Beyond the Drinking Water Directive: The use of reporter gene assays as an added tool for effect-based monitoring of polycyclic aromatic hydrocarbons and polychlorinated biphenyls in drinking water sources.

Polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) are legacy organic micropollutants (OMPs) that are sporadically detected in drinking water (DW) sources. The European Drinking Water Directive requires EU member states to monitor 5 PAHs in DW and its sources. The Dutch national regulations require 6 additional PAHs to be monitored and 7 polychlorinated biphenyls (PCBs). These indicator compounds act as representatives for large compound classes. PCBs alone comprise 209 congeners, it is evident that conventional chemical target analysis (GC-tQ-MS) alone is not sufficient to monitor these entire compound classes. This study investigated the application of reporter gene assays as effect-based methods (EBMs) to monitor PAHs and PCBs in DW sources. Herein, it was assessed what added value the bioassays can bring compared to the current approach of chemical target analysis for PCBs and PAHs. Regulated and non-regulated PAHs and PCBs were tested in four bioassays to determine the relative potency factors (RPFs) for these compounds. Non-regulated congeners were found to be active in the PAH-CALUX and anti-AR CALUX. An assessment of surface water (SW) spiked with standard mixtures containing PAHs and PCBs confirmed the predictable behavior of the PAH-CALUX. Moreover, the bioassay was able to detect AhR-mediated activity caused by non-regulated PAHs and PCBs, whereas this would have been missed by conventional chemical target analysis. Last, a field study was conducted in Dutch DW sources at six sampling moments. The PAH-CALUX detected AhR-mediated activity at all sampling moments and an ecological effect-based trigger (EBT) value was exceeded on multiple accounts. Combined application of GC-tQ-MS and the PAH-CALUX ensures compliancy with monitoring legislation and provides additional insights into potential hazards to humans and the environment.

The contribution of PFAS to thyroid hormone-displacing activity in Dutch waters: A comparison between two in vitro bioassays with chemical analysis.

Per- and polyfluoroalkyl substances (PFAS) are a group of xenobiotics that are widely distributed throughout the aquatic environment. Many PFAS are possible thyroid hormone (TH) system disrupting compounds, because they have the capacity to -amongst other- inhibit the TH thyroxine (T4) from binding to its transport protein transthyretin (TTR). This study investigated the occurrence of TH-displacing activity in the Dutch water cycle, and more specifically, the contribution of PFAS to this effect. Over one year of monitoring data of 29 PFAS (linear and branched) showed the continuous presence of PFAS in drinking waters and their surface water sources. Secondly, the FITC-T4 and TTR-TRß-CALUX bioassays were mutually compared using positive (HPLC-grade water spiked with PFOA) and negative control samples (HPLC-grade water), as well as relative potency factors (RPFs) of up to 20 PFAS congeners. Both assays were found to be suitable for measuring TH-displacing activity in water samples. As a third aim, a field study was performed in the Dutch water cycle that was comprised of samples from drinking water, surface water, PFAS contaminated sites, and 2 wastewater treatment plants. All samples were analyzed with 1. chemical analysis for 29 PFAS, 2. the FITC-T4 bioassay, and 3. the TTR-TRß-CALUX bioassay. The bioassays mutually showed good correlation (R2 0.85). Bioanalytical equivalent concentrations (BEQ) based on chemically-determined concentrations and RPFs (BEQchem) revealed that analyzed PFAS only explained ≤4.1 % of their activity in water extracts measured by both bioassays (BEQbio). This indicated that as yet unknown compounds contribute to the majority of the measured TH-displacing activity. Moreover, water treatment processes (e.g. DW production from SW) showed a larger contribution of target PFAS to the BEQbio. This could be a first lead to identify unknown compounds that contribute to this activity, and as such, enable the assessment of possible risks associated by the occurrence of TH-displacing activity in water.

Everything in excess is opposed to nature, even vitamin D: a case report.

