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

An automatic deep learning approach for coronary artery calcium segmentation

Coronary artery calcium (CAC) is a significant marker of atherosclerosis and cardiovascular events. In this work we present a system for the automatic quantification of calcium score in ECG-triggered non-contrast enhanced cardiac computed tomography (CT) images. The proposed system uses a supervised deep learning algorithm, i.e. convolutional neural network (CNN) for the segmentation and classification of candidate lesions as coronary or not, previously extracted in the region of the heart using a cardiac atlas. We trained our network with 45 CT volumes; 18 volumes were used to validate the model and 56 to test it. Individual lesions were detected with a sensitivity of 91.24%, a specificity of 95.37% and a positive predicted value (PPV) of 90.5%; comparing calcium score obtained by the system and calcium score manually evaluated by an expert operator, a Pearson coefficient of 0.983 was obtained. A high agreement (Cohen's k = 0.879) between manual and automatic risk prediction was also observed. These results demonstrated that convolutional neural networks can be effectively applied for the automatic segmentation and classification of coronary calcifications

A distal renal tubular acidosis showing hyperammonemia and hyperlactacidemia

Introduction: distal renal tubular acidosis (dRTA) presents itself with variable clinical manifestations and often with late expressions that impact on prognosis. Case report: A 45-day-old male infant was admitted with stopping growth, difficult feeding and vomiting after meals. Clinical tests and labs revealed a type 1 renal tubular acidosis, even if the first blood tests showed ammonium and lactate increase. We had to exclude metabolic diseases before having a certain diagnosis. Conclusions: blood and urine investigations and genetic tests are fundamental to formulate dRTA diagnosis and to plan follow-up, according to possible phenotypic expressions of recessive and dominant autosomal forms in patients with dRTA

Lieb-Robinson Bounds for Spin-Boson Lattice Models and Trapped Ions

We derive a Lieb-Robinson bound for the propagation of spin correlations in a model of spins interacting through a bosonic lattice field, which satisfies a Lieb-Robinson bound in the absence of spin-boson couplings. We apply these bounds to a system of trapped ions and find that the propagation of spin correlations, as mediated by the phonons of the ion crystal, can be faster than the regimes currently explored in experiments. We propose a scheme to test the bounds by measuring retarded correlation functions via the crystal fluorescence

Compensatory Feto-Placental Upregulation of the Nitric Oxide System during Fetal Growth Restriction

Background: Fetal Growth Restriction is often associated with a feto-placental vascular dysfunction conceivably involving endothelial cells. Our study aimed to verify this pathogenic role for feto-placental endothelial cells and, coincidentally, demonstrate any abnormality in the nitric oxide system. Methods: Prenatal assessment of feto-placental vascular function was combined with measurement of nitric oxide (in the form of S-nitrosohemoglobin) and its nitrite byproduct, and of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine. Umbilical vein endothelial cells were also harvested to determine their gene profile. The study comprised term pregnancies with normal (n = 40) or small-for-gestational-age (n = 20) newborns, small-for-gestational-age preterm pregnancies (n = 15), and bi-chorial, bi-amniotic twin pregnancies with discordant fetal growth (n = 12). Results: Umbilical blood nitrite (p<0.001) and S-nitrosohemoglobin (p = 0.02) rose with fetal growth restriction while asymmetric dimethylarginine decreased (p = 0.003). Nitrite rise coincided with an abnormal Doppler profile from umbilical arteries. Fetal growth restriction umbilical vein endothelial cells produced more nitrite and also exhibited reciprocal changes in vasodilator (upwards) and vasoconstrictor (downwards) transcripts. Elevation in blood nitrite and S-nitrosohemoglobin persisted postnatally in the fetal growth restriction offspring. Conclusion: Fetal growth restriction is typified by increased nitric oxide production during pregnancy and after birth. This response is viewed as an adaptative event to sustain placental blood flow. However, its occurrence may modify the endothelial phenotype and may ultimately represent an element of risk for cardiovascular disease in adult life.Fil: Pisaneschi, Silvia. Università degli Studi di Pisa; Italia. Scuola Superiore Sant’Anna; ItaliaFil: Strigini, Francesca A. L.. Università degli Studi di Pisa; ItaliaFil: Sanchez, Angel Matias. Università degli Studi di Pisa; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Begliuomini, Silvia. Università degli Studi di Pisa; ItaliaFil: Casarosa, Elena. Università degli Studi di Pisa; ItaliaFil: Ripoli, Andrea. National Research Council. Institute of Clinical Physiology, ; ItaliaFil: Ghirri, Paolo. Università degli Studi di Pisa; ItaliaFil: Boldrini, Antonio. Università degli Studi di Pisa; ItaliaFil: Fink, Bruno. Noxygen Science Transfer and Diagnostics; AlemaniaFil: Genazzani, Andrea R.. Università degli Studi di Pisa; ItaliaFil: Coceani, Flavio. Scuola Superiore Sant’Anna; ItaliaFil: Simoncini, Tommaso. Università degli Studi di Pisa; Itali

Systematic differences between BNP immunoassays: comparison of methods using standard protocols and quality control materials

Background: Recent studies suggested that there are marked systematic differences among BNP immunoassays. In this study we compared the BNP data and clinical results obtained with different immunoassays, including a new method (ST-AIA-PACK, TOSOH Corporation). Methods: BNP was measured on plasma-EDTA samples of healthy subjects (HS, n = 126) and patients with heart failure (HF, n = 31 NYHA I, II; n = 46 NYHA III, IV) using the ST-AIA-PACK and the Triage Biosite (Beckman Coulter) methods. Control samples distributed in the CardioOrmoCheck external quality assessment were also measured with TOSOH and the most used BNP immunoassays in Italy. Results: TOSOH method showed a good correlation (R = 0.976; n = 327) but a mean bias (−46.9%) compared to Triage Biosite. On the base of the results obtained in 10 samples of the CardioOrmoCheck study, TOSOH method showed a strict agreementwith ADVIA Centaur, while it underestimated BNP in comparisonwith Triage (−52.5%) and ARCHITECT methods (−39.4%). The agreement of ST-AIA-PACK and Triage Biosite methods for classification of HF patients was tested using 100 ng/L of BNP; the positive agreement between methods was 65%, overall agreement was 73%. Conclusions: Our results confirm that there are marked differences in measured values among commercial methods for BNP assay