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The discovery of X-rays was followed by a variety of attempts to treat infectious diseases and various other non-cancer diseases with ionizing radiation, in addition to cancer. There has been a recent resurgence of interest in the use of such radiotherapy for non-cancer diseases. Non-cancer diseases for which use of radiotherapy has currently been proposed include refractory ventricular tachycardia, neurodegenerative diseases (e.g. Alzheimer's disease and dementia), and Coronavirus Disease 2019 (COVID-19) pneumonia, all with ongoing clinical studies that deliver radiation doses of 0.5–25 Gy in a single fraction or in multiple daily fractions. In addition to such non-cancer effects, historical indications predominantly used in some countries (e.g. Germany) include osteoarthritis and degenerative diseases of the bones and joints. This narrative review gives an overview of the biological rationale and ongoing preclinical and clinical studies for radiotherapy proposed for various non-cancer diseases, discusses the plausibility of the proposed biological rationale, and considers the long-term radiation risks of cancer and non-cancer diseases. A growing body of evidence has suggested that radiation represents a double-edged sword, not only for cancer, but also for non-cancer diseases. At present, clinical evidence has shown some beneficial effects of radiotherapy for ventricular tachycardia, but there is little or no such evidence of radiotherapy for other newly proposed non-cancer diseases (e.g. Alzheimer's disease, COVID-19 pneumonia). Patients with ventricular tachycardia and COVID-19 pneumonia have thus far been treated with radiotherapy when they are an urgent life threat with no efficient alternative treatment, but some survivors may encounter a paradoxical situation where patients were rescued by radiotherapy but then get harmed by radiotherapy. Further studies are needed to justify the clinical use of radiotherapy for non-cancer diseases, and optimize dose to diseased tissue while minimizing dose to healthy tissue. [ABSTRACT FROM AUTHOR]

Holobionts are assemblages of microbial symbionts and their macrobial host. As extant representatives of some of the oldest macro-organisms, corals and algae are important for understanding how holobionts develop and interact with one another. Using untargeted metabolomics, we show that non-self interactions altered the coral metabolome more than self-interactions (i.e. different or same genus, respectively). Platelet activating factor (PAF) and Lyso-PAF, central inflammatory modulators in mammals, were major lipid components of the coral holobionts. When corals were damaged during competitive interactions with algae, PAF increased along with expression of the gene encoding Lyso-PAF acetyltransferase; the protein responsible for converting Lyso-PAF to PAF. This shows that self and non-self recognition among some of the oldest extant holobionts involve bioactive lipids identical to those in highly derived taxa like humans. This further strengthens the hypothesis that major players of the immune response evolved during the pre-Cambrian.

High-dose ionizing radiation is associated with circulatory disease. Risks from lower-dose fractionated exposures, such as from diagnostic radiation procedures, remain unclear. In this study we aimed to ascertain the relationship between fractionated low-to-medium dose radiation exposure and circulatory disease mortality in a cohort of 13,568 tuberculosis patients in Massachusetts, some with fluoroscopy screenings, between 1916 and 1961 and follow-up until the end of 2002. Analysis of mortality was in relation to cumulative thyroid (cerebrovascular) or lung (all other circulatory disease) radiation dose via Poisson regression. Over the full dose range, there was no overall radiation-related excess risk of death from circulatory disease (n = 3221; excess relative risk/Gy -0.023; 95% CI -0.067, 0.028; p = 0.3574). Risk was somewhat elevated in hypertensive heart disease (n = 89; excess relative risk/Gy 0.357; 95% CI -0.043, 1.030, p = 0.0907) and slightly decreased in ischemic heart disease (n = 1950; excess relative risk/Gy -0.077; 95% CI -0.130, -0.012; p = 0.0211). However, under 0.5 Gy, there was a borderline significant increasing trend for all circulatory disease (excess relative risk/Gy 0.345; 95% CI -0.032, 0.764; p = 0.0743) and for ischemic heart disease (excess relative risk/Gy 0.465; 95% CI, -0.032, 1.034, p = 0.0682). Pneumolobectomy increased radiation-associated risk (excess relative risk/Gy 0.252; 95% CI 0.024, 0.579). Fractionation of dose did not modify excess risk. In summary, we found no evidence of radiation-associated excess circulatory death risk overall, but there are indications of excess circulatory death risk at lower doses (

