Celiac Disease and Pediatric Type 1 Diabetes: Diagnostic and Treatment Dilemmas

Despite the advent of sensitive and specific serologic testing, routine screening for celiac disease (CD) in diabetic populations may not be universal practice, and many clinicians struggle to find the optimal approach to managing CD in pediatric Type 1 diabetes (T1D) patients. While some clinicians advocate screening for CD in all patients with T1D, others are unsure whether this is warranted. The diagnosis of patients who present with symptomatic CD, including malabsorption and obvious pathology upon biopsy, remains straightforward, with improvements noted on a gluten-free diet. Many patients identified by screening, however, tend to be asymptomatic. Evidence is inconclusive as to whether the benefits of screening and potentially treating asymptomatic individuals outweigh the harms of managing a population already burdened with a serious illness. This review focuses on current knowledge of CD in children and youth with T1D, highlighting important elements of the disease's pathophysiology, epidemiology, clinical presentation, and diagnostic challenges

Impact of X/Y genes and sex hormones on mouse neuroanatomy

Biological sex influences brain anatomy across many species. Sex differences in brain anatomy have classically been attributed to differences in sex chromosome complement (XX versus XY) and/or in levels of gonadal sex steroids released from ovaries and testes. Using the four core genotype (4CG) mouse model in which gonadal sex and sex chromosome complement are decoupled, we previously found that sex hormones and chromosomes influence the volume of distinct brain regions. However, recent studies suggest there may be more complex interactions between hormones and chromosomes, and that circulating steroids can compensate for and/or mask underlying chromosomal effects. Moreover, the impact of pre vs post-pubertal sex hormone exposure on this sex hormone/sex chromosome interplay is not well understood. Thus, we used whole brain high-resolution ex-vivo MRI of intact and pre-pubertally gonadectomized 4CG mice to investigate two questions: 1) Do circulating steroids mask sex differences in brain anatomy driven by sex chromosome complement? And 2) What is the contribution of pre- versus post-pubertal hormones to sex-hormone-dependent differences in brain anatomy? We found evidence of both cooperative and compensatory interactions between sex chromosomes and sex hormones in several brain regions, but the interaction effects were of low magnitude. Additionally, most brain regions affected by sex hormones were sensitive to both pre- and post-pubertal hormones. This data provides further insight into the biological origins of sex differences in brain anatomy

Obesity is positively associated with dehydroepiandrosterone sulfate concentrations at 7 y in Chilean children of normal birth weight.

BACKGROUND: In low-birth-weight girls, obesity increases the risk of premature adrenarche and metabolic complications. However, the consistency of this association in normal-birth-weight children and its potential mediators remain unknown. OBJECTIVES: The objectives were to assess the associations between obesity indicators and dehydroepiandrosterone sulfate (DHEAS) at 7 y of age and to evaluate the role of hormonal markers on these associations. DESIGN: We assessed in 969 participants (6.9 y; 48% girls; all Tanner I) in the Growth and Obesity Chilean Cohort Study the associations between DHEAS and weight, BMI, waist circumference (WC), waist-to-height ratio, skinfold thickness, and percentage total fat (bioimpedance) and determined whether these associations were related to insulin, insulin-like growth factor I (IGF-I), and leptin. We also compared BMI and height growth from 0 to 7 y of age in nonobese and obese children with normal and high DHEAS (≥75th percentile) at 7 y. RESULTS: DHEAS concentrations were similar between girls (30.3 ±1.86 μg/dL) and boys (29.4 ±1.73 μg/dL) (P > 0.05); 17.3% of children were obese (BMI-for-age z score ≥2 SD). Adiposity indicators were positively and similarly associated with DHEAS [ie, BMI, β standardized regression coefficient: 0.23 (95% CI: 0.17, 0.29); WC, β standardized regression coefficient: 0.23 (95% CI: 0.16, 0.30)]; these associations were only partially related to IGF-I and leptin. Obese children had twice the risk of high DHEAS (OR: 2.16; 95% CI: 1.51, 3.09); at 7 y, obese children with high DHEAS were fatter and more centrally obese than their counterparts (P 0.05). None of the results differed by sex (P > 0.05). CONCLUSION: In children of normal birth weight, obesity is positively associated with DHEAS at 7 y of age