SUMMARY: Vitamin D intoxication in children is rare but its incidence is increasing as vitamin D is supplemented more often and in higher doses. Children with cystic fibrosis (CF) are at risk for vitamin D intoxication due to incorrect compounded preparations of liposoluble vitamins. Here, we report a severe vitamin D intoxication in a 4-year-old girl with CF, due to an error in the compounded vitamin A, D, E, and K preparation, presenting clinically with weight loss, constipation, polydipsia, polyuria, and nycturia. The administered compounded preparation contained 10 000-fold the prescribed vitamin D dose. The patient was treated with hyperhydration, loop diuretics, and bisphosphonates. Serum calcium levels normalized after 4 days but serum 25-hydroxyvitamin D levels remained elevated even up to 2 months after treatment. LEARNING POINTS: Vitamin D intoxication should be ruled out when patients with cystic fibrosis (CF) present with acute polyuria, constipation, and weight loss. Prompt treatment is necessary to avert life-threatening complications. Regularly measuring serum calcium and 25-hydroxyvitamin D concentrations in children with CF receiving vitamin A, D, E, and K supplements is important during their follow-up.

[Psychiatric disorders in adults with Prader-Willi syndrome: a systematic literature review]. / Psychiatrische comorbiditeit bij volwassenen met prader-willisyndroom: systematisch literatuuroverzicht.

BACKGROUND: Prader-Willi syndrome (PWS) is a genetic syndrome characterized by dysmorphic features and endocrine, cognitive and psychiatric problems. Psychiatric problems interfere with the transition from pediatric to adult care. Psychiatric expertise is needed to facilitate this transition. AIM: To provide a literature review on the prevalence and clinical presentation of psychiatric disorders in adults with PWS. METHOD: A systematic literature review following the PRISMA-guidelines. RESULTS: Thirty-three articles were included. Most adults with PWS had a specific behavioral profile with disruptive, autistic and compulsive characteristics. Psychotic symptoms occured in one third of adults with PWS, mostly in patients with maternal uniparental disomy. Mood disorders were present in 10 to 20% of adults with PWS and often accompanied by psychotic features. Studies were limited and heterogeneous in samples and methods. CONCLUSION: There is a broad spectrum of psychiatric symptoms in adults with PWS. The clinical presentation does not fully fit within the DSM categories and shows differences between genetic subgroups. Longitudinal studies assessing the psychiatric symptoms with standardized methods are needed to improve practices on diagnosing, prevention, and treatment.

How to manage osteoporosis before the age of 50.

This narrative review discusses several aspects of the management of osteoporosis in patients under 50 years of age. Peak bone mass is genetically determined but can also be affected by lifestyle factors. Puberty constitutes a vulnerable period. Idiopathic osteoporosis is a rare, heterogeneous condition in young adults due in part to decreased osteoblast function and deficient bone acquisition. There are no evidence-based treatment recommendations. Drugs use can be proposed to elderly patients at very high risk. Diagnosis and management of osteoporosis in the young can be challenging, in particular in the absence of a manifest secondary cause. Young adults with low bone mineral density (BMD) do not necessarily have osteoporosis and it is important to avoid unnecessary treatment. A determination of BMD is recommended for premenopausal women who have had a fragility fracture or who have secondary causes of osteoporosis: secondary causes of excessive bone loss need to be excluded and treatment should be targeted. Adequate calcium, vitamin D, and a healthy lifestyle should be recommended. In the absence of fractures, conservative management is generally sufficient, but in rare cases, such as chemotherapy-induced osteoporosis, antiresorptive medication can be used. Osteoporosis in young men is most often of secondary origin and hypogonadism is a major cause; testosterone replacement therapy will improve BMD in these patients. Diabetes is characterized by major alterations in bone quality, implying that medical therapy should be started sooner than for other causes of osteoporosis. Primary hyperparathyroidism, hyperthyroidism, Cushing's syndrome and growth hormone deficiency or excess affect cortical bone more often than trabecular bone.

Metabolic Syndrome and Its Components in Young Adults Conceived by ICSI.

