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Objective: To assess the long-term outcome of epilepsy with auditory features (EAF) and to identify the clinical predictors for prognosis. Methods: The study involved consecutive EAF patients with a follow-up of ≥5 years. Terminal remission (TR) was defined as a period of ≥5 consecutive years of seizure freedom at the last follow-up. We used Kaplan-Meier estimate to calculate the cumulative time-dependent probability of conversion to TR. Log-rank test and multivariate Cox regression analyses were performed to study the association between time to TR and prognostic determinants. Results: We included 123 EAF patients (male/female = 58/65) with a median follow-up of 11 years (1626.9 person-years). Most were sporadic cases (68.3%), whereas 31.7% reported a family history of epilepsy. At last assessment, 42 patients had achieved TR (34.1%). Of the remaining 81 cases with no TR (65.9%), 37% had been in remission for 1-4 years and 62.9% still had seizures within the past year. The cumulative rates of TR were 26.6%, 35.7%, and 51.6% at 10, 20, and 30 years from inclusion. On multivariate analysis, age at onset > 10 years (hazard ratio [HR] = 3.2, P = .028), auditory aura characterized by distortions only versus simple/complex hallucinations (HR = 2.9, P = .041), and unremarkable scalp electroencephalogram (EEG) versus EEG with focal epileptiform activity (HR = 3.5, P = .041) were associated with TR. Significance: Our data show a wide prognostic spectrum of EAF, ranging from mild forms with spontaneous remission, to severely refractory epilepsy addressed to surgery. The outcome, less favorable than expected from previous studies, appears to be primarily a function of 3 prognostic negative risk factors: age at onset < 10 years, auditory aura characterized by complex auditory hallucinations, and focal epileptiform abnormalities on scalp EEG. These predictors, easy to collect even at the first visit, may inform both clinicians and patients about the long-term prognosis and aid patient management.

Purpose To investigate the performance of various algorithms for deformable image registration (DIR) to propagate regions of interest (ROIs) using multiple commercial platforms. Methods and materials Thirteen institutions participated in the study with six commercial platforms: RayStation (RaySearch Laboratories, Stockholm, Sweden), MIM (Cleveland, OH, USA), VelocityAI and Smart Adapt (Varian Medical Systems, Palo Alto, CA, USA), Mirada XD (Mirada Medical Ltd, Oxford, UK), and ABAS (Elekta AB, Stockholm, Sweden). The DIR algorithms were tested on synthetic images generated with the ImSimQA package (Oncology Systems Limited, Shrewsbury, UK) by applying two specific Deformation Vector Fields (DVF) to real patient data-sets. Head-and-neck (HN), thorax, and pelvis sites were included. The accuracy of the algorithms was assessed by comparing the DIR-mapped ROIs from each center with those of reference, using the Dice Similarity Coefficient (DSC) and Mean Distance to Conformity (MDC) metrics. Statistical inference on validation results was carried out in order to identify the prognostic factors of DIR performances. Results DVF intensity, anatomic site and participating center were significant prognostic factors of DIR performances. Sub-voxel accuracy was obtained in the HN by all algorithms. Large errors, with MDC ranging up to 6 mm, were observed in low-contrast regions that underwent significant deformation, such as in the pelvis, or large DVF with strong contrast, such as the clinical tumor volume (CTV) in the lung. Under these conditions, the hybrid DIR algorithms performed significantly better than the free-form intensity based algorithms and resulted robust against intercenter variability. Conclusions The performances of the systems proved to be site specific, depending on the DVF type and the platforms and the procedures used at the various centers. The pelvis was the most challenging site for most of the algorithms, which failed to achieve sub-voxel accuracy. Improved reproducibility was observed among the centers using the same hybrid registration algorithm.