The Familial Clustering of Age at Menarche in Extended Twin Families

The timing of puberty is complex, possibly involving many genetic factors that may interact with environmental influences. Familial resemblance for age at menarche was studied in a sample of 4,995 female twins, 1,296 sisters, 2,946 mothers and 635 female spouses of male twins. They had indicated their age at menarche as part of a larger longitudinal survey. We assessed assortative mating for age at menarche, gene–environment interaction effects and estimated the heritability of individual differences in pubertal timing. There was significant evidence of gene–environment interaction, accounting for 1.5% of the variance. There was no indication of consistent mate assortment on age at menarche. Individual differences in age at menarche are highly heritable, with additive genetic factors explaining at least 70% of the true variation. An additional 1.5% of the variation can be explained by a genotype–environment interaction effect where environmental factors are more important in individuals genetically predisposed for late menarche

Журнал отмечает свое десятилетие. Ученые - современники о журнале

Item does not contain fulltextBACKGROUND: Growth hormone (GH) treatment is effective in improving adult height (AH) in short children born SGA. However, there is a wide variation in height gain, even after adjustment for predictive variables. It is therefore important to investigate new factors which can influence the response to GH. OBJECTIVE: To investigate the efficacy of GH treatment (1 mg/m(2/) day) in short SGA children on AH. To assess the relation between spontaneous catch-up growth after birth and growth during puberty on the total height gain SDS to AH. PATIENTS: Longitudinal GH trial in 170 children. RESULTS: Median age at start of GH was 7.1 years and height -3.0 SDS. AH was -1.8 SDS (TH-corrected AH -1.1 SDS) in boys and -1.9 SDS (TH-corrected AH -1.3 SDS) in girls. Spontaneous catch-up growth after birth was >/=0.5 SDS in 42% of children. In contrast to expectation, spontaneous catch-up growth was negatively correlated with total height gain SDS during GH (P = 0.009). During puberty, height SDS declined (-0.4 SDS in boys and -0.5 SDS in girls) resulting in a lower total height gain SDS than expected. Pubertal height gain was 25.5 cm in boys and 15.3 cm in girls, significantly lower compared to AGA children (P < 0.001). At onset of puberty, BA for boys and girls was moderately advanced (P = 0.02 and P < 0.001, respectively). Growth velocity was comparable to AGA children during the first two years of puberty, but thereafter significantly lower until reaching AH (P < 0.001). CONCLUSION: In contrast to our hypothesis, children with greater spontaneous catch-up growth after birth show a lower total height gain SDS during GH. Height SDS declines from mid-puberty, due to a marked early deceleration of growth velocity

Effects of Gonadotropin-Releasing Hormone Agonist Therapy on Body Mass Index and Height in Girls with Central Precocious Puberty

Treatment with gonadotropin-releasing hormone (GnRH) agonist is the treatment of choice for central precocious puberty (CPP). Many of the previous studies concerning the auxological effects of treatment with GnRH agonist in CPP have focused on final height. Much less attention has been paid to changes in body weight. However, concerns have been expressed that CPP may be associated with increased body mass index (BMI) both at initial presentation and during GnRH agonist treatment. We retrospectively reviewed the height and BMI of 38 girls with CPP. All patients were treated with GnRH agonist over 18 months. The height standard deviation score (SDS) for chronological age was significantly decreased during GnRH agonist treatment, whereas the height SDS for bone age was significantly increased. The predicted adult height was increased from 157.78±6.45 cm before treatment to 161.41±8.97 cm at 12 months after treatment. The BMI SDS for chronological age was significantly increased during treatment. The BMI SDS of normal-weight girls increased more than did the BMI SDS of overweight girls, but the increase was not significant. Preventive measures, such as increased physical activity, can be introduced to minimize possible alterations in body weight, and a long-term follow-up study is required to elucidate whether GnRH agonist treatment in Korean girls with CPP affects adult obesity

