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Abstract Background Raw data obtained through bioelectrical impedance analysis (BIA) have been applied in different populations to assess body fluids and cell integrity. Assessing raw BIA parameters in specific muscles is an emerging method for evaluating muscle function. We investigated the associations of the BIA-derived variables of resistance (R), reactance (Xc) and phase angle (PhA) measured through whole-body (WB) and muscle-localized (ML) methods with performance in the countermovement jump (CMJ) and 50-meter (m) sprint. Methods Thirty-one male track and field athletes (16.5 ± 1.6 years) were assessed. Fat-free mass (FFM) and Fat mass percentage (%FM) were determined by skinfold thickness. BIA at 50 kHz was employed to obtain the WB and ML (right thigh) parameters. The WB and ML-BIA parameters were adjusted by height (R/H, Xc/H) and segment length (R/L, Xc/L). The CMJ assessment was conducted via a contact mat; the software recorded the jump height. The 50-m sprint time was measured via two sets of photocells. Pearson’s correlation and linear multiple regression were performed. Results ML-PhA was inversely related to the 50-m sprint (β=-0.56) and by itself explained 29% of the sprint time variation. It remained a significant predictor even after adjusting for age, height, FFM and peak height velocity (PHV). ML-R/L was directly related to 50-m sprint (β = 0.48) and inversely related to CMJ performance (β=-0.54), explaining 20% and 27% of the variation in 50-m sprint and CMJ performance, respectively. Similarly, it remained a significant predictor in the adjusted models. Correlations between WB-BIA (PhA, R/H) and performance tests were found to be dependent on covariates. Conclusions In this sample, the ML-BIA parameters of R/L and PhA were significantly associated with performance independent of age, height, FFM and PHV. Higher ML-PhA values were associated with better sprint times, whereas higher ML-R/L values were associated with worse sprint times and CMJ performance.

Summary: Background: Oligogenic inheritance has been suggested as a possible mechanism to explain the broad phenotype observed in individuals with differences of sex development (DSD) harbouring NR5A1/SF-1 variants. Methods: We investigated genetic patterns of possible oligogenicity in a cohort of 30 individuals with NR5A1/SF-1 variants and 46,XY DSD recruited from the international SF1next study, using whole exome sequencing (WES) on family trios whenever available. WES data were analysed using a tailored filtering algorithm designed to identify rare variants in DSD and SF-1-related genes. Identified variants were subsequently tested using the Oligogenic Resource for Variant Analysis (ORVAL) bioinformatics platform for a possible combined pathogenicity with the individual NR5A1/SF-1 variant. Findings: In 73% (22/30) of the individuals with NR5A1/SF-1 related 46,XY DSD, we identified one to seven additional variants, predominantly in known DSD-related genes, that might contribute to the phenotype. We found identical variants in eight unrelated individuals with DSD in DSD-related genes (e.g., TBCE, FLNB, GLI3 and PDGFRA) and different variants in eight genes frequently associated with DSD (e.g., CDH23, FLNB, GLI2, KAT6B, MYO7A, PKD1, SPRY4 and ZFPM2) in 15 index cases. Our study also identified combinations with NR5A1/SF-1 variants and variants in novel candidate genes. Interpretation: These findings highlight the complex genetic landscape of DSD associated with NR5A1/SF-1, where in several cases, the use of advanced genetic testing and filtering with specific algorithms and machine learning tools revealed additional genetic hits that may contribute to the phenotype. Funding: Swiss National Science Foundation and Boveri Foundation Zurich.

Objective: To develop growth charts for weight-for-age, height-for-age, and body mass index (BMI)-for-age for both genders aged 2 to 18 years for Brazilian patients with Williams-Beuren Syndrome (WBS). Methods: This is a multicenter, retrospective, and longitudinal study, data were collected from the medical records of boys and girls with a confirmed diagnosis of WBS in three large university centers in the state of Sao Paulo, Brazil. Growth charts stratified by gender and age in years were developed using LMSchartmaker Pro software. The LMS (Lambda Mu Sigma) method was used to model the charts . The quality of the settings was checked by worm plots. Results: The first Brazilian growth charts for weight-for-age, height-for-age, and BMI-for-age stratified by gender were constructed for WBS patients aged 2 to 18 years. Conclusion: The growth charts developed in this study can help to guide family members and to improve the health care offered by health professionals.

ABSTRACT Objective: Considering the rarity and clinical and molecular diversity of Wolfram syndrome (WS), the objective of this study was to identify patients with a clinical presentation suggestive of WS following up at a single Brazilian diabetes service and analyze their clinical and molecular characteristics. Subjects and methods: The study included all patients with a clinical presentation of WS following up between 1991 and 2022 with early-onset diabetes mellitus and other WS signs and symptoms. A retrospective analysis was conducted, including patients’ age, sex, consanguinity, age at symptom onset, diagnosis of diabetes mellitus, optic atrophy, diabetes insipidus, neurological and psychiatric disorders, hearing loss, urinary disorders, hypogonadism, and WFS1 molecular analysis. Results: Eight patients were identified, all of whom were diagnosed with diabetes mellitus at an average age of 3.7 years. Optic atrophy, diabetes insipidus, and hearing loss were common, while psychiatric and neurological alterations were observed in some cases. Genetic analysis revealed pathogenic variants in homozygosity or compound heterozygosity. The most frequent variant was p. Val412Serfs29, present in five of the seven families. Conclusions: This study represents the second-largest Brazilian sample of WS and is the first cohort from a single center in Southeast Brazil. The patients had an early, severe, and complete clinical presentation. The genetic variants identified were consistent with previous literature descriptions. The variant p. Val412Serfs29 was particularly common in this cohort, highlighting its relevance in the region.

