Dioctatin Activates ClpP to Degrade Mitochondrial Components and Inhibits Aflatoxin Production.

Aflatoxin contamination of crops is a serious problem worldwide. Utilization of aflatoxin production inhibitors is attractive, as the elucidation of their modes of action contributes to clarifying the mechanism of aflatoxin production. Here, we identified mitochondrial protease ClpP as the target of dioctatin, an inhibitor of aflatoxin production of Aspergillus flavus. Dioctatin conferred uncontrolled caseinolytic capacity on ClpP of A. flavus and Escherichia coli. Dioctatin-bound ClpP selectively degraded mitochondrial energy-related proteins in vitro, including a subunit of respiratory chain complex V, which was also reduced by dioctatin in a ClpP-dependent manner in vivo. Dioctatin enhanced glycolysis and alcohol fermentation while reducing tricarboxylic acid cycle metabolites. These disturbances were accompanied by reduced histone acetylation and reduced expression of aflatoxin biosynthetic genes. Our results suggest that dioctatin inhibits aflatoxin production by inducing ClpP-mediated degradation of mitochondrial energy-related components, and that mitochondrial energy metabolism functions as a key determinant of aflatoxin production.

Proposed diagnostic reference levels for general radiography and mammography in Japan.

Diagnostic reference levels (DRLs 2015) in Japan were first published in 2017, on the Japan Network for Research and Information on Medical Exposures network. Medical facilities in Japan are now presumably reconsidering radiation doses at their facilities and approaching protection optimisation through the application of DRLs 2015. However, since more than 3 years have elapsed since publication, radiation doses received by patients in Japan may have diverged from DRLs 2015. We therefore undertook the present study. Based on our questionnaire survey implemented in 2017, we estimated the entrance skin dose (ESD) under general radiography fields and the mean glandular dose (MGD) under mammography, to compile a report on the doses received by patients under general radiography fields and mammography, and to propose new DRLs as replacements for DRLs 2015. Radiation doses under general radiography fields and mammography were estimated from the results of the 2017 questionnaire survey and applied to determine new DRLs at 75% values of dose distributions in general radiography fields and at 95% values of dose distributions in mammography. Among all the modes for general radiography fields and mammography, median ESD and MGD were significantly smaller with flat panel detector systems than with computed radiography systems. Comparison of the results with DRLs 2015 values showed a trend toward decreases in all imaging methods of the general radiography fields and mammography ranging from 5.0% (child chest radiography) to 31.7% (skull radiography). Moreover, responses showed that DRLs 2015 were recognised and used for comparison at many facilities. We have described the doses received by patients in general radiography fields and mammography in 2017 and proposed new DRLs as replacements for DRLs 2015. The DRLs we proposed for general radiography fields and mammography were determined to be lower than DRLs 2015 for all modes.

Consideration of diagnostic reference levels for pediatric chest X-ray examinations.

The use of diagnostic reference levels (DRLs) is currently recommended, and dose evaluation is considered to be important for establishing a Japanese radiological protection system in radiological medicine. Children, in particular, are sensitive to radiation, and their exposure levels must be taken into account. The DRL for the entrance surface dose (ESD) used in pediatric chest X-ray examinations in Japan is 0.2 mGy. However, the bodies of infants and young children show major changes with rapidly developing organs. Thus, the possibility that organ development may also be affected by radiation exposure should be taken into account. Therefore, radiological technologists must be conservative in setting radiographic conditions for pediatric examinations. The objective of this study was to evaluate the doses used in pediatric chest X-ray examinations at our hospital and compare them with the current DRLs, considering the assumption that setting conditions individually for different ages and subject thicknesses and performing more detailed dose evaluations will help reduce radiation exposure. The study was carried out to estimate the ESDs in 163 pediatric patients who underwent frontal or lateral chest X-ray examinations at our hospital. All doses were lower than 0.2 mGy, the dose recommended in the Japanese DRLs 2015. The doses showed a strong correlation with age, but a weaker correlation with subject thickness. These results suggest that instead of considering a common DRL for all children, the DRL should be evaluated on the basis of age.

PROPOSAL FOR LOCAL DIAGNOSTIC REFERENCE LEVELS IN GENERAL RADIOGRAPHY IN JAPAN.

