Dietary short chain fatty acids protect against type 1 diabetes

The short-chain fatty acids (SCFAs) acetate and butyrate, which are released from specialized diets by gut microbes, protect non-obese diabetic (NOD) mice against insulitis and slow the progression of diabetes

An Unusual Case of Presacral Carcinoid Tumor and the Approach of Management

Introduction: Gut derived neuroendocrine tumors (NETs) are a heterogenous group of tumors classified as Gastroenteropancreatic (GEP) NETs. These tumors can be found along the gastrointestinal tract from the foregut, mid, to the hindgut. They are referred to as carcinoid tumors due to their potential to secrete bioactive hormones.Presacral tumors are a subset of GEP NETs that are histologically similar. They are uncommon tumors that are found at the presacral space and are often clinically silent with no associated carcinoid syndrome. Presentation of Case: We report a case of 49 year old female who was diagnosed with a presacral carcinoid tumor. Her initial presentation, investigations that led up to the final diagnosis and management of the tumor are discussed. Conclusion: Presacral carcinoid tumors are NETs that are clinically and histologically similar to GEPs arising from the colon or rectum. Management of such tumors is often surgical resection of localized disease with a long follow-up of surveillance to detect recurrence and metastasis

Regulatory B Cells: Role in Type 1 Diabetes

This is the final version. Available on open access from Frontiers Media via the DOI in this recordRegulatory B cells (Bregs) have an anti-inflammatory role and can suppress autoimmunity, by employing both cytokine secretion and cell-contact mediated mechanisms. Numerous Breg subsets have been described and have overlapping phenotypes in terms of their immune expression markers or cytokine production. A hallmark feature of Bregs is the secretion of IL-10, although IL-35 and TGFβ−producing B cells have also been identified. To date, few reports have identified an impaired frequency or function of Bregs in individuals with type 1 diabetes; thus our understanding of the role played by these Breg subsets in the pathogenesis of this condition is limited. In this review we will focus on how regulatory B cells are altered in the development of type 1 diabetes, highlighting both frequency and function and discuss both human and animal studies.Research EnglandMedical Research Council (MRC

Dietary short chain fatty acids protect against type 1 diabetes

The short-chain fatty acids (SCFAs) acetate and butyrate, which are released from specialized diets by gut microbes, protect non-obese diabetic (NOD) mice against insulitis and slow the progression of diabetes

A Formal, Resource Consumption-Preserving Translation of Actors to Haskell

We present a formal translation of an actor-based language with cooperative scheduling to the functional language Haskell. The translation is proven correct with respect to a formal semantics of the source language and a high-level operational semantics of the target, i.e. a subset of Haskell. The main correctness theorem is expressed in terms of a simulation relation between the operational semantics of actor programs and their translation. This allows us to then prove that the resource consumption is preserved over this translation, as we establish an equivalence of the cost of the original and Haskell-translated execution traces.Comment: Pre-proceedings paper presented at the 26th International Symposium on Logic-Based Program Synthesis and Transformation (LOPSTR 2016), Edinburgh, Scotland UK, 6-8 September 2016 (arXiv:1608.02534

Activated but functionally impaired memory Tregs are expanded in slow progressors to type 1 diabetes

This is the final version. Available on open access from Springer via the DOI in this recordData availability: The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.Aims/hypothesis Slow progressors to type 1 diabetes are individuals positive for multiple pancreatic islet autoantibodies who have remained diabetes-free for at least 10 years; regulation of the autoimmune response is understudied in this group. Here, we profile CD4+ regulatory T cells (Tregs) in a small but well-characterised cohort of extreme slow progressors with a median age 43 (range 31–72 years), followed up for 18–32 years. Methods Peripheral blood samples were obtained from slow progressors (n = 8), age- and sex-matched to healthy donors. One participant in this study was identified with a raised HbA1c at the time of assessment and subsequently diagnosed with diabetes; this donor was individually evaluated in the analysis of the data. Peripheral blood mononuclear cells (PBMCs) were isolated, and to assess frequency, phenotype and function of Tregs in donors, multi-parameter flow cytometry and T cell suppression assays were performed. Unsupervised clustering analysis, using FlowSOM and CITRUS (cluster identification, characterization, and regression), was used to evaluate Treg phenotypes. Results Unsupervised clustering on memory CD4+ T cells from slow progressors showed an increased frequency of activated memory CD4+ Tregs, associated with increased expression of glucocorticoid-induced TNFR-related protein (GITR), compared with matched healthy donors. One participant with a raised HbA1c at the time of assessment had a different Treg profile compared with both slow progressors and matched controls. Functional assays demonstrated that Treg-mediated suppression of CD4+ effector T cells from slow progressors was significantly impaired, compared with healthy donors. However, effector CD4+ T cells from slow progressors were more responsive to Treg suppression compared with healthy donors, demonstrated by increased suppression of CD25 and CD134 expression on effector CD4+ T cells. Conclusions/interpretations We conclude that activated memory CD4+ Tregs from slow progressors are expanded and enriched for GITR expression, highlighting the need for further study of Treg heterogeneity in individuals at risk of developing type 1 diabetes.Diabetes UKJDR

