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Graphene, a single layer of carbon atoms, is a material that has held a leading position in material research owing to its excellent properties, allowing its use in innovative technologies. In spite of many advantages, the graphene’s potentially hazardous effect on the environment as well as human health constitutes a major drawback. Year after year, safety data sheets (SDS) constitute the main reference on a material’s potential hazards and the methods to prevent or address them if needed. However, SDS content has been heavily criticized due to incomplete, incorrect, or missing information and the cost required to produce and maintain it. The primary objective of this work is to introduce a stepwise process of knowledge management regarding SDSs, by identifying unexplored or neglected sections in a holistic approach. In this light, this work examines 37 graphene SDS, using modified Hodson’s criteria. The quality evaluation revealed that approximately 5% (2/37) of the datasheets were deemed reliable without restrictions (excellent), the majority 49% (18/37) were categorized as reliable with restrictions (good), while about reaching almost 46% (17/37) were deemed non-informative. It is noteworthy that approximately 73% of the SDS require major improvements; thus, the majority did not provide adequate data to be properly assessed. Section 15 could potentially trigger fundamental changes in the product status. The comprehensive evaluation of all 16 sections will enhance the capacity to conduct research mapping and formulate opinions on nanomaterials, thereby stimulating innovation.

K-Ras4B is one the most frequently mutated proteins in cancer, yet mechanistic details of its activation such as its homodimerization on the membrane remain elusive. The structural determinants of K-Ras4B homodimerization have been debated with different conformations being proposed in the literature. Here, we perform microsecond all-atom Molecular Dynamics (MD) simulations on the K-Ras4B monomer in solution, the K-Ras4B monomer on the membrane, and two experimentally-based K-Ras4B dimer models of the α4-α5 interface to investigate the stability of these structures bound to GTP on a model cell membrane. We then evaluate the complexes for their propensity to form stable dimers on the plasma membrane in the presence and absence of Raf[RBD–CRD] effectors. We find that Raf[RBD-CRD] effectors enhance dimer stability, suggesting that the presence of effectors is necessary for K-Ras4B dimers stabilization on the cell membrane. Moreover, we observe, for the first time, a dynamic water channel at the K-Ras4B dimer interface, and identify putative allosteric connections in the K-Ras4B dimer interface. To discover novel K-Ras4B interfaces, we perform coarse-grained MD simulations in two dissociated K-Ras4B monomers on the membrane, which reveal that the dominant dimer interface is the α4-α5 interface. Finally, a druggability analysis is performed in the different K-Ras4B structures in the monomeric states. Strikingly, all known binding pockets of K-Ras4B are identified only in the structure that is membrane-bound, but not in the solution structure. Based on these results, we propose that modulating the protein-membrane interactions can be an alternative strategy for inhibiting K-Ras4B signaling.

The 2015 American Thyroid Association risk stratification system (ATA RSS) is used in patients with differentiated thyroid carcinoma (DTC) to assess their risk of persistent/recurrent disease. Our aims were to validate the 2015 ATA RSS in a registry of DTC patients and to examine whether the addition of factors not included in it, such as pre-radioactive iodine therapy stimulated thyroglobulin (pre-RAI sTg), gender, and age could increase its predictive ability. We studied 403 patients with DTC, treated at a tertiary center from 1990 to 2018 and subjected to total thyroidectomy. All patients had received RAI therapy, except those with low-risk papillary microcarcinoma. Of our patients, 81.9% were women and 91.1% had papillary thyroid carcinoma. After a median follow-up of 5.0 years, 53 cases of persistent and 21 cases of recurrent disease were recorded. The proportion of variance explained (PVE) regarding the outcome (presence or absence of recurrent/persistent disease) using the 2015 ATA RSS alone was 18.3% (persistence) and 16.9% (recurrence), increasing to 74.4% and 52.0%, respectively, when pre-RAI sTg was added to the logistic regression model. Gender and age were not associated with the disease outcome. In ROC analysis, pre-RAI sTg had a high predictive value for persistent (AUC 0.983, 95% CI 0.962–1.000) and recurrent disease (AUC 0.856, 95% CI 0.715–0.997). The optimal cut-offs and sensitivity, specificity, and positive and negative predictive value for pre-RAI sTg were the following: for persistence 12.75 ng/ml, 100%, 90.5%, 64%, and 100%, and for recurrence 8.05 ng/ml, 77.8%, 85.5%, 36.8%, and 97%. The 2015 ATA RSS displayed moderate performance in predicting recurrent/persistent disease in patients with DTC, which improved with the inclusion of pre-RAI sTg values; pre-RAI sTg was an independent predictor of the disease outcome, with high negative prognostic value.

