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Resumen En la actualidad, la obesidad en el nino esta mundialmente considerada como una enfermedad de proporciones epidemicas. En 20 anos, se ha incluido de forma duradera dentro del panorama pediatrico; muchas enfermedades, consideradas hasta ahora como exclusivas de la edad adulta (hipertension arterial «idiopatica», dislipidemia, diabetes tipo 2) han hecho su aparicion en los ninos y adolescentes, con dificultades inimaginables de gestion a corto y sobre todo largo plazo. Estos factores aumentan el riesgo cardiovascular y pueden presentarse agrupados en un mismo paciente, formando una entidad nosologica que adquiere el nombre de sindrome metabolico. Actualmente no existe un consenso unanime para definir el sindrome metabolico en el nino. El tratamiento del sindrome metabolico se basa principalmente en el tratamiento de la obesidad y en ocasiones en el tratamiento de la comorbilidades. La elaboracion de estrategias de prevencion y tratamiento requiere una vision global del sindrome metabolico, interpretado como una entidad dinamica y no estatica.

Purpose: Osteoporosis (Op) and metabolic syndrome (MetS) are two common disorders showing common pathogenic patterns. This cross-sectional study was performed to evaluate if MetS and its constitutive elements are associated to an increased risk of low bone mineral density (BMD) in free-living women examined by Dual-energy X-ray absorptiometry (DXA) for suspected Op. Methods: 13,182 free-living Caucasian women referring to “COMEGEN” general practitioners cooperative operating in Naples, Italy, performed a contextual evaluation of BMD by DXA and all MetS constitutive elements (systolic and diastolic blood pressure, waist circumference, serum levels of triglycerides, high-density lipoprotein cholesterol, and fasting glucose) between June 1st 2008 and May 31st 2018. Subjects aged less than 40 years or with signs or symptoms suggestive of secondary Op were excluded from the study. Results: MetS is associated to an increased risk of low BMD (Odds Ratio 1.19; 95% Confidence Interval 1.08–1.31). Among MetS constitutive elements, hypertension was associated to increased risk of low BMD, whereas high fasting glucose level/diabetes were associated to reduced risk of low BMD. Conclusions: The significant association between Op and MetS in free-living women examined by DXA for suspected Op suggests the advisability of a contextual evaluation of both disorders in this setting.

Purpose We have recently demonstrated a significant association between osteoporosis (Op) and metabolic syndrome (MetS) in Caucasian women examined by Dual-energy X-ray absorptiometry (DXA) for suspected Op. This cross-sectional study was performed to evaluate the association between MetS and Op in Caucasian men enrolled in the same geographical area, with identical criteria and in the same time range. Methods Among subjects enrolled in the SIMON study, we selected the medical records of all free-living men who performed a contextual evaluation of both bone mineral density (BMD) by DXA and MetS constitutive elements (arterial blood pressure, waist circumference, serum levels of triglycerides, high-density lipoprotein cholesterol, and fasting glucose). All enrolled subjects refer to “COMEGEN” general practitioners’ cooperative operating in Naples, Southern Italy. Results Overall, the medical records of 880 men were examined. No significant association between MetS and Op was observed. Among MetS constitutive elements, waist circumference was inversely related to Op risk. Conclusion In Caucasian men examined by DXA for suspected Op, no significant association was observed between Op and MetS. The study results contrast to those observed in women enrolled in the same geographical area, with identical criteria and in the same time range and may be related to sexual dimorphism occurring in clinical expressiveness of both MetS and Op.

The European hare (Lepus europaeus) is cosmopolitan species, living in a variety of habitats and showing a diversified diet, that has been described mainly from agricultural meadows and crops, with little information available for extreme environments. Here, we describe, for the first time, the diet of the European hare from Mount Vesuvius, using DNA metabarcoding and high- throughput sequencing on DNA extracted from faecal pellets, a proxy for a population living in a volcanic environment. The DNA from pellets was first genetically assigned to European hare using high-resolution melting analysis. The diet of the hare on Vesuvius is mainly composed of herbaceous species belonging to Fabaceae (86.26% of total diet). The most frequent plant items ingested by the species are Galega officinalis and Lupinus angustifolius (67.10% of total diet), although these are detected only sporadically in the study area. Indeed, the spectrum of available plants also includes other easily accessible wild (i.e. Lolium sp., Bromus sp., Rumex sp.) and cultivated (i.e. Solanum lycopersicum, Cucumis melo, Pisum sativum) plant items, found only in traces in the diet of the hares. Our contribution adds information on the trophic ecology of the European hare, exploring its ability to live in an extreme environment. This could be useful to set a management strategy for conservation of the species, which is ecologically relevant on Vesuvius as prey for birds and mammals, as well as a vegetation modulator via selective grazing by endozoochory. Furthermore, our study represents the latest information on the diet of the hare living in an environment that no longer exists: an extensive fire destroyed about 80% of the woody area after our sampling. The post-fire regrowth is transforming the original environment and consequently the trophic availability for the European hare.

