Zinc transporter 8 and MAP3865c homologous epitopes are recognized at T1D onset in Sardinian children

Our group has recently demonstrated that Mycobacterium avium subspecies paratuberculosis (MAP) infection significantly associates with T1D in Sardinian adult patients. Due to the potential role played by MAP in T1D pathogenesis, it is relevant to better characterize the prevalence of anti-MAP antibodies (Abs) in the Sardinian population, studying newly diagnosed T1D children. Therefore, we investigated the seroreactivity against epitopes derived from the ZnT8 autoantigen involved in children at T1D onset and their homologous sequences of the MAP3865c protein. Moreover, sera from all individuals were tested for the presence of Abs against: the corresponding ZnT8 C-terminal region, the MAP specific protein MptD, the T1D autoantigen GAD65 and the T1D unrelated Acetylcholine Receptor. The novel MAP3865c281–287 epitope emerges here as the major C-terminal epitope recognized. Intriguingly ZnT8186–194 immunodominant peptide was cross-reactive with the homologous sequences MAP3865c133–141, strengthening the hypothesis that MAP could be an environmental trigger of T1D through a molecular mimicry mechanism. All eight epitopes were recognized by circulating Abs in T1D children in comparison to healthy controls, suggesting that these Abs could be biomarkers of T1D. It would be relevant to investigate larger cohorts of children, followed over time, to elucidate whether Ab titers against these MAP/Znt8 epitopes wane after diagnosis

Characterization of a disease-associated mutation affecting a putative splicing regulatory element in intron 6b of the cystic fibrosis transmembrane conductance regulator (CFTR) gene

Cystic fibrosis (CF) is a common recessive disorder caused by >1600 mutations in the CF transmembrane conductance regulator (CFTR) gene. About 13% of CFTR mutations are classified as “splicing mutations,” but for almost 40% of these, their role in affecting the pre-mRNA splicing of the gene is not yet defined. In this work, we describe a new splicing mutation detected in three unrelated Italian CF patients. By DNA analyses and mRNA studies, we identified the c.1002–1110_1113delTAAG mutation localized in intron 6b of the CFTR gene. At the mRNA level, this mutation creates an aberrant inclusion of a sequence of 101 nucleotides between exons 6b and 7. This sequence corresponds to a portion of intron 6b and resembles a cryptic exon because it is characterized by an upstream ag and a downstream gt sequence, which are most probably recognized as 5′- and 3′-splice sites by the spliceosome. Through functional analysis of this splicing defect, we show that this mutation abolishes the interaction of the splicing regulatory protein heterogeneous nuclear ribonucleoprotein A2/B1 with an intronic splicing regulatory element and creates a new recognition motif for the SRp75 splicing factor, causing activation of the cryptic exon. Our results show that the c.1002–1110_1113delTAAG mutation creates a new intronic splicing regulatory element in intron 6b of the CFTR gene exclusively recognized by SRp75

Efficient Support for Video Communications in Wireless Home Networks

This paper investigates the performance of video communications over wireless networks employing the recently proposed Time-Division Unbalanced Carrier Sense Multiple access (TDuCSMA) coordination function. TDuCSMA is fully IEEE 802.11 standard compliant but offers novel bandwidth management capabilities. In this work the peculiar characteristics of TDuCSMA are configured and exploited to maximize the performance of video communications in a realistic home networking scenario. Simulation results show significant performance improvements with respect to legacy IEEE 802.11 network. The video quality gains are up to 13 dB PSNR with 500 ms playout buffer, while the average delay of the video packets is much lower, for the same amount of video traffic offered to the network. These results significantly contribute to enhance the quality of experience of the users of the video communicatio

GPCALMA: a Grid Approach to Mammographic Screening

The next generation of High Energy Physics experiments requires a GRID approach to a distributed computing system and the associated data management: the key concept is the "Virtual Organisation" (VO), a group of geographycally distributed users with a common goal and the will to share their resources. A similar approach is being applied to a group of Hospitals which joined the GPCALMA project (Grid Platform for Computer Assisted Library for MAmmography), which will allow common screening programs for early diagnosis of breast and, in the future, lung cancer. HEP techniques come into play in writing the application code, which makes use of neural networks for the image analysis and shows performances similar to radiologists in the diagnosis. GRID technologies will allow remote image analysis and interactive online diagnosis, with a relevant reduction of the delays presently associated to screening programs.Comment: 4 pages, 3 figures; to appear in the Proceedings of Frontier Detectors For Frontier Physics, 9th Pisa Meeting on Advanced Detectors, 25-31 May 2003, La Biodola, Isola d'Elba, Ital

Dietary determinants of changes in waist circumference adjusted for body mass index - a proxy measure of visceral adiposity

Background Given the recognized health effects of visceral fat, the understanding of how diet can modulate changes in the phenotype “waist circumference for a given body mass index (WCBMI)”, a proxy measure of visceral adiposity, is deemed necessary. Hence, the objective of the present study was to assess the association between dietary factors and prospective changes in visceral adiposity as measured by changes in the phenotype WCBMI. Methods and Findings We analyzed data from 48,631 men and women from 5 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Anthropometric measurements were obtained at baseline and after a median follow-up time of 5.5 years. WCBMI was defined as the residuals of waist circumference regressed on body mass index, and annual change in WCBMI (¿WCBMI, cm/y) was defined as the difference between residuals at follow-up and baseline, divided by follow-up time. The association between energy, energy density (ED), macronutrients, alcohol, glycemic index (GI), glycemic load (GL), fibre and ¿WCBMI was modelled using centre-specific adjusted linear regression, and random-effects meta-analyses to obtain pooled estimates. Men and women with higher ED and GI diets showed significant increases in their WCBMI, compared to those with lower ED and GI [1 kcal/g greater ED predicted a ¿WCBMI of 0.09 cm (95% CI 0.05 to 0.13) in men and 0.15 cm (95% CI 0.09 to 0.21) in women; 10 units greater GI predicted a ¿WCBMI of 0.07 cm (95% CI 0.03 to 0.12) in men and 0.06 cm (95% CI 0.03 to 0.10) in women]. Among women, lower fibre intake, higher GL, and higher alcohol consumption also predicted a higher ¿WCBMI. Conclusions Results of this study suggest that a diet with low GI and ED may prevent visceral adiposity, defined as the prospective changes in WCBMI. Additional effects may be obtained among women of low alcohol, low GL, and high fibre intake

