Serum creatine kinase isoenzymes in children with osteogenesis imperfecta

This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention. Introduction The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period. Methods This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups. Results Serum CKbb was progressively and significantly increased in group A (p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged. Conclusions This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs

A quantitative proteomic approach to identify significantly altered protein networks in the serum of patients with lymphangioleiomyomatosis (LAM)

Lymphangioleiomyomatosis (LAM) is a rare and progressive cystic lung condition affecting approximately 3.4-7.5/million women, with an average lag time between symptom onset and diagnosis of upwards of 4 years. The aim of this work was to identify altered proteins in LAM serum which may be potential biomarkers of disease. Serum from LAM patient volunteers and healthy control volunteers were pooled and analysis carried out using quantitative 4-plex iTRAQ technology. Differentially expressed proteins were validated using ELISAs and pathway analysis was carried out using Ingenuity Pathway Analysis. Fourteen proteins were differentially expressed in LAM serum compared to control serum (p<0.05). Further screening validated the observed differences in extracellular matrix remodelling proteins including fibronectin (30% decrease in LAM, p = 0.03), von Willebrand Factor (40% reduction in LAM, p = 0.03) and Kallikrein III (25% increase in LAM, p = 0.03). Pathway networks elucidated the relationships between the ECM and cell trafficking in LAM. This study was the first to highlight an imbalance in networks important for remodelling in LAM, providing a set of novel potential biomarkers. These understandings may lead to a new effective treatment for LAM in the future. © 2014 Banville et al

Polymorphisms in metabolic genes, their combination and interaction with tobacco smoke and alcohol consumption and risk of gastric cancer: a case-control study in an Italian population.

BACKGROUND: The distribution and the potential gene-gene and gene-environment interaction of selected metabolic genetic polymorphisms was investigated in relation to gastric cancer risk in an Italian population. METHODS: One hundred and seven cases and 254 hospital controls, matched by age and gender, were genotyped for CYP1A1, CYP2E1, mEH, GSTM1, GSTT1, NAT2 and SULT1A1 polymorphisms. Haplotype analysis was performed for EPHX1 exons 3 and 4, as well as CYP2E1 RsaI (*5 alleles) and CYP2E1 DraI (*5A or *6 alleles). The effect modification by alcohol and cigarette smoking was tested with the heterogeneity test, while the attributable proportion (AP) was used to measure the biological interaction from the gene-gene interaction analysis. RESULTS: Gastric cancer risk was found to be associated with the inheritance of GSTT1 null genotype (OR = 2.10, 95%CI: 1.27-3.44) and the SULT1A1 His/His genotype (OR = 2.46, 95%CI: 1.03-5.90). No differences were observed for the haplotype distributions among cases and controls. For the first time an increased risk was detected among individuals carrying the *6 variant allele of CYP2E1 if ever-drinkers (OR = 3.70; 95%CI: 1.45-9.37) with respect to never-drinkers (OR = 0.18; 95% CI: 0.22-1.46) (p value of heterogeneity among the two estimates = 0.001). Similarly, the effect of SULT1A1 variant genotype resulted restricted to ever-smokers, with an OR of 2.58 (95%CI: 1.27-5.25) for the carriers of His allele among smokers, and an OR of 0.86 (95%CI: 0.45-1.64) among never-smokers (p value of heterogeneity among the two estimates = 0.03). The gene-gene interaction analyses demonstrated that individuals with combined GSTT1 null and NAT2 slow acetylators had an additional increased risk of gastric cancer, with an OR of 3.00 (95%CI: 1.52-5.93) and an AP of 52%. CONCLUSION: GSTT1, SULT1A1 and NAT2 polymorphisms appear to modulate individual's susceptibility to gastric cancer in this Italian population, particularly when more than one unfavourable genotype is present, or when combined with cigarette smoke. The increased risk for the carriers of CYP2E1*5A or *6 alleles among drinkers need to be confirmed by larger prospective studies

First CNGS events detected by LVD

The CERN Neutrino to Gran Sasso (CNGS) project aims to produce a high energy, wide band $\nu_{\mu}$ beam at CERN and send it toward the INFN Gran Sasso National Laboratory (LNGS), 732 km away. Its main goal is the observation of the $\nu_{\tau}$ appearance, through neutrino flavour oscillation. The beam started its operation in August 2006 for about 12 days: a total amount of $7.6~10^{17}$ protons were delivered to the target. The LVD detector, installed in hall A of the LNGS and mainly dedicated to the study of supernova neutrinos, was fully operating during the whole CNGS running time. A total number of 569 events were detected in coincidence with the beam spill time. This is in good agreement with the expected number of events from Montecarlo simulations.Comment: Accepted for publication by the European Physical Journal C ; 7 pages, 11 figure