La sindrome metabolica è un fattore di rischio per nefrolitiasi. Questo studio è stato effettuato per valutare il profilo clinico e biochimico di pazienti con nefrolitiasi recidivante da ossalato di calcio e sindrome metabolica. Sono stati arruolati un totale di 526 calcolotici, 184 dei quali con sindrome metabolica, e 214 controlli. I calcolotici con sindrome metabolica hanno mostrato un'escrezione di sodio superiore [media (95% intervallo di confidenza), 196 (176-218) vs 160 (150-168) mmol/24h; p

Introduction et but de l’etude La voie leptine-melanocortines joue un role-cle dans l’homeostasie energetique. Les variants homozygotes sur les genes de cette voie sont associes a une obesite severe et precoce avec anomalies endocriniennes. Le role des variants heterozygotes sur ces memes genes n’est pas etabli dans l’obesite. Le but de l’etude etait de decrire leur frequence et la relation genotype/phenotype dans une cohorte d’enfants et d’adultes avec obesite severe. Materiel et methodes Le sequencage direct sur au moins un gene de la voie (LEP, LEPR, POMC, PCSK1 et MC4R) a ete realise chez 6347 patients avec obesite severe et/ou precoce. La fonctionnalite des variants a ete determinee a partir des consequences proteiques predites, de 7 outils de prediction, et des etudes fonctionnelles decrites. Le phenotype incluait l’âge de debut d’obesite et sa severite, le comportement alimentaire et les anomalies endocriniennes associees. Le phenotype des sujets porteurs heterozygotes (n = 60 dont 29 enfants) a ete compare a celui des homozygotes (n = 16 dont 4 enfants) mais aussi selon la fonctionnalite des variants et le nombre de variants heterozygotes presents chez un meme patient (variants combines) a la recherche d’un effet cumulatif. Resultats et analyse statistique La frequence des variants homozygotes etait de 0,8 % (n = 26) et des variants heterozygotes de 3,3 % (n = 110) dont 1,7 % de variants heterozygotes avec impact fonctionnel (LEP n = 0/22, LEPR n = 23/40, POMC n = 10/21, PCSK1 n = 23/27). Douze sujets (12 %) etaient porteurs de plusieurs variants heterozygotes (MC4R inclus). Chez les enfants, aucune difference significative n’a ete mise en evidence pour l’âge de debut d’obesite et sa severite entre les porteurs heterozygotes et homozygotes. L’IMC moyen des adultes etait significativement superieur pour les porteurs homozygotes compare a celui des porteurs heterozygotes (IMC 66 vs 53 kg/m2, p = 0,015). De meme, l’âge de debut d’obesite etait plus precoce (0,4 vs 5,4 ans, p Conclusion La presence d’un ou plusieurs variants heterozygotes avec impact fonctionnel sur la voie leptine-melanocortines est associee a une obesite severe et precoce avec parfois des anomalies endocriniennes et donc un phenotype proche de celui des sujets porteurs homozygotes. Ces donnees sont donc en faveur de la recherche systematique de variants sur cette voie cle du controle de la prise alimentaire en cas d’obesite precoce et severe avec ou sans anomalie endocrinienne associee afin de discuter l’indication d’un traitement par agoniste MC4R.

Simple nodular goiter and Hashimoto's thyroiditis are 2 frequent nonmalignant thyroid diseases. Tobacco smoking has detrimental effects on the endocrine system and in particular on thyroid function and morphology. The objective of this cross-sectional study, involving 1800 Caucasian adults from a geographical area with mild iodine deficiency, was to evaluate the relationship between tobacco smoking, smoking cessation, and the prevalence of simple nodular goiter and Hashimoto's thyroiditis. Thyroid status was evaluated by ultrasonic exploration of the neck, measurement of FT3, FT4, TSH, antibodies against thyroid peroxidase and thyroglobulin, and urinary iodine excretion. The fine-needle aspiration biopsy of significant nodules was also performed. Smoking habits were evaluated by a specific questionnaire and the calculation of number of pack years. Both current and previous smokers showed an increased risk of simple nodular goiter compared to never smokers after adjustment for potential confounders and known goitrogen factors. Interestingly, the simple nodular goiter risk was similar for never smokers and for previous smokers declaring a time since cessation of smoking for more than 69 months. Smoking habit was not associated to an increased risk of Hashimoto's thyroiditis. Smoking appears to be an independent risk factor for simple nodular goiter but not for Hashimoto's thyroiditis in an area with mild iodine deficiency. A prolonged withdrawal of smoking dramatically reduces the risk of simple nodular goiter occurrence.

Negli ultimi due decenni, l'identificazione delle proprietà biologiche del Fibroblast Growth Factor 23 (FGF23) ha notevolmente ampliato le conoscenze sulla regolazione endocrina e paracrina dell'omeostasi dei fosfati e sulle relazioni intercorrenti tra asse rene-intestino-tessuto osseo e sistema biologico vitamina D-FTH-calcio-fosfati. Lo studio delle proprietà biologiche di FGF23 ha inoltre aperto interessanti campi di ricerca in ambito clinico e farmacologico.