Summary: Background: Steroidogenic factor 1 (SF-1/NR5A1) is essential for human sex development. Heterozygous NR5A1/SF-1 variants manifest with a broad range of phenotypes of differences of sex development (DSD), which remain unexplained. Methods: We conducted a retrospective analysis on the so far largest international cohort of individuals with NR5A1/SF-1 variants, identified through the I-DSD registry and a research network. Findings: Among 197 individuals with NR5A1/SF-1 variants, we confirmed diverse phenotypes. Over 70% of 46, XY individuals had a severe DSD phenotype, while 90% of 46, XX individuals had female-typical sex development. Close to 100 different novel and known NR5A1/SF-1 variants were identified, without specific hot spots. Additionally, likely disease-associated variants in other genes were reported in 32 individuals out of 128 tested (25%), particularly in those with severe or opposite sex DSD phenotypes. Interestingly, 48% of these variants were found in known DSD or SF-1 interacting genes, but no frequent gene-clusters were identified. Sex registration at birth varied, with

ABSTRACT Objective: This study aimed to analyze if anthropometric factors and physical appearance are associated to QoL in Turner syndrome (TS). Materials and methods: Observational, analytical, and cross-sectional study. The SF-36 was applied along with an additional questionnaire regarding specific characteristics of TS. Results: There were no differences in quality of life (QoL) in TS women regarding median height and appropriate height according to parental target height, however, participants satisfied and who did not desire to change their height had better scores in the mental health and role emotional domains than those not satisfied and desired to change it. When comparing participants who were or were not bothered by physical appearance, the results showed that those not bothered by physical appearance had a better score in the vitality and social function domains. Considering patients who did or did not desire to change physical appearance, those who did not want to change their physical appearance had higher scores in the mental component and in the social function and mental health domains of the SF-36. Conclusion: This study indicated that anthropometric factors and physical appearance may possibly be associated to QoL in TS, and also emphasizes the need to develop and validate an official questionnaire regarding specific TS characteristics in order to assess in more detail how specific characteristics of TS interfere with their QoL.

Background Complications are frequently reported after hypospadias repair and there is a need to understand the factors that influence their occurrence.Methods Data from boys with hypospadias born between 2000 and 2020 were obtained from the International Disorders of Sex Development (I-DSD) Registry. Logistic regressions, fisher’s exact tests and spearman’s correlation tests were performed on the data to assess associations between clinical factors and complication rates.Results Of the 551 eligible boys, data were available on 160 (29%). Within the cohort, the median (range) External Masculinization Score (EMS) was 6 (2, 9). All presented with one or more additional genital malformation and 61 (38%) presented with additional extragenital malformations. Disorders of androgen action, androgen synthesis and gonadal development were diagnosed in 28 (18%), 22 (14%) and 9 (6%) boys, respectively. The remaining 101 (62%) patients were diagnosed as having non-specific 46,XY Disorders of Sex Development. Eighty (50%) boys had evidence of abnormal biochemistry, and gene variants were identified in 42 (26%). Median age at first hypospadias surgery was 2 years (0, 9), and median length of follow-up was 5 years (0, 17). Postsurgical complications were noted in 102 (64%) boys. There were no significant associations with postsurgical complications.Conclusions Boys with proximal hypospadias in the I-DSD Registry have high rates of additional comorbidities and a high risk of postoperative complications. No clinical factors were significantly associated with complication rates. High complication rates with no observable cause suggest the involvement of other factors which need investigation.

ABSTRACT Objective: Herein, we compared ambulatory blood pressure (ABP) between young adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase enzyme (21OHase) deficiency and a control group. Additionally, we analyzed correlations between the glucocorticoid dose and androgen levels and ABP parameters. Subjects and methods: This case-control study included 18 patients (6 males and 12 females) and 19 controls (8 males and 11 females) matched by age (18-31 years). ABP monitoring was used to estimate blood pressure (BP) over a 24-h period. Results: No difference was noted between patients and controls in terms of systolic BP (males, 115.5 ± 5.6 vs. 117.0 ± 9.3, P = 0.733; and females, 106.4 ± 7.9 vs. 108.4 ± 7.6, P = 0.556, respectively) and diastolic BP during 24 h (males, 62.8 ± 7.5 vs. 66.2 ± 5.6, P = 0.349; and females, 62.7 ± 4.9 vs. 62.3 ± 4.9, P = 0.818, respectively). Systolic and diastolic BP and pulse pressure during daytime and nocturnal periods were similar between patients and controls. Furthermore, no differences were detected in the percentage of load and impaired nocturnal dipping of systolic and diastolic BP between patients and controls during the 24-h period. Additionally, the glucocorticoid dose (varying between r = −0.24 to 0.13, P > 0.05) and androgens levels (varying between r = 0.01 to 0.14, P > 0.05) were not associated with ABP parameters. Conclusion: No signs of an elevated risk for hypertension were observed based on ABP monitoring in young adults with CAH attributed to 21OHase deficiency undergoing glucocorticoid replacement therapy.

Objective: Population-level monitoring of body composition requires accurate, biologically-relevant, yet feasible methods for estimating percent body fat (%BF). The aim of this study was to develop and cross-validate an equation for %BF from Body Mass Index (BMI), age, and sex among children with intellectual disability (ID). This study further aimed to examine the performance of an existing BMI-based equation (Deurenberg equation) for %BF in children with ID. Method: Participants were 107 children (63 boys; aged 6-15 years) with ID randomly allocated to development (n = 81) and cross-validation (n = 26) samples. Dual-Energy X-Ray Absorptiometry provided the criterion %BF. Results: The model including BMI, age, and sex (0 = male; 1 = female) had a significant goodness-of-fit in determining %BF (p

Local development in Cuba represents in recent times a topic of great importance in public agendas, from which Higher Education assumed it as a priority in its strategic planning. On this basis, the management of the professional training process of university students should focus on territorial needs, based on the development of activities and actions that respond to social needs and contribute to their professional performance. To this end, the training process should facilitate the articulation of knowledge, innovation, as well as the development of skills for entrepreneurship and the training of social leaders to enhance the fulfillment of economic policies. Taking these aspects into account, the objective of this research is to propose a system of actions to contribute to the integration of university processes to the management of local development. In order to achieve this objective, theoretical and empirical methods were used, which made it possible to achieve as main result the design of a proposal of actions that contributes to provide ways to ensure that the training process of professionals is developed in an integrated manner to the management of local development, facilitating structural changes and improving the quality of life of the population.

