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Olena Mandrik,1–3 Johan L Severens,1 Olena Doroshenko,4 Vladymir Pan'kiv,5 Nonna Kravchun,6 Maryna Vlasenko,7 Mykola Hulchiy,8 Maryna Baljuk,9 Yuliia Komisarenko,10 Eugene Martsynik,11 Liubov Sokolova,12 Olga Zalis'ka,2 Boris Mankovsky131Erasmus University Rotterdam, Rotterdam, the Netherlands; 2Danylo Halytsky Lviv National Medical University, Lviv, 3MSD Ukraine, 4Ukrainian Institute for Strategic Research, 5Ukrainian Scientific Centre of Endocrine Surgery, 6Institute of Problems of Endocrine Pathology na VY Danylevskogo, Ukrainian Academy of Medical Sciences, Kyiv, 7Vinnitsa National Medical University named after MI Pyrogov, Vinnytsia, 8Kyiv City Teaching Endocrinological Center, Kyiv, 9Danilevsky Institute of Endocrine Pathology Problems, Ukrainian Academy of Medical Sciences, Kharkov, 10OO Bogomolets National Medical University, Kyiv, 11Medical Academy of Dnepropetrovsk, Dnepropetrovsk, 12Institute of Endocrinology and Metabolism after V.P. Komissarenko, National Academy of Medical Sciences of Ukraine, Kyiv, 13PL Shupik National Medical Academy of Postgraduate Education, Kyiv, UkraineAbstract: This study evaluates the impact of hypoglycemia on the lives of Ukrainian patients with type 2 diabetes mellitus. The secondary objective was to explore patient–physician relationships and the attitudes of patients towards various informational resources on diabetes management. Three focus groups with 26 patients were conducted. Qualitative information was evaluated using content analysis. The results show that patients with type 2 diabetes mellitus in Ukraine are adapting to potential attacks of hypoglycemia; however, they still experience periodic manifestations of hypoglycemia that significantly affect their psychological well-being. This result is similar to observations made in other countries. Ukrainian patients >40 years old mainly receive information on disease management from endocrinologists, and rarely use internet resources on diabetes management. Information provision was especially important at the early stage of the disease, when patients lack information on hypoglycemia manifestations and could therefore fail to identify and manage it properly.Keywords: diabetes, quality of life, developing countries, Europe, eastern

Context: Polycystic ovary syndrome (PCOS) is a common cause of anovulation. It may also negatively affect the endometrium, which could lead to implantation failure and proliferative aberrations., Objective: Our objective was to study sex hormone receptors in the endometrium of women with PCOS., Design: This is a cross-sectional study and lifestyle intervention., Setting: Clinical and laboratory research unit was undertaken at a university hospital., Participants: Twenty overweight/obese women fulfilling all three PCOS criteria (anovulation, hyperandrogenism, and polycystic ovaries), 10 body mass index-matched regularly menstruating controls, 11 normal-weight women with PCOS, and 11 normal-weight controls., Intervention: Intervention for this study included dietary management and physical exercise., Main Outcome Measures: mRNA levels and immunostaining of estrogen receptor α (ERα) and β (ERβ), nongenomic estrogen receptor α36 (ERα36), and G-protein-coupled estrogen receptor-1 (GPER), and the androgen receptor (AR) on cycle days 6-8 and cycle days 21-23., Results: Before intervention, mRNA levels of ERα, ERα36, and the ERα/ERβ mRNA ratio were lower in proliferative endometrium of overweight/obese PCOS women compared with controls (P < .05). After intervention, ERα protein and the ERα/ERβ protein ratio in proliferative endometrium increased and were higher in PCOS women with improved menstrual function than in those without improvement (P < .05). In the subgroup of PCOS women with restored ovulation, only higher protein levels of GPER were found in secretory endometrium (P < .01). However, PCOS women who remained anovulatory had higher protein levels of ERα, GPER, and AR on cycle days 21-23 than controls (P < .05)., Conclusions: Lifestyle intervention alters, but does not fully restore, ER and AR expression in proliferative and secretory endometrium of obese women with PCOS.