Primary pachydermoperiostosis (PDP) is a rare syndrome, characterized by digital clubbing, periostosis, and pachydermia. We have evaluated biochemical bone turnover markers, including components of interleukin-6 (IL-6) and osteoprotegerin/receptor activator of nuclear factor (NF)-?B ligand (OPG/RANKL) systems, in an 18-year-old man affected by primary PDP. The acute phase of the disease was characterized in our patient by high serum levels of IL-6 and RANKL. The observed high serum levels of these parameters are associated with increased values in markers of bone resorption (degradation products of C-terminal telopeptides of type-I collagen and urinary hydroxyproline/creatinine ratio) and reduced serum levels of bone alkaline phosphatase, a marker of bone formation. Serum levels of osteotrophic hormones were in the normal range. Our data suggest that, despite the radiographic findings, the acute phase of primary PDP is characterized by increased bone resorption, probably mediated by IL-6 and RANKL. Read More: http://informahealthcare.com/doi/abs/10.1080/03009740701772457

Background/aim: To study the characteristics of interleukin 6 (IL6), soluble form of interleukin 6 receptor (sILR)/IL6 complex in obese children and adolescents and its relationship with insulin resistance (IR). Subjects and methods: 66 obese children and adolescents [34 boys, mean age 10.3 ± 2.9 years, z-score of body mass index (BMI) 4.76 ± 1.36] and 24 non-obese healthy sex- and age-matched controls. Fasting levels of glucose, insulin, IL6, sIL6, sgp130 were measured. IR was assessed by homeostasis model assessment of IR (HOMA-IR). Results: Obese subjects showed increased levels of insulin and IL-6 and higher HOMA-IR compared to controls (117.67 ± 50.9 vs. 62.42 ± 29.4 pmol/L, 2.73 ± 0.98 vs. 1.07 ± 0.41 pg/ml and 4.03 ± 2.16 vs. 1.83 ± 1.05 for insulin, IL-6 and HOMA-IR, respectively, p < 0.01 in all cases). sIL-6R levels were significantly lower in obese subjects (34.7 ± 14.2 vs. 55.6 ± 15.2 ng/ml in controls, p = 0.005), whereas sgp130 levels were not significantly different. In obese subjects, IL-6 directly correlated with z-score BMI (r = 0.481, p = 0.009) and with waist-to-height ratio (r = 0.494, p = 0.007), while sIL6-R was inversely related to HOMA-IR (r = -0.522, p = 0.002). Insulin resistant subjects showed higher levels of IL6 and lower levels of sIL6R (3.31 ± 0.72 vs. 2.25 ± 0.64 pg/ml, p = 0.020 and 25.3 ± 9.3 vs. 42.5 ± 10.4 ng/ml, p = 0.013, respectively). Conclusions: In obese children and adolescents, IR is associated with elevated levels of IL-6 and diminished values of sIL-6R.

In spite of the fact that cadmium( II) has been recognized as a highly toxic element and that excessive exposure to this metal ion has been reported to have many adverse effects on human health, very few selective and specific fluorescent probes are available for imaging Cd2+ in living cells. Herein, we report the spectroscopic and photochemical characterization of 5-(5-chloro-8-hydroxyquinolinylmethyl)- 2,8-dithia-5-aza-2,6-pyridinophane (L) as a fluorescent sensor for the selective imaging of Cd2+ in living cells. In particular, the response of L to Cd2+ was first assessed in aqueous solutions, sodium dodecyl sulfate micelles, and liposomes, and subsequently in living cells by fluorescence microscopy techniques. Cytofluorimetric analyses of leukemic HL-60 cells loaded with L also allowed evaluation of the toxicity of the probe and the selective analysis of its intracellular fluorescence in the presence of Cd2+. Furthermore, the 1:1 complex species [Cd(L)H2O]2+ responsible for the OFF–ON chelation enhancement of fluorescence (CHEF) effect on L was structurally characterized; time-dependent DFT calculations allowed the prediction of theoretical excitations, which were comparable with the experimental ones.

The metropolitan Park of Naples hills (Italy) was instituted by the regional law 17/2003 with the aim of the green area’s safeguard of the city hills. However, in consequence of the waste emergency in the Campanian region, the Italian government decided the opening of a dump in Chiaiano, a quarter located inside the Park. Through the utilization of the birds as bioindicators, we studied the environmental quality of the whole area, correlating the avifaunal indices to some landscape indices. The results show, generally, that the various areas of the park were constituted from a fragmented landscape and not many mature birds communities. The dump site, called Chiaiano wood, was not so different from other areas of the park because of a similar landscape, formed from old chestnut coppices alternated to cultivation and buildings. This is an important nesting site for some predators, as Falco peregrinus and Falco tinnunculus and of some Chiroptera. This is why the dump might cause the lost of rocky habitats in the Chiaiano wood with a remarkable impact on the ecosystem.

Some years ago was realized a project for the grey partridge reintroduction in Salerno district ( Fusco et. al., 2001), experimenting some techniques constituting a reintroduction model for this species effective on the whole Italian Apennines. One of the critical points of the reintroductions is that the hunting activity, even if legally practised, can to cause the extinction of the installed populations, because of a low carrying capacity of this population on the reintroduction area. Consequently it is necessary to find out some different regulations of the hunting activities and a strong control on the area for the installation of a durable population, self-sufficient and large on the region. Besides previous experience showed that the reintroduction success is due to the connection between the released animal and the surrounding land (VV AA,1985), then we utilized acclimatizing cages against the dispersion for the resolution of this problem. Thank to this work, we acquired a remarkable know- how regarding to the reintroduction techniques of the partridge. In fact we put systems right, based on the eco-ethological characteristics of this species. Particularly the most important aspects considered were : Environmental suitability of the area; imprinting of the breeding animals; social behavior; feeding; minimum dimension of the population; genetic structure; adaptation; predatory pressure; bio-medical aspects. In this work we applied the same reintroduction model in Rocca d’Evandro, town of the Caserta district (South Italy). The practicable analysis showed the necessity of some environmental improvements. Particularly in the flatting areas near the Garigliano river is necessary a wider environmental heterogeneity of the farm-natural landing and a bigger numbers of the hedges and of the scrubbed rows. On the hills the landing structure is suitable, but it is necessary some seeding with autumnal productions to the aim to improve the carrying capacity.