Ras proteins are membrane-anchored GTPases that regulate key cellular signaling networks. It has been recently shown that different anionic lipid types can affect the properties of Ras in terms of dimerization/clustering on the cell membrane. To understand the effects of anionic lipids on key spatiotemporal properties of dimeric K-Ras4B, we perform all-atom molecular dynamics simulations of the dimer K-Ras4B in the presence and absence of Raf[RBD/CRD] effectors on two model anionic lipid membranes: one containing 78% mol DOPC, 20% mol DOPS, and 2% mol PIP2 and another one with enhanced concentration of anionic lipids containing 50% mol DOPC, 40% mol DOPS, and 10% mol PIP2. Analysis of our results unveils the orientational space of dimeric K-Ras4B and shows that the stability of the dimer is enhanced on the membrane containing a high concentration of anionic lipids in the absence of Raf effectors. This enhanced stability is also observed in the presence of Raf[RBD/CRD] effectors although it is not influenced by the concentration of anionic lipids in the membrane, but rather on the ability of Raf[CRD] to anchor to the membrane. We generate dominant K-Ras4B conformations by Markov state modeling and yield the population of states according to the K-Ras4B orientation on the membrane. For the membrane containing anionic lipids, we observe correlations between the diffusion of K-Ras4B and PIP2 and anchoring of anionic lipids to the Raf[CRD] domain. We conclude that the presence of effectors with the Raf[CRD] domain anchoring on the membrane as well as the membrane composition both influence the conformational stability of the K-Ras4B dimer, enabling the preservation of crucial interface interactions.

Somatic mutations in the GNAS1 gene, which encodes the alpha-subunit of G stimulatory proteins (gsp), are frequently detected in somatotroph pituitary tumors and have been associated to specific clinical and histopathological characteristics. However, the question whether the presence of a somatic gsp mutation affects the response to somatostatin analog treatment remains unresolved.Following a literature search, we performed a meta-analysis, including 8 eligible studies, in order to estimate the effect of gsp mutation on the percent reduction of growth hormone (GH) levels during an acute octreotide suppression test (OST). A total of 310 patients with acromegaly [126 gsp (+) and 184 gsp (-)] were included in the analysis.The presence of the gsp mutation was related with a greater reduction in GH levels on OST [Weighted Mean Difference (WMD): 9.08 % (95 % CI, 2.73, 15.42); p = 0.005; random effects model]. There was significant heterogeneity for this effect estimate (I(2) = 58 %, p value for heterogeneity = 0.02). A sensitivity analysis after exclusion of a study with different methodology of OST provided similar estimates [WMD: 6.93 % (95 % CI, 1.40, 12.46); p = 0.01], albeit with no significant heterogeneity (I(2) = 35 %, p value for heterogeneity = 0.16).The present meta-analysis suggests a role for gsp mutation as a prognostic factor of treatment response to somatostatin analogs.

BACKGROUND The current trend in the management of low risk differentiated thyroid carcinoma is to follow less aggressive strategies. OBJECTIVE To assess the long-term morbidity and mortality outcomes of low-risk papillary thyroid carcinoma (PTC) patients undergoing minimal intervention. DESIGN We retrospectively analyzed 137 patients with low-risk PTC (stage I: n=77; stage II: n=60). Of these patients, 107 (Group 1) had macro-PTC and underwent near-total thyroidectomy and received postoperatively 50mCi RAI. The remaining 30 patients (Group 2) had micro-PTC (

SummaryObjective Growth hormone (GH) and insulin-like growth factor I (IGF-I) are the principal biomarkers used to assess disease activity in acromegaly, and any discrepancy between them renders interpretation of results inconclusive. Purpose of this study was to assess the frequency of this discrepancy and identify parameters that might affect its occurrence. Design A systematic review of MEDLINE and Scopus was performed (1987–2013) followed by a meta-analysis to address the frequency of discrepant results between GH and IGF-I levels. Meta-regression and subgroup analyses were performed assessing the effects of the year of publication, the different types of GH testing and GH assays used, as well as the impact of treatment with somatostatin analogues (SSAs) on the occurrence of this discrepancy. Results The analysis retrieved 39 eligible studies totalling 7071 patients. The pooled discordance rate between GH and IGF-I was 25·7% (95% CI: 22·3–29·4), and the predominant format was that of elevated IGF-I with normal GH levels (15·3%, 95% CI: 12·5–18·7). No significant correlation between the discordance rate and the year of publication was shown; whereas, the use of ultrasensitive GH assays resulted in higher discordance rates (30·7%, 95% CI: 25·9–35·9 vs 19·8%, 95% CI: 14·1–27·2, P = 0·04) as did treatment with SSAs (32·5%, 95% CI: 27·8–37·4) vs (21·6%, 95% CI: 17·8–25·6, P = 0·001). Conclusions Discrepancy between GH and IGF-I results is encountered in a quarter of treated patients with acromegaly, especially when using ultrasensitive GH assays or in patients receiving SSAs, a fact that the clinician should take into consideration when making clinical decisions.

