Publications by authors named "Takashi Nakano"

787 Publications

Prospective Evaluation of Quality of Life and Functional Outcomes after Carbon Ion Radiotherapy for Inoperable Bone and Soft Tissue Sarcomas.

Cancers (Basel) 2021 May 25;13(11). Epub 2021 May 25.

Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-15, Showa-machi, Maebashi 371-8511, Gunma, Japan.

Carbon-ion radiotherapy (CIRT) represents a definitive treatment for inoperable bone and soft tissue sarcoma (BSTS). This prospective study analyzed 61 patients with inoperable BSTS who were treated with CIRT to evaluate QOL, functional outcomes, and predictive factors in patients with inoperable BSTS treated with definitive CIRT. The Musculoskeletal Tumor Society (MSTS) scoring system and the Short Form (SF)-8 questionnaire were completed before and at 1, 3, 6, 12, and 24 months after CIRT. The median follow-up period was 38 months. The main site of primary disease was the pelvis (70.5%), and the most common pathologic diagnosis was chordoma (45.9%). The 3-year overall survival and local control rates were 87.8% and 83.8%, respectively. The MSTS score and physical component score (PCS) of SF-8 did not change significantly between the baseline and subsequent values. The mental component score of SF-8 significantly improved after CIRT. Multivariate analysis showed that the normalized MSTS and normalized PCS of SF-8 at the final follow-up were significantly affected by performance status at diagnosis and sex. CIRT showed clinical efficacy, preserving the physical component of QOL and functional outcomes and improving the mental component of QOL, suggesting its potential value for the treatment of patients with inoperable BSTS.
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http://dx.doi.org/10.3390/cancers13112591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199366PMC
May 2021

Evaluation of SARS-CoV-2 RNA quantification by RT-LAMP compared to RT-qPCR.

J Infect Chemother 2021 Jul 11;27(7):1068-1071. Epub 2021 May 11.

Department of Central Clinical Laboratory, Osaka Medical College Hospital, Osaka, Japan; Infection Control Center, Osaka Medical College Hospital, Osaka, Japan.

Introduction: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by a novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The viral load of SARS-CoV-2 is associated with mortality in COVID-19 patients. Measurement of viral load requires the use of reverse transcription quantitative PCR (RT-qPCR), which in turn requires advanced equipment and techniques. In this study, we aimed to evaluate the viral load measurement using reverse transcription loop-mediated isothermal amplification (RT-LAMP), which is a simpler procedure compared to RT-qPCR.

Materials And Methods: RNA was extracted by using the QIAamp Viral RNA Mini Kit. The RT-LAMP assay was performed by using the Loopamp® 2019-SARS-CoV-2 detection reagent kit and 10-fold serial dilutions of known viral load RT-LAMP were used to measure Tt, which is the time until the turbidity exceeds the threshold. Based on the relationship between viral load and Tt, the linearity and detection sensitivity of the calibration curve were evaluated. In addition, 117 clinical specimens were measured, and RT-qPCR and RT-LAMP assay results were compared.

Results: The dilution linearity of the calibration curve was maintained at five orders of magnitude 1.0× 10 to 1.0 × 10 copies/μL, and was confirmed to be detectable down to 1.0 × 10 copies/μL. The limit of quantification of RNA extracted from clinical specimens using RT-LAMP correlated well with that obtained using RT-qPCR (r = 0.930).

Conclusion: The findings indicate that RT-LAMP is an effective method to determine the viral load of SARS-CoV-2.
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http://dx.doi.org/10.1016/j.jiac.2021.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112399PMC
July 2021

Analysis of radiotherapy-induced alteration of CD8 T cells and PD-L1 expression in patients with uterine cervical squamous cell carcinoma.

Oncol Lett 2021 Jun 6;21(6):446. Epub 2021 Apr 6.

Signal Transduction Program, Gunma University Initiative for Advanced Research, Gunma University, Maebashi, Gunma 371-8511, Japan.

Radiotherapy induces an immune response in the cancer microenvironment that may influence clinical outcome. The present study aimed to analyse the alteration of CD8 T-cell infiltration and programmed death-ligand 1 (PD-L1) expression following radiotherapy in clinical samples from patients with uterine cervical squamous cell carcinoma. Additionally, the current study sought to analyse the association between these immune responses and clinical outcomes. A total of 75 patients who received either definitive chemoradiotherapy or radiotherapy were retrospectively analyzed. CD8 T-cell infiltration and PD-L1 expression were determined by immunohistochemistry using biopsy specimens before radiotherapy (pre-RT) and after 10 Gy radiotherapy (post-10 Gy). The PD-L1 rate was significantly increased from 5% (4/75) pre-RT to 52% (39/75) post-10 Gy (P<0.01). Despite this increase in the PD-L1 rate post-10 Gy, there was no significant association between both pre-RT and post-10 Gy and overall survival (OS), locoregional control (LC) and progression-free survival (PFS). On the other hand, the CD8 T-cell infiltration density was significantly decreased for all patients (median, 23.1% pre-RT vs. 16.9% post-10 Gy; P=0.038); however, this tended to increase in patients treated with radiotherapy alone (median, 17.7% pre-RT vs. 24.0% post-10 Gy; P=0.400). Notably, patients with high CD8 T-cell infiltration either pre-RT or post-10 Gy exhibited positive associations with OS, LC and PFS. Thus, the present analysis suggested that CD8 T-cell infiltration may be a prognostic biomarker for patients with cervical cancer receiving radiotherapy. Furthermore, immune checkpoint inhibitors may be effective in patients who have received radiotherapy, since radiotherapy upregulated PD-L1 expression in cervical cancer specimens.
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http://dx.doi.org/10.3892/ol.2021.12707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045163PMC
June 2021

Stereotactic body radiotherapy for adenoid cystic carcinoma metastatic to the lung: a case report.