Although combination chemotherapy and radiotherapy have become the standard of care in numerous tumors, the mechanisms of interaction are often still unclear. The purpose of this study was to analyze the efficacy of radiation treatment and cisplatin sequences and to investigate their mechanisms of interaction. Three melanoma cell lines were used to evaluate in vitro radiation-induced cytotoxicity before and after cisplatin treatment. Expression levels of a panel of genes were determined by real-time RT-PCR. Cytotoxic effect was evaluated by flow cytometry analysis and Comet assay. We also used normal human dermal fibroblasts (HUDE) to evaluate the cytotoxicity of the two treatments by clonogenic assay. Radiation and cisplatin used singly were not particularly effective in reducing proliferation in melanoma cells. Conversely, radiation treatment followed by cisplatin showed a strong synergistic interaction in all cell lines, with a ratio index ranging from 16 to >100. The synergistic effect was accompanied by apoptosis induction (up to 40%) and an increase in the percentage of comet-shaped nucleoids from 85% to 99%. In parallel, our results also showed that radiation treatment of HUDE fibroblasts followed by cisplatin only induced weak cytotoxicity. Our findings highlight the efficacy of the sequence radiation cisplatin in reducing cell proliferation and in inducing apoptosis in melanoma cell lines. This sequence also modulated a network of proteins involved in DNA damage repair. J. Cell. Physiol. 229: 1548–1556, 2014. © 2014 Wiley Periodicals, Inc.

An examination of the occurrence and distribution of phthalate esters in the alimentary canal of a polyhybrid of Tilapia gave evidence of different and selective patterns of distribution in the organ tissues: the phthalate esters were shown to be concentrated in the stomach and anterior intestine. The restricted distribution of phthalate esters can have implications for the physiology of the digestive system. The phthalates, stored in the oxyntic cells of the gastric tubular glands, probably interfere with the digestive process. The strategic location of the enterocytes in the anterior intestine implies that they can hamper the reabsorption of digestion products. The endocrine disrupting effects known for these chemicals are probably related to the absorption of them via the alimentary canal.

Background Population-based surveys on the quality of life of people with Down syndrome (DS) are difficult to perform because of ethical and legal policies regarding privacy and confidential information, but they are essential for service planning. Little is known about the sample size and variability of quality of life of people with DS living in the city of Rome, which has a population of 2.7 million inhabitants. The aim of the present study is to explore the needs and challenges in health, social integration and daily life, of people with DS living in Rome. Methodology A cross-sectional, census-based survey was conducted in 2006. All family doctors (3016 in total) of the National Health Service were involved by the Statistical Bureau of the Municipality of Rome. As per the census, every resident citizen is registered with a family doctor and every person with disabilities is coded. Associations for Down Syndrome encouraged their members to participate in the research. Questionnaires were completed by families of people with DS, in accordance with privacy laws. Findings An initial survey, conducted via a letter and a telephone contact with family doctors, identified 884 people with DS residing in the city of Rome. Data on the medical and social conditions of 518 people with DS, ranging in age from 0 to 64 years, were collected. Some 88% of these were living with their original family; 82.1% had one or more siblings, and 19.5% had lost one or both parents. A full 100% of children with DS were enrolled in the public school system. This ensures that they are fully occupied and entirely integrated in society. After secondary school there is a lack of opportunities. Thus, only 10% of adults were working with a regular contract. A mere 42.2% of people with DS aged 25–30 were involved in some form of regular activity (although not always on a daily basis). After the age of 30, the percentage of people demonstrating decline in function increased sharply, while disability-related support decreased. In other words, as people with DS age, daily life evolves increasingly around the home, with only occasional outdoor activities. Conclusion The health, employment and social needs of the majority of people with DS in the city of Rome are not being met. The findings of this study underscore the urgent need for more comprehensive inclusion in society of adults with DS and for the provision of support services to create an enabling environment for inclusion. Because of the variability of performance among individuals with DS, there is a need to create more case-specific options in terms of work, living arrangements, social networking and medical services. Schooling and social inclusion in childhood alone do not guarantee a satisfactory quality of life in adulthood. It is argued herewith that policy of inclusion and support should extend over the entire lifetime of people with DS.

