High-Accuracy Relative Biological Effectiveness Values Following Low-Dose Thermal Neutron Exposures Support Bimodal Quality Factor Response with Neutron Energy

Theoretical evaluations indicate the radiation weighting factor for thermal neutrons differs from the current International Commission on Radiological Protection (ICRP) recommended value of 2.5, which has radiation protection implications for high-energy radiotherapy, inside spacecraft, on the lunar or Martian surface, and in nuclear reactor workplaces. We examined the relative biological effectiveness (RBE) of DNA damage generated by thermal neutrons compared to gamma radiation. Whole blood was irradiated by 64 meV thermal neutrons from the National Research Universal reactor. DNA damage and erroneous DNA double-strand break repair was evaluated by dicentric chromosome assay (DCA) and cytokinesis-block micronucleus (CBMN) assay with low doses ranging 6–85 mGy. Linear dose responses were observed. Significant DNA aberration clustering was found indicative of high ionizing density radiation. When the dose contribution of both the 14N(n,p)14C and 1H(n,γ)2H capture reactions were considered, the DCA and the CBMN assays generated similar maximum RBE values of 11.3 ± 1.6 and 9.0 ± 1.1, respectively. Consequently, thermal neutron RBE is approximately four times higher than the current ICRP radiation weighting factor value of 2.5. This lends support to bimodal peaks in the quality factor for RBE neutron energy response, underlining the importance of radiological protection against thermal neutron exposures.

The expediency of using a plant protection system using the microbiological fungicide BisolbiSan, W in the cultivation of winter wheat in the Southern natural and agricultural zone of the Rostov region

The authors analyzed the biological effectiveness of the integrated plant protection system formed when the microbiological fungicide BisolbiSan, Zh was included in the classical protection scheme adopted in the farms of the Rostov region. The biological effectiveness of the integrated protection system, including the fungicide BisolbiSan, was analyzed, the impact of the studied protection system on the yield, the quality of the grain obtained, the phytosanitary condition of the crop during the growing season on winter wheat crops of the variety Nakhodka with the use of a plant protection system, including the fungicide BisolbiSan, Zh. The fungicide BisolbiSan, containing a culture of rhizospheric bacteria Bacillus subtilis strain H-13, suppresses the germination of spores and mycelium growth of phytopathogenic fungi due to the multilateral action of bacterial metabolites, without causing the formation of resistance in pathogens. It was found that the protection system used practically does not cause a decrease in grain quality — in terms of the average protein and gluten content, the grain at the experimental site even slightly exceeds the grain obtained from the control site by 16.88% and 27.8%. With the cost of winter wheat grain of 1100 rubles/kg, an increase in the yield in the experiment of 3.8 kg/ha in relation to control and the cost of an experimental protection system in the amount of 3,357 rubles/ha, revenue amounted to 823 rubles/ha.

Biological Effectiveness of Plant Polyphenols under Greenhouse Conditions, Against Wilt and Root Rot Complex of Chickpea (Cicer arietinum L.)

Chickpea (Cicer arietinum L.) production is constantly compromised by a complex of pathogens which cause wilt and root rot (WRR). Therefore, biological control and organic products have regained great importance in the last few years. In this work, polyphenols were obtained from ethanolic extracts through the ultrasound-microwave assisted technique from the plant species chinese privet leaves (Ligustrum lucidum) and moringa leaves (Moringa oleifera). A qualitative analysis through reverse phase high-performance liquid chromatography electrospray ionization mass spectrometry (RP-HPLC-ESI-MS) was conducted, so that their biological effectiveness under greenhouse conditions was determined by each group of polyphenols against Fusarium oxysporum f. sp. ciceris, Fusarium solani, and Macrophomina phaseolina which comprise the wilt and root rot complex. A complete randomized block design was established with three blocks and five treatments with nine replications each. Treatments were: Polyphenols of Ligustrum lucidum, polyphenols of Moringa oleifera, the fungicide Benomyl, the inoculated check, and the untreated check. The analysis of variance was performed and mean comparison with Duncan`s multiple range test (0.05). The results indicate that all groups of polyphenol had in their chemical composition, some compounds of known microbial activity, such as hydroxycinnamic acid, flavones, anthocyanins, catechins, and alkyphenols. Under greenhouse conditions, plants that had the lowest incidence and severity of the disease, were those treated with polyphenols from L. lucidum with 66% incidence, and were statistically different to the rest of the treatments.