BACKGROUND: Intracytoplasmic sperm injection (ICSI) conception presents the early embryo with a radically different environment, which may lead to permanent alterations to key cardiometabolic processes. Blood pressure, indicators of insulin resistance, and lipid profiles have previously been studied in offspring born after in vitro fertilisation (IVF) and ICSI, with conflicting findings. Also, results in young adults born after ICSI are lacking. AIM: We investigated if young adult men and women conceived by ICSI more frequently have metabolic syndrome and its individual features in comparison to spontaneously conceived controls. DESIGN: Cardiometabolic and anthropometric parameters from 126 longitudinally followed young adults conceived by ICSI were compared to those of 133 controls. RESULTS: At age 18 years, only 1 of the participants displayed the metabolic syndrome (1 control woman). Mean concentrations of total cholesterol, triglycerides, insulin, HOMA-IR, and blood pressure were comparable between the ICSI conceived and control participants. A higher proportion (19.6%) of men conceived by ICSI had low (<40 mg/dl) HDL cholesterol compared to controls (5.6%). CONCLUSIONS: While men conceived by ICSI, but not women, had lower mean HDL cholesterol concentrations in comparison to controls, other markers of the metabolic syndrome were not affected by the mode of conception.

Adult Height after Growth Hormone Treatment at Pubertal Onset in Short Adolescents Born Small for Gestational Age: Results from a Belgian Registry-Based Study.

OBJECTIVES: Information on the efficacy of GH treatment in short SGA children starting their treatment in adolescence is limited. Therefore, adult height (AH), total height gain, and pubertal height gain were evaluated in short SGA children who started GH treatment at pubertal onset. PATIENT AND METHODS: Growth data of 47 short SGA adolescents (22 boys) who started GH treatment at pubertal onset (PUB group) were compared with results from 27 short SGA patients (11 boys) who started GH therapy at least 1 year before pubertal onset (PrePUB group). RESULTS: The PUB group achieved a mean (±SD) total height gain of 0.8 ± 0.7 SDS and an AH of -2.5 ± 0.7 SDS after 4.1 ± 1.1 years of GH treatment with a dosage of 41.8 ± 8.4 µg/kg/day. These results were comparable with those in the PrePUB group, which was treated for a longer duration (5.8 ± 2.1 years), resulting in a total height gain of 1.1 ± 0.7 SDS and an AH of -2.1 ± 1.0 SDS. Multiple regression analysis showed a significantly lower height gain in pubertal patients, females, and patients weighing less at start of GH treatment. An AH above -2 SDS and above the parent-specific lower limit of height was, respectively, reached in 28% and 70% of PUB and 44% and 67% of PrePUB patients (NS). AH SDS was positively correlated with the height SDS at start of GH. CONCLUSIONS: Short SGA adolescents starting GH therapy at an early pubertal stage have a modest and variable height gain. A normal AH can be expected in one third of the patients, especially in those with a smaller height deficit at onset of GH treatment.

Body fat content, fat distribution and adipocytokine production and their correlation with fertility markers in young adult men and women conceived by intracytoplasmic sperm injection (ICSI).

OBJECTIVE: Differences in body fat content during childhood and adolescence have been described in offspring conceived by in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI). However, data on body fat and its distribution as well as on adipocytokine production in young adults conceived by ICSI are nonexistent. We investigated if young adult men and women conceived by ICSI have a normal body fat patterning and adipocytokine production. DESIGN: Cohort study. PATIENTS: One hundred twenty-seven young adults conceived by ICSI and 138 peers born after spontaneous conception. MEASUREMENTS: Anthropometric parameters (skinfold thickness, hip and waist circumferences), dual X-ray absorptiometry (whole body and regional) measurements and adipocytokine levels (leptin and adiponectin) were analysed in relation to fertility markers (serum anti-Mullerian hormone (AMH) and inhibin B). RESULTS: While at age 18 years, a normal body fat distribution and normal leptin and adiponectin production was found in both male and female ICSI offspring, young men conceived by ICSI had a higher peripheral fat deposition in comparison with spontaneously conceived peers. No correlation between AMH and inhibin B with leptin or adiponectin was observed. CONCLUSION: While men conceived by ICSI, but not women, had a higher peripheral fat deposition, body fat distribution as well as mean levels of adipocytokines were not affected by the mode of conception.

Clinical presentation and outcome of children with central diabetes insipidus associated with a self-limited or transient pituitary stalk thickening, diagnosed as infundibuloneurohypophysitis.

