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In cases of radiological accidents, especially for victims exposed to high-dose total-body irradiation (TBI), the administration of appropriate approved hematopoietic drugs is the most rapid medical treatment for preventing severe acute radiation syndrome, which is associated with a high mortality rate. However, at present, there are few suitable pharmaceutical drugs available in Japan, aside from granulocyte colony-stimulating factor (G-CSF). Depending on the situation surrounding the accident, various drug treatment options and the development of effective drug therapies may be required. In the present study, we assessed various combinations of seven commercially available drugs-G-CSF, erythropoietin (EPO), romiplostim (RP), ancer (AN), cepharanthine (CE), leucon (LC) and leukoprol (LP)-in mice exposed to a lethal dose of 7 or 8 Gy of X-ray irradiation. Each drug was administered as a single or mixed intraperitoneal injection once or twice daily for three consecutive days. The single administration of the approved hematopoietic drugs CE, LC, or LP twice a day for 3 days significantly improved the 30-day survival rate of lethal TBI mice (p less than 0.05; 75%, 100%, or 100%, respectively) compared with the untreated TBI mice, accompanied by a gradual increase in the body weight. Furthermore, the combined administration of RP, EPO and G-CSF or single administration of RP alone gradually increased the body weight of mice exposed to lethal TBI, with 30-day survival rates of 75% or 100%, respectively (p less than 0.05). This study suggested that some new domestically approved hematopoietic drugs may have radiomitigative potential for mice exposed to lethal TBI, and the 12-h interval administration of LC or LP for 3 days to 7-Gy-TBI mice and 12-h interval administration of RP alone for 3 days to 8-Gy-TBI mice were the most suitable medications with respect to the 30-day survival rate. As long as the threat of nuclear disaster exists, diverse efforts in thefield of radiation emergency medicine, including the development of effective drug therapies, will be necessary.

Immune effector cell-associated neurotoxicity syndrome usually occurs within the first four weeks of chimeric antigen receptor (CAR)-T cell therapy. In addition, prolonged cytopenia is a long-term adverse effect following the use of CAR T-cell therapies. Here, we present a case of prolonged severe cytopenia followed by fatal CAR T-cell-mediated encephalitis. A 22-year-old male patient was referred to our hospital for a second relapse of B-cell precursor acute lymphoblastic leukemia (ALL), which was diagnosed 22 months after hematopoietic stem cell transplantation from an unrelated donor. CAR T-cells (tisagenlecleucel) were infused during the third cycle of complete remission after chemotherapy. The patient developed grade 2 cytokine release syndrome requiring a single dose of tocilizumab. Cytopenia was profound from day 30 onward, but no other serious complications were observed. On day 50, the patient developed sensory impairment, disturbing behavior, and confusion. Brain magnetic resonance imaging (MRI) scan and cerebrospinal fluid (CSF) analysis revealed no pathological findings. Severe neutropenia persisted despite G-CSF treatment, and the patient's neurological symptoms rapidly progressed from day 65. Brain MRI revealed hydrocephalus. The CSF showed elevated xanthochromia, mononuclear cell counts, and protein levels. A therapeutic attempt with prednisolone for encephalitis was ineffective, and the patient died on day 77 owing to neurological toxicity. Late-onset CAR T-cell-mediated encephalitis was suspected, although the CSF was not assessed for CAR T-cells. In addition, the patient developed prolonged and severe cytopenia. To the best of our knowledge, this is the first report of prolonged severe cytopenia followed by late-onset CAR T-cell-mediated encephalitis. These unexpected long-term adverse effects may occur and should also be considered., Competing Interests: The authors declare no conflict of interest. Disclosure forms provided by the authors are available on the website., (Copyright Ⓒ2024 Asia-Pacific Blood and Marrow Transplantation Group (APBMT).)

