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ABSTRACT Objective Leptin has been suggested as a potential biomarker of cardiovascular risk. This paper aims to ascertain, based on a sample of prepubertal children, which serum leptin value best suited to identify metabolic syndrome (MS). Subjects and methods This observational, cross-sectional study recruited children from the outpatient pediatrics clinic, with the purpose of validating serum leptin level cutoffs to identify MS. All obese and overweight children who met eligibility criteria were included in the study, as was a sample of normal-weight children. The sample underwent clinical assessment and blood fasting glucose, lipid profile, insulin, and leptin were measured. Sensitivity and specificity were estimated for each leptin measurement, using MS as the outcome. These values were used to construct a receiver operating characteristic (ROC) curve. The association between MS and leptin was assessed using logistic models to predict MS. Results A total of 65 normal weight, 46 overweight, and 164 obese children were analyzed (160 boys, 115 girls; age: 93.7 ± 17.8 months). The most appropriate leptin cutoff was 13.4 ng/mL (sensitivity 67.6%; specificity 68.9%; accuracy 72.1%). The logistic model indicated that leptin levels above 13.4 ng/dL were significantly associated with MS and that, for every 1 ng/dL increase in leptin levels, the odds of MS increase by 3% (p = 0.002; OR 1.03; 95% CI 1.01-1.05). Conclusions Leptin may be a useful biomarker of cardiovascular risk in prepubertal children, with an optimal cutoff of 13.4 ng/mL. Identification of potential new risk markers for cardiovascular disease in children could contribute to the development of preventive strategies.

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ABSTRACT Objective To investigate the relationship between markers of adiposity and common carotid artery (CIMT) in obese children born small for gestational age (SGA) versus appropriate for gestational age (AGA), to establish cut-off values for CIMT in obese pediatric populations. Subjects and methods A cross-sectional study was carried out over a 1-year period (Jul 2013 – June 2014). We analyzed 122 obese patients aged 4-20 (mean age 14.9 ± 2.28). Twenty-six patients were born SGA. CIMT was measured in all the patients. Using ROC curve, cut-off values were obtained for both groups. Results We demonstrated a correlation between CIMT and adiponectin, leptin and high sensitivity C-reactive protein (hsCRP) (r = -0.25, r = 0.279, r = 0.498) in obese children. CIMT in obese children born SGA were significantly increased as compared with obese children born AGA of similar age, sex and body mass index (BMI) (p = 0.0035). A CIMT cut off value of 0.049 cm has been obtained with a high sensitivity and specificity. Conclusion CIMT is a well-known marker of subclinical atherosclerosis and its measurement is a noninvasive and inexpensive method of detecting subclinical atherosclerosis. Being born SGA increases the atherogenic risk. Obese children with CIMT above 0.049 cm should be screened for metabolic syndrome (MetS).

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ABSTRACT Objective Vitamin D has several metabolic functions and possible reproductive functions. This study aimed to determine the prevalence of vitamin D deficiency among Brazilian women of reproductive age, and to evaluate the relationship between serum 25-hydroxyvitamin D [25(OH)D] concentrations and infertility causes. Subjects and methods This retrospective cross-sectional study evaluated data from a private Brazilian assisted reproduction center that were collected between January 1 and May 5, 2012. Serum 25(OH)D concentrations were measured and compared for infertile and fertile women. Concentrations of 25(OH)D that were < 20 ng/mL were defined as deficiency and concentrations of 21-30 ng/mL were defined as hypovitaminosis D. Results Among the 369 evaluated women, 81.1% exhibited hypovitaminosis D and 32.0% exhibited deficiency. The infertile and control patients did not exhibit any significant differences in the prevalence of vitamin D deficiency (30.2% vs. 35%, respectively; p = 0.33) or in the mean 25(OH)D concentrations (24.3 ± 7.9 ng/mL vs. 23.8 ± 8.7 ng/mL, respectively; p = 0.51). Furthermore, there were no significant differences in the mean 25(OH)D concentrations among subgroups of patients with single infertility factors, or between these subgroups and the control group. Conclusions A high proportion of Brazilian women of reproductive age exhibited vitamin D deficiency, regardless of their fertility status. Thus, it may be useful to evaluate this population for vitamin D deficiency, although future studies are needed to determine whether this deficiency might affect the outcomes of treatments for infertility.