J Med Case Rep 2021 Apr 11;15(1):156. Epub 2021 Apr 11.

Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.

Background: Adenoid cystic carcinoma (ACC) is a rare malignant tumor involving mostly the head and neck region, and frequently the salivary glands. The development of lung metastasis after treatment of the primary tumor is a common occurrence in ACC. Although lung metastases show a slow rate of growth, approximately 10% of patients die from distant metastases. The radioresistance of ACC limits the efficacy of conventional radiotherapy for lung metastases, and the optimal dose remains to be determined. Stereotactic body radiotherapy (SBRT) using CyberKnife can deliver a high dose to the lung tumor, while sparing the surrounding normal lung tissues, leading to favorable local control in non-squamous cell lung cancer and metastatic lung tumors. We report a case of lung metastases from ACC treated successfully with SBRT using CyberKnife.

Case Presentation: A 76-year-old Japanese man with ACC who was treated with carbon ion radiotherapy for a primary oropharynx tumor presented with three metastatic lesions in the lung. The tumor masses were located in the right upper, right lower, and left lower lobes of the lungs. Surgical resection was not indicated because of the presence of multiple tumors. The patient underwent SBRT at 60 Gy in 10 sequential fractions for each tumor. The biologically effective dose based on an alpha/beta ratio of 2 Gy was 240 Gy per tumor. The percentage of the total lung volume irradiated with >20 Gy was 4.9%, 3.2%, and 2.6% for each tumor. The patient developed acute radiation pneumonitis during the initial therapy, which resolved at 6 months after the CyberKnife treatment. At 21 months after the first CyberKnife treatment, three tumors showed no signs of recurrence. No late toxicity was observed.

Conclusions: SBRT using CyberKnife is an effective and feasible approach to the management of multiple lung metastases of ACC.
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http://dx.doi.org/10.1186/s13256-021-02781-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037832PMC
April 2021

Impact of Carbon Ion Radiotherapy on Inoperable Bone Sarcoma.

Cancers (Basel) 2021 Mar 4;13(5). Epub 2021 Mar 4.

Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan.

Management of patients with bone sarcoma who are unsuitable for surgery is challenging. We aimed to analyze the clinical outcomes among such patients who were treated with carbon ion radiotherapy (C-ion RT). We reviewed the medical records of the patients treated with C-ion RT between April 2011 and February 2019 and analyzed the data of 53 patients. Toxicities were classified using the National Cancer Institute's Common Terminology Criteria for Adverse Events (Version 4.0). The median follow-up duration for all patients was 36.9 months. Histologically, 32 patients had chordoma, 9 had chondrosarcoma, 8 had osteosarcoma, 3 had undifferentiated pleomorphic sarcoma, and 1 had sclerosing epithelioid fibrosarcoma. The estimated 3-year overall survival (OS), local control (LC), and progression-free survival (PFS) rates were 79.7%, 88.6%, and 68.9%, respectively. No patients developed grade 3 or higher acute toxicities. Three patients developed both grade 3 radiation dermatitis and osteomyelitis, one developed both grade 3 radiation dermatitis and soft tissue infection, and one developed rectum-sacrum-cutaneous fistula. C-ion RT showed favorable clinical outcomes in terms of OS, LC, and PFS and low rates of toxicity in bone sarcoma patients. These results suggest a potential role for C-ion RT in the management of this population.
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http://dx.doi.org/10.3390/cancers13051099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961536PMC
March 2021

PREVALENCE OF DIABETES IN TUBERCULOSIS PATIENTS IN KATHMANDU VALLEY, NEPAL.

Jpn J Infect Dis 2021 Mar 31. Epub 2021 Mar 31.

Osaka Medical Collage, Japan.

This descriptive cross-sectional study collected data of the prevalence of diabetes mellitus (DM) among tuberculosis (TB) at the Urban DOTS (Directly observed treatment, short-course) Centers in the Kathmandu, Bhaktapur, and Lalitpur districts of Nepal. The prevalence of DM was assessed in 67 previously treated TB cases (PTTB) and 214 new TB cases. DM was diagnosed in 8 PTTB and 20 new TB patients. Clinical interviews identified 14 cases of DM, the rapid blood glucose test diagnosed 4 cases, and the oral glucose tolerance test (OGTT) diagnosed 4 cases. Impaired glucose tolerance and impaired fasting glycemia were found in 8 and 5 cases, respectively. The 18-24 age group had the largest number of new TB cases (82; 38.3%). However, the comorbidity of DM and TB was higher in the 35 years and older age group and was found in 24.2% of PTTB and in 23.1% of new TB cases. To provide the evidence of impacts of DM screening for TB cases, larger number of samples should be analyzed. The DM screening for TB patients is expected to start in developing countries. It should be initiated by clinical interview about DM and glucose tests by rapid kits.
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http://dx.doi.org/10.7883/yoken.JJID.2019.375DOI Listing
March 2021

Kaposi's sarcoma-associated herpesvirus ORF17 plays a key role in capsid maturation.

Virology 2021 Jun 25;558:76-85. Epub 2021 Feb 25.

Department of Cell Biology, Kyoto Pharmaceutical University, 1 Misasagi-Shichono, Yamashina, Kyoto, 607-8412, Japan. Electronic address:

Kaposi's sarcoma-associated herpesvirus is a human rhadinovirus of the gammaherpesvirus sub-family. Although herpesviruses are well-studied models of capsid formation and its processes, those of KSHV remain unknown. KSHV ORF17 encoding the viral protease precursor (ORF17-prePR) is thought to contribute to capsid formation; however, functional information is largely unknown. Here, we evaluated the role of ORF17 during capsid formation by generating ORF17-deficient and ORF17 protease-dead KSHV. Both mutants showed a decrease in viral production but not DNA replication. ORF17 R-mut, with a point-mutation at the restriction or release site (R-site) by which ORF17-prePR can be functionally cleaved into a protease (ORF17-PR) and an assembly region (ORF17-pAP/-AP), failed to play a role in viral production. Furthermore, wild type KSHV produced a mature capsid, whereas ORF17-deficient and protease-dead KSHV produced a B-capsid, (i.e., a closed body possessing a circular inner structure). Therefore, ORF17 and its protease function are essential for appropriate capsid maturation.
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http://dx.doi.org/10.1016/j.virol.2021.02.009DOI Listing
June 2021

Correlation of student performance on clerkship with quality of medical chart documentation in a simulation setting.

