Papers - TUGAWA Takesi

データベースを用いた国内小児新型コロナウイルス感染症の臨床症状に関する評価

勝田 友博, 清水 直樹, 神谷 元, 天羽 清子, 大城 誠, 菅 秀, 津川 毅, 西村 直子, 菱木 はるか, 藤岡 雅司, 細矢 光亮, 水野 由美, 吉川 哲史, 和田 泰三, 石和田 稔彦, 是松 聖悟, 中野 貴司, 宮入 烈, 尾内 一信, 齋藤 昭彦, 森内 浩幸, 多屋 馨子, 日本小児科学会予防接種・感染症対策委員会

日本小児科学会雑誌 ( (公社)日本小児科学会 )  127 ( 1 ) 79 - 83  2023.01

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2020年2月～2022年4月に専用データベースに報告された小児コロナウイルス感染症2019患者のうち、0～15歳の5411例(男児2889例、女児2522例)の急性期における臨床的特徴を解析した。オミクロン株流行により感染経路は家庭内感染から学校・幼稚園・保育所へ変化した。オミクロン株流行期に初発症状でけいれん発作を起こした割合は1～4歳で13.4%、5～11歳で7.4%、オミクロン株流行期に初発症状で悪心・嘔吐を認めた割合は1～4歳で12.2%、5～11歳で22.6%、12～15歳で14.6%であり、いずれもデルタ株流行前またはデルタ株流行期と比較して大幅に増加した。最終的に全体の約2%にけいれんを伴う合併症が報告された。肺炎の合併率は変異株の違いによる変化をほとんど認めなかった。発症後28日を超えた症例報告書が提出された1697例(男児899例、女児798例、年齢中央値6.3歳)のうち、55例(3.2%)に発症後28日を超えても何らかの症状が残存した。

Acute and Postacute Clinical Characteristics of Coronavirus Disease 2019 in Children in Japan.

Tomohiro Katsuta, Yuta Aizawa, Kensuke Shoji, Naoki Shimizu, Kenji Okada, Takashi Nakano, Hajime Kamiya, Kiyoko Amo, Naruhiko Ishiwada, Satoshi Iwata, Makoto Oshiro, Nobuhiko Okabe, Seigo Korematsu, Shigeru Suga, Takeshi Tsugawa, Naoko Nishimura, Haruka Hishiki, Masashi Fujioka, Mitsuaki Hosoya, Yumi Mizuno, Isao Miyairi, Chiaki Miyazaki, Tsuneo Morishima, Tetsushi Yoshikawa, Taizo Wada, Kazunobu Ouchi, Hiroyuki Moriuchi, Keiko Tanaka-Taya, Akihiko Saitoh

The Pediatric infectious disease journal   42 ( 3 ) 240 - 246  2022.11  [Refereed]  [International journal]

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BACKGROUND: The clinical features of coronavirus disease 2019 (COVID-19) in children have been changing because of the emergence and rapid spread of variants of concern (VOC). The increase in cases infected with VOC has brought concern with persistent symptoms after COVID-19 in children. This survey aimed to analyze the clinical manifestations and persistent symptoms of pediatric COVID-19 cases in Japan. METHODS: We analyzed the clinical manifestations of pediatric COVID-19 cases reported between February 2020 and April 2022 in Japan, using a dedicated database updated voluntarily by the members of the Japan Pediatric Society. Using the same database, we also analyzed persistent symptoms after COVID-19 in children who were diagnosed between February 2020 and November 2021. RESULTS: A total of 5411 and 1697 pediatric COVID-19 cases were included for analyzing clinical manifestations and persistent symptoms, respectively. During the Omicron variant predominant period, the percentage of patients with seizures increased to 13.4% and 7.4% in patient groups aged 1-4 and 5-11 years, respectively, compared with the pre-Delta (1.3%, 0.4%) or Delta period (3.1%, 0.0%). Persistent and present symptoms after 28 days of COVID-19 onset were reported in 55 (3.2%). CONCLUSIONS: Our survey showed that the rate of symptomatic pediatric COVID-19 cases increased gradually, especially during the Omicron variant predominant period, and a certain percentage of pediatric cases had persistent symptoms. Certain percentages of pediatric COVID-19 patients had severe complications or prolonged symptoms. Further studies are needed to follow such patients.