Abstract Objectives: to evaluate the bone mass in prepubertal patients with Turner Syndrome (TS) according to height age (HA) and verify the influence of karyotype and adiposity. Methods: retrospective and analytical study of prepubertal TS patients. The variables analyzed were: karyotype, age at bone densitometry (BD), height, body mass index (BMI) and BD result. The result of the BD was corrected using HA. BMI and BD were calculated on Z score for chronological age (CA) and for HA. Results: thirty-seven prepubertal patients were selected and after exclusion criteria, 13 cases between 10 and 13 years old were included in the study. The BD for HA was significantly higher than for CA (0.39 ± 1.18 x −1.62 ± 1.32), without karyotype (p=0.369) and BMI (p=0.697) influence. Conclusion: prepubertal TS patients present normal BD when corrected for HA, without influence of karyotype and BMI.

ABSTRACT BACKGROUND: Knowledge of clinical and laboratory differences between chromosomal and undefined causes aids etiological research on non-obstructive azoospermia. OBJECTIVE: Compare clinical and laboratory differences between men with non-obstructive azoospermia due to chromosomal anomalies versus undefined causes DESIGN AND SETTING: A cross-sectional retrospective study conducted at a public university hospital in Campinas (Brazil) METHODS: All men aged 20–40 years with non-obstructive azoospermia were included in the analysis. RESULTS: The 107 cases included 14 with Klinefelter syndrome (KS) (13%), 1 with mosaic KS, 4 with sex development disorders (2 testicular XX, 1 NR5A1 gene mutation, and 1 mild androgen insensitivity syndrome) (4%), 9 with other non-obstructive azoospermia etiologies (8%), and 79 with undefined causes. The 22 chromosomal anomaly cases (14 KS, 1 mosaic KS, 2 testicular XX, 4 sex chromosome anomalies, and 1 autosomal anomaly) were compared with the 79 undefined cause cases. The KS group had lower average testicular volume, shorter penile length, and lower total testosterone levels but greater height, arm span, serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, and gynecomastia frequency (absent in the undefined group and affecting more than half of the KS group). Patients with testicular XX DSD had LH, FSH, and penile length data intermediate between the KS and undefined cause groups, testicular volume similar to the KS group, and other data similar to the undefined group. CONCLUSION: Clinical and laboratory data differentiate men with non-obstructive azoospermia and chromosomal anomalies, particularly KS and testicular XX, from those with undefined causes or other chromosomal anomalies.

The main objective of this article is to propose a microcredit program to stimulate Local Economic Development projects. This definition is based on the preponderant role of local development in Cuba, which has become a public policy of strategic importance as a complement to the National Economic and Social Development Plan until 2030, as well as a central and articulating axis of the public agendas of governments at the municipal and provincial levels. However, there is evidence of financial limitations to implement development project ideas in the state and non-state sector, as a consequence, among other factors, of the limited offers of financial mechanisms that stimulate entrepreneurs to put their business ideas into operation. The methods used in the research were: historical-logical, systemic and modeling to determine the trends in the management of microcredits in terms of local development and to support the proposed procedure for the allocation of microcredits to finance local economic development projects. The proposed microcredit program represents a support tool to solve the scientific problem stated in this research. The procedure has a set of suggestions that will facilitate its application, which are variable according to the criteria of the local actors.

Abstract We compared the effect of dapagliflozin versus glibenclamide on the ratio of lean-to total mass in patients with type 2 diabetes mellitus, carotid subclinical atherosclerosis, HbA1c 7.0–9.0% and 40–70 years-old. Ninety-eight patients (61% male; mean age 57 ± 7 years) were randomized into dapagliflozin 10 mg/day or glibenclamide 5 mg/day on top of metformin. Body composition was measured by Dual Energy X-Ray at randomization and after 12 weeks of treatment. Glycemic control was equivalent in both groups. Dapagliflozin decreased total body mass (−2741 g [95% CI: −3360 to 1945]; p

BackgroundApplied research using the phase angle (PhA) in children and adolescents has increased notably. Using multilevel modeling in a fully Bayesian framework, we examined the relationships between PhA, age, sex, biological maturity status, and body size in 10–16-year-old adolescents.MethodsThe sample comprised 519 adolescents (women, n = 241; men, n = 278) from Campinas, São Paulo, Brazil. Biological maturity status was assessed with self-examination of pubertal development for sexual maturity and maturity offset protocol to estimate age at peak height velocity (PHV) for somatic maturity status. Stature and body mass were measured by anthropometry. Phase angle was calculated based on raw resistance and reactance values (50 kHz frequency) obtained by bioelectrical impedance with the foot-to-hand technology.ResultsThe multilevel regression analysis revealed that boys had significantly higher values of phase angle than girls, adjusting for age group and sexual maturity status. Overall, older and more mature adolescents had higher values of phase angle. When considering aligning variation in the phase angle by distance to estimated PHV (maturity offset), there was a higher association between the phase angle and time before and after predicted age at PHV for boys (r = 0.31, 90% CI: 0.23 to 0.39) than girls (r = 0.2, 90% CI: 0.11 to 0.28). When including body mass in the multilevel models, corresponding changes in the overall body mass mediate most of the influence of the maturity status and age group on the phase angle.ConclusionThe present study demonstrated that the variability in phase angle is related to inter-individual variation in sex, age, and maturity status, as well as differences in body size. Research with adolescents considering phase angle should use multilevel modeling with standardized parameters as default to adjust for the concurrent influence of sex, age, maturity status, and body size.

Complete androgen insensitivity syndrome (CAIS) is a rare condition characterized by 46,XY karyotype, female external genitalia, absence of uterus, and testes located intra-abdominally, in the inguinal ring or in the labia majora. In the present study, the frequency of testicular malignancy in prepubertal and pubertal patients with CAIS who underwent gonadectomy or gonadal biopsy were evaluated. Systematic review was performed using electronic databases according to the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines. The samples included 15 articles published between 1998 and 2019. From a total of 456 patients who underwent gonadectomy or gonadal biopsy, 6.14% had a premalignant lesion and most were postpubertal (82.14%). A malignant lesion was found in 1.3% and all were postpubertal. Because the risk of malignancy is very low in prepubertal patients with CAIS, gonadectomy may be delayed until puberty is complete, allowing it to progress naturally; however, close follow-up of the patient is required.

