Objective This study aimed at investigating the relationship between occupational exposure to external ionising radiation and central nervous system (CNS) tumours mortality in healthcare workers working in France.Design and setting The Occupational Radiation-Induced Cancer in Medical staff (ORICAMs) nested case–control study was conducted based on the dosimetric records of the national register of occupational dosimetry (Système d’information de la surveillance de l’exposition aux rayonnements ionisants).Participants and methods 33 CNS tumour deaths occurred between 2002 and 2012 among the ORICAMs cohort composed of 164 015 healthcare workers. Each case was matched to five controls alive at the time of the corresponding case’s death, based on sex, year of birth, date of enrolment in the cohort and duration of follow-up. All participants were badge monitored for external radiation exposure, expressed in Hp(10). Conditional logistic regression was used to analyse the dose–response relationship between radiation dose and CNS mortality.Results Cases were exposed to a mean cumulative career radiation dose of 5.8±13.7 (max: 54.3) millisievert (mSv) compared with 4.1±15.2 (142.2) mSv for controls. No statistically significant association was found between CNS tumour mortality and cumulative whole-body career dose (OR=1.00, 95% CI 0.98 to 1.03), duration of exposure (OR=1.03; 95% CI 0.95 to 1.12) or age at first exposure (OR=0.98; 95% CI 0.91 to 1.06).Conclusion We found no evidence of an association between external radiation exposure and CNS tumour risk in healthcare workers. Limitations of the study include low statistical power and short duration of follow-up.

Medical personnel represent the largest group of workers occupationally exposed to ionizing radiation. Although the health risks associated with occupational exposure to low doses of ionizing radiation in the medical field have been investigated in several national cohorts, no study has been conducted in France to date. The ORICAMs (Occupational Radiation Induced Cancer in Medical staff) cohort is a nationwide French longitudinal cohort of medical workers exposed to ionizing radiation aiming to investigate the risk of radiation-associated cancer and non-cancer mortality. The ORICAMs cohort was set up in 2011 and includes all medical personnel monitored for ionizing radiation exposure with at least one dosimetric record in the SISERI database (the national registry for monitoring ionizing radiation exposure in workers) over the period 2002-2012. Causes of death were abstracted from death certificates and coded according to ICD-10. The follow-up ended on 31/12/2013. Standardized mortality ratios (SMRs) were calculated by cause of death to compare the mortality in the cohort to that in the French population, by gender, age group and calendar period. Among the 164,015 workers included in the cohort (60% women) a total of 1,358 deaths (892 in male and 466 in female) were reported. The observed number of all-cause deaths was significantly lower than expected based on national rates in both male (SMR = 0.35; 95% CI: 0.33, 0.38; n(deaths) = 892) and female (SMR = 0.41; 95% CI: 0.38, 0.45; n(deaths) = 466). This analysis leads to the conclusion that mortality in French workers exposed to medical radiation is significantly lower than the national reference rates. However, these results based on a comparative analysis with national rates may be impacted by the healthy worker effect towards low SMRs, and do not enable to establish a potential relationship between occupational exposure and mortality risk, even if we may suspect an impact of high SES of these professionals on the observed decreased mortality. Thus, further dose-response analyses based on individual ionizing radiation exposure and job's type will be conducted to characterize correlation between risk of cancer mortality and occupational exposure.

