β-Hexachlorocyclohexane Drives Carcinogenesis in the Human Normal Bronchial Epithelium Cell Line BEAS-2B

Organochlorine pesticides constitute the majority of the total environmental pollutants, and a wide range of compounds have been found to be carcinogenic to humans. Among all, growing interest has been focused on β-hexachlorocyclohexane (β-HCH), virtually the most hazardous and, at the same time, the most poorly investigated member of the hexachlorocyclohexane family. Considering the multifaceted biochemical activities of β-HCH, already established in our previous studies, the aim of this work is to assess whether β-HCH could also trigger cellular malignant transformation toward cancer development. For this purpose, experiments were performed on the human normal bronchial epithelium cell line BEAS-2B exposed to 10 µM β-HCH. The obtained results strongly support the carcinogenic potential of β-HCH, which is achieved through both non-genotoxic (activation of oncogenic signaling pathways and proliferative activity) and indirect genotoxic (ROS production and DNA damage) mechanisms that significantly affect cellular macroscopic characteristics and functions such as cell morphology, cell cycle profile, and apoptosis. Taking all these elements into account, the presented study provides important elements to further characterize β-HCH, which appears to be a full-fledged carcinogenic agent

The Low Energy Tagger for the KLOE-2 experiment

The KLOE experiment at the upgraded DAFNE e+e- collider in Frascati (KLOE-2) is going to start a new data taking at the beginning of 2010 with its detector upgraded with a tagging system for the identification of gamma-gamma interactions. The tagging stations for low-energy e+e- will consist in two calorimeters The calorimeter used to detect low-energy e+e- will be placed between the beam-pipe outer support structure and the inner wall of the KLOE drift chamber. This calorimeter will be made of LYSO crystals readout by Silicon Photomultipliers, to achieve an energy resolution better than 8% at 200 MeV.Comment: 4 pages, 5 figures, in the proceedings of "Frontier detectors for frontier physics", isola d'Elba, Italy, May 200

β-hexachlorocyclohexane: a small molecule with a big impact on human cellular biochemistry

Organochlorine pesticides (OCPs) belong to a heterogeneous class of organic compounds blacklisted by the Stockholm Convention in 2009 due to their harmful impact on human health. Among OCPs, β-hexachlorocyclohexane (β-HCH) is one of the most widespread and, at the same time, poorly studied environmental contaminant. Due to its physicochemical properties, β-HCH is the most hazardous of all HCH isomers; therefore, clarifying the mechanisms underlying its molecular action could provide further elements to draw the biochemical profile of this OCP. For this purpose, LNCaP and HepG2 cell lines were used as models and were subjected to immunoblot, immunofluorescence, and RT-qPCR analysis to follow the expression and mRNA levels, together with the distribution, of key biomolecules involved in the intracellular responses to β-HCH. In parallel, variations in redox homeostasis and cellular bioenergetic profile were monitored to have a complete overview of β-HCH effects. Obtained results strongly support the hypothesis that β-HCH could be an endocrine disrupting chemical as well as an activator of AhR signaling, promoting the establishment of an oxidative stress condition and a cellular metabolic shift toward aerobic glycolysis. In this altered context, β-HCH can also induce DNA damage through H2AX phosphorylation, demonstrating its multifaceted mechanisms of action

The effect of maxillary protraction, with or without rapid palatal expansion, on airway dimensions: A systematic review and meta-analysis

Aim The use of maxillary protraction appliances (MPAs) and Facemask (FM), with or without a rapid maxillary expansion (RME), have become a routine orthopaedic treatment procedure for the treatment of Class III in growing individuals; several authors have suggested that maxillary protraction could have a positive impact on airway dimensions. The purpose of this systematic review and meta- analysis was to assess the efficacy of maxillary protraction appliances (MPAs), with or without a rapid maxillary expansion (RME), on airway dimensions in children in mixed or early permanent dentition. Methods An electronic search was performed on PubMed, Medline, Scopus, The Cochrane Library, EMBASE and the System for Information on Grey Literature in Europe until November 30th, 2019. The Newcastle-Ottawa (NOS) scale was used to assess the studies’ quality. Review Manager 5.3 (provided by the Cochrane Collaboration) was used to synthesize the effects on airway dimensions. Results After full text assessment, 8 studies were included in the qualitative and quantitative synthesis. NOS scores ranged 6 to 9 indicating high quality. The effects of two therapeutic protocols were compared, treatment with MPAs only (113 subjects treated - 65 controls) and the treatment with MPAs + RME (137 subjects treated-87 controls). The MPAs only treatment group displayed a significantly increase in nasopharyngeal airway dimension at PNS-AD1 (random: mean difference, 1.39 mm, 95% CI, 0.32 mm, 2.47 mm, p= 0.01) and at PNS-AD2 (random: mean difference, 1.70 mm, 95% CI, 1.14 mm, 2.26 mm, p= 0.00001). No statistically significant changes were found post treatment in MPAs + RME treatment groups at PNS-AD1 (P= 0.15), PNS-AD2 (P= 0.17), McNamara’s upper pharynx (MPAs + RME P= 0.05, MPAs P= 0.99) and McNamara lower pharynx (MPAs + RME P= 0.25, MPAs P= 0.40). Conclusion MPAs only treatment can increase the pharyngeal thickness after treatment both at PNS-A1 and PNS-AD2. MPA+ RME had no effect on sagittal widths compared with controls, but the effect on the transverse dimension could not be assessed

