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Background: The Consultation and Relational Empathy (CARE) measure is a patient-reported measure of physician empathy which is widely used internationally. The Japanese version of the CARE measure has very high internal reliability, suggesting that a shorter version may have adequate validity and reliability., Objective: To investigate a valid shorter version of the Japanese CARE measure., Methods: We conducted a pilot study using secondary analysis of previous data obtained from 9 general practitioners and 252 patients and used to develop the Japanese CARE measure. All 1,023 possible combinations of the Japanese CARE items (n = 1-10) were candidates for the short measure. The internal consistency (Cronbach's alpha) and the correlations between candidate short questionnaires and the original questionnaire were calculated. After selecting the most valid short questionnaire, inter-rater reliability was determined using generalizability theory, and construct validity (Spearman's rho) was determined using patient satisfaction., Results: Two items were selected for a pilot shorter version: item 6 "Showing care and compassion" and item 9 "Helping you to take control." These showed high internal consistency and correlations with the 10-item measure (Cronbach's alpha = 0.920, correlation = 0.979). Forty-five questionnaires per doctor allowed us to reliably differentiate between practitioners. The construct validity for the pilot short measure was high (Spearman's rho 0.706, P < 0.001)., Conclusion: We generated a pilot 2-item version of the Japanese CARE measure. This pilot 2-item version provides a basis for future validation studies of short CARE measures in other languages., (© The Author(s) 2022. Published by Oxford University Press.)

Biogenesis of ribosomal subunits involves enzymatic modifications of rRNA that fine-tune functionally important regions. The universally conserved prokaryotic dimethyltransferase KsgA sequentially modifies two universally conserved adenosine residues in helix 45 of the small ribosomal subunit rRNA, which is in proximity of the decoding site. Here we present the cryo-EM structure of Escherichia coli KsgA bound to an E. coli 30S at a resolution of 3.1 Å. The high-resolution structure reveals how KsgA recognizes immature rRNA and binds helix 45 in a conformation where one of the substrate nucleotides is flipped-out into the active site. We suggest that successive processing of two adjacent nucleotides involves base-flipping of the rRNA, which allows modification of the second substrate nucleotide without dissociation of the enzyme. Since KsgA is homologous to the essential eukaryotic methyltransferase Dim1 involved in 40S maturation, these results have also implications for understanding eukaryotic ribosome maturation., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objectives: This study aimed to search for scientific evidence concerning the accuracy of computer-assisted analysis for diagnosing maxillofacial radiolucent lesions., Methods: A systematic review was conducted according to the statements of Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols and considering 10 databases, including the gray literature. Protocol was registered at the International Prospective Register of Systematic Reviews (CRD42018089945). The population, intervention, comparison and outcome strategy was used to define the eligibility criteria and only diagnostic test studies were included. Their risk of bias was assessed by the Joanna Briggs Institute Critical Appraisal tool. Random-effects model meta-analysis was performed and heterogeneity among the included studies was estimated using the I 2 statistic. The grade of recommendation, assessment, development, and evaluation (GRADE) tool assessed the quality of evidence and strength of recommendation across included studies., Results: Out of 715 identified citations, four papers, published between 2009 and 2017, fulfilled the criteria and were included in this systematic review. A total of 191 lesions, classified as periapical granuloma and cyst, dentigerous cyst or keratocystic odontogenic tumor, were analyzed. All selected articles scored low risk of bias. The pooled accuracy estimation, regardless of the classification method used, was 88.75% (95% CI = 85.19-92.30). Heterogeneity test reached moderate values (I 2 = 57.89%). According to the GRADE tool, the analyzed outcome was classified as having low level of certainty., Conclusions: The overall evaluation showed all studies presented high accuracy rates of computer-aided diagnosis systems in classifying radiolucent maxillofacial lesions compared to histopathological biopsy. However, due to the moderate heterogeneity found among the studies included in this meta-analysis, a pragmatic recommendation about the use of computer-assisted analysis is not possible.