F. Orzan, S. Pellegatta, P. L. Poliani, F. Pisati, V. Caldera, F. Menghi, D. Kapetis, C. Marras, D. Schiffer and G. Finocchiaro (2011) Neuropathology and Applied Neurobiology37, 381–394 Enhancer of Zeste 2 (EZH2) is up-regulated in malignant gliomas and in glioma stem-like cells Aims: Proteins of the Polycomb repressive complex 2 (PRC2) are epigenetic gene silencers and are involved in tumour development. Their oncogenic function might be associated with their role in stem cell maintenance. The histone methyltransferase Enhancer of Zeste 2 (EZH2) is a key member of PRC2 function: we have investigated its expression and function in gliomas. Methods:EZH2 expression was studied in grade II–IV gliomas and in glioma stem-like cells (GSC) by quantitative PCR and immunohistochemistry. Effects of EZH2 down-regulation were analysed by treating GSC with the histone deacetylase (HDAC) inhibitor suberoylanide hydroxamic acid (SAHA) and by shRNA. Results: DNA microarray analysis showed that EZH2 is highly expressed in murine and human GSC. Real-time PCR on gliomas of different grade (n = 66) indicated that EZH2 is more expressed in glioblastoma multiforme (GBM) than in low-grade gliomas (P = 0.0013). This was confirmed by immunohistochemistry on an independent set of 106 gliomas. Treatment with SAHA caused significant up-regulation of PRC2 predicted target genes, GSC disruption and decreased expression of EZH2 and of the stem cell marker CD133. Inhibition of EZH2 expression by shRNA was associated with a significant decrease of glioma proliferation. Conclusion: The data suggest that EZH2 plays a role in glioma progression and encourage the therapeutic targeting of these malignancies by HDAC inhibitors.

We previously reported that transient administration of phthalates induced actin cytoskeleton disruption in Py1a osteoblasts. However, the mechanism of this transient effect was not elucidated. In this study we provided evidence that the actin cytoskeletal re-established conditions are dependent on new actin expression and synthesis. To assess the role of phthalates in modulating the distribution of actin, confocal and electron microscopy studies were carried out. Results indicated a modification of actin distribution after phthalate administration. In addition, a relation with the nucleoskeletal component lamin A supports the hypothesis that phthalates may participate in regulatory cell processes involving actin in Py1a osteoblasts. The present study also supports the mitogenic effects of phthalates, which involve microfilament disruption, nuclear actin and lamin A. In particular, the increased levels of cyclin D3, which in mammalian cells plays a critical role in G1 to S transition and is a putative proto-oncogene in benzyl butyl phthalate treated cells, suggested a possible effect of the endocrine disruptor in cancer processes.

Dose-point kernels (DPKs) can be widely applied to therapeutic nuclear medicine to obtain more accurate absorbed dose assessments in internal dosimetry assuming a spherical geometry. Recently, EGSnrc-the latest in the family of EGS Monte Carlo codes--has been tested for isotropic monoenergetic electrons and Y-90 beta spectrum in spherical geometry. The availability of SPECT images allows one to take into account heterogeneities in activity distribution within tumors, and to perform dose calculations using voxel dosimetry based on Monte Carlo simulations in a Cartesian geometry. The purpose of this study is to evaluate the differences of dose distributions scored in Cartesian voxels also known as Dose Voxel Kernels (DVKs) for five beta-emitting (131I, 89Sr, 153Sm, 186Re, and 90Y) and Auger-emitting (111In) radionuclides, when their computation is made using these two Monte Carlo codes from the same family to check if the new physics in EGSnrc simulation system produces DVK very different from those calculated with EGS4. We have calculated the DVKs for point and voxel sources in Cartesian scoring grids of different spatial resolutions. Our results for the point source, scored in the finer spatial resolution, show a poor agreement between EGSnrc and EGS4 (up to about 20%) for voxels closer to the origin, and a better agreement (below 5%) for longer distances for all radionuclides. For the voxel source, where doses were scored in the coarser spatial resolution, dose deposition in the central voxel is in good agreement for all the radionuclides; while surrounding voxels exhibit a slightly worse agreement.

