Central nervous system tumours and occupational ionising radiation exposure: a nested case-control study among the ORICAMs cohort of healthcare workers in France.

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.

Cohort profile: ORICAMs, a French cohort of medical workers exposed to low-dose ionizing radiation.

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; ndeaths = 892) and female (SMR = 0.41; 95% CI: 0.38, 0.45; ndeaths = 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.

Radiation and CNS effects: summary of evidence from a recent symposium of the Radiation Research Society.

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.

Ionizing radiation exposure during adulthood and risk of developing central nervous system tumors: systematic review and meta-analysis.

Many studies on ionizing radiation (IR) exposure during childhood have shown deleterious effects on the central nervous system (CNS), however results regarding adult exposure are inconsistent, and no systematic reviews have been performed. The objectives are to synthesize the findings and draw evidence-based conclusions from epidemiological studies on the risk of benign and malignant brain and CNS tumors in humans exposed to low-to-moderate doses (< 0.5 Gy) of IR during adulthood/young adulthood. A systematic literature search of four electronic databases, supplemented by a hand search, was performed to retrieve relevant epidemiological studies published from 2000 to 2022. Pooled excess relative risk (ERRpooled) was estimated using a random effect model. Eighteen publications were included in the systematic review and twelve out of them were included in a meta-analysis. The following IR sources were considered: atomic bombs, occupational, and environmental exposures. No significant dose-risk association was found for brain/CNS tumors (ERRpooled at 100 mGy = - 0.01; 95% CI: - 0.05, 0.04). Our systematic review and meta-analysis did not show any association between exposure to low-to-moderate doses of IR and risk of CNS tumors. Further studies with histological information and precise dose assessment are needed.

Risk of Developing Non-Cancerous Central Nervous System Diseases Due to Ionizing Radiation Exposure during Adulthood: Systematic Review and Meta-Analyses.

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.

Socialization of Providencia stuartii Enables Resistance to Environmental Insults.

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.

Porin self-association enables cell-to-cell contact in Providencia stuartii floating communities.

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 self-associate 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 cell-to-cell contact but also contribute to intercellular communication.

Providencia stuartii form biofilms and floating communities of cells that display high resistance to environmental insults.

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.