Polymicrogyria is a malformation of cortical development. The aetiology of polymicrogyria remains poorly understood. Using whole-exome sequencing we found de novo heterozygous missense GRIN1 mutations in 2 of 57 parent-offspring trios with polymicrogyria. We found nine further de novo missense GRIN1 mutations in additional cortical malformation patients. Shared features in the patients were extensive bilateral polymicrogyria associated with severe developmental delay, postnatal microcephaly, cortical visual impairment and intractable epilepsy. GRIN1 encodes GluN1, the essential subunit of the N-methyl-d-aspartate receptor. The polymicrogyria-associated GRIN1 mutations tended to cluster in the S2 region (part of the ligand-binding domain of GluN1) or the adjacent M3 helix. These regions are rarely mutated in the normal population or in GRIN1 patients without polymicrogyria. Using two-electrode and whole-cell voltage-clamp analysis, we showed that the polymicrogyria-associated GRIN1 mutations significantly alter the in vitro activity of the receptor. Three of the mutations increased agonist potency while one reduced proton inhibition of the receptor. These results are striking because previous GRIN1 mutations have generally caused loss of function, and because N-methyl-d-aspartate receptor agonists have been used for many years to generate animal models of polymicrogyria. Overall, our results expand the phenotypic spectrum associated with GRIN1 mutations and highlight the important role of N-methyl-d-aspartate receptor signalling in the pathogenesis of polymicrogyria.

Aminoacyl-tRNA synthetases (aaRS) are essential enzymes catalyzing the formation of aminoacyl-tRNAs, the immediate precursors for encoded peptides in ribosomal protein synthesis. Previous studies have suggested a link between tRNA aminoacylation and high-molecular-weight cellular complexes such as the cytoskeleton or ribosomes. However, the structural basis of these interactions and potential mechanistic implications are not well understood. To biochemically characterize these interactions we have used a system of two interacting archaeal aaRSs: an atypical methanogenic-type seryl-tRNA synthetase and an archaeal ArgRS. More specifically, we have shown by thermophoresis and surface plasmon resonance that these two aaRSs bind to the large ribosomal subunit with micromolar affinities. We have identified the L7/L12 stalk and the proteins located near the stalk base as the main sites for aaRS binding. Finally, we have performed a bioinformatics analysis of synonymous codons in the Methanothermobacter thermautotrophicus genome that supports a mechanism in which the deacylated tRNAs may be recharged by aaRSs bound to the ribosome and reused at the next occurrence of a codon encoding the same amino acid. These results suggest a mechanism of tRNA recycling in which aaRSs associate with the L7/L12 stalk region to recapture the tRNAs released from the preceding ribosome in polysomes.

Background: Empathy is an important attribute in medicine, influencing both the process and outcome of consultations. However, there are no validated tools available in Japan to gather patient feedback on physicians' empathy. The Consultation and Relational Empathy (CARE) Measure developed in the UK is widely used internationally., Objectives: To investigate the psychometric properties of a Japanese version of the CARE Measure., Method: Following two cycles of translation and back translation, the Japanese CARE Measure was completed by 317 patients in a primary medical care clinic in Japan. Tests of internal reliability and validity included Cronbach's alpha, item-total correlations and factor analysis. Predicted associations between CARE Measure score and other variables were assessed by Spearman's rho., Results: Low numbers of missing values (8.2-9.8%) and 'not applicable' responses (0-1.3%) suggested high acceptability and face validity of the Japanese CARE Measure. Internal reliability was high (Cronbach's alpha 0.984) and was reduced by the removal of any of 10 items. High corrected item-total correlations (0.897-0.946) suggested homogeneity. Factor analysis showed a single solution with high item loadings (0.917-0.957). Construct validity was supported by a significant relationship (Spearman's rho 0.74, P < 0.001) with overall satisfaction with the consultation., Conclusion: The Japanese CARE Measure appears to be valid and reliable in a primary medical care setting. Further work is required to determine its ability to discriminate between doctors.

A web-based computed tomography (CT) dose calculation system (WAZA-ARI) is being developed based on the modern techniques for the radiation transport simulation and for software implementation. Dose coefficients were calculated in a voxel-type Japanese adult male phantom (JM phantom), using the Particle and Heavy Ion Transport code System. In the Monte Carlo simulation, the phantom was irradiated with a 5-mm-thick, fan-shaped photon beam rotating in a plane normal to the body axis. The dose coefficients were integrated into the system, which runs as Java servlets within Apache Tomcat. Output of WAZA-ARI for GE LightSpeed 16 was compared with the dose values calculated similarly using MIRD and ICRP Adult Male phantoms. There are some differences due to the phantom configuration, demonstrating the significance of the dose calculation with appropriate phantoms. While the dose coefficients are currently available only for limited CT scanner models and scanning options, WAZA-ARI will be a useful tool in clinical practice when development is finalised.

