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ABSTRACT Objective This study was designed to identify the major musculoskeletal symptoms of individuals with obesity, to assess their health-related quality of life, and to evaluate the correlation between the musculoskeletal symptoms and the individuals’ health-related quality of life. Materials and methods Cross-sectional study. Instruments used “Nordic Musculoskeletal Questionnaire” and “The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)”. Results In total, 41 subjects were evaluated, of which 90.15% were female. The mean age of the subjects was 40.78 ± 9.85 years and their mean body-mass index was 46.87 ± 8.08. All subjects reported musculoskeletal pain in at least one anatomical region and 80.49% had pain in three or more regions. The activity limitations due to pain were reported by 75.61% of them. The most affected regions by pain were the ankles and/or feet, lower back, knees and wrists/hands/fingers. The most associated regions with activity limitations due to pain were the ankles and/or feet, knees and lower back. The presence of pain showed a negative correlation with the domains physical functioning (PF), role-physical (RP) and body pain (BP). The activity limitations showed a negative correlation with the domains PF, BP, social functioning (SF) and role-emotional (RE). Conclusion Our data showed a high prevalence of musculoskeletal pain and limitation in activities due to pain in obese subjects. The musculoskeletal symptoms had negative correlations with physical and mental components of the health-related quality of life, highlighting the importance of ensuring that patients with obesity have access to interdisciplinary care, for the prevention and rehabilitation of musculoskeletal disorders.

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ABSTRACT Objective Obesity can cause systemic arterial hypertension (SAH) and type 2 diabetes mellitus (DM2) factor that is also influenced by genetic variability. The present study aims to investigate the association between gene polymorphisms related with obesity on the prevalence of SAH and DM2 in the preoperative period and 1 year after Roux-en-Y gastric bypass surgery. Subjects and methods In total, 351 obese women in a Brazilian cohort completed the study. The clinical diagnosis of SAH and DM2 was monitored from medical records. Twelve gene polymorphisms (rs26802; rs572169; rs7799039; rs1137101; rs3813929; rs659366; rs660339; rs1800849; rs7498665; rs35874116; rs9701796; and rs9939609) were determined using real-time polymerase chain reaction and TaqMan assay. Results In the preoperative period, prevalence of SAH and DM2 was 57% and 22%, respectively. One year postoperatively, 86.8% subjects had remission of DM2 and 99.5% had control of SAH. Subjects with T allele from the serotonin receptor gene (5-HT2C, rs3813929) had five times greater chance of DM2, and the CC genotype from uncoupling protein 3 gene (UCP3, rs1800849) had three times greater chance in the preoperative period. Conclusion These findings indicate that polymorphisms rs3813929 and rs1800849 from 5-HT2C and UCP3 genes were related to DM2 prevalence among the Brazilian obese women candidates for bariatric surgery.

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ABSTRACT Objective The aim of the present study was to evaluate parameters of bone and mineral metabolism after bariatric surgery. Subjects and methods This sectional study included data from medical records from 61 bariatric surgery (BS) patients (minimum period of 6 months after the procedure) and from 30 class II and III obese patients as a control group (Cont), consisting of daily dietary intake of macronutrients, calcium and sodium, serum 25(OH)D and parathyroid hormone (PTH) and other biochemical serum and urinary parameters. Bone alkaline phosphatase (BAP), leptin, fibroblast growth factor-23 (FGF-23) and deoxypyridinoline (DPYD) were determined from available banked serum and urinary samples. Results Mean body mass index (BMI), median energy, carbohydrate, protein and sodium chloride consumption were significantly lower in the BS versus Cont, but calcium and lipids were not. No significant differences were found in ionized calcium, 25(OH)D, PTH and fibroblast growth factor 23 (FGF-23) between groups. Mean serum BAP was significantly higher for BS versus Cont and had a positive correlation with time after the surgical procedure. Mean serum leptin was significantly lower and median urinary DPYD higher in BS versus Cont. Conclusion The present study showed an increase in bone markers of both bone formation and resorption among bariatric patients up to more than 7 years after the surgical procedure, suggesting that an increased bone turnover persists even at a very long-term follow-up in such patients.