Background: Increased incidence of papillary thyroid carcinoma (PTC) is observed as a consequence of radiation exposure in connection to the Chornobyl nuclear plant accident in 1986. In this study, we report a cohort of adult Ukrainian patients diagnosed with PTC from 2004 to 2008 following exposure at the age of 18 years or younger., Methods: In total, 70 patients were identified and clinically characterized. The common BRAF 1799T>A mutation was assessed by pyrosequencing, the RET/PTC1 and RET/PTC3 (NCOA4) rearrangements by RT-PCR, and the expression of Ki-67 (MIB-1 index), BCL2, cyclin A, and cyclin D1 by immunohistochemistry., Results: In total, 46/70 (66%) cases carried a BRAF mutation and/or a RET/PTC rearrangement. A BRAF mutation was detected in 26 tumors, RET/PTC1 in 20 cases, and RET/PTC3 in four cases. In four of these cases, BRAF mutation and RET/PTC rearrangement were coexisting. The BRAF mutation was underrepresented among PTCs with accompanying chronic lymphocytic thyroiditis (CLT) compared with PTCs without this feature (12 vs 44%). MIB-1 proliferation index determined by double staining with leukocyte common antigen was low (mean 0.8%; range 0.05-4.5%). Moreover, increased expression of cyclin A was observed in PTCs with a tumor size >2 cm compared with PTCs ≤2 cm (1.2 vs 0.6%). BCL2 and cyclin D1 showed frequent expression but without associations to clinical characteristics or amplification of the CCND1 locus., Conclusions: Our results suggest that this cohort has frequent BRAF mutation, RET/PTC1 rearrangement, and low proliferation index. Furthermore, BRAF 1799T>A was underrepresented in PTCs with CLT, and cyclin A expression was associated with increased PTC tumor size.

Objective: Thyroid proteomics is a new direction in thyroid cancer research aiming at etiological understanding and biomarker identification for improved diagnosis., Methods: Two-dimensional electrophoresis was applied to cytosolic protein extracts from frozen thyroid samples (ten follicular adenomas, nine follicular carcinomas, ten papillary carcinomas, and ten reference thyroids). Spots with differential expression were revealed by image and multivariate statistical analyses, and identified by mass spectrometry., Results: A set of 25 protein spots significant for discriminating between the sample groups was identified. Proteins identified for nine of these spots were studied further including 14-3-3 protein beta/alpha, epsilon, and zeta/delta, peroxiredoxin 6, selenium-binding protein 1, protein disulfide-isomerase precursor, annexin A5 (ANXA5), tubulin alpha-1B chain, and α1-antitrypsin precursor. This subset of protein spots carried the same predictive power in differentiating between follicular carcinoma and adenoma or between follicular and papillary carcinoma, as compared with the larger set of 25 spots. Protein expression in the sample groups was demonstrated by western blot analyses. For ANXA5 and the 14-3-3 proteins, expression in tumor cell cytoplasm was demonstrated by immunohistochemistry both in the sample groups and an independent series of papillary thyroid carcinomas., Conclusion: The proteins identified confirm previous findings in thyroid proteomics, and suggest additional proteins as dysregulated in thyroid tumors.

Background: The accurate diagnosis of thyroid tumors is challenging. Proteomics has emerged as a promising approach for the discovery of molecular diagnostic markers as a potential complement to routine diagnostics., Methods: Protein fractions from 29 frozen thyroid tumor tissue samples (10 papillary carcinomas, 9 follicular carcinomas, and 10 follicular adenomas) as well as from normal thyroid tissue were analyzed by surface enhanced laser desorption/ionization time-of-flight mass spectrometry followed by validation by Western blotting and immunohistochemistry., Results: A Ca2+ binding protein belonging to the S100 family, S100A6, was differentially expressed between papillary and follicular thyroid tumors. Moreover, two posttranslationally modified forms of S100A6 were observed and verified by liquid chromatography-coupled tandem mass spectrometry. Validation by Western blotting displayed a significantly higher expression of S100A6 in papillary thyroid carcinoma (PTC) in comparison with the other tumor groups or normal tissue (p < 0.05). Immunohistochemical analysis on 98 tumors showed that PTC cases had a significantly stronger cytosolic staining and a larger proportion of stained nuclei than follicular tumors. BRAF gene mutation was not significantly associated with S100A6 protein levels., Conclusion: This study supports a role of S100A6 in thyroid tumorigenesis and as a potential aid in the discrimination between follicular thyroid tumors and PTC.