Celiac disease in pediatric patients according to HLA genetic risk classes: a retrospective observational study

Background: Celiac disease (CD) is an autoimmune enteropathy in which HLA-DQ haplotypes define susceptibility. Our aim was to evaluate if belonging to a certain HLA-DQ class risk could be associated to the clinical, serological and histological presentation of CD. Methods: We performed a retrospective observational monocentric study including all 300 patients diagnosed with CD, who underwent HLA typing. Clinical, serological and histological data was collected from clinical records and their association with HLA-DQ class risk was verified through statistical tests. Results: In our sample mean age at onset was 6.7 ± 4.2 years, with a prevalence of females (n = 183; 61%), typical symptoms (n = 242; 80.6%) and anti-tTG IgA ≥ 100 U/mL (n = 194; 64.7%). Family history was present only in 19% (n = 57) of patients, and it was not significantly associated with any of the clinical and demographical data analyzed or the belonging to a certain HLA-DQ class risk. We found in the male population more frequently a coexistence of CD and atopic syndrome (males: n = 47; 40.2%; females: n = 50; 27.3%; p = 0.020). Early age of onset, instead, was associated with typical symptoms (m = 6.4 ± 4; p = 0.045) and elevated liver enzymes (m = 5 ± 3.8; p < 0.001), while later age of onset was associated with presence of other autoimmune diseases (m = 8.2 ± 4; p = 0.01). We observed statistically significant influences of HLA class risk on antibodies and liver enzymes levels: G1, G4 and G2 classes showed more frequently anti-tTG IgA ≥ 100 U/mL (n = 44; 80%, n = 16; 69.6%, n = 48; 67.6% respectively; p-value = 0.037), and in patients from G2 class we found enhanced liver enzymes (n = 28; 39.4%; p-value = 0.005). HLA class risk was still significantly associated with anti-tTG ≥ 100 (p = 0.044) and with hypertransaminasemia (p = 0.010) after a multiple logistic regression adjusted for the effect of gender, age at onset and family history. Conclusions: We failed to prove an association between HLA-DQ genotypes and the clinical features in our CD pediatric patients. Although, our results suggest an effect of the DQB1–02 allele not only on the level of antibodies to tTG, but possibly also on liver involvement

An Overview of Mitochondrial Protein Defects in Neuromuscular Diseases

none8noNeuromuscular diseases (NMDs) are dysfunctions that involve skeletal muscle and cause incorrect communication between the nerves and muscles. The specific causes of NMDs are not well known, but most of them are caused by genetic mutations. NMDs are generally progressive and entail muscle weakness and fatigue. Muscular impairments can differ in onset, severity, prognosis, and phenotype. A multitude of possible injury sites can make diagnosis of NMDs difficult. Mitochondria are crucial for cellular homeostasis and are involved in various metabolic pathways; for this reason, their dysfunction can lead to the development of different pathologies, including NMDs. Most NMDs due to mitochondrial dysfunction have been associated with mutations of genes involved in mitochondrial biogenesis and metabolism. This review is focused on some mitochondrial routes such as the TCA cycle, OXPHOS, and β-oxidation, recently found to be altered in NMDs. Particular attention is given to the alterations found in some genes encoding mitochondrial carriers, proteins of the inner mitochondrial membrane able to exchange metabolites between mitochondria and the cytosol. Briefly, we discuss possible strategies used to diagnose NMDs and therapies able to promote patient outcomeopenMarra Federica, Lunetti Paola, Curcio Rosita, Lasorsa Francesco Massimo, Capobianco Loredana, Porcelli Vito, Dolce Vincenza, Fiermonte Giuseppe and Scarcia PasqualeMarra, Federica; Lunetti, Paola; Curcio, Rosita; Lasorsa Francesco, Massimo; Capobianco, Loredana; Porcelli, Vito; Dolce, Vincenza; Fiermonte Giuseppe and Scarcia, Pasqual

S.A.G.NET: Rete GPS dell'Appennino meridionale.

