Background/Objectives: This study investigates determinants of sleep duration and its impact on nutritional status, resting energy expenditure (REE), cardiometabolic risk factors and hormones in children/adolescents. Subjects/Methods: In 207 girls and 207 boys (13.0±3.4 (6.1-19.9) years) body mass index standard deviation score (BMI SDS), waist circumference (WC) z-score, body composition (air-displacement plethysmography), REE (ventilated hood system; n ¼ 312) and cardiometabolic risk factors/hormones (n ¼ 250) were assessed. Greater than 90th percentile of BMI/WC references was defined as overweight/overwaist. Sleep duration, media consumption (TV watching/computer use), physical activity, dietary habits, parental BMI, socio-economic status and early infancy were assessed by questionnaire. Short sleep was defined as o10 h per day for children o10 years and otherwise o9 h per day. Results: Total 15.9% participants were overweight, mean sleep duration was 8.9±1.3 h per day. Age explained most variance in sleep (girls: 57.0%; boys: 41.2%) besides a high nutrition quality score (girls: 0.9%) and a low media consumption (boys: 1.3%). Sleep was inversely associated with BMI SDS/WC z-score (girls: r ¼ À0.17/À0.19, Po0.05; boys: r ¼ À0.21/À0.20, Po0.01), which was strengthened after adjusting for confounders. Short vs long sleep was associated with 5.5-/2.3-fold higher risks for obesity/overwaist (girls). After adjusting for age, REE (adjusted for fat-free mass) was positively associated with sleep in boys (r ¼ 0.16, Po0.05). Independently of age and WC z-score, short sleep was associated with lower adiponectin levels in boys (11.7 vs 14.4 mg/ml, Po0.05); leptin levels were inversely related to sleep in girls (r ¼ À0.23, Po0.05). Homoeostasis model assessment-insulin resistance (r ¼ À0.20, Po0.05) and insulin levels (r ¼ À0.20, Po0.05) were associated with sleep (girls), which depended on WC z-score. Conclusions: Age mostly determined sleep. Short sleep was related to a higher BMI SDS/WC z-score (girls/boys), a lower REE (boys), higher leptin (girls) and lower adiponectin levels (boys).

The serum detection of S100B, a new melanoma marker, has shown clinical significance in early studies. The aim of our study of 1,339 serum samples from 412 different melanoma patients and 107 control patients was to prove the prognostic value of serum S100B levels in melanoma patients at different stages of disease and at follow-up (median: 30 months). Using a cutoff level of 0.2 μg/l S100B, 5 of 286 patients (1.7%) with primary tumors (stage I/II), 14/73 (19.2%) patients with locoregional metastasis (stage III) and 57/84 (67.9%) patients with advanced disease (stage IV) were S100B positive (statistically significant differences for stage I/II vs. III, I/II vs. IV, and III vs. IV, p < 0.001). The estimated overall survival time was significantly longer (p < 0.001) for patients with S100B values below 0.2 μg/l compared to patients with elevated S100B levels (≥0.2 μg/l), which was independent of the stage of disease (I–IV). Regarding prognosis, we were furthermore able to distinguish different subgroups among stage III and IV patients using S100B serum levels (p < 0.01). Patients with different cutaneous non-melanoma diseases served as S100B-negative controls. S100B serum evaluations using the Sangtec^®100 IRMA are highly specific and sensitive for the detection of metastatic melanoma. S100B has been shown to be a relevant prognostic factor for survival in a study with a large sample size of melanoma patients including close follow-up evaluations.