Giants are humanlike creatures of prodigious size and strength present in the myths and legends of many cultures. Cyclopes were a race of giants depicted in ancient Greek mythology and literature. Apart from their extraordinary stature, they were also characterised by the presence of one single eye, located in the centre of their forehead. One of them, Polyphemus, plays a central role in one of the most exiting episodes of Homer’s Odyssey. Besides, descriptions of cases of extremely tall individuals appear in the medical literature as early as in the 16 th century A.D. Post mortem evidence of pituitary tumors were identified in most of these cases, pointing towards acromegaly / gigantism as the most likely cause. More recent case reports on real life giants enriched with the use of radiographic imaging have yielded similar results and even familial cases have been identified. Today, pituitary adenomas over secreting growth hormone (GH) are recognised as the most common cause of acromegaly and advances have been made in understanding their aetiology and pathogenesis. Medical interpretation of the case of Cyclopes covers the differential diagnosis of familial tall stature concurrent with vision impairment in the form of bitemporal hemianopia. Combining textual evidence from Homer’s Odyssey with current scientific data has led us to the conclusion that gigantism in the context of Familial Isolated Pituitary Adenoma (FIPA) or X-linked acro-gigantism (X-LAG) due to mutations either in AIP or GPR101 is the possible culprit: a change in DNA sequence functioning as a link between myth and reality, proving not only that Cyclopes could have really existed, but also that giants are still living among us.

Exercise challenges homeostasis and establishes a new dynamic equilibrium. Elite Rhythmic Gymnasts (RG's) begin exercise at an early age, undergo physical and psychological stress, and adopt negative energy balance to retain a lean physique. The aim of the present study was to evaluate the effect of negative energy balance, acute and chronic exercise on salivary adiponectin, resistin and visfatin levels and their interaction with salivary cortisol, and insulin levels in elite RG's. This study is unique in character, as all variables were assessed on the field of competition. The study included 51 elite RG's participating in "Kalamata 2010 World Cup" in Kalamata, Greece on April 2010. Twenty-seven healthy age-matched girls were used as controls. Anthropometric values were assessed; baseline and post exercise salivary cortisol, insulin, adiponectin, resistin, and visfatin levels were measured. Comparisons regarding hormonal features between RG's and controls were adjusted for BMI and body fat percentage. Salivary adiponectin levels were higher (p0.05) and visfatin lower (p=0.094) in RG's compared with controls, while no significant changes were observed regarding salivary cortisol, insulin, and resistin levels. In elite RG's acute intensive anaerobic exercise led to increased salivary insulin levels (p0.001), reduced salivary adiponectin (p0.001) and visfatin levels (p0.05), and no changes in salivary resistin levels. Moreover, diurnal variation of salivary cortisol was lost. In elite RG's salivary adiponectin is upregulated and salivary visfatin is downregulated after chronic intensive exercise and negative energy balance, while both salivary adiponectin and visfatin levels are suppressed after short term intensive anaerobic exercise.

Weight loss is a characteristic finding of patients with Alzheimer's disease (AD). It seems that precedes cognitive impairment by some years, but the underlying causes are not fully understood. Ghrelin and leptin are involved in energy homeostasis, and may be implicated in weight losing observed in these patients.To examine the potential relationship between ghrelin and leptin levels and weight loss in patients with AD.The study included 27 patients (10 men and 17 women) with AD of moderate severity, and 23 controls (10 males and 13 females), matched for age and BMI. Body fat and lean mass content were assessed using a portable apparatus. Cognitive function was assessed with the Mini-Mental State Examination. Basal serum samples for the measurement of leptin, ghrelin, insulin and glucose were obtained, and serum ghrelin, insulin and glucose were measured after a 75-gr glucose load in both groups.Patients with Alzheimer Disease (AD) have lower lean mass content compared to controls. Basal ghrelin and leptin is similar in patients with AD and controls. The area-under-the-curve for ghrelin (AUC) is lower in male patients with AD compared to control males, while no difference was observed between females AD and controls.Male patients with AD, in contrast with female patients, fail to maintain a normal energy homeostasis even in the early stages of the disease, as shown by the decreased lean mass content in males AD compared to controls. Disruption of the normal compensatory modulation of ghrelin secretion might contribute to the metabolic changes observed in male patients with AD.