The prognosis of patients with osteosarcoma who experience recurrence or progression (R/P) is extremely poor, and more effective and less toxic therapies are needed. In the current study, the clinical data of osteosarcoma patients who experienced R/P were retrospectively analyzed to verify the reliability of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression or MGMT promoter methylation for predicting the response to off-label temozolomide (TMZ)-containing chemotherapy. Of the 30 evaluable patients, 9 (30%) showed no/low MGMT protein expression, whereas all 16 evaluable patients had unmethylated MGMT promoter irrespective of MGMT protein expression levels. Twenty-three patients received TMZ-containing chemotherapy for measurable lesions (n = 14) or as adjuvant therapy following resection of recurrent lesions (n = 9). Among 14 patients with radiologically measurable lesions, the objective response rate was higher in the MGMT no/low-expression group (50.0%) than in the MGMT intermediate/high-expression group with borderline significance (0%, p = 0.066). The 6-month progression-free survival (PFS) rate in patients with radiologically measurable lesions was significantly higher in the MGMT no/low-expression group (50.0%) than in the MGMT intermediate/high-expression group (0%, p = 0.036). In the multivariate analysis of the 23 patients receiving TMZ-containing chemotherapy, MGMT expression and disease status before TMZ-containing chemotherapy were significantly associated with PFS. No severe adverse effects were observed during TMZ-containing chemotherapy. MGMT protein expression, but not MGMT promoter methylation, could predict a favorable outcome in patients receiving TMZ-containing chemotherapy., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Coronavirus disease 2019 (COVID-19) is characterized by high interleukin-6 levels. Clinical data supporting tocilizumab, a monoclonal antibody that targets interleukin-6 receptor-alpha, for treating Japanese patients with severe COVID-19 pneumonia are needed., Methods: This single-arm phase 3 study investigated tocilizumab (8 mg/kg) plus standard of care (SOC) in Japanese patients hospitalized with severe COVID-19 pneumonia. Clinical status was assessed using a 7-category ordinal scale on day 28 (primary endpoint) and day 14 (secondary endpoint). Other secondary endpoints were time to improvement (≥2 category improvement) and time to hospital discharge. Safety was assessed as the incidence of adverse events (AEs)., Results: Among 48 patients enrolled, 44 (91.7 %) scored ≥3 on the 7-category ordinal scale at baseline. At day 28, 35 patients (72.9 %) scored 1 and 5 (10.4 %) scored 7 on the 7-category ordinal scale; 36 (75.0 %, 95 % confidence interval [CI]: 60.40 %-86.36 %) and 39 (81.3 %, 95 % CI: 67.37 %-91.05 %) patients achieved ≥2- and ≥1-category improvement, respectively; 6 patients (12.5 %, 95 % CI: 4.73 %-25.25 %) demonstrated ≥1-category worsening. At day 14, 25 (52.1 %, 95 % CI: 37.19 %-66.71 %) and 33 patients (68.8 %, 95 % CI: 53.75 %-81.34 %) achieved ≥2- and ≥1-category improvement, respectively; 5 patients (10.4 %, 95 % CI: 3.47 %-22.66 %) demonstrated ≥1-category worsening. Median times (95 % CI) to improvement and hospital discharge were 11 (9-15) and 15 (11-18) days, respectively. Forty patients (83.3 %) experienced AEs; the incidence of ≥grade 3 AEs was 25 %., Conclusion: Tocilizumab plus SOC may provide improved clinical status in Japanese patients with severe COVID-19 pneumonia; no new safety signals were identified., Competing Interests: Declaration of competing interest AH discloses consulting fees from Chugai Pharmaceutical Co. Ltd and Kowa Company Ltd. MY, NO, YK, and NM disclose research grants from Chugai Pharmaceutical Co. Ltd. MY and YK provided honoraria lectures for Chugai Pharmaceutical Co. Ltd. NM provided honoraria lectures for MSD, Shionogi Inc., Asahi Kasei Pharma, and Zeria Pharmaceutical Co., Ltd. NK, RS, and RO are employees of Chugai Pharmaceutical Co. Ltd. TN discloses consulting fees from Chugai Pharmaceutical Co. Ltd and research grants from Chugai Pharmaceutical Co. Ltd, Eli Lilly Japan K.K., and Shionogi & Co., Ltd, and provided honoraria lectures for Chugai Pharmaceutical Co. Ltd, Eli Lilly Japan K.K., AstraZeneca K.K., GlaxoSmithKline Plc, and Pfizer Japan Inc., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

[Purpose] In Japan, one measure against the novel coronavirus disease-2019 infection involves the public use of surgical masks. Research indicates that exercising while wearing a mask increases the physical burden, particularly affecting young people during high-intensity exercise. This study examined the effects of wearing masks while running in male university students. [Participants and Methods] The participants were 20 healthy male university students (21.6 ± 1.6 years). The participants underwent cardiopulmonary exercise tests with the masks on and off on different days until exhaustion. The following parameters were measured: exercise duration, Borg Scale rating (respiratory or lower extremities), surface temperature around the mouth, time to sweat onset, metabolic reaction, pulmonary ventilation, and cardiovascular reaction parameters. [Results] The results showed that VO 2 max remained consistent between the mask-on and mask-off conditions. However, minute ventilation, respiratory rate, and heart rate decreased in the mask-on condition, which correlated with a reduction in exercise duration. Furthermore, running with the mask significantly decreased the VE/VO 2 , VE/ VO 2 , Borg Scale rating of the lower extremities, and the time to sweat onset. [Conclusion] Running with a surgical mask affected respiratory function and decreased exercise duration in healthy male university students. However, it did not induce any changes in VO 2 max., Competing Interests: The authors declare no conflict of interest., (2024©by the Society of Physical Therapy Science. Published by IPEC Inc.)

A new technique for ex situ solid-state nuclear magnetic resonance imaging of polymeric films has been developed. This method uses the static magnetic field gradient generated by a water-cooled copper electromagnet. The imaging process involves scanning the sample in the plane of the film under a static magnetic field gradient. Two-dimensional (2D) 19F MRI measurements are attempted, where the fast Fourier transform (FFT) spectra of the second half of a Hahn echo peak is used for the depth (X-axis) direction, and the sample film is mechanically moved for the Y-axis, which is in-plane with respect to the film surface and normal to the inter-magnetic-pole line (Z-axis). The sample is a poly(tetrafluoroethylene) [PTFE] film with carved stripes on its surface. Furthermore, three-dimensional (3D) measurements of the film surface and thickness orientations were also performed for an analogous PTFE film. For 2D profiling on the film surface, 2D sample-moving was used. For depth profiling, FFT spectrum analysis was undertaken for each voxel situated at a specific (Y, Z) coordinate within the film. As a result, a 3D image of the sample and its corresponding geometry were obtained, although the scanning area was restricted to a part of the sample. Finally, numerical simulations of the spatial distribution of the static magnetic field were performed to confirm the validity of the present method., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Introduction: The current study investigated the relationship between the characteristics of a darts game, including the throwing motion toward a target, and mild cognitive impairment (MCI). To this end, we examined the associations between cognitive function and mental health, and the shift in center of gravity while throwing darts. In a preliminary investigation, a 1-month dart game intervention was conducted among older individuals living in the community. The participants were divided into the non-MCI and MCI groups, and the relationship between center of gravity movement during throwing and the presence of dementia was examined., Methods: The intervention lasted for 1 month and was tested on healthy older individuals (aged ≥ 65 years) recruited from the community. The Japanese version of the Montreal Cognitive Assessment and the Trail Making Test was used to assess cognitive function. Mental health was evaluated using the Kessler Psychological Distress Scale and the Subjective Well-being Inventory. The center of pressure was analyzed to determine the center of gravity shift during dart throwing., Results: The analysis of factors influencing the determination of the MCI score during the intervention revealed a tendency for the center of gravity shift to be associated as a protective factor in the non-MCI group, although this association did not reach statistical significance (odds ratio = 0.942, p  = 0.084). In the MCI group, a significant effect of age was observed in the MCI score (odds ratio = 1.539, p  = 0.007)., Conclusion: The current findings suggest that conducting center of gravity shift testing could potentially provide a helpful tool for predicting early decline in cognitive function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Kawabata, Iida, Kunishige, Fukuda, Miyaguchi and Harada.)

