoods. We then consider how this influences residents' neighboring behavior, their level of attachment to the neighborhood and their sense of neighborhood cohesion. We find that the distance of a neighborhood to one form of social hole-industrial areas-has a particularly strong negative effect on all three dependent variables. The presence of the other form of social hole-parks-has a weaker negative effect. Neighborhood wedges also impact social interaction. Both the length of a river and the number of highway fragments in a neighborhood has a consistent negative effect on neighboring, attachment and cohesion