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ABSTRACT Objective This study sought to investigate the effects of vitamin D supplementation and aquatic exercise on pulmonary function in postmenopausal women. Materials and methods This prospective and controlled study included 104 women (62 ± 6.5 years) divided into three groups: a control group lacking vitamin D and calcium supplementation which remained sedentary (CG; n = 17); a control group receiving vitamin D and calcium supplementation which remained sedentary (CDG, n = 33); and a group that completed aquatic exercises three times a week and received vitamin D and calcium supplementation (DTG, n = 54). Data before and after 6 months of the study were analyzed, including serum 25-hydroxyvitamin D (25(OH)D) and calcium concentrations, peak expiratory flow (PEF), forced vital capacity (FVC), and cirtometry. Results We observed significant increases in 25(OH)D concentrations in CDG (52.9 ± 2.4 to 69.1 ± 2.2; nmol/L; p < 0.0001) and DTG groups (55.5 ± 3 to 71.5 ± 3 nmol/L; p < 0.0001). PEF increased by 7 ± 2% (p = 0.0080) in CDG group and 11 ± 2% (p < 0.0001) in DTG group, whereas FVC increased by 7 ± 2% (p = 0.0016) in the CDG group and 10 ± 2% (p < 0.0001) in the DTG group, whereas CG had no changes in any of these parameters. The increment value of cirtometry in DTG group (+43 ± 3%) were significantly (p < 0.0001) higher than those in CG (−4 ± 8%) and CDG (+4 ± 9%) groups. Conclusion Our data suggest that vitamin D supplementation improves pulmonary function parameters in postmenopausal women.

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ABSTRACT Objective This study aimed to compare the effects of two lifestyle intervention programs for type 2 diabetes mellitus (T2DM) prevention – traditional or interdisciplinary psychoeducation-based intervention – in daily habits and cardiometabolic risk factors and investigate the role of the psychoeducational approach for the retention of individuals in the program. Subjects and methods Between 2008 and 2010, in a public health service, 183 pre-diabetic individuals were allocated to two 18-month interventions involving diet and physical activity. Physical activity, diet, quality of life (QOL) and depression and biochemical measurements were obtained. Linear mixed-effect models were used to assess the effect of the interventions. A student t test was used to compare dropouts versus non-dropouts. Results Improvements in energy intake and physical activity were greater in the interdisciplinary than the traditional intervention. A decrease in fat mass and blood pressure was more pronounced with interdisciplinary intervention. Dropouts from the traditional intervention only had higher BMI and lower fiber intake and QOL than non-dropouts. Conclusion The interdisciplinary psychoeducation-based intervention revealed useful for reducing cardiometabolic risk and retaining individuals with worse health profiles. This approach represents a feasible strategy for motivating high-risk individuals to adopt a long-term healthy lifestyle.

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ABSTRACT Objective Complexes like conjugated linoleic acid (CLA) reduce the percentage of body fat by increasing energy expenditure, fat oxidation, or both. The aim of this study was to verify if CLA is able to mimic caloric restriction (CR), and determine the effects of CLA on liver metabolic profile of young adult male Wistar rats. Materials and methods We divided 36 animals into the following groups: 1) Control; 2) CLA (1% of daily food intake, 21 days, orogastric intubation); 3) Restr (fed 60% of the diet offered to controls); and 4) CLA Restr. Liver tissues were processed for biochemical and molecular or mitochondrial isolation (differential centrifugation) and blood samples were collected for biochemical analyses. Results Treatment of the animals for 21 days with 1% CLA alone or combined with CR increased liver weight and respiration rates of liver mitochondria suggesting significant mitochondrial uncoupling. We observed a decrease in adipose tissue leading to insulin resistance, hyperinsulinemia, and hepatic steatosis due to increased liver cholesterol and triacylglycerol levels, but no significant effects on body mass. The expression of hepatic cellular connexins (43 and 26) was significantly higher in the CLA group compared with the Control or Restr groups. Conclusion CLA does not seem to be a safe compound to induce mass loss because it upregulates the mRNA expression of connexins and induces hepatic mitochondrial changes and lipids disorders.