Microdosimetric characterization of a clinical proton therapy beam: comparison between simulated lineal energy distributions in spherical water targets and experimental measurements with a silicon detector

Objective Treatment planning based on computer simulations were proposed to account for the increase in the relative biological effectiveness (RBE) of proton radiotherapy beams near to the edges of the irradiated volume. Since silicon detectors could be used to validate the results of these simulations, it is important to explore the limitations of this comparison. Approach Microdosimetric measurements with a MicroPlus Bridge V2 silicon detector (thickness = 10 µm) were performed along the Bragg peak of a clinical proton beam. The lineal energy distributions, the dose mean values, and the RBE calculated with a biological weighting function were compared with simulations with PHITS (microdosimetric target = 1 µm water sphere), and published clonogenic survival in vitro RBE data for the V79 cell line. The effect of the silicon-to-water conversion was also investigated by comparing three different methodologies (conversion based on a single value, novel bin-to-bin conversions based on SRIM and PSTAR). Main results Mainly due to differences in the microdosimetric targets, the experimental dose-mean lineal energy and RBE values at the distal edge were respectively up to 53% and 28% lower than the simulated ones. Furthermore, the methodology chosen for the silicon-to-water conversion was proven to affect the dose mean lineal energy and the RBE10 up to 32% and 11% respectively. The best methodology to compensate for this underestimation was the bin-to-bin silicon-to-water conversion based on PSTAR. Significance This work represents the first comparison between PHITS-simulated lineal energy distributions in water targets and corresponding experimental spectra measured with silicon detectors. Furthermore, the effect of the silicon-to-water conversion on the RBE was explored for the first time. The proposed methodology based on the PSTAR bin-to-bin conversion appears to provide superior results with respect to commonly used single scaling factors and is recommended for future studies.

Biological effectiveness of quillay (Quillaja saponaria) extracts for the control of yellow aphids (Melanaphis sacchari) in sorghum

Objective: To evaluate and define a plant extract for the control of the yellow aphid in order to prevent environmental contamination and improve crop profitability. Design/Methodology/Approach: In a sorghum plot —located in the municipality of Jantetelco, Morelos— with a high incidence of yellow aphids, three doses —2-, 4-, and 6-mL L-1 of water of Quillaja saponaria extract, 0.2-mL L-1 of water of Imidacloprid, and 10-mL L-1 of water of calcium polysulfide—, as well as an absolute control, were evaluated. The applications were carried out using a 15-L manual spray backpack, which had been previously calibrated and had a fan nozzle. A randomized block experimental design—with six treatments and four repetitions— was used. The experimental unit was made up of five 5-m long rows with 0.70 m between rows, resulting in a 17.5 m2 total area per experimental unit. The three central furrows were the useful plot, leaving 0.5 m at each end of the furrow. The total size of the experimental plot was 420 m2. Results: The biological effectiveness during the samplings was as follows: both the Quillaja saponaria (6-, 4- and 2-mL L-1 water doses) and Imidacloprid treatments had a 100% effectiveness. Study limitations/implications: This study was carried out in sorghum crops. Findings/conclusions: Treatments based on Quillaja saponaria extracts on M. sacchari in sorghum crops showed 100% biological effectiveness from the first application and no phytotoxicity was observed in any treatment

A New Low-Energy Proton Irradiation Facility to Unveil the Mechanistic Basis of the Proton-Boron Capture Therapy Approach

Protontherapy (PT) is a fast-growing cancer therapy modality thanks to much-improved normal tissue sparing granted by the charged particles’ inverted dose-depth profile. Protons, however, exhibit a low biological effectiveness at clinically relevant energies. To enhance PT efficacy and counteract cancer radioresistance, Proton–Boron Capture Therapy (PBCT) was recently proposed. PBCT exploits the highly DNA-damaging α-particles generated by the p + 11B→3α (pB) nuclear reaction, whose cross-section peaks for proton energies of 675 keV. Although a significant enhancement of proton biological effectiveness by PBCT has been demonstrated for high-energy proton beams, validation of the PBCT rationale using monochromatic proton beams having energy close to the reaction cross-section maximum is still lacking. To this end, we implemented a novel setup for radiobiology experiments at a 3-MV tandem accelerator; using a scattering chamber equipped with an Au foil scatterer for beam diffusion on the biological sample, uniformity in energy and fluence with uncertainties of 2% and 5%, respectively, was achieved. Human cancer cells were irradiated at this beamline for the first time with 685-keV protons. The measured enhancement in cancer cell killing due to the 11B carrier BSH was the highest among those thus far observed, thereby corroborating the mechanistic bases of PBCT.

