The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Volume 255, Issue 3
November
Displaying 1-10 of 10 articles from this issue
Editorial: Review Series in Disaster Medicine
  • Susumu Fujii, Sayuri Nonaka, Masaharu Nakayama
    Article type: Review
    2021 Volume 255 Issue 3 Pages 183-194
    Published: 2021
    Released on J-STAGE: December 02, 2021
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    Disaster response procedures have been developed and improved following the Great East Japan Earthquake. Innovative services have also been created through digital transformation, including an acceleration and deepening of artificial intelligence technology. Things that were once technically impossible are now possible. These innovative technologies will spread across various fields, and disaster response will not be an exception. The Ministry of Health, Labour and Welfare is promoting the use of personal health records in a way that effectively supports the management of treatments by using data from wearable devices and specific applications. During the COVID-19 pandemic, the trade-off between protecting personal information and enabling social benefits, such as in the use of digital tracking, and infodemics, including misinformation, have become new social challenges. Reviewing past disaster preparedness and the services and value provided by digital transformation indicates what new disaster preparedness should be. Digital transformation does not require literacy (ability to collect, analyze, and use information) but competence (beneficial behavioral traits derived from experience). Understanding behavior through data and enabling rational behavior are crucial. By increasing human productivity, we can save time and improve self- and mutual-help in times of disaster. Medical information and digital services must be properly used in normal times. A society that uses such services will be more disaster resilient.

Regular Contribution
  • Eiji Suzuki, Jumpei Temmoku, Yuya Fujita, Makiko Yashiro-Furuya, Tomoy ...
    Article type: Regular Contribution
    2021 Volume 255 Issue 3 Pages 195-202
    Published: 2021
    Released on J-STAGE: November 10, 2021
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    The aim of this study was to compare the characteristics of Japanese patients with elderly-onset Adult-onset Still’s disease (AOSD) and those with younger-onset AOSD. Patients were classified into elderly-onset (≥ 65 years, n = 20) and younger-onset (< 65 years, n = 62) groups according to age at AOSD diagnosis. Analyses included the comparison of clinical features, treatments, and Pouchot and modified Pouchot (mPouchot) scores between the two groups. The frequencies of sore throat, lymphadenopathy, and splenomegaly were significantly lower in the elderly-onset group than in the younger-onset group (30.5% vs. 80.6%, p = 0.0004; 15.0% vs. 54.8%, p = 0.0019; 30.0% vs. 61.3%, p = 0.0203; respectively). There were no significant differences in the frequencies of complications, such as macrophage activation syndrome and disseminated intravenous coagulation, between the patients with elderly-onset or younger-onset AOSD. Serum ferritin levels were higher in the elderly-onset group than in the younger-onset group, albeit without statistical significance (median, 9,423 vs. 4,164 ng/mL, p = 0.1727). Pouchot score was lower in the elderly-onset group than in the younger-onset group (median score, 5.5 vs. 4.0, p = 0.0008); however, there was no significant difference in the mPouchot score between the two groups. Our analyses revealed that elderly-onset AOSD was associated with certain characteristics that were distinct from those of younger-onset AOSD and that the disease severity in patients with elderly-onset AOSD, determined by Pouchot score at the time of AOSD diagnosis, was similar to or less than that in patients with younger-onset AOSD.

  • Qihong Liang, Wei Zhong
    Article type: Regular Contribution
    2021 Volume 255 Issue 3 Pages 203-212
    Published: 2021
    Released on J-STAGE: November 10, 2021
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    As a member of the deubiquitinating protease family, ubiquitin specific peptidase 18 (USP18) is well acknowledged for its roles in stabilizing downstream protein substrates and inhibiting type I interferon signaling. USP18 has been reported to exert distinct roles in different cancer types. However, its expression and function in papillary thyroid carcinoma (PTC) remain unknown. Here we collected 156 PTC patients and retrospectively retrieved their clinicopathological characteristics as well as their survival data. Among them, USP18 was hypoexpressed in 47 PTC samples (30.1%) and significantly correlated with oncogenic characteristics. According to univariate and multivariate analyses, low USP18 can act as an independent prognostic indicator for unfavorable progression-free survival of PTC patients. Ectopic overexpression and knockdown assays indicated that USP18 can negatively regulate the proliferation of PTC cell lines. The anti-tumor effect of USP18 was finally validated by xenografts results from nude mice. Taken together, PTC patients with low level of USP18 have worse survival compared to those possess high USP18 expression. Downregulated USP18 may be involved in the proliferation of PTC, and USP18 expression can serve as an independent survival predictor.

