International Journal of Endocrinology The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Papillary Thyroid Carcinoma Arising in Children and Adolescent Hashimoto’s Thyroiditis: Ultrasonographic and Pathologic Findings Wed, 10 Feb 2016 12:02:40 +0000 Objectives. We compared the ultrasonography and pathology features of papillary thyroid carcinoma (PTC) in pediatric and adolescents with Hashimoto’s thyroiditis (HT) with those of non-HT patients. Materials and Methods. Eleven patients who were surgically confirmed to have pediatric or adolescent PTC from 2006 to 2014 were included in this study. We retrospectively analyzed the preoperative ultrasonography and pathology features of PTC arising in HT and non-HT patients. Results. On ultrasonography, thyroid gland was lobulated and enlarged, with many scattered microcalcifications in four of five HT patients. Four of six non-HT patients had suspicious masses with calcifications. The diffuse sclerosing variant of PTC (DSVPTC) was found in three of five HT patients, but none in non-HT patients. Macroscopic or microscopic extrathyroidal extension was evident in all of the HT patients and four of the non-HT patients. Neck lymph node metastases were in all HT patients and five of non-HT patients. Conclusions. Three of five PTCs in pediatric and adolescent HT patients were DSVPTC, whereas all PTCs of the non-HT patients were classic type. On ultrasonography, thyroid gland was diffusely enlarged with scattered microcalcifications in four of five HT patients. All five HT cases had aggressive disease, including extrathyroidal extension and cervical lymph node metastases. Sun Hye Jeong, Hyun Sook Hong, Eun Hye Lee, and Jeong Ja Kwak Copyright © 2016 Sun Hye Jeong et al. All rights reserved. The Impacts of SLC22A1 rs594709 and SLC47A1 rs2289669 Polymorphisms on Metformin Therapeutic Efficacy in Chinese Type 2 Diabetes Patients Wed, 10 Feb 2016 10:29:36 +0000 Background. We aimed to investigate the distributive characteristics of SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms and their influence on metformin efficacy in Chinese T2DM patients. Methods. The distributions of SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms were determined in 267 T2DM patients and 182 healthy subjects. Subsequently, 53 newly diagnosed patients who received metformin monotherapy were recruited to evaluate metformin efficacy. Results. No significant difference was found between T2DM patients and healthy subjects in SLC22A1 rs594709 and SLC47A1 rs2289669 allele frequencies and genotype frequencies. After metformin treatment, SLC22A1 rs594709 GG genotype patients showed a higher increase in FINS () and decrease in HOMA-IS () and QUICKI () than A allele carriers. SLC47A1 rs2289669 GG genotype patients had a higher decrease in TChol () and LDL-C () than A allele carriers. Among SLC22A1 rs594709 AA genotype, patients with SLC47A1 rs2289669 AA genotype showed a higher decrease in FBG (), PINS (), and HOMA-IR () than G allele carriers. However, among SLC22A1 rs594709 G allele carriers, SLC47A1 rs2289669 AA genotype patients showed a higher decrease in TChol () than G allele carriers. Conclusion. Our data suggest that SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms may influence metformin efficacy together in Chinese T2DM patients. Di Xiao, Yu Guo, Xi Li, Ji-Ye Yin, Wei Zheng, Xin-Wen Qiu, Ling Xiao, Rang-Ru Liu, Sai-Ying Wang, Wei-Jing Gong, Hong-Hao Zhou, and Zhao-Qian Liu Copyright © 2016 Di Xiao et al. All rights reserved. Long-Term Quality of Life and Pregnancy Outcomes of Differentiated Thyroid Cancer Survivors Treated by Total Thyroidectomy and I131 during Adolescence and Young Adulthood Mon, 08 Feb 2016 12:06:33 +0000 Introduction. Differentiated thyroid cancer (DTC) is rare and confers good prognosis. Long-term health related quality of life (HRQoL) and pregnancy outcomes are not well known in subjects treated during adolescence and young adulthood. Methods. Cross-sectional analysis of HRQoL and global self-esteem, using SF-36 and ISP-25 surveys, and of pregnancy outcomes in female survivors of DTC treated by total thyroidectomy and I131 before age of 25 years. Results. Forty-five of 61 patients (74%) responded to the survey. Cumulative I131 activity was ≤3.85 GBq in 18 subjects and >3.85 GBq in 27 subjects. Mean time from diagnosis was 7.6 ± 5.2 years for the group ≤ 3.85 GBq versus 16.9 ± 11.6 years for the group > 3.85 GBq (). No significant alteration in long-term HRQoL and global self-esteem was observed. Thirty pregnancies after I131 were noted in patients from the group > 3.85 GBq and 10 in patients from the group ≤ 3.85 GBq. Frequency of miscarriages was of 17% (group > 3.85 GBq) and 10% (group ≤ 3.85 GBq) with 9 and 24 live births, respectively. No congenital malformations or first year mortality was noted. Conclusion. Long-term HRQoL, global self-esteem, and pregnancy outcomes are not affected in young female survivors of DTC. Melanie Metallo, Lelia Groza, Laurent Brunaud, Marc Klein, Georges Weryha, and Eva Feigerlova Copyright © 2016 Melanie Metallo et al. All rights reserved. Comparison between New-Onset and Old-Diagnosed Type 2 Diabetes with Ketosis in Rural Regions of China Thu, 04 Feb 2016 13:07:04 +0000 Objectives. Type 2 diabetes (T2D) with ketosis was common because of late diagnosis and lacking adequate treatment in rural regions of China. This study aimed to provide the data of T2D with ketosis among inpatients in a south-west border city of China. Methods. Data of 371 patients of T2D with ketosis who were hospitalized between January 2011 and July 2015 in Baoshan People’s Hospital, Yunnan, China, were analyzed. New-onset and old-diagnosed T2D patients presenting with ketosis were compared