HDL meets triglyceride

Abstract: The study by Liu et al in this issue of the Journal of Lipid Research leverages data from the UK Biobank to explore the impact of HDL-TG on atherosclerotic cardiovascular disease risk. The investigators observed that elevated serum triglyceride levels were associated with reduced HDL particle diameter and with increased HDL-TG. Using observational and Mendelian randomization analyses, HDL-TG levels were independently associated with atherosclerotic cardiovascular disease risk even after adjusting for multiple confounders and other risk factors. The results emphasize the need for a broader evaluation of lipid parameters that extends beyond traditional measurements and suggest that incorporating metrics like HDL-TG could enhance risk stratification

Perforated Paper-Based Piezoresistive Force Sensor

15th Conference on Ph.D Research in Microelectronics and Electronics (PRIME) -- JUL 15-18, 2019 -- Lausanne, SWITZERLANDIn this work, a paper-based disposable piezoresistive force sensor has been designed, fabricated and tested along with peripheral electronic circuit. Strathmore (R) 400 series Bristol paper is employed as the substrate and it is coated with graphite and silver ink to form a perforated cantilever beam which constitutes the sensor part of the force sensing system. The proposed force sensing system can measure a force ranging to 24 mN with a force resolution of 196 mu N. The implemented sensor has a sensitivity of 8.63 mV/mN.Dialogue Semiconductor,Cadence,Coilcraft,Melexis,Springer,IEEE,IEEE Circuits & Syst Soc,Ecole Polytechnique Federale Lausanne,ams,Ecole Polytechnique Federale Lausanne, RFIC Grp,Ecole Polytechnique Federale Lausanne, ICLAB LabTUBITAK project [117E236]The authors would like to sincerely thank TUBITAK project no:117E236 and project members Oznur Mete & Berkay Alcicek

Differential expression of Ormdl genes in the islets of mice and humans with obesity

SummaryThe orosomucoid-like proteins (Ormdl1-3) are emerging as the critical regulators of sphingolipid homeostasis, inflammation and ER stress. However, their roles in β-cells and obesity remain unknown. Here, we showed that islets isolated from overweight/obese human donors displayed marginally reduced ORMDL1-2 expression while ORMDL3 expression was significantly reduced as compared to islets from lean donors. In contrast, Ormdl3 expression was significantly upregulated in the islets of leptin-deficient obese (ob/ob) mice compared to lean mice. We identified that the difference in expression of Ormdl3 between mouse and human islets was leptin-dependent, as treatment of ob/ob mice with leptin significantly reduced Ormld3 expression. Furthermore, Ormdl1-3 were significantly upregulated upon chemically-induced ER stress, but they showed differential responsiveness to cytokines in a β-cell line. Knockdown of Ormdl3 substantially increased expression of apoptotic markers, which was rescued by a pharmacological inhibitor of ceramide synthase. Taken together we demonstrate leptin-dependent regulation of Ormdl3 expression in ob/ob islets, highlight the possible importance of β-cell stress conditions in differential Ormdl expression and identify a critical role for Ormdl3 in β-cell survival.</jats:p

Acquired FVIII and FIX Inhibitors after Pregnancy: A Case Report

Acquired hemophilia is a relatively rare clinical presentation, and most cases present with acquired FVIII inhibitor. The co-occurrence of inhibitors to multiple coagulation factors is uncommon. These autoantibodies may induce spontaneous life-threatening bleeding in patients who have had no previous bleeding disorder. Herein, we present a patient with postpartum acquired FVIII and FIX inhibitors who developed intramuscular hematoma and hemothorax during follow-up. She was then treated with activated prothrombin complex concentrate and methylprednisolone. (C) 2016 S. Karger AG, Base

Design of efficacious somatic cell genome editing strategies for recessive and polygenic diseases

Abstract Gene correction of multiple alleles for compound heterozygous recessive or polygenic diseases is a promising therapeutic strategy. However, the targeting of multiple alleles using genome editors in a single cell could lead to mixed genotypes and adverse events that amplify during tissue morphogenesis. Here we demonstrate that SpyCas9-based S1mplex genome editors can be designed and developed to correct two distinct mutant alleles within a single human cell precisely. Gene-corrected cells in a patient-derived, induced pluripotent stem cell (iPSC) model of Pompe disease robustly expressed the corrected transcript from both corrected alleles. The translated protein from the gene-corrected cells was properly processed after translation and was able to enzymatically cross-correct diseased cells at levels equivalent to standard-of-care, enzyme replacement therapy (ERT). Using a novel in silico model for the in vivo delivery of these and many other genome editors into a developing liver of a human infant, we identify progenitor cell targeting, delivery efficiencies, and suppression of imprecise editing outcomes at the on-target site as key design parameters controlling the potency and efficacy of in vivo somatic cell genome editing. Both single and double gene correction are efficacious for in vivo somatic cell editing strategies, while double gene correction is more effective than single-gene correction for autologous cell therapy with ex vivo gene-corrected cells. This work establishes that precise gene correction using genome editors to correct multiple distinct gene variants could be efficacious in the treatment of recessive and polygenic disorders.</jats:p

Design of efficacious somatic cell genome editing strategies for recessive and polygenic diseases

AbstractCompound heterozygous recessive or polygenic diseases could be addressed through gene correction of multiple alleles. However, targeting of multiple alleles using genome editors could lead to mixed genotypes and adverse events that amplify during tissue morphogenesis. Here we demonstrate that Cas9-ribonucleoprotein-based genome editors can correct two distinct mutant alleles within a single human cell precisely. Gene-corrected cells in an induced pluripotent stem cell model of Pompe disease expressed the corrected transcript from both corrected alleles, leading to enzymatic cross-correction of diseased cells. Using a quantitative in silico model for the in vivo delivery of genome editors into the developing human infant liver, we identify progenitor targeting, delivery efficiencies, and suppression of imprecise editing outcomes at the on-target site as key design parameters that control the efficacy of various therapeutic strategies. This work establishes that precise gene editing to correct multiple distinct gene variants could be highly efficacious if designed appropriately.</jats:p

Effect of Glycemic Regulation on Endocan Levels in Patients With Diabetes: A Preliminary Study

Endothelial-specific molecule 1 (endocan) is expressed by endothelial cells and may have a major role in the regulation of cell adhesion and in the pathogenesis of inflammatory disorders. We aimed to assess change in endocan levels after 3 months of lifestyle change recommendations and guideline-based treatment. Diabetic patients (n = 77) who had neither chronic kidney disease nor chronic inflammatory disease were included. After baseline evaluation, the patients were advised lifestyle changes, and their medical treatment was determined individually according to recommendations of the American Diabetes Association (ADA) guidelines. At the end of third month patients were reevaluated. Baseline endocan levels were significantly increased in the study group compared with the control group. The third-month laboratory workup showed significant reductions in hemoglobin A1c, urinary albumin-to-creatinine ratio (UACR), and endocan levels. Only -UACR was independently correlated with -endocan in multivariate linear regression analysis. Our findings suggest that serum endocan concentrations are elevated in patients with type 2 diabetes and decrease following anti-hyperglycemic treatment. Furthermore, decrease in endocan concentrations might be associated with improved glycemic control and reductions in UACR