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ABSTRACT Objective The aim of this study was to evaluate the association between thyroid function abnormalities and breast cancer and, in particular, the prognostic markers of breast cancer.. Subjects and methods Baseline levels of thyrotropin, free triiodothyronine, free thyroxine and thyroid autoantibodies were measured in 97 women with primary breast cancer, 27 women with benign breast disease, and 4 women with atypical ductal hyperplasia. Their baseline levels were compared with those in 48 healthy women with a normal mammography in the last 2 years. Results There were no significant associations between history of thyroid disease and breast cancer (p = 0.33). The mean baseline levels of triiodothyronine and thyrotropin did not differ significantly between the compared groups. The mean baseline levels of free thyroxine were found to be significantly higher in the breast cancer group, even after adjusting for thyroid replacement therapy. The presence of thyroid antibodies did not differ significantly between the compared groups. In a subgroup analysis, breast cancer cases with thyroid disease and particularly hypothyroidism had a significantly lower incidence of lymph node metastases compared with breast cancer cases without thyroid disease. Conclusions Our data confirmed the proliferative effect of thyroid hormones on breast cells, which had previously been shown in vitro. Additionally, thyroid disease and particularly hypothyroid function appeared to be associated with a lower incidence of lymph node metastases. Further studies to determine the prognostic role of thyroid hormones in breast cancer are warranted.

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ABSTRACT Objective This study investigated the possible blood changes in wistar rats elderly with and without treatment with anabolic steroids submitted physical training. Materials and methods Elderly rats (32) were divided into four groups: normal (N), treated normal (NT), diabetic (D) and treated diabetic (DT). They were submitted to 20 sessions of swimming with overload (5% body weight), 40 min/day for four weeks. The NT and DT groups received application of testosterone twice a week. At the end of the sessions, the animals were subjected to swimming until exhaustion and then killed for removal of blood and visceral fat. We evaluated maximum swim time, weight of visceral fat, erythrogram, leukogram, lipidogram and serum levels of glucose, lactate, aspartate aminotransferase and creatine kinase. The results were compared using one-way ANOVA followed by the post hoc Tukey test. Results In elderly diabetic rats, the use of anabolic associated with physical training in older rats resulted in improvement in erythrogram, lipidogram and physical performance for high-intensity aerobic exercise. However, it was related to changes in leukocyte count, probably associated with inflammation. Conclusion The combination of the use of testosterone with physical training, followed by maximal effort test caused changes hematological and biochemical can be associated with improvement in physiological characteristics, with increase of the swimming time and decrease of visceral fat levels, improvement in aerobic metabolism of fatty acids and glucose in normal and diabetic animals.

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ABSTRACT Objective The aim of this study was to evaluate for 12 months the changes of body weight using Depot Medroxyprogesterone Acetate (DMPA) and if these changes are related to inflammatory markers. Subjects and methods Twenty women of childbearing age who chose the DMPA, without previous use of this method, BMI < 30 kg/m2, and 17 women using IUD TCu 380A, participated in the study. At the baseline and after one year, changes in weight gain, body composition by the bioimpedance electric method, resting energy expenditure (REE) by the indirect calorimetry method, inflammatory markers and HOMA-IR were assessed. Results After 12 months of evaluation, we could observe a significant increase in the DMPA group in weight (3,01 kg) and BMI, while the IUD group’s only significant increase was observed in the BMI. Relative to REE there was an increase of basal metabolic rate (BMR) in both groups after one year. The sub-group DMPA that gained < 3 kg had increased significant weight, BMI and body surface (BS) with respiratory quotient (RQ) reduction, while the sub-group that gained ≥ 3 kg had a significant increase in weight, BMI, BS, fat-free mass, fat mass, BMR, Leptin, HOMA-IR and waist circumference, with RQ significantly reduced. Conclusion Our study found significant changes in weight, body composition and metabolic profile of the population studied in the first 12 months of contraceptive use. These changes mainly increased body weight, leptin levels and HOMA-IR which can contribute to the development of some chronic complications, including obesity, insulin resistance and diabetes mellitus.