according to clinical characteristics, laboratory results, and chronic diabetic complications. Results. Overall, the blood glucose control was poor in our study subjects. Male predominated in both groups (male prevalence was 68% in new-onset and 64% in old-diagnosed groups). Overweight and obesity accounted for 50% in new-onset and 46% in old-diagnosed cases. Inducements of ketosis were 13.8% in new-onset and 38.7% in old-diagnosed patients. Infections were the first inducements in both groups. The prevalence of chronic complications of diabetes was common in both groups. Conclusions. More medical supports were needed for the early detection and adequate treatment of diabetes in rural areas of China. Shichun Du, Xia Yang, Degang Shi, and Qing Su Copyright © 2016 Shichun Du et al. All rights reserved. Intrahepatic Fat Content and Markers of Hepatic Fibrosis in Obese Children Thu, 04 Feb 2016 07:07:19 +0000 Aim. We evaluated both direct and indirect hepatic fibrosis markers in obese children and their relationship with intrahepatic fat (IHF) content. We also aimed to investigate the possible roles of IHF and fibrosis markers in metabolic syndrome (MS). Methods. 189 obese children were divided into simple obese (SOB), simple steatosis (SS), and nonalcoholic steatohepatitis (NASH) groups according to their IHF and blood alanine transaminase (ALT) levels. They were also scored for the MS components. IHF was assessed as a continuous variable by proton magnetic resonance spectroscopy (1H-MRS). In addition, 30 nonobese children were enrolled as controls and their direct hepatic fibrosis markers and IHF were assessed. Results. Age was related to IHF, NFS, and FIB-4. Both NFS and APRI were related to IHF more significantly than the direct markers. In the estimation of liver function impairment, indirect markers had greater AUROC than direct markers. In MS, IHF and all the fibrosis markers showed similar AUROC. Conclusions. Both direct and indirect markers played a valuable role in evaluating MS. Indirect markers were more effective in distinguishing fatty hepatitis. Age is an important factor underlying hepatic steatosis and fibrosis even in children. Wei Wu, Hongxi Zhang, Xiaoqin Xu, Ke Huang, and Junfen Fu Copyright © 2016 Wei Wu et al. All rights reserved. Prenatal and Childhood Growth, Chemerin Concentrations, and Metabolic Health in Adult Life Sun, 24 Jan 2016 12:35:53 +0000 Several noncommunicable diseases have their origins in early developmental phases. One factor possibly explaining the association between early growth and later health could be adipocyte function. The objective of this study was to assess the association between the adipocytokine chemerin and early growth and later health. 1074 participants from Helsinki Birth Cohort Study born 1934–1944 with information on prenatal and childhood growth participated. Metabolic outcomes include glucose tolerance, adiposity, and chemerin concentration. Mean chemerin concentrations were 5.0 ng/mL higher in women than in men (95% CI 2.7 to 7.2, ). The strongest correlate of chemerin concentration was adult waist circumference and body fat percentage (, and , , resp.). After adjustment for body fat percentage, chemerin concentration was 5.4 ng/mL lower in subjects with type 2 diabetes than in those with normal glucose tolerance (−0.2 to 10.9, ). It was 3.0 ng/mL higher in those with metabolic syndrome than in those without (0.6 to 5.3, ). No measure of early growth was associated with chemerin concentration. Our findings do not support a role for chemerin in linking early growth with later metabolic health. Johan G. Eriksson, Mika Venojärvi, and Clive Osmond Copyright © 2016 Johan G. Eriksson et al. All rights reserved. The Impact and Successes of a Paediatric Endocrinology Fellowship Program in Africa Wed, 20 Jan 2016 13:21:33 +0000 Background. The prevalence and distribution of endocrine disorders in children in Africa are not well known because most cases are often undiagnosed or diagnosed too late. The awareness of this led to the launch of the Paediatric Endocrinology Training Center for Africa (PETCA) designed to improve quality and access to health care by training paediatricians from Africa in paediatric endocrinology. Methods. The fellowship is undertaken over an 18-month period: six months of clinical and theoretical training in Kenya, nine months of project research at the fellow’s home country, and three months of consolidation in Kenya. Upon completion, certified paediatricians are expected to set up centers of excellence. Results. There have been two phases, phase I from January 2008 to October 2012 and phase II from January 2012 to April 2015. Fifty-four fellows from 12 African countries have been certified, 34 (phase I) and 20 (phase II). Over 1,000 patients with wide ranging diabetes and endocrine disorders have been diagnosed and treated and are being followed up at the centers of excellence. Conclusion. The successes of the PETCA initiative demonstrate the impact a capacity building and knowledge transfer model can have on people in resource-poor settings using limited resources. Gordon Otieno Odundo, Thomas Ngwiri, Olivia Otuoma, Paul Laigong, Renson Mukhwana, Mary Slessor Limbe, and Nadia Musimbi Chanzu Copyright © 2016 Gordon Otieno Odundo et al. All rights reserved. Circulating Visfatin in Hypothyroidism Is Associated with Free Thyroid Hormones and Antithyroperoxidase Antibodies Sun, 17 Jan 2016 11:49:39 +0000 We hypothesized that regulation of visfatin in hypothyroidism might be altered by coexisting chronic autoimmune thyroiditis. This is a prospective case-control study of 118 subjects. The autoimmune study group (AIT) consisted of 39 patients newly diagnosed with hypothyroidism in a