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Polymer crystallization, particularly near the glass transition, exhibits strong nonlinearities and prolonged metastability that enable fabrication of devices with complex hierarchal structure from nm to mm. A fascinating example arises in the production of bioresorbable scaffolds (BRS) from poly(L-lactide) (PLLA), in which a sequence of processes (extrusion, stretch-blow molding and crimping) create diverse semicrystalline morphologies, side-by-side within a span of a hundred microns (Figure 1). To discover how these structures form, we need to examine transient structure under conditions that mimic manufacturing processes. An apparatus that enables scattering measurements during the stretch-blow molding step, called “tube expansion” imposes a nearly constant-width elongation as it converts an extruded “preform” into an “expanded tube”. To increase the range of accessible properties of PLLA-based BRS, we use this apparatus to examine inorganic nanotubes as potential reinforcing agents that also enhance radiopacity, relevant to clinical applications. Understanding how their microstructure develops during processing is relevant to increasing strength to enable thinner devices and improving radiopacity to enable imaging during implantation. Consistent with the premise of this MS, in-situ X-ray scattering reveals unanticipated phenomena in the transient microstructure of PLLA/WS2NTs nanocomposites during “tube expansion” (Figure 2).

Aims Childhood and adolescent obesity has been defined as a planetary epidemic by WHO “globesity”. The obesogenic environment, defined as a life environment promoting a high-energy intake and a sedentary lifestyle, significantly contributes to the genesis and the diffusion of the globesity. In the last decades, several authors and working groups tried to develop methodological instruments in order to guarantee a reliable analysis of an obesogenic environment. Their efforts have led to the production of a relatively large number of questionnaires with different characteristics. The general aim of these questionnaires is to identify the factors that significantly contribute to the creation of an obesogenic environment around children and adolescents. As a result of this work, a number of studies were carried out using such questionnaires. Aim of this review is to evaluate ad hoc questionnaires useful to identify and analyze obesogenic environment. Data synthesis The search was carried out in February–March 2017 using the PubMed-Medline and Scopus databases (time interval: the last 10 years). After the selection and verification phases, a total of 14 studies were selected and therefore included in the present review. Conclusions The questionnaires constructed and validated to analyze multiple constitutive elements of an obesogenic environment at the same time are complex and must be administered by qualified and trained staff. On the other hand, when two or more questionnaires are used to analyze different factors, the questionnaires used are generally shorter, self-administered, and generally easier to understand and interpret.

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 Müllerian 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 Müllerian 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 Müllerian 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

Minimally invasive approach to the adrenal gland was first reported in 1992. Since then, the experience with the laparoscopic technique for adrenal disease in children has been limited. We report our experience with minimally invasive adrenal surgery in children. Two young girls (2 and 4 years old) with a left adrenal mass were operated using minimally invasive surgery (MIS) in our Unit. Ultrasonography and MRI showed in the oldest a 2 x 3 cm adrenal mass, while in the youngest a 5.5 x 5 cm adrenal tumor was found. According to the pre-existing literature, we approached the smallest lesion via retroperitoneoscopy, and the largest one laparoscopically. The operating time was 110 minutes for retroperitoneoscopy and 75 minutes for laparoscopy. No major intra or postoperative complications occurred. There were no conversions to open surgery. Postoperative hospital stay was 5 days for both patients. In both cases, the anatomo-pathological result was an adenoma. Minimally invasive adrenalectomy is a safe and feasible procedure in children with good results. For lesions smaller than 3-4 cm retroperitonescopy is feasible, while for tumors larger than 5 cm, due to malignancy risk, the laparoscopic approach is indicated. To keep oncologic criteria it is important to avoid tumor rupture and to extract the specimen in an endobag.