Background: The exact mechanism of weight gain (WG) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with idiopathic Parkinson’s disease remains unknown. Objectives: To investigate a possible involvement of ghrelin, neuropeptide Y (NPY) and leptin in WG after DBS. Methods: Twenty-three Parkinson patients were submitted for body composition measurements and blood sampling 3 days before, and 3 and 6 months after STN DBS. Peripheral concentrations of ghrelin, NPY, and leptin were determined, as well as the L-dopa equivalent daily dose. Patients were clinically evaluated using the Unified Parkinson’s Disease Rating Scale. Results: Three months after surgery, a significant WG was observed (3.09 ± 5.00 kg; p = 0.007) with no further increase at 6 months. Three months postoperatively, NPY circulating levels increased significantly (p = 0.05), while the increase of ghrelin levels reached statistical significance at 6 months (p = 0.001). WG was significantly associated with changes of ghrelin and leptin levels at 3 and 6 months, respectively. Conclusions: STN DBS seems to temporarily dysregulate the hypothalamic secretion of NPY and ghrelin. The variation of weight may be attributed to an increased production of ghrelin and leptin. A possible neuroprotective role of DBS, exerted through the increase of ghrelin levels, should be further studied.

The aim of this study was to determine the impact of intensive training on adult final height in elite female rhythmic and artistic gymnasts. The study included 215 rhythmic gymnasts (RG) and 113 artistic gymnasts (AG). AG were below the 50th percentile, while RG were taller than average. Final adult height was lower than target height in AG, while in RG, it exceeded target height. AG started training earlier than RG (p

The aim of this study was to evaluate the effects of intensive physical exercise and acute psychological stress during high level athletic competition as reflected on the levels of salivary cortisol in elite artistic gymnasts (AGs).The study included 239 AGs (142 females-97 males) who participated in the European Championship of Gymnastics in 2006 and 81 adolescents (40 females-41 males), matched for age, as controls. All athletes participated voluntarily in all or parts of the study, providing samples or data for each of the variables measured. Height, weight, body fat, lean body mass (LBM), bone age and Tanner stage of puberty were assessed and data concerning the time of thelarche, adrenarche and menarche as well as, the onset and the intensity (hours per week) of training were obtained.Saliva samples were collected, the morning before training and in the afternoon shortly after the competition. From controls, the saliva samples were collected in the morning. Cortisol concentrations were measured using a chemiluminescence method. Acute stress was assessed using a questionnaire designed for the study.No difference was found between morning and afternoon salivary cortisol levels in both male and female AGs (females: AM: 15.45±7.45nmol/l vs PM: 15.73±9.38nmol/l; males: AM: 10.21±5.52nmol/l vs PM: 9.93±13.8nmol/l, p0.05). Female AGs presented higher levels of morning salivary cortisol than female controls (p0.05). Both male and female AGs had higher degree of psychological stress in comparison with controls (p0.001, p0.013, respectively). Female AGs had higher morning and afternoon salivary cortisol levels (p0.01, p0.01, respectively) and higher degree of stress (p0.003) than males.In elite AGs the diurnal rhythm of salivary cortisol has been abolished, probably due to the strenuous training and competition conditions. Female AGs presented higher levels of morning salivary cortisol and psychological stress compared to both male AGs and female controls. The long term consequences of these modifications of the HPA axis remain to be elucidated.

Genetic potential for growth can be fully expressed only under favorable environmental conditions. Although moderate physical activity has beneficial effects on growth, excessive physical training may negatively affect it. Sports favoring restricted energy availability, in the presence of high energy expenditure, are of particular concern. In gymnastics, a different pattern in skeletal maturation and linear growth was observed, resulting in an attenuation of growth potential in artistic gymnasts (AG), more pronounced in males than in females. In female rhythmic gymnasts (RG), the genetic predisposition to growth was preserved owing to a late catchup growth phenomenon. In all other sports not requiring strict dietary restrictions, no deterioration of growth has been documented so far. Intensive physical training and negative energy balance alter the hypothalamic pituitary set point at puberty, prolong the prepubertal stage, and delay pubertal development and menarche in a variety of sports. In elite RG and AG, prepubertal stage is prolonged and pubertal development is entirely shifted to a later age, following the bone maturation rather than the chronological age.

Bone mass (BM) and skeletal size are similar in prepubertal girls and boys and double between the onset of puberty and early adult life. Sex steroids are responsible for the maturation in human skeleton, as well as for the sexual dimorphism, observed after the onset of puberty. Physical activity in childhood is critical for maximizing bone growth and thus for preventing osteoporosis during older age. Therefore, it constitutes the most effective prevention strategy available. In athletes, high-impact loading activities have been shown to improve BM, whereas in sports requiring a lean somatotype (therefore leading to a negative energy balance), the delay in skeletal maturation and pubertal development predisposes athletes to osteopenia and osteoporosis. Although the early onset of training, the continuous intensive exercise and its long duration attenuate bone acquisition, the excess mechanical load to which these athletes are exposed from a young age exerts beneficial effects on bone formation that lead to a positive net-effect on BM.