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Rhinovirus Infection and Virus-Induced Asthma

Yuriko Hayashi, Mitsuru Sada, Tatsuya Shirai, Kaori Okayama, Ryusuke Kimura, Mayumi Kondo, Mitsuaki Okodo, Takeshi Tsugawa, Akihide Ryo, Hirokazu Kimura

Viruses ( MDPI AG )  14 ( 12 ) 2616 - 2616  2022.11  [Refereed]

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While the aetiology of asthma is unclear, the onset and/or exacerbation of asthma may be associated with respiratory infections. Virus-induced asthma is also known as virus-associated/triggered asthma, and the reported main causative agent is rhinovirus (RV). Understanding the relationship between viral infections and asthma may overcome the gaps in deferential immunity between viral infections and allergies. Moreover, understanding the complicated cytokine networks involved in RV infection may be necessary. Therefore, the complexity of RV-induced asthma is not only owing to the response of airway and immune cells against viral infection, but also to allergic immune responses caused by the wide variety of cytokines produced by these cells. To better understand RV-induced asthma, it is necessary to elucidate the nature RV infections and the corresponding host defence mechanisms. In this review, we attempt to organise the complexity of RV-induced asthma to make it easily understandable for readers.

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Detailed Molecular Interactions between Respiratory Syncytial Virus Fusion Protein and the TLR4/MD-2 Complex In Silico.

Mao Akagawa, Tatsuya Shirai, Mitsuru Sada, Norika Nagasawa, Mayumi Kondo, Makoto Takeda, Koo Nagasawa, Ryusuke Kimura, Kaori Okayama, Yuriko Hayashi, Toshiyuki Sugai, Takeshi Tsugawa, Haruyuki Ishii, Hisashi Kawashima, Kazuhiko Katayama, Akihide Ryo, Hirokazu Kimura

Viruses   14 ( 11 )  2022.10  [Refereed]  [International journal]

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Molecular interactions between respiratory syncytial virus (RSV) fusion protein (F protein) and the cellular receptor Toll-like receptor 4 (TLR4) and myeloid differentiation factor-2 (MD-2) protein complex are unknown. Thus, to reveal the detailed molecular interactions between them, in silico analyses were performed using various bioinformatics techniques. The present simulation data showed that the neutralizing antibody (NT-Ab) binding sites in both prefusion and postfusion proteins at sites II and IV were involved in the interactions between them and the TLR4 molecule. Moreover, the binding affinity between postfusion proteins and the TLR4/MD-2 complex was higher than that between prefusion proteins and the TLR4/MD-2 complex. This increased binding affinity due to conformational changes in the F protein may be able to form syncytium in RSV-infected cells. These results may contribute to better understand the infectivity and pathogenicity (syncytium formation) of RSV.

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Liver Enzyme Elevation Related to Human Parainfluenza Virus Type 3 Infection.

Yoshimasa Kudo, Tomohiro Wakabayashi, Shuichi Miyamoto, Yuta Sasaoka, Yoshiyuki Sakai, Takeshi Tsugawa

The Pediatric infectious disease journal   41 ( 10 ) e437-e438  2022.10  [Refereed]  [International journal]

Authorship：   Last author

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The human parainfluenza viruses are common causes of upper and lower respiratory tract infection; however, nonrespiratory infections with human parainfluenza viruses are rare, and there are no reports of pediatric cases of liver enzyme elevation. We present 2 pediatric patients who developed liver enzyme elevation related to human parainfluenza virus type 3 infection.

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A novel ZC4H2 variant in a female with severe respiratory complications.

Tomohiro Wakabayashi, Miyako Mizukami, Kojiro Terada, Aki Ishikawa, Shiro Hinotsu, Masaki Kobayashi, Koji Kato, Tomoo Ogi, Takeshi Tsugawa, Akihiro Sakurai

Brain & development   44 ( 8 ) 571 - 577  2022.09  [Refereed]  [International journal]

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INTRODUCTION: An X-linked ZC4H2 variant is associated with a variety of phenotypes that have abnormalities related to external malformation and neurodevelopment. There have been no reports on severe respiratory dysfunction resulting in surgical treatments not being possible due to the deformity resulting from in this disease. Here we report a female with arthrogryposis multiplex congenita with a severe respiratory complication. CASE: A two-year-old girl had arthrogryposis multiplex congenita at delivery and subsequently had hypotonia and feeding difficulty. A novel ZC4H2 frameshift variant was identified by whole-exome sequencing in her genome. At eight months, she had recurrent aspiration pneumonia. A tracheostomy and gastrostomy were required; however, surgical intervention was not possible because of her short neck and complicated airway. CONCLUSION: We compared this case with previous reports. The truncation group had more described phenotypes than the non-truncation group. The patient had the most severe respiratory dysfunction in truncating variant.