Importance: Recent evidence indicates the efficacy of β-amyloid immunotherapy for the treatment of Alzheimer disease, highlighting the need to promote β-amyloid removal from the brain. Cilostazol, a selective type 3 phosphodiesterase inhibitor, promotes such clearance by facilitating intramural periarterial drainage., Objective: To determine the safety and efficacy of cilostazol in mild cognitive impairment., Design, Setting, and Participants: The COMCID trial (A Trial of Cilostazol for Prevention of Conversion from Mild Cognitive Impairment to Dementia) was an investigator-initiated, double-blind, phase 2 randomized clinical trial. Adult participants were registered between May 25, 2015, and March 31, 2018, and received placebo or cilostazol for up to 96 weeks. Participants were treated in the National Cerebral and Cardiovascular Center and 14 other regional core hospitals in Japan. Patients with mild cognitive impairment with Mini-Mental State Examination (MMSE) scores of 22 to 28 points (on a scale of 0 to 30, with lower scores indicating greater cognitive impairment) and Clinical Dementia Rating scores of 0.5 points (on a scale of 0, 0.5, 1, 2, and 3, with higher scores indicating more severe dementia) were enrolled. The data were analyzed from May 1, 2020, to December 1, 2020., Interventions: The participants were treated with placebo, 1 tablet twice daily, or cilostazol, 50 mg twice daily, for up to 96 weeks., Main Outcomes and Measures: The primary end point was the change in the total MMSE score from baseline to the final observation. Safety analyses included all adverse events., Results: The full analysis set included 159 patients (66 [41.5%] male; mean [SD] age, 75.6 [5.2] years) who received placebo or cilostazol at least once. There was no statistically significant difference between the placebo and cilostazol groups for the primary outcome. The least-squares mean (SE) changes in the MMSE scores among patients receiving placebo were -0.1 (0.3) at the 24-week visit, -0.8 (0.3) at 48 weeks, -1.2 (0.4) at 72 weeks, and -1.3 (0.4) at 96 weeks. Among those receiving cilostazol, the least-squares mean (SE) changes in MMSE scores were -0.6 (0.3) at 24 weeks, -1.0 (0.3) at 48 weeks, -1.1 (0.4) at 72 weeks, and -1.8 (0.4) at 96 weeks. Two patients (2.5%) in the placebo group and 3 patients (3.8%) in the cilostazol group withdrew owing to adverse effects. There was 1 case of subdural hematoma in the cilostazol group, which may have been related to the cilostazol treatment; the patient was successfully treated surgically., Conclusions and Relevance: In this randomized clinical trial, cilostazol was well tolerated, although it did not prevent cognitive decline. The efficacy of cilostazol should be tested in future trials., Trial Registration: ClinicalTrials.gov Identifier: NCT02491268.

Pediatric colorectal cancer (CRC) is extremely rare, with little information about genetic profiles compared with adult CRC. Here, a 13-year-old male with advanced CRC underwent cancer gene panel testing, which detected 4 genetic abnormalities ( MET amplification in addition to TP53 , SMAD4 , and CTNNA1 mutations) that might be associated with a poor prognosis. Based on high-level MET amplification, he received a multikinase inhibitor, cabozantinib, after failure of first-line and second-line chemotherapy, resulting in transient disease stabilization. Tailored targeted therapy based on molecular profiling can be an effective treatment strategy for rare cancers such as pediatric CRC., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aims/introduction: It remains to be fully elucidated whether nutrition education by dietitians can lead to specific positive changes in the food choices of patients with diabetes., Materials and Methods: A total of 96 patients with type 2 diabetes and diabetic kidney disease were randomly assigned to the intensive intervention group that received nutritional education at every outpatient visit and the control group that received nutritional education once a year. The total energy intake, energy-providing nutrients and 18 food groups were analyzed at baseline, and 1 and 2 years after the intervention in 87 patients. Furthermore, the relationship between the changes in hemoglobin A1c, body composition and changes in the total energy or energy-producing nutrient intake was analyzed in 48 patients who did not use or change hypoglycemic agents during the study period., Results: The total energy intake, carbohydrates, cereals, confections, nuts and seeds, and seasonings significantly decreased, and fish and shellfish intake significantly increased during the study period in the intensive intervention group, whereas these changes were not observed in the control group. The decrease in the total energy intake and carbohydrates after 2 years was significantly greater in the intensive intervention group than in the control group. The change in the total energy and carbohydrate intake showed a significant positive correlation with that in muscle mass. The multivariate analysis showed that the decrease in total energy intake was independently associated with that in muscle mass., Conclusion: Dietitian-supported intensive dietary intervention helps improve the diet of patients with type 2 diabetes., (© 2022 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare pediatric brain tumor with abnormalities in SMARCB1 located in 22q11.2. We report a case of AT/RT associated with Phelan-McDermid syndrome (PMS) characterized by congenital developmental disorder, mental retardation, and ring chromosome 22 with 22q13.3-qter depletion, for which we performed whole-genome sequencing (WGS). A 4-year-old girl with a developmental disability was referred to our hospital due to dysphoria. Brain magnetic resonance imaging showed a 5-cm well-demarcated mass that extended bilaterally in the frontal lobes. G-banding was performed preoperatively due to a history of developmental retardation. Ring chromosome 22 and deletion of 22q13.3-qter were observed, and she was diagnosed with PMS. She underwent gross total resection of the tumor, and the pathological diagnosis was AT/RT. WGS showed somatic SMARCB1 mutation (p.R201X) and somatic loss of the entire chromosome 22 in the tumor, but not in the blood sample. WGS confirmed previously unreported BRCA2 mutations, 6q loss, and 14q acquisition during tumor progression, but no other significant findings associated with tumor progression. The present case is discussed with reference to a systematic review of previous reports of AT/RT associated with PMS. PMS patients with ring chromosome 22 should be carefully followed up for AT/RT occurrence., (© 2022. The Author(s), under exclusive licence to The Japan Society of Brain Tumor Pathology.)