BackgroundThere are limited data on the histopathology of papillary thyroid carcinomas (PTCs) diagnosed in irradiated populations. We evaluated the associations between iodine-131 dose and the histopathological characteristics of post-Chernobyl PTCs, the changes in these characteristics over time, and their associations with selected somatic mutations.MethodsThis study included 115 PTCs diagnosed in a Ukrainian-American cohort (n=13,243) during prescreening and four successive thyroid screenings. Of these PTCs, 65 were subjected to somatic mutation profiling. All individuals were

Several studies reported an increased risk of thyroid cancer in children and adolescents exposed to radioactive iodines, chiefly iodine-131 ((131)I), after the 1986 Chornobyl (Ukrainian spelling) nuclear power plant accident. The risk of benign thyroid tumors following such radiation exposure is much less well known. We have previously reported a novel finding of significantly increased risk of thyroid follicular adenoma in a screening study of children and adolescents exposed to the Chornobyl fallout in Ukraine. To verify this finding, we analyzed baseline screening data from a cohort of 11,613 individuals aged ≤18 years at the time of the accident in Belarus (mean age at screening = 21 years). All participants had individual (131)I doses estimated from thyroid radioactivity measurements and were screened according to a standardized protocol. We found a significant linear dose response for 38 pathologically confirmed follicular adenoma cases. The excess odds ratio per gray of 2.22 (95% confidence interval: 0.41, 13.1) was similar in males and females but decreased significantly with increasing age at exposure (P < 0.01), with the highest radiation risks estimated for those exposed at

BackgroundRecent studies of children and adolescents who were exposed to radioactive iodine-131 (I-131) after the 1986 Chernobyl nuclear accident in Ukraine exhibited a significant dose-related increase in the risk of thyroid cancer, but the association of radiation doses with tumor histologic and morphologic features is not clear.MethodsA cohort of 11,664 individuals in Belarus who were aged ≤18 years at the time of the accident underwent 3 cycles of thyroid screening during 1997 to 2008. I-131 thyroid doses were estimated from individual thyroid activity measurements taken within 2 months after the accident and from dosimetric questionnaire data. Demographic, clinical, and tumor pathologic characteristics of the patients with thyroid cancer were analyzed using 1-way analysis of variance, chi-square tests or Fisher exact tests, and logistic regression.ResultsIn total, 158 thyroid cancers were identified as a result of screening. The majority of patients had T1a and T1b tumors (93.7%), with many positive regional lymph nodes (N1; 60.6%) but few distant metastases (M1;

The 1986 accident at the Chernobyl nuclear power plant remains the most serious nuclear accident in history, and excess thyroid cancers, particularly among those exposed to releases of iodine-131 remain the best-documented sequelae. Failure to take dose-measurement error into account can lead to bias in assessments of dose-response slope. Although risks in the Ukrainian-US thyroid screening study have been previously evaluated, errors in dose assessments have not been addressed hitherto. Dose-response patterns were examined in a thyroid screening prevalence cohort of 13,127 persons aged

Risks of noncancer causes of death, particularly cardiovascular disease, associated with exposures to high-dose ionizing radiation, are well known. Recent studies have reported excess risk in workers who are occupationally exposed to low doses at a low dose rate, but the risks of moderately fractionated exposures, such as occur during diagnostic radiation procedures, remain unclear. The Canadian Fluoroscopy Cohort Study includes 63,707 tuberculosis patients exposed to multiple fluoroscopic procedures in 1930-1952 and followed-up for death from noncancer causes in 1950-1987. We used a Poisson regression to estimate excess relative risk (ERR) per Gy of cumulative radiation dose to the lung (mean dose = 0.79 Gy; range, 0-11.60). The risk of death from noncancer causes was significantly lower in these subjects compared with the Canadian general population (P < 0.001). We estimated small, nonsignificant increases in the risk of death from noncancer causes with dose. We estimated an ERR/Gy of 0.176 (95% confidence interval: 0.011, 0.393) (n = 5,818 deaths) for ischemic heart disease (IHD) after adjustment for dose fractionation. A significant (P = 0.022) inverse dose fractionation effect in dose trends of IHD was observed, with the highest estimate of ERR/Gy for those with the fewest fluoroscopic procedures per year. Radiation-related risks of IHD decreased significantly with increasing time since first exposure and age at first exposure (both P < 0.05). This is the largest study of patients exposed to moderately fractionated low-to-moderate doses of radiation, and it provides additional evidence of increased radiation-associated risks of death from IHD, in particular, significantly increased radiation risks from doses similar to those from diagnostic radiation procedures. The novel finding of a significant inverse dose-fractionation association in IHD mortality requires further investigation.