Introduction Des mutations dans le gene MKRN3 ont ete rapportees dans des formes familiales de PPCi. Ce gene est soumis a l’empreinte maternelle et aurait un effet inhibiteur sur la secretion de GnRH. Le but de ce travail a ete d’evaluer la frequence des mutations de MKRN3 et de decrire le phenotype des patients mutes. Patients et methodes Patients atteints avec PPCi definie par : Tanner Stade 2 avant 8 ans chez la fille et 9 ans chez le garcon ; pic de LH > 5 UI/L lors du test GnRH ; IRM cerebrale normale. Les formes familiales sont definies par : puberte precoce documentee et/ou menarche ≤ 10 ans chez les apparente(e)s. Resultats Quarante-six patients ont ete inclus : 28 formes familiales et 18 formes sporadiques. Six mutations considerees comme pathogenes ont ete retrouvees dans 13 familles (46 %) et 1 mutation faux sens heterozygote dans 1 cas sporadique (0,05 %). L’analyse familiale a confirme la transmission de l’allele mute par le pere. L’âge median au debut de la puberte etait plus jeune chez les patients mutes que chez les non mutes (6 ans [5,4–6]) vs 7 ans [5,8–7], p = 0,02), le profil hormonal n’etait pas different entre les 2 groupes. Conclusion Les anomalies du gene MKRN3 sont actuellement a l’origine des causes genetiques les plus frequentes des PPCi familiales, incitant a sequencer ce gene a fortiori en cas de PPC du cote paternel. La mise en evidence d’une mutation de MKRN3 permettra de depister et de traiter plus tot les membres de la fratrie possiblement porteurs.

Transfer of excitation from cadmium to sodium atoms was investigated in anheat pipe oven illuminated by a pulsed laser tuned on the intercombinationtransition of cadmium. A rich emission spectrum with cadmium as well assodium lines was observed. Intramultiplet mixing distributes the initialexcited level population 5p3P1 to the nearby fine structurelevels 5p3P0,2 of the same multiplet. We have experimentalevidence that the energy transfer pathway is from Cd (5p3PJ) to Na(4p2PJ) which is collisionally rapidly converted toNa(3d2DJ), from which the strongest emission was observed.PACS No.: 34.90+q

We report experimental rate coefficients for the reverse heteronuclear energy-pooling collisions $\mathrm{K}(5D)+\mathrm{Na}(3S)\ensuremath{\rightarrow}\mathrm{K}(4P)+\mathrm{Na}(3P)$ and $\mathrm{K}(7S)+\mathrm{Na}(3S)\ensuremath{\rightarrow}\mathrm{K}(4P)+\mathrm{Na}(3P)$ at thermal energies. Both reactions are exothermic and very high rates were observed showing that reverse exothermic energy-pooling is an order of magnitude more efficient than the corresponding forward endothermic energy-pooling reactions. This is in accordance with the general behavior of the exothermic and endothermic energy-pooling rate coefficients in alkali-metal atoms. In the experiment the potassium atoms were excited in two steps to either the $5D$ or $7S$ state via the $4P$ level using two broadband cw dye lasers. A double-modulation technique has been used to select the fluorescence contributions at the $\mathrm{Na}{(3P}_{J})$ exit channels due only to the above reactions. The ground-state sodium and potassium atom densities were measured by the absorption of lines from a K-Na hollow-cathode lamp. The measured densities and fluorescence intensities have been used to obtain absolute reverse energy-pooling rate coefficients. The contribution to the rate coefficients from other processes are discussed.

Le retard constitutionnel de croissance et de puberte (RCCP) est une cause frequente de petite taille ou, apres un ralentissement temporaire de la croissance, on atteint, selon la definition classique, une taille normale par rapport au potentiel genetique. Patients et methodes. - Du fait de l'absence d'unanimite sur l'atteinte de la cible genetique de ces patients, nous avons juge utile d'evaluer la taille definitive de 20 patients (11 garcons et neuf filles), suivis pour RCCP, en la mettant en rapport avec leur cible genetique et la prediction de la taille definitive par la methode de Bayley et Pinneau, avant la puberte. Ces enfants n'avaient jamais ete traites. Resultats. - On a observe, chez tous les patients, une amelioration spontanee de la taille, de la puberte a l'âge adulte (de -2,9 ± 0,7 SDS a -1,3 ± 0,6 SDS chez les garcons et de -2,6 ± 0,6 SDS a -0,9 ± 0,3 SDS chez les filles ; p < 0,001). Chez les garcons, la taille definitive (166,4 ± 4,1 cm) mesuree a l'âge moyen de 21 ans, etait en harmonie avec la cible genetique (165,7 ± 3,9) et avec la prediction staturale (167,3 ± 3,1). Chez les filles, la taille definitive atteinte (156,6 ± 2,0) mesuree a l'âge moyen de 20,4 ans, correspondait a la cible genetique (153,3 ± 4,2) et a la prediction de taille precedemment effectuee (155,6 ± 2,3). Conclusion. - Dans notre etude, les patients avec RCCP ont la taille definitive prevue et atteignent leur potentiel familial sans traitement.

