Ancient Greek for Kids: From Theory to Praxis

This essay presents the methods, as well as the pedagogical effects, findings and results of introducing Ancient Greek in the curriculum of children between three and 12 years old as evidenced over 27 years in the method of Elliniki Agogi. Elliniki Agogi is an award-winning private educational institute established in Greece in the mid-1990s at a time when the teaching of Ancient Greek was questioned and dramatically reduced from the public curriculum. Its aim is to safeguard learning that has its roots in Ancient Greek and to continue to introduce students to the Greek civilisation and its language, using effective, entertaining and artistic methods. This endeavour was based on specific pedagogical models; by learning through experience and through a communication-orientated educational process. With concomitant, cautious organisation and preparation of each lesson a diversified educational curriculum is created that connects the students to their distant past while experiencing positive emotions, filled with ethical paradigms that contribute later to master a fully-shaped personality. 27 years later, studies have come to prove the positive influence of learning Ancient Greek in children's linguistic and mental abilities. The following study conducted is distinctive in the detailed pedagogical method it provides and validates the importance of teaching the Ancient Greek language to children as early as possible

Efficacy and treatment costs of Zoledronate versus Pamidronate in Paediatric Osteoporosis

Intravenous pamidronate has been used in the treatment of osteogenesis imperfecta (OI) in children for over 20 years. The more potent zoledronate is an attractive alternative as it is administered less frequently. This study compares the clinical efficacy of intravenous pamidronate (1.5 mg/kg/day over 2 days, every 3 months) versus zoledronate (0.05 mg/kg/dose every 6 months) in 40 children (20 per group) with mild to moderate OI and the treatment costs of the two drugs in a tertiary centre for children with osteoporosis. Lumbar spine bone mineral density and fracture rate did not differ between drug groups following 1 and 2 years of treatment, respectively. Total cost per treatment course per patient was £1157 for pamidronate and £498 for zoledronate. Therefore, zoledronate is a considerably cheaper alternative to pamidronate with comparable efficacy, resulting in substantial annual savings for healthcare providers and a more convenient option for patients due to fewer hospital visits.</jats:p

Key features of puberty onset and progression can help distinguish self-limited delayed puberty from congenital hypogonadotrophic hypogonadism

Introduction: Delayed puberty (DP) is a frequent concern for adolescents. The most common underlying aetiology is self-limited DP (SLDP). However, this can be difficult to differentiate from the more severe condition congenital hypogonadotrophic hypogonadism (HH), especially on first presentation of an adolescent patient with DP. This study sought to elucidate phenotypic differences between the two diagnoses, in order to optimise patient management and pubertal development. Methods: This was a study of a UK DP cohort managed 2015-2023, identified through the NIHR clinical research network. Patients were followed longitudinally until adulthood, with a definite diagnosis made: SLDP if they had spontaneously completed puberty by age 18 years; HH if they had not commenced (complete, cHH), or had commenced but not completed puberty (partial, pHH), by this stage. Phenotypic data pertaining to auxology, Tanner staging, biochemistry, bone age and hormonal treatment at presentation and during puberty were retrospectively analysed. Results: 78 patients were included. 52 (66.7%) patients had SLDP and 26 (33.3%) patients had HH, comprising 17 (65.4%) pHH and 9 (34.6%) cHH patients. Probands were predominantly male (90.4%). Male SLDP patients presented with significantly lower height and weight standard deviation scores than HH patients (height p=0.004, weight p=0.021). 15.4% of SLDP compared to 38.5% of HH patients had classical associated features of HH (micropenis, cryptorchidism, anosmia, etc. p=0.023). 73.1% of patients with SLDP and 43.3% with HH had a family history of DP (p=0.007). Mean first recorded luteinizing hormone (LH) and inhibin B were lower in male patients with HH, particularly in cHH patients, but not discriminatory. There were no significant differences identified in blood concentrations of FSH, testosterone or AMH at presentation, or in bone age delay. Discussion: Key clinical markers of auxology, associated signs including micropenis, and serum inhibin B may help distinguish between SLDP and HH in patients presenting with pubertal delay, and can be incorporated into clinical assessment to improve diagnostic accuracy for adolescents. However, the distinction between HH, particularly partial HH, and SLDP remains problematic. Further research into an integrated framework or scoring system would be useful in aiding clinician decision-making and optimization of treatment.  