The present study aimed to propose local diagnostic reference levels (DRLs) formulated by calculating entrance surface doses for general radiography at 20 facilities of Aichi prefecture in Japan, by comparing these values with DRLs established in Japan in 2015 (DRLs 2015) and assessing radiation dose differences among facilities. X-ray outputs (half-value layer and air kerma) of each facility were measured with a non-invasive type of detector. The results were employed to formulate local DRLs based on the 75th percentiles of dose distributions. These local DRLs were lower than the DRLs 2015 for all examinations. If proposed local DRLs from other 46 prefectures can be collected, this paper can be used to benefit the next effort to draft better DRL for Japan.

[Evaluation of Entrance Surface Dose in Chest Radiography Using Clinical Images: Estimation of Subject Thickness Using Two-direction Radiography].

The International Commission on Radiological Protection recommends adaptation of the diagnostic reference levels as an indicator of optimization of protection, and diagnostic reference levels of 2015 were also published in Japan in 2015 (Japan DRLs 2015). The entrance surface dose (ESD) is evaluated to the published standard subject thickness in Japan DRLs 2015. However, the standard radiographic settings of each facility may not be a radiographic condition of the standard subject thickness of Japan DRLs 2015. We measure and record the thickness of the subject in every examination, and it can solve this problem, but it is difficult to carry out it in the actual clinical scene. In this study, we aimed to estimate the subject thickness by using chest clinical images and to calculate ESD for each radiography. We evaluated and compared with Japan DRLs 2015 using these data. The subject thickness was estimated from 200 cases of digital imaging and communications in medicine (DICOM) image obtained by both the frontal and lateral views of the chest radiography. Also, at the same time, the radiographic settings were acquired from the information of the DICOM tag. The subject thickness was 23.60 cm on the average, and the median of the ESD was 0.104 mGy. Also, the median of the ESD at the standard subject thickness of 20 cm in Japan DRLs 2015 was 0.075 mGy. The ESD can be calculated without measuring the body thickness of the patient of every examination by using the method of this study.

Evaluation of the Patient Exposure in General Radiography for Some Facilities: Comparison with DRL and Evaluation of the Difference among Facilities.

The first diagnostic reference levels (DRLs 2015) in Japan were published in June 2015. The purpose of this study was to compare the calculated entrance surface doses with the values of DRLs 2015, and evaluate differences in patient exposure among facilities. Semiconductor dosimeter was installed, and dosimetry was performed using equipment and radiographic condition of each facility. As a result, a dose higher than the value of DRLs 2015 was used in 12 kinds of examination. In child chest examination, the doses of the three facilities (0.26 mGy, 0.28 mGy, 0.60 mGy) exceeded the value of DRLs 2015 (0.2 mGy). Review of the radiographic condition is necessary because the doses exceeding DRLs 2015 tended to have a high current time product. The examination with the largest difference between facilities was the lateral of thoracic spine, with a difference of about 46 times, and the examination with the smallest difference was the ankle joint, with a difference of about three times. When reviewing, it is necessary to focus mainly on examinations that have a large difference between facilities. In the future, it can be said that it is necessary to set diagnostic reference range (DRR) or achievable dose (AD) to understand how high or low dose of the own facility are compared with facilities nationwide.

[Derivation of the optimum exposure condition for Guthmann-method by the fuzzy measure theory].

The purpose of this study is to decide the optimum exposure condition of Guthmann-method by the fuzzy measure theory. The samples for the fuzzy measure theory were created using the pelvis-phantom irradiated with various tube voltages (90-120 kV) and additional filters (0.5 mmAl+0.05 mmCu, 0.5 mmAl+0.1 mmCu). And we selected 6 samples on each exposure condition. The measuring points of Guthmann-method were specified as primary objective points. Sharpness, graininess and contrast were evaluated in each point. The fuzzy numerical integration was calculated with the rating score of each quality factor and the fuzzy measure. We set threshold to the fuzzy numerical integration and extracted the threshold sample which was able to visually recognize the measuring points on each exposure condition. We selected a sample which had the lowest entrance surface dose in the extracted images. And the exposure condition of this sample (110 kV, 5 mAs, 0.5 mmAl+0.05 mmCu) was adopted. The visual evaluation using the fuzzy measure theory may be useful as an examination method of the exposure condition for Guthmann-method.