Dose advantage of abdominal deep inspiratory breath-hold (aDIBH) in postoperative adjuvant radiotherapy for left breast cancer.

PURPOSE: We explored the dosimetric efficacy of the abdominal deep inspiration breath hold (aDIBH) technique using an audio-guided device in patients with left breast cancer undergoing postoperative adjuvant radiotherapy compared to free breathing (FB). METHODS: A total of 35 patients with early stage left breast cancer underwent two computed tomography simulation scans each with aDIBH and FB after breast-conserving surgery. Treatment planning was optimized using the Pinnacle3 9.10 planning system. The heart, left anterior descending coronary artery (LADCA), and left lung was defined as organs at risk (OARs). The dosimetric differences in the planning target volume (PTV) and OARs were compared between aDIBH and FB. RESULTS: Compared with FB, the heart moved farther caudally and away from the chest wall, and the volume of heart became smaller under aDIBH due to expansion of the lungs. The D mean of the heart, LADCA and left lung of aDIBH were respectively reduced by 332.79 ± 264.61 cGy (P < 0.001), 1290.37 ± 612.09 cGy (P < 0.047) and 69.94 ± 117.73 cGy (P < 0.001). The V20 and V30 of the OARs were also significantly reduced with statistical differences (P < 0.05). In addition, there was no significant difference in the dosimetric parameters of the PTV between the two groups (P > 0.05). CONCLUSIONS: Implementation of the aDIBH technique for postoperative radiotherapy after breast-conserving surgery of the left breast cancer could reduce irradiation of the heart dose, LADCA dose and left lung dose, without compromising target coverage.

A performance comparison study between two HPGe lung counters with different detector configurations.

This study compares the performance of old and new lung counters in the National Institutes for Quantum Sciences and Technology of Japan. The total sensitive area of the detector crystals for the new lung counter is ~15% smaller than that for the old lung counter. Minimum detectable activities (MDAs) for 241Am and 239Pu were evaluated through experiments using a Lawrence Livermore National Laboratory torso phantom. Despite differences in detector configuration, the MDAs were found to be comparable between the two lung counters. For a chest wall thickness of 2.1 cm and a counting time of 30 min, the MDAs of 241Am and 239Pu were 5.7 and 2300 Bq for the old lung counter, and 5.5 and 2600 Bq for the new lung counter, respectively. Experimental results for the relative sensitivities between left-side and right-side detectors suggested that the new lung counter offered better measurement geometry.

Oxytocin: A Shield against Radiation-Induced Lung Injury in Rats.

BACKGROUND: Radiation-induced lung injury (RILI), a serious side effect of thoracic radiotherapy, can lead to acute radiation pneumonitis (RP) and chronic pulmonary fibrosis (PF). Despite various interventions, no effective protocol exists to prevent pneumonitis. Oxytocin (OT), known for its anti-inflammatory, antiapoptotic, and antioxidant properties, has not been explored for its potential in mitigating RILI. MATERIALS AND METHODS: This study involved 24 female Wistar albino rats, divided into three groups: control group, radiation (RAD) + saline, and RAD + OT. The RAD groups received 18 Gy of whole-thorax irradiation. The RAD + OT group was treated with OT (0.1 mg/kg/day) intraperitoneally for 16 weeks. Computerizing tomography (CT) imaging and histopathological, biochemical, and blood gas analyses were performed to assess lung tissue damage and inflammation. RESULTS: Histopathological examination showed significant reduction in alveolar wall thickening, inflammation, and vascular changes in the RAD + OT group compared to the RAD + saline group. Biochemical analysis revealed decreased levels of TGF-beta, VEGF, and PDGF, and increased BMP-7 and prostacyclin in the RAD + oxytocin group (p < 0.05). Morphometric analysis indicated significant reductions in fibrosis, edema, and immune cell infiltration. CT imaging demonstrated near-normal lung parenchyma density in the RAD + oxytocin group (p < 0.001). CONCLUSION: Oxytocin administration significantly mitigates radiation-induced pneumonitis in rats, implying that is has potential as a therapeutic agent for preventing and treating RILI.