Aims/introduction: This randomized controlled trial aimed to determine whether frequent nutritional education improves the clinical parameters associated with the onset and progression of diabetic kidney disease in type 2 diabetes mellitus patients., Materials and Methods: A total of 96 patients with type 2 diabetes and diabetic kidney disease were randomly assigned to the intensive intervention group that received nutritional education at every outpatient visit, and the usual intervention group that received nutritional education once a year. The anthropometric parameters, blood pressure, blood chemistry, albuminuria, protein and salt intake, and prescribed medications of 87 patients who completed the 2-year follow up were analyzed., Results: In the intensive intervention group, body mass index and salt intake significantly decreased over the study period. Hemoglobin A1c levels and body fat percentage were significantly lower in the intensive intervention group than in the usual intervention group. At the end of the 2-year intervention period, the intensive intervention group had significantly lower salt intake (8.1 vs 9.4 g/day) than the usual intervention group. A significant positive correlation was found between salt intake and albuminuria in the overall group and intensive intervention group (r = 0.26, P = 0.02, and r = 0.36, P = 0.02, respectively). The intensive intervention group had a significantly lower insulin use rate than the usual intervention group after the 2-year intervention period (18% vs 42%). No differences were found in estimated glomerular filtration rate and albuminuria., Conclusion: Intensive nutritional education is useful for alleviating the risk factors associated with the onset and progression of diabetic kidney disease., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Early detection of the family Chlamydiaceae as pathogens is essential worldwide for the rapid and sufficient management of atypical pneumonia. GENECUBE (TOYOBO) is a novel fully automated gene analyzer capable of amplifying and detecting target DNAs within 50 min. In this study, we developed a new PCR assay with a specific quenching probe (PCR-QC assay) for rapidly distinguishing between Chlamydia pneumoniae (CPN) and Chlamydia psittaci (CPS). The PCR-QC assay enabled us to precisely and simultaneously detect the 2 different types of DNA fragments even in a mixed sample by identifying unique melting temperatures. Next, we examined a total of 300 frozen samples from patients with respiratory tract infection using the PCR-QC assay and the cell culture method as the gold standard. Kappa index for agreement between the PCR-QC assay and the culture method was 0.43 (95% confidential interval (CI): 0.08-0.78). The sensitivity and specificity of the PCR-QC assay were 36.3% (4/11; 95% CI: 10.9-69.2%)) and 99.0% (286/289; 95% CI: 97.0-99.8%), respectively. The samples positive for CPN (n = 13) or CPS (n = 1) by either method were also examined by a conventional PCR TaqMan assay, which produced the same results as those from the PCR-QC assay. Furthermore, the PCR-QC assay using GENECUBE shortened the full detection time for CPN or CPS (within 50 min vs. more than 2 to 3 h) compared with conventional PCR TaqMan assays. Therefore, the new PCR-QC assay system equipped with GENECUBE is useful for rapidly detecting CPN or CPS pathogens in clinical laboratory, and may improve the management of atypical pneumonia., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Current consensus recognizes the benefits of early intervention in palliative care consultation teams (PCCTs). As consultants, we should now attempt to improve the quality of our teams by utilizing a method mainly used in the business field. We aimed to investigate the effects of iterative evaluation of customer satisfaction surveys, filled by physicians and ward nurses in this study, for quality improvement of PCCTs., Methods: In October 2019, the participants filled the first questionnaire survey about palliative care and PCCTs at a 678-bed hospital, and improvement areas were uncovered. Refinements were planned and implemented, and then reevaluated using the second questionnaire survey in March 2020., Results: In addition to the characteristics of our clients evaluated from approximately 500 valid responses, the first survey showed that the response rate of the questionnaire, knowledge of palliative care and PCCTs, and publicity of the PCCT were recognized as issues needing attention. We planned to contrive ways to collect questionnaires, hold monthly workshops for palliative care, launch newsletters of palliative care, and go on client rounds. The second survey revealed improvements in the physicians' response rate (p = 0.02), the accuracy rate of application of PCCTs in Japan (p < 0.01), and ward nurses' confidence in opioid use (p = 0.04) and tendency toward easier accessibility to the PCCT (p = 0.07)., Conclusion: Continual quality improvements through iterative, customer satisfaction survey-driven evaluation are a widely established practice in the business field. By using this appropriately, we could enable PCCTs to improve their quality.