course of chronic autoimmune thyroiditis. The nonautoimmune study group (TT) consisted of 40 patients thyroidectomized due to the differentiated thyroid cancer staged pT1. The control group comprised 39 healthy volunteers adjusted for age, sex, and BMI with normal thyroid function and negative thyroid antibodies. Exclusion criteria consisted of other autoimmune diseases, active neoplastic disease, diabetes mellitus, and infection, which were reported to alter visfatin level. Fasting blood samples were taken for visfatin, TSH, free thyroxine (FT4), free triiodothyronine (FT3), antithyroperoxidase antibodies (TPOAb), antithyroglobulin antibodies (TgAb), glucose, and insulin levels. The highest visfatin serum concentration was in AIT group, and healthy controls had visfatin level higher than TT (). Simple linear regression analysis revealed that visfatin serum concentration was significantly associated with autoimmunity (; ), FT4 (; ), FT3 (; ), and TPOAb (; ), and the relationships were further confirmed in the multivariate regression analysis. Nadia Sawicka-Gutaj, Ariadna Zybek-Kocik, Aleksandra Klimowicz, Michał Kloska, Dorota Mańkowska-Wierzbicka, Jerzy Sowiński, and Marek Ruchała Copyright © 2016 Nadia Sawicka-Gutaj et al. All rights reserved. Effects of Thyroid Peroxidase Antibody on Maternal and Neonatal Outcomes in Pregnant Women in an Iodine-Sufficient Area in China Thu, 14 Jan 2016 14:14:28 +0000 Purposes. To evaluate the effects of thyroid peroxidase antibodies (TPOAb) on maternal and neonatal adverse outcomes in pregnant women. Methods. 208 pregnant women at 24–28 weeks were divided into two groups, TPOAb-positive and TPOAb-negative groups. Thyroid function and TPOAb were determined in all subjects until 12 months postpartum. Levothyroxine was supplemented to maintain euthyroid with periodical checking of thyroid functions. The prevalence of postpartum thyroiditis (PPT), placenta previa, placental abruption, premature rupture of membrane, postpartum haemorrhage, polyhydramnios, oligohydramnios, preterm birth, low birth weight, congenital hypothyroidism, and neonatal diseases were observed in two groups. Results. Of all women, 11.54% had a PPT. The prevalence of PPT was significantly higher in TPOAb-positive than TPOAb-negative group (42.31% versus 7.14%, ), with 45.46% and 53.85% of PPT happening at 6 weeks postpartum in TPOAb-positive and TPOAb-negative groups. The incidence of polyhydramnios was significantly higher in TPOAb-positive than TPOAb-negative group (15.38% versus 2.74%, ). Conclusion. Pregnant women with TPOAb-positive had increased risk of PPT, predominantly happening at 6 weeks postpartum. TPOAb was associated with increased incidence of polyhydramnios and the underlying mechanisms required further investigation. Earlier screening of thyroid function during pregnancy and postpartum was warranted in our region. Xi Chen, Bai Jin, Jun Xia, Xincheng Tao, Xiaoping Huang, Lu Sun, and Qingxin Yuan Copyright © 2016 Xi Chen et al. All rights reserved. Differences in Ventilatory Threshold for Exercise Prescription in Outpatient Diabetic and Sarcopenic Obese Subjects Thu, 14 Jan 2016 09:11:13 +0000 Aim of the study was to examine cardiorespiratory parameters at individual ventilatory threshold (IVT) and peak exercise capacity () in outpatient diabetic and sarcopenic obese subjects. Seventeen obese subjects (BMI:  kg·m−1) and sixteen SO subjects (BMI:  kg·m−1) were compared with sixteen T2DM subjects (BMI:  kg·m−1). All groups performed an incremental exercise test on a treadmill according to their physical ability. , %, and maximal metabolic equivalent () were evaluated at maximal effort. Moreover, , %, %, %HRR, ΔHR, and METivt were assessed at IVT. No significant differences were found in any physiological parameters at maximal effort (, %, and ) in all groups. On the contrary, , %, %, %HRR, ΔHR, and were significantly lower in T2DM subjects as compared to OB and SO subjects at IVT (). Our results show that while at maximal effort there are no differences among groups, at IVT the physiological parameters are lower in T2DM subjects than in OB and SO subjects. Therefore, due to the differences observed in the groups, we suggest usng the IVT as a useful parameter to prescribe aerobic exercise in obese with sarcopenia or diabetes mellitus conditions. Gian Pietro Emerenziani, Maria Chiara Gallotta, Silvia Migliaccio, Emanuela A. Greco, Chiara Marocco, Luca di Lazzaro, Rachele Fornari, Andrea Lenzi, Carlo Baldari, and Laura Guidetti Copyright © 2016 Gian Pietro Emerenziani et al. All rights reserved. The Association of Peroxisome Proliferator-Activated Receptor δ and Additional Gene-Gene Interaction with C-Reactive Protein in Chinese Population Wed, 13 Jan 2016 09:28:52 +0000 Aims. To examine the association between 4 single nucleotide polymorphisms (SNPs) of peroxisome proliferator-activated receptors δ (PPARδ) polymorphisms and C-reactive protein (CRP) level and additional gene-gene interaction. Methods. Line regression analysis was performed to verify polymorphism association between SNP and CRP levels. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the interaction. Results. A total of 1028 subjects (538 men, 490 women) were selected. The carriers of the C allele (TC or CC) of rs2016520 were associated with a significant decreased level of CRP, regression coefficients was −0.338, and standard error was 0.104 (). The carriers of the G allele (CG or GG) of rs9794 were also significantly associated with decreased level of CRP, regression coefficients was −0.219, and standard error was 0.114 (). We also found a potential gene-gene interaction between rs2016520 and rs9794. Subjects with rs2016520-TC or CC, rs9794-CG or GG genotypes have lowest CRP level, difference (95% CI) = −0.50 (−0.69 to −0.21) (), compared to subjects with rs2016520-TT and rs9794-CC genotypes. Conclusions. rs2016520 and rs9794 minor allele of PPARδ and combined effect between the two SNP were associated with decreased CRP level. Xiao-Ying Ding, Hao-Zheng Yuan, Ru Gu, Yan-Feng Gao, Xiao-Gang Liu, and Ya Gao Copyright © 2016 Xiao-Ying Ding et al. All rights reserved. Pharmacogenetics of Risperidone and Cardiovascular Risk in Children and Adolescents Wed, 06 Jan 2016 14:17:33 +0000 Objective. To identify the frequency of obesity and metabolic complications in child and adolescent users of risperidone. Potential associations with clinical parameters and SNPs of the HTR2C, DRD2, LEP, LEPR, MC4R, and CYP2D6 genes were analyzed. Methods. Samples from 120 risperidone users (8–20 years old) were collected and SNPs were analyzed, alongside assessment of chronological and bone ages, prescribed and weight-adjusted doses, use of other psychotropic drugs, waist circumference, BMI -scores, blood pressure, HOMA-IR index, fasting levels of serum glucose, insulin, cholesterol, triglycerides, transaminases, and leptin. Results. Thirty-two (26.7%) patients were overweight and 5 (4.2%) obese. Hypertension was recorded in 8 patients (6.7%), metabolic syndrome in 6 (5%), and increased waist circumference in 20 (16.7%). The HOMA-IR was high for 22 patients (18.3%), while total cholesterol and triglycerides were high in 20 (16.7%) and 41 (34.2%) patients, respectively. SNP associations were found for LEP, HTR2C, and CYP2D6 with BMI; CYP2D6 with blood pressure, ALT, and HOMA-IR; HTR2C and LEPR with leptin levels; MC4R and DRD2 with HOMA-IR; HTR2C with WC; and LEP with ALT. Conclusions. Although not higher than in the general pediatric population, a high frequency of patients was overweight/obese, with abnormalities in metabolic parameters and some pharmacogenetic associations. Amilton Dos Santos-Júnior, Taciane Barbosa Henriques, Maricilda Palandi de Mello, Osmar Henrique Della Torre, Lúcia Arisaka Paes, Adriana Perez Ferreira-Neto, Letícia Esposito Sewaybricker, Thiago Salum Fontana, Eloisa Helena Rubello Valler Celeri, Gil Guerra-Júnior, and Paulo Dalgalarrondo Copyright © 2016 Amilton Dos Santos-Júnior et al. All rights reserved. Hospital Admission Patterns in Children with CAH: Admission Rates and Adrenal Crises Decline with Age Wed, 06 Jan 2016 12:02:13 +0000 Objective. To examine patterns of hospitalisation for acute medical conditions in children with congenital adrenal hyperplasia (CAH). Design. A retrospective study of hospitalisation using administrative data. Setting. All hospitals in NSW, Australia. Patients. All patients admitted with CAH and a random sample of admissions in patients aged 0 to 18 years without adrenal insufficiency (AI). Main Outcome Measures. Admissions and comorbidities by age and sex. Results. Of 573 admissions for medical problems in CAH children, 286 (49.9%) were in males, and 236 (41.2%) had a principal diagnosis of CAH or had an adrenal crisis (AC). 37 (6.5%) ACs were recorded. An infection was found in 43.5% () of the CAH patient admissions and 51.7% () of the non-AI group, . Children aged up to one year had the highest number of admissions () and six ACs (four in males). There were 21 ACs recorded for children aged 1–5 years. Older CAH children had fewer admissions and fewer ACs. No in-hospital deaths were recorded. Conclusions. Admission for medical problems in CAH children declines with age. An AC was recorded in 6.5% of the admissions, with the majority of ACs occurring in the 1 to 5 years age group and there were no deaths. R. Louise Rushworth, Henrik Falhammar, Craig F. Munns, Ann M. Maguire, and David J. Torpy Copyright © 2016 R. Louise Rushworth et al. All rights reserved. Elevated Systemic Neutrophil Count Is Associated with Diabetic Macroalbuminuria among Elderly Chinese Wed, 30 Dec 2015 11:41:54 +0000 Background. This study investigated an association between systemic absolute neutrophil count (ANC) and albuminuria in elderly Chinese people. Methods. A cross-sectional study was conducted on 2265 participants attending a routine medical examination in Minhang District as part of a Platform of Chronic Disease program. Their drug history, waist circumference, height, blood pressure, fasting blood glucose, ANC, and urine albumin levels were recorded. This study conformed to the requirements of the STROBE statement. Results. Of the 2265 subjects, 1254 (55.4%) were diabetic and 641 (28.3%) had albuminuria. The mean ANC of patients with diabetes comorbid with macroalbuminuria was significantly higher than that of both the nondiabetic patients and patients with diabetes with lower levels of albuminuria; the latter 2 groups had statistically similar ANC. ANC significantly and positively correlated with levels of urine albumin. Based on multivariate analysis, with each 109/L increase in ANC, the increase in rates of macroalbuminuria was significant but not in rates of albuminuria positivity. Based on areas under the receiver operating characteristic curve, ANC was the strongest factor predicting macroalbuminuria. Conclusions. Elevated ANC was associated with macroalbuminuria in diabetes, indicating that neutrophil-mediated inflammation may be involved in the exacerbation of albuminuria. Min Yang, Jun Liu, Jiong Xu, Tiange Sun, Li Sheng, Zaoping Chen, Fang Wang, Xinmei Huang, Yueyue Wu, Jianfeng Mao, and Rui Zhang Copyright © 2015 Min Yang et al. All rights reserved. Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal Tumors Wed, 30 Dec 2015 06:27:56 +0000 We previously showed a decreased expression of vitamin D receptor (VDR) mRNA/protein in a small group of adrenocortical carcinoma (ACC) tissues, suggesting the loss of a protective role of VDR against malignant cell growth in this cancer type. Downregulation of VDR gene expression may result from epigenetics events, that is, methylation of cytosine nucleotide of CpG islands in VDR gene promoter. We analyzed methylation of CpG sites in the VDR gene promoter in normal adrenals and adrenocortical tumor samples. Methylation of CpG-rich 5′ regions was assessed by bisulfite sequencing PCR using bisulfite-treated DNA from archival microdissected paraffin-embedded adrenocortical tissues. Three normal adrenals and 23 various adrenocortical tumor samples (15 adenomas and 8 carcinomas) were studied. Methylation in the promoter region of VDR gene was found in 3/8 ACCs, while no VDR gene methylation was observed in normal adrenals and adrenocortical adenomas. VDR mRNA and protein levels were lower in ACCs than in benign tumors, and VDR immunostaining was weak or negative in ACCs, including all 3 methylated tissue samples. The association between VDR gene promoter methylation and reduced VDR gene expression is not a rare event in ACC, suggesting that VDR epigenetic inactivation may have a role in adrenocortical carcinogenesis. Catia Pilon, Andrea Rebellato, Riccardo Urbanet, Vincenza Guzzardo, Rocco Cappellesso, Hironobu Sasano, Ambrogio Fassina, and Francesco Fallo Copyright © 2015 Catia Pilon et al. All rights reserved. The Role of miR-378a in Metabolism, Angiogenesis, and Muscle Biology Tue, 29 Dec 2015 10:57:23 +0000 MicroRNA-378a (miR-378a, previously known as miR-378) is one of the small noncoding RNA molecules able to regulate gene expression at posttranscriptional level. Its two mature strands, miR-378a-3p and miR-378a-5p, originate from the first intron of the peroxisome proliferator-activated receptor gamma, coactivator 1 beta (ppargc1b) gene encoding PGC-1β. Embedding in the sequence of this transcriptional regulator of oxidative energy metabolism implies involvement of miR-378a in metabolic pathways, mitochondrial energy homeostasis, and related biological processes such as muscle development, differentiation, and regeneration. On the other hand, modulating the expression of proangiogenic factors such as vascular endothelial growth factor, angiopoietin-1, or interleukin-8, influencing inflammatory reaction, and affecting tumor suppressors, such as SuFu and Fus-1, miR-378a is considered as a part of an angiogenic network in tumors. In the latter, miR-378a can evoke broader actions by enhancing cell survival, reducing apoptosis, and promoting cell migration and invasion. This review describes the current knowledge on miR-378a linking oxidative/lipid metabolism, muscle biology, and blood vessel formation. Bart Krist, Urszula Florczyk, Katarzyna Pietraszek-Gremplewicz, Alicja Józkowicz, and Jozef Dulak Copyright © 2015 Bart Krist et al. All rights reserved. Betatrophin Acts as a Diagnostic Biomarker in Type 2 Diabetes Mellitus and Is Negatively Associated with HDL-Cholesterol Thu, 24 Dec 2015 06:08:16 +0000 Objective. By assessing its circulating concentrations in type 2 diabetes mellitus (T2DM) patients, we aimed to explore the associations of betatrophin with various metabolic parameters and evaluate its diagnostic value in T2DM. Methods. A total of 58 non-diabetes-mellitus (NDM) subjects and 73 age- and sex-matched newly diagnosed T2DM patients were enrolled. Correlation analyses between circulating betatrophin levels and multiple metabolic parameters were performed. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of betatrophin concentration in T2DM. Results. Circulating betatrophin levels were approximately 1.8 times higher in T2DM patients than in NDM individuals (median 747.12 versus 407.41 pg/mL, ). Correlation analysis showed that betatrophin was negatively associated with high-density lipoprotein cholesterol (HDL-C) levels in all subjects. ROC curve analysis identified betatrophin as a potent diagnostic biomarker for T2DM. The optimal cut-off point of betatrophin concentration for predicting T2DM was 501.23 pg/mL. Conclusions. Serum betatrophin levels were markedly increased in newly diagnosed T2DM patients and further elevated in obese T2DM subjects. Betatrophin was negatively correlated with HDL-C levels. Our findings indicate that betatrophin could be a potent diagnostic biomarker for T2DM. Min Yi, Rong-ping Chen, Rui Yang, Xian-feng Guo, Jia-chun Zhang, and Hong Chen Copyright © 2015 Min Yi et al. All rights reserved. Oral Administration of Oleuropein and Its Semisynthetic Peracetylated Derivative Prevents Hepatic Steatosis, Hyperinsulinemia, and Weight Gain in Mice Fed with High Fat Cafeteria Diet Tue, 22 Dec 2015 13:55:19 +0000 The high consumption of olive tree products in the Mediterranean diet has been associated with a lower incidence of metabolic disorders and cardiovascular diseases. In particular, the protective effects of olive oil have been attributed to the presence of polyphenols such as oleuropein (Ole) and its derivatives. We have synthesized a peracetylated derivative of Ole (Ac-Ole) which has shown in vitro antioxidant and growth-inhibitory activity higher than the natural molecule. In this study, male C57BL/6JOlaHsd mice were fed with a standard (std), cafeteria (caf) diet, and caf diet supplemented with Ole (0.037 mmol/kg/day) and Ac-Ole (0.025 mmol/kg/day) for 15 weeks. We observed a significant reduction in the caf diet-induced body weight gain and increase of abdominal adipose tissue. Also, Ole and Ac-Ole prevented the development of hepatic steatosis. Finally, Ole and Ac-Ole determined a lower increase of HDL and LDL-cholesterol levels and corrected caf diet-induced elevation of plasma glucose concentrations by improving insulin sensitivity. The observed beneficial