This article summarizes a Symposium on 'Radiation risks of the central nervous system' held virtually at the 67th Annual Meeting of the Radiation Research Society, 3-6 October 2021. Repeated low-dose radiation exposure over a certain period could lead to reduced neuronal proliferation, altered neurogenesis, neuroinflammation and various neurological complications, including psychological consequences, necessitating further research in these areas. Four speakers from radiation biology, genetics and epidemiology presented the latest data from their studies seeking insights into this important topic. This symposium highlighted new and important directions for further research on mental health disorders, neurodegenerative conditions and cognitive impairment. Future studies will examine risks of mental and behavioral disorders and neurodegenerative diseases following protracted radiation exposures to better understand risks of occupational exposures as well as provide insights into risks from exposures to galactic cosmic rays. The Million Person Study of Low-Dose Health Effects (MPS) is evaluating the risk of cognitive dysfunction and dementia following intakes of radionuclides and after low-LET external radiation in the workplace. A recent study of Mayak workers in Russia suggested a link with Parkinson's disease following low-LET radiation. High-LET radiation from galactic cosmic ray simulations have reported the potential to accelerate the development of Alzheimer's disease, dementia and anxiety disorders in experimental studies. To date, seven MPS cohorts have evaluated Parkinson's disease at the level of mortality among 515,857 workers and veterans. The excess relative risks (ERR) per 100 mGy dose to brain was estimated for nuclear power plant workers (NPP), industrial radiographers (IR), medical radiation workers (MRW), nuclear weapons test participants and former DOE workers at Mallinckrodt Chemical Works, Mound facility in Ohio, and Los Alamos National Laboratory. There was a general tendency for the risk of Parkinson's disease to increase with increasing estimates of radiation dose to brain. The pooled ERR per 100 mGy for the combined NPP + IR + MRW cohorts was 0.30 (95% CI 0.08, 0.56). Confirmation of these associations are being sought from ongoing studies of an additional 300,000 workers and from linkages within the Centers for Medicare & Medicaid Services (CMS) databases for incidence data on Parkinson's disease for 600,000 workers. Further, a wide range of nonfatal conditions related to dementia and depression are being identified, as are cognitive impairment scores among 600,000 cohort workers alive in 1999 when the CMS data systems became available. Neuroinflammation and synaptic loss have been implicated in cognitive dysfunction seen after brain radiation exposure. Based on evidence that elements of the complement cascade are critical for synaptic pruning by microglia during development and are upregulated in neurodegenerative diseases and aging where synapse density is reduced, we previously demonstrated that deletion of complement receptor 3 (CR3), which is expressed on microglia, protected male mice from dendritic spine loss in the molecular layer of the hippocampus after radiation exposure. Using Thy1-eYFP mice with or without the CR3 receptor, we also found a clear correlation between microglial activation, spine loss and cognitive dysfunction 30 d after 10 Gy cranial irradiation, only in male mice, that is dependent on CR3 expression. Moreover, treatment with leukadherin-1 (LA1), which engages the CR3 receptor, prevents spine loss and cognitive dysfunction due to radiation exposure. To guide application of potential therapeutic interventions, we carried out time course analyses of synaptic density, microglial activation and complement deposition and found that these processes are initiated in the first few days following radiation exposure, suggesting a relatively acute response with long-lasting consequences.

Le personnel médical constitue actuellement le plus grand groupe de travailleurs exposés professionnellement à des sources artificielles de rayonnements ionisants (RI). Le risque de maladie associé à ces expositions chroniques à de faibles doses fait encore l'objet de débats chez ces professionnels. L'objectif était d’évaluer le risque de mortalité toutes causes confondues et par cause spécifique chez les travailleurs du secteur médical exposés aux RI en France au sein de la cohorte ORICAMS (« Occupational Radiation Induced Cancer in Medical Staff ») par rapport à la population générale. ORICAMS a été mise en place en 2011 par l'Institut de radioprotection et de sûreté nucléaire et inclut le personnel de santé suivi pour une exposition aux RI avec au moins une dosimétrie enregistrée dans le Système d'information de la surveillance des expositions aux RI sur la période 2002-2012. Les causes de décès ont été extraites des certificats de décès et codées selon la CIM-10. Le suivi s'est terminé le 31/12/2017. Des ratios standardisés de mortalité (SMR) ont été calculés par causes de décès pour comparer la mortalité de la cohorte à celle de la population française. Au total, 126 960 travailleurs ont été inclus dans la cohorte (62 % de femmes et 38 % d'hommes), parmi lesquels 2386 décès ont été enregistrés. Par rapport à la population générale, une baisse significative de la mortalité, toutes causes confondues, a été observée, ce qui est cohérent avec « l'effet du travailleur sain ». Cependant, des excès de décès pour certaines causes sont suspectés. Ces résultats préliminaires seront détaillés par cause de décès, par tranche d’âge, et par sexe lors du congrès. Des analyses dose-réponse basées sur l'exposition professionnelle individuelle cumulée aux RI permettront de caractériser plus précisément les risques radio-induits de cancer dans le cadre d'une exposition professionnelle. Les auteurs déclarent ne pas avoir de liens d'intérêts.

