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CsO2 is a member of the family of alkali superoxides (formula AO2 with A= Na, K, Rb and Cs) that exhibit magnetic behavior arising from open $p$-shell electrons residing on O2- molecules. We use neutron diffraction to solve the crystal and magnetic structures of CsO2, and observe a complex series of structures on cooling from room temperature to 1.6 K. These include an incommensurate modulation along the a-axis of the structure at intermediate temperatures, which then locks into a commensurate modulation that doubles the unit cell compared to the previously supposed orthorhombic unit cell. In both incommensurate and commensurate phases our structural solution involves a staggering of the cesium ion positions along the b-axis, in contrast to studies of other alkali superoxides in which staggered tilts of the O2- dimers relative to the c-axis are seen. Below T ~ 10 K we observe magnetic Bragg reflections arising from an antiferromagnetically ordered structure with a wavevector of k = (0,0,0) (relative to the doubled crystallographic unit cell), with moments that point predominantly along the b-axis with a small component along the a-axis that hints at possible anisotropic exchange coupling (consistent with the crystal structure). Measurements of the magnetic Bragg reflections in an applied magnetic field suggest a spin-flop transition takes place between 2 T and 4 T in which moments likely flop to point along the crystallographic a-axis. Our measurements indicate that CsO2 is an interesting example of magnetic properties being inherently linked to the crystal structure, in that the staggered displacement of the cesium ions activates antisymmetric exchange which then permits the observed spin canting., Comment: 13 pages, 11 figures, 6 tables

Noncollinear magnetism can play an important role in multiferroic materials but is relatively understudied in oxide heterostructures compared to their bulk counterparts. Using variable temperature magnetometry and neutron diffraction, we demonstrate the presence of helical magnetic ordering in CaMn7O12 and Ca1−xSrxMn7O12 (for x up to 0.51) thin films. Consistent with bulk Ca1−xSrxMn7O12, the net magnetization increases with Sr doping. Neutron diffraction confirms that the helical magnetic structure remains incommensurate at all values of x, while the fundamental magnetic wavevector increases upon Sr substitution. This result demonstrates a chemical-based approach for tuning helical magnetism in quadruple perovskite films and enables future studies of strain and interfacial effects on helimagnetism in oxide heterostructures.

Background: During the course of acromegaly, cardiovascular, respiratory, and metabolic co-morbidities contribute to enhanced mortality. In 2002, the Pituitary Society and the European Neuroendocrine Association sponsored a Consensus Workshop in Versailles during which guidelines for diagnosis and treatment of co-morbidities in acromegaly were defined. However, as for other guidelines previously issued in the field, no data are available on their clinical application. Aim: The aim of this work coordinated by the Italian Study group on co-morbidities evaluation and treatment in acromegaly (COM.E.T.A.) was to assess, on a national basis, the application in the clinical practice of the Versailles criteria for diagnosis and treatment of cardiovascular comorbities in acromegaly. Materials and methods: In January 2007 an ad hoc designed questionnaire was sent by mail to 130 endocrine Centers in Italy. Results: The guidelines have been generally well perceived and translated in clinical practice. Specifically: 1) echocardiography is considered the mainstay for the diagnosis and follow-up; 2) ambulatory blood pressure monitoring and blood lipid assessment are performed in most hypertensive patients; 3) most endocrinologists directly manage hypertension and are aware of the uncertainty of the effect of the control of the disease on blood pressure levels; 4) ACE inhibitors and angiotensin receptors blockers are first-choice anti-hypertensive treatment; 5) approximately half of the centers consider somatostatin analogues of paramount relevance for biochemical control of disease; 6) awareness that left ventricular hypertrophy and heart failure are the most relevant cardiovascular complications is high although the impact of ischemic, arrhythmic, and valvular complications on prognosis is less well perceived. Conclusion: The results of the present survey suggest that previuosly issued guidelines are generally carefully followed in the clinical practice. On the other side, a certain lack of awareness of emerging aspects of the cardiovascular comorbities of acromegaly confirms the necessity of periodically updating the guidelines based on the availability of new clinical information.