A histological and histochemical analyses were carried out on the entire alimentary canal of the rainbow trout Oncorhynchus mykiss. In particular the oesophageal region showed presence of terminal β-D-galactose(1–3)-N-acetylgalactosamine and α-N-acetylgalactosamine. In the anterior and posterior regions of the stomach, lining epithelium and gastric pits exhibited the presence of β-gal and α-GalNAc. In addition sialoglycoconjugates having sialic acid–β–galactose(1–3)-N-acetylgalactosamine and sialic acid-N-acetylgalactosamine as terminal tri- and di-saccharides, were demonstrated. In proximal and distal intestine goblet cells showed the presence of sialoglyconjugates, having sialic acid-β-gal(1–3)-GalNAc and sialic acid-GalNAc as terminal sequences, belonging to N-linked chains. In the enterocytes of the entire intestine, terminal GlcNAc, α-Gal, α-fucose were found.

Telomerase is a ribonucleoprotein enzyme that maintains the protective structures at the ends of eukaryotic chromosomes, called telomeres. Telomerase activity was observed and correlated with aggressiveness in different neoplasms such as breast, prostate, blood and brain cancers, among others. To investigate whether telomerase activity is an index of aggressiveness in bone and soft tissue lesions of the extremities, 66 biopsy samples from our tissue bank were studied. These samples included 43 high-grade sarcomas, 9 aggressive benign tumors and 14 totally benign lesions. The samples were collected from patients homogeneously treated at the Rizzoli Orthopaedic Institute with a follow-up ranging from 4 to 11 years (median, 7 years). A non-radioactive polymerase chain reaction-based enzyme-linked immunosorbent assay was used for the study. All tumors investigated were positive for telomerase activity. Among benign lesions, only 2 aneurysmal bone cysts showed higher telomerase activity than the cut-off point, whereas all the other benign lesions had lower activity. Our results indicate that high levels of telomerase activity in bone and soft tissue lesions correlate with more aggressive clinical behavior in patients treated with surgery alone. An interesting inverse correlation between telomerase activity and occurrence of pulmonary metastasis was detected in osteosarcoma patients treated with chemotherapy. A parallel increase of telomerase activity and malignancy was observed in the adipose and cartilagineous tissue lesions. Our data suggest that telomerase activity could be considered a marker of tumor aggressiveness for bone and soft tissue lesions. The results obtained in osteosarcoma samples suggest that low levels of telomerase activity may be predictive of the prognosis and should influence the therapeutic protocol.

Amongst the hundreds of cases of regional specific products being produced all over Europe, the Parmigiano Reggiano cheese system can be considered one of the most eloquent, mature and successful examples avant la lettre of rural development. About 8,000 dairy farmers, cheese dairies and ripening firms comply with the strict production regulations that guarantee the specificity of this product. Employment in the Parmigiano Reggiano production system is twice as high as in the industrial dairy system and the pressure of the system on the environment is significantly lower. As Parmigiano Reggiano cheese has to compete on the same market as more industrial Grana cheeses, the system is not immune to the cost-price squeeze affecting European agriculture. The accelerated introduction of cost reducing technologies may compromise the typicality of the product, endanger its competitive position on the market and weaken its future collective performance. A convergence of views and a strong cohesion among actors is necessary to reach new agreements about the direction being taken by technological development in order to safeguard the success Parmigiano Reggiano cheese has been able to generate in the past

A histochemical study using conventional and lectin methods was performed on the stomach of fasting and feeding adults of Tilapia spp. A battery of HRP-conjugated lectins combined with exoglycosidase digestion was used. The differences found in the epithelium, gastric pits and gastric glands between fasting and feeding subjects were related to the functional stages of the organ. Carbohydrate composition was also compared with that of mammals and birds.

The purpose of this article is to measure the loss of P from watersheds of differing management, to evaluate more precisely the nonpoint contribution of P to the Adriatic Sea

The carbohydrate histochemistry of the rabbit oviduct has been examined by the use of four lectins conjugated with horseradish peroxidase as histochemical reagents. Each lectin gave a very distinct typical pattern of binding, but for each lectin there was no difference between the distribution of binding sites in ampulla and isthmus. Wheat germ lectin bound exclusively with the connective tissue of the oviduct folds; winged pea lectin was detected only in the ciliated cells; peanut lectin binding sites were visualized in the secretory cells; the binding reactivity of soybean lectin was limited to the basal part of the cilia. Although it is very difficult at present to correlate the distribution of lectin binding sites with the function of the positive cells, some hypotheses have been advanced.