BACKGROUND: CaSR gene is a candidate for calcium nephrolithiasis. Single-nucleotide polymorphisms (SNPs) encompassing its regulatory region were associated with calcium nephrolithiasis. AIMS: We tested SNPs in the CaSR gene regulatory region associated with calcium nephrolithiasis and their effects in kidney. SUBJECTS AND METHODS: One hundred sixty-seven idiopathic calcium stone formers and 214 healthy controls were genotyped for four CaSR gene SNPs identified by bioinformatics analysis as modifying transcription factor binding sites. Strontium excretion after an oral load was tested in 55 stone formers. Transcriptional activity induced by variant alleles at CaSR gene promoters was compared by luciferase reporter gene assay in HEK-293 and HKC-8 cells. CaSR and claudin-14 mRNA levels were measured by real-time PCR in 107 normal kidney medulla samples and compared in patients with different CaSR genotype. RESULTS: Only rs6776158 (A>G), located in the promoter 1, was associated with nephrolithiasis. Its minor G allele was more frequent in stone formers than controls (37.8% vs 26.4%, P = .001). A reduced strontium excretion was observed in GG homozygous stone formers. Luciferase fluorescent activity was lower in cells transfected with the promoter 1 including G allele at rs6776158 than cells transfected with the A allele. CaSR mRNA levels were lower in kidney medulla samples from homozygous carriers for the G allele at rs6776158 than carriers for the A allele. Claudin-14 mRNA levels were also lower in GG homozygous subjects. CONCLUSIONS: Minor allele at rs6776158 may predispose to calcium stones by decreasing transcriptional activity of the CaSR gene promoter 1 and CaSR expression in kidney tubules.

Context:The incidence of type 1 diabetes has been increasing over time.Objective:We estimated the genetic and environmental components of type 1 diabetes susceptibility in a twin cohort of recent-onset cases to explore the sources of changing disease epidemiology.Design:We linked the population-based Italian Twin Registry with 14803 type 1 diabetes records from 36 pediatric diabetes care centers throughout Italy, except Sardinia, and identified 173 diabetic twins. Patients were positive for at least one autoantibody to islet cell, glutamate decarboxylase, tyrosine phosphatase, insulin, or zinc transporter 8 and were insulin dependent since their diagnosis. Zygosity was determined by DNA genotyping or by questionnaire.Outcome Measures:We estimated proband-wise concordance, cotwin recurrence risk with Kaplan-Meier method, and genetic and environmental proportions of susceptibility variance by structural equation models.Results:We recruited 104 diabetic twins (53 males) from 88 pairs (34 monozygotic, 54 dizygotic) and one triplet. The mean age at diagnosis was 8.1 yr (range 1.1-20.5 yr), and the median year of diagnosis was 2002. Proband-wise concordances were 45.5 and 16.4% in monozygotic and dizygotic pairs (P = 0.01). Recurrence risks in monozygotic and dizygotic cotwins were 37 and 12% after 10 yr from the proband's diagnosis (P = 0.005). Genetic contribution to type 1 diabetes susceptibility was 40% (95% confidence interval 8-78), and the shared and individual-specific environmental components were 51% (14-77) and 9% (4-19), respectively.Conclusions:In addition to the moderate genetic effects on type 1 diabetes susceptibility, our results draw attention to the substantial shared environmental effects, suggesting that exposures in fetal or early postnatal life may contribute to the increasing incidence of the disease.

Background. - Cases of diabetes mellitus associated with Turner syndrome are non-insulin-dependent. We report a case of insulin-dependent diabetes mellitus (IDDM) with Turner syndrome. Case report. - 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. Conclusions. - This case of IDDM seems to be the first reported in Turner syndrome. This IDDM could be a manifestation of autoimmunity.

The observation of a heteronuclear reverse energy pooling process is reported for the first time. The cross section for the collision processes K(5D)+Na(3S) $ o $ K(4P)+Na(3P) has been measured and compared to calculations carried out using a multicrossing Landau--Zener model.

To evaluate serum levels of osteoprotegerin (OPG), soluble receptor activator of the nuclear factor-kappa B (RANKL), and their relationship with FGF-23, lumbar bone mineral density (BMD), and bone turnover markers, five patients with tumor-induced osteomalacia (TIO) and 40 healthy controls were studied. TIO patients were followed for 360 days after surgical removal of underlying tumor (n = 2) or beginning of therapy with phosphate and calcitriol when surgical treatment was impossible (n = 3). At diagnosis, TIO patients had higher levels of FGF-23 and bone-specific alkaline phosphatase (bALP) and lower levels of cathepsin K (CathK), RANKL, and RANKL/OPG ratio compared to controls. During the follow-up, FGF-23 decreased significantly only in patients who underwent a surgical excision, while phosphate and BMD increased in all patients. The increases in BMD, phosphate, and renal phosphate reabsorption rate were directly related. In the first 60 days of follow-up, we observed a prolonged inhibition of RANKL, CathK, and bone resorption markers associated with a persistence of TIO symptoms and an increase in bALP. From day 60, levels of bone turnover markers returned progressively within the normal range and a clinical remission was observed. The inhibition of the RANKL/OPG pathway and the uncoupling of bone formation and resorption observed in patients with active TIO may be a compensatory mechanism, attempting to reduce worsening of osteomalacia. The BMD increase during TIO treatment is related to the improvement of phosphate rather than FGF-23 levels. A "hungry bone"-like syndrome was observed after surgical or pharmacological treatment.