PLoS One 2021 15;16(3):e0248569. Epub 2021 Mar 15.

Medical Education Center, Osaka Medical College, Osaka, Japan.

Background: Medical chart documentation is an essential skill acquired in a clinical clerkship (CC). However, the utility of medical chart writing simulations as a component of the objective structured clinical examination (OSCE) has not been sufficiently evaluated. In this study, medical chart documentation in several clinical simulation settings was performed as part of the OSCE, and its correlation with CC performance was evaluated.

Methods: We created a clinical situation video and images involving the acquisition of informed consent, cardiopulmonary resuscitation, and diagnostic imaging in the emergency department, and assessed medical chart documentation performance by medical students as part of the OSCE. Evaluations were conducted utilizing original checklist (0-10 point). We also analyzed the correlation between medical chart documentation OSCE scores and CC performance of 120 medical students who performed their CC in 2019 as 5th year students and took the Post-CC OSCE in 2020 as 6th year students.

Results: Of the OSCE components, scores for the acquisition of informed consent and resuscitation showed significant correlations with CC performance (P<0.001 for each). In contrast, scores for diagnostic imaging showed a slightly positive, but non-significant, correlation with CC performance (P = 0.107). Overall scores for OSCE showed a significant correlation with CC performance (P<0.001).

Conclusion: We conducted a correlation analysis of CC performance and the quality of medical chart documentation in a simulation setting. Our results suggest that medical chart documentation can be one possible alternative component in the OSCE.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248569PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959337PMC
March 2021

Rivaroxaban Attenuates Right Ventricular Remodeling in Rats with Pulmonary Arterial Hypertension.

Biol Pharm Bull 2021 May 20;44(5):669-677. Epub 2021 Feb 20.

Department of Cardiovascular Pharmacotherapy and Toxicology, Osaka University of Pharmaceutical Sciences.

Pulmonary arterial hypertension (PAH) is a progressive condition that frequently results in right ventricular (RV) remodeling. The objectives of this study are to investigate effects of rivaroxaban on RV remodeling in a rat model of PAH, created with Sugen5416 and chronic hypoxia, and the in vitro effects of rivaroxaban on human cardiac microvascular endothelial cells (HCMECs). To create the PAH model, male Sprague-Dawley rats were subcutaneously injected with Sugen5416 (20 mg/kg) and exposed to 2 weeks of hypoxia (10% O), followed by 2 weeks of exposure to normoxia. The animals were then divided into 2 groups with or without administration of rivaroxaban (12 mg/kg/d) for a further 4 weeks. HCMECs were cultured under hypoxic conditions (37 °C, 1% O, 5% CO) with Sugen5416 and with or without rivaroxaban. In the model rats, RV systolic pressure and Fulton index increased by hypoxia with Sugen5416 were significantly decreased when treated with rivaroxaban. In HCMECs, hypoxia with Sugen5416 increased the expression of protease-activated receptor-2 (PAR-2) and the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor-kappa B (NF-κB), while treatment with rivaroxaban significantly suppressed the expression of these proteins. Rivaroxaban attenuated RV remodeling in a rat model of PAH by reducing ERK, JNK and NF-κB activation. Rivaroxaban has the possibility of providing additive effects on RV remodeling in patients with PAH.
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http://dx.doi.org/10.1248/bpb.b20-01011DOI Listing
May 2021

Characterization of Salivary Microbiota in Patients with Atherosclerotic Cardiovascular Disease: A Case-Control Study.

J Atheroscler Thromb 2021 Feb 19. Epub 2021 Feb 19.

Department of Cardiology, Osaka Medical College.

Aims: Oral bacteria have been reported to be associated with the pathogenesis of atherosclerosis; however, the relationship between the oral microbiota and atherosclerosis remains unclear. The present study aimed to investigate whether or not salivary microbiota of patients with atherosclerotic cardiovascular disease (ACVD) differs from that of subjects without ACVD, and to characterize the salivary microbiota of patients with ACVD.

Methods: This study included 43 patients with ACVD and 86 age- and sex-matched non-ACVD individuals. 16S rRNA metagenomic analysis were performed using DNA isolated from the saliva samples of the participants. To select unique operational taxonomic unit (OTU) sets of ACVD, we conducted the random forest algorithm in machine learning, followed by confirmation via 10-fold cross-validation Results: There was no difference in richness or evenness between the ACVD and non-ACVD groups (alpha diversity; observed OTU index, p=0.503; Shannon's index, p=0.478). However, significant differences were found in the overall salivary microbiota structure (beta diversity; unweighted UniFrac distances, p=0.001; weighted UniFrac distances, p=0.001). The Actinobacteria phylum was highly abundant in patients with ACVD, while the Bacteroidetes phylum was less abundant. The random forest classifier identified 43 OTUs as an optimal marker set of ACVD. In a 10-fold cross validation using the validation data, an area under the curve (AUC) of 0.933 (95% CI, 0.855-1.000) was obtained.

Conclusions: The salivary microbiota in patients with ACVD was distinct from that of non-ACVD individuals, indicating that the salivary microbiota may be related to ACVD.
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http://dx.doi.org/10.5551/jat.60608DOI Listing
February 2021

Kynurenine 3-monooxygenase deficiency induces depression-like behavior via enhanced antagonism of α7 nicotinic acetylcholine receptors by kynurenic acid.