properties of Ole and Ac-Ole make these compounds and in particular Ac-Ole promising candidates for a potential pharmaceutic use in metabolic disorders. Saverio Massimo Lepore, Valeria Maria Morittu, Marilena Celano, Francesca Trimboli, Manuela Oliverio, Antonio Procopio, Carla Di Loreto, Giuseppe Damante, Domenico Britti, Stefania Bulotta, and Diego Russo Copyright © 2015 Saverio Massimo Lepore et al. All rights reserved. Diabetes in Socioeconomically Vulnerable Populations Mon, 21 Dec 2015 14:02:43 +0000 Anil Kapur, Maria I. Schmidt, and Alberto Barceló Copyright © 2015 Anil Kapur et al. All rights reserved. Role of FTO in Adipocyte Development and Function: Recent Insights Wed, 16 Dec 2015 09:42:25 +0000 In 2007, FTO was identified as the first genome-wide association study (GWAS) gene associated with obesity in humans. Since then, various animal models have served to establish the mechanistic basis behind this association. Many earlier studies focussed on FTO’s effects on food intake via central mechanisms. Emerging evidence, however, implicates adipose tissue development and function in the causal relationship between perturbations in FTO expression and obesity. The purpose of this mini review is to shed light on these new studies of FTO function in adipose tissue and present a clearer picture of its impact on obesity susceptibility. Myrte Merkestein and Dyan Sellayah Copyright © 2015 Myrte Merkestein and Dyan Sellayah. All rights reserved. Percutaneous Ultrasound-Guided Laser Ablation with Contrast-Enhanced Ultrasonography for Hyperfunctioning Parathyroid Adenoma: A Preliminary Case Series Wed, 16 Dec 2015 06:11:17 +0000 The study was to evaluate the safety and effectiveness of ultrasound-guided percutaneous laser ablation (pLA) as a nonsurgical treatment for primary parathyroid adenoma. Surgery was contraindicated in, or refused by, the included patients. No lesion enhancement on contrast-enhanced ultrasound immediately after pLA was considered “complete ablation.” Nodule size, serum calcium, and parathyroid hormone level were compared before and after pLA. Complete ablation was achieved in all 21 patients with 1 () or 2 () sessions. Nodule volume decreased from  mL at baseline to and  mL at 6 and 12 months after pLA (). At 1 day, 6 months, and 12 months after pLA, serum PTH decreased from  pmol/L at baseline to , , and  pmol/L, serum calcium decreased from  mmol/L at baseline to , , and  mmol/L, respectively (). At 12 months, treatment success (normalization of PTH and serum calcium) was achieved in 81%. No serious complications were observed. Ultrasound-guided pLA with contrast-enhanced ultrasound is a viable alternative to surgery for primary parathyroid adenoma. Tianan Jiang, Fen Chen, Xiang Zhou, Ying Hu, and Qiyu Zhao Copyright © 2015 Tianan Jiang et al. All rights reserved. The Intricate Network of Adipokines and Stroke Thu, 10 Dec 2015 09:59:41 +0000 Cerebrovascular disorders, particularly ischemic stroke, are one of the most common neurological disorders. High rates of overweight and obesity support an interest in the role of adipose tissue and adipose tissue releasing cytokines in inducing associated comorbidities. Adipokines can serve as a key messenger to central energy homeostasis and metabolic homeostasis. They can contribute to the crosstalk between adipose tissue and brain. However recent research has offered ambiguous data on the network of adipose tissue, adipokines, and vascular disorders. In our paper we provide a critical insight into the role of adipokines in evolution of ischemic stroke. Ema Kantorová, Ľubica Jesenská, Daniel Čierny, Kamil Zeleňák, Štefan Sivák, Matej Stančík, Peter Galajda, Vladimír Nosáľ, and Egon Kurča Copyright © 2015 Ema Kantorová et al. All rights reserved. Paraoxonase 2 Induces a Phenotypic Switch in Macrophage Polarization Favoring an M2 Anti-Inflammatory State Tue, 08 Dec 2015 13:24:56 +0000 Inflammatory processes are involved in atherosclerosis development. Macrophages play a major role in the early atherogenesis, and they are present in the atherosclerotic lesion in two phenotypes: proinflammatory (M1) or anti-inflammatory (M2). Paraoxonase 2 (PON2) is expressed in macrophages, and it was shown to protect against atherosclerosis. Thus, the aim of our study was to analyze the direct effect of PON2 on macrophage inflammatory phenotypes. Ex vivo studies were performed with murine peritoneal macrophages (MPM) harvested from control C57BL/6 and PON2-deficient (PON2KO) mice. PON2KO MPM showed an enhanced proinflammatory phenotype compared to the control, both in the basal state and following M1 activation by IFNγ and lipopolysaccharide (LPS). In parallel, PON2KO MPM also showed reduced anti-inflammatory responses in the basal state and also following M2 activation by IL-4. Moreover, the PON2-null MPM demonstrated enhanced phagocytosis and reactive oxygen species (ROS) production in the basal state and following M1 activation. The direct effect of PON2 was shown by transfecting human PON2 (hPON2) into PON2KO MPM. PON2 transfection attenuated the macrophages’ response to M1 activation and enhanced M2 response. These PON2 effects were associated with attenuation of macrophages’ abilities to phagocyte and to generate ROS. We conclude that PON2 promotes an M1 to M2 switch in macrophage phenotypes. Marie Koren-Gluzer, Mira Rosenblat, and Tony Hayek Copyright © 2015 Marie Koren-Gluzer et al. All rights reserved. The Role of the Multiple Hormonal Dysregulation in the Onset of “Anemia of Aging”: Focus on Testosterone, IGF-1, and Thyroid Hormones Tue, 08 Dec 2015 08:35:33 +0000 Anemia is a multifactorial condition whose prevalence increases in both sexes after the fifth decade of life. It is a highly represented