Evo-devo of human adolescence: beyond disease models of early puberty

Despite substantial heritability in pubertal development, much variation remains to be explained, leaving room for the influence of environmental factors to adjust its phenotypic trajectory in the service of fitness goals. Utilizing evolutionary development biology (evo-devo), we examine adolescence as an evolutionary life-history stage in its developmental context. We show that the transition from the preceding stage of juvenility entails adaptive plasticity in response to energy resources, other environmental cues, social needs of adolescence and maturation toward youth and adulthood. Using the evolutionary theory of socialization, we show that familial psychosocial stress fosters a fast life history and reproductive strategy rather than early maturation being just a risk factor for aggression and delinquency. Here we explore implications of an evolutionary-developmental-endocrinological-anthropological framework for theory building, while illuminating new directions for research

Individual differences in puberty onset in girls: Bayesian estimation of heritabilities and genetic correlations

We report heritabilities for individual differences in female pubertal development at the age of 12. Tanner data on breast and pubic hair development in girls and data on menarche were obtained from a total of 184 pairs of monozygotic and dizygotic twins. Genetic correlations were estimated to determine to what extent the same genes are involved in different aspects of physical development in puberty. A Bayesian estimation approach was taken, using Markovchain Monte Carlo simulation to estimate model parameters. All three phenotypes were to a significant extent heritable and showed high genetic correlations, suggesting that a common set of genes is involved in the timing of puberty in general. However, gonadarche (menarche and breast development) and adrenarche (pubic hair) are affected by different environmental factors, which does not support the three phenotypes to be regarded as indicators of a unitary physiological factor. © 2006 Springer Science+Business Media, Inc

Antibiotic Resistant Bloodstream Infections in Pediatric Patients Receiving Chemotherapy or Hematopoietic Stem Cell Transplant: Factors Associated with Development of Resistance, Intensive Care Admission and Mortality

Bloodstream infections (BSI) are a severe complication of antineoplastic chemotherapy or hematopoietic stem cell transplantation (HSCT), especially in the presence of antibiotic resistance (AR). A multinational, multicenter retrospective study in patients aged ≤ 18 years, treated with chemotherapy or HSCT from 2015 to 2017 was implemented to analyze AR among non-common skin commensals BSI. Risk factors associated with AR, intensive care unit (ICU) admission and mortality were analyzed by multilevel mixed effects or standard logistic regressions. A total of 1291 BSIs with 1379 strains were reported in 1031 patients. Among Gram-negatives more than 20% were resistant to ceftazidime, cefepime, piperacillin-tazobactam and ciprofloxacin while 9% was resistant to meropenem. Methicillin-resistance was observed in 17% of S. aureus and vancomycin resistance in 40% of E. faecium. Previous exposure to antibiotics, especially to carbapenems, was significantly associated with resistant Gram-negative BSI while previous colonization with methicillin-resistant S. aureus was associated with BSI due to this pathogen. Hematological malignancies, neutropenia and Gram-negatives resistant to >3 antibiotics were significantly associated with higher risk of ICU admission. Underlying disease in relapse/progression, previous exposure to antibiotics, and need of ICU admission were significantly associated with mortality. Center-level variation showed a greater impact on AR, while patient-level variation had more effect on ICU admission and mortality. Previous exposure to antibiotics or colonization by resistant pathogens can be the cause of AR BSI. Resistant Gram-negatives are significantly associated with ICU admission and mortality, with a significant role for the treating center too. The significant evidence of center-level variations on AR, ICU admission and mortality, stress the need for careful local antibiotic stewardship and infection control programs