Objective Somatic mutations in the GNAS1 gene, which encodes the alpha-subunit of G stimulatory proteins (gsp), are frequently detected in somatotroph pituitary tumors and have been associated to specific clinical and histopathological characteristics. However, the question whether the presence of a somatic gsp mutation affects the response to somatostatin analog treatment remains unresolved.

We studied 129 female rhythmic gymnasts (RG) and 142 female artistic gymnasts (AG) who participated in the 1999 Gymnastics World Championship for RG in Osaka, Japan, and the 1999 and 2001 Gymnastics World Championships for AG in Tianjin, China (n 48), and Ghent, Belgium (n 94), respectively. RG were taller than average, with a mean height SD score above the 50th percentile, whereas AG were relatively short, with a mean height SD score below the 50th percentile. Both RG and AG followed their respective reported target height SD score, which was above the 50th percentile for the RG and below the 50th percentile for the AG. The RG followed a growth pattern that was higher than their reported target height, whereas AG exhibited a negative growth pattern. RG and AG weighed less than the population mean, with the mean weight for age below the 50th percentile for both groups. RG were taller than AG (t 17.15; P < 0.001), with a higher reported target height SD score (t 6.44; P < 0.001), a greater height-reported target height (t 2.74; P < 0.001), and a lower mean body fat (t 11.83; P < 0.001) and body mass index (t 10.73; P < 0.001) than AG. AG started their training at an earlier age than RG (t 4.13; P < 0.001). Using multiple regression analysis, actual height SD score was independently influenced positively by weight SD score for both RG (b 0.421; t 4.317; P < 0.001) and AG (b 1.404; t 16.514; P

Rhythmic gymnasts performing under conditions of high intensity are exposed to particularly high levels of psychological stress and intense physical training, factors that can contribute to the observed delay in skeletal maturation and pubertal development, and alter optimal growth. The study was conducted in the field, during the International, European, and World Rhythmic Sports Gymnastics Championships of the years 1997-2000, and included 104 elite female rhythmic gymnasts, aged 12-23 yr. The study included height and weight measurements, estimation of body fat and skeletal maturation, and registration of parental height. Height, weight, target height, and predicted adult height were expressed as the SD score of the mean height and weight for age, according to Tanner's standards. Gymnasts were taller and thinner than average for age, with height velocity SD score for each age group above the 50th percentile for all age groups (n = 140, mean = 1.9 +/- 2.5). Interestingly, although height velocity in normal girls comes to an end by the age of 15, in our examined rhythmic gymnasts it continues up to the age of 18. There was a delay of skeletal maturation of 1.8 yr (n = 72, r = 0.730, P < 0.001), compensated by an acceleration of height velocity toward the end of puberty. The final adult height was identical to the estimated predicted height at first evaluation, and significantly higher than the genetically determined target height (n = 35, r = 0.58, P < 0.001), denoting that genetic predisposition to final height is not only achieved, but even exceeded. Using multiple regression analysis, target height was the only independent parameter that has been proven to influence positively the height velocity SD score (b = 0.233, t = 2.215, P = 0.029), denoting that genetic predisposition remains the main driving force for the observed efficient catch up growth. In conclusion, the elite rhythmic gymnasts compensate for their loss of pubertal growth spurt by a late acceleration of linear growth. Despite the delay in skeletal maturation, genetic predisposition of growth is not only preserved, but even exceeded.

OBJECTIVE Elite male artistic gymnasts (AG) are exposed to high levels of physical and psychological stress during adolescence and experience a significant late maturation in both linear growth and pubertal development. The aim of the present study was to determine the impact of intensive physical training on the adult final height in elite male AG. METHODS This study is unique in character, as all variables were measured on the field of competition. The study was prospective and longitudinal; however, the current analysis of data is cross-sectional. Data from 86 elite male AG were obtained during the gymnastics competitions of European and World Championships. Clinical evaluation included height and weight measurements, as well as assessment of pubic hair and genital development according to Tanner's stages of pubertal development. The laboratory investigation included determination of skeletal maturation. All athletes completed a questionnaire that included questions on personal (onset and intensity of training, number of competitions per year) and family data (paternal and maternal heights). RESULTS Male AG were below the 50th percentile for both final height and weight. Elite male AG had final height standard deviation score (SDS) lower than their genetic predisposition. Final height SDS was correlated positively with target height SDS (r = 0.430, p < 0.001) and weight SDS (r = 0.477, p < 0.001) and negatively to the intensity of training (r = -0.252, p = 0.022). The main factors influencing final height, by multiple regression analysis were weight SDS (p < 0.001) and target height SDS (p = 0.003). CONCLUSION In elite maleAG, final height falls short of genetic predisposition, still well within normal limits. Considering medical and psychological risks in general, and based on the results of this research project, the International Federation of Gymnastics has increased the age limit for participants in international gymnastics competitions by 1 year.