phenomenon in older adults and in one-third of cases is “unexplained.” Ageing process is also characterized by a “multiple hormonal dysregulation” with disruption in gonadal, adrenal, and somatotropic axes. Experimental studies suggest that anabolic hormones such as testosterone, IGF-1, and thyroid hormones are able to increase erythroid mass, erythropoietin synthesis, and iron bioavailability, underlining a potential role of multiple hormonal changes in the anemia of aging. Epidemiological data more consistently support an association between lower testosterone and anemia in adult-older individuals. Low IGF-1 has been especially associated with anemia in the pediatric population and in a wide range of disorders. There is also evidence of an association between thyroid hormones and abnormalities in hematological parameters under overt thyroid and euthyroid conditions, with limited data on subclinical statuses. Although RCTs have shown beneficial effects, stronger for testosterone and the GH-IGF-1 axis and less evident for thyroid hormones, in improving different hematological parameters, there is no clear evidence for the usefulness of hormonal treatment in improving anemia in older subjects. Thus, more clinical and research efforts are needed to investigate the hormonal contribution to anemia in the older individuals. Marcello Maggio, Francesca De Vita, Alberto Fisichella, Fulvio Lauretani, Andrea Ticinesi, Graziano Ceresini, Anne Cappola, Luigi Ferrucci, and Gian Paolo Ceda Copyright © 2015 Marcello Maggio et al. All rights reserved. Thyroid Function, Prevalent Coronary Heart Disease, and Severity of Coronary Atherosclerosis in Patients Undergoing Coronary Angiography Thu, 03 Dec 2015 13:19:31 +0000 This study investigated if free T4 and TSH concentrations or thyroid function categories were associated with prevalent CHD and the severity of coronary atherosclerosis in a population undergoing coronary angiography. This was a cross-sectional study including 1799 patients who were consecutively admitted and underwent coronary angiography. We evaluated the severity of coronary atherosclerosis using Gensini score. In the entire study population, free T4 level was inversely associated with prevalent CHD (OR = 0.95, 95% CI 0.91–0.99, ) and the natural log-transformed Gensini score (ln(Gensini score)) (β = −0.03, 95% CI −0.05–−0.01, ). The odds of CHD increased gradually across hyperthyroidism, subclinical hypothyroidism, and overt hypothyroidism groups using the euthyroid group as the reference, and the trend is borderline significant ( for trend = 0.051). When comparing to the euthyroid group, ln(Gensini score) of the overt hypothyroidism group was significantly higher (), but the trend was not significant ( for trend = 0.08). A significant association of thyroid function with CHD or ln(Gensini score) in euthyroid patients was not observed. The present study demonstrated an association of thyroid function with prevalent CHD and the severity of coronary atherosclerosis in a population undergoing coronary angiography. However, this association was not observed in euthyroid individuals. Yan Ling, Jingjing Jiang, Minghui Gui, Lin Liu, Qiqige Aleteng, Bingjie Wu, Shanshan Wang, Xiaojing Liu, and Xin Gao Copyright © 2015 Yan Ling et al. All rights reserved. Simultaneous Quantification of 25-Hydroxyvitamin D3 and 24,25-Dihydroxyvitamin D3 in Rats Shows Strong Correlations between Serum and Brain Tissue Levels Wed, 02 Dec 2015 13:12:07 +0000 While vitamin D3 is recognized as a neuroactive steroid affecting both brain development and function, efficient analytical method in determining vitamin D3 metabolites in the brain tissue is still lacking, and the relationship of vitamin D3 status between serum and brain remains elusive. Therefore, we developed a novel analysis method by using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to simultaneously quantify the concentrations of 25-hydroxyvitamin D3 (25(OH)D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) in the serum and brain of rats fed with different dose of vitamin D3. We further investigated whether variations of serum vitamin D3 metabolites could affect vitamin D3 metabolite levels in the brain. Serum and brain tissue were analyzed by HPLC-MS/MS with electrospray ionization following derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD). The method is highly sensitive, specific, and accurate to quantify 25(OH)D3 and 24,25(OH)2D3 in animal brain tissue. Vitamin D3 metabolites in brain tissue were significantly lower in rats fed with a vitamin D deficiency diet than in rats fed with high vitamin D3 diet. There was also a strong correlation of vitamin D3 metabolites in serum and brain. These results indicate that vitamin D3 status in serum affects bioavailability of vitamin D3 metabolites in the brain. Ying Xue, Xin He, Huan-De Li, Yang Deng, Miao Yan, Hua-Lin Cai, Mi-Mi Tang, Rui-Li Dang, and Pei Jiang Copyright © 2015 Ying Xue et al. All rights reserved. Effects of Ghrelin on Triglyceride Accumulation and Glucose Uptake in Primary Cultured Rat Myoblasts under Palmitic Acid-Induced High Fat Conditions Wed, 02 Dec 2015 10:59:45 +0000 This study aimed to study the effects of acylated ghrelin on glucose and triglyceride metabolism in rat myoblasts under palmitic acid- (PA-) induced high fat conditions. Rat myoblasts were treated with 0, 10−11, 10−9, or 10−7 M acylated ghrelin and 0.3 mM PA for 12 h. Triglyceride accumulation was determined by Oil-Red-O staining and the glycerol phosphate dehydrogenase-peroxidase enzymatic method, and glucose uptake was determined by isotope tracer. The glucose transporter 4 (GLUT4), AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and uncoupling protein 3 (UCP3) were