  • Olivera Milošević-Djordjević, Jovana Tubić Vukajlović, Aleksandra Mark ...
    Article type: Regular Contribution
    2021 Volume 255 Issue 3 Pages 213-219
    Published: 2021
    Released on J-STAGE: November 10, 2021
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    The measurement of micronuclei (MN) in umbilical blood lymphocytes of newborns are increasingly used in cytogenetic epidemiology as one of the preferred methods for assessing chromosomal damage resulted from maternal exposure to mutagen. In the present study, we evaluated the effect of strong environmental contamination (EC) (which occured in the City of Kragujevac, Central Serbia in 1999) on the MN frequency in group of 22 newborns born in Kragujevac 18 years after EC, using cytokinesis-block micronucleus (CBMN) assay. The mean MN frequency in umbilical lymphocytes of these newborns was 5.14 ± 2.17/1,000 binucleated (BN) cells, which is significantly lower than mean MN frequency of newborns born 12 months after contamination (9.36 ± 5.60/1,000 BN cells). Sex of newborns, age of mothers, cigarette smoking, and number of pregnancies did not affect the MN frequency of newborns. Our results showed that in utero exposure to environmental pollution affected genome instability of the fetuses, but that by improving the quality of environmental conditions there was a decrease in mean MN frequency of newborns born 18 years after contamination. In general, genome of umbilical lymphocytes shows a realistic picture of all changes in body and the environment.

  • Sho Sekiguchi, Eijiro Yamada, Yasuyo Nakajima, Shunichi Matsumoto, Sat ...
    Article type: Regular Contribution
    2021 Volume 255 Issue 3 Pages 221-227
    Published: 2021
    Released on J-STAGE: November 11, 2021
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    Achieving the optimal glucose level time in range (TIR), as recently proposed by the “International Consensus on Time in Range,” is challenging. We retrospectively analyzed data from 192 patients, including 58 with type 1 diabetes, using the FreeStyle Libre Pro system. This device was used by physicians for continuous glucose monitoring (CGM) and for making therapeutic decisions based on unbiased data, as the patients were blinded to their blood glucose levels during monitoring. The desired 70% TIR among patients with type 2 diabetes corresponded to an HbA1c of 7.7%. Importantly, however, a 70% TIR for patients with type 1 diabetes corresponded to an HbA1c of 6.9%, which diverged markedly from the HbA1c of 7.9% that corresponded to the desired 4% time below range (TBR). Moreover, these dissociations were observed more in patients with type 1 diabetes with a higher % coefficient of variation (> 36%). Hence, while the TIR is strongly correlated with HbA1c, it is difficult to coordinate with the TBR in Japanese patients with type 1 diabetes. As these metrics (which are critical indicators in clinical practice) are rapidly gaining popularity globally, including in Japan, our data strongly support the cautious use of new CGM metrics such as TIR and TBR/time above range, and emphasize the importance of individualized treatment in achieving the optimal TIR and TBR, especially in patients with type 1 diabetes.