OBJECTIVE: Despite lymphocytic or autoimmune infundibuloneurohypophysitis (INH) is an increasingly recognized aetiology in children with central diabetes insipidus (CDI); clinical data on epidemiology (clinical evolution, predisposing factors, complications), diagnosis and management of this entity are limited and mostly based on published case reports. The aim of this study was to gain a broader insight in the natural history of this disease by analysing the clinical presentation, radiological pituitary stalk changes, associated autoimmunity and hormonal deficiencies in children with CDI and a self-limiting or transient stalk thickening (ST), diagnosed as autoimmune infundibuloneurohypophysitis, during the last 15 years in four Belgian university hospitals. DESIGN AND PATIENTS: The medical files of nine CDI patients with a ST at initial presentation and no signs of Langerhans cell histiocytosis or germinoma at presentation and/or during follow-up of more than 1.5 years were reviewed. RESULTS: Age at presentation ranged from 3 to 14 years. Two patients had a positive family history of autoimmunity. Three children presented with associated growth failure, two with nausea and one with long-standing headache. Median maximal diameter of the stalk was 4.6 mm (2.7-10 mm). Four patients had extra-pituitary brain anomalies, such as cysts. One patient had central hypothyroidism, and another had a partial growth hormone deficiency at diagnosis. Within a mean follow-up of 5.4 (1.5-15) years, stalk thickening remained unchanged in two patients, regressed in one and normalized in six children. CDI remained in all, while additional pituitary hormone deficiencies developed in only one patient. CONCLUSIONS: In this series of children INH with CDI as initial presentation, CDI was permanent and infrequently associated with anterior pituitary hormone deficiencies, despite a frequent association with nonstalk cerebral lesions.

Gastric emptying of solids in children: reference values for the (13) C-octanoic acid breath test.

BACKGROUND: (99m) Technetium scintigraphy ((99m) TS) is the 'gold standard' for measuring gastric emptying (GE), but it is associated with a radiation exposure. For this reason, the (13) C-octanoic acid breath test ((13) C-OBT) was developed for measuring GE of solids. The objective of this study was to determine normal values for gastric half-emptying time (t1/2 GE) of solids in healthy children. METHODS: Gastric emptying of a standardized solid test meal consisting of a pancake evaluated with (99m) TS and (13) C-OBT was compared in 22 children aged between 1 and 15 years with upper gastrointestinal symptoms. Subsequently, the (13) C-OBT was used to determine normal values for GE of the same solid test meal in 120 healthy children aged between 1 and 17 years. KEY RESULTS: The results showed a significant correlation (r = 0.748, p = 0.0001) between t1/2 GE measured with both techniques in the group of children with upper gastrointestinal symptoms. In the group of healthy children, mean t1/2 GE was 157.7 ± 54.0 min (range 71-415 min), but t1/2 GE decreased with age between 1 and 10 years and remained stable afterward. There was no influence of gender, weight, height, body mass index, and body surface area on t1/2 GE. CONCLUSIONS & INFERENCES: Normal values for GE of solids measured with the (13) C-OBT using a standardized methodology were determined in healthy children. We propose to use this method and corresponding reference ranges to study GE of solids in children with gastrointestinal problems.

Evaluation of the hypothalamic-pituitary-adrenal axis and its relationship with central respiratory dysfunction in children with Prader-Willi syndrome.

BACKGROUND: Children with Prader-Willi Syndrome (PWS) have been considered at risk for central adrenal insufficiency (CAI). Hypothalamic dysregulation has been proposed as a common mechanism underlying both stress-induced CAI and central respiratory dysfunction during sleep. OBJECTIVE: To evaluate CAI and sleep-related breathing disorders in PWS children. PATIENTS AND METHODS: Retrospective study of cortisol response following either insulin tolerance test (ITT) or glucagon test (GT) in 20 PWS children, and comparison with 33 non- Growth Hormone deficient (GHD) controls. Correlation between sleep related breathing disorders and cortisol response in 11 PWS children who received both investigations. RESULTS: In PWS children, the cortisol peak value showed a significant, inverse correlation with age (Kendall's τ = -0.411; p = 0.012). A similar though non-significant correlation was present between cortisol increase and age (τ = -0.232; p = 0.16). Similar correlations were found in controls. In only 1 of 20 PWS children (5 %), ITT was suggestive of CAI. Four patients had an elevated central apnea index but they all exhibited a normal cortisol response. No relationship was found between peak cortisol or cortisol increase and central apnea index (respectively p = 0.94 and p = 0.14) or the other studied polysomnography (PSG) parameters. CONCLUSIONS: CAI assessed by ITT/GT is rare in PWS children. Our data do not support a link between CAI and central respiratory dysregulation.