Risks of noncancer causes of death, particularly cardiovascular disease, associated with exposures to high-dose ionizing radiation, are well known. Recent studies have reported excess risk in workers who are occupationally exposed to low doses at a low dose rate, but the risks of moderately fractionated exposures, such as occur during diagnostic radiation procedures, remain unclear. The Canadian Fluoroscopy Cohort Study includes 63,707 tuberculosis patients exposed to multiple fluoroscopic procedures in 1930-1952 and followed-up for death from noncancer causes in 1950-1987. We used a Poisson regression to estimate excess relative risk (ERR) per Gy of cumulative radiation dose to the lung (mean dose = 0.79 Gy; range, 0-11.60). The risk of death from noncancer causes was significantly lower in these subjects compared with the Canadian general population (P < 0.001). We estimated small, nonsignificant increases in the risk of death from noncancer causes with dose. We estimated an ERR/Gy of 0.176 (95% confidence interval: 0.011, 0.393) (n = 5,818 deaths) for ischemic heart disease (IHD) after adjustment for dose fractionation. A significant (P = 0.022) inverse dose fractionation effect in dose trends of IHD was observed, with the highest estimate of ERR/Gy for those with the fewest fluoroscopic procedures per year. Radiation-related risks of IHD decreased significantly with increasing time since first exposure and age at first exposure (both P < 0.05). This is the largest study of patients exposed to moderately fractionated low-to-moderate doses of radiation, and it provides additional evidence of increased radiation-associated risks of death from IHD, in particular, significantly increased radiation risks from doses similar to those from diagnostic radiation procedures. The novel finding of a significant inverse dose-fractionation association in IHD mortality requires further investigation.

Recent evidence showing host specificity of colonizing bacteria supports the view that multicellular organisms are holobionts comprised of the macroscopic host in synergistic interdependence with a heterogeneous and host-specific microbial community. Whereas host-bacteria interactions have been extensively investigated, comparatively little is known about host-virus interactions and viral contribution to the holobiont. We sought to determine the viral communities associating with different Hydra species, whether these viral communities were altered with environmental stress, and whether these viruses affect the Hydra-associated holobiont. Here we show that each species of Hydra harbors a diverse host-associated virome. Primary viral families associated with Hydra are Myoviridae, Siphoviridae, Inoviridae, and Herpesviridae. Most Hydra-associated viruses are bacteriophages, a reflection of their involvement in the holobiont. Changes in environmental conditions alter the associated virome, increase viral diversity, and affect the metabolism of the holobiont. The specificity and dynamics of the virome point to potential viral involvement in regulating microbial associations in the Hydra holobiont. While viruses are generally regarded as pathogenic agents, our study suggests an evolutionary conserved ability of viruses to function as holobiont regulators and, therefore, constitutes an emerging paradigm shift in host-microbe interactions.

Ionizing radiation is one of the known risk factors for cataract development, however, there is still debate regarding the level of risk after low dose exposures. One of the largest sources of radiation exposure to the lens of the eye is diagnostic CT scans. The aim of this study was to examine whether ionizing radiation associated with head CT scans increases cataract risk in residents of Ontario, Canada. Data were collected from January 1, 1994 to December 31, 2015 (22 years) from anonymized Ontario Health Insurance Plan (OHIP) medical records for over 16 million subjects. A lens dose was estimated for each CT scan using the National Cancer Institute dosimetry system for CT (NCICT) program combined with Canada-specific CTDIvol data. Multivariate Cox proportional hazards analysis was performed with cataract extraction surgery as the primary outcome and lens dose as the main variable of interest, with inclusion of various medical and demographic covariates. Lag periods of 3, 5 and 7 years were incorporated. When lens dose was treated as a continuous variable, hazard ratios (per 100 mGy) ranged from 0.82 (0.80–0.84) to 1.10 (1.09–1.11) depending on the lag period. As a secondary analysis, when individuals were binned based on their total cumulative dose, no significant dose response pattern was observed in the low dose region. Overall, within the bounds of this study, the data do not support an increased risk of vision impairing cataracts after diagnostic head CT scan radiation exposure. [ABSTRACT FROM AUTHOR]