Background: High-dose ionizing radiation (IR) (>0.5 Gy) is an established risk factor for cognitive impairments, but this cannot be concluded for low-to-moderate IR exposure (<0.5 Gy) in adulthood as study results are inconsistent. The objectives are to summarize relevant epidemiological studies of low-to-moderate IR exposure in adulthood and to assess the risk of non-cancerous CNS diseases. Methods: A systematic literature search of four electronic databases was performed to retrieve relevant epidemiological studies published from 2000 to 2022. Pooled standardized mortality ratios, relative risks, and excess relative risks (ERR) were estimated with a random effect model. Results: Forty-five publications were included in the systematic review, including thirty-three in the quantitative meta-analysis. The following sources of IR-exposure were considered: atomic bomb, occupational, environmental, and medical exposure. Increased dose-risk relationships were found for cerebrovascular diseases incidence and mortality (ERRpooled per 100 mGy = 0.04; 95% CI: 0.03–0.05; ERRpooled at 100 mGy = 0.01; 95% CI: −0.00–0.02, respectively) and for Parkinson’s disease (ERRpooled at 100 mGy = 0.11; 95% CI: 0.06–0.16); Conclusions: Our findings suggest that adult low-to-moderate IR exposure may have effects on non-cancerous CNS diseases. Further research addressing inherent variation issues is encouraged.

Providencia stuartii is a highly-social pathogen responsible for nosocomial chronic urinary tract infections. The bacterium indeed forms floating communities of cells (FCC) besides and prior-to canonical surface-attached biofilms (SAB). Within P. stuartii FCC, cells are riveted one to another owing to by self-interactions between its porins, viz. Omp-Pst1 and Omp-Pst2. In pathophysiological conditions, P. stuartii is principally exposed to high concentrations of urea, ammonia, bicarbonate, creatinine and to large variations of pH, questioning how these environmental cues affect socialization, and whether formation of SAB and FCC protects cells against those. Results from our investigations indicate that FCC and SAB can both form in the urinary tract, endowing cells with increased resistance and fitness. They additionally show that while Omp-Pst1 is the main gateway allowing penetration of urea, bicarbonate and ammonia into the periplasm, expression of Omp-Pst2 enables resistance to them.

BACKGROUND AND AIM: Humans are daily exposed to low-dose ionizing radiation (IR), either from natural (cosmic, background radiation) or artificial (medical or industrial) sources. Many studies have suggested that low-dose IR could have a deleterious impact on the brain, but results are not consistent. This study aims to identify evidence from a wide range of literature and present a synthesis of findings on the impact of low-to-moderate doses IR exposure in adulthood on the risk of developing brain tumors and cognitive alterations. METHODS: We performed a systematic review and meta-analysis following the PRISMA guidelines. Searches were performed using PubMed, Scopus, Web of Science and Google Scholar databases. Articles dealing with IR exposure and brain tumors and/or cognitive disorders in adults were retrieved and screened by two independent reviewers. IR exposure sources and scenarios included space travel, Chernobyl disaster, atomic bomb, occupational exposures in nuclear energy and medical sectors. The Newcastle-Ottawa scale for cohort and case-control studies was used for quality assessment. Pooled estimators were computed when quantitative data was available. RESULTS:Out of the 3816 recorded articles, 83 studies were included in the systematic review. Most of the included studies did not demonstrate an increased risk or significant association between exposure to IR in adults and brain cancer. Likewise, there was no strong evidence that IR received during adulthood could have adverse effects on cognitive functions. CONCLUSIONS:The present review does not suggest higher risk of developing brain tumors nor a deleterious impact on cognitive functions after exposure to IR during adulthood among the studied populations. However, the high variability of the assessment tools used by the different studies concerning cognitive disorders made it difficult to synthesize the results. Also, further studies with adequate dosimetry and dose-response assessments would be needed to support these conclusions. Quantitative results of the meta-analysis will be presented at the congress. KEYWORDS: Ionizing radiation, cancer and cancer precursors, mental health outcomes, epidemiology