Calcium and bone homeostasis in heterozygous carriers of CYP24A1 mutations: A cross-sectional study.

BACKGROUND: Bi-allelic CYP24A1 mutations can cause idiopathic infantile hypercalcemia (IIH), adult-onset nephrocalcinosis, and possibly bone metabolism disturbances. It is currently unclear if heterozygous carriers experience clinical problems or biochemical abnormalities. Our objective is to gain insight in the biochemical profile and health problems in CYP24A1 heterozygotes. STUDY DESIGN: Cross-sectional evaluation of participants. Data of previously reported carriers are reviewed. SETTING AND PARTICIPANTS: Outpatient clinic of a tertiary care hospital. Participants were eight family members of an infant with a well-characterized homozygous CYP24A1 mutation c.1186C>T p.(Arg396Trp). OUTCOMES: Serum vitamin D metabolites. Symptoms or biochemical signs of hypercalcemia, hypercalciuria or nephrocalcinosis. Bone health in heterozygous as compared to wild type (WT) subjects. MEASUREMENTS: Genotyping by Sanger sequencing; vitamin D metabolites by liquid chromatography tandem mass spectrometry; renal, calcium and bone markers by biochemical analyses; presence of nephrocalcinosis by renal ultrasound; bone health by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. RESULTS: Six participants were heterozygous carriers of the mutation. None of the heterozygous subjects had experienced IIH. One had a documented history of nephrolithiasis, two others had complaints compatible with this diagnosis. No major differences between WT and heterozygous subjects were found regarding bone health, serum or urinary calcium or 25OHD/24,25(OH)2D ratio. Literature reports on three out of 33 heterozygous cases suffering from IIH. In all three, the 25OHD/24,25(OH)2D ratio was highly elevated. Nephrocalcinosis was frequently reported in family members of IIH cases. LIMITATIONS: Small sample size, lack of a large control group. CONCLUSIONS: Our and literature data suggest that most heterozygous CYP24A1 mutation carriers have a normal 25OHD/24,25(OH)2D ratio, are usually asymptomatic and have a normal skeletal status but may possibly be at increased risk of nephrocalcinosis. A review of the available literature suggests that an elevated 25OHD/24,25(OH)2D ratio may be associated with symptoms of IHH, irrespective of carrier status.

Relation of adrenal-derived steroids with bone maturation, mineral density and geometry in healthy prepubertal and early pubertal boys.

BACKGROUND: Little is known about the effects of adrenal steroids on skeletal maturation and bone mass acquisition in healthy prepubertal boys. OBJECTIVE: To study whether adrenal-derived steroids within the physiological range are associated with skeletal maturation, areal and volumetric bone mineral density (aBMD and vBMD) and bone geometry in healthy prepubertal and early pubertal boys. METHODS: 98 healthy prepubertal and early pubertal boys (aged 6-14 y) were studied cross-sectionally. Androstenedione (A) and estrone (E1) were determined by liquid chromatography tandem mass spectrometry and DHEAS was determined by immunoassay. Whole body and lumbar spine aBMD and bone area were determined by dual-energy X-ray absorptiometry. Trabecular (distal site) and cortical (proximal site) vBMD and bone geometry were assessed at the non-dominant forearm and leg using peripheral QCT. Skeletal age was determined by X-ray of the left hand. RESULTS: Adrenal-derived steroids (DHEAS, A and E1) are positively associated with bone age in prepubertal and early pubertal children, independently of age. There are no associations between the adrenal-derived steroids and the studied parameters of bone size (lumbar spine and whole body bone area, trabecular or cortical area at the radius or tibia, periosteal circumference and cortical thickness at the radius or tibia) or BMD (aBMD or vBMD). CONCLUSION: In healthy prepubertal and early pubertal boys, serum adrenal-derived steroid levels, are associated with skeletal maturation, independently of age, but not with bone size or (v)BMD. Our data suggest that adrenal derived steroids are not implicated in the accretion of bone mass before puberty in boys.

Sex steroids in relation to sexual and skeletal maturation in obese male adolescents.

BACKGROUND: Childhood obesity is associated with an accelerated skeletal maturation. However, data concerning pubertal development and sex steroid levels in obese adolescents are scarce and contrasting. OBJECTIVES: To study sex steroids in relation to sexual and skeletal maturation and to serum prostate specific antigen (PSA), as a marker of androgen activity, in obese boys from early to late adolescence. METHODS: Ninety obese boys (aged 10-19 y) at the start of a residential obesity treatment program and 90 age-matched controls were studied cross-sectionally. Pubertal status was assessed according to the Tanner method. Skeletal age was determined by an x-ray of the left hand. Morning concentrations of total testosterone (TT) and estradiol (E2) were measured by liquid chromatography-tandem mass spectrometry, free T (FT) was measured by equilibrium dialysis, and LH, FSH, SHBG, and PSA were measured by immunoassays. RESULTS: Genital staging was comparable between the obese and nonobese groups, whereas skeletal bone advancement (mean, 1 y) was present in early and midadolescence in the obese males. Although both median SHBG and TT concentrations were significantly (P < .001) lower in obese subjects during mid and late puberty, median FT, LH, FSH, and PSA levels were comparable to those of controls. In contrast, serum E2 concentrations were significantly (P < .001) higher in the obese group at all pubertal stages. CONCLUSION: Obese boys have lower circulating SHBG and TT, but similar FT concentrations during mid and late puberty in parallel with a normal pubertal progression and serum PSA levels. Our data indicate that in obese boys, serum FT concentration is a better marker of androgen activity than TT. On the other hand, skeletal maturation and E2 were increased from the beginning of puberty, suggesting a significant contribution of hyperestrogenemia in the advancement of skeletal maturation in obese boys.

Validation of the Flemish version of the Quality of Life in Short Stature Youth (QoLISSY) questionnaire.

OBJECTIVES: The Quality of Life in Short Stature Youth (QoLISSY) questionnaire was recently developed in five European countries to assess health-related quality of life in children and adolescents with idiopathic short stature or growth hormone deficiency from child and parent perspectives. In addition to the existing French version, a Flemish version is needed for use of QoLISSY in the Flemish speaking part of Belgium. METHODS: Children (8-18 years) and their parents recruited from two Belgian paediatric endocrinology clinics completed the QoLISSY in a cross-sectional study. Cronbach's Alpha and test-retest reliability was assessed. Validity was examined by correlation with the generic KIDSCREEN questionnaire as well as by group comparisons according to diagnostic and treatment status. RESULTS: The QoLISSY scales had an acceptable internal consistency with Cronbach's Alpha ranging from 0·80 to 0·94 (child version) and from 0·77 to 0·92 (parent version). Test-retest reliability correlation coefficients ranged from r = 0·75 to 0·89 in the child version and from r = 0·58 to 0·85 in the parent version. Moderate correlations with the generic KIDSCREEN questionnaire suggested construct validity. Differences between child groups according to child age, underlying diagnosis, and degree of height deficit were found. Correlations with the European QoLISSY were significant for all scales. DISCUSSION: The Flemish QoLISSY instrument is a psychometrically sound, reliable, and valid short stature specific questionnaire measuring health-related quality of life. It is expected to be of great use in upcoming clinical research on growth disorders and growth hormone treatment in Belgium and Europe.

[Plantar pressure platform as clinical assesment tool in the analysis of foot posture with the foot posture index]. / Die Druckmessplattform als klinisch-diagnostisches Instrument zur Analyse der Fußstatik nach dem Foot Posture Index.