Energy-pooling collisions between low-lying excited states of Ba have been studied. We have used a CW dye laser to excite the level in Ba. Radiative decay and collisions with Ba or buffer-gas atoms (Ar, He) populate also the , and metastable levels. The spatial density distributions of these excited levels were measured by the absorption of lines from a Ba hollow-cathode lamp as a function of laser frequency. When the laser was on the exact atomic resonance we observed fluorescence from the , , , , , , and states populated by energy-pooling collisions of Ba(, ). By changing the buffer gas pressure the fluorescence intensity ratio between - and - transitions changes dramatically. This is found to be due to redistribution of population among metastable levels, both in magnitude and space. In addition, we have found that the and metastable levels are also populated when the laser is tuned to the blue from the 553.5 nm line under which conditions a pronounced red-shifted light cone (cone emission) is observed.

Contexte Le test GnRH/LHRH est largement utilise dans l’exploration des HHC. Pourtant, son interet, qui n’a pas ete evalue, est incertain. Objectif Evaluer les reponses des gonadotrophines a cette stimulation chez des HHC/SK, RPS et des hommes normaux (C) de facon a preciser ses performances diagnostiques. Patients et methodes Etude chez 127 HHC dont 54 % SK (25,5 ± 9,9 ans) ; 90 RPS (14,9 ± 1,0 ans) non traites et 31 C (25,9 ± 5,2 ans). Volume testiculaire (VT) mesure par orchidometre. Test GnRH (100 μg) avec dosages de LH et FSH (methode sandwich) ; sensibilite 0,05 UI/L pour les deux. Dosage Elisa d’inhibine B (IB), sensibilite : 5 pg/mL. Resultats Les bases et les pics de LH (UI/L) etaient : C, base : 4,2 ± 0,9 [2,9–6,1], pic : 17,9 ± 3,7 [11,1–26,0] ; HHC, base : 0,8 ± 1,0 [0,0–7,0], pic : 6,8 ± 7,6 [0,1–41,5] ; RPS, base : 1,2 ± 0,8 [0,0–3,7], pic : 13,1 ± 6,5 [0,4–33,4]. Parmi les 127 HHC, 36 avaient des pics de LH dans l’intervalle des pics des controles et 69/127 HHC avait des pics de LH dans l’intervalle des pics des RPS. Chez les HHC, il existait une correlation entre le pic de LH et le VT (r = 0,39 ; p Discussion Le pic de LH chez les HHC/SK est tres variable. Il depend de la profondeur du deficit gonadotrope. Il existe un chevauchement important entre les trois populations. Le pic de LH n’apporte aucune plus-value diagnostique/a la LH de base pour distinguer les HHC/SK des C et des RPS.

We present simulations of bound–bound and bound–free emissions of the NaCd* excimer, along with new experimental results concerning the red band system. The simulations, based on ab initio potential energy curves, confirm that the initial states are 2 2Σ+ for the red emission and 2 2Π for the blue emission of NaCd*. The two main peaks in the blue band system are due to spin–orbit splitting. The band shape obtained in the simulations is extremely variable, depending on the population distribution of the vibrational states of NaCd*. The comparison of simulated and measured spectra leads us to conclude that, in the experimental conditions adopted here and in previous work, the thermal equilibration of the excimer is far from complete.

We report the observation of reactive collisions involving laser excited metastable 5p 3 P 1 Cd atoms and ground state Na 2 molecules. As result of these collisions the NaCd intermetallic excimer is formed in a bound excited electronic state and its typical bound-free emission to the ground state is detected. Experimental comparison of this new collision channel with the photochemical production of NaCd in collisions between electronically excited Na 2 and ground state Cd atoms is presented.

For decades the vitamin D biological system has been considered almost exclusively as the master integrator of calcium-phosphate homeostasis and bone metabolism. More recently, the discovery that many human tissues and cells, which do not directly participate in mineral ion homeostasis, express the vitamin D receptor (VDR) and are able to convert the circulating pro-hormone 25-hydroxyvitamin D in its active form, 1,25-dihydroxyvitamin D, has provided new insights into the biological function of this peculiar endocrine system. Several reports have highlighted a variety of human diseases possibly related to vitamin D insufficiency or deficiency (respectively defined as 25-hydroxyvitamin D serum levels lower than 30 or lower than 20 ng/ml). In particular, experimental and observational studies, including those published in this journal issue, support the concept that vitamin D deficiency is involved in the pathogenesis of congestive heart failure, a disabling condition affecting over 15 million of patients worldwide. Considering that circulating levels of 25-hydroxyvitamin D represent the accepted clinical indicator of individual vitamin D status, the measurement of this pro-hormone can be regarded as an appropriate and cost-effective screening tool in patients with chronic heart failure.