Background Endoscopic retrograde cholangiopancreatography (ERCP) is associated with elevated levels of pancreatic enzymes and pancreatitis. Gabexate, a protease inhibitor, has been used to prevent pancreatic damage related to ERCP. Methods We conducted a multicenter, double-blind comparison of gabexate (1 g given by intravenous infusion starting 30 to 90 minutes before endoscopy and continuing for 12 hours afterward) with placebo (mannitol and sodium chloride, administered in the same fashion). A total of 435 adults scheduled to undergo ERCP and, when indicated, endoscopic sphincterotomy underwent randomization; 17 were excluded from the final analysis for various reasons. The remaining 418 patients (mean age, 60.4 years) — 208 in the gabexate group and 210 in the placebo group — were analyzed. Acute pancreatitis was considered to be present if serum amylase or lipase levels (or both) were five times greater than the upper limits of normal in association with the onset of pancreatic pain. Results After th...

Wine can be considered an integral part of the Mediterranean diet and moderate alcohol intake can be beneficial for health. This health-promoting effect is presumably due to the presence of antioxidant substances. It is also known that excessive alcohol intake can lead to liver cirrhosis. A main pathogenetic mechanism in liver cirrhosis is the activation of hepatic stellate cells which acquire a myofibroblast-like phenotype. Excessive production of oxidative stress products may initiate the activation process. Phenolic compounds contained in red wine have been shown to have antifibrotic properties on activated hepatic stellate cells. In vitro and in vivo studies are needed for a better evaluation of the clinical relevance of these findings.

Colonoscopy is the investigation of choice to evaluate ulcerative colitis, but the reliability of the assessment of endoscopic signs is not clear.The aim of this study was to evaluate interobserver agreement for the identification of endoscopic lesions typical of ulcerative colitis, and the influence of training.Four experienced observers and 11 endoscopists under training assessed 49 still images selected from endoscopic video recordings.The agreement rate between experienced observers was excellent or good (k0.39) for recognition of 10 out of 14 signs or patterns (loss of vascular pattern, erythema, oedema, granular mucosa, blood, pseudopolyp, erosion, ulcer, normal pattern, severe activity), and was poor for pus, stricture, mild activity, moderate activity. The rates between endoscopists under training were excellent or good for 6 items (loss of vascular pattern, erythema, oedema, pseudopolyp, normal pattern, severe activity).Trained observers can reproducibly record most endoscopic signs of ulcerative colitis. A reliable overall scoring of severity should be based on a simple three-grading scale, i.e. normal pattern, moderate activity, severe activity. Acceptable agreement rates can be obtained by endoscopists under training on some well-defined endoscopic appearances.

Fetus-to-fetus transplantation has been suggested for the treatment of hemoglobinopathies in utero. However, dissimilar results have to date been obtained by different groups. We describe a case in which fetus-to-fetus transplantation in HLA-identical twins was performed at the 19th week of gestation by infusion of 0.8 ml of fetal blood from normal to beta-thalassemia affected fetus with the main aim of inducing tolerance. No evidence of engraftment, determined by KM19 polymorphism, was present after 2 years of the procedure. Moreover, an alloreactive cytotoxic T lymphocyte precursor (CTLp) study of affected fetus vs donor and other different stimulators showed that immunization vs tolerance was the real effect of the procedure.