A Programming Interface for Creating Data According to the SPAR Ontologies and the OpenCitations Data Model

The OpenCitations Data Model (OCDM) is a data model for bibliographic metadata and citations based on the SPAR Ontologies and developed by OpenCitations to expose all the data of its collections as sets of RDF statements compliant with an ontology named OpenCitations Ontology. In this paper, we introduce oc_ocdm, i.e. a Python library developed for creating OCDM-compliant RDF data even if the programmer has no expertise in Semantic Web technologies. After an introduction of the library and its main characteristics, we show a number of projects within the OpenCitations infrastructure that adopt it as their building block unit

Implications on Inelastic Dark Matter from 100 Live Days of XENON100 Data

The XENON100 experiment has recently completed a dark matter run with 100.9 live-days of data, taken from January to June 2010. Events in a 48kg fiducial volume in the energy range between 8.4 and 44.6 keVnr have been analyzed. A total of three events have been found in the predefined signal region, compatible with the background prediction of (1.8 \pm 0.6) events. Based on this analysis we present limits on the WIMP-nucleon cross section for inelastic dark matter. With the present data we are able to rule out the explanation for the observed DAMA/LIBRA modulation as being due to inelastic dark matter scattering off iodine at a 90% confidence level.Comment: 3 pages, 3 figure

Dark Matter Results from 100 Live Days of XENON100 Data

We present results from the direct search for dark matter with the XENON100 detector, installed underground at the Laboratori Nazionali del Gran Sasso of INFN, Italy. XENON100 is a two-phase time projection chamber with a 62 kg liquid xenon target. Interaction vertex reconstruction in three dimensions with millimeter precision allows to select only the innermost 48 kg as ultra-low background fiducial target. In 100.9 live days of data, acquired between January and June 2010, no evidence for dark matter is found. Three candidate events were observed in a pre-defined signal region with an expected background of 1.8 +/- 0.6 events. This leads to the most stringent limit on dark matter interactions today, excluding spin-independent elastic WIMP-nucleon scattering cross-sections above 7.0x10^-45 cm^2 for a WIMP mass of 50 GeV/c^2 at 90% confidence level.Comment: 5 pages, 5 figures; matches accepted versio

Comment on "On the subtleties of searching for dark matter with liquid xenon detectors"

In a recent manuscript (arXiv:1208.5046) Peter Sorensen claims that XENON100's upper limits on spin-independent WIMP-nucleon cross sections for WIMP masses below 10 GeV "may be understated by one order of magnitude or more". Having performed a similar, though more detailed analysis prior to the submission of our new result (arXiv:1207.5988), we do not confirm these findings. We point out the rationale for not considering the described effect in our final analysis and list several potential problems with his study.Comment: 3 pages, no figure

Removing krypton from xenon by cryogenic distillation to the ppq level

The XENON1T experiment aims for the direct detection of dark matter in a cryostat filled with 3.3 tons of liquid xenon. In order to achieve the desired sensitivity, the background induced by radioactive decays inside the detector has to be sufficiently low. One major contributor is the $\beta$-emitter $^{85}$Kr which is an intrinsic contamination of the xenon. For the XENON1T experiment a concentration of natural krypton in xenon $\rm{^{nat}}$Kr/Xe < 200 ppq (parts per quadrillion, 1 ppq = 10$^{-15}$ mol/mol) is required. In this work, the design of a novel cryogenic distillation column using the common McCabe-Thiele approach is described. The system demonstrated a krypton reduction factor of 6.4$\cdot$10$^5$ with thermodynamic stability at process speeds above 3 kg/h. The resulting concentration of $\rm{^{nat}}$Kr/Xe < 26 ppq is the lowest ever achieved, almost one order of magnitude below the requirements for XENON1T and even sufficient for future dark matter experiments using liquid xenon, such as XENONnT and DARWIN

On-line recognition of supernova neutrino bursts in the LVD detector

In this paper we show the capabilities of the Large Volume Detector (INFN Gran Sasso National Laboratory) to identify a neutrino burst associated to a supernova explosion, in the absence of an "external trigger", e.g., an optical observation. We describe how the detector trigger and event selection have been optimized for this purpose, and we detail the algorithm used for the on-line burst recognition. The on-line sensitivity of the detector is defined and discussed in terms of supernova distance and electron anti-neutrino intensity at the source.Comment: Accepted for pubblication on Astroparticle Physics. 13 pages, 10 figure