The Matese carbonatic massive occupies the northernmost part of the campanian Apennine while Sannio mounts, located to the East of massive, consists primarily of quaternary deposits and represent the area of Apennine chain degrading to East towards the Bradanica foredeep. The area was affected in historical time by several destructive earthquakes. The first ground deformation studies in this area started from 1990-2000 with the definition of geodetic networks, covering all or part of the massive Matese, with the aim of evaluating seismogenic sources responsible for the seismicity of the area. In 2002, a careful inspection of the existing GPS benchmarks was carried out; those which had a good state of preservation and a good level of reliability were included into a new geodetic Matese network, consisting of 38 3D benchmarks. Several surveys were conducted in 2000, 2002 and 2004,with the aim of defining the strain field, defined by plano-altimetric components. In 2005, an intensive work of gathering and validating available data started, integrating data collected by previous surveys with those collected during the new survey carried out in 2006. This work describes in detail the various stages of implementing the final network S.A.G.NET, whose geometry was also bound to the distribution of the known seismogenic sources present in the area. We also show the first results obtained from data collected from2000 to 2006 and the resulting kinematic model for this area

Optical coherence tomography angiography findings in Huntington’s disease

Objectives: To evaluate the retinal and choriocapillaris vascular networks in macular region and the central choroidal thickness (CCT) in patients affected by Huntington disease (HD), using optical coherence tomography angiography (OCTA) and enhanced depth imaging spectral-domain OCT (EDI SD-OCT). Methods: We assessed the vessel density (VD) in superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) using OCTA, while CCT was measured by EDI SD-OCT. Results: Sixteen HD patients (32 eyes) and thirteen healthy controls (26 eyes) were enrolled in this prospective study. No significant difference in retinal and choriocapillaris VD was found between HD patients and controls while CCT turned to be thinner in patients respect to controls. There were no significant relationships between OCTA findings and neurological parameters. Conclusion: The changes in choroidal structure provide useful information regarding the possible neurovascular involvement in the physiopathology of HD. Choroidal vascular network could be a useful parameter to evaluate the vascular impairment that occurs in this neurodegenerative disease

Therapeutic sequences in patients with grade 1−2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group

Purpose: Many different treatments are suggested by guidelines to treat grade 1−2 (G1−G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1−G2 NET. Methods: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation. Results: Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1–G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with ≥2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n = 36), (B) SSA to everolimus (n = 31), (C) SSA to chemotherapy (n = 17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n = 15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p = 0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p = 0.04), as well as the rate of dose reduction/discontinuation (p = 0.03). Conclusions: SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1−G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy

Advanced Stirling Convertor Dual Convertor Controller Testing at NASA Glenn Research Center in the Radioisotope Power Systems System Integration Laboratory

NASA Glenn Research Center developed a nonnuclear representation of a Radioisotope Power System (RPS) consisting of a pair of Advanced Stirling Convertors (ASCs), Dual Convertor Controller (DCC) EMs (engineering models) 2 and 3, and associated support equipment, which were tested in the Radioisotope Power Systems System Integration Laboratory (RSIL). The DCC was designed by the Johns Hopkins University Applied Physics Laboratory (JHU/APL) to actively control a pair of ASCs. The first phase of testing included a Dual Advanced Stirling Convertor Simulator (DASCS), which was developed by JHU/APL and simulates the operation and electrical behavior of a pair of ASCs in real time via a combination of hardware and software. RSIL provides insight into the electrical interactions between a representative radioisotope power generator, its associated control schemes, and realistic electric system loads. The first phase of integration testing included the following spacecraft bus configurations: capacitive, battery, and super-capacitor. A load profile, created based on data from several missions, tested the RPS's and RSIL's ability to maintain operation during load demands above and below the power provided by the RPS. The integration testing also confirmed the DCC's ability to disconnect from the spacecraft when the bus voltage dipped below 22 volts or exceeded 36 volts. Once operation was verified with the DASCS, the tests were repeated with actual operating ASCs. The goal of this integration testing was to verify operation of the DCC when connected to a spacecraft and to verify the functionality of the newly designed RSIL. The results of these tests are presented in this paper

Comparative analysis of density histograms and visual scores in incremental and volumetric high-resolution computed tomography of the chest in idiopathic pulmonary fibrosis patients

Background: Volumetric high-resolution computed tomography (HRCT) of the chest has recently replaced incremental CT in the diagnostic workup of idiopathic pulmonary fibrosis (IPF). Concomitantly, visual and quantitative scores have been proposed for disease extent assessment to ameliorate disease management. Purpose: To compare the performance of density histograms (mean lung attenuation, skewness, and kurtosis) and visual scores, along with lung function correlations, in IPF patients submitted to incremental or volumetric thorax HRCT. Material and methods: Clinical data and CT scans of 89 newly diagnosed and therapy-naive IPF patients were retrospectively evaluated. Results: Forty-six incremental and 43 volumetric CT scans were reviewed. No differences of density histograms and visual scores estimates were found by comparing two HRCT techniques, with an optimal inter-operator agreement (concordance correlation coefficient >0.90 in all instances). Single-breath diffusing lung capacity for carbon monoxide (DLCOsb) was inversely related with the Best score (r = −00.416; p = 0.014), the Kazerooni fibrosis extent (r = −0.481; p = 0.004) and the mean lung attenuation (r = −0.382; p = 0.026), while a positive correlation was observed with skewness (r = 0.583; p = 0.001) and kurtosis (r = 0.543; p = 0.001) in the incremental HRCT sub-group. Similarly, in the volumetric CT sub-cohort, DLCOsb was significantly associated with skewness (r = 0.581; p = 0.007) and kurtosis (r = 0.549; p = 0.018). Correlations with visual scores were not confirmed. Forced vital capacity significantly related to all density indices independently on HRCT technique. Conclusions: Density histograms and visual scores similarly perform in incremental and volumetric HRCT. Density quantification displays an optimal reproducibility and proves to be superior to visual scoring as more strongly correlated with lung function

