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Objective: To evaluate the use of two questionnaires assessing awareness of hypoglycemia, in a pediatric type 1 diabetes (T1D) population. Methods: Prospective observational study with children (aged 9‐18 years) and parents (for children aged 2‐11 years) answering the Gold and Clarke questionnaires assessing awareness of hypoglycemia. Psychometric properties of the questionnaires were evaluated, and the most appropriate cut‐off score to classify participants as having normal vs impaired awareness of hypoglycemia (IAH) was determined by ability to recognize subsequent hypoglycemia and hypoglycemia severity, documented in a 4‐week blood glucose diary. Questionnaires were readministered at follow‐up assessment approximately 1.5 years later. Results: In total, 112 participants (51% male) with median (IQR) age 13.7 (11.1‐15.8) years, T1D duration 4.7 (2.2‐7.8) years, and HbA1c 62 (57‐73) mmol/mol (7.8%) were included. Both questionnaires demonstrated acceptable psychometric properties. Using score ≥3 to classify IAH gave a prevalence of IAH of 41% (Gold) and 22% (Clarke). When classified using the Gold questionnaire, IAH participants had higher incidences of mild asymptomatic hypoglycemia, whereas with the Clarke questionnaire, they had higher incidences of clinically significant and severe hypoglycemia. Subgroup analyses confirmed these associations only in participants aged ≥9 years. Follow‐up was completed in 90% of the participants, and a change of awareness status was observed in 22% to 36%. Conclusions: The Gold and Clarke questionnaires may be used to assess awareness of hypoglycemia in pediatric T1D in those ≥9 years of age, but the more detailed Clarke questionnaire has higher specificity and is superior in predicting risk of clinically significant hypoglycemia. [ABSTRACT FROM AUTHOR]

Objectives. To investigate the possible long-term effects of metformin exposure on growth and development of the offspring born to mothers with polycystic ovary syndrome (PCOS). The drug passes through the placenta and can potentially influence the fetus. Patients and methods. This is a follow-up study of a randomized, controlled trial on PCOS women, randomized to metformin or placebo in pregnancy. Out of 37 children aged 7-9 years, 25 agreed to participate. Primary outcome measures were growth, body composition and metabolic parameters. Results. There were no differences in height, weight or body composition between those exposed to metformin and those exposed to placebo. We found a higher fasting glucose level in the metformin group (4.93 mmol/L vs. 4.60 mmol/L, p = 0.04). In the metformin group there was a trend towards higher systolic blood pressure (106 mmHg vs. 101 mmHg, p = 0.05) and a lower LDL cholesterol level (2.42 mmol/L vs. 2.99 mmol/L, p = 0.07). Conclusion. Metformin exposure during fetal life does not seem to influence growth and body composition at the age of 8 years. A higher fasting glucose level and a possible higher systolic blood pressure and lower LDL cholesterol level in the metformin group may be coincidental and should be further explored. [ABSTRACT FROM AUTHOR]

Phosphatase of regenerating liver-3 (PTP4A3/PRL-3) is a dual-specificity phosphatase that is upregulated in various types of cancers and is related to poor prognosis and aggressive tumor behavior. The expression level of PRL-3 is elevated in response to several antiapoptotic cytokines, including IL6, in cancer cells from patients with multiple myeloma (MM) and can promote survival and migration. Here, it is demonstrated that PRL-3 activates Src kinase in the IL6-dependent MM cell line INA-6. Inhibition of PRL-3 by a small-molecule inhibitor of PRL-3 or by shRNA resulted in inactivation of Src. In addition to activation of Src, PRL-3 also activated the Src family kinase (SFK) members LYN and HCK in INA-6 cells. Forced expression of catalytically inactive mutant PRL-3 decreased the activation of these three SFK members while the total level of HCK and FYN remained elevated. Inhibitors of Src increased sensitivity of cells overexpressing PRL-3 to the PRL-3 inhibitor through joint downregulation of both PRL-3 and Mcl-1. In conclusion, PRL-3 protected MM cells against apoptosis by dysregulating both the total levels and the activation levels of specific SFK members that are important for IL6 signal transduction in MM cells. Eventually, this led to increased levels of Mcl-1., Implications: This study suggests PRL-3 and SFKs are key mediators of the IL6-driven signaling events and points to both PRL-3 and SFK members as potential targets for treatment of MM. Mol Cancer Res; 15(1); 69-77. ©2016 AACR., (©2016 American Association for Cancer Research.)