Key features of puberty onset and progression can help distinguish self-limited delayed puberty from congenital hypogonadotrophic hypogonadism

IntroductionDelayed puberty (DP) is a frequent concern for adolescents. The most common underlying aetiology is self-limited DP (SLDP). However, this can be difficult to differentiate from the more severe condition congenital hypogonadotrophic hypogonadism (HH), especially on first presentation of an adolescent patient with DP. This study sought to elucidate phenotypic differences between the two diagnoses, in order to optimise patient management and pubertal development.MethodsThis was a study of a UK DP cohort managed 2015-2023, identified through the NIHR clinical research network. Patients were followed longitudinally until adulthood, with a definite diagnosis made: SLDP if they had spontaneously completed puberty by age 18 years; HH if they had not commenced (complete, cHH), or had commenced but not completed puberty (partial, pHH), by this stage. Phenotypic data pertaining to auxology, Tanner staging, biochemistry, bone age and hormonal treatment at presentation and during puberty were retrospectively analysed.Results78 patients were included. 52 (66.7%) patients had SLDP and 26 (33.3%) patients had HH, comprising 17 (65.4%) pHH and 9 (34.6%) cHH patients. Probands were predominantly male (90.4%). Male SLDP patients presented with significantly lower height and weight standard deviation scores than HH patients (height p=0.004, weight p=0.021). 15.4% of SLDP compared to 38.5% of HH patients had classical associated features of HH (micropenis, cryptorchidism, anosmia, etc. p=0.023). 73.1% of patients with SLDP and 43.3% with HH had a family history of DP (p=0.007). Mean first recorded luteinizing hormone (LH) and inhibin B were lower in male patients with HH, particularly in cHH patients, but not discriminatory. There were no significant differences identified in blood concentrations of FSH, testosterone or AMH at presentation, or in bone age delay.DiscussionKey clinical markers of auxology, associated signs including micropenis, and serum inhibin B may help distinguish between SLDP and HH in patients presenting with pubertal delay, and can be incorporated into clinical assessment to improve diagnostic accuracy for adolescents. However, the distinction between HH, particularly partial HH, and SLDP remains problematic. Further research into an integrated framework or scoring system would be useful in aiding clinician decision-making and optimization of treatment.

Study of the occurrence of the metabolic syndrome and other endocrine disorders in children born after in vitro fertilization (IVF)

Objective: To investigate the occurrence of the metabolic profile and other endocrine disorders in IVF children. Populations and methods: 106 children conceived after classic IVF and 68 naturally conceived controls, aged 4-14 y, were studied. Morning circulating fasting glucose, total cholesterol, triglycerides, HDL, LDL, apolipoprotein-A1, apolipoprotein-B, lipoprotein(a), uric acid, insulin, leptin, adiponectin, high sensitivity interleukin-6(hsIL-6), high sensitivity C-reactive protein(hsCRP), retinol binding protein-4(RBP4), neutrophil gelatinase-associated lipocalin (NGAL) and visfatin, LH, FSH, prolactin, insulin, cortisol, IGF-I, total testosterone, D4-androstendione, dehydroepiandrosterone sulfate, 17-OH-progesterone, estradiol, T3, T4, TSH and antithyroid antibodies were determined. As criteria for the metabolic syndrome we used 1) BMI>95th centile 2) triglycerides>95th centile 3) HDL95th centile for the age and gender of Greek children, 5) FGIR95η ΕΘ § Τριγλυκερίδια >95η ΕΘ § HDL 95η ΕΘ § FGIR (Fasting Glucose to Insulin Ratio) <7 Αποτελέσματα: Τα παιδιά της IVF ομάδας είχαν σημαντικά μικρότερο βάρος και μήκος γέννησης σε σχέση με τους μάρτυρες, ήταν σε μεγαλύτερο ποσοστό μικρόσωμα για την ηλικία κύησης (small for gestational age, SGA), δίδυμα και πρόωρα. Βρέθηκαν ήπιες αυξήσεις της αρτηριακής πίεσης και των τριγλυκεριδίων στα IVF-παιδιά σε σχέση με τους μάρτυρες, αλλά δεν υπήρχαν διαφορές στην εμφάνιση του μεταβολικού συνδρόμου ή στους κλασσικούς δείκτες ινσουλινοαντίστασης (ΗΟΜΑ, FGIR). Δεν βρέθηκαν σημαντικές διαφορές στα επίπεδα λεπτίνης, αντιπονεκτίνης, hsCRP, hsIL-6 και βισφατίνης μεταξύ των ομάδων, ενώ τα IVF παιδιά παρουσίασαν σημαντικά υψηλότερα επίπεδα RBP-4 και NGAL. Επιπλέον, βρέθηκε σημαντικά μεγαλύτερη επίπτωση εμμένουσας υπερθυρεοτροπιναιμίας στα IVF παιδιά σε σχέση με τους μάρτυρες. Δεν βρέθηκαν διαφορές στην επίπτωση της πρώιμης αδρεναρχής και στα επίπεδα των ανδρογόνων και των ορμονολογικών δεικτών της εφηβείας μεταξύ του συνόλου των IVF-παιδιών και μαρτύρων. Συζήτηση: Παρ’ όλες τις ήπιες αυξήσεις της αρτηριακής πίεσης και των τριγλυκεριδίων, στα IVF παιδιά δεν βρέθηκαν επηρεασμένες οι τιμές των παραδοσιακών αντιποκινών και των δεικτών χαμηλού βαθμού φλεγμονής, ενώ τα επίπεδα των RBP4 και NGAL ήταν σημαντικά υψηλότερα σε σχέση με τους μάρτυρες, υποδεικνύοντας πιθανόν την ύπαρξη πρώιμων προδιαθεσικών παραγόντων εμφάνισης ινσουλινοαντίστασης σε αυτά τα παιδιά. Επιπλέον, μια σημαντική αύξηση των τιμών της TSH ορού, συμβατή με μια ήπια αντίσταση στην TSH βρέθηκε στα IVF παιδιά σε σχέση με τους μάρτυρες, η οποία πιθανώς οφείλεται σε μία επιγενετική μεταβολή στη ρύθμιση του άξονα TSH-T3/T4 στα παιδιά αυτά. Τα αποτελέσματα αυτής της μελέτης δείχνουν ότι οι παραπάνω μεταβολικές και ενδοκρινολογικές παρεκκλίσεις δεν είναι απλά αποτέλεσμα την ενδομήτριας υπολειπόμενης αύξησης, αλλά μπορεί να αντιπροσωπεύουν επιγενετικές τροποποιήσεις που σχετίζονται με τους περιγεννητικούς χειρισμούς της βλαστοκύστης. Αυτά τα ευρήματα υπογραμμίζουν τη σημασία της συνεχιζόμενης παρακολούθησης των IVF παιδιών

