Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling

Organoid technologies have become a powerful emerging tool to model liver diseases, for drug screening, and for personalized treatments. These applications are, however, limited in their capacity to generate functional hepatocytes in a reproducible and efficient manner. Here, we generated and characterized the hepatic organoid (eHEPO) culture system using human induced pluripotent stem cell (iPSC)-derived EpCAM-positive endodermal cells as an intermediate. eHEPOs can be produced within 2 weeks and expanded long term (>16 months) without any loss of differentiation capacity to mature hepatocytes. Starting from patient-specific iPSCs, we modeled citrullinemia type 1, a urea cycle disorder caused by mutations in the argininosuccinate synthetase (ASST) enzyme. The disease-related ammonia accumulation phenotype in eHEPOs could be reversed by the overexpression of the wild-type ASS1 gene, which also indicated that this model is amenable to genetic manipulation. Thus, eHEPOs are excellent unlimited cell sources to generate functional hepatic organoids in a fast and efficient manner

RESEARCH BURDEN OF INTERSTITIAL LUNG DISEASES IN TURKEY - RBILD

Introduction: The aim of our study is to investigate the etiological distribution of ILD in Turkey by stratifying the epidemiological characteristics of ILD cases, and the direct cost of initial diagnosis of the diag-nosed patients. Material-Method: The study was conducted as a multicenter, prospective, cross-sectional, clinical observation study. Patients over the age of 18 and who accepted to participate to the study were included and evaluated as considered to be ILD. The findings of diagnosis, examination and treatment carried out by the cent-ers in accordance with routine diagnostic procedures were recorded observationally. Results: In total,1070 patients were included in this study. 567 (53%) of the patients were male and 503 (47%) were female. The most frequently diagnosed disease was IPF (30.5%). Dyspnea (75.9%) was the highest incidence among the presenting symptoms. Physical examination found bibasilar inspiratory crackles in 56.2 % and radiological findings included reticular opacities and interlobular septal thickenings in 55.9 % of the cases. It was observed that clinical and radiological findings were used most frequently (74.9%) as a diagnostic tool. While the most common treatment approaches were the use of systemic steroids and antifibrotic drugs with a rate of 30.7% and 85.6%, respectively. The total median cost from the patient's admission to diagnosis was 540 Turkish Lira. Conclusion: We believe that our findings compared with data from other countries will be useful in showing the current situation of ILD in our country to discuss this problem and making plans for a solution

Impact of Obesity on the Metabolic Control of Type 2 Diabetes: Results of the Turkish Nationwide Survey of Glycemic and Other Metabolic Parameters of Patients with Diabetes Mellitus (TEMD Obesity Study)

Background: Obesity is the main obstacle for metabolic control in patients with type 2 diabetes. Turkey has the highest prevalence of obesity and type 2 diabetes in Europe. The effect of obesity on the metabolic control, and the macro-and microvascular complications of patients are not apparent. Objectives: This nationwide survey aimed to investigate the prevalence of overweight and obesity among patients with type 2 diabetes and to search for the impact of obesity on the metabolic control of these patients. We also investigated the independent associates of obesity in patients with type 2 diabetes. Methods: We consecutively enrolled patients who were under follow-up for at least 1 year in 69 tertiary healthcare units in 37 cities. The demographic, anthropometric, and clinical data including medications were recorded. Patients were excluded if they were pregnant, younger than 18 years, had decompensated liver disease, psychiatric disorders interfering with cognition or compliance, had bariatric surgery, or were undergoing renal replacement therapy. Results: Only 10% of patients with type 2 diabetes (n = 4,648) had normal body mass indexes (BMI), while the others were affected by overweight (31%) or obesity (59%). Women had a significantly higher prevalence of obesity (53.4 vs. 40%) and severe obesity (16.6 vs. 3.3%). Significant associations were present between high BMI levels and lower education levels, intake of insulin, antihypertensives and statins, poor metabolic control, or the presence of microvascular complications. Age, gender, level of education, smoking, and physical inactivity were the independent associates of obesity in patients with type 2 diabetes. Conclusion: The TEMD Obesity Study shows that obesity is a major determinant of the poor metabolic control in patients with type 2 diabetes. These results underline the importance of prevention and management of obesity to improve health care in patients with type 2 diabetes. Also, the results point out the independent sociodemographic and clinical associates of obesity, which should be the prior targets to overcome, in the national fight with obesity. (c) 2019 The Author(s) Published by S. Karger AG, Base

Turkish nationwide survEy of glycemic and other Metabolic parameters of patients with Diabetes mellitus (TEMD study)

Aims: Turkey has the highest prevalence of diabetes in Europe. It is therefore essential to know the overall cardiovascular risk and reveal the predictors of metabolic control in Turkish adults with diabetes mellitus