Pyrroloquinoline Quinone Alleviates Mitochondria Damage in Radiation-Induced Lung Injury in a MOTS-c-Dependent Manner.

Radiation-induced lung injury (RILI) is a prevalent complication of thoracic tumor radiotherapy and accidental radiation exposure. Pyrroloquinoline quinone (PQQ), a novel vitamin B, plays a crucial role in delaying aging, antioxidation, anti-inflammation, and antiapoptosis. This study aims to investigate the protective effect and mechanisms of PQQ against RILI. C57BL/6 mice were exposed to a 20 Gy dose of X-ray radiation on the entire thorax with or without daily oral administration of PQQ for 2 weeks. PQQ effectively mitigated radiation-induced lung tissue damage, inflammation, oxidative stress, and epithelial cell apoptosis. Additionally, PQQ significantly inhibited oxidative stress and mitochondrial damage in MLE-12 cells. Mechanistically, PQQ upregulated the mRNA and protein levels of MOTS-c in irradiated lung tissue and MLE-12 cells. Knockdown of MOTS-c by siRNA substantially attenuated the protective effects of PQQ on oxidative stress, inflammation, and apoptosis. In conclusion, PQQ alleviates RILI by preserving mitochondrial function through a MOTS-c-dependent mechanism, suggesting that PQQ may serve as a promising nutraceutical intervention against RILI.

A novel predictor for dosimetry data of lung and the radiation pneumonitis incidence prior to SBRT in lung cancer patients.

Normal tissue complication probability (NTCP) models for radiation pneumonitis (RP) in lung cancer patients with stereotactic body radiation therapy (SBRT), which based on dosimetric data from treatment planning, are limited to patients who have already received radiation therapy (RT). This study aims to identify a novel predictive factor for lung dose distribution and RP probability before devising actionable SBRT plans for lung cancer patients. A comprehensive correlation analysis was performed on the clinical and dose parameters of lung cancer patients who underwent SBRT. Linear regression models were utilized to analyze the dosimetric data of lungs. The performance of the regression models was evaluated using mean squared error (MSE) and the coefficient of determination (R2). Correlational analysis revealed that most clinical data exhibited weak correlations with dosimetric data. However, nearly all dosimetric variables showed "strong" or "very strong" correlations with each other, particularly concerning the mean dose of the ipsilateral lung (MI) and the other dosimetric parameters. Further study verified that the lung tumor ratio (LTR) was a significant predictor for MI, which could predict the incidence of RP. As a result, LTR can predict the probability of RP without the need to design an elaborate treatment plan. This study, as the first to offer a comprehensive correlation analysis of dose parameters, explored the specific relationships among them. Significantly, it identified LTR as a novel predictor for both dose parameters and the incidence of RP, without the need to design an elaborate treatment plan.

Guidelines for power and time variables for microwave ablation in porcine lung in vitro.

PURPOSE: Determination of the appropriate ablative parameters is the key to the success and safety of microwave ablation (MWA) of lung tumors. The purpose of this study was to provide guidelines and recommendations for the optimal time and power for lung tumor MWA. MATERIAL AND METHODS: MWA using a 2450-MHz system was evaluated in a porcine lung. The independent variables were power (30, 40, 50, 60, 70, and 80 W) and time (2, 4, 6, 8, 10, and 12 min), and the outcome variable was the volume of ablation. Lung tissues were procured after MWA for measurement and histological evaluation. Analysis of variance was used for statistical analysis, followed by least significant difference (LSD) t-tests where appropriate. A P value of <0.05 was considered statistically significant. RESULTS: The outcome variable (ablative volume) was significantly affected by time, power, and time/power interaction (P < 0.05). When the total output energy was kept constant, the combination of higher power and shorter time obtained a larger ablative volume, especially in the low- and medium-energy groups (P < 0.01). CONCLUSIONS: We propose guidelines for ablative volume based on different time and power variables to provide a reference for clinical applications.

Flavone attenuates nicotine-induced lung injury in rats exposed to gamma radiation via modulating PI3K/Nrf2 and FoxO1/NLRP3 inflammasome.