Persistent hyperinsulinemic hypoglycemia (PHH) in adults that is not caused by an insulinoma is a rare and not well-characterized disease that has been named nesidioblastosis. In this study, we defined and scrutinized criteria for its histologic diagnosis, assessed its relative incidence, and discussed its pathogenesis. In pancreatic specimens from 15 adult patients with PHH in whom no insulinoma was detected and in 18 adult control patients, the endocrine tissue was screened for islet and beta-cell changes. The diagnostic reliability of the findings was checked by an interobserver analysis. The relative frequency of the disease was assessed in a series of 232 patients with PHH. Finally, genetic analysis of the menin gene was performed. Among the various indicators of islet changes, beta-cell hypertrophy characterized by enlarged and hyperchromatic beta-cell nuclei was the most significant and diagnostic finding in patients with PHH. The interobserver analysis revealed 100% specificity and 87.7% sensitivity. The hyperfunctional state of the beta-cells was not associated with changes in the subcellular distribution of insulin and proinsulin, proliferative activity, or mutations of the menin gene. Our results indicate that diffuse nesidioblastosis in adult patients with PHH resembles that seen in neonates suffering from PHH. The most important criterion for the diagnosis is the beta-cell hypertrophy. As approximately 4% of adult patients with PHH are affected by diffuse nesidioblastosis, this disease is not as rare as it has been thought to be. Pathogenetically, the defective insulin secretion could be based on a molecular defect.

In the immunohistology of malignant melanoma the use of polyclonal antibodies against protein S100 is well established. Recently, it was shown that S100B, a subunit of the S100 protein family, is detectable in the serum of melanoma patients and correlates with the stage of the disease in patients with metastatic melanoma. In the present study, the first evaluation of a large number of treatment observations (n = 77) in 64 different patients during chemotherapy and/or immunotherapy for advanced metastatic melanoma (stage IV) is presented. All patients received treatment according to standardized protocols comprising 8 weeks of treatment followed by routine staging procedures to evaluate therapeutic outcome. In 13 patients with tumour enlargement after first-line therapy, a second-line treatment was subsequently given. S100B immunoradiometric assay (IRMA) tests were performed before, during and after treatment at scheduled time points. In the interim analysis at 4 weeks 29 of 37 (78%) patients with tumour progression during treatment showed a raised S100B level. In the final analysis at 8 weeks, 31 of these 37 patients (84%) demonstrated rising S100B values (P < 0.001). Patients who responded to treatment (stable or regressing metastatic disease) showed constant or declining S100B levels in 38 of 40 patients (95%) at the interim analysis, at 8 weeks this was further increased to 39 of 40 patients (98%; P < 0.001). Thus, the use of S100B for monitoring treatment is adequate in the majority of cases. Our observations are of great interest for therapeutic trials of adjuvant and palliative therapies as the rise of S100B levels might indicate that re-staging and/or changes in therapy strategies should be chosen.

Nitrogen-bisphosphonates (n-BP), often referred to as aminobisphosphonates, are the most commonly prescribed drugs for the treatment of disorders of bone fragility. However, long-term continuous treatment predisposes certain individuals to serious rare side effects, such as bisphosphonate-associated osteonecrosis of the jaw (BAONJ). n-BP use is known to unintentionally activate a subset of innate T cells called Vg9Vd2 T cells, but the consequence of this chronic immune stimulation has remained unexplored. The primary objectives of this study were to 1) determine the fate of Vg9Vd2 T cells in osteoporotic patients on n-BP therapy as a function of time and type of therapy; 2) evaluate the proportion of Vg9Vd2 T cells in patients who had recently experienced n-BP-associated ONJ. We found there is a notable loss of Vg9Vd2 T cells over time in osteoporotic patients on n-BP therapy, particularly those on intravenous (iv) therapy (Spearman r ¼ À0.55, p < 0.0001 iv; r ¼ À0.3, p < 0.03 oral) (n ¼ 68); no difference was observed in total T cells, monocytes, or granulocytes. Importantly, the observed negative effect on Vg9Vd2 T cells coincides with the reported route of administration and timing of the rare occurrence of BAONJ. Patients (n ¼ 6) who had experienced BAONJ were all found to be significantly deficient in Vg9Vd2 T cells (median ¼ 0.07%) in comparison to age-and sex-matched treatment-naïve controls (N ¼ 11; median ¼ 2.40%), U ¼ 0, p ¼ 0.001; this was the only consistent difference in the leukocytes assessed. All BAONJ cases had an underlying condition that further contributed to impaired immunity. We propose Vg9Vd2 T cells show a strong potential to serve as harbingers of possible adverse immune effects of n-BP therapy, particularly in those patients already having a compromised immune system as they may be most vulnerable to the development of conditions such as BAONJ. ß