Objective: To indicate neck circumference (NC) cutoff points to identify excess weight at different stages of somatic maturation and evaluate the association between NC and body mass index (BMI). Methods: Cross-sectional study with 1715 adolescents. BMI was classified according to the World Health Organization (WHO) criteria. Somatic maturation was obtained through the peak growth velocity (PGV). To define the cutoff points, curves of the receiver operating characteristic (ROC) model were constructed. The agreement between the anthropometric evaluation instruments was analyzed. The association between the variables was verified. Results: Of the girls, 93 were in the pre-PGV stage, 266 in the PGV stage, and 481 in the post-PGV stage. Of the boys, 264 were in the pre-PGV stage, 334 in the PGV stage, and 277 in the post-PGV stage. For the pre-PGV group, the cutoff point was 28 cm for females and 29 cm for males; for the group during PGV, the cutoff points were 30 cm for females and 33 cm for males; in the post-PGV group the cutoff values were 32 cm in females and 35 cm in males. The prevalence of excess weight was higher in the pre-PGV stage in males and in the PGV stage in females. The correlation coefficients were higher in the pre-PGV and PGV stages. Conclusion: The cutoff points for NC found in this study showed good sensitivity and specificity to identify excess weight in Brazilian adolescents and can be used as a reference in epidemiological studies.

Objective: Steroid measurement is a challenge in pediatric endocrinology. Currently, liquid chromatography with tandem mass spectrometry (LC-MS/MS) is considered a gold standard for this purpose. The aim of this study was to co mpare both LC-MS/MS and immunoassay (IA) for androgens before and after human recom binant chorionic gonadotropin (rhCG) stimulus in children with 46,XY disorders o f sex development (DSD). Methods: Nineteen patients with 46,XY DSD were evaluated; all of them w ere prepubertal and non-gonadectomized. Testosterone, dihydrotestosterone (DHT), DHEA and androstenedione were measured by IA and LC-MS/MS before and 7 d ays after rhCG injection. The correlation between IA and LC-MS/MS was analyzed by the intraclass correlation coefficient (ICC) and Spearman’s rank correlation coe fficient (SCC). For concordance analysis the Passing and Bablok (PB) regression and the Bland and Altman (BA) method were used. Results: Testosterone showed excellent correlation (ICC = 0.960 and SCC = 0.964); DHT showed insignificant and moderate correlations as indicated by I CC (0.222) and SCC (0.631), respectively; DHEA showed moderate correlation (ICC = 0.585 and SCC = 0.716); and androstenedione had poor and moderate correlations in ICC ( 0.363) and SCC (0.735), respectively. Using the PB method, all hormones showed a linear correlation, but proportional and systematic concordance errors were detected fo r androstenedione, systematic errors for testosterone and no errors for DHEA and D HT. By the BA method, there was a trend of IA to overestimate testosterone and andros tenedione and underestimate DHEA and DHT when compared to LC-MS/MS. Conclusion: Traditional IA should be replaced by LC-MS/MS for the androgen s measurement in prepubertal children whenever is possible.

Objective: To evaluate, in a sample of patients with disorders of sex development (DSD), data related to the age at referral and their correlation with the initial complaints, gender at referral, defined gender after diagnosis and etiological diagnosis. Methods: Retrospective review of the age at the first consultation and the reason for it, initial social gender and gender after the diagnosis, karyotype and etiological diagnosis of all cases treated at a DSD outpatient clinic between 1989 and 2016. Cases that did not involve DSD and DSD diagnoses that do not usually involve ambiguous genitalia, thus not requiring specialized monitoring, were excluded. Results: Of the 1793 treated cases, 1139 were diagnosed with some type of DSD. This study excluded 430 cases (272 with Turner's syndrome, 66 with Klinefelter syndrome, and 92 with pure gonadal dysgenesis), thus a total 709 individuals were included. Of these, 82.9% were referred due to ambiguous genitalia; only one-quarter were still in the first month of life, and 6.6% were referred due to pubertal delay, with most of them aged 10 years or older. Of these patients, 68.6% had a diagnosis of XY DSD, 22.4% of XX DSD, and 9% of sex chromosome abnormalities. Conclusions: This study presents the largest series in the literature of patients with DSD treated in a single center. The time of referral of the majority of patients with ambiguous genitalia fell short of the ideal, and milder cases of ambiguous genitalia and many with pubertal manifestations were referred even later. The results reinforce the importance of continuing education for professionals who will have the first contact with these patients, mainly pediatricians and neonatologists. Resumo: Objetivo: Avaliar em uma amostra de pacientes com distúrbios da diferenciação do sexo (DDS), dados relacionados à idade, ao encaminhamento e sua correlação com as queixas iniciais, ao sexo ao encaminhamento e ao sexo final e diagnóstico etiológico. Métodos: Revisão retrospectiva da idade por ocasião da primeira consulta e motivo da mesma, sexo social inicial e após definição do diagnóstico, cariótipo e diagnóstico etiológico de todos os casos atendidos em um ambulatório especializado em DDS entre 1989 e 2016. Foram excluídos casos que não compreendiam DDS e diagnósticos de DDS que não cursam comumente com ambiguidade genital, não necessitam de acompanhamento especializado. Resultados: Dos 1.793 casos atendidos, 1.139 foram diagnosticados com algum DDS. Excluíram-se 430 (272 síndrome de Turner, 66 síndrome de Klinefelter e 92 disgenesia gonadal pura), totalizando 709. Desses, 82,9% foram encaminhados por ambiguidade genital, somente um quarto ainda no primeiro mês de vida e 6,6% por atraso puberal, a maioria com 10 anos ou mais; 68,6% tiveram diagnóstico de DDS XY; 22,4% DDS XX e 9% de anomalias dos cromossomos sexuais. Conclusões: Este estudo apresenta a maior casuística na literatura de pacientes com DDS atendidos em um único serviço. O momento de encaminhamento da maioria dos pacientes com ambiguidade genital foi aquém do ideal e casos mais leves de ambiguidade e muitos com manifestações puberais foram encaminhados ainda mais tardiamente. Os resultados reforçam a importância do ensino continuado a profissionais que terão o primeiro contato com esses pacientes, principalmente pediatras e neonatologistas.