Prolonged exposure to different occupational or environmental toxicants triggered oxidative stress and inflammatory reactions mediated lung damage. This study was designed to explore the influence and protective impact of flavone on lung injury in rats intoxicated with nicotine (NIC) and exposed to radiation (IR). Forty rats were divided into four groups; group I control, group II flavone; rats were administered with flavone (25 mg/kg/day), group III NIC + IR; rats were injected intraperitoneally with NIC (1 mg/kg/day) and exposed to γ-IR (3.5 Gy once/week for 2 weeks) while group IV NIC + IR + flavone; rats were injected with NIC, exposed to IR and administered with flavone. Redox status parameters and histopathological changes in lung tissue were evaluated. Nuclear factor-kappa B (NF-κB), forkhead box O-class1 (FoxO1) and nucleotide-binding domain- (NOD-) like receptor pyrin domain-containing-3 (NLRP3) gene expression were measured in lung tissues. Moreover, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and phosphatidylinositol three kinase (PI3K) were measured using ELISA kits. Our data demonstrates, for the first time, that flavone protects the lung from NIC/IR-associated cytotoxicity, by attenuating the disrupted redox status and aggravating the antioxidant defence mechanism via activation of the PI3K/Nrf2. Moreover, flavone alleviates pulmonary inflammation by inhibiting the inflammatory signaling pathway FOXO1/NF-κB/NLRP3- Inflammasome. Collectively, the obtained results exhibited a notable efficiency of flavone in alleviating lung injury induced by NIC and IR via modulating PI3K/Nrf2 and FoxO1/NLRP3 Inflammasome.

Early lymphocyte levels and low doses radiation exposure of lung predict lymphopenia in radiotherapy for lung cancer.

Introduction: Radiation induced lymphopenia (RIL) deteriorate survival and diminishes the benefit of immune checkpoint inhibitors in combined treatment of lung cancer. Given the inconsistent data across various studies on the predictors of RIL, we aim to methodically elucidate these predictors and formulate a practical guide for clinicians. Methods: We conducted observational cohort study in four tertiary cancer centers. Patients with non-small cell lung cancer and small cell lung cancer, without lymphopenia grade >1, who underwent standalone radiotherapy (RT) in minimum 15 fractions were eligible. Dose-volume parameters of structures and clinical factors were comprehensively analyzed using various predictors selection methods and statistical models (Linear Regressors, Elastic Net, Bayesian Regressors, Huber Regression, regression based on k-nearest neighbors, Gaussian Process Regressor, Decision Tree Regressor, Random Forest Regressor, eXtreme Gradient Boosting, Automated Machine Learning) and were ranked to predict lymphocytes count nadir (alc_nadir). Results: Two hundred thirty eight patients (stage I-3.4%, II-17.6%, III-75.2%, IV-3.8%) who underwent RT to median dose of 60 Gy were analyzed. Median alc_nadir was 0.68K/mm3. The 60 feature sets were evaluated in 600 models (RMSE 0.27-0.41K/mm³). The most important features were baseline lymphocyte count (alc_1), mean lung_dose, lung v05, lung v10, heart v05 and effective dose to immune cells (edic). In patients with alc_1 ≤ 2.005K/mm3, median alc_nadir predictions were 0.54K/mm3 for lung_v05p > 51.8% and 0.76K/mm3 for lung_v05p ≤ 51.8%. Lymphopenia was rare in patients with alc_1 > 2.005K/mm3. Discussion: RIL was most severe in patients with low early lymphocyte counts, primarily triggered by low RT doses in the heart and lungs.

Automatic planning for functional lung avoidance radiotherapy based on function-guided beam angle selection and plan optimization.