Behav Brain Res 2021 May 16;405:113191. Epub 2021 Feb 16.

Department of Disease Control and Prevention, Fujita Health University Graduate School of Health Science, Aichi, Japan; Japanese Drug Organization of Appropriate Use and Research, Aichi, Japan.

Tryptophan (TRP) is metabolized via the kynurenine (KYN) pathway, which is related to the pathogenesis of major depressive disorder (MDD). Kynurenine 3-monooxygenase (KMO) is a pivotal enzyme in the metabolism of KYN to 3-hydroxykynurenine. In rodents, KMO deficiency induces a depression-like behavior and increases the levels of kynurenic acid (KA), a KYN metabolite formed by kynurenine aminotransferases (KATs). KA antagonizes α7 nicotinic acetylcholine receptor (α7nAChR). Here, we investigated the involvement of KA in depression-like behavior in KMO knockout (KO) mice. KYN, KA, and anthranilic acid but not TRP or 3-hydroxyanthranilic acid were elevated in the prefrontal cortex of KMO KO mice. The mRNA levels of KAT1 and α7nAChR but not KAT2-4, α4nAChR, or β2nAChR were elevated in the prefrontal cortex of KMO KO mice. Nicotine blocked increase in locomotor activity, decrease in social interaction time, and prolonged immobility in a forced swimming test, but it did not decrease sucrose preference in the KMO KO mice. Methyllycaconitine (an α7nAChR antagonist) antagonized the effect of nicotine on decreased social interaction time and prolonged immobility in the forced swimming test, but not increased locomotor activity. Galantamine (an α7nAChR allosteric agonist) blocked the increased locomotor activity and prolonged immobility in the forced swimming test, but not the decreased social interaction time in the KMO KO mice. In conclusion, elevation of KA levels contributes to depression-like behaviors in KMO KO mice by α7nAChR antagonism. The ameliorating effects of nicotine and galantamine on depression-like behaviors in KMO KO mice are associated with the activation of α7nAChR.
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http://dx.doi.org/10.1016/j.bbr.2021.113191DOI Listing
May 2021

Dosimetric feasibility of computed tomography-based image-guided brachytherapy in locally advanced cervical cancer: a Japanese prospective multi-institutional study.

J Radiat Res 2021 May;62(3):502-510

Department of Molecular Imaging and Theranostics, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.

The aim of this study was to assess the feasibility of planning dose-volume histogram (DVH) parameters in computed tomography-based 3D image-guided brachytherapy for locally advanced cervical cancer. In a prospective multi-institutional study, 60 patients with stage IIA2-IVA cervical cancer from eight institutions were treated with external beam radiotherapy using central shielding and intracavitary or hybrid (combined intracavitary/interstitial) brachytherapy (HBT). The dose constraints were set as a cumulative linear quadratic equivalent dose (EQD2) of at least 60 Gy for high-risk clinical target volume (HR-CTV) D90, D2cc ≤ 75 Gy for rectum, D2cc ≤ 90 Gy for bladder and D2cc ≤ 75 Gy for sigmoid. The median HR-CTV D90 was 70.0 Gy (range, 62.8-83.7 Gy) in EQD2. The median D2cc of rectum, bladder and sigmoid was 57.1 Gy (range, 39.8-72.1 Gy), 68.9 Gy (range, 46.5-84.9 Gy) and 57.2 Gy (range, 39.2-71.2 Gy) in EQD2, respectively. In 76 of 233 sessions (33%), 23 patients underwent HBT, and the median number of interstitial needles was 2 (range, 1-5). HBT for a bulky HR-CTV (≥40 cm3) significantly improved the HR-CTV D90 compared with intracavitary brachytherapy alone (P = 0.010). All patients fulfilled the dose constrains for target and at risk organs by undergoing HBT in one-third of sessions. We conclude that the planning DVH parameters used in our protocol are clinically feasible.
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http://dx.doi.org/10.1093/jrr/rraa138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127675PMC
May 2021

Robustness of daily dose for each beam angle and accumulated dose for inter-fractional anatomical changes in passive carbon-ion radiotherapy for pancreatic cancer: Bone matching versus tumor matching.

Radiother Oncol 2021 04 27;157:85-92. Epub 2021 Jan 27.

Gunma University Heavy Ion Medical Center, Japan.

Purpose: We aimed to assess the robustness of accumulated dose distributions for inter-fractional changes in passive carbon-ion radiotherapy for pancreatic cancer.

Methods: Ninety-five daily CT image sets acquired after the treatment of eight patients with pancreatic cancer were used in this prospective study. Dose distributions with treatment beam fields were recalculated for bone matching (BM) and tumor matching (TM) positions on all daily CT images, the accumulated doses being calculated using deformable image registration methods. The prescribed dose was 55.2 Gy (relative biological effectiveness [RBE]) in 12 fractions. Dose volume parameters of V95 (%) for CTV and GTV, and D2cc (Gy(RBE)) for the stomach and duodenum were evaluated.

Results: The medians (range) of CTV V95 (%) were 91.9 (86.1-100.0), 80.5 (56.1-90.6), and 86.4 (72.5-96.5) for the Plan, accumulated with BM and TM, respectively; GTV values (%) were 98.0 (85.7-100.0), 93.3 (65.7-99.9), and 96.2 (84.8-100.0), respectively. There were significant differences between all combinations apart from the Plan and TM for both targets. The values of stomach D2cc (Gy(RBE)) were 36.0 (16.9-43.4), 36.7 (17.9-45.0), and 35.2 (16.8-43.5), respectively; duodenum values (Gy(RBE)) were 25.2 (21.3-40.3), 30.1 (23.3-48.6), and 28.3 (20.4-50.6), respectively. There was a significant difference between the Plan and BM for duodenum only.

