A Longitudinal Assessment of Change in Blood Pressure Among Participants in the Heart Smarts Program

Many low-income areas of the United States are considered food deserts because people living in those communities have limited access to fresh fruits and vegetables (FFV); lack of FFV is tied to numerous health issues, including cardiovascular disease and obesity. The Heart Smarts Program (HSP) provides increased access to FFV in food deserts, as well as providing participants with nutrition education courses and health screenings, including blood pressure. The purpose of this study is to examine HSP participants who have been with the program for differing lengths of time in order to determine if length of participation has an impact on magnitude of change in blood pressure. Participants are self-selected members of the community who frequent the corner stores in which the HSP operates and who have chosen to participate in health screenings. The blood pressure readings of participants who had two or more screenings with the HSP were analyzed to determine the longitudinal impact of participation in the HSP on change in blood pressure. Analysis of the average change in both systolic and diastolic blood pressures between four groups of participants who had taken part in the HSP for differing lengths of time showed no significant difference (p=0.625, p=0.259). This indicates that increased length of participation in the HSP is not associated with a larger drop in blood pressure when compared to those who have participated for a shorter time. However, this study does not examine changes in weight, eating habits, and level of nutrition education, and therefore it is unable to determine the longitudinal effects of the HSP as a whole

CD11c+ Cells Are Gatekeepers for Lymphocyte Trafficking to Infiltrated Islets During Type 1 Diabetes.

Type 1 diabetes (T1D) is a T cell mediated autoimmune disease that affects more than 19 million people with incidence increasing rapidly worldwide. For T cells to effectively drive T1D, they must first traffic to the islets and extravasate through the islet vasculature. Understanding the cues that lead to T cell entry into inflamed islets is important because diagnosed T1D patients already have established immune infiltration of their islets. Here we show that CD11

Mapping of a hybrid insulin peptide in the inflamed islet β-cells from NOD mice

There is accumulating evidence that pathogenic T cells in T1D recognize epitopes formed by post-translational modifications of β-cell antigens, including hybrid insulin peptides (HIPs). The ligands for several CD4 T-cell clones derived from the NOD mouse are HIPs composed of a fragment of proinsulin joined to peptides from endogenous β-cell granule proteins. The diabetogenic T-cell clone BDC-6.9 reacts to a fragment of C-peptide fused to a cleavage product of pro-islet amyloid polypeptide (6.9HIP). In this study, we used a monoclonal antibody (MAb) to the 6.9HIP to determine when and where HIP antigens are present in NOD islets during disease progression and with which immune cells they associate. Immunogold labeling of the 6.9HIP MAb and organelle-specific markers for electron microscopy were employed to map the subcellular compartment(s) in which the HIP is localized within β-cells. While the insulin B9-23 peptide was present in nearly all islets, the 6.9HIP MAb stained infiltrated islets only in NOD mice at advanced stages of T1D development. Islets co-stained with the 6.9HIP MAb and antibodies to mark insulin, macrophages, and dendritic cells indicate that 6.9HIP co-localizes within insulin-positive β-cells as well as intra-islet antigen-presenting cells (APCs). In electron micrographs, the 6.9HIP co-localized with granule structures containing insulin alone or both insulin and LAMP1 within β-cells. Exposing NOD islets to the endoplasmic reticulum (ER) stress inducer tunicamycin significantly increased levels of 6.9HIP in subcellular fractions containing crinosomes and dense-core granules (DCGs). This work demonstrates that the 6.9HIP can be visualized in the infiltrated islets and suggests that intra-islet APCs may acquire and present HIP antigens within islets

Broad Repertoire of T Cell Autoreactivity Directly from Islets of Donors with Type 1 Diabetes (T1D)