Purpose This cross-sectional study evaluated the relationship between adipokines (leptin, adiponectin, visfatin, and resistin) and adiposity indexes regarding sex and cranial radiotherapy exposure among young acute lymphocytic leukemia survivors. Methods A multivariate analysis of covariance (MANCOVA) was used to evaluate the joint effect of sex, cranial radiotherapy, and body mass index (BMI) z-score (model 1) or fat mass index (FMI) (model 2) on adipokines. Results This study included 55 survivors of childhood acute lymphocytic leukemia between 15 and 23 years of age from both sexes (56.4% female); 43.6% of the sample had undergone cranial radiotherapy (18–24 Gy). The BMI z-score, the FMI, and sex (P

The group of disorders known as 46,XY gonadal dysgenesis (GD) is characterized by anomalies in testis determination, including complete and partial GD (PGD) and testicular regression syndrome (TRS). Several genes are known to be involved in sex development pathways, however approximately 50% of all cases remain elusive. Recent studies have identified variants in DHX37, a gene encoding a putative RNA helicase essential in ribosome biogenesis and previously associated with neurodevelopmental disorders, as a cause of PGD and TRS. To investigate the potential role of DHX37 in disorders of sexual development (DSD), 25 individuals with 46,XY DSD were analyzed and putative pathogenic variants were found in four of them. WES analyses were performed on these patients. In DHX37, the variant p.(Arg308Gln), recurrent associated with DSD, was identified in one patient; the p.(Leu467Val), predicted to be deleterious, was found together with an NR5A1 loss-of-function variant in patient 2; and, the p.(Val999Met) was identified in two unrelated patients, one of whom (patient 3) also carried a pathogenic NR5A1 variant. For both patients carrying DHX37 and NR5A1 pathogenic variants, a digenic inheritance is suggested. Our findings support the importance of DHX37 variants as a cause of disorders of sex development, implying a role in testis development.

Abstract BACKGROUND: Because normal male sexual differentiation is more complex than normal female sexual differentiation, there are more cases of disorders of sex development (DSDs) with 46,XY karyotype that have unclear etiology. However, Leydig and Sertoli cell markers are rarely used in distinguishing such individuals. OBJECTIVES: To evaluate the function of Leydig and Sertoli cells in individuals with genital ambiguity, 46,XY karyotype, palpable gonads and normal testosterone secretion. STUDY DESIGN AND SETTING: Case-control study with 77 patients, including eight with partial androgen insensitivity syndrome, eight with 5α-reductase deficiency type 2 (5ARD2) and 19 with idiopathic 46,XY DSD, and 42 healthy controls, from the Interdisciplinary Study Group for Sex Determination and Differentiation (GIEDDS), at the State University of Campinas (UNICAMP), Campinas, Brazil. METHODS: Baseline levels of gonadotropins, anti-Müllerian hormone (AMH), inhibin B, insulin-like 3 (INSL3), testosterone and dihydrotestosterone in cases, and AMH, inhibin B, and INSL3 levels in controls, were assessed. RESULTS: There was no significant difference in age between cases and controls (P = 0.595). AMH and inhibin B levels were significantly lower in cases than in controls (P = 0.031 and P < 0.001, respectively). INSL3 levels were significantly higher in cases than in controls (P = 0.003). Inhibin B levels were lower in 5ARD2 patients (P = 0.045) and idiopathic patients (P = 0.001), in separate comparisons with the controls. CONCLUSION: According to our findings, we can speculate that inhibin B levels may be used to differentiate among DSD cases.

Abstract Background Endothelial dysfunction (ED) is a hallmark in type 2 diabetes mellitus (T2DM) that favor both atherogenesis and ischemia and reperfusion injury (IRI). Sodium-glucose-2 co-transporter inhibitors (SGLT2i) may hypothetically improve microvascular and macrovascular functions via a broad spectrum of mechanisms, being superior to traditional antidiabetic therapy such as sulfonylurea, even in subjects under equivalent glycemic control. Hence, the present clinical trial was designed to compare the effect of these two treatments on markers of arterial wall function and inflammation in T2DM patients as well as on the potential mediating parameters. Method and results ADDENDA-BHS2 is a prospective, single-center, active‐controlled, open, randomized trial. Ninety-eight participants (40–70 years old) with HbA1c 7–9% were randomized (1:1, stratified by gender, BMI and HbA1c levels) to either dapagliflozin 10 mg/day or glibenclamide 5 mg/day on top of metformin. The primary endpoint was the change of flow-mediated dilation (FMD) after a 12-week period of treatment evaluated at rest and after IRI between dapagliflozin and glibenclamide arms. Secondary outcomes were defined as the difference between treatments regarding: plasma nitric oxide (NO) change after FMD, plasma isoprostane, plasma levels of vascular inflammatory markers and systemic inflammatory markers, plasma levels of adipokines, anthropometric measures, glucose control parameters, office and ambulatory BP control. Safety endpoints were defined as systolic and diastolic function assessed by echocardiography and retinopathy change. Serious adverse events were recorded. The study protocol was approved by the Independent Scientific Advisory Committee. Conclusion The ADDENDA-BHS2 trial is an investigator-initiated clinical trial comparing the effect of dapagliflozin versus glibenclamide on several aspects of vascular function in high cardiovascular risk T2DM patients. Besides, a large clinical and biochemical phenotype assessment will be obtained for exploring potential mediations and associations. Trial registration Clinical trial registration: NCT 02919345 (September, 2016)

ABSTRACT Objective: To identify the prevalence of overweight in adolescents according to different classification criteria for obesity and somatic maturation stages. Methods: Cross-sectional study in 10 schools in a city from Southern Brazil, with 1715 adolescents. Height, weight, waist circumference, and neck circumference (NC) data were collected. Body Mass Index was classified according to World Health Organization (WHO) and Centers for Disease Control and Prevention criteria, and the waist-to-height ratio (WHtR) was classified according to Brazilian and European cut-off points. Somatic maturation was obtained through the Peak Height Velocity. The prevalence data were compared between sex and stages of somatic maturation; the concordance between different criteria was verified. Results: The prevalence of overweight was high in both sexes; WHO criteria showed that 34.5% of boys and 29.3% of girls were overweight. For the WHtR, the prevalence was 28.4% in boys and 23.7% in girls. NC classified 13.8% of boys and 15.8% of girls as being overweight. The prevalence of overweight was higher in adolescents before complete somatic maturation. Conclusions: The prevalence of overweight was high among adolescents. The boys presented higher frequency of overweight, except if NC was used to classify them. Adolescents before somatic maturation had a higher prevalence of overweight. NC showed a lower ability to track obese adolescents.

