Secondary prevention of type 1 diabetes mellitus: stopping immune destruction and promoting ß-cell regeneration

Type 1 diabetes mellitus results from a cell-mediated autoimmune attack against pancreatic ß-cells. Traditional treatments involve numerous daily insulin dosages/injections and rigorous glucose control. Many efforts toward the identification of ß-cell precursors have been made not only with the aim of understanding the physiology of islet regeneration, but also as an alternative way to produce ß-cells to be used in protocols of islet transplantation. In this review, we summarize the most recent studies related to precursor cells implicated in the regeneration process. These include embryonic stem cells, pancreas-derived multipotent precursors, pancreatic ductal cells, hematopoietic stem cells, mesenchymal stem cells, hepatic oval cells, and mature ß-cells. There is controversial evidence of the potential of these cell sources to regenerate ß-cell mass in diabetic patients. However, clinical trials using embryonic stem cells, umbilical cord blood or adult bone marrow stem cells are under way. The results of various immunosuppressive regimens aiming at blocking autoimmunity against pancreatic ß-cells and promoting ß-cell preservation are also analyzed. Most of these regimens provide transient and partial effect on insulin requirements, but new regimens are beginning to be tested. Our own clinical trial combines a high dose immunosuppression with mobilized peripheral blood hematopoietic stem cell transplantation in early-onset type 1 diabetes mellitus

Performance and egg quality of laying hens fed different dietary levels of cashew nut shell liquid

Organic acids have stood out as alternatives to antibiotic growth promoters, especially those extracted from plants, such as anacardic acid, which is present in cashew nut shell liquid (CNSL). This study evaluates the effects of CNSL as a source of anacardic acid in diets of laying hens on performance, egg quality, lipid stability of yolk and microbiological analysis of excreta. A total of 216 commercial Hisex White laying hens were housed in cages and distributed in a completely randomized design with six treatments and six replicates of six birds per treatment. Treatments consisted of a diet without antibiotic growth promoter (AGP); diet with AGP (Halquinol 60% at 0.1 g/kg and Enramycin 8% at 0.1 g/kg); and four diets without AGP and with the inclusion of 2.5, 5.0, 7.5 and 10.0 g/kg CNSL. No effects of dietary addition of AGP and CNSL were observed in bird performance and external quality of eggs. A quadratic effect was observed for lipid oxidation in egg yolk, the minimum value of which was found at 5.8 g/kg CNSL. There were no significant effects of treatments on total mesophilic, total coliform and thermotolerant coliform counts on excreta. In conclusion, adding up to 10.0 g/kg of CNSL as source of anacardic acid in laying hen diet did not influence performance or egg quality, but the addition from 7.5 g/kg of CNSL upwards reduced lipid oxidation and improved the yolk colour.Keywords: Anacardium occidentale, lipid oxidation, natural antioxidant, organic aci

Detection of embryo mortality and hatch using thermal differences among incubated chicken eggs

Accurate diagnosis of both the stage of embryonic mortality and the hatch process in incubated eggs is a fundamental component in troubleshooting and hatchery management. However, traditional methods disturb incubation, destroy egg samples, risk contamination, are time and labour-intensive and require specialist knowledge and training. Therefore, a new method to accurately detect embryonic mortality and hatching time would be of significant interest for the poultry industry if it could be done quickly, cheaply and be fully integrated into the process. In this study we have continuously measured individual eggshell temperatures and the corresponding micro-environmental air temperatures throughout the 21 days of incubation using standard low-cost temperature sensors. Moreover, we have quantified the thermal interaction between eggs and air by calculating thermal profile changes (temperature drop time, drop length and drop magnitude) that allowed us to detect four categories of egg status (infertile/early death, middle death, late death and hatch) during incubation. A decision tree induction classification model accurately (93.3%) predicted the status of 105 sampled eggs in comparison to the classical hatch residue breakout analyses. With this study we have provided a major contribution to the optimisation of incubation processes by introducing an alternative method for the currently practiced hatch residue breakout analyses.status: publishe

A level II reliability approach to tunnel support design

A reliability approach to tunnel support design is presented in this paper. The aim of the work is the incorporation of classical Level II techniques to the current design method based on the study of the ground-support interaction diagram

A novel system to map protein interactions reveals evolutionarily conserved immune evasion pathways on transmissible cancers

Around 40% of humans and Tasmanian devils (Sarcophilus harrisii) develop cancer in their lifetime, compared to less than 10% for most species. In addition, devils are affected by two of the three known transmissible cancers in mammals. Immune checkpoint immunotherapy has transformed human medicine, but a lack of species-specific reagents has limited checkpoint immunology in most species. We developed a cut-and-paste reagent development system and used the fluorescent fusion protein system to show that immune checkpoint interactions are conserved across 160,000,000 years of evolution, CD200 is highly expressed on transmissible tumor cells, and coexpression of CD200R1 can block CD200 surface expression. The system’s versatility across species was demonstrated by fusing a fluorescent reporter to a camelid-derived nanobody that binds human programmed death ligand 1. The evolutionarily conserved pathways suggest that naturally occurring cancers in devils and other species can be used to advance our understanding of cancer and immunological tolerance.</p

Immunological Balance Is Associated with Clinical Outcome after Autologous Hematopoietic Stem Cell Transplantation in Type 1 Diabetes

Transplantation and autoimmunit