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Molecular Evolution of the Pseudomonas aeruginosa DNA Gyrase gyrA Gene.

Mitsuru Sada, Hirokazu Kimura, Norika Nagasawa, Mao Akagawa, Kaori Okayama, Tatsuya Shirai, Soyoka Sunagawa, Ryusuke Kimura, Takeshi Saraya, Haruyuki Ishii, Daisuke Kurai, Takeshi Tsugawa, Atsuyoshi Nishina, Haruyoshi Tomita, Mitsuaki Okodo, Shinichiro Hirai, Akihide Ryo, Taisei Ishioka, Koichi Murakami

Microorganisms   10 ( 8 )  2022.08  [Refereed]  [International journal]

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DNA gyrase plays important roles in genome replication in various bacteria, including Pseudomonasaeruginosa. The gyrA gene encodes the gyrase subunit A protein (GyrA). Mutations in GyrA are associated with resistance to quinolone-based antibiotics. We performed a detailed molecular evolutionary analyses of the gyrA gene and associated resistance to the quinolone drug, ciprofloxacin, using bioinformatics techniques. We produced an evolutionary phylogenetic tree using the Bayesian Markov Chain Monte Carlo (MCMC) method. This tree indicated that a common ancestor of the gene was present over 760 years ago, and the offspring formed multiple clusters. Quinolone drug-resistance-associated amino-acid substitutions in GyrA, including T83I and D87N, emerged after the drug was used clinically. These substitutions appeared to be positive selection sites. The molecular affinity between ciprofloxacin and the GyrA protein containing T83I and/or D87N decreased significantly compared to that between the drug and GyrA protein, with no substitutions. The rate of evolution of the gene before quinolone drugs were first used in the clinic, in 1962, was significantly lower than that after the drug was used. These results suggest that the gyrA gene evolved to permit the bacterium to overcome quinolone treatment.

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Genotypes and transmission routes of noroviruses causing sporadic acute gastroenteritis among adults and children, Japan, 2015-2019.

Saho Honjo, Koji Kuronuma, Yoshihiro Fujiya, Mami Nakae, Susumu Ukae, Hiroshi Nihira, Masaki Yamamoto, Yusuke Akane, Kenji Kondo, Satoshi Takahashi, Hirokazu Kimura, Hiroyuki Tsutsumi, Yukihiko Kawasaki, Takeshi Tsugawa

Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases   104   105348 - 105348  2022.08  [Refereed]  [International journal]

Authorship：   Last author  , Corresponding author

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Noroviruses (NoVs) are major causes of acute viral gastroenteritis at all ages worldwide. The molecular epidemiology of sporadic cases remains poorly understood, especially in adults. Additionally, no studies have analyzed the transmission route in sporadic acute gastroenteritis. In this study, we investigated cases of very mild sporadic NoV acute gastroenteritis in adults (medical staff) who do not visit the outpatient clinic and child outpatients. We also evaluated genotype differences between adults and children and possible transmission routes in adults during 5 years. The number of NoV positives were 58 in adults and 124 in children. In adults, the NoV positivity rate in this study was higher (64.4%) than that in previous reports of outpatients (10%) and inpatients (5%) in the United State. This finding suggested that the NoV positivity rate might be high in adults with very mild acute gastroenteritis. In adults, human-to-human transmission rates from children and food-borne transmission (raw oysters) were 21.6% (11/51) and 19.6% (10/51), respectively. Among adults, GII.2, GII.4, and GII.17 were the predominant genotypes, with rates of 32.7%, 30.9%, and 21.8%, respectively. Among children, GII.4 and GII.2 were the predominant genotypes, with rates of 45.5% and 40.6%, respectively. GII.17 was only detected in 0.8% (1/123) of children. Trends in NoV genotypes are expected to differ depending on the patient's age. Investigating sporadic cases including the patient's background (age and transmission route) may be helpful to monitor the trend of NoV strains, forecast prevalent NoV GII genotypes, and develop NoV vaccines.