Type 1 diabetes (T1D) is an autoimmune disease characterized by the infiltration of lymphocytes into the insulin-producing β-cells in the pancreas. We have isolated live T cells sorted or grown directly from the isolated, handpicked islets of human donors with T1D. We received ~500 islet equivalent EQ of variable purity (10-90%) from 12 donors with T1D (disease duration 0.42-20 years) and from seven control donors and two donors with type 2 diabetes (T2D). A total of 321 T cell lines and clones were derived from the islets of donors with T1D (3 lines from the 9 control donors). These are 131 CD4+ lines and clones, 47 CD8+ lines and 143 lines that contain both CD4+ and CD8+ T cells. From 50 lines and clones examined to date, we have determined the autoreactivity of 19 and have seen a broad repertoire of T cell autoreactivity in the islets, including characterized targets and post-translationally modified targets. Autoreactivity of CD4+ T cell lines was to three different peptides from glutamic acid decarboxylase 65 (GAD; GAD115-127, GAD274-286, GAD555-567), proinsulin76-90, and to chromogranin A or proinsulin expressed by DR4+DQ8+ B cells transduced with lentivirus containing constructs with the open reading frames corresponding to whole autoantigens. Reactivity to modified peptides included the glucose-regulated protein 78 and islet amyloid polypeptide with arginine to citrulline modifications (GRP78292-305(Arg-Cit297) and IAPP65-84(Arg-Cit 73, 81)), deaminations (IA-2545-562(Gln-Glu 548, 551, 556), and to several insulin hybrid peptides. These autoreactive CD4+ T cell lines and clones secreted only pro-inflammatory cytokines (IFN-γ, TNFα) upon peptide stimulation. For CD8+ T cells from islets, from one donor with T1D, we saw binding of a pool of HLA-A2 pentamers loaded with insulin B10-18, IA-2797-805 and insulin specific glucose-6-phosphatase catalytic subunit related protein, IGRP265-273. These results have implications for the development of successful prevention and reversal therapeutic strategies in T1D

CD11c+ Cells Are Gatekeepers for Lymphocyte Trafficking to Infiltrated Islets During Type 1 Diabetes

Type 1 diabetes (T1D) is a T cell mediated autoimmune disease that affects more than 19 million people with incidence increasing rapidly worldwide. For T cells to effectively drive T1D, they must first traffic to the islets and extravasate through the islet vasculature. Understanding the cues that lead to T cell entry into inflamed islets is important because diagnosed T1D patients already have established immune infiltration of their islets. Here we show that CD11c+ cells are a key mediator of T cell trafficking to infiltrated islets in non-obese diabetic (NOD) mice. Using intravital 2-photon islet imaging we show that T cell extravasation into the islets is an extended process, with T cells arresting in the islet vasculature in close proximity to perivascular CD11c+ cells. Antigen is not required for T cell trafficking to infiltrated islets, but T cell chemokine receptor signaling is necessary. Using RNAseq, we show that islet CD11c+ cells express over 20 different chemokines that bind chemokine receptors expressed on islet T cells. One highly expressed chemokine-receptor pair is CXCL16-CXCR6. However, NOD. CXCR6−/− mice progressed normally to T1D and CXCR6 deficient T cells trafficked normally to the islets. Even with CXCR3 and CXCR6 dual deficiency, T cells trafficked to infiltrated islets. These data reinforce that chemokine receptor signaling is highly redundant for T cell trafficking to inflamed islets. Importantly, depletion of CD11c+ cells strongly inhibited T cell trafficking to infiltrated islets of NOD mice. We suggest that targeted depletion of CD11c+ cells associated with the islet vasculature may yield a therapeutic target to inhibit T cell trafficking to inflamed islets to prevent progression of T1D

Luxury brands consumption: The segment of “Chandlers”

The purpose of this paper is to introduce the segment of “chandlers” to the Russian academic society and to describe the specifics of their contemporary consumer behavior. The term “chandler” for this study was borrowed from American classical literature and applied to marketing. The study was conducted in April 2016 and comprised of two stages. The first stage was a series of in-depth interviews with seven representatives of the target audience from Moscow. It allowed to formulate the hypotheses which were proved/disproved by these hypotheses during the online survey. 117 relevant respondents were chosen for the study (72 — from Moscow, 45 — from regional city Ufa). The results allowed to formulate a preliminary conclusion there are no сhandlers in Ufa now. The most popular luxury brands for the Moscow сhandlers and specifics of their consumption were determined. This research is the first descriptive step to understanding the specifics of contemporary сhandlers — how they manage to consume luxury in the form of material artefacts and services, while being kept on a shoestring budget. The research entails a few limitations. The investigation comprised only a limited numbers of the respondents from Russian cities as Moscow and Ufa. In future, more consumers will be involved in the sample to cover more cities in Russia and respondents from other countries will be included. Upon the research completion a range of the recommendations has been provided to the luxury producers whose brands are already presented in Moscow and also for those who are planning to open their stores there. The results may serve as a guide for marketing tools development in the luxury industry. The originality of the paper lies in the term “chandlers’ segment” which is introduced in marketing theory for the first time

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure