Resilience after a nuclear accident: readiness in using mobile phone applications to measure radiation and health indicators in various groups (SHAMISEN SINGS project).

An anonymous web-based survey was developed to check different aspects (SHAMISEN SINGS project): stakeholder awareness and perceptions of available mobile applications (apps) for measuring ionising radiation doses and health/well-being indicators; whether they would be ready to use them in the post-accidental recovery; and what are their preferred methodologies to acquire information etc. The results show that participation of the citizens would be most beneficial during post-accident recovery, providing individual measurements of external ionizing dose and health/well-being parameters, with possible follow-up. Also, participants indicated different preferences for sources to gain knowledge on ionising radiation and for the functions that an ideal app should have. The level of awareness and readiness to use apps to measure ionising radiation dose depended on two main aspects: individual differences (age & gender) and whether people were from countries affected by the previous major accidents. We concluded that stakeholders could have benefits from the data management plan: (1) it potentiates resilience at individual and community level; (2) citizens' measurements contribute to environmental monitoring and public health screening; (3) linkages between different types of data (environmental exposure, individual behavioural diaries, and measurements of health indicators) allow to perform more rigorous epidemiological studies.

Hydroxytyrosol Counteracts Triple Negative Breast Cancer Cell Dissemination via Its Copper Complexing Properties.

Polyphenols have gained increasing attention for their therapeutic potential, particularly in conditions like cancer, due to their established antioxidant and anti-inflammatory properties. Recent research highlights their ability to bind to transition metals, such as copper. This is particularly noteworthy given the key role of copper both in the initiation and progression of cancer. Copper can modulate the activity of kinases required for the epithelial-mesenchymal transition (EMT), a process fundamental to tumor cell dissemination. We have previously demonstrated the copper-binding capacity of oleuropein, a secoiridoid found in Olea europaea. In the present study, we investigated the effect of hydroxytyrosol, the primary oleuropein metabolite, on the metastatic potential of three triple-negative breast cancer cell lines (MDA-MB-231, MDA-MB-468, and SUM159). We found that hydroxytyrosol modulated the intracellular copper levels, influencing both the epithelial and mesenchymal markers, by downregulating copper-dependent AKT phosphorylation, a member of the EMT signaling cascade, through Western blot, RT-qPCR, and immunofluorescence. Indeed, by optical spectra, EPR, and in silico approaches, we found that hydroxytyrosol formed a complex with copper, acting as a chelating agent, thus regulating its homeostasis and affecting the copper-dependent signaling cascades. While our results bring to light the copper-chelating properties of hydroxytyrosol capable of countering tumor progression, they also provide further confirmation of the key role of copper in promoting the aggressiveness of triple-negative breast cancer cells.

A real-time system to report abnormal events involving staff in a nuclear medicine therapy unit.

A system for internal and voluntary reporting of abnormal events in a Nuclear Medicine Therapy Unit is described. This system is based on the Internet of Things and is composed of an application for mobile devices and a wireless network of detectors. The application is addressed to healthcare professionals and is intended to be a user-friendly tool to make the reporting procedure little laborious. The network of detectors allows for a real-time measurement of the dose distribution in the patient's room. The staff was involved in all stages, from the design of the dosimetry system and mobile application up to their final testing. Face-to-face interviews were carried out with 24 operators in different roles in the Unit (radiation protection experts, physicians, physicists, nuclear medicine technicians and nurses). The preliminary results of the interviews and the current state of development of the application and the detection network will be described.

Salty Crackers as Fortuitous Dosimeters: A Novel PSL Method for Rapid Radiation Triage.