BACKGROUND: The foot posture index is a static measurement that splits up the foot posture into neutral, pronatus and supinatus. However, the relation between the foot posture and the plantar pressure standards is not well known. For this, the objective of this research is to check the relationship between the foot posture and plantar pressure standard. SUBJECTS AND MATERIAL: 144 participants (101 women and 43 men), mean age 25.4 ± 6.3 years, were measured for the FPI. The pedobarometric measurement was made with the plantar pressure platform, we measured total surface (cm2), mean pressure (kPa) and maximum pressure (kPa), these measurements were correlated with the FPI measurements. RESULTS: 288 feet were analysed with regard to the correlation between point 5 of FPI (medial arch height) and the plantar surface total area (p = 0.038): lower arch height and supinated foot are related to the maximum pressure points with p = 0.029. The total contact surface can be determined with the final score of the FPI, the scores of FPI 3, 5 and 6 FPI (r2 = 0.059, p < 0.001) with a 5.9 % prediction. CONCLUSION: The supinatus foot is correlated statistically significantly through the maximum pressure and the plantar surface with the pronatus foot.

Associations of sex steroids with bone maturation, bone mineral density, bone geometry, and body composition: a cross-sectional study in healthy male adolescents.

BACKGROUND: Although both testosterone (T) and estradiol (E2) are considered essential in the regulation of the male skeleton, there are few data concerning the relative contribution of T and E2 on bone mineral density (BMD), bone geometry, and bone maturation in healthy boys. OBJECTIVE: The objective of the study was to analyze the relationship between T and E2 and BMD, bone geometry, skeletal maturation, and body composition. METHODS: This is a cross-sectional study in 199 healthy boys (aged 6-19 y). T and E2 were determined by liquid chromatography tandem mass spectrometry. Whole-body and lumbar areal bone mineral density (aBMD) and bone area, lean mass, and fat mass were determined by dual-energy X-ray absorptiometry. Trabecular (distal site) and cortical (proximal site) volumetric BMD (vBMD) and bone geometry were assessed at the nondominant forearm and leg using peripheral quantitative computed tomography. Skeletal age was determined by an X-ray of the left hand. RESULTS: T was positively associated with lean mass (P < .001), lumbar and whole-body bone area (P < .001), trabecular and cortical area (P < .01), and periosteal circumference (P < .01) at the radius. E2 was positively associated with lumbar and whole-body aBMD (P < .001), trabecular vBMD at the radius and tibia (P < .01), and cortical thickness at the radius (P < .05). E2 was an independent negative predictor of the endosteal circumference (P < .01). Moreover, E2 was positively associated with bone age advancement (P < .001). CONCLUSION: Circulating E2 is positively associated with bone maturation and aBMD and vBMD and negatively with endosteal circumference in healthy boys, whereas T is a determinant of lean mass and bone size. These findings underscore the important role of E2 in skeletal development in boys.

Gender-specific alterations in salivary cortisol levels in pubertal intracytoplasmic sperm injection offspring.

BACKGROUND: There is accumulating evidence that in vitro conception in humans may be associated with adverse health outcomes later in life. It has been proposed that suboptimal early life conditions may 'program' key endocrine systems. A disturbance of the hypothalamic-pituitary-adrenal (HPA) axis leading to alterations in cortisol secretion in the offspring may be such a mechanism. To date, no data on cortisol levels in children conceived by intracytoplasmic sperm injection (ICSI) are available in the literature. METHODS: In this cross-sectional study, salivary cortisol known as a key regulator of metabolism was measured and results were compared between 201 pubertal ICSI children and 196 spontaneously conceived (SC) counterparts. RESULTS: ICSI females had lower mean salivary cortisol levels (9.0 µg/l; 95% CI 8.1-9.9) than SC females (10.6 µg/l; 95% CI 9.7-11.5; p = 0.01). This difference remained after adjusting for current characteristics, early life factors and maternal characteristics. In ICSI males, no difference in cortisol levels was found in comparison with the SC group. CONCLUSION: In our study, 14-year-old female but not male ICSI teenagers were found to have lower salivary cortisol concentrations in comparison with SC peers. However, before definite conclusions can be drawn, our results should be completed by longitudinal sampling.