  • Masaaki Naganuma, Masatoshi Akiyama, Konosuke Sasaki, Kay Maeda, Koki ...
    Article type: Regular Contribution
    2021 Volume 255 Issue 3 Pages 229-237
    Published: 2021
    Released on J-STAGE: November 17, 2021
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    De novo aortic insufficiency is often documented during long-term left ventricular assist device (LVAD) support, despite the absence of aortic insufficiency at the time of LVAD implantation. However, whether aortic insufficiency affects long-term mortality and symptomatic heart failure in LVAD-supported patients remains controversial. We aimed to examine whether aortic insufficiency development influenced mortality and symptomatic heart failure following LVAD implantation. Fifty-three patients who underwent durable LVAD implantation between January 1, 2008 and April 31, 2017 were retrospectively examined in a single center institute. After discharge, we performed the echocardiographic examination in accordance with the Japanese registry for the mechanically assisted circulatory support protocol. Aortic insufficiency was graded on an interval scale (severe = 4, moderate = 3, mild = 2, trivial or none = 1). Kaplan-Meier estimates for long-term mortality at the follow-up were generated. We used a logistic regression model to identify risk factors for symptomatic heart failure. The overall median duration of LVAD support was 856.3 ± 430.8 days (range, 12-1,744 days). We did not observe a significant difference in long-term mortality in patients with aortic insufficiency ≥ 3 grade compared with patients with aortic insufficiency < 3 grade (P = 0.767; log-rank). Aortic insufficiency was associated with an increased risk for heart failure event after discharge (odds ratio, 4.12; confidence interval, 1.48-16.93; P = 0.005). Aortic insufficiency was an independent risk factor for symptomatic heart failure and was not associated with long-term mortality. Aortic insufficiency progression was associated with symptomatic heart failure.

  • Tetsuya Akaishi, Shigeki Kushimoto, Yukio Katori, Noriko Sugawara, Kao ...
    Article type: Regular Contribution
    2021 Volume 255 Issue 3 Pages 239-246
    Published: 2021
    Released on J-STAGE: November 20, 2021
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    The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global public health concern in 2021. However, the risk of attending schools during the pandemic remains unevaluated. This study estimated the secondary transmission rate at schools using the results of a real-time reverse transcription-polymerase chain reaction (RT-PCR) screening test performed between July 2020 and April 2021, before starting the nationwide mass vaccination. A total of 1,924 students (20 RT-PCR-positive; 1.0%) from 52 schools or preschools were evaluated, together with 1,379 non-adults (95 RT-PCR-positive; 6.9%) exposed to SARS-CoV-2 in non-school environments. Assuming that the infectious index cases were asymptomatic and the transmission at schools followed a Bernoulli process, we estimated the probability of transmission after each contact at school as approximately 0.005 (0.5% per contact) with the current infection prevention measures at schools in Japan (i.e., hand hygiene, physical distancing, wearing masks, and effective ventilation). Furthermore, assuming that all children are capable of carrying the infection, then contact between an index case and 20-30 students per day at schools would yield the expected value for secondary cases of ≥ 1.0, during the 10 days of the infectious period. In conclusion, with the current infection prevention measures at schools in Japan, secondary transmission at schools would occur in approximately every 200 contacts. When considering this rate, compliance with the current infection prevention measures at schools and early detection and quarantine of the index cases would be effective in preventing the spread of COVID-19 at schools.

  • Yingfei Dou, Hankun Xu, Xiaoqian Wu, Pei Liu
    Article type: Regular Contribution
    2021 Volume 255 Issue 3 Pages 247-256
    Published: 2021
    Released on J-STAGE: November 26, 2021
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    As the most common tumor of central nervous system in adults, glioma is characterized with poor prognosis. Tac2-N (TC2N) is a newly discovered protein that play potential roles in lung cancer and breast cancer progression. Here we aimed to investigate the expression, clinical significance, and function of TC2N in glioma. The mRNA level of TC2N in glioma patients was extracted from TCGA datasets. Immunohistochemistry staining was conducted to test protein expression of TC2N in glioma tissues. Chi-square test was used to assess correlations between TC2N expression and patients’ clinicopathological characteristics. Kaplan-Meier method was used to plot survival curves. The prognostic predictive role of TC2N was evaluated by univariate and multivariate analyses. Knockdown assays were performed in U87 and U251 cell lines, respectively. Cell proliferation, colony formation, and subcutaneous mice xenografts were used to reveal the tumor-related role of TC2N in glioma. Compared with normal brain tissues, the mRNA level of TC2N was significantly higher in glioma tissues, whose dysregulated higher mRNA level was correlated with poorer overall survival. Similarly, higher protein expression of TC2N was observed in cases with larger tumor size and advanced WHO grades. Univariate and multivariate analyses identified TC2N as a novel independent prognostic factor of gliomas. In vitro and in vivo data demonstrated that TC2N interference can remarkably prevent glioma cell proliferation and tumor growth. In conclusion, high TC2N expression is significantly correlated with poor overall survival of glioma patients via enhancing tumor growth.