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.

Osteoporosis and nephrolithiasis are common multifactorial disorders with high incidence and prevalence in the adult population worldwide. Both are associated with high morbidity and mortality if not correctly diagnosed and accurately treated. Nephrolithiasis is considered a risk factor for reduced bone mineral density. Aim of this retrospective longitudinal study was to evaluate if osteoporosis is a predictive factor for the nephrolithiasis occurrence. Free-living subjects referring to “COMEGEN” general practitioners cooperative operating in Naples, Southern Italy. Twelve thousand seven hundred ninety-four Caucasian subjects (12,165 female) who performed bone mineral density by dual-energy X-ray absorptiometry and have a negative personal history for nephrolithiasis. Subjects aged less than 40 years or with signs or symptoms suggestive of secondary osteoporosis were excluded from the study. In a mean lapse of time of 19.5 months, 516 subjects had an incident episode of nephrolithiasis. Subjects with osteoporosis had an increased risk of nephrolithiasis than subjects without osteoporosis (Hazard Ratio = 1.33, 95% Confidence Interval 1.01–1.74, p = 0.04). Free-living adult subjects over the age of 40 with idiopathic osteoporosis have an increased risk of incident nephrolithiasis, suggesting the advisability of appropriate investigation and treatment of the metabolic alterations predisposing to nephrolithiasis in patients with osteoporosis. The study protocol was approved by the ASL Napoli 1 Ethical Committee, protocol number 0018508/2018

In this work, the introduction of small variations in the electrical impedance ofHF (High Frequency) RFID (Radio Frequency Identification) tags has been exploited in the proximity sensing of temperature by applying Polyvinylidene Fluoride (PVDF) interdigital capacitive sensors as a modification of the transponder’s circuitry. The adopted electrical parasitic sensing load introduces a shift in the primary resonance peakof the tag. Theimpedance spectra have been acquired by a dedicated laboratory setup allowing to apply simultaneously thermal forcing and RF signals to the transponder itself. Thesensitivity of the modified taghas been assessed after taking into account the thermal response of the transponder chipwhich is relevant in the formulation of thermal-sensing transponders.

Adequate vitamin D status is essential for skeletal health. Paget’s disease of bone (PDB) is a common metabolic skeletal disorder, but data regarding the vitamin D status in PDB patients are lacking. We performed a case–control study to estimate vitamin D status in 708 PDB patients and in 1803 healthy controls from Italy and an observational prospective study to evaluate the efficacy–safety profile of oral cholecalciferol treatment [400.000 International Units (UI) of cholecalciferol administered in cycles of 8 weeks until 25OHD levels reaches 70 nmol/L as primary therapy and 50.000 UI of cholecalciferol administered every 2 weeks for 52 weeks for the maintenance therapy] in 82 PDB patients with hypovitaminosis D, i.e., 25OHD

Coronary Heart Disease (CHD) is one of the leading causes of death worldwide, claiming over seven million lives each year. Permanent metal stents, the current standard of care for CHD, inhibit arterial vasomotion and induce serious complications such as late stent thrombosis. Bioresorbable vascular scaffolds (BVSs) made from poly L-lactide (PLLA) overcome these complications by supporting the occluded artery for 3-6 months and then being completely resorbed in 2-3 years, leaving behind a healthy artery. The BVS that recently received clinical approval is, however, relatively thick (~150 μm, approximately twice as thick as metal stents ~80 μm). Thinner scaffolds would facilitate implantation and enable treatment of smaller arteries. The key to a thinner scaffold is careful control of the PLLA microstructure during processing to confer greater strength in a thinner profile. However, the rapid time scales of processing (~1 s) defy prediction due to a lack of structural information. Here, we present a custom-designed instrument that connects the strain-field imposed on PLLA during processing to in situ development of microstructure observed using synchrotron X-ray scattering. The connection between deformation, structure and strength enables processing-structure-property relationships to guide the design of thinner yet stronger BVSs. © 2018 by the authors.