The National Institute of Radiological Sciences (NIRS) has initiated a development project for hypo-fractionated multi-ion therapy. In the treatment, heavy ions up to neon ions will be used as a ...primary beam, which is a high linear energy transfer (LET) radiation. The fractionated dose of the treatment will be 10 Gy or more. The microdosimetric kinetic (MK) model overestimates the biological effectiveness of high-LET and high-dose radiations. To address this issue, the stochastic microdosimetric kinetic (SMK) model has been developed as an extension of the MK model. By taking the stochastic nature of domain-specific and cell nucleus-specific energies into account, the SMK model could estimate the biological effectiveness of radiations with wide LET and dose ranges. Previously, the accuracy of the SMK model was examined by comparison of estimated and reported survival fractions of human cells exposed to pristine helium-, carbon-, and neon-ion beams. In this study, we verified the SMK model in treatment planning of scanned helium-, carbon-, oxygen-, and neon-ion beams as well as their combinations through the irradiations of human undifferentiated carcinoma and human pancreatic cancer cells. Treatment plans were made with the ion-species beams to achieve a uniform 10% survival of the cells within a cuboid target. The planned survival fractions were reasonably reproduced by the measured survival fractions in the whole region from the plateau to the fragment tail for all planned irradiations. The SMK model offers the accuracy and simplicity required in hypo-fractionated multi-ion therapy treatment planning.
There are few studies on the relationship between the frequency of acupuncture use and subjective health status. Therefore, we investigated this relationship using data of a previously performed ...cross-sectional survey of patients visiting Japanese acupuncture clinics.
This study used data from a cross-sectional survey conducted in 2011 on patients visiting 180 acupuncture clinics nationwide that were run by members of the alumni association of Meiji University of Integrative Medicine Faculty of Acupuncture and Moxibustion, and did not provide treatment other than acupuncture. We calculated the frequency of visits to acupuncture clinics (< 24 times, 24-47 times, 48-95 times, or ≥ 96 times per year) and the Short Form-36 (SF-36) summary scores (physical, mental, role/social) based on the response of the questionnaire conducted at the time of the survey. Multiple linear regression analysis with multiple imputation was performed with three SF-36 summary scores as the dependent variables, and the frequency of visits to acupuncture clinics as the independent variable.
The questionnaire was distributed to 2,379 outpatients of acupuncture clinics, 1,409 of whom met the criteria and were included in the analysis. More frequent visits to acupuncture clinics were associated with lower scores on all three SF-36 summary scores. Compared to those who visited < 24 times a year, those who visited ≥ 96 times a year had unstandardized regression coefficients (95% confidence interval) of -5.6 (-7.8 to -3.3) for the physical, -2.0 (-3.9 to -0.1) for the mental, and -2.9 (-5.4 to -0.4) for the role/social SF-36.
Frequent visits to acupuncture clinics were associated with poor subjective health status, especially physical health.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The purpose is to verify experimentally whether application of magnetic fields longitudinal and perpendicular to a proton beam alters the biological effectiveness of the radiation.
Proton beams with ...linear energy transfer of 1.1 and 3.3 keV/μm irradiated human cancer and normal cells under a longitudinal (perpendicular) magnetic field of B
(B
) = 0, 0.3, or 0.6 T. Cell survival curves were constructed to evaluate the effects of the magnetic fields on the biological effectiveness. The ratio of dose that would result in a survival fraction of 10% without the magnetic field D
to the dose with the magnetic field D
, R
= D
/D
, was determined for each cell line and magnetic field.
For cancer cells exposed to the 1.1- (3.3-) keV/μm proton beams, R
s were increased to 1.10 ± 0.07 (1.11 ± 0.07) and 1.11 ± 0.07 (1.12 ± 0.07) by the longitudinal magnetic fields of B
= 0.3 and 0.6 T, respectively. For normal cells, R
s were increased to 1.13 ± 0.06 (1.17 ± 0.06) and 1.17 ± 0.06 (1.30 ± 0.06) by the B
s. In contrast, R
s were not changed significantly from 1 by the perpendicular magnetic fields of B
= 0.3 and 0.6 T for both cancer and normal cells exposed to 1.1- and 3.3-keV/μm proton beams.
The biological effectiveness of proton beams was significantly enhanced by longitudinal magnetic fields of B
= 0.3 and 0.6 T, whereas the biological effectiveness was not altered by perpendicular magnetic fields of the same strengths. This enhancement effect should be taken into account in magnetic resonance imaging guided proton therapy with a longitudinal magnetic field.