Hormonal determination in saliva offers several advantages. Peptides enter the salivary glands either by active transport mechanisms or are expressed and secreted by the salivary glands themselves. The collection of saliva is a noninvasive, easily repeatable and less stressful technique than blood withdrawal. The purpose of the present study was to introduce a method for measuring salivary resistin, visfatin and adiponectin levels and to evaluate their associations with serum levels. Resistin, visfatin and adiponectin levels were measured in serum and saliva of 50 healthy adult volunteers (17 male and 33 female) using commercial enzyme immunoassay kits for serum with minor modifications. The present study documented the determination of resistin and adiponectin levels in saliva and the significant correlation of salivary levels with serum levels (r=0.441, p

Bone mass (BM) and skeletal size are similar in prepubertal girls and boys and double between the onset of puberty and early adult life. Sex steroids are responsible for the maturation in human skeleton, as well as for the sexual dimorphism, observed after the onset of puberty. Physical activity in childhood is critical for maximizing bone growth and thus for preventing osteoporosis during older age. Therefore, it constitutes the most effective prevention strategy available. In athletes, high-impact loading activities have been shown to improve BM, whereas in sports requiring a lean somatotype (therefore leading to a negative energy balance), the delay in skeletal maturation and pubertal development predisposes athletes to osteopenia and osteoporosis. Although the early onset of training, the continuous intensive exercise and its long duration attenuate bone acquisition, the excess mechanical load to which these athletes are exposed from a young age exerts beneficial effects on bone formation that lead to a positive net-effect on BM.

Iodine deficiency (ID) is still a major universal health problem. Iodine deficiency disorders (IDDs) affect people of all ages, among whom the most vulnerable are children and adolescents. The aim of the present study was to assess the long-term effects on growth and pubertal development of correcting severe ID in areas of Azerbaijan between 1999 and 2000.Iodized oil was administered orally to 293,000 children, aged 6-16 years. Among those, 364 children were randomly selected and were examined 1 year before the administration of iodized oil (Group I-neg, iodine negative) and 295 children (Group I-Rx, iodine treated) were examined 4 years (Group I-R x 4, iodine treated 4 years later; n = 173) or 5 years (Group I-R x 5, iodine treated 5 years later; n = 122) after the last dose of iodide.In Group I-neg the median urine iodine concentration (UIC) (mcg/L) was 36 (mean: 36.272 +/- 11.036) and increased significantly (p0.001) in Group I-R x 4: 188 (mean: 230.969 +/- 155.818) and in Group I-R x 5: 175 (mean: 201.176 +/- 130.369). The prevalence of goiter was 99% in Group I-neg and 2% in Group I-R x 4. Children in Group I-Rx had a greater standard deviation score (SDS) for height (-0.1364 +/- 1.279, n = 294) than children in Group I-neg (-0.5019 +/- 1.17, n = 363) (p0.001, t = -3.817), which was more significant for boys. SDS for weight was similar in both groups (Group I-neg: -0.17 +/- 0.78, n = 363; Group I-Rx: -0.115 +/- 0.917, n = 294). The rate of puberty development as judged by the development of breast and pubic hair was normalized in both sexes after the correction of ID.Our results demonstrate that long-term correction of severe ID leads to sustained improvement of linear growth accompanied by a normalization of the time of onset of pubertal development for both sexes.

Context: In animals, acute iodine administration results in acute intrathyroidal inhibition of iodinations followed by escape of the inhibition if the excessive iodine intake continues. In humans, the intrathyroidal nonhormonal and hormonal iodine concentration after exposure to large doses of iodine for a relatively long period of time is not known. Objective: To determine whether, in human thyroid, administration of large doses of iodine for a relatively long time results in alterations of intrathyroidal hormonal (HI) T4 and T3 and total iodine (TI) content, as well as whether changes in serum concentration of thyroid hormones and TSH would occur after iodine administration or discontinuation. Design: In 33 euthyroid patients with single thyroid nodule or hyperparathyroidism, Lugol solution (80 mg iodine) was administered for 15 d before operation. Groups of six to eight patients underwent operation 0, 5, 10, and 15 d after iodine withdrawal. TI, HI in a sample of thyroid tissue, and serum concentration of T4, T3, and TSH were measured. In 21 normal euthyroid subjects who did not undergo operation, a similar protocol was used and serial blood measurements were taken. Main Outcome Measure: Intrathyroidal TI, HI, and serum thyroid hormone and TSH measurements were the main outcome measure. Results: Intrathyroidal HI content and serum T4 and T3 were unchanged during and after iodine discontinuation. TI was increased during iodine administration and returned to control values 5 d after discontinuation of iodine. The ratio of HI/TI was decreased and returned to control values 15 d after the iodine was discontinued. Serum TSH was increased during iodine administration and returned to control values 10 d after iodine withdrawal. Conclusions: In humans, administration of iodine for a relatively long period of time was accompanied by increased intrathyroidal TI, but no changes in HI or demonstrable increases of serum T4 and T3 were observed. It is hypothesized that the maintenance of normal intrathyroidal HI is the result of the combined inhibitory effect of iodine on thyroid hormone synthesis and on the release of T4 and T3 from the thyroid.