Introduction: The purpose of this study is to examine self-awareness of patients with Alzheimer disease (AD) regarding forgetfulness and physical status, with the goal of further psychological understanding of these patients., Methods: The 255 subjects included 33 healthy volunteers and 48 patients with mild cognitive impairment who were elderly community residents selected from the 2017 Wakuya Project and 174 consecutive outpatients with AD at the Tajiri Clinic. Test data were selected from a pooled database. Results from the Mini-Mental State Examination, Clinical Dementia Rating (CDR), Short Falls Efficacy Scale International (FES), and Everyday Memory Checklist (EMC) were used in the study. FES and EMC data were also obtained from family members for comparison., Results: EMC scores in the AD groups (mild to moderate and moderate to severe) were significantly higher (more complaining memory impairment) than those in the CDR 0 (healthy) group and significantly lower (less self-awareness for memory impairment) than the corresponding EMC scores of families of the subjects. In contrast, FES scores of the AD groups did not differ significantly from those of the CDR 0 group, and these scores were higher (more fear of falling) than those of family members. Additionally, family-FES scores of the AD groups were higher than those of the CDR 0 and 0.5 groups., Conclusion: The results showed an evidence of the heterogeneity of awareness, an emotional response (concern or fear, FES), and a cognitive appraisal of function (EMC). These may be explained whereby awareness of/fear of falling increases with AD due to a preserved emotional awareness, whereas awareness of cognitive impairment is impaired due to memory deficits., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Introduction. Resistance against macrolide antibiotics in Mycoplasma pneumoniae is becoming non-negligible in terms of both appropriate therapy and diagnostic stewardship. Molecular methods have attractive features for the identification of Mycoplasma pneumoniae as well as its resistance-associated mutations of 23S ribosomal RNA (rRNA). Hypothesis/Gap Statement. The automated molecular diagnostic sytem can identify macrolide-resistant M. pneumoniae . Aim. To assess the performance of an automated molecular diagnostic system, GENECUBE Mycoplasma, in the detection of macrolide resistance-associated mutations. Methodology. To evaluate whether the system can distinguish mutant from wild-type 23S rRNA, synthetic oligonucleotides mimicking known mutations (high-level macrolide resistance, mutation in positions 2063 and 2064; low-level macrolide resistance, mutation in position 2067) were assayed. To evaluate clinical oropharyngeal samples, purified nucleic acids were obtained from M. pneumoniae -positive samples by using the GENECUBE system from nine hospitals. After confirmation by re-evaluation of M. pneumoniae positivity, Sanger-based sequencing of 23S rRNA and mutant typing using GENECUBE Mycoplasma were performed. Results. The system reproducibly identified all synthetic oligonucleotides associated with high-level macrolide resistance. Detection errors were only observed for A2067G (in 2 of the 10 measurements). The point mutation in 23S rRNA was detected in 67 (26.9 %) of 249 confirmed M. pneumoniae -positive clinical samples. The mutations at positions 2063, 2064 and 2617 were observed in 65 (97.0 %), 2 (3.0 %) and 0 (0.0 %) of the 67 samples, respectively. The mutations at positions 2063 and 2064 were A2063G and A2064G, respectively. The results from mutant typing using GENECUBE Mycoplasma were in full agreement with the results from sequence-based typing. Conclusion. GENECUBE Mycoplasma is a reliable test for the identification of clinically significant macrolide-resistant M. pneumoniae .

Recently, a new rapid assay for the detection of tcdB gene of Clostridioides difficile was developed using the GENECUBE. The assay can directly detect the tcdB gene from stool samples without a purification in approximately 35 minutes with a few minutes of preparation process. We performed a prospective comparative study of the performance of the assay at eight institutions in Japan. Fresh residual stool samples (Bristol stool scale ≥5) were used and comparisons were performed with the BD MAX Cdiff assay and toxigenic cultures. For the evaluation of 383 stool samples compared with the BD MAX Cdiff assay, the sensitivity, and specificity of the two assays was 99.0% (379/383), 98.1% (52/53), 99.1% (327/330), respectively. In the comparison with toxigenic culture, the total, sensitivity, and specificity were 96.6% (370/383), 85.0% (51/60), and 98.8% (319/323), respectively. The current investigation indicated the GENECUBE Clostridioides difficile assay has equivalent performance with the BD MAX Cdiff assay for the detection of tcdB gene of C. difficile., Competing Interests: This study was financially supported by TOYOBO Co., Ltd. The GENECUBE assay and the fee for the BD MAX assay were provided by TOYOBO Co., Ltd. Yosuke Kawashima, and Akio Sugiyama are employees of TOYOBO Co., Ltd. Shigeyuki Notake received a lecture fee from TOYOBO Co., Ltd. Hiromichi Suzuki received a lecture fee and advisory fee from TOYOBO Co., Ltd. This study was concurrently performed with the clinical evaluation of the rapid membrane enzyme immunoassay (C. DIFF QUIK CHEK, Abbott Japan Co., Ltd.), and St. Marianna University School of Medicine and Tsukuba Medical Center Hospital received fees for experiments and research expenses for the quality evaluation of the C. DIFF QUIK CHEK. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Context: There is little evidence of the effectiveness of aromatherapy massage in palliative care despite its popularity., Objectives: This study aimed to investigate the effects of a 30-minute single session of aromatherapy massage at night time on quality of sleep and fatigue in palliative care., Methods: A randomized controlled trial from January 2018 to March 2019. After being stratified by sex, participants were randomly assigned to an aromatherapy massage group and a control group. The effects of aromatherapy massage were evaluated on the massage day and the next day using the Richards-Campbell Sleep Questionnaire and the Brief Fatigue Inventory., Results: Of the 74 participants, data of 27 participants in the treatment group and 30 participants in the control group were analyzed. Analysis of covariance indicated that quality of sleep and fatigue did not improve owing to the aromatherapy massage, although usual fatigue in preceding 24 hours and enjoyment of life subscales of the Brief Fatigue Inventory showed signs of contribution (P = 0.07 and 0.09, respectively). Post hoc analyses indicated that higher age and performance status were factors with moderate correlation with better sleep (P = 0.03; r = 0.45 and P = 0.03; r = 0.40, respectively), and that older patients tended to experience greater improvement in fatigue (P = 0.02; r = -0.47)., Conclusion: A single aromatherapy massage session is no more effective than not having a massage in improving sleep quality in palliative care settings. However, older patients and those in poor health conditions may benefit from aromatherapy massage., (Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Sarcopenia is prevalent in patients with chronic kidney disease and is associated with increased mortality; however, limited data are available on whether kidney transplantation can improve muscle wasting. Therefore, the present study aimed to assess changes in body composition before and after kidney transplantation., Methods: Between April 2015 and January 2018, 80 de novo consecutive adult patients with end-stage kidney disease who underwent kidney transplantation were prospectively enrolled. Muscle and fat masses were measured via bioelectrical impedance analysis using InBody 770 at  - 2 and 7 days and 3, 6, and 12 months after transplantation. Presarcopenia is characterized by low muscle mass according to the skeletal muscle mass index. Changes in body composition and prevalence of presarcopenia were compared before and after transplantation. Risk factors for presarcopenia were identified using logistic regression analysis., Results: Muscle mass significantly decreased at 3 months after transplantation. Consequently, the prevalence of presarcopenia was significantly higher after transplantation (3 months: 47.5%, 6 months: 42.5%, and 12 months: 38.8%) than that before transplantation (25.0%). Similarly, the body fat percentage was significantly higher at 3 months after transplantation than that before transplantation. Presarcopenia before transplantation was an independent risk factor for presarcopenia at 12 months after transplantation (odds ratio: 51.8, 95% CI 5.77-464, p < 0.001)., Conclusions: Muscle wasting deteriorated and body fat percentage increased from 3 months after kidney transplantation. Presarcopenia before transplantation led to presarcopenia after transplantation, which may deteriorate with an increase in body fat percentage.