The present study is concerned with the immunohistochemical characterization in situ of the mononuclear infiltrate accompanying the formation of septa and the development of cirrhosis in the liver of rats treated with dimethylnitrosamine (DMN), i.p. (10 microliters/kg, 3 days a week for 3 weeks). Monoclonal antibodies against macrophages, pan T cells, T cell subsets and B cells have been applied on cryostat sections of animals given DMN for 7, 14 and 21 days. The maximum increase of macrophages and lymphocytes was observed at days 7 and 14 respectively. At all times T lymphocytes appeared as the major component of the inflammatory infiltrate with a largely predominant population of cytotoxic/suppressor T cells. At day 21, with evidence of nodulation of parenchyma, macrophages levelled off while T cells remained numerous without changes in the inducer-helper T cells/cytotoxic-suppressor T cells ratio which remained always less than 1. B cells were always few. These findings illustrate the early influx of lymphocytes in DMN-induced liver injury and help to define the lymphocyte subsets associated with inflammation and fibrosis in a reproducible animal model.

A patient with Hunter syndrome, or mucopolysaccharidosis type II (MPS-osis II), was subjected to bone marrow transplantation (BMT), at the age of 2 9/12 years. A two-year follow-up ensued to the purpose of comparing clinical, biochemical, neuropsychologic status pre- and post-BMT. From the clinical standpoint, a complete normalization of hepatosplenomegaly was observed. In addition the skin decreased in thickness and joint mobility improved. The echocardiography showed normalization of left ventricle size. With the exception of verbal capabilities, there was no further deterioration of the neuropsychologic profile. The ultrastructural examination of the liver showed an almost total disappearance of storage material. Normal iduronate sulfatase levels in leukocytes and lymphoblasts were constantly found after BMT. A qualitative and quantitative improvement in urinary glycosaminoglycan (GAG) excretion was also found. The effectiveness of the BMT in our patient is also assessed in the context of the few cases of MPS-osis II that have been reported to date. A final evaluation of the efficacy of BMT in MPS-osis II will be possible only when a higher number of patients, diagnosed as early as possible and transplanted within the first months of life, can be followed-up for more extended periods of time.

Objective: To conduct a literature review to assess the effectiveness of first trimester ultrasonographic markers of spina bifida (SB) integrating data with our prospective experience. Methods: The analysis of the SB cases that we prospectively detected in the first trimester, between January 2012 and February 2014, and a systematic review of all the papers evaluating the effectiveness of SB ultrasonographic markers at 11–14 weeks, namely brain stem diameter (BS), fourth ventricle/intracranial translucency (IT), cisterna magna (CM), brain stem/occipital bone distance (BSOB), the ratio between BS and BSOB. Some studies assess only the effectiveness of IT, others include more parameters, and few include them all. Results: We prospectively detected four SB cases, three open (OSB) and one closed (CSB), in a low risk population undergoing first trimester screening. In the three OSB, CM (in 2/3 cases) and BSOB (3/3) distance were below the 5th percentile, BS and BS/BSOB ratio (3/3) were above the 95th percentile. In the CSB, all the measurements were within normal limits. Conclusion: The literature and our data agree that most fetuses with OSB demonstrate in the first trimester positive sonographic markers in the posterior fossa, but additional prospective studies are needed to establish the best protocol for OSB screening.

Purpose: Control of thyroid function in hyperthyroid women during pregnancy is based on antithyroid drugs (ATD) [propylthiouracil (PTU) and methimazole (MMI)]. While a teratogenic effect has been suggested for MMI and, more recently, for PTU, a clear demonstration is still lacking. Aim of this study was to assess the safety of ATD during pregnancy. Methods: A total of 379 pregnancies were retrospectively recruited in eight Italian Departments of Endocrinology and divided in five groups: (1) MMI-treated and euthyroid throughout pregnancy (n = 89); (2) MMI-treated and hyperthyroid on at least two occasions (n = 35); (3) PTU-treated women and euthyroid throughout pregnancy (n = 32); (4) PTU-treated women and hyperthyroid on at least two occasions (n = 20); and (5) non-ATD-treated (n = 203). Data on maternal thyroid function, miscarriages, type of delivery, neonatal weight, length and TSH, perinatal complications and congenital malformation were analyzed. Results: The gestational age at delivery, the rate of vaginal delivery, neonatal weight, length and neonatal TSH did not significantly differ among groups. In all groups, the rates of spontaneous miscarriage and of major congenital malformations were not higher than in the general population. No newborns were born with a phenotype similar to those described in the "MMI embryopathy". Conclusions: While a clear demonstration of a teratogenic effect of MMI is currently lacking, it seems reasonable to follow the current guidelines and advice for PTU treatment in hyperthyroid women during the first trimester of pregnancy. Further, large and prospective worldwide studies will be needed to fully clarify the issue of ATD safety during pregnancy. © 2015 Italian Society of Endocrinology (SIE).