Objective.This study aims to develop a fully automatic planning framework for functional lung avoidance radiotherapy (AP-FLART).Approach.The AP-FLART integrates a dosimetric score-based beam angle selection method and a meta-optimization-based plan optimization method, both of which incorporate lung function information to guide dose redirection from high functional lung (HFL) to low functional lung (LFL). It is applicable to both contour-based FLART (cFLART) and voxel-based FLART (vFLART) optimization options. A cohort of 18 lung cancer patient cases underwent planning-CT and SPECT perfusion scans were collected. AP-FLART was applied to generate conventional RT (ConvRT), cFLART, and vFLART plans for all cases. We compared automatic against manual ConvRT plans as well as automatic ConvRT against FLART plans, to evaluate the effectiveness of AP-FLART. Ablation studies were performed to evaluate the contribution of function-guided beam angle selection and plan optimization to dose redirection.Main results.Automatic ConvRT plans generated by AP-FLART exhibited similar quality compared to manual counterparts. Furthermore, compared to automatic ConvRT plans, HFL mean dose,V20, andV5were significantly reduced by 1.13 Gy (p< .001), 2.01% (p< .001), and 6.66% (p< .001) respectively for cFLART plans. Besides, vFLART plans showed a decrease in lung functionally weighted mean dose by 0.64 Gy (p< .01),fV20by 0.90% (p= 0.099), andfV5by 5.07% (p< .01) respectively. Though inferior conformity was observed, all dose constraints were well satisfied. The ablation study results indicated that both function-guided beam angle selection and plan optimization significantly contributed to dose redirection.Significance.AP-FLART can effectively redirect doses from HFL to LFL without severely degrading conventional dose metrics, producing high-quality FLART plans. It has the potential to advance the research and clinical application of FLART by providing labor-free, consistent, and high-quality plans.

Estimation of radon concentration in groundwater in the mining zone of Haryana, India, for lungs and stomach annual effective dose.

The groundwater is being used for drinking and irrigation purposes in vast swathes of the Aravalli Mountain range. Since the radioisotope presence in groundwater is affected by the local mining processes, the radiation monitoring in groundwater of mining regions is of paramount importance. In the present work, we have estimated the 222Rn presence in the mining region of Aravalli in the southern part of Haryana. We measured the Radon concentration in 51 water samples from the intended area using the RAD7 alpha detector. The measured radon concentration in some of the water samples collected from the vicinity of the mining zone is higher than that of the United Nations Scientific Committee on the Effects of Atomic Radiation recommended value. Furthermore, we have estimated the annual effective doses for the lungs and stomach contributed by ingestion and inhalation. Though the calculated dose values in collected samples are not in the critical range, further monitoring of background radiation in the Aravalli region is required.

Mitigating Viral Impact on the Radiation Response of the Lung.

Inflammation is a key factor in both influenza and radiation-induced lung pathophysiology. This implies a commonality of response to pulmonary damage from these insults and suggests exacerbated pathology may occur after combined exposure. We therefore tested the hypothesis that past inflammation from viral infection alters the lung microenvironment and lowers tolerance for radiation injury. Mice were inoculated with influenza A virus (IAV) and three weeks later, after virus clearance, mice received total-body irradiation (TBI). Survival as well as systemic and local lung inflammation were assessed, and strategies to mitigate pulmonary injury were investigated. After IAV infection alone, body condition recovered within 3 weeks, however inflammatory pathways remained active for 15 weeks. IAV infection exacerbated subsequent TBI responses, evident by increased lethality, enhanced histologically evident lung injury and an altered lung macrophage phenotype. To mitigate this enhanced sensitivity, captopril [an angiotensin converting enzyme inhibitor (ACEi)] was administered to limit tissue inflammation, or inflammatory monocyte-derived macrophage recruitment was blocked with a C-C chemokine receptor type 2 (CCR2) inhibitor. Both treatments abrogated the changes in circulating immune cells observed 4 weeks after TBI, and attenuated pro-inflammatory phenotypes in lung alveolar macrophages, appearing to shift immune cell dynamics towards recovery. Histologically apparent lung injury was not improved by either treatment. We show that latent lung injury from viral infection exacerbates radiation morbidity and mortality. Although strategies that attenuate proinflammatory immune cell phenotypes can normalize macrophage dynamics, this does not fully mitigate lung injury. Recognizing that past viral infections can enhance lung radiosensitivity is of critical importance for patients receiving TBI, as it could increase the incidence of adverse outcomes.

