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 δ-UACR was independently correlated with δ-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.

Summary The orosomucoid-like (Ormdl) proteins play a critical role in sphingolipid homeostasis, inflammation, and ER stress, all of which are associated with obesity and βcell dysfunction. However, their roles in β cells and obesity remain unknown. Here, we show that islets from overweight/obese human donors displayed marginally reduced ORMDL1-2 expression, whereas ORMDL3 expression was significantly downregulated compared with islets from lean donors. In contrast, Ormdl3 was substantially upregulated in the islets of leptin-deficient obese ( ob/ob ) mice compared with lean mice. Treatment of ob / ob mice and their islets with leptin markedly reduced islet Ormld3 expression. Ormdl3 knockdown in a β cell line induced expression of pro-apoptotic markers, which was rescued by ceramide synthase inhibitor fumonisin B1. Our results reveal differential expression of Ormdl3 in the islets of a mouse model and humans with obesity, highlight the potential effect of leptin in this differential regulation, and suggest a role for Ormdl3 in β cell apoptosis.

The distinction between primary and reactive thrombocytosis by bone marrow histology is very important. Reactive thrombocytosis, the most common cause of thrombocytosis, can be expected in postsplenectomy states; however, close hematological evaluation of prolonged thrombocytosis is essential to identify patients who may have an underlying myeloproliferative neoplasm. We report a 37-year-old woman who was found to have portal, mesenteric, and splenic vein thrombosis with thrombocytosis, two months after she had a splenectomy for spontaneous splenic rupture. Other reactive conditions and myeloproliferative neoplasms (MPN) were excluded, and subsequently, the diagnosis of triple-negative essential thrombocythemia (ET) was established by bone marrow histology. This case of primary thrombocythemia following splenectomy in a young patient illustrates some of the diagnostic difficulties associated with postsplenectomy thrombocytosis. Continuing reports of anecdotal experiences in managing similar complex scenarios is essential and remains the only reference for clinicians facing these rare conditions.

Compound 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.

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.