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Delayed dexamethasone treatment at initiation of oxygen supplementation for coronavirus disease 2019 is associated with the exacerbation of clinical condition.

Yuta Ibe, Tomoyuki Ishigo, Satoshi Fujii, Yoshihiro Fujiya, Koji Kuronuma, Takeshi Tsugawa, Satoshi Takahashi, Masahide Fukudo

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   28 ( 7 ) 875 - 883  2022.07  [Refereed]  [International journal]

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INTRODUCTION: Coronavirus disease 2019 (COVID-19) frequently causes inflammatory lung injury as its symptoms progress. While dexamethasone reportedly reduces inflammation and prevents progression to respiratory failure, the appropriate time to administer dexamethasone in patients with COVID-19 remains unclear. METHODS: This was a single-center, retrospective cohort study, where we consecutively enrolled patients hospitalized with COVID-19 who received oxygen and oral dexamethasone (n = 85). We assessed the association between the number of days to the initiation of dexamethasone and the cumulative rate of exacerbation defined as death or initiation of mechanical ventilation within 28 days of symptom onset. RESULTS: The optimal cut-off value from the initiation of oxygen supplementation to that of dexamethasone administration was two days (sensitivity, 85%; specificity, 59%), whereas that from oxygen saturation (SpO2) < 95% to the initiation of dexamethasone administration was five days (sensitivity, 78%; specificity, 59%). adjusting for age, sex, body mass index, Charlson comorbidity index score, time of oxygen supplementation (two or more days), and SpO2 < 95% (five or more days), Cox regression analysis results showed that delayed dexamethasone administration since the initiation of oxygen supplementation was significantly associated with a higher risk of death or greater need for mechanical ventilation (hazard ratio: 5.51, 95% confidence interval, 1.79-16.91). CONCLUSIONS: In patients with COVID-19 and hypoxemia, early administration of dexamethasone, preferably less than two days from initiation of oxygen supplementation, may be required to improve clinical outcomes.

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House Dust Mite Subcutaneous Immunotherapy and Lung Function Trajectory in Children and Adolescents with Asthma.

Kazutaka Nogami, Mizuho Nagao, Takafumi Takase, Yasuaki Yasuda, Shingo Yamada, Mayumi Matsunaga, Miyuki Hoshi, Kana Hamada, Yu Kuwabara, Takeshi Tsugawa, Takao Fujisawa

Children (Basel, Switzerland)   9 ( 4 )  2022.04  [Refereed]  [International journal]

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Background: Allergen-specific immunotherapy is currently the only disease-modifying treatment for allergic asthma, and it has been shown to improve control of asthma while reducing both drug use and asthma exacerbations. However, its effects on lung function—especially its long-term effects—remain controversial. We aimed to identify factors associated with a possible beneficial effect of allergen-specific immunotherapy on lung function in asthma by retrospectively evaluating the long-term changes in lung function in children with asthma who received house dust mite subcutaneous immunotherapy (HDM-SCIT). Methods: We enrolled children with asthma who had undergone HDM-SCIT for more than 1 year. Clinical information and lung function measurements were retrieved from the electronic chart system. To characterize the trajectory of lung function change, we performed linear regression analysis to evaluate the maximal expiratory flow at 50% of the forced vital capacity during two periods: before and during HDM-SCIT. Slopes from a least-squares regression line for the two periods, i.e., S1 before HDM-SCIT and S2 during HDM-SCIT, were compared. The subjects were then classified into two groups: an improving group (Group I) defined as S2 − S1 > 0, and a declining group (Group D) defined as S2 − S1 < 0. The clinical factors at the start of HDM-SCIT were compared between the two groups. Results: A total of 16 patients were analyzed. Eight patients were classified into each of Group I and Group D. The mean ages were 10.5 and 11.8 years, and the mean treatment periods were 4.1 and 3.9 years. Group I had a significantly lower blood eosinophil count and a significantly higher HDM-specific IgE level than Group D. Logistic regression showed a strong relationship between those two markers and the lung function trajectory. Conclusion: Control of the blood eosinophil count in highly HDM-sensitized patients may increase the beneficial effect of HDM-SCIT on lung function.