Purpose: We studied lethal and mutagenic bystander effects in normal human fibroblasts irradiated with low-energy-carbon ions.
Materials and methods: After cells reached confluence, cells were ...irradiated with initial energies of 6 MeV/n carbon ions. The residual energy and LET value were 4.6 MeV/n and 309 keV/µm. The doses used for survival and mutational studies were 0.082 and 0.16 Gy. Irradiation was carried out using 4 different irradiation conditions and plating conditions: (1) The entire cell area on the Mylar film was irradiated (We abbreviate as 'all irradiation'); (2) Irradiated and unirradiated cells were pooled in a 1:1 ratio and plated as a single culture until the plating for lethal and mutagenic experiments (We abbreviate as 'mixed population'); (3) Only half of the area on the Mylar film were irradiated using an ion-beam stopper (We abbreviate as 'half irradiation'); and (4) Only half of the area of the cells were irradiated, and a specific inhibitor of gap junctions was added to the culture (We abbreviate as 'half irradiation with inhibitor'). Cell samples were analyzed for lethal and mutagenic bystander effects, including a PCR evaluation of the mutation spectrum.
Results: The surviving fraction of all irradiation was the same as the half irradiation case. The surviving fractions of both mixed population and the half irradiation with inhibitor were the same level and higher than those of all irradiation and half irradiation. The mutation frequencies at the HPRT (the hypoxanthine-guanine phosphoribosyl transferase) locus of all irradiation and half irradiation were at the same level and were higher than those of mixed population and half irradiation with inhibitor, respectively.
Conclusion: There is evidence that the bystander effects for both lethality and mutagenicity occurred in the unirradiated half of the cells, in which only half of the cells were irradiated with the carbon ions. These results suggest that the bystander cellular effects via gap-junction-mediated cell-cell communication are induced by high-LET-carbon ions.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Drug-induced pseudoaldosteronism is a typical adverse effect of Kampo formulas. Previous research described the potential risks of Kampo formula-linked pseudoaldosteronism. However, few studies ...assessed the risk factors using a real-world database and a data-mining approach. Using the Japanese Adverse Drug Event Report database, we extracted pseudoaldosteronism reports for 148 Kampo formulas covered by Japanese national health insurance. Adverse events were decided according to the preferred terminology of the Medical Dictionary for Regulatory Activities/Japanese version 25.1. We calculated reporting odds ratio (RORs) and identified Kampo formulas as suspected causes of pseudoaldosteronism. Moreover, we evaluated clinical factors associated with Kampo formula-induced pseudoaldosteronism via logistic regression. From April 2004 to November 2022, 6334 adverse events related to the Kampo formulas were reported. We selected 2471 reports containing complete clinical data, including 210 reports on pseudoaldosteronism. In the pseudoaldosteronism group, 69.0% of patients were female, and 85.2% were ≥70 years old. The formulas most commonly associated with pseudoaldosteronism were Shakuyakukanzoto, Yokukansan, and Ryokeijutsukanto (ROR 95% confidence interval {CI} = 18.3 13.0-25.9, 8.1 5.4-12.0, and 5.5 1.4-21.9, respectively). Logistic analysis identified female sex (odds ratio OR 95% CI = 1.7 1.2-2.6; P = 0.006), older age (≥70, 5.0 3.2-7.8; P < 0.001), low body weight (<50 kg, 2.2 1.5-3.2; P < 0.001), diuretics usage (2.1 1.3-4.8; P = 0.004), hypertension (1.6 1.1-2.4; P = 0.014), and dementia (7.0 4.2-11.6; P < 0.001) as pseudoaldosteronism-related factors. Additionally, the daily Glycyrrhiza dose (OR = 2.1 1.9-2.3; P < 0.001) and duration of administration (>14 days, OR = 2.8 1.7-4.5; P < 0.001) were associated with adverse events. We did not observe an interaction between aging and hypertension. Careful follow-up is warranted during long-term Glycyrrhiza-containing Kampo formula use in patients with multiple clinical factors for pseudoaldosteronism.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
DNA damage is generated by various intrinsic and extrinsic sources such as reactive oxygen species (ROS) and environmental mutagens, and causes genomic alterations. DNA damage response (DDR) is ...activated to induce cell cycle arrest and DNA repair. Oxidation resistance 1 (OXR1) is a protein that defends cells against oxidative stress. We previously reported that OXR1 protein functions in the regulation of G2-phase cell cycle arrest in cells irradiated with gamma-rays, suggesting that OXR1 directly responds to DNA damage. To clarify the functions of OXR1 against ROS-independent DNA damage, HeLa and OXR1-depleted HeLa cells were treated with heavy-ion beams and the ROS-independent DNA-damaging agent methyl methanesulfonate (MMS). First, OXR1-depleted cells exhibited higher sensitivity to MMS and heavy-ion beams than control cells. Next, OXR1 depletion increased micronucleus formation and shortened the duration of G2-phase arrest after treatment with MMS or heavy-ion beams. These results suggest that OXR1 functions in the maintenance of cell survival and genome stability in response to DNA damage. Furthermore, the OXR1 protein level was increased by MMS and heavy-ion beams in HeLa cells. Together with our previous study, the present study suggests that OXR1 plays an important role in the response to DNA damage, not only when DNA damage is generated by ROS.