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ABSTRACT Objective The objective of this study was to correlate the values of abdominal circumference (AC) and body mass index (BMI) with the levels of total testosterone (TT), free testosterone (FT) and sexual hormone binding globulin (SHBG). We aimed to analyze the association between the anthropometric values and variations in the hormonal levels. Subjects and methods A transversal prospective study was conducted. A total of 159 patients were included in the study. Results BMI was inversely correlated with TT and SHBG (p = 0.02 and p = 0.006, respectively). AC was also inversely correlated withTT and SHBG (p = 0.006 and p < 0.0001, respectively). However, BMI did not correlate signicantly with these hormonal levels after adjusting for age. Conclusion This finding led to the conclusion that AC had a stronger inverse correlation than BMI with TT and SHBG. Our data suggested that AC alone can be used as an anthropometric parameter to help simplify the identification of men with low serum TT levels.

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ABSTRACT Radioiodine (RAI)-refractory thyroid cancer is an uncommon entity, occurring with an estimated incidence of 4-5 cases/year/million people. RAI refractoriness is more frequent in older patients, in those with large metastases, in poorly differentiated thyroid cancer, and in those tumors with high 18-fluordeoxyglucose uptake on PET/CT. These patients have a 10-year survival rate of less than 10%. In recent years, new therapeutic agents with molecular targets have become available, with multikinase inhibitors (MKIs) being the most investigated drugs. Two of these compounds, sorafenib and lenvatinib, have shown significant objective response rates and have significantly improved the progression-free survival in the two largest published prospective trials on MKI use. However, no overall survival benefit has been achieved yet. This is probably related to the crossover that occurs in most patients who progress on placebo treatment to the open treatment of these studies. In consequence, the challenge is to correctly identify which patients will benefit from these treatments. It is also crucial to understand the appropriate timing to initiate MKI treatment and when to stop it. The purpose of this article is to define RAI refractoriness, to summarize which therapies are available for this condition, and to review how to select patients who are suitable for them.

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SUMMARY Metastatic pheochromocytomas (PHEOs) and paragangliomas (sPGLs) are rare neural crest-derived tumors with a poor prognosis. About 50% of them are due to germ-line mutations of the SDHB gene. At present, there is no cure for these tumors. Their therapy is palliative and represented by different options among which antiangiogenic drugs, like sunitinib, have been hypothesized to be effective especially in malignant SDHB mutated tumors. We report the effects of sunitinib therapy in a SDHB mutation carrier affected by a malignant sPGL. During 101 weeks of therapy at different doses, sunitinib was able to cause a partial response and then a stable disease for a total of 78 weeks. This favorable response is the longest, out of the 35 so far reported in the literature, registered in a patient treated exclusively with sunitinib but, similarly to the other responses, the effect was limited in time. From our analysis of the scanty data present in the literature, the effect of sunitinib does not seem to be different among wild-type patients and those carrying a cluster 1 germ-line mutation. Sunitinib seems able to slow the disease progression in some patients with malignant PHEO/PGL and therefore may represent a therapeutic option, although randomized controlled studies are needed to assess its efficacy definitively in the treatment of these aggressive tumors.

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SUMMARY Paraneoplastic syndromes are a heterogeneous group of malignant diseases caused by events which involve endocrine, immune and metabolic aspects and whose symptoms vary according to the substance produced and the primary tumor. Hypercalcemia is a frequent complication in cancer patients. Prognosis of cancer patients with hypercalcemia is usually poor. A factor called parathyroid hormone related peptide, whose actions are similar to those of the parathyroid hormone, is thought to be the most common cause of malignancy associated hypercalcemia. Non-islet hypoglycemic cell tumor consists of a rare syndrome characterized by the presence of a solid tumor and severe fasting hypoglycemia determined by an insulin-independent pathway. We report a case of a 59-year-old-man with a renal tumor and a T-cell rich large B cell lymphoma who was hospitalized due to severe hypercalcemia and hypoglycemia. The laboratory examination reported hypercalcemia with inhibited PTH and hypoglycemia with inhibited insulin secretion, arriving to the conclusion of tumoral peptide production. He received denosumab and corticoid therapy. The patient died one month later despite initial improvement after medical treatment. While a single paraneoplastic manifestation may be expected in most tumors, the coexistence of two or more of them is rare, except in hepatocellular carcinomas, and it has not yet been described in renal tumors.