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繰り返す腰椎穿刺により脳脊髄液漏出をきたした脊髄性筋萎縮症I型の1例

加藤 辰輔, 土田 晃輔, 福村 忍, 津川 毅

臨床小児医学 ( (財)小児愛育協会 )  69 ( 1-6 ) 55 - 59  2022.03  [Refereed]

Authorship：   Last author

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はじめに:ヌシネルセンは、脊髄性筋萎縮症に対するアンチセンス・オリゴヌクレオチド製剤で、髄腔内に投与される。今回、繰り返す腰椎穿刺により、脳脊髄液漏出をきたした脊髄性筋萎縮症I型を経験した。症例:脊髄性筋萎縮症I型の5歳女児。2歳よりL3-4間に23ゲージ針穿刺によるヌシネルセン髄腔内投与を4ヵ月ごとに繰り返した。12回目の投与後、穿刺部より髄液の漏れおよび腰部皮下浮腫を生じた。頭痛などの症状は認めず、圧迫、安静により、数日で浮腫、髄液漏は消失した。以後は穿髄間を変更し、再発は認めていない。14回目を最後に、経口のアンチセンス・オリゴヌクレオチド製剤に切り替えた。考察:繰り返す腰椎穿刺の際は、髄液漏の出現に注意が必要である。リスク回避には、穿刺髄間を同一にしないこと、細く非侵襲的な脊髄針の選択、経口製剤へ移行が考慮される。(著者抄録)

Transient personality changes with bilateral thalamic infarction in a 12-year-old girl.

Shuhei Adachi, Shinobu Fukumura, Shinsuke Kato, Takeshi Mikami, Takeshi Tsugawa

Pediatrics international : official journal of the Japan Pediatric Society   64 ( 1 ) e15352  2022.01  [Refereed]  [International journal]

Authorship：   Last author

DOI PubMed

Long-term sensor-augmented pump therapy for neonatal diabetes mellitus: a case series.

Yuya Fukuda, Akira Ishii, Hotaka Kamasaki, Shintaro Fusagawa, Kojiro Terada, Lisa Igarashi, Masaki Kobayashi, Shigeru Suzuki, Takeshi Tsugawa

Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology   31 ( 3 ) 178 - 184  2022  [Refereed]  [Domestic journal]

Authorship：   Last author

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Neonatal diabetes mellitus (NDM) is a rare metabolic disorder that is mainly present in the first 6 months of life and necessitates insulin treatment. Sensor-augmented pump (SAP) therapy has been widely used in children with type 1 diabetes mellitus, but its use in patients with NDM is limited. We report three patients with NDM who received SAP therapy using the MiniMed™ 640G system starting in the neonatal period. Two patients were treated for 3 months, and one patient continued treatment up to an age of 22 mo. The MiniMed 640G system can automatically suspend insulin delivery (SmartGuard™ Technology) to avoid hypoglycemia when the sensor glucose level is predicted to approach the predefined threshold. We suggest that SmartGuard Technology is particularly useful for infants in whom hypoglycemia cannot be identified. The MiniMed 640G system automatically records the trends of sensor glucose levels and the total daily dose of insulin, which can make the management more accurate and reduce the family's effort. SAP therapy for patients with NDM automatically prevents severe hypoglycemia and is useful for long-term management; however, attention should be paid to its application.

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Detailed Evolutionary Analyses of the F Gene in the Respiratory Syncytial Virus Subgroup A.

Mariko Saito, Hiroyuki Tsukagoshi, Mitsuru Sada, Soyoka Sunagawa, Tatsuya Shirai, Kaori Okayama, Toshiyuki Sugai, Takeshi Tsugawa, Yuriko Hayashi, Akihide Ryo, Makoto Takeda, Hisashi Kawashima, Nobuhiro Saruki, Hirokazu Kimura

Viruses   13 ( 12 )  2021.12  [Refereed]  [International journal]