T Cells Recognizing a Peptide Contaminant Undetectable by Mass Spectrometry

Synthetic peptides are widely used in immunological research as epitopes to stimulate their cognate T cells. These preparations are never completely pure, but trace contaminants are commonly revealed by mass spectrometry quality controls. In an effort to characterize novel major histocompatibility complex (MHC) Class I-restricted β-cell epitopes in non-obese diabetic (NOD) mice, we identified islet-infiltrating CD8+ T cells recognizing a contaminating peptide. The amount of this contaminant was so small to be undetectable by direct mass spectrometry. Only after concentration by liquid chromatography, we observed a mass peak corresponding to an immunodominant islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)206-214 epitope described in the literature. Generation of CD8+ T-cell clones recognizing IGRP206-214 using a novel method confirmed the identity of the contaminant, further underlining the immunodominance of IGRP206-214. If left undetected, minute impurities in synthetic peptide preparations may thus give spurious results

Factors influencing satisfaction with the process of orthodontic treatment in adult patients

Introduction: Despite the increases in adults undergoing orthodontic treatment in both the public and private sectors, satisfaction with the treatment process has not been widely explored. In this study, we investigated factors influencing satisfaction with the process of orthodontic treatment in adult patients. / Methods: This was a prospective cross-sectional qualitative study. Participants were adults who had completed orthodontic treatment with fixed appliances and were recruited from 2 sites (a National Health Service public sector teaching hospital and a private specialist practice). Data were collected using in-depth interviews, and a content thematic analysis with a framework approach was used to analyze the data. / Results: A total of 26 adults were recruited (13 at each site). Five main themes were identified relating to patient satisfaction with the process of treatment: communication, staff, physical environment, appointments, and impact of appliance treatment. Effective communication was a dominant theme, particularly relating to explanations during treatment and making patients feel involved in their own care. / Conclusions: In general, adult orthodontic patients were satisfied with the process of treatment, and good communication played a major part in this. Despite the differences in working models in the public and private sectors, many similarities arose when comparing the factors between the 2 sites

Protection of islet grafts through transforming growth factor-beta-induced tolerogenic dendritic cells

In type 1 diabetes, the insulin-producing β-cells are destroyed by the immune system. One way of restoring glucose control is to transplant β-cells from a donor. Although this procedure may restore endogenous insulin production, immunosuppressive treatment is needed to prevent the recipient from rejecting the donor-derived islets. We investigated the possibilities of transient expression of the immunosuppressive cytokine transforming growth factor (TGF)-β within islets to achieve long-term graft tolerance. We found that brief expression of TGF-β prevented rejection of syngeneic islets, that there was reduction of dendritic cell (DC) activation in the graft, and that there was reduced reactivation of T cells in the graft-draining lymph nodes. In vitro exposure of bone marrow–derived DCs to TGF-β reduced expression of costimulatory molecules CD80 and CD86, as well as production of proinflammatory cytokines such as interleukin-12 p70 in DCs, but did not alter levels of major histocompatibility complex classes I and II. Furthermore, the capacity of TGF-β–treated bone marrow–derived DCs to activate both CD4+ and CD8+ T cells was reduced. Adding TGF-β–conditioned tolerogenic DCs to the grafted islets led to long-term survival of the graft, demonstrating that TGF-β–induced tolerogenic DCs can provide an effective means to restore immune tolerance in an already established autoimmune disease