Low-dose radiation therapy for COVID-19 pneumonia: Comparison of dosimetry and life-time attributable risk of cancer with conventional AP-PA fields and bone marrow sparing VMAT.

PURPOSE: Low-dose radiation therapy (LDRT) to lungs did show encouraging results in COVID-19 patients in some clinical trials. However, there has been some concern regarding the long-term risk of radiation-induced cancer (RIC). Compared to the conventional AP-PA field technique, volumetric modulated arc therapy (VMAT) can potentially reduce the dose to the marrow and other organs at risk (OARs) and thus minimize the risk of cancer. We designed a dosimetry study to study if VMAT can reduce the exposure to the marrow and other OAR doses and curtail the estimated life-time attributable risk (LAR) of cancer. METHODS AND MATERIALS: We retrieved the computed tomography scan data of 10 patients (aged 40-60 years, median 48 years) who have been already treated for any malignancy in the region of the thorax. A dose of 1.0 Gy in single fraction was prescribed to both lungs. All the organs were delineated as per the established guidelines. The dosimetry achieved by the two plans was compared to find the difference. Mean OAR doses were used to estimate the LAR for both plans and compared. RESULTS: Planning target volume coverage parameters like conformity index and homogeneity index were significantly better with VMAT (P value < 0.05 for all). The mean dose to most OARs was significantly lower with VMAT (P value < 0.05 for all). The mean dose to the marrow was significantly lower with VMAT (59.05 vs 81.9 cGy with P value < 0.05). The overall LAR was significantly lower with VMAT as compared to the conventional plan (0.357% vs 0.398%, P value < 0.05). CONCLUSION: Compared to the conventional technique, VMAT provides better OAR dosimetry for lung irradiation (a prescription dose of 1.0 Gy or more) in COVID-19 pneumonia. VMAT significantly reduces the risk of RIC. We therefore suggest if lung LDRT is used for COVID-19 patients, VMAT is the preferred technique for a prescription dose of ≥1.0 Gy.

Radioprotective effect of the anti-diabetic drug metformin.

Metformin is a biguanide currently used in the treatment of diabetes mellitus type 2. Besides its anti-glycemic effects, metformin has been reported to induce different cellular pleiotropic effects, depending on concentration and time of treatment. Here we report one administration of metformin (0.5 mM) has radioprotective effects in vitro on BJ human fibroblasts, increasing DNA damage repair and increasing SOD1 expression in the nucleus. Importantly, metformin (200 mg/kg) pre-administration for only 3 days in wild type 129/sv mice, decreases the formation of micronuclei in bone marrow cells and DNA damage in colon and lung tissues compared to control irradiated mice at sub-lethal and lethal doses, increasing the overall survival fraction by 37% after 10Gy total body irradiation. We next pre-treated with metformin and then exposed 129/sv mice, to a galactic cosmic rays simulation (GCRsim), at the NASA Space Radiation Laboratory (NSRL). We found metformin pre-treatment decreases the presence of bone marrow micronuclei and DNA damage in colon and lung tissues and an increase of 8-oxoguanine DNA glycosylase-1 (OGG1) expression. Our data highlight a radioprotective effect of metformin through an indirect modulation of the gene expression involved in the cellular detoxification rather than its effects on mitochondria.

[Normal mouse serum alleviates radiation pneumonitis in mice by inhibiting the focal adhesion signaling pathway].