The fruits of Opuntia ficus-indica (L.) Mill., the most worldwide cultivated species of Cactaceae family, contain viable seeds (100-250) of large size. This characteristic influences the commercial quality of the fruit. The study of floral biology in Opuntia allows to understand the behaviour of the plant during reproductive phase and perhaps to distinguish clones with different fruits behaviour (with seed and seedless). The study resulted in a palynological characterization by optical and scanning microscopy (SEM), followed by a qualitative analysis on the male line with pollen viability and in vitro germination tests, in addition to a pollen-pistil interaction survey. The plant material collected, during June-July 2010, consisted of clonal samples of the same genetic origin collected from populations characterizing the Sicilian cultivation area and distinguished in seedly cultivar ‘Gialla’ (yellow) and ‘Rossa’ (red) and seedless cultivar ‘Bianca’ (white). The palynological characterization revealed that Opuntia pollen has a radio-symmetric shape with a reticulated surface, poly-panto-porate with a perimeter from circular to polygonal. Moreover, the membrane of the pore appears finely granulated. Scanning microscopy reveals that the pollen has an intectated, reticulated and hetero-brochated exine with about 20-24 pores with a thin membrane. The average viability of the pollen was 91.2% (±4.6) in ‘Bianca’ cultivar, 82.40% (± 9.88) for both seedly cultivars. In vitro germination rate was 28.76% (± 6.59) in the white cultivar, 27.85% (± 5.15) as overall average in ‘Gialla’ and ‘Rossa’ cultivar. In vivo germination rate in the seedless cultivar (75.77% ± 5.32) was higher than what was that recorded in the other two (53.5% ± 6.5).

The goal of evidence-based practice guidelines is to optimize the management of emerging diseases, such as differentiated thyroid cancer (DTC). The aim of this study was to assess therapeutic approaches for DTC in Italy and to see how closely these practices conformed to those recommended in the 2009 American Thyroid Association (ATA) guidelines.The Italian Thyroid Cancer Observatory was established to collect data prospectively on thyroid cancers consecutively diagnosed in participating centers (uniformly distributed across the nation). Data on the initial treatment of all pathologically confirmed DTC cases present in the database from January 1, 2013 (database creation) to January 31, 2016, were analyzed.A total of 1748 patients (77.2% females; median age 48.1 years [range 10-85 years]) were enrolled in the study. Most (n = 1640; 93.8%) were papillary carcinomas (including 84 poorly differentiated/aggressive variants); 6.2% (n = 108) were follicular and Hürthle cell carcinomas. The median tumor diameter was 11 mm (range 1-93 mm). Tumors were multifocal in 613 (35%) and presented extrathyroidal extension in 492 (28%) cases. Initial treatments included total thyroidectomy (involving one or two procedures; n = 726; 98.8%) and lobectomy (n = 22; 1.2%). A quarter of the patients who underwent total thyroidectomy had unifocal, intrathyroidal tumors ≤1 cm (n = 408; 23.6%). Neck dissection was performed in 40.4% of the patients (29.5% had central compartment dissection). Radioiodine remnant ablation (RRA) was performed in 1057 (61.2%) of the 1726 patients who underwent total thyroidectomy: 460 (41.2%) of the 983 classified by 2009 ATA guideline criteria as low-risk, 570 (87.1%) of the 655 as intermediate-risk, and 82 (93.1%) of the 88 as high-risk patients (p 0.001). RRA was performed in 44% of the cases involving multifocal DTCs measuring ≤1 cm.The treatment approaches for DTCs used in Italy display areas of inconsistency with those recommended by the 2009 ATA guidelines. Italian practices were characterized by underuse of thyroid lobectomy in intrathyroidal, unifocal DTCs ≤1 cm. The use of RRA was generally consistent with risk-stratified recommendations. However, its frequent use in small DTCs (≤1 cm) that are multifocal persists, despite the lack of evidence of benefit. These data provide a baseline for future assessments of the impact of international guidelines on DTC management in Italy. These findings also illustrate that the dissemination and implementation of guideline recommendations, and the change in practice patterns, require ongoing education and time.