BACKGROUND: The prevalence of Paget's disease of bone (PDB) is unknown in peninsular Southern Italy, although an elevated clinical severity of the disease was reported in patients from Campania. AIM: This study was performed to evaluate the epidemiological and genetic characteristics of PDB in a rural area of Calabria, the southernmost region in the Italian peninsula. SUBJECTS AND METHODS: We examined 1068 consecutive pelvic radiographs of patients older than 40 yr referred for any reason to the "Spinelli" Hospital, Belvedere Marittimo, from January 1st 2004 to December 31st 2006. In subjects with radiological findings of pelvic PDB, a 99m Technetium methylene diphosphonate bone scan and the sequence analysis of the sequestosome 1 (SQSTM1) gene were subsequently performed. RESULTS: In the examined geographic area, the crude radiographic prevalence of pelvic PDB was 0.74% (8/1068; male:female 5:3, mean age 71.6 ± 13.1 yr) whereas the estimated overall prevalence of PDB between 0.82% and 1.21%. PDB patients from Calabria showed clinical characteristics similar to those reported in patients from Campania. The disease was also frequently complicated by osteoarthritis and the right side of the body was more affected than the left. The SQSTM1 gene analysis revealed the presence of a novel missense mutation (M401V) in exon 8 in one subject with a familial and aggressive form of PDB. CONCLUSION: The study results confirmed that patients with PDB from rural districts of Southern Italy show an earlier onset and an increased clinical severity of the disease that appears mostly independent from the presence of germinal SQSTM1 mutations.

Phosphate plays a vital role in several biological processes including energy and nucleic acid metabolism, cell signaling and bone mineralization. Several endocrine factors coordinately act on the intestine, kidney and bone to maintain their physiological homeostasis. A number of peptides, collectively known as phosphatonins, have recently been identified as regulators of phosphate metabolism in physiological and pathological conditions. These factors--fibroblast growth factors (FGF) 23 and 7, secreted frizzled related protein 4 (sFRP-4), and matrix extracellular phosphoglycoprotein (MEPE)--primarily regulate tubular phosphate reabsorption by acting on the transmembrane expression of SLC34 sodium-phosphate cotransporters. FGF- 23, FGF-7 and sFRP-4 also inhibit the biosynthesis of 1,25(OH)2D3, leading to decreased intestinal phosphate absorption. In this review, we discuss the biological properties of these peptides, their physiological roles, and the alterations in their concentrations in various hypophosphatemic and hyperphosphatemic clinical disorders.

To evaluate growth and pubertal development in children with IDDM and the influence of the age at onset of IDDM and the degree of metabolic control on final height. We conducted a retrospective evaluation of 62 subjects followed longitudinally both clinically and metabolically from the onset of IDDM until final height was reached. Height at diagnosis was within the normal percentiles in boys (0.5 +/- 1.0 standard deviation score [SDS]) and girls (0.4 +/- 1.0 SDS), but above the genetic target height (-1.0 +/- 0.9 SDS in boys and -1.1 +/- 0.6 SDS in girls; P = 0.0001 for both comparisons). Although a lesser height gain was observed during the ensuing years, the final height reached by boys (-0.4 +/- 1.1 SDS) and girls (-0.4 +/- 0.9 SDS) was higher than the genetic target height. Blunted total pubertal growth was observed both in boys (24.5 +/- 3.6 cm) and girls (20.1 +/- 4.2 cm). The decrease in height gain was independent of the duration of IDDM, the degree of metabolic control, or the insulin requirement. The greater the height at diagnosis, with respect to the genetic target height, the lesser was the subsequent height gain to reach final adult height (r = 0.34, p < 0.01). BMI increased with age as normally occurs in healthy children, independent of the duration of disease and the degree of metabolic control. Pubertal development began and progressed normally both in boys and girls. In boys, a testicular volume of 4 ml was reached at a mean age of 12.1 +/- 0.9 years. In girls, breast enlargement occurred at a mean age of 10.4 +/- 1.2 years and the mean age of menarche was 12.8 +/- 1.4 years. Pubertal development and progression occurred independent of the age at onset of IDDM, the glycemic control, or the insulin requirement during the pubertal period. Children with IDDM have normal onset of puberty and normal sexual maturation. Even though final height falls within the normal percentiles, the diminished height gain after diagnosis requires further investigation.

En France, des dizaines de milliers d’enfants et d’adolescents sont en surpoids. La majorite n’a qu’un exces de quelques kg, mais un petit nombre rentre dans la definition de « superobesite », ce qui correspond a un IMC de 50 a l’âge adulte. Les defauts metaboliques ne sont pas le probleme principal de ces adolescents. Progressivement desocialises, ils ne forment plus aucun projet d’avenir, et n’imaginent pas pouvoir se sortir un jour de leur etat. De 1995 a 2010 nous avons pris en charge une grande cohorte d’enfants obeses : plus de 90 % ne purent stabiliser leur poids, ni ameliorer de facon perceptible les consequences de l’obesite. En 2010, nous avons tire les consequences de nos echecs, en decidant de consacrer notre effort a la tres grande obesite. Apres une experience de pose d’anneaux gastriques, nous avons abandonne cette technique pour concentrer notre offre de soins sur un programme de sleeve gastrectomie par trocart unique. Indications : prediction d’un poids superieur a 120 kg a 16–18 ans, echec de la prise en charge classique. Procedure : parcours d’un an avec consultations et hospitalisations de jour. Detection des complications. Decision finale selon une procedure RCP. A trois annees de la mise en place du programme, notre unite assure maintenant une trentaine d’interventions par an. Les resultats ont ete brillants, sans complications a ce jour et surtout la perception par tous les patients d’une amelioration de la qualite de vie. L’evidence d’une obesite massive, resistante, evoluant rapidement a l’adolescence, est devenue notre indication.