OBJECTIVE: To evaluate the therapeutic effect of normal mouse serum on radiation pneumonitis in mice and explore the possible mechanism. METHODS: Mouse models of radiation pneumonitis induced by thoracic radiation exposure were given intravenous injections of 100 µL normal mouse serum or normal saline immediately after the exposure followed by injections once every other day for a total of 8 injections. On the 15th day after irradiation, histopathological changes of the lungs of the mice were examined using HE staining, the levels of TNF-α, TGF-ß, IL-1α and IL-6 in the lung tissue and serum were detected using ELISA, and the percentages of lymphocytes in the lung tissue were analyzed with flow cytometry. Highth-roughput sequencing of exosome miRNA was carried out to explore the changes in the signaling pathways. The mRNA expression levels of the immune-related genes were detected by qRT-PCR, and the protein expressions of talin-1, tensin2, FAK, vinculin, α-actinin and paxillin in the focal adhesion signaling pathway were detected with Western blotting. RESULTS: In the mouse models of radiation pneumonitis, injections of normal mouse serum significantly decreased the lung organ coefficient, lowered the levels of TNF-α, TGF-ß, IL-1α and IL-6 in the serum and lung tissues, and ameliorated infiltration of CD45+, CD4+ and Treg lymphocytes in the lung tissue (all P < 0.05). The expression levels of Egfr and Pik3cd genes at both the mRNA and protein levels and the protein expressions of talin-1, tensin2, FAK, vinculin, α?actinin and paxillin were all significantly down-regulated in the mouse models after normal mouse serum treatment. CONCLUSION: Normal mouse serum ameliorates radiation pneumonitis in mice by inhibiting the expressions of key proteins in the Focal adhesion signaling pathway.

Evaluation of chest CT-scans following lung stereotactic ablative radiotherapy: Challenges and new insights.

Stereotactic ablative radiotherapy (SABR) is increasingly used for the treatment of early-stage non-small cell lung cancer (ES-NSCLC) and for pulmonary metastases. In patients with ES-NSCLC, SABR is highly successful with reported 5-year local control rates of approximately 90%. However, the assessment of local control following lung SABR can be challenging as radiological changes arising from radiation-induced lung injury (RILI) can be observed in up to 90% of patients. These so-called 'benign' radiological changes evolve with time and are often asymptomatic. Several radiological and metabolic features have been explored to help distinguish RILI from local recurrences (LR). These include the Response Evaluation Criteria for Solid Tumors (RECIST), high-risk features (HRF's) and maximum standardized uptake value (SUVmax) on FDG-PET-CT. However, use of some of these approaches have poor predictive values and low specificity for recurrence. A proposed new workflow for the evaluation of post-lung SABR radiological changes will be reviewed which uses the presence of so-called 'actionable radiological features' to trigger changes to imaging schedules and identifies the need for a multidisciplinary board review. Furthermore, this critical review of post-lung SABR imaging will highlight current challenges, new insights, and unknowns in this field.

SARS-CoV-2 Spike Protein Induces Oxidative Stress and Senescence in Mouse and Human Lung.

BACKGROUND/AIM: There is concern that people who had COVID-19 will develop pulmonary fibrosis. Using mouse models, we compared pulmonary inflammation following injection of the spike protein of SARS-CoV-2 (COVID-19) to radiation-induced inflammation to demonstrate similarities between the two models. SARS-CoV-2 (COVID-19) induces inflammatory cytokines and stress responses, which are also common to ionizing irradiation-induced acute pulmonary damage. Cellular senescence, which is a late effect following exposure to SARS-CoV-2 as well as radiation, was investigated. MATERIALS AND METHODS: We evaluated the effect of SARS-CoV-2 spike protein compared to ionizing irradiation in K18-hACE2 mouse lung, human lung cell lines, and in freshly explanted human lung. We measured reactive oxygen species, DNA double-strand breaks, stimulation of transforming growth factor-beta pathways, and cellular senescence following exposure to SARS-CoV-2 spike protein, irradiation or SARS-COV-2 and irradiation. We also measured the effects of the antioxidant radiation mitigator MMS350 following irradiation or exposure to SARS-CoV-2. RESULTS: SARS-CoV-2 spike protein induced reactive oxygen species, DNA double-strand breaks, transforming growth factor-ß signaling pathways, and senescence, which were exacerbated by prior or subsequent ionizing irradiation. The water-soluble radiation countermeasure, MMS350, reduced spike protein-induced changes. CONCLUSION: In both the SARS-Co-2 and the irradiation mouse models, similar responses were seen indicating that irradiation or exposure to SARS-CoV-2 virus may lead to similar lung diseases such as pulmonary fibrosis. Combination of irradiation and SARS-CoV-2 may result in a more severe case of pulmonary fibrosis. Cellular senescence may explain some of the late effects of exposure to SARS-CoV-2 spike protein and to ionizing irradiation.