In-vessel inspection before head removal: TMI II: Phase I. (Conceptual development)

The objective of the task is to provide for an internal inspection of the reactor vessel and the fuel assemblies prior to reactor vessel head removal. Because the degree of damage to equipment and fuel in the TMI-II reactor is not precisely known, it is important that as much information as possible be obtained on present conditions inside the reactor. This information will serve to benchmark the various analyses already completed or underway and will also guide the development of programs to obtain more information on the TMI-II core damage. In addition, the early look will provide data for planning the reactor disassembly program

Molecular analysis of TP53, Ki-Ras and P16 methylation status in tissue and plasma of subjects affected by gastrointestinal cancer (GIC)

BACKGROUND: Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same alteration both in the plasma and in the tumor tissue. At univariate analysis, Ki-Ras mutations proved to be significantly related to quicker relapse (P <0.01), whereas only a trend towards statistical significance (P = 0.083) was observed for the TP53 mutations CONCLUSIONS: Detection of Ki-Ras and TP53 mutation in plasma should be significantly related to disease recurrence. These data suggest that patients with a high risk of recurrence can be identified by means of the analysis of tumor-derived plasma DNA with the use of fairly non-invasive techniques

Linguistic profile automated characterisation in pluripotential clinical high-risk mental state (CHARMS) conditions: methodology of a multicentre observational study

Introduction: Language is usually considered the social vehicle of thought in intersubjective communications. However, the relationship between language and high- order cognition seems to evade this canonical and unidirectional description (ie, the notion of language as a simple means of thought communication). In recent years, clinical high at-risk mental state (CHARMS) criteria (evolved from the Ultra-High-Risk paradigm) and the introduction of the Clinical Staging system have been proposed to address the dynamicity of early psychopathology. At the same time, natural language processing (NLP) techniques have greatly evolved and have been successfully applied to investigate different neuropsychiatric conditions. The combination of at-risk mental state paradigm, clinical staging system and automated NLP methods, the latter applied on spoken language transcripts, could represent a useful and convenient approach to the problem of early psychopathological distress within a transdiagnostic risk paradigm. Methods and analysis: Help-seeking young people presenting psychological distress (CHARMS+/− and Clinical Stage 1a or 1b; target sample size for both groups n=90) will be assessed through several psychometric tools and multiple speech analyses during an observational period of 1-year, in the context of an Italian multicentric study. Subjects will be enrolled in different contexts: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa—IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Mental Health Department—territorial mental services (ASL 3—Genoa), Genoa, Italy; and Mental Health Department—territorial mental services (AUSL—Piacenza), Piacenza, Italy. The conversion rate to full-blown psychopathology (CS 2) will be evaluated over 2 years of clinical observation, to further confirm the predictive and discriminative value of CHARMS criteria and to verify the possibility of enriching them with several linguistic features, derived from a fine-grained automated linguistic analysis of speech. Ethics and dissemination: The methodology described in this study adheres to ethical principles as formulated in the Declaration of Helsinki and is compatible with International Conference on Harmonization (ICH)-good clinical practice. The research protocol was reviewed and approved by two different ethics committees (CER Liguria approval code: 591/2020—id.10993; Comitato Etico dell’Area Vasta Emilia Nord approval code: 2022/0071963). Participants will provide their written informed consent prior to study enrolment and parental consent will be needed in the case of participants aged less than 18 years old. Experimental results will be carefully shared through publication in peer- reviewed journals, to ensure proper data reproducibility. Trial registration number DOI:10.17605/OSF.IO/BQZTN

The NA62 LAV front-end electronics

The branching ratio for the decay $K^+ \to \pi^+\nu\bar{\nu}$ is sensitive to new physics; the NA62 experiment will measure it to within about 10%. To reject the dominant background from channels with final state photons, the large-angle vetoes (LAVs) must detect particles with better than 1 ns time resolution and 10% energy resolution over a very large energy range. Our custom readout board uses a time-over-threshold discriminator coupled to a TDC as a straightforward solution to satisfy these requirements. A prototype of the readout system was extensively tested together with the ANTI-A2 large angle veto module at CERN in summer 2010.Comment: prepared for the TWEPP 2011 conference proceeding

Effect of pomiferin administration on kidney ischaemia-reperfusion injury in rats

The aim of the study was to analyse protective effects of different doses of pomiferin in therapy of reperfusion injury. Rats were randomly divided into five groups (n=10). One group was intact. Three medicated groups and one placebo group were subjected to ischaemia and reperfusion of the left kidney. Pomiferin was administrated by single gastric gavage in 2 ml of 0.5% Avicel solution in doses of 5, 10 and 20 mg/kg. The placebo group was given only Avicel solution. On day 15, all the animals were exsanguinated and the reperfused kidneys were recovered. Selected biochemical markers were assessed in blood: antioxidative enzymes, total antioxidative capacity, malondialdehyde, creatinine, urea and uric acid. Creatinine, urea and total proteins were analysed in urine and 24-hour diuresis was recorded. The kidney tissue samples were used for histopathological examination