The issue of urban sustainability is considered within the context of the metropolis of Rome, the capital of Italy. The aim is pursued through an Urban Biosphere Reserve proposal, drawn up by an interdisciplinary group of experts comprising landscape ecologists, geologists, plant ecologists, zoologists, geographers, city planners and environmental psychologists. The potential applicability of this project on an international level is discussed, with particular focus on its importance as (i) one of the first proposals of an Urban Biosphere Reserve encompassing the whole municipality of a large city, (ii) an original approach to urban ecosystem investigations within the framework of landscape ecology principles, and (iii) a good example of cooperation between scientists and local decision-makers to preserve the cultural and landscape identity in an urban and periurban context.

Background: The functional organization of polarized epithelia depends mostly on adhesion molecules belonging to the integrin and cadherin families. These molecules either recognize basement membrane components, such as laminins, or form intercellular junctions via homotypic interactions. Such tissue organization is often disrupted upon neoplastic transformation, and the resulting loss of functional polarization and cell cohesion might be a prerequisite for the invasive and metastatic behavior of carcinomas. Purpose: We studied modifications of thyroid adhesive mechanisms at various stages of neoplastic progression in terms of adhesion molecule expression, topography, and functional regulation by tyrosine kinases. Starting from this working hypothesis, we sought to identify one or more biological markers that would be suggestive of malignant transformation and poorer prognosis and that could be developed as a reliable indicator(s) in early diagnostic steps. Methods: The study was carried out on both surgical samples and the corresponding fine-needle aspiration biopsy smears (numbers of specimens collected: 19 adenomas, seven follicular carcinomas, 13 papillary carcinomas, and 39 normal tissues). Immunohistochemistry of tissue sections and smears and immuno-precipitation and western blot analysis of protein extracts were done with a battery of monoclonal and polyclonal antibodies. Northern blotting was performed on RNA extracts from frozen tissue samples and use of an integrin subunit beta(4) complementary DNA probe. Results: Our findings can be summarized as follows: 1) In normal thyroid cells, the cooperative role of integrin alpha(6) beta(4) and laminin 5/kalinin in hemidesmosome-mediated adhesion is missing, and recognition of the basal lamina occurs via integrin alpha(3) beta(1) and laminin 1 and/or 2 (this pattern being maintained in adenomas but altered in carcinomas regardless of their histotype or differentiation grade); 2) only in carcinomas with clinical and/or histologic aggressiveness do neoexpression of integrin subunit beta(4) and loss of laminin 2/merosin occur, indicating de novo assembly of integrin alpha(6) beta(4); 3) pericellular redistribution and cytoskeletal disconnection of the E-cadherin-catenin complex occur; and 4) basal E-cadherin tyrosine phosphorylation decreases in carcinomas as compared with that in normal and adenomatous tissues. Conclusions: The malignant progression of thyroid tumors involves marked rearrangements of cell-basement membrane and cell-cell adhesion molecules and changes in their cytoskeleton linkage. These rearrangements are also easily and reproducibly detected on fine-needle aspiration biopsy smears. Implications: Immunodetection of adhesion molecules in sections and/or fine-needle smears may complement the toolbox of thyroid surgical pathologists; it may expand the possibilities of achieving a correct early diagnosis of thyroid tumors and of gaining some prognostic information on thyroid tumors.