Dosimetric analysis of six whole-breast irradiation techniques in supine and prone positions.

In breast cancer radiation therapy, minimizing radiation-related risks and toxicity is vital for improving life expectancy. Tailoring radiotherapy techniques and treatment positions can reduce radiation doses to normal organs and mitigate treatment-related toxicity. This study entailed a dosimetric comparison of six different external beam whole-breast irradiation techniques in both supine and prone positions. We selected fourteen breast cancer patients, generating six treatment plans in both positions per patient. We assessed target coverage and organs at risk (OAR) doses to evaluate the impact of treatment techniques and positions. Excess absolute risk was calculated to estimate potential secondary cancer risk in the contralateral breast, ipsilateral lung, and contralateral lung. Additionally, we analyzed the distance between the target volume and OARs (heart and ipsilateral lung) while considering the treatment position. The results indicate that prone positioning lowers lung exposure in X-ray radiotherapy. However, particle beam therapies (PBTs) significantly reduce the dose to the heart and ipsilateral lung regardless of the patient's position. Notably, negligible differences were observed between arc-delivery and static-delivery PBTs in terms of target conformity and OAR sparing. This study provides critical dosimetric evidence to facilitate informed decision-making regarding treatment techniques and positions.

Note on dose conversion for radon exposure.

The epidemiological approach to converting radon exposure to effective dose is examined. Based on the definition of the effective dose, the dose conversion is obtained from the equivalence of lung-specific detriment associated with low-LET radiation and with radon exposure. This approach most reliably estimates effective dose per radon exposure on the basis of epidemiological data and implicitly includes the radiation weighting factor required to calculate the effective dose from radon exposure using the dosimetric approach, applying biokinetic and dosimetric models. Consistency between the results of the epidemiological and dosimetric approaches is achieved by using a radiation weighting factor of about 10 for alpha particles instead of the current ICRP value of 20. In contrast, the epidemiological approach implemented in ICRP 65, and referred to as dose conversion convention, was based on direct comparison of total radiation detriment with lung detriment from radon exposure. With the revision of radiation detriments in ICRP 103, this approach can be judged to overestimate the effective dose per radon exposure by about a factor of two because the tissue weighting factor for lung differs from the value of relative detriment to which it relates.

Ondansetron or beta-sitosterol antagonizes inflammatory responses in liver, kidney, lung and heart tissues of irradiated arthritic rats model.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder mainly affecting joints, yet the systemic inflammation can influence other organs and tissues. The objective of this study was to unravel the ameliorative capability of Ondansetron (O) or ß-sitosterol (BS) against inflammatory reactions and oxidative stress that complicates Extra-articular manifestations (EAM) in liver, kidney, lung, and heart of arthritic and arthritic irradiated rats. METHODS: This was accomplished by exposing adjuvant-induced arthritis (AIA) rats to successive weekly fractions of total body γ-irradiation (2 Gray (Gy)/fraction once per week for four weeks, up to a total dose of 8 Gy). Arthritic and/or arthritic irradiated rats were either treated with BS (40 mg/kg b.wt. /day, orally) or O (2 mg/kg) was given ip) or were kept untreated as model groups. RESULTS: Body weight changes, paw circumference, oxidative stress indices, inflammatory response biomarkers, expression of Janus kinase-2 (JAK-2), Signal transducer and activator of transcription 3 (STAT3), high mobility group box1 (HMGB1), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), as well as pro- and anti-inflammatory mediators in the target organs, besides histopathological examination of ankle joints and extra-articular tissues. Treatment of arthritic and/or arthritic irradiated rats with BS or O powerfully alleviated changes in body weight gain, paw swelling, oxidative stress, inflammatory reactions, and histopathological degenerative alterations in articular and non-articular tissues. CONCLUSION: The obtained data imply that BS or O improved the articular and EAM by regulating oxidative and inflammatory indices in arthritic and arthritic irradiated rats.