Abstract Background Musculoskeletal injuries are the main cause of premature discharge from military service and can sometimes lead to permanent disabilities. Some intrinsic risk factors are well discussed in the literature. However, the relation between body composition variables and the risk for musculoskeletal injury is not well known or recognized. Methods This prospective study evaluated 205 Brazilian military students. At the beginning of military service, health status and sports experience prior to military service were registered. Anthropometric variables were evaluated, and bone and body composition variables were measured using dual-energy X-ray absorptiometry. The occurrence of musculoskeletal injuries throughout the year was registered at the military physiotherapy service. At the end of 1 year of follow-up, risk factors were analysed by comparing the variables between the injured and non-injured students. Results No difference in previous health status was found between injured and non-injured groups, whereas sports experience prior to military service was identified as a protective factor (Odds Ratio (OR) 0.323; 95% CI: 0.108–0.968; p = 0.044). Anthropometric, bone, and body composition variables could not be identified as risk factors for musculoskeletal injuries in Brazilian military students. Conclusion Anthropometric, bone, and body composition variables could not be considered risk factors for musculoskeletal injuries in Brazilian military students.

Abstract Background Dopamine is involved in several cerebral physiological processes, and single nucleotide polymorphisms (SNP) in the dopamine D2 receptor gene (DRD2) have been associated with numerous neurological and mental disorders, including those involving alterations in cognitive and emotional processes. Methods The aim of this study was to evaluate the association between the SNPs c.957C > T (rs6277) and c.-585A > G (rs1799978) in the DRD2 gene and behavioral characteristics of children and adolescents based on an inventory of the Child Behavior Checklist (CBCL). Children and adolescents between 8 and 20 years old who were clinically followed-up were genotyped for the SNPs c.957C > T and c.-585A > G, and related to data of the CBCL/6–18 scale assessment performed with the help of caregivers. The chi-squared test was used to assess the differences in the frequencies of the C and T alleles in the polymorphism c.957C > T and of the A and G alleles in the polymorphism c.-585A > G with respect to the grouped CBCL scores at a significance level of 5%. Multiple logistic regression models were performed, to control whether sex and/or ethnicity could influence the results. Results Eighty-five patients were assessed overall, and the presence of the T allele (C/T and T/T) of DRD2 c.957C > T polymorphism was found to be significantly associated with the occurrence of defiant and oppositional problems and with attention and hyperactivity problems. There were no associations detected with polymorphism DRD2 c.-585A > G polymorphism. Both SNPs were in Hardy-Weinberg-equilibrium. Conclusions Although the findings of this study are preliminary, due to its small number of participants, the presence of T allele (C/T, T/T) in c.957C > T SNP was associated with difficulty in impulse control, self-control of emotions, and conduct adjustment, which can contribute to improving the identification of mental and behavioral phenotypes associated with gene expression.

Objective: To develop growth charts for weight-for-age, height-for-age, and body mass index (BMI)-for-age for both genders aged 2 to 18 years for Brazilian patients with Williams-Beuren Syndrome (WBS). Methods: This is a multicenter, retrospective, and longitudinal study, data were collected from the medical records of boys and girls with a confirmed diagnosis of WBS in three large university centers in the state of Sao Paulo, Brazil. Growth charts stratified by gender and age in years were developed using LMSchartmaker Pro software. The LMS (Lambda Mu Sigma) method was used to model the charts . The quality of the settings was checked by worm plots. Results: The first Brazilian growth charts for weight-for-age, height-for-age, and BMI-for-age stratified by gender were constructed for WBS patients aged 2 to 18 years. [ABSTRACT FROM AUTHOR]

Optimizing bone mass gain during childhood and adolescence may help prevent bone diseases in advanced ages. The aim of this study was to verify the bone mineral density (BMD) and bone mineral content (BMC) in female adolescent’s handball players. This is a cross-sectional study where 68 female adolescents (12–17 years) were allocated into two groups: handball players (n = 29) (HG) and control group (n = 39) (CG). BMC and BMD from total body (TB), total body less head (TBLH), lumbar spine (L1–L4), femoral neck (FN), Ward’s triangle (WT) and respectively Z-scores were measured using dual-energy X-ray absorptiometry (DXA). Sexual maturity, menarche, PHV, time of sun exposure, physical activity level and Calcium and vitamin D intake were assessed. The HG showed significantly higher BMC, BMD as well Z-scores values (p≤0.05) of total body, TBLH, femoral neck, hip and lumbar spine than the CG. When the values were adjusted for lean soft tissue (LST) the HG showed significantly higher BMC of femoral neck (p≤0.05), as well as BMD of TBLH and femoral neck (p≤0.05) and Z-score values all bone sites except hip, than the CG. We conclude that handball players have significantly higher bone mass values compared to group of girls of the same age.