Ionizing radiation induces severe oxidative stress, resulting in individual death by acute radiation syndrome. The nuclear factor-erythroid-2-related factor 2 (Nrf2) plays an important role in the antioxidant response pathway. Recently, romiplostim (RP), an idiopathic thrombocytopenic purpura therapeutic drug, was reported to completely rescue mice exposed to lethal total-body irradiation (TBI). However, the details underlying the mechanism for reducing radiation damage remain largely unknown. To elucidate the involvement of the master redox regulator Nrf2 in the radio-mitigative efficacy of RP on TBI-induced oxidative stress, expression of Nrf2 target genes in hematopoietic tissues such as bone marrow, spleen, and lung from mice treated with RP for three consecutive days after 7 Gy of X-ray TBI was analyzed. RP promoted the recovery of bone marrow cells from day 10 and the significant up-regulation of reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) dehydrogenase quinone 1 (Nqo1), glutamate-cysteine ligase catalytic subunit (Gclc) and glutamate-cysteine ligase modifier subunit (Gclm) was observed compared to the TBI mice. RP also promoted the recovery of splenic cells on day 18, and the significant up-regulation of Nqo1, Gclc and Gclm in spleen both on day 10 and 18 and Nqo1 and Gclm in lung on day 10 was observed compared to the TBI mice. The present study suggests that the radio-mitigative effects of RP indicates on the activation of Nrf2 target genes involved in redox regulation and the antioxidative function, especially Nqo1, Gclc and Gclm. It is indicating the importance of these genes in the maintenance of biological homeostasis in response to radiation-induced oxidative stress.

Objective: Driving ability in older people is affected by declining motor, cognitive and visual functions. We compared perceptual and cognitive skills and driving behaviour in a Japanese population., Methods: We used a driving simulator to measure the effects of spatial navigation skills and eye movements on driving ability. Participants were 34 older and 20 young adults who completed a simulated driving task involving a lane change and a right turn at an intersection. We used an eye tracker to measure gaze. We measured visual recognition (Benton Judgment of Line Orientation Test (BJLO)), spatial navigation (Card-Placing Test (CPT A & B)), visual perception (Raven's Colored Progressive Matrices (RCPM)) and driving ability (Stroke Drivers' Screening Assessment)., Results: Older participants scored significantly lower on the BJLO, CPT-A & B and RCPM, showed a significant correlation between gaze time and CPT-A & B scores (both p < .01) and had a longer gaze time. There were significant between-group differences in saccade switching (p < .01 right turn), distance per saccade (p < .05 for right turn and lane change) and saccade total distance (p < .05 right turn; p < .01 lane change). There was an association between age and rate of gaze at the right door mirror (p = 0.04)., Conclusion: The findings indicate that older drivers have poorer eye movement control and spatial navigation. This is likely to result in delayed responses and difficulties in predicting the on-coming driving environment. Driving simulation could help older drivers in their driving abilities.

Introduction: Patients with chronic kidney disease (CKD) depend on advice from healthcare professionals to avoid using unsuitable over-the-counter (OTC) drugs. Recently, qualified, registered nonpharmacist salespersons became licensed to sell OTC drugs in Japan. However, registered salespersons' knowledge and awareness of precautions regarding unsuitable OTC drugs for use in patients with CKD are unclear., Objectives: This study aimed to clarify the awareness, knowledge, and implementation of precautions by registered salespersons regarding OTC drugs used by patients with CKD. Additionally, we evaluated the change of registered salespersons' knowledge and awareness of this topic generated by a pharmacist intervention., Methods: A questionnaire survey and pharmacist intervention were applied to 175 registered salespersons. The intervention comprised a 50-minute lecture imparted by a pharmacist who was trained in nephrology. The knowledge, awareness, and implementation of precautions by participants with respect to nonsteroidal anti-inflammatory drugs (NSAIDs) and antacids were evaluated before and after the intervention., Results: Approximately half of the registered salespersons reported previous experience with selling OTC drugs that were inappropriate for patients with CKD (NSAIDs, 48.0%; antacids, 39.7%). Few participants recognized the need to check renal function when selling those drugs to such patients (NSAIDs, 25.7%; antacids, 47.5%). The registered salespersons' awareness and knowledge were significantly higher after the intervention than before it., Conclusion: The results indicate that before the intervention, the registered salespersons had low levels of awareness and knowledge regarding OTC drug use in patients with CKD despite having prior experience selling unsuitable OTC drugs. However, the pharmacist intervention improved the registered salespersons' awareness and knowledge. The educational program for registered salespersons might be necessary to prevent inappropriate OTC drug use by patients with CKD., Competing Interests: The authors have declared that no competing interests exist.

A 64-year-old man presented to the emergency department with sudden-onset upper abdominal pain and pain in the left chest area. His platelet count was 121.7×10 4 /µl. Computed tomography (CT) showed bilateral adrenal swelling and inflammation of the adjacent tissue. Diffusion-weighted magnetic resonance imaging (MRI) showed hyperintensity in the bilateral adrenal glands. The patient was diagnosed with bilateral adrenal infarction. A bone marrow biopsy yielded a diagnosis of essential thrombocythemia, and a positive JAK2 V617F mutation was detected. He presented with recurrent adrenal infarction and developed aortic mural thrombosis and splenic infarction. We administered aspirin and performed cytoreductive therapy with hydroxyurea and anagrelide; however, the patient then went into heart failure resulting from coronary artery stenosis. We then added prasugrel to the list of medicines administered to manage his condition. Bilateral adrenal infarction is a very rare thrombotic event of essential thrombocythemia. CT and MRI were useful for making the diagnosis; however, we also had to rule out acute coronary syndrome or intestinal ischemia. Our patient presented with strong thrombotic diathesis, which prompted us to use dual antiplatelet therapy; however, further studies are needed to confirm the efficacy and safety of this treatment.

A 64-year-old woman with lymphoma-associated demyelinating neuropathy was treated by 6 cycles of R-CHOP with intravenous immunoglobulin in the first 2 cycles. We noted substantial improvement in the findings of a nerve conduction study (NCS) after the first cycle, followed by more protracted improvement during the second to sixth cycles. The improvement of the neurological symptoms paralleled the findings of the NCS. Our case provides important information for understanding the etiology and optimization of treatments for lymphoma-associated demyelinating neuropathy.

The newly developed rapid diagnostic test (RDT, DK14-CA1, Denka Seiken Co., Ltd.) to detect Campylobacter antigen was evaluated using fecal specimens of patients with enteritis. The RDT is an immunochromatographic assay using colored latex and can detect Campylobacter antigen (C. jejuni and C. coli) from patients' stool samples within 15 minutes. A total of 227 stool samples obtained from patients with enteritis were examined and the results were compared with conventional culture methods. Overall sensitivity, specificity, accuracy and positive predictive value (PPV) were 75.6%, 98.6%, 89.9% and 97.0% respectively. Among 53 severe cases defined with their clinical findings, sensitivity, specificity, accuracy and PPV were 82.1%, 100%, 90.6% and 100% respectively. Mean time to obtain the result with the RDT was 7 minutes whereas the culture method took 2.2 days. This study revealed the usefulness of the newly developed RDT as a rapid detection tool for Campylobacter antigen. Although the RDT has a little lower sensitivity compared with culture method, the simple and rapid test can contribute to treatment decisions for patients with enteritis and can be used at the patient's bedside and in outpatient clinics.

The extracellular signal-regulated kinase (ERK) is one of the principal hub proteins that transmit growth signals from upstream oncogene products including Ras and BRaf to downstream effector proteins. However, there are both reports supporting and refuting the increase in ERK activity in cancer tissues expressing the active Ras and BRaf proteins. We considered that the cell density might account for this discrepancy. To examine this possibility, we prepared Madin-Darby canine kidney (MDCK) cells that expressed an active HRas, NRas, KRas, or BRaf and an ERK biosensor based on the principle of Förster resonance energy transfer (FRET). As we anticipated, expression of the active Ras or BRaf increased ERK activity at low cell densities. However, the ERK activity was markedly suppressed at high cell densities irrespective of the expression of the active Ras or BRaf. Western blotting analysis with Phos-tag gel revealed the decrease of tyrosine and threonine-diphosphorylated active ERK and the increase of tyrosine-monophosphorylated inactive ERK at high cell density. In addition, we found that calyculin A, an inhibitor for PPP-subfamily protein serine/threonine phosphatases, decreased the tyrosine-monophosphorylated ERK. Our study suggests that PPP-subfamily phosphatases may be responsible for cell density-dependent ERK dephosphorylation in cancer cells expressing active Ras or BRaf protein., Competing Interests: The authors have declared that no competing interests exist.

Nanocrystalline Li3VO4 dispersed within multiwalled carbon nanotubes (MWCNTs) was prepared using an ultracentrifugation (uc) process and electrochemically characterized in Li-containing electrolyte. When charged and discharged down to 0.1 V vs Li, the material reached 330 mAh g(-1) (per composite) at an average voltage of about 1.0 V vs Li, with more than 50% capacity retention at a high current density of 20 A g(-1). This current corresponds to a nearly 500C rate (7.2 s) for a porous carbon electrode normally used in electric double-layer capacitor devices (1C = 40 mA g(-1) per activated carbon). The irreversible structure transformation during the first lithiation, assimilated as an activation process, was elucidated by careful investigation of in operando X-ray diffraction and X-ray absorption fine structure measurements. The activation process switches the reaction mechanism from a slow "two-phase" to a fast "solid-solution" in a limited voltage range (2.5-0.76 V vs Li), still keeping the capacity as high as 115 mAh g(-1) (per composite). The uc-Li3VO4 composite operated in this potential range after the activation process allows fast Li(+) intercalation/deintercalation with a small voltage hysteresis, leading to higher energy efficiency. It offers a promising alternative to replace high-rate Li4Ti5O12 electrodes in hybrid supercapacitor applications.

Background: To effectively treat orthopaedic infections by methicillin-resistant strains, an early diagnosis is necessary. Bacterial cultures and real-time polymerase chain reaction (PCR) have been used to define methicillin-resistant staphylococci. However, even when patients display clinical signs of infections, bacterial culture and real-time PCR often cannot confirm infection. The aim of this study was to prospectively compare the utility of real-time PCR for the mecA gene detection following centrifugation of human samples with suspected orthopaedic infections., Results: In addition to the conventional real-time PCR method, we performed real-time PCR following centrifugation of the sample at 4,830×g for 10 min in a modified real-time PCR (M-PCR) method. We suspended cultured methicillin-resistant Staphylococcus aureus and generated standard dilution series for in vitro experiments. The in vitro detection sensitivity of the M-PCR method was approximately 5.06 times higher than that of the conventional real-time PCR method. We performed bacterial culture, pathological examination, real-time PCR, and M-PCR to examine the infectious fluids and tissues obtained from 36 surgical patients at our hospital. Of these, 20 patients who had undergone primary total hip arthroplasty were enrolled as negative controls. In addition, 15 patients were examined who were clinically confirmed to have an infection, including periprosthetic joint infection (eight patients), pyogenic spondylitis (two patients), infectious pseudoarthrosis (two patients), and after spine surgery (three patients). In one sample from a patient who developed infectious pseudoarthrosis and two samples from surgical site infections after spine surgery, the mecA gene was detected only by the M-PCR method. In one patient with infectious pseudoarthrosis, one patient with infection after arthroplasty, and two patients with purulent spondylitis, the detection sensitivity of the M-PCR method was increased compared with PCR (clinical sample average: 411.6 times)., Conclusions: These findings suggest that the M-PCR method is useful to detect methicillin-resistant strains infections. In addition, the centrifugation process only takes 10 min longer than conventional real-time PCR methods. We believe that the M-PCR method could be clinically useful to detect orthopaedic infections caused by methicillin-resistant strains.