Euthyroid Hyperthyrotropinemia in Children Born after in Vitro Fertilization

Context: Assisted reproduction techniques are now commonly used. Although classic in vitro fertilization (IVF) started almost 30 yr ago, few long-term systematic prospective studies of children conceived with assisted reproduction have been performed. Objective: Our objective was to investigate thyroid function in children conceived after IVF vs. naturally conceived controls. Populations and Methods: A total of 106 children conceived after classic IVF and 68 naturally conceived controls, aged 4-14 yr, were studied. All children were thoroughly examined, and serum T-3, T-4, TSH, anti-thyroid peroxidase, and anti-thyroglobulin antibodies were measured. A second TSH determination and a thyroid ultrasound were performed for TSH higher than 5 mu IU/ml, and children were considered to have persistent hyperthyrotropinemia, if the TSH elevation was confirmed. Results: Seven IVF children but none of the controls had persistent elevations of circulating TSH, suggesting euthyroid hyperthyrotropinemia or subclinical primary hypothyroidism (P = 0.044). TSH was significantly higher in the IVF group than in controls (P = 0.046), whereas no significant differences in the concentrations of T-3 or T-4 were observed. None of the children had detectable circulating antithyroid antibodies in either group. Conclusions: A significant elevation of serum TSH compatible with a mild TSH resistance of the thyroid were found in IVF children compared with controls. This was not due to the presence of antithyroid autoantibodies. We suggest that this might represent a slight epigenetic developmental abnormality related to the preimplantation manipulation of the embryo. Further studies are needed to confirm these findings and to better determine their etiopathogenesis and clinical significance. (J Clin Endocrinol Metab 94: 1338-1341, 2009

Gender Dimorphic Associations between N-Terminal Pro-Brain Natriuretic Peptide, Body Mass Index and Blood Pressure in Children and Adolescents