Acupuncture is known to improve exercise capacity in patients with chronic obstructive pulmonary disease (COPD), but its mechanism remains unknown. Whether acupuncture improves exercise capacity in ...patients with COPD through alleviation of leg fatigue and dyspnea is examined by applying causal mediation analysis to previous trial data.
Sixty-two patients with COPD completed treatments with either real or placebo acupuncture once a week for 12 weeks. Walk distance measured using the 6-minute walk test and intensities of leg fatigue and dyspnea in the modified Borg scale were evaluated at baseline and after treatment. The intervention effect of acupuncture against the placebo acupuncture on two mediators, changes in leg fatigue and dyspnea, and whether they mediated improvements in walk distance, were analyzed.
Linear regression analysis showed that the unstandardized regression coefficients 95% confidence interval (CI) for the intervention effect by acupuncture were -4.9 (-5.8--4.0) in leg fatigue and -3.6 (-4.3--2.9) in dyspnea. Mediation analysis showed that when changes in leg fatigue were considered as a mediator, direct effect, indirect effect and proportion mediated were 47.1 m (95% CI, 4.6-85.1), 34.3 m (-2.1-82.1), and 42.1%, respectively, and when changes in dyspnea were considered as a mediator, they were 9.8 m (-32.9-49.9), 72.5 m (31.3-121.0), and 88.1%, respectively, and the effects of joint mediator were -5.8 m (-55.4-43.9), 88.9 m (32.7-148.5), and 107.0%, respectively.
The improvement in exercise capacity by acupuncture is explained by changes in both leg fatigue and dyspnea.
Track-structure Monte Carlo simulations are useful tools to evaluate initial DNA damage induced by irradiation. In the previous study, we have developed a Gean4-DNA-based application to estimate the ...cell surviving fraction of V79 cells after irradiation, bridging the gap between the initial DNA damage and the DNA rejoining kinetics by means of the two-lesion kinetics (TLK) model. However, since the DNA repair performance depends on cell line, the same model parameters cannot be used for different cell lines. Thus, we extended the Geant4-DNA application with a TLK model for the evaluation of DNA damage repair performance in HSGc-C5 carcinoma cells which are typically used for evaluating proton/carbon radiation treatment effects. For this evaluation, we also performed experimental measurements for cell surviving fractions and DNA rejoining kinetics of the HSGc-C5 cells irradiated by 70 MeV protons at the cyclotron facility at the National Institutes for Quantum and Radiological Science and Technology (QST). Concerning fast- and slow-DNA rejoining, the TLK model parameters were adequately optimized with the simulated initial DNA damage. The optimized DNA rejoining speeds were reasonably agreed with the experimental DNA rejoining speeds. Using the optimized TLK model, the Geant4-DNA simulation is now able to predict cell survival and DNA-rejoining kinetics for HSGc-C5 cells.
The amount of potentially lethal damage repair (PLDR) is a significant factor in the process of modeling the survival curves of cells irradiated with fractionated carbon beams. Because the amount of ...PLDR generally depends on the features of the cells and the linear energy transfer (LET), the amount of PLDR of cells irradiated with fractionated carbon beams shows distinct differences from that of cells irradiated with X-rays. This study considered a new parameter dependent on the correlation between the PLDR trait (
T
) of the cells over a time interval (Δ) at the fractionated carbon beam irradiation. The survival curves of the cells irradiated with fractionated carbon beams n times were predicted using the
ζ
and the Ψ values from the delay assay. This study aims to overcome the barriers of traditional methods by developing a new survival curve model with new parameters based on an analysis of the PLDR traits of cells over time interval in fractionated carbon beam irradiation and to suggest a model that produces results significantly closer to the experimental data.
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