When a radiological and nuclear (R/N) emergency occurs, the categorization of individuals into those who are unaffected and those requiring medical intervention is a high priority. At times, a professional dosimeter is not available and therefore some common belongings may be used as fortuitous dosimeters. The preparation of these objects for the measurement should be such as to give the most accurate and precise results. This paper focused on the Photo-Stimulated Luminescence (PSL) response of salty crackers confronts the problem of sample preparation (mass, grain size), dose response and signal stability. The dose response was determined for doses up to 5 Gy, which allowed the calculation of the limit of detection. Additionally, the signal stability was investigated for samples irradiated with 0.3 and 3 Gy. The observed decrease of the signal does not prevent the detection in the dose range typical for R/N emergency. The main dosimetric characteristics were investigated by using two different models of PSL readers equipped with single (infrared) or double (infrared, blue light) stimulation. The results indicated that the limit of detection can be improved by applying blue light stimulation. Moreover, strong correlation of the measurements performed in the two different instruments, as well as the rapidity of the analysis and the simplicity of the operations, suggest that this method can be suitable for a rapid radiation triage of a large number of civilians in a mass casualty event. The study was simultaneously conducted by two laboratories (Ruder Boskovic Institute, RBI, Croatia and Istituto Superiore di Sanità, ISS, Italy) involved in the BioPhyMeTRE project (grant No. G5684) supported by NATO Science for Peace and Security Programme.

Lessons from past radiation accidents: Critical review of methods addressed to individual dose assessment of potentially exposed people and integration with medical assessment.

The experiences of the Chernobyl and Fukushima nuclear accidents showed that dosimetry was the essential tool in the emergency situation for decision making processes, such as evacuation and application of protective measures. However, at the consequent post-accidental phases, it was crucial also for medical health surveillance and in further adaptation to changed conditions with regards to radiation protection of the affected populations. This review provides an analysis of the experiences related to the role of dosimetry (dose measurements, assessment and reconstruction) regarding health preventive measures in the post-accidental periods on the examples of the major past nuclear accidents such as Chernobyl and Fukushima. Recommendations derived from the review are called to improve individual dose assessment in case of a radiological accident/incident and should be considered in advance as guidelines to follow for having better information. They are given as conclusions.

Protein oxidative damage and redox imbalance induced by ionising radiation in CHO cells.

Reactive oxygen species (ROS) are important mediators of the cytotoxicity induced by the direct reaction of ionising radiation (IR) with all critical cellular components, such as proteins, lipids, and nucleic acids. The derived oxidative damage may propagate in exposed tissues in a dose- and spatiotemporal dependent manner to other cell compartments, affecting intracellular signalling, and cell fate. To understand how cell damage is induced, we studied the oxidative events occurring immediately after cell irradiation by analysing the fate of IR-derived ROS, the intracellular oxidative damage, and the modification of redox environment accumulating in Chinese hamster ovary (CHO) within 1 h after cell irradiation (dose range 0-10 Gy). By using the immuno-spin trapping technique (IST), spectrophotometric methods, and electron paramagnetic resonance (EPR) spectroscopy, we showed that IR-derived ROS (i) induced an IST-detectable, antioxidant-inhibitable one-electron oxidation of specific intracellular proteins; (ii) altered the glutathione (GSH) content (which was found to increase below 2 Gy, and decrease at higher doses, leading to a redox imbalance); (iii) decreased glutathione peroxidase and glutaredoxin activity; (iv) modified neither glutathione reductase nor thioredoxin reductase activity; (v) were detected by spin trapping technique, but adduct intensity decreased due to cell competition for ROS; and (vi) induced no EPR-detectable radicals assignable to oxidised cellular components. In conclusion, our results showed that IR generated an early high oxidising potential (protein radical intermediates, redox imbalance, modified redox enzyme activity) in irradiated cells potentially able to propagate the damage and induce oxidative modification of secondary targets.

UNCERTAINTY ON RADIATION DOSES ESTIMATED BY BIOLOGICAL AND RETROSPECTIVE PHYSICAL METHODS.