Conclusions: TM is recommended over BM because it can achieve higher target dose coverage than BM. Nevertheless, it is not enough in some cases. Further technical improvements are necessary to improve the target dose coverage.
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http://dx.doi.org/10.1016/j.radonc.2021.01.011DOI Listing
April 2021

Recent acute reduction in macrolide-resistant Mycoplasma pneumoniae infections among Japanese children.

J Infect Chemother 2021 Feb 21;27(2):271-276. Epub 2020 Oct 21.

Department of Pediatrics, Kawasaki Medical School, Okayama, Japan. Electronic address:

Introduction: Mycoplasma pneumoniae contributes to numerous pneumonia cases among children and young adults. Therefore, this study aimed to investigate the prevalence of M. pneumoniae infections among Japanese children, occurring since 2008.

Methods: Nasopharyngeal swab specimens were obtained from all cases, following which real-time PCR was performed to identify M. pneumoniae. Further, the p1 genotypes of isolates were determined using the PCR restriction fragment length polymorphism typing method.

Results: The annual rate of macrolide-resistant M. pneumoniae (MRMP) infections peaked at 81.8% in 2012 and decreased annually until 2015. Although the infection rate increased to 65.3% in 2016, it decreased again to 14.3% in 2018. Although >90% of isolates harbored the type 1 genotype until 2012, this rate decreased, and approximately 80% harbored p1 genotypes other than type 1 in 2018. Furthermore, the occurrence rate of MRMP among the type 1 isolates was very high (82.4%), whereas that among p1 genotypes other than type 1 was very low (6.5%).

Conclusions: MRMP occurrence potentially decreased owing to changes in not only antibiotic usage but also in the distribution of p1 genotype among isolates.
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http://dx.doi.org/10.1016/j.jiac.2020.10.007DOI Listing
February 2021

Relationship between Photoelasticity of Polyurethane and Dielectric Anisotropy of Diisocyanate, and Application of High-Photoelasticity Polyurethane to Tactile Sensor for Robot Hands.

Polymers (Basel) 2020 Dec 31;13(1). Epub 2020 Dec 31.

Electrical Engineering Department, Graduate School of Science and Engineering, Kansai University, Suita, Osaka 564-8680, Japan.

Eight types of polyurethane were synthesized using seven types of diisocyanate. It was found that the elasto-optical constant depends on the concentration of diisocyanate groups in a unit volume of a polymer and the magnitude of anisotropy of the dielectric constant of diisocyanate groups. It was also found that incident light scattered when bending stress was generated inside photoelastic polyurethanes. A high sensitive tactile sensor for robot hands was devised using one of the developed polyurethanes with high photoelasticity.
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http://dx.doi.org/10.3390/polym13010143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795569PMC
December 2020

Regional collaboration to improve quality of radiation therapy in Asia.

J Med Imaging Radiat Oncol 2020 Dec 14. Epub 2020 Dec 14.

Quantum Medical Science Directorate, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan.

In Asia, several challenges hinder the delivery of high-quality cancer treatment, especially radiation therapy (RT). Many Asian countries face large-scale shortage of RT centres and treatment machines. Additionally, there is also a significant technological gap, with many RT centres in Asia still using outdated technology. There is an urgent need to improve radiation treatment quality in Asia. The Federation of Asian Organizations for Radiation Oncology (FARO) was set up to foster regional collaboration, which we believe can help to identify and solve some of these issues collectively. This report describes the background and rationale of starting FARO, and puts forth some of the early achievements of the group, including fact-finding and educational activities. Finally, we discuss future possibilities, including strategic proposals that may benefit the RT community and our patients in Asia.
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http://dx.doi.org/10.1111/1754-9485.13133DOI Listing
December 2020

Pelvic insufficiency fractures following carbon-ion radiotherapy for uterine carcinomas.

Radiother Oncol 2021 03 3;156:56-61. Epub 2020 Dec 3.

QST Hospital, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan. Electronic address:

Background And Purpose: There is growing evidence on the role of carbon-ion radiotherapy (C-ion RT) for gynaecological tumours. Pelvic insufficiency fracture (PIF) decreases the quality of life after photon beam radiotherapy (RT). However, there is little information on PIF after C-ion RT. This study retrospectively assessed incidence of PIF after C-ion RT for uterine carcinomas (UCs) and the associations of clinical and dosimetric parameters with PIF incidence.

Material And Methods: We performed a pooled analysis of 102 patients with UCs who underwent definitive C-ion RT alone and were followed up for >6 months without any additional RT in the pelvic region. PIF occurrence was surveyed using magnetic resonance imaging and/or computed tomography. Associations of clinical and dosimetric parameters with PIF incidence were analysed.

Results: The 2- and 5-year actuarial incidences of ≥grade 1 PIF in all pelvic regions were 22.3% and 42.4%, respectively. The most frequent site of involvement was the sacrum. Log-rank tests showed that higher volumes receiving >10 Gy (relative biological effectiveness) (V10), V20, V30, and V40, body mass index (BMI) under 18.5, and current smoking were associated with increased incidence of ≥grade 1 PIF in the sacrum.

Conclusions: We clarified the actuarial incidence of PIF after C-ion RT for UCs. Higher V10, V20, V30, V40, D, D, current smoking, BMI <18.5, and using the anterior-posterior direction in whole pelvic irradiation were associated with higher incidences of PIF in the sacrum. The present results may lead to further improvement of C-ion RT for UCs.
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http://dx.doi.org/10.1016/j.radonc.2020.11.030DOI Listing
March 2021

α-Emitting cancer therapy using At-AAMT targeting LAT1.

Cancer Sci 2021 Mar 22;112(3):1132-1140. Epub 2021 Jan 22.

Division of Science, Institute for Radiation Sciences, Osaka University, Osaka, Japan.

α-Methyl-l-tyrosine (AMT) has a high affinity for the cancer-specific l-type amino acid transporter 1 (LAT1). Therefore, we established an anti-cancer therapy, with At-labeled α-methyl-l-tyrosine ( At-AAMT) as a carrier of At into tumors. At-AAMT had high affinity for LAT1, inhibited tumor cell growth, and induced DNA double-stranded breaks in vitro. We evaluated the accumulation of At-AAMT in vivo and the role of LAT1. Treatment with 0.4 MBq/mouse At-AAMT inhibited tumor growth in the PANC-1 tumor model and 1 MBq/mouse At-AAMT inhibited metastasis in the lung of the B16F10 metastasis model. Our results suggested that At would be useful for anti-cancer therapy and that LAT1 is suitable as a target for radionuclide therapy.
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http://dx.doi.org/10.1111/cas.14761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935802PMC
March 2021

Intake Ratio of 131I to 137CS Derived from Thyroid and Whole-body Doses to Residents of Iwaki City in Japan's Fukushima Prefecture.

Health Phys 2021 Apr;120(4):387-399

National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba-city, Chiba 263-8555, Japan.

Abstract: It is very important to determine the precise internal thyroid doses of Fukushima residents involved in the 2011 Fukushima nuclear disaster, particularly for small children. This has been challenging due to the lack of direct human measurements to identify 131I, the biggest contributor to the thyroid doses. We previously used a dataset of late whole-body counter (WBC) measurements targeting 134Cs and 137Cs for the thyroid dose estimation in comparison with the intake ratios of 131I to 137Cs (or 134Cs) derived from thyroid and whole-body doses individually obtained from different subject groups, assuming simultaneous acute intake via inhalation. Herein, we applied the same method to the doses of residents in Iwaki city (located south of the Fukushima Daiichi Nuclear Power Plant) with a relatively high activity ratio (131I/137Cs) for the ground deposition density. Our analyses revealed that the intake ratio (131I/137Cs) for the Iwaki residents was 4.2-4.3, which is relatively consistent with the values obtained in other studies (average 3.0-5.0). No regional difference in the intake ratios from other areas was observed, but further studies are required to determine the accurate intake ratio in the early phase of the accident, in particular focusing on the reasonable interpretation of results of the late WBC measurements to evaluate the actual Cs intake.
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http://dx.doi.org/10.1097/HP.0000000000001345DOI Listing
April 2021

Effectiveness of four doses of pertussis vaccine during infancy diminished in elementary school age: A test-negative case-control study in Japan.

Vaccine 2021 01 20;39(1):11-17. Epub 2020 Nov 20.

Clinical Epidemiology Research Center, Medical Co. LTA (SOUSEIKAI), 3-5-1, Kashii-Teriha Higashi-ku, Fukuoka-city, Fukuoka 813-0017, Japan.

Objective: The Japanese national immunization program recommends that children receive 4 doses of acellular pertussis vaccine between 3 months and 2 years of age. Nevertheless, the number of pertussis cases is increasing in elementary school children aged 6-12 years. Therefore, a test-negative case-control study was conducted to assess the effectiveness of the pertussis vaccine program.

Methods: Subjects included children aged ≥3 months who visited a collaborating hospital due to pertussis-specific cough between October 2017 and November 2019. All subjects underwent diagnostic tests for pertussis, and those diagnosed as positive were regarded as cases. Subjects diagnosed as pertussis-negative were classified as controls. Vaccination history was collected using a questionnaire administered to parents with reference to immunization records. Logistic regression models were employed to calculate the odds ratio (OR) and 95% confidence interval for laboratory-confirmed pertussis.

Results: Of 187 recruited subjects (120 cases and 67 controls), questionnaire responses were obtained for 145 subjects (95 cases and 50 controls). Compared with unvaccinated subjects, the vaccine effectiveness (VE) of 4 doses was 70% among all subjects and reached to 90% with marginal significance among subjects under 6 years of age. However, among school-aged subjects, the VE was not suggestive of protection against pertussis (VE: 8%). For vaccinees given 4 doses, the OR for developing pertussis increased significantly with longer duration since the fourth dose (compared with <4.5 years, OR of 6.0-8.2 years = 5.74; OR of ≥8.3 years = 3.88; P for trend by duration < 0.01).

Conclusion: Effectiveness of administering 4 doses of pertussis vaccine during infancy decreases with time passed since the fourth dose. This regimen does not protect school-aged children against pertussis.
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http://dx.doi.org/10.1016/j.vaccine.2020.11.035DOI Listing
January 2021

In response to Liu et al.

Radiother Oncol 2021 02 20;155:e18-e19. Epub 2020 Nov 20.

Ion-beam Radiation Oncology Center, Kanagawa Cancer Center, Yokohama, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.radonc.2020.11.016DOI Listing
February 2021

Recurrent position and innervation pattern of recurrent peroneal nerve: A cadaveric study.

Knee 2020 Dec 13;27(6):1772-1777. Epub 2020 Nov 13.

Department of Anatomy, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.

Background: The recurrent peroneal nerve (RPN) branches from the common peroneal nerve or the deep peroneal nerve and it innervates to the lower patellar region. It has recently been reported that damage to the RPN causes pain in the lower patellar region; therefore, this study examined the recurrent position and the innervation pattern of the RPN.

Methods: Cases of knee deformity or atrophy were excluded, and 50 legs (25 males and 25 females) of 34 cadavers (15 males and 19 females) were examined to assess the recurrent position and the innervation pattern of the RPN.