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ABSTRACT Objective In the present study, we aimed to assess the associations of C1q gene polymorphisms with autoimmune thyroid diseases (AITD) susceptibility. Subjects and methods A set of 1,003 AITD patients (661 with Graves’ disease and 342 with Hashimoto’s thyroiditis) and 880 ethnically- and geographically-matched controls from Chinese Han population were included. Five common single nucleotide polymorphisms (SNPs) (rs294185, rs292001, rs682658, rs665691 and rs294179) in C1q gene locus were genotyped. Frequencies of genotypes and alleles were compared between patients and controls, and haplotype analysis was also performed. Results There was no statistically significant difference between AITD patients and controls in the frequencies of alleles of rs294185 (P = 0.41), rs292001 (P = 0.71), rs682658 (P = 0.68), rs665691 (P = 0.68) and rs294179 (P = 0.69). There was also no statistically significant difference between AITD patients and controls in the frequencies of genotypes of rs294185 (P = 0.72), rs292001 (P = 0.89), rs682658 (P = 0.83), rs665691 (P = 0.90) and rs294179 (P = 0.43). Stratified analyses showed that none of those five SNPs in C1q gene were associated with Graves’ disease or Hashimoto’s thyroiditis (all P values > 0.05). Haplotype analysis revealed that there were no obvious genetic associations of C1q gene polymorphisms with AITD susceptibility. Conclusions We, for the first time, identified the associations between C1q gene SNPs and AITD, and our findings suggested that five common SNPs in C1q gene were not associated with AITD susceptibility in Chinese Han population.

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ABSTRACT Objective The aim of this study was to evaluate how different parameters of short-term glycemic control would correlate with the perception of health-related quality of life (HRQoL) in patients with type 1 diabetes mellitus (T1D). Subjects and methods A total of 50 T1D patients aged 18 to 50 years were evaluated with the questionnaires Problem Areas in Diabetes (PAID) scale and Diabetes Quality of Life (DQOL) measure after 30 days of self-monitoring of blood glucose (SMBG). Glycemic control was evaluated using glycated hemoglobin (HbA1c), mean glucose levels (MGL) in the prior month’s data from SMBG (Accu-Check 360o), number of hypoglycemic episodes (< 70 mg/dL and < 50 mg/dL), and glycemic variability (GV). Results PAID correlated positively with MGL (r = 0.52; p < 0.001) and HbA1c (r = 0.36; p < 0.0097), but not with GV (r = 0.17; p = 0.23) or number of hypoglycemic episodes (r = 0.15; p = 0.17 for glucose < 70 mg/dL and r = 0.02; p = 0.85 for glucose < 50 mg/dL). After multiple linear regression, only MGL remained independently related to PAID scores. DQOL scores had a positive correlation with MGL (r = 0.45; p = 0.001), but not with HbA1c (r = 0.23; p = 0.09), GV (r = 0.20; p = 0.16), or number of hypoglycemic episodes (r = 0.06 p = 0.68). Conclusion In T1D patients, MGL, but not HbA1c or number hypoglycemic episodes, was the glycemic control parameter that best correlated with short-term perception of HRQoL.

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ABSTRACT Objective This study aims to compare the prevalence of laryngopharyngeal reflux signs between two groups of patients undergoing thyroidectomy for voluminous goiter: substernal goiters and voluminous cervical goiter without thoracic extension. Subjects and methods A retrospective case-control study was performed with data retrieved of the charts of the patients submitted to thyroidectomies occurred at a tertiary care center (Head and Neck Surgery Department, University of São Paulo Medical School) between 2010 and 2014. The selected thyroidectomies were allocated in two groups for study: patients with substernal goiters and patients with voluminous cervical goiter without thoracic extension. Cervical goiters were selected by ultrasonography mensuration. Clinical criterion was used to define substernal goiter. Results The average thyroid volume in patients with substernal goiter was significantly greater than the average volume in patients with only cervical goiter (p < 0.001). The prevalence of signs of reflux laryngitis at laryngoscopy was significantly greater in substernal goiter patients (p = 0.036). Moreover, substernal goiter was considered as the unique independent variable for high reflux laryngitis signs at laryngoscopy (OR = 2.75; CI95%: 1.05-7.20; p = 0.039) when compared to only cervical goiter patients. Conclusion This study shows a significant association between substernal goiters and signs of laryngopharyngeal reflux at preoperative laryngoscopy. Therefore, when compared with voluminous cervical goiters, the substernal goiters increase the chance of reflux laryngitis signs in patients.

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ABSTRACT Objectives To analyze the role of moderate-to-vigorous physical activity (MVPA) in mediating the relationship between central adiposity and immune and metabolic profile in postmenopausal women. Materials and methods Cross-sectional study comprising 49 postmenopausal women (aged 59.26 ± 8.32 years) without regular physical exercise practice. Body composition was measured by dual-energy X-ray absorptiometry. Fasting blood samples were collected for assessment of nonesterified fatty acids, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), adiponectin, insulin and estimation of insulin resistance (HOMA-IR). Physical activity level was assessed with an accelerometer (Actigraph GTX3x) and reported as a percentage of time spent in sedentary behavior and MVPA. All analyses were performed using the software SPSS 17.0, with a significance level set at 5%. Results Sedentary women had a positive relationship between trunk fat and IL-6 (rho = 0.471; p = 0.020), and trunk fat and HOMA-IR (rho = 0.418; p = 0.042). Adiponectin and fat mass (%) were only positively correlated in physically active women (rho = 0.441; p = 0.027). Physically active women with normal trunk fat values presented a 14.7% lower chance of having increased HOMA-IR levels (β [95%CI] = 0.147 [0.027; 0.811]). Conclusions The practice of sufficient levels of MVPA was a protective factor against immunometabolic disorders in postmenopausal women.