A Computer Aided Detection system for mammographic images implemented on a GRID infrastructure

The use of an automatic system for the analysis of mammographic images has proven to be very useful to radiologists in the investigation of breast cancer, especially in the framework of mammographic-screening programs. A breast neoplasia is often marked by the presence of microcalcification clusters and massive lesions in the mammogram: hence the need for tools able to recognize such lesions at an early stage. In the framework of the GPCALMA (GRID Platform for Computer Assisted Library for MAmmography) project, the co-working of italian physicists and radiologists built a large distributed database of digitized mammographic images (about 5500 images corresponding to 1650 patients) and developed a CAD (Computer Aided Detection) system, able to make an automatic search of massive lesions and microcalcification clusters. The CAD is implemented in the GPCALMA integrated station, which can be used also for digitization, as archive and to perform statistical analyses. Some GPCALMA integrated stations have already been implemented and are currently on clinical trial in some italian hospitals. The emerging GRID technology can been used to connect the GPCALMA integrated stations operating in different medical centers. The GRID approach will support an effective tele- and co-working between radiologists, cancer specialists and epidemiology experts by allowing remote image analysis and interactive online diagnosis.Comment: 5 pages, 5 figures, to appear in the Proceedings of the 13th IEEE-NPSS Real Time Conference 2003, Montreal, Canada, May 18-23 200

Automated detection of lung nodules in low-dose computed tomography

A computer-aided detection (CAD) system for the identification of pulmonary nodules in low-dose multi-detector computed-tomography (CT) images has been developed in the framework of the MAGIC-5 Italian project. One of the main goals of this project is to build a distributed database of lung CT scans in order to enable automated image analysis through a data and cpu GRID infrastructure. The basic modules of our lung-CAD system, consisting in a 3D dot-enhancement filter for nodule detection and a neural classifier for false-positive finding reduction, are described. The system was designed and tested for both internal and sub-pleural nodules. The database used in this study consists of 17 low-dose CT scans reconstructed with thin slice thickness (~300 slices/scan). The preliminary results are shown in terms of the FROC analysis reporting a good sensitivity (85% range) for both internal and sub-pleural nodules at an acceptable level of false positive findings (1-9 FP/scan); the sensitivity value remains very high (75% range) even at 1-6 FP/scanComment: 4 pages, 2 figures: Proceedings of the Computer Assisted Radiology and Surgery, 21th International Congress and Exhibition, Berlin, Volume 2, Supplement 1, June 2007, pp 357-35

Epigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosis

Interest in the potential of DNA methylation in peripheral blood as a biomarker of cancer risk is increasing. We aimed to assess whether epigenome-wide DNA methylation measured in peripheral blood samples obtained before onset of the disease is associated with increased risk of breast cancer. We report on three independent prospective nested case-control studies from the European Prospective Investigation into Cancer and Nutrition (EPIC-Italy; n = 162 matched case-control pairs), the Norwegian Women and Cancer study (NOWAC; n = 168 matched pairs), and the Breakthrough Generations Study (BGS; n = 548 matched pairs). We used the Illumina 450k array to measure methylation in the EPIC and NOWAC cohorts. Whole-genome bisulphite sequencing (WGBS) was performed on the BGS cohort using pooled DNA samples, combined to reach 50× coverage across ~16 million CpG sites in the genome including 450k array CpG sites. Mean β values over all probes were calculated as a measurement for epigenome-wide methylation

Multiparameter characterisation of vertebral osteoporosis with 3-T MR = Valutazione multiparametrica dell’osteoporosi vertebrale con RM a 3 Tesla

Purpose. This study was undertaken to evaluate the diagnostic capabilities of 3-Tesla (T) magnetic resonance (MR) in vertebral osteoporosis. Materials and methods. Thirty subjects (ten healthy controls, ten with osteoporosis but no fracture, ten with osteoporotic vertebral fractures) underwent MR of the lumbar spine. Turbo spin echo (TSE) T1-, T2- and T2- spectral selection attenuated inversion recovery (SPAIR) weighted imaging and spectroscopy for the selective evaluation of water and fat content were performed. The apparent diffusion coefficient (ADC) was calculated, and diffusion tensor imaging (DTI) was performed to create a map of the spatial arrangement of the tissue structures. Results. Morphological imaging detected recent vertebral fractures. In osteoporotic patients, spectroscopic imaging demonstrated an increase in the saturated fats and a decrease in the ADC, whereas the data provided by DTI demonstrated a bone structure with medium-degree anisotropy. Discussion. Osteoporosis is characterised by trabecular thinning, with an increase in the intertrabecular spaces, which are filled with fats. The anisotropic study and the subsequent assessment of colour and vector maps can provide a noninvasive tool for assessing the risk of fracture due to osteoporosis