  • He Nie, Jiadong Pan, Fangmei An, Chuwei Zheng, Qinglin Zhang, Qiang Zh ...
    Article type: Regular Contribution
    2021 Volume 255 Issue 3 Pages 257-265
    Published: 2021
    Released on J-STAGE: December 01, 2021
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    Acute radiation enteritis is a common complication occurring in patients with pelvic and abdominal tumors who receive radiotherapy. Acute radiation enteritis seriously reduces the life quality, even threatens the lives of patients. Untargeted metabolomics is an emerging strategy to explore the novel biomarkers and uncover potential pathogenesis of acute radiation enteritis. Acute radiation enteritis rat model was established by single abdominal irradiation with a gamma-ray dose of 10 Gy. Serum from 15 acute radiation enteritis rats and 10 controls was extracted for metabolomics analysis by UHPLC-Q-TOF/MS. Clinical manifestations and morphological alterations of intestine confirmed the successful establishment of acute radiation enteritis. According to the metabolomics data, 6,044 positive peaks and 4,241 negative peaks were extracted from each specimen. OPLS-DA analysis and the heat map for cluster analysis showed satisfactory discriminatory power between acute radiation enteritis rats and controls. Subsequent analysis extracted 66 significantly differentially expressed metabolites, which might be potential biomarkers for acute radiation enteritis diagnosis. Moreover, Kyoto Encyclopedia of Genes and Genomes enrichment analyses uncovered the potential mechanisms through which differentially expressed metabolites participated in acute radiation enteritis pathogenesis. To sum up, we summarized several differentially expressed serum metabolites as potential biomarkers for diagnosis of acute radiation enteritis and provide latent clues for elucidating acute radiation enteritis pathology.

  • Mehmet Mustafa Altıntaş, Ayşegül Karadayı Büyüközsoy, Ömer Aydıner
    Article type: Regular Contribution
    2021 Volume 255 Issue 3 Pages 267-273
    Published: 2021
    Released on J-STAGE: December 01, 2021
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    The aim of this study was to evaluate the admission chest and abdominal computed tomography (CT) findings of patients who presented to the emergency department with complaints of abdominal pain, fever, and shortness of breath and who had RT-PCR-confirmed COVID-19 infection. Seventy-five patients with RT-PCR-confirmed (in laboratory) COVID-19 infection who underwent chest and abdominal CT were included in the study. The radiological scales [the COVID-19 Reporting and Data System (CO-RADS) and severity score] of the chest and abdominal findings were examined on CT images. Forty-one (54.7%) patients were male and 34 (45.3%) were female. The mean age of the patients was 63.03 (range 24-89) years. The most frequently calculated CO-RADS score was found to be 5 (n = 53, 70.7%). Bilateral (72.0%) and multibolar (74.7%) involvement, peripheral (72.0%) and posterior (60.0%) distribution, and ground-glass opacity (66.7%) pattern were the most common pulmonary findings. A positive correlation was observed between CO-RADS and total severty score (p < 0.001). All patients were hospitalized. One (1.3%) patient was surgically treated because of acute appendicitis. Nine (12.0%) patients were admitted to the intensive care unit. Six (8.0%) patients died in the intensive care unit. Patients presenting to the emergency department with both abdominal and respiratory complaints during the pandemic should be evaluated for COVID-19. Patients can be diagnosed early with the data collected from CT without waiting for the PCR result. Hospital staff can take the necessary protective measures against virus transmission early, minimizing the in-hospital transmission of the virus.

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