The efficacy and safety of chemical prophylaxis to prevent the development of deep venous thrombosis (DVT) or pulmonary embolism (PE) following spine surgery are controversial because of the possibility of epidural hematoma formation. Postoperative venous thromboembolism (VTE) after spine surgery occurs at a frequency similar to that seen after joint operations, so it is important to identify the risk factors for VTE formation following spine surgery. We therefore retrospectively studied data from patients who had undergone spinal surgery and developed postoperative VTE to identify those risk factors. We conducted a retrospective clinical study with logistic regression analysis of a group of 80 patients who had undergone spine surgery at our institution from June 2012 to August 2013. All patients had been screened by ultrasonography for DVT in the lower extremities. Parameters of the patients with VTE were compared with those without VTE using the Mann-Whitney U-test and Fisher exact probability test. Logistic regression analysis was used to analyze the risk factors associated with VTE. A value of P < 0.05 was used to denote statistical significance. The prevalence of VTE was 25.0% (20/80 patients). One patient had sensed some incongruity in the chest area, but the vital signs of all patients were stable. VTEs had developed in the pulmonary artery in one patient, in the superficial femoral vein in one patient, in the popliteal vein in two patients, and in the soleal vein in 18 patients. The Mann-Whitney U-test and Fisher exact probability test showed that, except for preoperative walking disability, none of the parameters showed a significant difference between patients with and without VTE. Risk factors identified in the multivariate logistic regression analysis were preoperative walking disability and age. The prevalence of VTE after spine surgery was relatively high. The most important risk factor for developing postoperative VTE was preoperative walking disability. Gait training during the early postoperative period is required to prevent VTE.

Objective: The aim of our study was to investigate clinical and nutritional factors associated with renal involvement in patients with type 2 diabetes., Patients: We performed a cross-sectional study of 71 patients with type 2 diabetes who were being educated at our hospital from September 2006 to February 2008. The patients were divided into two groups; Group I consisted of 40 patients with both an estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73 m(2) and normoalbuminuria, and Group II consisted of 31 patients with either microalbuminuria/overt proteinuria or an eGFR of <60 mL/min/1.73 m(2). We compared the age, body mass index (BMI), blood pressure, duration from onset of diabetes, use of hypoglycemic agents and insulin, biochemistry data, including HbA1c, pulse wave velocity corrected by blood pressure (PWVc) and the daily intake of several nutrients between the two groups. A multivariate logistic regression analysis was performed to identify factors independently associated with renal involvement., Results: Group II had significantly higher values for BMI, the duration of diabetes, triglycerides, uric acid and PWVc than Group I. Group II tended to have a high salt intake compared to Group I. The multivariate logistic analysis revealed that the daily salt intake, PWVc and uric acid were independent factors associated with renal involvement (odds ratio, 1.15, 1.84 and 2.00; 95% confidence interval, 1.02-1.31, 1.04-3.27 and 1.04-3.85, respectively)., Conclusion: Our data suggest that a high salt intake, in addition to arteriosclerosis, is associated with renal involvement in our cohort with type 2 diabetes.

Introduction: We reported impaired QT-rate dependence in early repolarization syndrome (ERS); however, contemporary data have shown peak incidence of sudden cardiac death (SCD) in ERS and Brugada syndrome (BrS) at mid-night and early morning. Taken together, we analyzed the nocturnal QT-rate dependence in both syndromes., Methods and Results: A total of 172 subjects were enrolled: 11 ERS, 11 BrS patients, 50 subjects with an uneventful ER pattern (ERP), and 100 non-J-wave control subjects. Ambulatory ECG-derived parameters (QT, QTc, and QT/RR slope) and day-night QT difference were analyzed and compared. Among the groups, there was no significant difference in the average QT or QTc; however, the 24-hour QT/RR slope was significantly smaller in ERS and BrS patients (0.103 ± 0.01 and 0.106 ± 0.01, respectively) than in the control group (0.156 ± 0.03, P < 0.001). Detailed analysis showed a lower day-night QT difference in ERS and BrS patients (19 ±18.7 and 24 ±14 milliseconds, respectively) than in the controls (40 ± 22 milliseconds, P = 0.007) with the lowest QT/RR slopes seen in the ERS and BrS groups from 0 to 3:00 am (QT/RR; 0.076 ± 0.02 vs. 0.092 ± 0.04 vs. 0.117 ± 0.04, for the ERS, BrS, and controls, respectively, P = 0.004) and from 3 to 6 am (QT/RR 0.074 ± 0.03 vs. 0.079 ± 0.02 vs. 0.118 ± 0.04, P < 0.001)., Conclusion: In a large population of age- and gender-matched groups, both ERS and BrS patients showed attenuated QT-rate dependence and impaired QT day-night modulation that may provide a baseline reentrant substrate. Importantly, QT/RR maladaptation was most evident at mid-night and early morning, which may explain the propensity of such patients to develop SCD during this critical period., (© 2014 Wiley Periodicals, Inc.)