BACKGROUND: Risks of most types of leukemia from exposure to acute high doses of ionizing radiation are well known, but risks associated with protracted exposures, as well as associations between radiation and chronic lymphocytic leukemia (CLL), are not clear. OBJECTIVES: We estimated relative risks of CLL and non-CLL from protracted exposures to low-dose ionizing radiation. METHODS: A nested case-control study was conducted in a cohort of 110,645 Ukrainian cleanup workers of the 1986 Chornobyl nuclear power plant accident. Cases of incident leukemia diagnosed in 1986-2006 were confirmed by a panel of expert hematologists/hematopathologists. Controls were matched to cases on place of residence and year of birth. We estimated individual bone marrow radiation doses by the Realistic Analytical Dose Reconstruction with Uncertainty Estimation (RADRUE) method. We then used a conditional logistic regression model to estimate excess relative risk of leukemia per gray (ERR/Gy) of radiation dose. RESULTS: We found a significant linear dose response for all leukemia [137 cases, ERR/Gy = 1.26 (95% CI: 0.03, 3.58]. There were nonsignificant positive dose responses for both CLL and non-CLL (ERR/Gy = 0.76 and 1.87, respectively). In our primary analysis excluding 20 cases with direct in-person interviews < 2 years from start of chemotherapy with an anomalous finding of ERR/Gy = -0.47 (95% CI: < -0.47, 1.02), the ERR/Gy for the remaining 117 cases was 2.38 (95% CI: 0.49, 5.87). For CLL, the ERR/Gy was 2.58 (95% CI: 0.02, 8.43), and for non-CLL, ERR/Gy was 2.21 (95% CI: 0.05, 7.61). Altogether, 16% of leukemia cases (18% of CLL, 15% of non-CLL) were attributed to radiation exposure. CONCLUSIONS: Exposure to low doses and to low dose-rates of radiation from post-Chornobyl cleanup work was associated with a significant increase in risk of leukemia, which was statistically consistent with estimates for the Japanese atomic bomb survivors. Based on the primary analysis, we conclude that CLL and non-CLL are both radiosensitive.

BACKGROUND: Although high doses of ionizing radiation have long been linked to circulatory disease, evidence for an association at lower exposures remains controversial. However, recent analyses suggest excess relative risks at occupational exposure levels. OBJECTIVES: We performed a systematic review and meta-analysis to summarize information on circulatory disease risks associated with moderate- and low-level whole-body ionizing radiation exposures. METHODS: We conducted PubMed/ISI Thomson searches of peer-reviewed papers published since 1990 using the terms radiation AND heart AND disease, OR radiation AND stroke, OR radiation AND circulatory AND disease. Radiation exposures had to be whole-body, with a cumulative mean dose of < 0.5 Sv, or at a low dose rate (< 10 mSv/day). We estimated population risks of circulatory disease from low-level radiation exposure using excess relative risk estimates from this meta-analysis and current mortality rates for nine major developed countries. RESULTS: Estimated excess population risks for all circulatory diseases combined ranged from 2.5%/Sv [95% confidence interval (CI): 0.8, 4.2] for France to 8.5%/Sv (95% CI: 4.0, 13.0) for Russia. CONCLUSIONS: Our review supports an association between circulatory disease mortality and low and moderate doses of ionizing radiation. Our analysis was limited by heterogeneity among studies (particularly for noncardiac end points), the possibility of uncontrolled confounding in some occupational groups by lifestyle factors, and higher dose groups (> 0.5 Sv) generally driving the observed trends. If confirmed, our findings suggest that overall radiation-related mortality is about twice that currently estimated based on estimates for cancer end points alone (which range from 4.2% to 5.6%/Sv for these populations).