Background: Obesity and hypertension are often comorbid, but the pathophysiologic mechanisms that link them are not fully understood. Natriuretic peptides might play a role in this association. The majority of studies show lower brain natriuretic peptide (BNP) concentrations as well as lower concentrations of the N-terminal of the prohormone (NT-proBNP) in obese than normal body mass index (BMI) adults and higher BNP concentrations in hypertensive than in normotensive individuals. In children, there are no studies examining the relations between NT-proBNP, BMI and blood pressure. Materials and Methods: Ninety-six children, 24 obese/25 normal BMI boys, and 23 obese/24 normal BMI girls, aged 10-16 years, were studied. Plasma NT-proBNP was measured using electrochemiluminescence. Results: In males, NT-proBNP concentrations were lower in the obese than the normal BMI group but higher in the obese hypertensive than the obese normotensive group (p = 0.04). In addition, a significant positive correlation was noted between plasma NT-proBNP and blood pressure (p = 0.03) only in obese males. In females, no correlations were detected between NT-proBNP, BMI and systolic or diastolic blood pressure. Conclusions: Longitudinal studies are needed to define the role of NT-proBNP as a screening biomarker in obese children, particularly males, to determine their risk for developing arterial hypertension. Copyright (C) 2010 S. Karger AG, Base

Gender dimorphic increase in RBP-4 and NGAL in children born after IVF: an epigenetic phenomenon?

Background In vitro fertilisation (IVF) has been widely used during the last decades. Recent studies demonstrated some alterations in IVF children’s metabolic profile compared with controls. The recently reported lipocalins retinol-binding protein 4 (RBP-4) and neutrophil gelatinase-associated lipocalin (NGAL), as well as visfatin, which are associated with glucose intolerance and could help in the early detection of metabolic abnormalities, have not been studied in IVF children as yet. We studied the lipocalins RBP-4 and NGAL as well as visfatin in children born after IVF. Subjects and methods A total of 100 children born after IVF (47 boys) and 60 controls born after normal conception (30 boys), aged 414year, were studied cross-sectionally. All children had a physical examination, their fasting glucose, insulin, lipid profile, RBP-4, NGAL, and visfatin were determined and their homoeostasis model assessment (HOMA) index was calculated. Results Children born after IVF had significantly higher RBP-4 (P=0 center dot 009) and NGAL (P=0 center dot 028) levels than controls. When divided by gender, RBP-4 remained higher in IVF girls (P=0 center dot 002), whereas NGAL was higher in IVF boys (P=0 center dot 021). Linear regression analysis had revealed that the differences are attributed to the IVF procedure per se. Conclusions In our study, IVF children had significantly higher RBP-4 and NGAL levels than controls, suggesting early metabolic derangements that could be attributed to an epigenetic phenomenon. These results are in accordance with our earlier findings of higher blood pressure and triglycerides in IVF children than controls. Further prospective studies in IVF children will determine the natural course of their metabolic profile

Retinol-binding protein 4 and lipocalin-2 in childhood and adolescent obesity: When children are not just “Small Adults”

BACKGROUND: Although there is much evidence regarding the physiologic and pathogenic roles of the newly described adipokines retinol-binding protein 4 (RBP4) and lipocalin-2 as potential promoters of insulin resistance in obese adults, relatively little information exists regarding their roles in obese children. METHODS: We investigated the circulating concentrations of RBP4 and lipocalin-2 in 80 obese girls (ages 915 years) and their relationships with high-sensitivity C-reactive protein (hs-CRP) and the adipokines leptin and adiponectin. We divided participants by their body mass index standard deviation scores (BMI SDSs) into 4 groups of 20 girls each: overweight [mean BMI SDS (SD), 1.8 (0.4)], obese [2.2 (0.4)],morbidly obese (3.6 (0.4)], and lean controls [-0.11 (0.4)]. We measured plasma-soluble RBP4, the RBP4-binding protein transthyretin, lipocalin-2, hs-CRP, leptin, and adiponectin and calculated the homeostatic assessment model (HOMA) index from fasting glucose and insulin concentrations. RESULTS: Unexpectedly, plasma RBP4 and lipocalin-2 concentrations were correlated negatively with BMI SDS values (P = 0.005, and P &lt; 0.03, respectively). These results were different from those of adults and were not correlated with the HOMA index. In contrast, hs-CRP and leptin concentrations were positively correlated with BMI SDS values (P &lt; 0.0001, and P &lt; 0.00001, respectively), as expected, whereas the adiponectin concentration was negatively correlated (P 0.008). CONCLUSIONS: Although the correlations of leptin, adiponectin, and hs-CRP concentrations with BMI in children are similar to those of adults, the correlations of RBP4 and lipocalin-2 with BMI in children are the inverse of those observed in adults. Thus, although systemic inflammation and mild insulin resistance are present in childhood obesity, RBP4 and lipocalin-2 concentrations are not increased in children as they are in obese adults with long-standing severe insulin resistance and type 2 diabetes. (C) 2008 American Association for Clinical Chemistry