TRAIL and DcR1 Expressions Are Differentially Regulated in the Pancreatic Islets of STZ- versus CY-Applied NOD Mice

TNF-related apoptosis-inducing ligand (TRAIL) is an important component of the immune system. Although it is well acknowledged that it also has an important role in Type 1 Diabetes (T1D) development, this presumed role has not yet been clearly revealed. Streptozotocin (STZ) and Cyclophosphamide (CY) are frequently used agents for establishment or acceleration of T1D disease in experimental models, including the non-obese diabetic (NOD) mice. Although such disease models are very suitable for diabetes research, different expression patterns for various T1D-related molecules may be expected, depending on the action mechanism of the applied agent. We accelerated diabetes in female NOD mice using STZ or CY and analyzed the expression profiles of TRAIL ligand and receptors throughout disease development. TRAIL ligand expression followed a completely different pattern in STZ- versus CY-accelerated disease, displaying a prominent increase in the former, while appearing at reduced levels in the latter. Decoy receptor 1 (DcR1) expression also increased significantly in the pancreatic islets in STZ-induced disease. Specific increases observed in TRAIL ligand and DcR1 expressions may be part of a defensive strategy of the beta islets against the infiltrating leukocytes, while the immune-suppressive agent CY may partly hold down this defense, contributing further to diabetes development

Leptin receptor signaling regulates protein synthesis pathways and neuronal differentiation in pluripotent stem cells

The role of leptin receptor (OB-R) signaling in linking pluripotency with growth and development and the consequences of dysfunctional leptin signaling on progression of metabolic disease is poorly understood. Using a global unbiased proteomics approach we report that embryonic fibroblasts (MEFs) carrying the db/db mutation exhibit metabolic abnormalities, while their reprogrammed induced pluripotent stem cells (iPSCs) show altered expression of proteins involved in embryonic development. An upregulation in expression of eukaryotic translation initiation factor 4e (Eif4e) and Stat3 binding to the Eif4e promoter was supported by enhanced protein synthesis in mutant iPSCs. Directed differentiation of db/db iPSCs toward the neuronal lineage showed defects. Gene editing to correct the point mutation in db/db iPSCs using CRISPR-Cas9, restored expression of neuronal markers and protein synthesis while reversing the metabolic defects. These data imply a direct role for OB-R in regulating metabolism in embryonic fibroblasts and key developmental pathways in iPSCs.publishedVersio

A nationwide multicentre study in Turkey for establishing reference intervals of haematological parameters with novel use of a panel of whole blood

IntroductionA nationwide multicentre study was conducted to establish well-defined reference intervals (RIs) of haematological parameters for the Turkish population in consideration of sources of variation in reference values (RVs). Materials and methodsK2-EDTA whole blood samples (total of 3363) were collected from 12 laboratories. Sera were also collected for measurements of iron, UIBC, TIBC, and ferritin for use in the latent abnormal values exclusion (LAVE) method. The blood samples were analysed within 2 hours in each laboratory using Cell Dyn and Ruby (Abbott), LH780 (Beckman Coulter), or XT-2000i (Sysmex). A panel of freshly prepared blood from 40 healthy volunteers was measured in common to assess any analyser-dependent bias in the measurements. The SD ratio (SDR) based on ANOVA was used to judge the need for partitioning RVs. RIs were computed by the parametric method with/without applying the LAVE method. ResultsAnalyser-dependent bias was found for basophils (Bas), MCHC, RDW and MPV from the panel test results and thus those RIs were derived for each manufacturer. RIs were determined from all volunteers’ results for WBC, neutrophils, lymphocytes, monocytes, eosinophils, MCV, MCH and platelets. Gender-specific RIs were required for RBC, haemoglobin, haematocrit, iron, UIBC and ferritin. Region-specific RIs were required for RBC, haemoglobin, haematocrit, UIBC, and TIBC. ConclusionsWith the novel use of a freshly prepared blood panel, manufacturer-specific RIs’ were derived for Bas, Bas%, MCHC, RDW and MPV. Regional differences in RIs were observed among the 7 regions of Turkey, which may be attributed to nutritional or environmental factors, including altitude

Investigating the impact of CO2 emissions on the COVID-19 pandemic by generalized linear mixed model approach with inverse Gaussian and gamma distributions

Carbon dioxide (CO2) rate within the atmosphere has been rising for decades due to human activities especially due to usage of fuel types such as coal, cement, flaring, gas, oil, etc. Especially in 2020, COVID-19 pandemic caused major economic, production, and energy crises all around the world. As a result of this situation, there was a sharp decrease in the global CO2 emissions depending on the fuel types used during this pandemic. The aim of this study was to explore the effects of “CO2 emissions due to the fuel types” on “percentage of deaths in total cases” attributed to the COVID-19 pandemic using generalized linear model and generalized linear mixed model (GLMM) approaches with inverse Gaussian and gamma distributions, and also to obtain global statistical inferences about 169 World Health Organization member countries that will disclose the impact of the CO2 emissions due to the fuel types during this pandemic. The response variable is taken as “percentage of deaths in total cases attributed to the COVID-19 pandemic” calculated as “(total deaths/total confirmed cases attributed to the COVID-19 pandemic until December 31, 2020)*100.” The explanatory variables are taken as “production-based emissions of CO2 from different fuel types,” measured in tonnes per person, which are “coal, cement, flaring, gas, and oil.” As a result of this study, according to the goodness-of-fit test statistics, “GLMM approach with gamma distribution” called “gamma mixed regression model” is determined as the most appropriate statistical model for investigating the impact of CO2 emissions on the COVID-19 pandemic. As the main findings of this study, 1 t CO2 emissions belonging to the fuel types “cement, coal, flaring, gas, and oil” per person cause increase in deaths in total cases attributed to the COVID-19 pandemic by 2.8919, 2.6151, 2.5116, 2.5774, and 2.5640%, respectively

Cross-Validation of the Turkish Version of the 28-Item Impact of Vision Impairment Profile Test

Purpose: To translate the original 28-item Impact of Vision Impairment Profile into Turkish and to investigate its validity and reliability. Methods: Patients with no limitations to respond and affected by a chronic eye disease including retinitis pigmentosa (RP), age-related macular degeneration (ARMD) and diabetic macular edema which cause low vision were enrolled. The Turkish version of the IVI test was administered to all participants. The linguistic translation followed the international guidelines of forward and backward translation. 256 subjects who had a Snellen visual acuity of 6/12 or worse in the eye with best corrected visual acuity (BCVA) completed the Turkish version of the IVI-28 item. Psychometric evaluation of the Turkish IVI test involved the assessment of internal consistency, test-retest reliability, convergent and known-groups validity. Results: The mean (±SD) age of the participants was 53.67 ± 17.22 years. There were 256 patients with one of the following conditions: 105 RP (41%), 77 ARMD (30%), 74 DME (29%). Patients with lower visual acuity (VA) had lower index scores than those with higher VA (p = 0.001), which showed a sufficient responsiveness. Conclusion: Statistical analysis showed that Turkish version of the IVI-28 item is a valid and reliable instrument to measure vision-related quality of life (VRQoL) in patients with low vision.</p