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ABSTRACT Objective We evaluated the prevalence of glutamic acid decarboxylase (GADA) and tyrosine phosphatase-protein antibodies (IA2A), their titers and their relation to first phase insulin response (FPIR) and glucose tolerance in autoimmune thyroid diseases (ATDs) patients. Subjects and methods Graves’ disease (GD; n = 181) and Hashimoto’s thyroiditis (HT; n = 143) patients in addition to healthy controls (n = 93) were studied. Secondly, FPIR and oral glucose tolerance tests (OGTT) were performed in 11 anti-pancreatic islet–cell (+) and in 20 anti-pancreatic–cell (-) patients. Results There was a non significant trend for higher prevalence of GADA positivity in GD vs HT (7.2% vs 2% p = 0.06), but the GADA titers were higher in HT. We also did not find a significant difference in IA2 prevalence (0.7% vs 0.0%) between these two groups or compared to the control group. In the subsequent analysis, low FPIR was found in 10% of these patients but without statistical difference for OGTT between pancreatic antibody–positive and –negative patients. Conclusion A trend for greater prevalence of GADA was observed for GD patients than for HT or control. However, the titers of these autoantibodies were higher in HT patients, but there was no significant relation to insulin secretion and glucose tolerance at that moment and stage of autoimmune diseases.

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ABSTRACT Objective Overweight seems to be related to a higher prevalence of sleep disturbances. Decreased sleep duration and altered sleep quality are risk factors for obesity. Our aim was to compare the sleep pattern of overweight children with that of a matched control group and assess the relationship between sleep quality and obesity. Materials and methods Retrospective cohort study comparing 41 overweight children with a normal-weight control group, both submitted to polysomnography. The samples were matched for age, sex, and apnea-hypopnea index. Body mass index (BMI) z-scores were calculated using World Health Organization (WHO) growth charts. Insulin resistance in the study group was determined using the homeostatic model assessment for insulin resistance (HOMA-IR). Sleep patterns were compared. The statistical analysis was performed using SPSS® version 21. Results The mean age (± standard deviation) of the population was 10 ± 3.4 years (min. 5 years; max. 17 years). Fifty-six percent of the participants in both groups were girls. N3% was lower in the study group (18.95 ± 6.18%) compared with the control group (21.61 ± 7.39%; t (40) = 2.156, p = 0.037). We found a correlation in the study group between HOMA-IR and N3% (Rs = -0.434, p = 0.008). Conclusion The present study suggests a link between overweight/obesity and altered sleep quality due to compromised non-rapid eye movement sleep, an indirect marker of sleep quality. There was also a link between slow-wave sleep duration and insulin resistance. We must find a strategy to provide adequate slow-wave sleep duration to reduce the obesity epidemic at young ages. Further research is needed.

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ABSTRACT Objective The aim of this study was to measure quality of life (QOL) impairment in individuals currently suffering from Graves’ ophthalmopathy (GO) and to determine the correlation of GO-specific QOL scores with disease severity and activity. Subjects and methods Seventy three GO-specific QOL surveys were prospectively analysed and compared with GO status. The GO-specific QOL survey was translated into Spanish and applied to Argentine patients with Graves’ disease (GD). Results were compared with presence or absence of GO, Clinical Activity Score (CAS), severity score, age, gender and thyroid function. Results Fifty-six patients answered the survey and underwent complete ophthalmic evaluation, 15 did not have GO and were considered to be a control group. Appearance QOL score for patients with GO (53 ± 31.4) was lower than the control group (88.3 ± 17) (p < 0,000), no difference was observed in functional QOL score. There was a negative correlation between GO severity and both functional (r = -0.575; p < 0.000) and appearance QOL (r = -0.577; p < 0.000). Functional QOL differed between patients with active GO vs control group (p = 0.043). Patients with active and inactive GO had lower appearance QOL scores than control group (p < 0.000, p < 0.001 respectively). Conclusions GO has significant impact on the life of these Argentine patients. QOL was worse in GO patients than in control group, functional QOL was mostly affected by the activity and appearance QOL was mainly altered by the effects of the disease. Patients with more severe GO had lower scores on both QOL scales.