The pathways leading to female sexual determination in mammals are incompletely defined. Loss-of-function mutations in the WNT4 gene appear to cause developmental abnormalities of sexual differentiation in women and mice. We recruited six patients with different degrees of Miillerian abnormalities, with or without renal aberrations and a normal female 46,XX karyotype. A clear androgen excess was found only in one patient. This 19-year-old woman was affected by primary amenorrhoea, absence of Miillerian ducts derivatives, clinical (acne and hirsutism) and biochemical (repeatedly high levels of testosterone) signs of androgen excess. Direct sequencing of her WNT4 gene followed by functional studies in human ovarian cells (OVCAR3) was performed. This patient carried the novel R83C loss-of-function dominant negative mutation in her WNT4, confirming the role of WNT4 in the development and maintenance of the female phenotype in women. Our study can also help refine the phenotype of WNT4 deficiency in humans. In fact, it appears that at least in this limited casuistic small group of patients, the absence of a uterus (and not other Mullerian abnormalities) and the androgen excess are the pathognomonic signs of WNT4 defects, suggesting that this might be a clinical entity distinct from the classic Mayer-Rokitansky-Kuster-Hauser syndrome.

BACKGROUND AND STUDY AIMS: It is difficult to measure the prevalence of hereditary non-polyposis colorectal cancer (HNPCC) in geographical areas that do not have tumor registers, as is the case in the present study, and it was therefore decided to assess the prevalence in Italy using different methods. PATIENTS AND METHODS: The pedigree was established for 485 of 501 colorectal cancer patients diagnosed with colorectal carcinomas. Patients were included consecutively in 13 gastroenterology centers; they had not taken part in prevention examinations. Information was collected regarding the neoplastic pathology observed in the families, confirmed in 90% of cases among 3515 first-degree relatives and in 79.5% of cases among 7068 second-degree relatives. RESULTS: In the 3515 first-degree relatives (1002 parents, 1560 siblings and 953 children), 61 colorectal carcinomas, 29 carcinomas in the digestive tract outside the colon, and 99 carcinomas in other locations were reported. Only five of the 485 patients (1%) satisfied the Amsterdam criteria (three cancers, two of which were in first-degree relatives in different generations and one in a relative younger than 50). When broadening the criteria that we are proposing (satisfying only two of the three Amsterdam criteria), the prevalence would increase to 3% (15 cases). CONCLUSIONS: Modifying the criteria makes it easier to identify new mutations or confirm the existence of those already known, as well as allowing preventative treatment in relatives who are apparently healthy.

OBJECTIVE To evaluate growth and pubertal development in children with IDDM and the influence of the age at onset of IDDM and the degree of metabolic control on final height. RESEARCH DESIGN AND METHODS We conducted a retrospective evaluation of 62 subjects followed longitudinally both clinically and metabolically from the onset of IDDM until final height was reached. RESULTS Height at diagnosis was within the normal percentiles in boys (0.5 ± 1.0 standard deviation score [SDS]) and girls (0.4 ± 1.0 SDS), but above the genetic target height (−1.0 ± 0.9 SDS in boys and −1.1 ± 0.6 SDS in girls; P = 0.0001 for both comparisons). Although a lesser height gain was observed during the ensuing years, the final height reached by boys (−0.4 ± 1.1 SDS) and girls (−0.4 ± 0.9 SDS) was higher than the genetic target height. Blunted total pubertal growth was observed both in boys (24.5 ± 3.6 cm) and girls (20.1 ± 4.2 cm). The decrease in height gain was independent of the duration of IDDM, the degree of metabolic control, or the insulin requirement. The greater the height at diagnosis, with respect to the genetic target height, the lesser was the subsequent height gain to reach final adult height (r = 0.34, p < 0.01). BMI increased with age as normally occurs in healthy children, independent of the duration of disease and the degree of metabolic control. Pubertal development began and progressed normally both in boys and girls. In boys, a testicular volume of 4 ml was reached at a mean age of 12.1 ± 0.9 years. In girls, breast enlargement occurred at a mean age of 10.4 ± 1.2 years and the mean age of menarche was 12.8 ± 1.4 years. Pubertal development and progression occurred independent of the age at onset of IDDM, the glycemic control, or the insulin requirement during the pubertal period. CONCLUSIONS Children with IDDM have normal onset of puberty and normal sexual maturation. Even though final height falls within the normal percentiles, the diminished height gain after diagnosis requires further investigation.

The aim of this study was to determine whether the proportion of circulating B cells expressing the differentiative antigen CD5 was increased in children affected by type 1 diabetes, and whether the number of these cells was correlated with the presence of anti-islet cell autoantibodies. Sixteen children affected by insulin-dependent diabetes mellitus (type 1) were investigated for the presence of B lymphocytes bearing the CD5 surface molecule, T-cell-specific activation markers, organ- and nonorgan-specific autoantibodies. The number of CD5+CD19+ cells was higher in type 1 children with a very recent onset of the disease, as compared with patients on insulin therapy for more than 30 days and controls (P < 0.05). No correlation was found between the number of CD5+CD19+ cells and the presence of either organ- or nonorgan-specific autoantibodies. Our results indicate that CD5+CD19+ cells are involved in the pathogenesis of type 1 diabetes in children. A potential immunoregulatory role of this B cell population is discussed.