Results: The recurrent position of the RPN was 27.9 ± 3.6 mm from the tip of the fibula. The RPN innervated to the patellar tendon in five of the 50 legs (10%), to the infrapatellar fat pad in 13 legs (26%), and to both the patellar tendon and the infrapatellar fat pad in 20 legs (40%), and to neither the patellar tendon nor the infrapatellar fat pad in 12 legs (24%). No significant sex differences were observed in the recurrent position and the innervation pattern of the RPN.

Conclusions: In all cases, the recurrent position of the RPN was almost fixed from the tip of the fibula. The RPN frequently innervated to the patellar tendon or the infrapatellar fat pad (76%) in both males and females. These findings would be useful in knee surgery to preserve the RPN or for the diagnosis of pain in the lower patellar region.
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http://dx.doi.org/10.1016/j.knee.2020.09.012DOI Listing
December 2020

Novel Indicator to Ascertain the Status and Trend of COVID-19 Spread: Modeling Study.

J Med Internet Res 2020 11 30;22(11):e20144. Epub 2020 Nov 30.

Department of Physics, Faculty of Science, Kyushu University, Fukuoka, Japan.

Background: In the fight against the pandemic of COVID-19, it is important to ascertain the status and trend of the infection spread quickly and accurately.

Objective: The purpose of our study is to formulate a new and simple indicator that represents the COVID-19 spread rate by using publicly available data.

Methods: The new indicator K is a backward difference approximation of the logarithmic derivative of the cumulative number of cases with a time interval of 7 days. It is calculated as a ratio of the number of newly confirmed cases in a week to the total number of cases.

Results: The analysis of the current status of COVID-19 spreading over countries showed an approximate linear decrease in the time evolution of the K value. The slope of the linear decrease differed from country to country. In addition, it was steeper for East and Southeast Asian countries than for European countries. The regional difference in the slope seems to reflect both social and immunological circumstances for each country.

Conclusions: The approximate linear decrease of the K value indicates that the COVID-19 spread does not grow exponentially but starts to attenuate from the early stage. The K trajectory in a wide range was successfully reproduced by a phenomenological model with the constant attenuation assumption, indicating that the total number of the infected people follows the Gompertz curve. Focusing on the change in the value of K will help to improve and refine epidemiological models of COVID-19.
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http://dx.doi.org/10.2196/20144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708296PMC
November 2020

Muscle Spindles in the Levator Palpebrae Superioris Muscle of Human Adults.

J Craniofac Surg 2021 Jun;32(4):1532-1534

Department of Oculoplastic, Orbital and Lacrimal Surgery, Aichi Medical University Hospital.

Abstract: In this experimental anatomic study, the authors examined the number and distribution of muscle spindles in the levator palpebrae superioris (LPS) muscle of human adults. This study included 11 orbits from 11 cadavers (mean age at death, 81.9 years). The LPS muscles were harvested and equally divided into 5 sections using transverse incisions. Muscle spindles were counted in each section. Consequently, muscle spindles were identified in 4 (36.4%) of the 11 orbits studied. One to 4 muscle spindles were identified in each of these 4 orbits. All muscle spindles were found in the most proximal section (the muscle origin), and no muscle spindles were identified in the other sections. The results indicate that the LPS muscle is associated with a smaller number of muscle spindles as compared with the rest of the extraocular muscles. Since higher muscle spindle numbers are associated with finer motor movements, eyelid opening does not seem to require much precision, compared to ocular movement.
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http://dx.doi.org/10.1097/SCS.0000000000007135DOI Listing
June 2021

Effect of a vaccine information statement (VIS) on immunization status and parental knowledge, attitudes, and beliefs regarding infant immunization in Japan.

Vaccine 2020 11 1;38(50):8049-8054. Epub 2020 Nov 1.

The Committee on Immunization and Infectious Diseases, Japan Pediatric Society, Japan; Division of Basic Nursing, Fukuoka Nursing College, Fukuoka, Japan.

Background: Because of the overabundance of vaccination information on the internet, in the media, and on social media, providing clear and correct information on immunization is critical for parental decision-making. In 2018, the Japan Pediatric Society created and distributed a Vaccine Information Statement (VIS) to provide appropriate immunization information to caregivers. The objectives of the present study were to evaluate the effect of the VIS on immunization rates, adherence to schedule, and parental understanding of immunization in Japan.

Methods: This cross-sectional study was conducted at 18 centers in 2 prefectures in Japan. Caregivers were assigned to an intervention group, which received the VIS and a questionnaire when their child reached the age of 1 month, and a control group, which received only the questionnaire. Using the self-reported questionnaires, we evaluated vaccination rates and schedule adherence at age 2 months, and parental knowledge, attitudes, and beliefs regarding immunization. Three months later, the questionnaires were returned, and the findings were compared between the 2 groups.

Results: We contacted 422 and 428 persons in the intervention and control groups, respectively, and 111/422 (26.3%) and 119/428 (27.8%) returned the surveys. Vaccination rates and adherence rates for the first dose of 4 recommended vaccines did not differ significantly (P > 0.25); however, there were some positive effects on items related to vaccine knowledge (P = 0.03), perceived benefits (P = 0.02), perceived barriers (P < 0.001), and perceived behavioral control (P = 0.01).

Conclusion: The VIS improved parent comprehension of infant immunization. Future studies should examine if the effects of such an intervention persist and affect vaccine uptake throughout childhood.
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http://dx.doi.org/10.1016/j.vaccine.2020.10.049DOI Listing
November 2020

Incidence of Mumps Deafness in Japan, 2005-2017: Analysis of Japanese Insurance Claims Database.

J Epidemiol 2020 Oct 24. Epub 2020 Oct 24.

Department of Pediatrics, Shizuoka Kosei Hospital.

Background: Mumps deafness causes serious problems, and incidence data are needed to identify its disease burden. However, such data are limited, and the reported incidence is highly variable. Nationwide studies in Japan with a large age range are lacking.