Biological and physical retrospective dosimetry are recognised as key techniques to provide individual estimates of dose following unplanned exposures to ionising radiation. Whilst there has been a relatively large amount of recent development in the biological and physical procedures, development of statistical analysis techniques has failed to keep pace. The aim of this paper is to review the current state of the art in uncertainty analysis techniques across the 'EURADOS Working Group 10-Retrospective dosimetry' members, to give concrete examples of implementation of the techniques recommended in the international standards, and to further promote the use of Monte Carlo techniques to support characterisation of uncertainties. It is concluded that sufficient techniques are available and in use by most laboratories for acute, whole body exposures to highly penetrating radiation, but further work will be required to ensure that statistical analysis is always wholly sufficient for the more complex exposure scenarios.

RENEB - Running the European Network of biological dosimetry and physical retrospective dosimetry.

PURPOSE: A European network was initiated in 2012 by 23 partners from 16 European countries with the aim to significantly increase individualized dose reconstruction in case of large-scale radiological emergency scenarios. RESULTS: The network was built on three complementary pillars: (1) an operational basis with seven biological and physical dosimetric assays in ready-to-use mode, (2) a basis for education, training and quality assurance, and (3) a basis for further network development regarding new techniques and members. Techniques for individual dose estimation based on biological samples and/or inert personalized devices as mobile phones or smart phones were optimized to support rapid categorization of many potential victims according to the received dose to the blood or personal devices. Communication and cross-border collaboration were also standardized. To assure long-term sustainability of the network, cooperation with national and international emergency preparedness organizations was initiated and links to radiation protection and research platforms have been developed. A legal framework, based on a Memorandum of Understanding, was established and signed by 27 organizations by the end of 2015. CONCLUSIONS: RENEB is a European Network of biological and physical-retrospective dosimetry, with the capacity and capability to perform large-scale rapid individualized dose estimation. Specialized to handle large numbers of samples, RENEB is able to contribute to radiological emergency preparedness and wider large-scale research projects.

Uncertainty of fast biological radiation dose assessment for emergency response scenarios.

PURPOSE: Reliable dose estimation is an important factor in appropriate dosimetric triage categorization of exposed individuals to support radiation emergency response. MATERIALS AND METHODS: Following work done under the EU FP7 MULTIBIODOSE and RENEB projects, formal methods for defining uncertainties on biological dose estimates are compared using simulated and real data from recent exercises. RESULTS: The results demonstrate that a Bayesian method of uncertainty assessment is the most appropriate, even in the absence of detailed prior information. The relative accuracy and relevance of techniques for calculating uncertainty and combining assay results to produce single dose and uncertainty estimates is further discussed. CONCLUSIONS: Finally, it is demonstrated that whatever uncertainty estimation method is employed, ignoring the uncertainty on fast dose assessments can have an important impact on rapid biodosimetric categorization.

An altered redox balance and increased genetic instability characterize primary fibroblasts derived from xeroderma pigmentosum group A patients.

Xeroderma pigmentosum (XP)-A patients are characterized by increased solar skin carcinogenesis and present also neurodegeneration. XPA deficiency is associated with defective nucleotide excision repair (NER) and increased basal levels of oxidatively induced DNA damage. In this study we search for the origin of increased levels of oxidatively generated DNA lesions in XP-A cell genome and then address the question of whether increased oxidative stress might drive genetic instability. We show that XP-A human primary fibroblasts present increased levels and different types of intracellular reactive oxygen species (ROS) as compared to normal fibroblasts, with O2₋• and H2O2 being the major reactive species. Moreover, XP-A cells are characterized by decreased reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios as compared to normal fibroblasts. The significant increase of ROS levels and the alteration of the glutathione redox state following silencing of XPA confirmed the causal relationship between a functional XPA and the control of redox balance. Proton nuclear magnetic resonance (¹H NMR) analysis of the metabolic profile revealed a more glycolytic metabolism and higher ATP levels in XP-A than in normal primary fibroblasts. This perturbation of bioenergetics is associated with different morphology and response of mitochondria to targeted toxicants. In line with cancer susceptibility, XP-A primary fibroblasts showed increased spontaneous micronuclei (MN) frequency, a hallmark of cancer risk. The increased MN frequency was not affected by inhibition of ROS to normal levels by N-acetyl-L-cysteine.

