Activation of Stress Kinases in the Brain of Mucopolysaccharidosis IIIB mice

The accumulation of heparan sulfate (HS) in lysosomes is the primary consequence of the enzyme defect (α-N-acetylglucosaminidase) in mucopolysaccharidosis type IIIB. This accumulation triggers a cascade of pathological events that progressively leads to CNS pathology. Here we examined the activation of the three major stress kinases in the neuronal tissue of a murine model of the disease. ERK1/2 was significantly higher in the cortex of 1–2-month-old affected animals compared with wild-type (Wt) littermates. Similarly, ERK1/2 was stimulated in neurons cultured from MPS IIIB mice. SAPK/JNK was also found to be activated in the cortex of 1–2-month-old affected animals compared with Wt subjects, and the same was found for cultured neurons. In contrast, the active form of p38MAPK was lower in the cortex of 1-month-old MPS IIIB mice compared with Wt animals, but no significant difference was found between the two p38MAPK analyzed in normal and affected neurons cultured in vitro. These data indicate the possible involvement of MAPK dysregulation in the early stage of MPS IIIB brain disease. © 2011 Wiley-Liss, Inc

The effect of four mutations on the expression of iduronate-2-sulfatase in mucopolysaccharidosis type II

AbstractMucopolysaccharidosis type II (Hunter syndrome; OMIM 309900) is a rare X-linked recessive lysosomal storage disorder caused by the deficiency of the enzyme iduronate-2-sulfatase (IDS; EC 3.1.6.13). Different alterations at the IDS locus, mostly missense mutations, have been demonstrated, by expression study, as deleterious, causing significant consequences on the enzyme function or stability. In the present study we report on the results of the transient expression of the novel K347T, 533delTT, N265I and the already described 473delTCC (previously named ΔS117) mutations in the COS 7 cells proving their functional consequence on IDS activity. This type of information is potentially useful for genotype–phenotype correlation, prognosis and possible therapeutic intervention

Deep-MEG: spatiotemporal CNN features and multiband ensemble classification for predicting the early signs of Alzheimer's disease with magnetoencephalography

AbstractIn this paper, we present the novel Deep-MEG approach in which image-based representations of magnetoencephalography (MEG) data are combined with ensemble classifiers based on deep convolutional neural networks. For the scope of predicting the early signs of Alzheimer's disease (AD), functional connectivity (FC) measures between the brain bio-magnetic signals originated from spatially separated brain regions are used as MEG data representations for the analysis. After stacking the FC indicators relative to different frequency bands into multiple images, a deep transfer learning model is used to extract different sets of deep features and to derive improved classification ensembles. The proposed Deep-MEG architectures were tested on a set of resting-state MEG recordings and their corresponding magnetic resonance imaging scans, from a longitudinal study involving 87 subjects. Accuracy values of 89% and 87% were obtained, respectively, for the early prediction of AD conversion in a sample of 54 mild cognitive impairment subjects and in a sample of 87 subjects, including 33 healthy controls. These results indicate that the proposed Deep-MEG approach is a powerful tool for detecting early alterations in the spectral–temporal connectivity profiles and in their spatial relationships

Preventing the acute skin side effects in patients treated with radiotherapy for breast cancer: the use of corneometry in order to evaluate the protective effect of moisturizing creams

BACKGROUND AND PURPOSE: The purpose of this study was to add, to the objective evaluation, an instrumental assessment of the skin damage induced by radiation therapy. MATERIALS AND METHODS: A group of 100 patients affected by breast cancer was recruited in the study over one year. Patients were divided into five groups of 20 patients. For each group it was prescribed a different topical treatment. The following products were used: Betaglucan, sodium hyaluronate (Neoviderm®), Vitis vinifera A. s-I-M.t-O.dij (Ixoderm®), Alga Atlantica plus Ethylbisiminomethylguaicolo and Manganese Cloruro (Radioskin1®) and Metal Esculetina plus Ginko Biloba and Aloe vera (Radioskin 2®); Natural triglycerides-fitosterols (Xderit®); Selectiose plus thermal water of Avene (Trixera+®). All hydrating creams were applied twice a day starting 15 days before and one month after treatment with radiations. Before and during treatment patients underwent weekly skin assessments and corneometry to evaluate the symptoms related to skin toxicity and state of hydration. Evaluation of acute cutaneous toxicity was defined according to the RTOG scale. RESULTS: All patients completed radiotherapy; 72% of patients presented a G1 cutaneous toxicity, 18% developed a G2 cutaneous toxicity, 10% developed a G3 toxicity, no one presented G4 toxicity. The corneometry study confirmed the protective role of effective creams used in radiation therapy of breast cancer and showed its usefulness to identify radiation-induced dermatitis in a very early stage. CONCLUSIONS: The preventive use of topic products reduces the incidence of skin side effects in patients treated with radiotherapy for breast cancer. An instrumental evaluation of skin hydration can help the radiation oncologist to use strategies that prevent the onset of toxicity of high degree. All moisturizing creams used in this study were equally valid in the treatment of skin damage induced by radiotherapy

analysis of exhaled breath fingerprints and volatile organic compounds in copd

Exhaled air contains many volatile organic compounds (VOCs) produced during human metabolic processes, in both healthy and pathological conditions. Analysis of breath allows studying the modifications of the profile of the exhaled VOCs due to different disease states, including chronic obstructive pulmonary disease (COPD). The early diagnosis of COPD is complicated and the identification of specific metabolic profiles of exhaled air may provide useful indication to better identify the disease. The aim of our study was to characterize the specific exhaled VOCs by means of the electronic nose and by solid phase micro-extraction associated to gas chromatography–mass spectrometry (SPME GC-MS). Exhaled air was collected and measured in 34 subjects, 7 healthy and 27 former smokers affected by COPD (GOLD 1–4). The signals of the electronic nose sensors were higher in COPD patients with respect to controls, and allowed to accurately classify the studied subjects in healthy or COPD. GC-MS analysis identified 37 VOCs, nine of which were significantly correlated with COPD. In particular the concentration of two of these were positively correlated whereas seven were negatively correlated with COPD. The partial least squares discriminant analysis (PLS-DA) carried out with these nine VOCs produced a significant predictive model of disease. This study shows that COPD patients exhibit qualitative and quantitative differences in the chemical compositions of exhale. These differences are detectable both by the GC-MS and the six-sensor e-nose. The use of electronic nose may represent a suitable, non-invasive diagnostic tool for characterization of COPD

Le infezioni catetere vascolare correlate: risultati di tre anni di sorveglianza (2001-2003)

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