ObjectiveMultiple endocrine neoplasia type 2 (MEN 2) is a genetic disease characterized by medullary thyroid carcinoma (MTC) associated (MEN 2A and 2B) or not familial MTC (FMTC) with other endocrine neoplasia due to germline RET gene mutations. The prevalence of these rare genetic diseases and their corresponding RET mutations are unknown due to the small size of the study population.MethodsWe collected data on germline RET mutations of 250 families with hereditary MTC followed in 20 different Italian centres.Results and conclusionsThe most frequent RET amino acid substitution was Val804Met (19.6%) followed by Cys634Arg (13.6%). A total of 40 different germline RET mutations were present. Six families (2.4%) were negative for germline RET mutations. The comparison of the prevalence of RET germline mutations in the present study with those published by other European studies showed a higher prevalence of Val804Met and Ser891Ala mutations and a lower prevalence of Leu790Phe and Tyr791Phe (PPFurthermore, the phenotype data collection showed an unexpected higher prevalence of FMTC (57.6%) with respect to other MEN 2 syndromes (34% MEN 2A and 6.8% of MEN 2B). In conclusion, we observed a statistically significant different pattern of RET mutations in Italian MEN 2 families with respect to other European studies and a higher prevalence of FMTC phenotype. The different ethnic origins of the patients and the particular attention given to analysing apparently sporadic MTC for RET germline mutations may explain these findings.

Background: In the USA, about 30 200 well-differentiated thyroid carcinomas were diagnosed in 2007, but the prevalence of thyroid nodules is much higher (about 5% of the adult population). Unfortunately, the preoperative characterisation of follicular thyroid nodules is still a challenge, and many benign lesions, which remain indeterminate after fine-needle aspiration (FNA) cytology are referred to surgery. About 85% of these thyroid nodules are classified as benign at final histology. We aimed to assess the diagnostic effect of galectin-3 expression analysis in distinguishing preoperatively benign from malignant follicular thyroid nodules when FNA findings were indeterminate. Methods: 544 patients were enrolled between June 1, 2003, and Aug 30, 2006. We used a purified monoclonal antibody to galectin-3, a biotin-free immunocytohistochemical assay, and a morphological and phenotypic analysis of FNA-derived cell-block preparations. Galectin-3-expression analysis was applied preoperatively on 465 follicular thyroid proliferations that were candidates for surgery, and its diagnostic accuracy was compared with the final histology. Findings: 31 patients were excluded because they had small galectin-3-negative thyroid nodules; we did not have data for 47 patients; and one patient with an oncocytic nodule was excluded. 331 (71%) of the assessable 465 preoperative thyroid FNA samples did not express galectin-3. 280 (85%) of these galectin-3-negative lesions were classified as benign at final histology. Galectin-3 expression was detected, instead, in 134 of 465 (29%) thyroid proliferations, 101 (75%) of which were confirmed as malignant. The overall sensitivity of the galectin-3 test was 78% (95% CI 74-82) and specificity was 93% (90-95). Estimated positive predictive value was 82% (79-86) and negative predictive value was 91% (88-93). 381 (88%) of 432 patients with follicular thyroid nodules who were referred for thyroidectomy were correctly classified preoperatively by use of the galectin-3 test. However, 29 (22%) of 130 cancers were missed by the galectin-3 method. Interpretation: Our findings show that if the option of surgery was based theoretically on galectin-3 expression alone, only 134 thyroid operations would have been done in 465 patients; therefore a large proportion (71%) of unnecessary thyroid surgical procedures could be avoided, although a number of galectin-3-negative cancers could be potentially missed. The galectin-3 test proposed here does not replace conventional FNA cytology, but represents a complementary diagnostic method for those follicular nodules that remain indeterminate. Funding: Compagnia di San Paolo, Turin, Italy, and Italian Association for Cancer Research (AIRC), Rome, Italy. © 2008 Elsevier Ltd. All rights reserved.