Abstract Background Ultrasensitive assays to measure pre-pubertal gonadotropins levels could help identify patients with Turner syndrome (TS) in mid-childhood, but studies in this field are scarce. The aim of this study was to analyze gonadotropins levels in girls with TS throughout childhood. Methods Retrospective longitudinal study conducted with 15 girls with TS diagnosed with 10 years). In newborn/mini-puberty and late childhood/adolescence pre-pubertal or pubertal gonadotropins were considered normal; in early childhood and mid-childhood concentrations above the pre-pubertal range were considered abnormal. Results Abnormally high FSH alone was found in four of five patients in newborn/mini-puberty, 13 of 15 during early childhood and nine of 15 during mid-childhood. In the group of 12 patients in late childhood/adolescence, the three girls with spontaneous puberty had only normal levels; the remaining showed only post-menopausal concentrations. In mid-childhood one patient exhibited only pre-pubertal FSH. Conversely, most LH measurements in early and mid-childhood were normal. Conclusion Karyotyping of girls with short stature and high FSH levels would allow early diagnosis of Turner syndrome in a significant number of patients, particularly when resources for chromosome study of all girls with growth deficiency are limited.

Objectives: To determine the prevalence of congenital hypothyroidism in children with filter paper TSH levels (f‐TSH) between 5 and 10 μUI/mL in the neonatal screening. Methods: This was a retrospective study including children screened from 2003 to 2010, with f‐TSH between 5 and 10 μIU/mL, who were followed‐up during the first two years of life when there was no serum TSH normalization. The diagnosis of congenital hypothyroidism was defined as serum TSH ≥10 μIU/mL and start of levothyroxine treatment up to 2 years of age. Results: Of the 380,741 live births, 3,713 (1.04%) had f‐TSH between 5 and 10 μIU /mL and, of these, 339 (9.13%) had congenital hypothyroidism. Of these, 76.11% of the cases were diagnosed in the first three months of life and 7.96% between 1 and 2 years of age. Conclusion: The study showed that 9.13% of the children with f‐TSH between 5 and 10 μIU/mL developed hypothyroidism and that in approximately one‐quarter of them, the diagnosis was confirmed only after the third month of life. Based on these findings, the authors suggest the use of a 5 μIU/mL cutoff for f‐TSH and long‐term follow‐up of infants whose serum TSH has not normalized to rule out congenital hypothyroidism.

The aim of this study was to identify the prevalence and concordance of excess weight (BMI) and body fat (fat %) in adolescents of both sexes from cities of Rio Branco-AC and Porto Velho-RO. This study evaluated 4,310 adolescents, 2,167 from Rio Branco and 2,143 from Porto Velho. No difference (p=0.46) for excess weight between adolescents from Rio Branco (34.8%) and Porto Velho (33.8%) was observed. Fat percentage was significantly higher (p

Primary ovarian insufficiency (POI) is a heterogeneous disorder associated with several genes. The majority of cases are still unsolved. Our aim was to identify the molecular diagnosis of a Brazilian cohort with POI. Genetic analysis was performed using a customized panel of targeted massively parallel sequencing (TMPS) and the candidate variants were confirmed by Sanger sequencing. Additional copy number variation (CNV) analysis of TMPS samples was performed by CONTRA. Fifty women with POI (29 primary amenorrhea and 21 secondary amenorrhea) of unknown molecular diagnosis were included in this study, which was conducted in a tertiary referral center of clinical endocrinology. A genetic defect was obtained in 70% women with POI using the customized TMPS panel. Twenty-four pathogenic variants and two CNVs were found in 48% of POI women. Of these variants, 16 genes were identified as BMP8B, CPEB1, INSL3, MCM9, GDF9, UBR2, ATM, STAG3, BMP15, BMPR2, DAZL, PRDM1, FSHR, EIF4ENIF1, NOBOX, and GATA4. Moreover, a microdeletion and microduplication in the CPEB1 and SYCE1 genes, respectively, were also identified in two distinct patients. The genetic analysis of eleven patients was classified as variants of uncertain clinical significance whereas this group of patients harbored at least two variants in different genes. Thirteen patients had benign or no rare variants, and therefore the genetic etiology remained unclear. In conclusion, next-generation sequencing (NGS) is a highly effective approach to identify the genetic diagnoses of heterogenous disorders, such as POI. A molecular etiology allowed us to improve the disease knowledge, guide decisions about prevention or treatment, and allow familial counseling avoiding future comorbidities.

A strategy to prevent bone loss diseases (i.e., osteoporosis) would be to enhance the increase of bone mass during childhood and adolescence. The purpose of this study was to compare bone mineral density (BMD) and bone mineral content (BMC) between female adolescent handball players and peers who did not play (control group), and to assess the changes in BMD and BMC after eight-months of competitive period. Fifty-eight female adolescents (12–17 years old) were allocated into two groups: handball players (HG: n = 27) and control group (CG: n = 31). BMC and BMD were measured using dual-energy X-ray absorptiometry, and z-scores were calculated. Sexual maturity, menarche, peak height velocity (PHV), sun exposure and calcium intake were assessed. At baseline, the handball players showed greater BMC and BMD than control group (p < 0.05). These differences between groups disappeared after adjusting for weight, BMI, menarche and lean soft tissue. After competitive period, significant time-effects for BMC and BMD of total TBLH and lumbar spine (p < 0.01) were observed in the handball players. HG increased BMC and BMD of total body and lumbar spine after eight-month. The Z-score analysis showed significant group effects with greater BMD of total body, lumbar spine, femur and hip than control group. The results showed that after eight-month competitive handball period, there was an increase in BMD of total body for handball players.