assessed by RT-PCR and western blot. Compared to 0.3 mM PA, ghrelin at 10−9 and 10−7 M reduced triglyceride content (5.855 ± 0.352 versus 5.030 ± 0.129 and 4.158 ± 0.254 mM, ) and prevented PA-induced reduction of glucose uptake (1.717 ± 0.264 versus 2.233 ± 0.333 and 2.333 ± 0.273 10−2 pmol/g/min, ). The relative protein expression of p-AMPKα/AMPKα, UCP3, and p-ACC under 0.3 mM PA was significantly reduced compared to controls (all ), but those in the 10−9 and 10−7 M ghrelin groups were significantly protected from 0.3 mM PA (all ). In conclusion, acylated ghrelin reduced PA-induced triglyceride accumulation and prevented the PA-induced decrease in glucose uptake in rat myoblasts. These effects may involve fatty acid oxidation. Lingling Han, Jia Li, Ying Chen, Wei Wang, Dan Zhang, and Guoliang Liu Copyright © 2015 Lingling Han et al. All rights reserved. Percutaneous Ethanol Sclerotherapy of Symptomatic Nodules Is Effective and Safe in Pregnant Women: A Study of 13 Patients with an Average Follow-Up of 6.8 Years Mon, 30 Nov 2015 14:21:56 +0000 Background. Because of the increased risk of surgery, thyroid nodules causing compression signs and/or hyperthyroidism are concerning during pregnancy. Patients and Methods. Six patients with nontoxic cystic, four with nontoxic solid, and three with overt hyperthyroidism caused by toxic nodules were treated with percutaneous ethanol injection therapy (PEI). An average of 0.68 mL ethanol per 1 mL nodule volume was administered. Mean number of PEI treatments for patients was 2.9. Success was defined as the shrinkage of the nodule by more than 50% of the pretreatment volume (V0) and the normalization of TSH and FT4 levels. The average V0 was 15.3 mL. Short-term success was measured prior to labor, whereas long-term success was determined during the final follow-up (an average of 6.8 years). Results. The pressure symptoms decreased in all but one patient after PEI and did not worsen until delivery. The PEI was successful in 11 (85%) and 7 (54%) patients at short-term and long-term follow-up, respectively. Three patients underwent repeat PEI which was successful in 2 patients. Conclusions. PEI is a safe tool and seems to have good short-term results in treating selected symptomatic pregnant patients. Long-term success may require repeat PEI. Tamas Solymosi, Zsolt Melczer, Istvan Szabolcs, Endre V. Nagy, and Miklos Goth Copyright © 2015 Tamas Solymosi et al. All rights reserved. Free Triiodothyronine Levels Are Associated with Diabetic Nephropathy in Euthyroid Patients with Type 2 Diabetes Mon, 30 Nov 2015 11:09:59 +0000 Objective. To investigate the association of thyroid function and diabetic nephropathy (DN) in euthyroid patients with type 2 diabetes. Methods. A total of 421 patients were included in this cross-sectional study. The following parameters were assessed: anthropometric measurements, fast plasma glucose, serum creatinine, lipid profile, HbA1c, free triiodothyronine (FT3), free thyroxine, thyroid-stimulating hormone levels, and urinary albumin-to-creatinine ratio (UACR). Patients with UACR of ≥30 mg/g were defined as those suffering from DN. Results. Of the 421 patients, 203 (48.2%) suffered from DN, and no difference was found between males and females. The patients with DN yielded significantly lower FT3 levels than those without DN (). The prevalence of DN showed a significantly decreasing trend across the three tertiles based on FT3 levels (59.6%, 46.4%, and 38.6%, ). After adjustment for gender and age, FT3 levels were found to correlate positively with estimated glomerular filtration rate () and negatively with UACR (). Multiple linear regression analysis showed that FT3 level was independently associated with UACR (, , and ). Conclusion. Serum FT3 levels are inversely associated with DN in euthyroid patients with type 2 diabetes, independent of traditional risk factors. Jingcheng Wu, Xiaohua Li, Yang Tao, Yufei Wang, and Yongde Peng Copyright © 2015 Jingcheng Wu et al. All rights reserved. BRAF Mutations in an Italian Regional Population: Implications for the Therapy of Thyroid Cancer Thu, 26 Nov 2015 13:29:28 +0000 Background. Molecular diagnostics has offered new techniques for searching for mutations in thyroid indeterminate lesions. The study’s aim was to evaluate the BRAF mutations’ incidence in an Italian regional population. Subjects and Methods. 70 Caucasian patients born in Liguria with indeterminate or suspicious cytological diagnoses. Results. A BRAF gene mutation was successfully analyzed in 56/70 patients. The mutation was BRAF V600E in 12/56 cases (21%) and BRAF K601E in 2/56 (4%). Of the BRAF mutated samples on cytological diagnosis (14/56 cases), 2/14 cases (14%) were benign on final histology and 12/14 (86%) were malignant. All BRAF-mutated cases on cytology that were found to be benign on histological examination carried the K601E mutation. Of the nonmutated BRAF cases (42/56, 75%) which were later found to be malignant on definitive histology, 5 cases were follicular carcinomas (36%), 3 cases were incidentally found to be papillary microcarcinomas (22%), 2 were cases papillary carcinomas (14%), 1 was case follicular variant of papillary carcinoma (7%), 1 was case medullary carcinoma (7%), 1 case was Hurtle cell tumor (7%), and 1 case was combined cell carcinoma and papillary oncocytic carcinoma (7%). Conclusions. The presence of the BRAF V600E mutation may suggest a more aggressive surgical approach. BRAF K601E mutation did not correlate with malignancy indexes. Eleonora Monti, Michela Bovero, Lorenzo Mortara, Giorgia Pera, Simonetta Zupo, Elena Gugiatti, Mariella Dono, Barbara Massa, Gian Luca Ansaldo, and Giusti Massimo Copyright © 2015 Eleonora Monti et al. All rights reserved.