The observation of a heteronuclear reverse energy pooling process is reported. The cross section for the collision processes K(5D)+Na(3S){r_arrow}K(4P)+Na(3P) has been measured and compared to calculations carried out using a multicrossing Landau-Zener model. {copyright} {ital 1997} {ital The American Physical Society}

Constitutional delay of growth and puberty (CDGP) is a frequent cause of short stature in childhood. Controversial results have been reported on the full achievement of these patients of their target height.The final adult height of 20 patients with CDGP (11 male and 9 female), who did not received hormonal treatment, was compared with their target height and with the predicted adult height, by the Bayley-Pinneau method obtained before the onset of puberty.A spontaneous improvement of the stature from pre-puberty to adulthood was observed in all patients (from -2.9 +/- 0.7 SDS to -1.3 +/- 0.6 SDS in male and from -2.6 +/- 0.6 SDS to -0.9 +/- 0.3 SDS in female; P0.001). Adult height in male (166.4 +/- 4.1 cm) at the mean age of 21 years was very close to the target height (165.7 +/- 3.9 cm) and to the predicted adult height (167.3 +/- 3.1 cm). Also in female, final height (156.6 +/- 2.0 cm) did not differ from target height (153.3 +/- 4.2 cm) and from predicted adult height (155.6 +/- 2.3 cm).In our experience, patients with CDGP reach their predicted adult height and achieve their genetic potential without medical treatment.

Non Insulin Dependent Diabetes Mellitus (NIDDM) in pediatric age remains not well defined as a nosological entity. The so-called Maturity Onset Diabetes of the Young (MODY), for example, recognizes three different etiologies. Three cases are presented as an example of different possibilities of onset and evolution in pediatric age: a 12.5 year old girl presents a positive familial history of NIDDM, a slow onset of the disease and goes on well with administration of an oral hypoglycemic drug; a 12.5 year old girl too, with a positive familial history of NIDDM, with acute onset of the disease, needed an oral hypoglycemic drug when she was overweight. Having lost the ponderal excess, she goes on very well with the diet alone; a 13 year old girl without any familial history of NIDDM, who presented a dramatic onset in occasion of an intercurrent illness; she required insulin therapy only during a steroidal therapy period, administered for ovaric polycystosis. The authors argue over the age of onset, the familial history and the therapeutic approach to NIDDM in pediatric age.

In juvenile IDDM patients, immunosuppression with cyclosporin A allows partial beta-cell function recovery and transient remissions of insulin dependency. The effects of this therapeutic approach, however, have not been evaluated in the long-term, since no reported trial exceeded 1 year. Here we analyze 130 diabetic children followed at our institution during the first years of their disease. Cyclosporin was given to 83 of them at an initial dose of 7.2 ± 0.1 mg·kg−1·day−1, which was decreased stepwise then interrupted after 6–62 months, depending on the response to therapy. A total of 47 diabetic children, who served as control subjects in two trials, were pooled for comparison. Over 4 years, the cyclosporin-treated group kept plasma C-peptide ∼ twice as high as the control group (P < 0.02). It took 5.8 ± 0.6 years for C-peptide secretion stimulated by glucagon to become undetectable in the cyclosporin group versus 3.2 ± 0.6 years in the control group (P < 0.02). Average insulin dose remained lower by 0.2–0.4 U·kg−1·day−1 and glycated hemoglobin by ∼ 1% in cyclosporin-treated patients (P < 0.02), who also had less hypoglycemia than the diabetic control subjects (P < 0.05). After 4 years, differences between the groups became nonsignificant. We observed no significant secondary effects of cyclosporin. In conclusion, positive effects of low-dose cyclosporin in recently diagnosed clinical IDDM patients are prolonged beyond interruption of the drug. The magnitude and duration of the benefit, however, do not appear sufficient to justify this immunosuppressive treatment in clinical practice.

Cases of diabetes mellitus associated with Turner syndrome are noninsulin-dependent. We report a case of insulin-dependent diabetes mellitus (IDDM) with Turner syndrome.An 11 year-old girl with Turner syndrome was investigated for glucose tolerance that was normal with glycosylated hemoglobin at 5.1%. The patient was then given growth hormone plus oxandrolone until the age of 15 yr 3 mo; estrogen replacement was initiated at 15 yr 9 mo and progesterone 6 months later. At the age of 16.5 yrs, the patient developed manifestations of diabetes mellitus with polyuria, polydipsia, weight loss. Blood glucose concentration was 415 mg/dl with ketoacidosis. She was given insulin; at that time, blood insulin level was 7 mU/ml, C-peptide 0.8 ng/ml and glycosylated hemoglobin Alc 8.2%. Islet cell auto-antibodies were positive (1/80) and histocompatibility antigens were A1, A2, B14, B18, CW7, DR7, DR11, DQ7. After 6 months of treatment, blood insulin and C-peptide after IV glucagon were nil. There was no familial case of IDDM.This case of IDDM seems to be the first reported in Turner syndrome. This IDDM could be a manifestation of autoimmunity.

The case is reported of a young girl who was bitten on the hand by a viper and developed compartment syndrome of the intrinsic muscles more than 24 h later. Multiple dorsal and volar fasciotomies resolved the acute episode with complete restitutio ad integrum. The clinical case is discussed in detail and the literature on these rare complications of snake bites in European countries reviewed.