Therapeutic Efficacy of Variable Biological Effectiveness of Proton Therapy in U-CH2 and MUG-Chor1 Human Chordoma Cell Death

Background: Chordoma is a cancer of spinal cord, skull base, and sacral area. Currently, the standard of care to treat chordoma is resection followed by radiation therapy. Since, chordoma is present in the spinal cord and these are very sensitive structures and often complete removal by surgery is not possible. As a result, chordoma has a high chance of recurrence and developing resistance to radiation therapy. In addition, treatment of chordoma by conventional radiation therapy can also damage normal tissues surrounding chordoma. Thus, current therapeutic options to treat chordoma are insufficient and novel therapies are desperately needed to treat locally advanced and metastatic chordoma. (2) Methods: In the present investigation, human chordoma cell lines of sacral origin MUG-Chor1 and U-CH2 were cultured and irradiated with Proton Beam Radiation using the clinical superconducting cyclotron and pencil-beam (active) scanning at Middle and End of the Spread-Out Bragg Peak (SOBP). Proton radiation was given at the following doses: Mug-Chor1 at 0, 1, 2, 4, and 8 Gy and U-CH2 at 0, 4, 8, 12, and 16 Gy. These doses were selected based on a pilot study in our lab and attempted to produce approximate survival fractions in the range of 1, 0.9, 0.5, 0.1, and 0.01, respectively, chosen for linear quadratic model fitting of the dose response. (3) Results: In this study, we investigated relative biological effectiveness (RBE) of proton radiation at the end of Spread Out Bragg Peak assuming that the reference radiation is a proton radiation in the middle of the SOBP. We observed differences in the survival of both Human chordoma cell lines, U-CH2 and MUG-Chor1. The data showed that there was a significantly higher cell death at the end of the Bragg peak as compared to middle of the Bragg peak. Based on the linear quadratic (LQ) fit for cell survival we calculated the RBE between M-SOBP and E-SOBP at 95% CI level and it was observed that RBE was higher than 1 at E-SOBP and caused significantly higher cell killing. Proton field at E-SOBP caused complex DNA damage in comparison to M-EOBP and the genes such as DNA topoisomerase 1, GTSE1, RAD51B were downregulated in E-SOBP treated cells. Thus, we conclude that there seems to be substantial variation in RBE (1.3–1.7) at the E-SOBP compared with the M-SOBP.

Study of the RBE depth dependence of protons using a damage diagnostic algorithm and its application in proton therapy based on Monte Carlo simulation

The present study aimed to calculate the yields of DNA breaks and the variation of relative biological effectiveness (RBE) at different depths for protons using Geant4-DNA. For this purpose, an atomic model of DNA and a DNA damage classification matrix were used to calculate different DNA break yields for 62-MeV protons. As the reference radiation, the secondary electron spectrum produced by 60Co was evaluated. This helped to calculate the SSB and DSB yields. Moreover, RBE was found to be between 1.1 at the first point and 1.51 in the Bragg peak region. In this region, it was 37% greater than the 5-mm depth in the plateau region. Considering different threshold energies, the energy deposition at 10.79 eV had the most contribution to the total damage. As the results suggested, the depth dependence of RBE should be taken into account for proton therapy. It was also found that DNA break yields significantly depend on the threshold energy value.

A long-term survival case with proton beam therapy for advanced sphenoid sinus cancer with hypopituitarism

Sphenoid sinus malignancies are rare diseases. Secondary hypopituitarism associated with sphenoid sinus malignancy is not well known. A 41-year-old male complained of right ptosis. Neurological findings revealed right oculomotor, trochlear and glossopharyngeal nerve palsy. Imaging diagnosis suggested a tumor that had spread bilaterally from the sphenoid sinus to the ethmoid sinus, nasopharynx and posterior pharyngeal space. Biopsy revealed squamous cell carcinoma (SCC). Based on these findings, a clinical diagnosis of SCC of the sphenoid sinus was made. Removal of the tumor without damaging nearby organs would have been difficult because the tumor extended to the bilateral optic nerves, optic chiasma and internal carotid artery, and surgeons, therefore, recommended proton beam therapy (PBT). Before PBT, the hypopituitarism occurred in the patient and we administered hydrocortisone and levothyroxine. During treating for hypopituitarism, we performed PBT with nedaplatin and 5-fluorouracil. The daily PBT fractions were 2.2 relative biological effectiveness (RBE) for the tumor received total dose of 81.4 Gy RBE. The acute side effect of grade 2 dermatitis according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Occurred after PBT. The patient needs to take hydrocortisone and levothyroxine, but he remains in complete remission 8 years after treatment without surgery or chemotherapy. Visual function is gradually declining, but there is no evidence of severe radiation-induced optic neuropathy.