The genetic potentials for growth can be fully expressed only under favourable environmental conditions. Excessive physical training may negatively affect growth, especially during puberty. Sports that require a strict control of energy input in the presence of a high energy output are of particular concern. In gymnastics, a different pattern in skeletal maturation was observed, leading to an attenuation of growth potential ins Artistic Gymnasts (AG), more pronounced in males than in females, whereas in female Rhythmic Gymnasts (RG) the genetic predisposition to growth was preserved because of a late catch-up growth phenomenon. In all other sports not requiring strict dietary restrictions, no deterioration of growth has been documented. Intensive physical training and negative energy balance modify the hypothalamic pituitary set point at puberty, prolong the prepubertal stage and delay pubertal development and menarche in a variety of sports. In elite RG and AG the prepubertal stage is prolonged and pubertal development is entirely shifted to a later age, paralleling the bone age rather than the chronological age. Bone formation, and, consequently, BMD are enhanced by physical activity. In athletes, high-impact loading activities have been shown to improve BMD, while in sports requiring a lean somatotype, the delay in skeletal maturation and pubertal development, resulting from hypoestrogenemia, predisposes athletes to osteopenia. In AG, an increase in bone density is observed using the bone age as denominator.

Different attempts were made to identify the variables that may be involved in the clinical course of cerebrovascular ischemia. In the case of stroke with mild severity (SMS), the clinical significance of neuroendocrine changes as well as of post-stroke depression (PSD) remains unknown. We therefore evaluated the presence of neuroendocrine changes in the acute and post-acute phase of SMS, and their potential role during convalescence. Serum cortisol, T4, T3, FT4, FT3, TSH and PRL levels were measured in 17 euthyroid patients with stroke on admission (day 1), following morning (day 2), 7 days and 3 months later. TSH and PRL secretion after TRH test were measured. Stroke severity on admission was determined by Scandinavian Stroke Scale (SSS). Montgomery-Asberg Depression Rating Scale (Madrs) was used for assessment of post-stroke depression. On admission, TSH and T3, were within normal limits and were greater compared to values on day 2. Lower basal TSH and decreased TSH response to TRH on day 2, were associated with stroke of greater severity. Delta-PRL after TRH on day 2 was higher in patients who develop PSD. Changes in serum thyroid hormones in SMS, reflects those of non-thyroidal illness. A mild stimulation of hypothalamic-pituitary-adrenal axis was detected. We provide evidence that PRL response to TRH, in the acute phase of stroke may be used as an index for early detection of PSD.

Elite gymnasts are subjected to intense training, which may alter pubertal development.The objective of the investigation was to study the impact of gymnastics on pubertal development in rhythmic (RGs) and artistic gymnasts (AGs).Evaluation of somatometric parameters, pubertal stage, and intensity of training in the competition field were studied.The study was conducted at European and world championships of years 1997-2004.Subjects included 433 elite RGs and 427 AGs, aged 11-23 yr.There were no interventions.Mean chronological and bone ages of each pubertal stage and their relation to the intensity of training were measured.AGs and RGs showed a delay in skeletal maturation (Delta age-bone age, 2.13 and 1.28, respectively; P0.001). AGs were subjected to higher levels of physical training. Thelarche occurred at 12.9 yr for RGs and 13.2 yr for AGs (P = 0.003) and pubarche at 12.5 and 12.9 yr, respectively (P = 0.002). Puberty was delayed but normally progressed. AGs entered each pubertal stage later than RGs. The delay was influenced by the amount of energy output. Menarcheal age was 14.6 yr for RGs and 14.9 yr for AGs. Menarche was influenced in AGs by bone age (b = 0.333; t = 2.521; P = 0.020), pubarche (b = 0.322; t = 2.401; P = 0.026), and body fat (b = -0.458; t = -3.412; P = 0.003) and in RGs by bone age (b = 0.378; t = 3.689; P0.001) and pubarche (b = 0.525; t = 6.017; P0.001).In RGs and AGs, pubertal development was shifted to a later age, maintaining a normal rate of progression, which followed the bone age. AGs, who were exposed to a greater and more sustained energy output than RGs, presented a more pronounced delay in both skeletal maturation and pubertal development.