Objective: To develop Brazilian growth charts for body mass index (BMI-for-age) for individuals with Down syndrome (DS). The secondary objective was to compare the BMI-for-age with the Centers for Disease Control and Prevention standards (CDC). Methods: A retrospective and cross-sectional growth study of 706 youth with DS (56.7% males) was performed in 51 centers in São Paulo state, Brazil. Weight and height were used to calculate the BMI (kg/m2). The LMS method was applied to construct the growth charts. Z-scores were based on the CDC 2000 growth standards. Results: The BMI-for-age reference charts showed excellent goodness of fit statistics for boys and girls with DS aged 2–18 years. At 2 years of age, the mean BMI Z-scores of boys and girls with DS were lower compared to those of the CDC (Z-score = −0.2). In contrast, children with DS aged 3–18 years had higher mean Z-scores for BMI-for-age when compared to those of the CDC (Z-scores = +0.2 to +1.3). Conclusions: The BMI of Brazilian youth with DS differs from those references established by CDC. These are the first Brazilian BMI-for-age charts for individuals with DS and will hopefully guide clinicians and parents in the evaluation and management of the nutritional status in children and adolescents with DS in Brazil. Resumo: Objetivo: Desenvolver curvas específicas de Índice de Massa Corporal (IMC-para-idade) para população brasileira com síndrome de Down (SD). O objetivo secundário foi comparar os valores de IMC-para-idade com os valores normativos do Centro para o Controle de Doenças dos Estados Unidos (CDC). Métodos: Trata-se de estudo do tipo retrospectivo e transversal. A amostra foi constituída de 706 jovens com SD (56,7%, meninos) recrutados em 51 instituições no estado de São Paulo, Brasil. Peso e estatura foram obtidos e empregados para o cálculo de IMC (Kg/m2). O método LMS foi usado para a construção das curvas. Escores Z foram calculados com base na referência do CDC 2000. Resultados: As curvas de referência de IMC-para-idade para meninos e meninas com SD na faixa etária entre 2-18 anos apresentaram excelente ajuste estatístico. Aos dois anos de idade, o escore Z médio IMC de crianças com SD apresentou-se menor quando comparado ao CDC (escore Z = -0,2). Em contraste, os escores Z médios de IMC de jovens com SD foram superiores nas idades entre 3-18 anos (escores Z = +0,2 a +1,3). Conclusões: A população brasileira com SD apresentou diferentes padrões de IMC quando comparada às referências do CDC. As curvas desenvolvidas nesse estudo representam a primeira referência nacional de IMC-para-idade para jovens com SD. Espera-se, portanto, que essas curvas possam guiar pais e profissionais na avaliação do estado nutricional de crianças e adolescentes com SD no território brasileiro. Keywords: Trisomy 21, Body mass index, Weight, Height, Growth charts, Nutritional status, Palavras-chave: Trissomia 21, Índice de massa corporal, Peso, Estatura, Curvas de crescimento, Estado nutricional

Objective: To develop Brazilian growth charts for body mass index (BMI‐for‐age) for individuals with Down syndrome (DS). The secondary objective was to compare the BMI‐for‐age with the Centers for Disease Control and Prevention standards (CDC). Methods: A retrospective and cross‐sectional growth study of 706 youth with DS (56.7% males) was performed in 51 centers in São Paulo state, Brazil. Weight and height were used to calculate the BMI (kg/m2). The LMS method was applied to construct the growth charts. Z‐scores were based on the CDC 2000 growth standards. Results: The BMI‐for‐age reference charts showed excellent goodness of fit statistics for boys and girls with DS aged 2–18 years. At 2 years of age, the mean BMI Z‐scores of boys and girls with DS were lower compared to those of the CDC (Z‐score = −0.2). In contrast, children with DS aged 3‐18 years had higher mean Z‐scores for BMI‐for‐age when compared to those of the CDC (Z‐scores = +0.2 to +1.3). Conclusions: The BMI of Brazilian youth with DS differs from those references established by CDC. These are the first Brazilian BMI‐for‐age charts for individuals with DS and will hopefully guide clinicians and parents in the evaluation and management of the nutritional status in children and adolescents with DS in Brazil.

RESUMO Objetivo: Verificar a efetividade de intervenções educacionais baseadas na orientação sobre atividade física e nutrição em escolares. Fonte de dados: Foi realizada busca sistemática em quatro bancos e bases de dados eletrônicos, com artigos publicados entre outubro de 2007 e janeiro de 2017 que abordaram a realização de intervenções educacionais com ênfase em educação nutricional e atividade física ou exercício físico em escolares com idades entre 10 e 19 anos. Síntese dos dados: Foram selecionados 12 artigos para esta revisão. Desses estudos, quatro incluíram a intervenção educacional; quatro associaram intervenções educacionais à inclusão de alimentos saudáveis e atividade física; dois estudos relacionaram as orientações e a atividade física; e, por fim, dois ligaram as orientações com o consumo de alimentos saudáveis. Conclusões: As intervenções baseadas na orientação de atividade física e/ou nutrição foram eficientes, com resultados superiores nos estudos que associaram a prática de atividade física à orientação. Entretanto, observou-se a necessidade da realização de novos estudos que abordem as intervenções educacionais em escolares.

O objetivo do estudo foi realizar uma revisão sistemática sobre os programas de intervenção, com ações de atividades físicas e/ou educação nutricional, na redução de fatores de risco à saúde (sobrepeso/obesidade e alterações no perfil metabólico), em adolescentes escolares brasileiros. Foi realizada busca nas bases de dados eletrônicas Medline (PubMed), Lilacs, Embase, Scielo e Banco de Teses da Capes. Identificaram-se 1.568 estudos e 21 textos completos foram analisados, dos quais, cinco foram incluídos na revisão. A maioria dos estudos envolveu a prática de atividades físicas combinada à educação nutricional em diferentes regiões do país e todas as intervenções mostraram efeitos positivos na redução de fatores de risco à saúde. Conclui-se que todos os estudos nesta revisão demonstraram alterações positivas após as intervenções, mesmo que não significativas estatisticamente, reforçando a importância de programas de intervenção para a promoção de uma vida mais saudável e para reduzir os fatores de risco à saúde, em adolescentes.

OBJECTIVE: To assess body composition modifications in post-pubertal schoolchildren after practice of a physical activity program during one school year. METHODS: The sample consisted of 386 students aged between 15 and 17 years and divided into two groups: the study group (SG) comprised 195 students and the control group (CG), 191. The SG was submitted to a physical activity program and the CG attended conventional physical education classes. Body composition was assessed using body mass index (BMI), percentage of body fat (%BF), fat mass (FM), and lean mass (LM). RESULTS: A positive effect of the physical activity program on body composition in the SG (p < 0.001) was observed, as well as on the interaction time x group in all the variables analyzed in both genders. A reduction in %BF (mean of differences = -5.58%) and waist circumference (-2.33 cm), as well as an increase in LM (+2.05 kg) were observed in the SG for both genders, whereas the opposite was observed in the CG. CONCLUSION: The practice of programmed physical activity promotes significant reduction of body fat in post-pubertal schoolchildren.