A nationwide survey was conducted in Japan on paediatric CT among children of public health and school nurses to examine a possibility for a follow-up study on radiation effects. A survey questionnaire was sent out to 3173 public primary and junior high schools and 317 public health centres during October to December in 2009. According to the collected responses, 410 (16.2 %) children received the CT scans and the total number of CT scans was 585. Most of respondents expressed a high interest in radiation health effects and an intent to participate in the epidemiological study that will follow-up the health conditions of children. This study provides information to discuss the feasibility of the epidemiological study on health effects in children who received CT scans.

A web-based dose computation system, WAZA-ARI, is being developed for patients undergoing X-ray CT examinations. The system is implemented in Java on a Linux server running Apache Tomcat. Users choose scanning options and input parameters via a web browser over the Internet. Dose coefficients, which were calculated in a Japanese adult male phantom (JM phantom) are called upon user request and are summed over the scan range specified by the user to estimate a normalised dose. Tissue doses are finally computed based on the radiographic exposure (mA s) and the pitch factor. While dose coefficients are currently available only for limited CT scanner models, the system has achieved a high degree of flexibility and scalability without the use of commercial software.

When normal human fibroblast cells (MRC-5) received a priming irradiation of 3-20 mGy 4 h prior to irradiation with 1000 mGy, the number of DNA double-stranded breaks (DSBs) decreased significantly to 18.2-18.7 per cell compared with 21 per cell when there was no priming irradiation. This result indicates that a priming irradiation of 3-20 mGy induces a radioadaptive response in MRC-5. The authors' previous study had indicated that DSBs induced by ≤ 20 mGy are due to a radiation-induced bystander effect. These findings suggest that radiation-induced bystander effects might contribute to induction of the radioadaptive response. To test this hypothesis, MRC-5 were suspended in lindane, an inhibitor of radiation-induced bystander effects, which was added to the medium for the priming irradiation of 3-20 mGy. Lindane inhibited the protective effect of priming irradiation on DSBs caused by subsequent irradiation with 1000 mGy. Thus, radiation-induced bystander effects may play a role in radioadaptive responses.

A web system of WAZA-ARI is being developed to assess radiation dose to a patient in a computed tomography examination. WAZA-ARI uses one of organ dose data sets corresponding to the options selected by a user to describe examination conditions. The organ dose data have been derived by the Particle and Heavy Ion Transport code system, combined with Japanese male (JM) phantom. The configuration of JM phantom is adjusted to the averaged JM adult. In addition, a new phantom is introduced by removing arms from JM phantom to take into account for dose calculations in torso examinations. Some of the organ doses by JM phantom without arms are compared with results obtained by using a MIRD-type phantom, which was applied in some previous dosimetry systems.

Medical procedures denoted as interventional radiology require operation near an X ray beam, which brings high dose exposures to the operators' hands. For the effectual control of their extremity doses, a prototype of a real-time wrist dosemeter has been developed, hand dose monitor (HDM), based on a single silicon detector. Experiments were performed to test its response to diagnostic X rays. The HDM was highly sensitive and showed a linear response down to doses of a few tens of microsieverts. Though dose rate, energy and angular dependence of the response were observed in some extreme conditions, the HDM was proved to be of practical use if it was appropriately calibrated. Since an HDM enables personnel to check their hand doses on a real-time basis, it would enable medical staff to control the exposure themselves.

Murine acute myeloid leukemia is characterized by chromosome 2 aberrations, and genesis of the marker chromosome 2 by radiation is suspected to be an initiating event of radiation leukemogenesis. A detailed analysis of the type and frequency of chromosome 2 aberrations in murine bone marrow cells at an early stage after irradiation is provided here. A total of 40 male C3H/He mice was exposed to 137Cs gamma-ray at a dose of 1, 2 or 3 Gy, and sacrificed 24 hours after irradiation. Metaphase samples prepared from bone marrow cells were Q-banded for karyotyping or painted with DNA probes specific to chromosome 2. In 5 mice analyzed by karyotyping, one mouse showed high frequency of the marker aberrations as well as other chromosome 2 aberrations. Chromosome painting analysis for the rest of the mice also detected 3 animals showing significantly high frequencies of chromosome 2 aberrations. Dose-dependence of the frequencies was observed even among those mice that tended to be sensitive. The results indicated that there was a subgroup of mice carrying hypersensitive chromosome 2. The subgroup could be leukemia-sensitive if radiation-induced chromosome aberrations are responsible for an early change in myeloid leukemogenesis.