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

Analysis of the melanocortin receptor 1 (MC1R) gene in Sicilian goat breeds

AbstractMammalian coat colour is mainly determined by the distribution of two different types of melanins: pheomelanin (red/yellow pigments) and eumelanin (black pigments). Their synthesis is regulated by the melanocortin 1 receptor (MC1R/Extension locus) that binds the α-melanocyte-stimulating hormone (α-MSH) and the agouti signalling protein (ASIP, coded by the Agouti locus). In mammals, several studies have reported that loss-of-function mutations in MC1R lead to red/yellow pigmentation, while gain-of-function mutations lead to black/dark colours. Mutations at the Agouti locus exert, in general, epistatic interactions on the Extension locus. In goats, classical genetic studies have indicated that variations at the Agouti locus may be the main source of colour variability within and between breeds, while the effect of the Extension locus on this phenotypic trait has been only partially deduced. In order to better understand the role of the Extension locus on coat colour in this species, here we analysed..

A mini-phoswich scintillator as a possible stop detector for the NUMEN project

AbstractIn the framework of the NUMEN project, aimed at the investigation of the nuclear matrix elements connected to the neutrinoless double beta decay by means of the Double Charge Exchange nuclear reactions (Cappuzzello et al., 2015), a high granularity stop detector for heavy ions is needed. It has to allow the identification of ions up to Z≈10 while maintaining a total energy resolution around 2%. As the use of silicon detectors is not possible, due to their poor radiation hardness, scintillators are being investigated as possible candidates. In this paper we show a promising result obtained using a plastic+inorganic phoswich scintillator readout by means of a Silicon Photo Multiplier

Silicon detectors for the n-TOF neutron beams monitoring

During 2014 the second experimental area EAR2 was completed at the n-TOF neutron beam facility at CERN. As the neutrons are produced via spallation, by means of a high-intensity 20 GeV pulsed proton beam impinging on a thick target, the resulting neutron beam covers an enormous energy range, from thermal to several GeV. In this paper we describe two beam diagnostic devices, designed and built at INFN-LNS, both exploiting silicon detectors coupled with neutron converter foils containing 6Li. The first one is based on four silicon pads and allows to monitor the neutron beam flux as a function of the neutron energy. The second one, based on position sensitive silicon detectors, is intended for the reconstruction of the beam profile, again as a function of the neutron energy. Several electronic setups have been explored in order to overcome the issues related to the gamma flash, namely a huge pulse present at the start of each neutron bunch which may blind the detectors for some time. The two devices have been characterized with radioactive sources at INFN-LNS and then tested at n-TOF. The wide energy and intensity range they proved capable of sustaining, made them quite attractive and suitable to be used in both EAR1 and EAR2 n-TOF experimental areas, where they became immediately operational.Comment: submitted to Review of Scientific Instrument

Cytokine-Enhanced Vaccine and Suicide Non-Viral Gene Therapy in Advanced Metastatic Melanoma Patients: Two Case Reports

The prognostic for metastatic melanoma is very poor when treated with standard cytotoxic chemotherapies and it is often refractory to check point inhibitors and/or molecular targets. In this context the development of new treatments with better efficacy and safety profiles is highly desirable. Based on our successful experience applying suicide and immune gene therapy in a veterinary clinical setting, we are proposing its translation to human patients. We are presenting here the first-in-human safety assay of this approach. We report two cases of refractory metastatic melanoma. The first-one was a 27-years-old pharyngeal mucosal melanoma patient with a primary tumor in his left tonsil. Despite transient slowing down, the disease successively progressed to radiotherapy, radical surgery, ipilimumab, nivolumab, imatinib and temozolomide. The second-one was a 72-years-old malignant melanoma patient with a primary tumor in his left hallux. Despite transient slowing down, the disease successively progressed to hallux amputation, inguinal lymphadenectomy, radiotherapy, interferon-alpha, ipilimumab, pembrolizumab and temozolomide. The proposed treatment included local intratumoral suicide gene therapy concomitant with a subcutaneous vaccine composed by allogeneic tumor extracts and liposomes with plasmids bearing IL-2 and GM-CSF genes. The treatment was safe: the only side effects were from mild to moderate and manageable: pyrexia, swelling of the injected tumor and partial hair loss (alopecia). Due to disease progression both patients were withdrawn from the study before completing the complete series of interventions. These preliminary data encourage the completion of further clinical trials to establish the possible clinical benefit of the proposed approach.Fil: Finocchiaro, Liliana Maria Elena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Simonovich, V.A.. Hospital Italiano; ArgentinaFil: Hernández Herrera, Heliana L.. Hospital Italiano; ArgentinaFil: Glikin, Gerardo Claudio. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

A Robotic arm for optical and gamma radwaste inspection

We propose Radibot, a simple and cheap robotic arm for remote inspection, which interacts with the radwaste environment by means of a scintillation gamma detector and a video camera representing its light (< 1 kg) payload. It moves vertically thanks to a crane, while the other three degrees of freedom are obtained by means of revolute joints. A dedicated algorithm allows to automatically choose the best kinematics in order to reach a graphically selected position, while still allowing to fully drive the arm by means of a standard videogame joypad

Clinical significance of endometrial abnormalities: an observational study on 1020 women undergoing hysteroscopic surgery

Background: The overall clinical significance of the finding of endometrial abnormalities in predicting premalignant/malignant endometrial lesions is still incompletely determined. For this reason the management, surgical or expectant, of women in which an endometrial abnormality has been detected is debated. Methods: This retrospective study was carried out on 1020 consecutive women, 403 premenopausal and 617 postmenopausal, who underwent operative hysteroscopy in a University Hospital for suspected endometrial abnormalities, which were detected by transvaginal ultrasound (TVS) and/or office hysteroscopy. In these women, the clinical characteristics and findings at TVS and hysteroscopy were evaluated in relation to the presence/absence of premalignant/malignant endometrial lesions at pathology report. Results: The clinical characteristics considered were significantly different when the study women were compared according to their menopausal status. Premalignant/malignant lesions were found in 34/1020 (3.33%) women. Complex hyperplasia with atypia and endometrial cancer were detected in 22 (2.15%) and 12 (1.17%) cases, respectively. The postmenopausal women had a significantly higher risk of premalignant/malignant lesions than premenopausal women (O.R. = 5.098 [95% C.I.: 1.782–14.582], P &lt; 0.005). This risk was even higher when abnormal uterine bleeding (AUB) was present (O.R. = 5.20 [95% C.I.: 2.38–11.35], P &lt; 0.0001). The most significant associations with premalignant/malignant endometrial lesions were BMI, AUB in postmenopause, overall polyp size, atypical aspect of endometrial polyps at hysteroscopy, postmenopausal status, diabetes mellitus and patient age. Conclusions: The results of the present study suggest that the proper, aggressive or expectant, management of endometrial abnormalities should take into account both ultrasonographic and hysteroscopic findings together with the specific clinical characteristics of the patients