Steroids determination in saliva offers several advantages. The collection of saliva is a noninvasive, less stressful technique than blood withdrawal and reflects the circulating unbound fractions. The suitability of saliva for 17-hydroxyprogesterone and cortisol determinations has been documented in healthy subjects as well as in diseases like Congenital Adrenal Hyperplasia and Cushing syndrome. The aim of the study was to compare the influence of different collection methods on the results of 17-hydroxyprogesterone measurement in saliva collected by different ways, using commercially available RIAs developed for plasma. 17-hydroxyprogesterone was determined in 64 healthy adult volunteers (30 males, 34 females) in serum (Group SE) and in saliva collected before meals at 8-10 p.m. by directly spitting into a plastic tube (Group SP), using a cotton swab (Group SA) and using a polyester swab Salivette (Group SB). We used a commercially available direct radioimmunoassay without separation technique. The 17-hydroxyprogesterone mean values (ng/ml) were 1.16+/-1.3 (Group SE), 0.056+/-0.046 (Group SP), 0.089+/-0.048 (Group SA) and 0.058+/-0.049 (Group SB). The detection limit was 0.010 ng/ml. The correlations between the values in serum (Group SE) and in saliva were: r=0.77, p0.05 (Group SP); r=0.62, p0.05 (Group SA); r=0.70, p0.05 (Group SB). The saliva values corresponding to the serum cut-off point of 3 ng/ml upper limit of normal values were in ng/ml 0.13 (Group SP), 0.16 (Group SA) and 0.11 (Group SB). In conclusion, 17-hydroxyprogesterone determinations in saliva using commercially available RIAs primarily developed for serum, is a reliable and easy to perform procedure. The three different methods of saliva collection showed 17-hydroxyprogesterone concentrations to have good agreement.

We studied 262 athletes who were 13-23 yr old. There were 93 male and 169 female artistic gymnasts (AG). This study is unique in character, because all variables were measured on the field of competition (24th European Championship). Male AG had a higher height SD score than female (P < 0.001), with a higher reported target height SD score (P < 0.001), a higher predicted final height (P = 0.007), a lower Delta height - target height (P < 0.001), a less delayed bone age (P < 0.001), a greater body mass index (BMI) (P < 0.001), a lower mean body fat (P

Physical exercise enhances bone acquisition during adolescence. The aim of the study was to evaluate the influence of intensive physical exercise on bone acquisition in adolescent elite artistic gymnasts. The study included 262 athletes (93 males and 169 females, aged 13-23 yr) participating in the 24th European Championship held in Greece. Bone age compared with chronological age was delayed by 2 yr for females (n = 120) and 1 yr for males (n = 68). For both sexes, the growth chart of bone mineral density (BMD) followed a normal pattern when estimated according to bone age rather than chronological age. For females, BMD was positively correlated with bone age, chronological age, height, body weight, body mass index, body fat, lean body mass, and with age of onset of training, and negatively with duration of exercise and intensity of training (P values range from0.05 to0.0001). Multiple regression analysis revealed that age of onset of training was the major parameter attenuating the effect of exercise on BMD (P0.001). The latter was related to the stage of puberty (P0.05). For males, BMD was correlated positively with bone age, height, body weight, and lean body mass (P values range from0.01 to 0.0001). Multiple regression analysis revealed that the more powerful factor influencing BMD was weight (P0.01). In conclusion, bone acquisition in adolescents under intensive physical training follows the normal pattern only when estimated according to bone age. The age of onset, the duration, and the intensity of exercise attenuate the bone acquisition, at least in female artistic gymnasts.

Optimal growth depends upon both environmental and genetic factors. Among environmental factors that could alter growth and sexual maturation are stress and intensive physical training. The influence of these factors has been documented in a variety of sports, but there is limited information on rhythmic gymnasts, who have entirely different training and performance requirements.The study was conducted during the 13th European Championships in Patras, Greece, and included 255 female rhythmic gymnasts, aged 11–23 yr. The study included measurement of height and weight, assessment of breast and pubic hair development, estimation of body fat and skeletal maturation, and registration of menarcheal age and parental height.Gymnasts were taller than average height for age, with mean height above and mean weight below the 50th percentile. Actual height sd score was positively correlated to weight sd score (P < 0.001), number of competitions (P = 0.01), and body mass index (BMI; P < 0.001). Predicted adult height sd score was positively correlated to weight sd score (P < 0.001) and negatively to body fat (P = 0.004).There was a delay in skeletal maturation of 1.3 yr (P < 0.001). Pubertal development was following bone age rather than chronological age. The mean age of menarche was significantly delayed from that of their mothers and sisters (P = 0.008 and P = 0.05, respectively), was positively correlated to the intensity of training and to the difference between chronological age and bone age (P < 0.001 and P = 0.002, respectively), and was negatively correlated to body fat (P < 0.001).In the elite female rhythmic gymnasts, psychological and somatic efforts have profound effects on growth and sexual development. Despite these aberrations, adult height is not expected to be affected.