Advanced Stirling Convertor Dual Convertor Controller Testing at NASA Glenn Research Center in the Radioisotope Power Systems System Integration Laboratory

NASA Glenn Research Center (GRC) developed a non-nuclear representation of a Radioisotope Power System (RPS) consisting of a pair of Advanced Stirling Convertors (ASC), a Dual Convertor Controller (DCC) EM (engineering model) 2 & 3, and associated support equipment, which were tested in the Radioisotope Power Systems System Integration Laboratory (RSIL). The DCC was designed by the Johns Hopkins University/Applied Physics Laboratory (JHU/APL) to actively control a pair of Advanced Stirling Convertors (ASC). The first phase of testing included a Dual Advanced Stirling Convertor Simulator (DASCS) which was developed by JHU/APL and simulates the operation and electrical behavior of a pair of ASC's in real time via a combination of hardware and software. RSIL provides insight into the electrical interactions between a representative radioisotope power generator, its associated control schemes, and realistic electric system loads. The first phase of integration testing included the following spacecraft bus configurations: capacitive, battery, and supercapacitor. A load profile, created based on data from several missions, tested the RPS and RSIL ability to maintain operation during load demands above and below the power provided by the RPS. The integration testing also confirmed the DCC's ability to disconnect from the spacecraft when the bus voltage dipped below 22 V or exceeded 36 V. Once operation was verified with the DASCS, the tests were repeated with actual operating ASC's. The goal of this integration testing was to verify operation of the DCC when connected to a spacecraft and to verify the functionality of the newly designed RSIL. The results of these tests are presented in this paper

La rete GPS dell'isola d'Ischia: Deformazioni del suolo in un'area vulcanica attiva (1998-2010).

This work shows the experience acquired by the INGV-Osservatorio Vesuviano GPS Team to study the displacement field at Ischia island. After the last GPS survey, carried out in June 2010, we decided to reorganize and to reprocess the GPS data. The results were integrated with those of the three permanent GPS stations operating on the island. Data quality and repeatability have been evaluated. In order to define the GPS velocity field, we combined multi-year solutions in the period from 1998 to 2010.We defined a local reference system and analyzed the time series for a realistic error estimate. After a description of recent volcanic history and dynamics of Ischia, we describe the data-set, data processing strategy, and finally, some considerations on the achieved results are exposed

GPS Monitoring at Vesuvio, Campi Flegrei Caldera and Ischia Island (Southern Italy)

The Neapolitan volcanic area is located in the southern part of the Campanian plain and includes three active volcanoes (Vesuvius, Campi Flegrei Caldera and Ischia Island). This area shows different dynamical behaviours. Campi Flegrei caldera represents one well known and peculiar example of ground deformations (bradyseism), with periods of intense uplift during the 1969-72 and 1982-84, followed by subsidence phase with some episodic mini-uplifts superimposed. Contrary, Vesuvius is a substantially stable volcano, with small and localized subsidence mainly in the crater zone. Ischia Island has been characterized by subsidence in the S and NW sectors of the island. The presence of these three volcanoes in a dense populated area, makes ground deformation detection a crucial point in the risk mitigation. Ground deformation is an important volcanic precursor, because linked to magma overpressure and migration, thus, continuous monitoring and modelling is one of the main instruments to attempt for a short time forecast of eruptive activity. Since several years, the INGV – Osservatorio Vesuviano installed a permanent GPS network (NeVoCGPS), constituted of 27 stations, in the Neapolitan volcanic area with a configuration that guarantees a continuous and fast 3D information about the dynamics of the area. All the GPS stations are managed by remote control, the data are daily downloaded automatically. After an automatic quality control procedure, the data processing is performed by the Bernese Processing Engine (BPE) of the Bernese GPS software v. 5.0. In this work, the entire chain of data acquisition and processing is described and some results obtained in last years are presented