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ABSTRACT Objective Patients infected with the human immunodeficiency virus (HIV) have an increased risk of metabolic disorders and alterations on irisin levels. Therefore, the purpose of the current investigation was to quantify the circulating irisin concentration in HIV-infected subjects under highly active antiretroviral therapy and to determine possible correlations between irisin levels with fat mass, fat-free mass, body mass index (BMI), and muscle strength. Subjects and methods Cross-sectional study of 10 men (36.7 ± 11.3 years) and 10 women (42.5 ± 10.3 years) infected with HIV, recruited from the Specialized Service Center in the State Center of Reference for High and Medium Complexity. Blood samples were collected to determine plasma irisin levels, glucose, HDL, total cholesterol, triglycerides, and LDL. Body composition (fat mass, fat-free mass) and anthropometrics (body mass index; BMI) were measured by bioelectrical impedance. Muscle strength was assessed using a mechanic hand dynamometer and one maximum repetition tests. Results Irisin levels correlated positively with fat mass (r = 0.67; p = 0.001) and BMI (r = 0.48; p = 0.036). In contrast, there was an inverse correlation between irisin levels and fat-free mass (r = -0.41; p = 0.008) and five strength parameters: right hand grip (r = -0.46; p = 0.044); left hand grip (r = -0.50; p = 0.027), relative hand grip (r = -0.79; p = 0.001), bench press (r = -0.58; p = 0.009), leg press (r = -0.40; p = 0.085), and biceps curl (r = -0.059; p = 0.009). Conclusion Irisin levels correlated positively with body fat and negatively with fat-free mass and strength parameters in HIV-infected patients. Female patients infected with HIV receiving highly active antiretroviral therapy have higher levels of irisin compared with men in a similar circumstance.

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ABSTRACT Aromatase is a cytochrome P450 enzyme (CYP19A1 isoform) able to catalyze the conversion of androgens to estrogens. The aromatase gene mutations highlighted the action of estrogen as one of the main regulators of bone maturation and closure of bone plate. The use of aromatase inhibitors (AI) in boys with short stature has showed its capability to improve the predicted final height. Anastrozole (ANZ) and letrozole (LTZ) are nonsteroidal inhibitors able to bind reversibly to the heme group of cytochrome P450. In this review, we describe the pharmacokinetic profile of both drugs, discussing possible drug interactions between ANZ and LTZ with other drugs. AIs are triazolic compounds that can induce or suppress cytochrome P450 enzymes, interfering with metabolism of other compounds. Hydroxilation, N-dealkylation and glucoronidation are involved in the metabolism of AIs. Drug interactions can occur with azole antifungals, such as ketoconazole, by inhibiting CYP3A4 and by reducing the clearance of AIs. Antiepileptic drugs (lamotrigine, phenobarbital, and phenytoin) also inhibit aromatase. Concomitant use of phenobarbital or valproate has a synergistic effect on aromatase inhibition. Therefore, it is important to understand the pharmacokinetics of AIs, recognizing and avoiding possible drug interactions and offering a safer prescription profile of this class of aromatase inhibitors. Arch Endocrinol Metab. 2017;61(3):391-7.

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ABSTRACT Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from parafollicular C cells of the thyroid and associated with mutations in the proto-oncogene REarranged during Transfection (RET). The prognosis of MTC depends on clinical stage, with a 95.6% 10-year survival rate among patients with localized disease and 40% among patients with advanced disease. Standard chemotherapy and radiotherapy have no significant impact on the overall survival of these patients and two tyrosine kinase receptor inhibitors (TKIs), vandetanib and cabozantinib, have been recently approved for the systemic treatment of locally advanced or metastatic MTC. However, since patients with MTC and residual or recurrent disease may have an indolent course with no need for systemic treatment, and since these drugs are highly toxic, it is extremely important to select the patients who will receive these drugs in a correct manner. It is also essential to carefully monitor patients using TKI regarding possible adverse effects, which should be properly managed when occurring.

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SUMMARY Oral melanoacanthoma is a mucocutaneous, pigmented, rare, benign, and probably reactive lesion. This paper reports for the first time in the literature a case of multifocal oral melanoacanthoma in a patient diagnosed with Addison’s disease and concomitant Graves’ disease with hyperthyroidism. The patient presented with oral pigmented lesions, which were hypothesized to be mucosal pigmentation associated with Addison’s disease. Due to their unusual clinical pattern, these oral lesions were biopsied and diagnosed as oral melanoacanthoma on histopathology and immunohistochemistry for HMB-45. At the moment of this report, the patient was being treated for her systemic conditions, but the lesions had not regressed. Reactive hyperpigmentation of the skin and mucous membranes may be found in Addison’s disease and hyperthyroidism. This case reinforces the hypothesis of a reactive nature for oral melanoacanthoma and highlights the need for investigation of endocrine disorders in patients with multifocal oral melanoacanthoma.