Introduction Currently, medical workers represent the largest group of workers occupationally exposed to ionizing radiation (IR), reaching 7.4 million practitioners worldwide. The risk of radiation associated cancer is still under debate for low-doses IR exposures for these professionals. Some publications have reported an excess of central nervous system (CNS) tumors in interventional cardiologists, but the link with the profession has never been established in a large, properly controlled epidemiological study. Objectives The ORICAMs (Occupational Radiation-Induced Cancer in Medical Staff) nested case-control study aims to assess the dose-response relationship between IR exposure and CNS tumor. Methods This study includes medical workers with at least one dosimetric record in the national dose registry called SISERI (Système d’Information de la Surveillance de l’Exposition aux Rayonnements Ionisants) between 2002 and 2012. Follow-up ended in 2019. Individual cumulative doses for each worker will be provided by SISERI. CNS death cases will be matched 1:5 by gender, year of birth, and date of enrollment, with controls alive at the time of case death. Associations between CNS cancer death and cumulative dose will be investigated using conditional logistic regressions. Results The study will quantify the relationship between occupational exposure to low doses of IR and CNS tumor mortality risks in medical workers. The inclusion of 45 CNS cases and their matched controls will allow detecting at least an odds ratio of 1.5 for a statistical power of 80% and an alpha significance level of 5%. Conclusion This study will improve the knowledge of the health risks associated with repeated low-dose IR exposures and will contribute to improve radiation protection strategies for medical workers. This cohort will be part of the international BECOME (Brain cancEr risk in pooled Case-cOntrol study of MEdical workers) project, which will address the same objectives, but using joint analyses of data from France, South Korea and the United States.

The gram-negative pathogen Providencia stuartii forms floating communities within which adjacent cells are in apparent contact, before depositing as canonical surface-attached biofilms. Because porins are the most abundant proteins in the outer membrane of gram-negative bacteria, we hypothesized that they could be involved in cell-to-cell contact and undertook a structure-function relationship study on the two porins of P. stuartii, Omp-Pst1 and Omp-Pst2. Our crystal structures reveal that these porins can selfassociate through their extracellular loops, forming dimers of trimers (DOTs) that could enable cell-to-cell contact within floating communities. Support for this hypothesis was obtained by studying the porin-dependent aggregation of liposomes and model cells. The observation that facing channels are open in the two porin structures suggests that DOTs could not only promote cellto-cell contact but also contribute to intercellular communication.

Biofilms are organized communities of bacterial cells that are responsible for the majority of human chronic bacterial infections. Providencia stuartii is a Gram-negative biofilm-forming bacterium involved in high incidence of urinary tract infections in catheterized patients. Yet, the structuration of these biofilms, and their resistance to environmental insults remain poorly understood. Here, we report on planktonic cell growth and biofilm formation by P. stuartii, in conditions that mimic its most common pathophysiological habitat in humans, i.e. the urinary tract. We observed that, in the planktonic state, P. stuartii forms floating communities of cells, prior to attachment to a surface and subsequent adoption of the biofilm phenotype. P. stuartii planktonic and biofilm cells are remarkably resistant to calcium, magnesium and to high concentrations of urea, and show the ability to grow over a wide range of pHs. Experiments conducted on a P. stuartii strain knocked-out for the Omp-Pst2 porin sheds light on the role it plays in the early stages of growth, as well as in the adaptation to high concentration of urea and to varying pH.