Methods: This was a retrospective observational investigation of the 2005-2017 mumps burden using employment-based health insurance claims data. Data were analyzed for 5,190,326 people aged 0-64 years to estimate the incidence of mumps deafness.

Results: Of 68,112 patients with mumps (36,423 males; 31,689 females), 102 (48 males; 54 females) developed mumps deafness-an incidence of 15.0 per 10,000 patients (1 in 668 patients). Fifty-four (52.9%) patients had mumps deafness in childhood (0-15 years), and 48 (47.1%) had mumps deafness in adolescence and adulthood (16-64 years); most cases occurred in childhood, the peak period for mumps onset. The incidence of mumps deafness per 10,000 patients was 73.6 in adolescence and adulthood, 8.4 times higher than the incidence of 8.8 in childhood (P < 0.001). In childhood, the incidence of mumps deafness was 7.2 times higher among 6-15-year-olds (13.8 [95% CI, 10.2-18.2]) than among 0-5-year-olds (1.9 [95% CI, 0.6-4.5]), and this difference was statistically significant (P < 0.001). No sex difference was observed.

Conclusions: The incidence of mumps deafness per 10,000 patients aged 0-64 years was 15.0 (1 in 668 patients). A secondary risk of deafness following mumps virus infection was identified not only for children, but also for adolescents and adults.
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http://dx.doi.org/10.2188/jea.JE20200233DOI Listing
October 2020

Construction and characterization of an infectious clone generated from Chikungunya virus SL11131 strain.

Virology 2021 Jan 6;552:52-62. Epub 2020 Oct 6.

Department of Microbiology and Infection Control, Osaka Medical College, Takatsuki, Japan.

Chikungunya virus (CHIKV) is a mosquito-borne RNA virus that causes Chikungunya fever in humans. In this study, we generated two DNA-based CHIKV infectious clones derived from an Indian Ocean Lineage SL11131 strain and a prototype Ross strain. When the replication capabilities of the infectious CHIKV in various cell lines were evaluated, the SL11131 strain was found to replicate more efficiently than the Ross strain in Aedes albopictus C6/36 cells, whereas SL11131 underwent limited replication in a BHK-21-derivative cell line named BHK-DRV. Infection experiments using chimeric CHIKV between SL11131 and Ross revealed that these different replication activities of SL11131 in C6/36 and BHK-DRV cells were determined by structural and nonstructural genes, respectively. Therefore, the infectious clones created in this study will be a useful tool for investigating the virological features of a recent epidemic strain of CHIKV and benefit the development of effective prevention and treatment of CHIKV infection.
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http://dx.doi.org/10.1016/j.virol.2020.09.006DOI Listing
January 2021

A text mining analysis of perceptions of the COVID-19 pandemic among final-year medical students.

Acute Med Surg 2020 Jan-Dec;7(1):e576. Epub 2020 Oct 2.

Medical Education Center Osaka Medical College Takatsuki Japan.

Aim: The coronavirus disease 2019 (COVID-19) pandemic has presented various challenges to medical schools. We performed a text mining analysis via essay task to clarify perceptions among final-year medical students toward the COVID-19 pandemic.

Methods: We posed the following essay question to 124 final-year medical students: "What should medical staff do during the COVID-19 pandemic; what should you do?" Responses were subjected to quantitative analysis using a text mining approach. Frequently occurring key words were extracted, followed by multidimensional scaling and co-occurrence network calculations.

Results: Of the 124 students, 123 (99.2%) responded to the essay question. The following seven key words were identified as high-frequency words: medical, infection, patient, human, myself, doctor, and information. Co-occurrence network calculations revealed that the word "medical" had a high degree of correlation with most key words, except for "doctor." The word "myself" was correlated with not only "medical" but also "infection," "human," and "doctor."

Conclusion: Our analysis of perceptions among final-year medical students toward the COVID-19 pandemic revealed that most medical students are strongly affected by the COVID-19 pandemic and are motivated to work as physicians among health care professionals.
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http://dx.doi.org/10.1002/ams2.576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531178PMC
October 2020

Recent advances in clinical studies of selenium supplementation in radiotherapy.

J Trace Elem Med Biol 2020 Dec 28;62:126653. Epub 2020 Sep 28.

Department of Public Health, Gunma University Graduate School of Medicine, Maebashi, Japan. Electronic address:

Background: Radiotherapy is one of the most important and common therapies for cancer patients. Selenium has been shown to be capable of reducing the side effects of radiotherapy because selenoproteins have anti-oxidative functions against reactive oxygen species that are induced by the radiation. They also function in DNA-repair and cytokine control.

Purpose: We explored the benefits and risks of selenium supplementation in radiotherapy in our previous review to establish guidelines. In the current study, we expanded the search to cover recent advances in clinical studies of selenium supplementation in radiotherapy.

Methods: We conducted an initial screening in the PubMed using the MeSH terms and keywords "selenium", "radiation", "therapy", and "radiotherapy" using the same methodology applied in our previous review. We identified 121 articles published between January 2013 and December 2019. We then identified eight articles (six studies) on selenium and radiotherapy by excluding 113 articles.

Results: In selenium supplementation studies, selenium doses of 300-500 μg/day with duration of 10 days to 6 months were used. Selenium supplementation improved the selenium nutritional conditions of the patients and reduced the side effects of radiotherapy. Selenium supplementation did not reduce the effectiveness of radiotherapy, and no toxicities were reported.

Conclusion: The results of our previous and current reviews showed that selenium supplementation offers specific benefits for several cancer types treated with radiotherapy. Here, we suggest a new guideline for selenium supplementation in radiotherapy. We recommend determining the selenium status of the patients before radiotherapy, and in cases of deficiency (<100 μg/L serum selenium level), selenium supplement can be beneficial.
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http://dx.doi.org/10.1016/j.jtemb.2020.126653DOI Listing
December 2020