Deletion in the uridine diphosphate glucuronyltransferase 2B17 gene is associated with delayed pubarche in healthy boys

Objective: Only a few genetic loci are known to be associated with male pubertal events. The ability of excreting testosterone (T) and other steroids in the urine depends on sulfation and glucuronidation. One of several essential glucuronidases is encoded by the UGT2B17 gene. In a preliminary report, we found that homozygous deletion of UGT2B17 in boys was associated with lower urinary excretion of T. We hypothesized that boys with a lower glucuronidation capacity may have altered androgen action and excretion affecting pubarche, as this represents a T-dependent event. Design, participants and measures: 668 healthy boys (cross-sectional) aged 6.1–21.9 years (COPENHAGEN puberty study conducted from 2005 to 2006) were included. 65 of the boys where followed longitudinally every 6 months. Participants were genotyped for UGT2B17 copy number variation (CNV). Clinical pubertal staging including orchidometry, anthropometry and serum reproductive hormone levels. Results: 59 of the 668 boys (8.8%) presented with a homozygous deletion of UGT2B17 (del/del). These boys experienced pubarche at a mean age of 12.73 years (12.00–13.46) vs 12.40 years (12.11–12.68) in boys heterozygous for deletion of UGT2B17 (del/ins) vs 12.06 years (11.79–12.33) in boys with the wild-type genotype (ins/ins) (P = 0.029, corrected for BMI z-score). The effect accounted for 0.34 years delay per allele (95% CI: 0.03–0.64). A comparable trend was observed for onset of testicular enlargement >3 mL but did not reach significance. Conclusion: CNV of UGT2B17 is a factor contributing to the timing of male pubarche

Cell-based therapy for the treatment of female stress urinary incontinence:an early cost–effectiveness analysis

Aim: To perform an early cost–effectiveness analysis of in vitro expanded myoblasts (IVM) and minced myofibers versus midurethral slings (MUS) for surgical treatment of female stress urinary incontinence. Methods: Cost–effectiveness and sensitivity analyses were performed using a decision tree comprising previously published data and expert opinions. Results &amp; conclusion: In the base case scenario, MUS was the cost-effective strategy with a negative incremental cost–effectiveness ratio compared with IVM and a positive incremental cost–effectiveness ratio compared with minced myofibers. However, the sensitivity analysis indicates that IVM may become an alternative providing greater effect at a higher cost. With the possibility of becoming more effective, IVM treatment would be advantageous over MUS given its reduced invasiveness and lower risks of complications. </jats:p

Municipal Support of Diabetes Management in Daycare, Kindergarten and School: A Qualitative Study of Differences, Challenges and Potentials

Diabetes care during institutional hours is a major challenge affecting the whole family. The aim of this study was to highlight challenges and potentials regarding municipal support in relation to diabetes care of children in school, kindergarten, and daycare. The dataset consists of 80 semi-structured online interviews with 121 municipal employees from 74 (of 98) municipalities in Denmark. Data were analysed using qualitative content analysis. The analysis produced four main themes: (1) Institutional staff initially feel insecure about diabetes care responsibilities, (2) There is a high degree of parental involvement and responsibilities during institutional hours, (3) The roles of health employees vary, and (4) Fluctuating allocation of special needs assistants (SNAs) creates challenges. The findings of this nationwide qualitative study show that, even though Denmark guarantees, by law, the child’s right to support in diabetes self-care in school and childcare institutions, diabetes management in Denmark still needs to be improved, with a view to ensuring equal support for all children with diabetes

Serum levels of insulin-like factor 3, anti-Müllerian hormone, inhibin B, and testosterone during pubertal transition in healthy boys: a longitudinal pilot study

Insulin-like factor 3 (INSL3) is a promising marker of Leydig cell function with potentially high clinical relevance. Limited data of INSL3 levels in relation to other reproductive hormones in healthy pubertal boys exist. In this study, we aimed to evaluate longitudinal serum changes in INSL3 compared with LH, FSH, testosterone, inhibin B, and anti-Müllerian hormone (AMH) during puberty in healthy boys. Ten boys were included from the longitudinal part of the COPENHAGEN Puberty Study. Pubertal evaluation, including testicular volume, was performed and blood samples were drawn every 6 months for 5 years. Serum concentrations of testosterone were determined by a newly developed LC–MS/MS method, and serum concentrations of INSL3, AMH, inhibin B, FSH, and LH respectively were determined by validated immunoassays. The results showed that serum INSL3 levels increased progressively with increasing age, pubertal onset, and testicular volume. In six of the ten boys, LH increased before the first observed increase in INSL3. In the remaining four boys, the increase in LH and INSL3 was observed at the same examination. The increases in serum concentrations of LH, testosterone, and INSL3 were not parallel or in ordered succession and varied interindividually. We demonstrated that INSL3 concentrations were tightly associated with pubertal onset and increasing testicular volume. However, the pubertal increases in LH, INSL3, and testosterone concentrations were not entirely parallel, suggesting that INSL3 and testosterone may be regulated differently. Thus, we speculate that INSL3 provides additional information on Leydig cell differentiation and function during puberty compared with traditional markers of testicular function

Pathological and Incidental Findings on Brain MRI in a Single-Center Study of 229 Consecutive Girls with Early or Precocious Puberty

Central precocious puberty may result from organic brain lesions, but is most frequently of idiopathic origin. Clinical or biochemical factors which could predict a pathological brain MRI in girls with CPP have been searched for. With the recent decline in age at pubertal onset among US and European girls, it has been suggested that only girls with CPP below 6 years of age should have brain MRI performed