Operational guidance for radiation emergency response organisations in Europe for using biodosimetric tools developed in EU MULTIBIODOSE project.

In the event of a large-scale radiological emergency, the triage of individuals according to their degree of exposure forms an important initial step of the accident management. Although clinical signs and symptoms of a serious exposure may be used for radiological triage, they are not necessarily radiation specific and can lead to a false diagnosis. Biodosimetry is a method based on the analysis of radiation-induced changes in cells of the human body or in portable electronic devices and enables the unequivocal identification of exposed people who should receive medical treatment. The MULTIBIODOSE (MBD) consortium developed and validated several biodosimetric assays and adapted and tested them as tools for biological dose assessment in a mass-casualty event. Different biodosimetric assays were validated against the 'gold standard' of biological dosimetry-the dicentric assay. The assays were harmonised in such a way that, in an emergency situation, they can be run in parallel in a network of European laboratories. The aim of this guidance is to give a concise overview of the developed biodosimetric tools as well as how and when they can be used in an emergency situation.

Multibiodose radiation emergency triage categorization software.

In this note, the authors describe the MULTIBIODOSE software, which has been created as part of the MULTIBIODOSE project. The software enables doses estimated by networks of laboratories, using up to five retrospective (biological and physical) assays, to be combined to give a single estimate of triage category for each individual potentially exposed to ionizing radiation in a large scale radiation accident or incident. The MULTIBIODOSE software has been created in Java. The usage of the software is based on the MULTIBIODOSE Guidance: the program creates a link to a single SQLite database for each incident, and the database is administered by the lead laboratory. The software has been tested with Java runtime environment 6 and 7 on a number of different Windows, Mac, and Linux systems, using data from a recent intercomparison exercise. The Java program MULTIBIODOSE_1.0.jar is freely available to download from http://www.multibiodose.eu/software or by contacting the software administrator: MULTIBIODOSE-software@gmx.com.

Radiation-induced signals analysed by EPR spectrometry applied to fortuitous dosimetry.

Dosimetry based on the detection by electron paramagnetic resonance (EPR) spectroscopy of ionizing radiation-induced radicals is an established method for the retrospective dosimetry of past exposures and the dosimetry of potentially exposed persons in radiological emergencies. The dose is estimated by measuring the physical damage induced in materials contained in objects placed on or next to the potentially exposed person. The aim of this paper is to survey the current literature about methodologies and materials that have been proposed for EPR dosimetry, in order to identify those that could be suitable for population triage according to criteria such as ubiquity, non invasiveness and easy sample collection, presence of a post-irradiation EPR signal, negligible background signal, linearity of dose-response relationship, minimum detection limit and post-irradiation signal stability. The paper will survey the features of sugar, plastics, glass, clothing tissues, and solid biological tissues (nails, hair and calcified tissues).

Radiation-induced damage analysed by luminescence methods in retrospective dosimetry and emergency response.

The increasing risk of a mass casualty scenario following a large scale radiological accident or attack necessitates the development of appropriate dosimetric tools for emergency response. Luminescence dosimetry has been reliably applied for dose reconstruction in contaminated settlements for several decades and recent research into new materials carried close to the human body opens the possibility of estimating individual doses for accident and emergency dosimetry using the same technique. This paper reviews the luminescence research into materials useful for accident dosimetry and applications in retrospective dosimetry. The properties of the materials are critically discussed with regard to the requirements for population triage. It is concluded that electronic components found within portable electronic devices, such as e.g. mobile phones, are at present the most promising material to function as a fortuitous dosimeter in an emergency response.