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We performed evolution, phylodynamics, and reinfection-related antigenicity analyses of respiratory syncytial virus subgroup A (RSV-A) fusion (F) gene in globally collected strains (1465 strains) using authentic bioinformatics methods. The time-scaled evolutionary tree using the Bayesian Markov chain Monte Carlo method estimated that a common ancestor of the RSV-A, RSV-B, and bovine-RSV diverged at around 450 years ago, and RSV-A and RSV-B diverged around 250 years ago. Finally, the RSV-A F gene formed eight genotypes (GA1-GA7 and NA1) over the last 80 years. Phylodynamics of RSV-A F gene, including all genotype strains, increased twice in the 1990s and 2010s, while patterns of each RSV-A genotype were different. Phylogenetic distance analysis suggested that the genetic distances of the strains were relatively short (less than 0.05). No positive selection sites were estimated, while many negative selection sites were found. Moreover, the F protein 3D structure mapping and conformational epitope analysis implied that the conformational epitopes did not correspond to the neutralizing antibody binding sites of the F protein. These results suggested that the RSV-A F gene is relatively conserved, and mismatches between conformational epitopes and neutralizing antibody binding sites of the F protein are responsible for the virus reinfection.

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Stereotyped Upper Limb Movement in MECP2 Duplication Syndrome.

Tomohiro Wakabayashi, Shinobu Fukumura, Satoru Takahashi, Kenji Kurosawa, Shuichi Miyamoto, Kosuke Tsuchida, Shinsuke Kato, Takeshi Tsugawa, Yoshiyuki Sakai, Yukihiko Kawasaki

Neurology   97 ( 2 ) 92 - 94  2021.07  [Refereed]  [International journal]

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The clinical characteristics of pediatric coronavirus disease 2019 in 2020 in Japan

Tomohiro Katsuta, Naoki Shimizu, Kenji Okada, Keiko Tanaka‐Taya, Takashi Nakano, Hajime Kamiya, Kiyoko Amo, Naruhiko Ishiwada, Satoshi Iwata, Makoto Oshiro, Nobuhiko Okabe, Ryutaro Kira, Seigo Korematsu, Shigeru Suga, Takeshi Tsugawa, Naoko Nishimura, Haruka Hishiki, Masashi Fujioka, Mitsuaki Hosoya, Yumi Mizuno, Mahito Mine, Isao Miyairi, Chiaki Miyazaki, Ichiro Morioka, Tsuneo Morishima, Tetsushi Yoshikawa, Taizo Wada, Hiroshi Azuma, Koichi Kusuhara, Kazunobu Ouchi, Akihiko Saitoh, Hiroyuki Moriuchi

Pediatrics International ( Wiley )   2021.07  [Refereed]

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Children's decision making in cancer therapy: A long-term observational study.

Ryoko Michinobu, Masaki Yamamoto, Tsukasa Hori, Takahiro Mikami, Keita Igarashi, Kotoe Iesato, Akira Takebayashi, Takeshi Tsugawa, Yukihiko Kawasaki, Hiroyuki Tsutsumi

Pediatrics international : official journal of the Japan Pediatric Society   64 ( 1 ) e14700  2021.03  [Refereed]  [International journal]

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BACKGROUND: The survival rate of children with cancer has increased substantially in recent years. Shared decision making (i.e., the ability of children with cancer to express their will and share it with medical personnel) has become a particularly important issue. The nature and developmental processes of children's decision making in hospital should be understood. There is, however, a lack of research in this area. METHODS: From January 2016 to March 2018, we conducted a longitudinal qualitative observational study, within the context of medical anthropology, in a hospital pediatric ward in Japan. We investigated the nature and development of decision making among seven children aged 5-12 years with hematologic cancers. We recorded their everyday behaviors, interactions, narratives, and events in the ward. The recording was conducted systematically and thematically analyzed using both variable-oriented and process-oriented modes to assess causal relationships between the phenomena. RESULTS: The thematic analysis identified three thematic scenes in which children developed their will regarding cancer treatment: (1) adjusting to hospital life, (2) forming friendships with other children, and (3) communicating with medical personnel. Sharing information, building trusting relationships, and sharing treatment goals with medical personnel were identified as forms of children's participation in medical decision making. Through cultivated friendships, children's peer groups were sources of resilience and strength in overcoming difficulties in hospital life. CONCLUSIONS: The development of children's decision making in a pediatric oncology ward was based on various rich human relationships. Such relationships should be promoted to substantially improve shared decision making.

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Transient Angioedema of the Small Bowel because of Intravenous Nonionic Iodinated Contrast Media.

Tomohiro Wakabayashi, Yuta Sasaoka, Yoshiyuki Sakai, Shuichi Miyamoto, Takeshi Tsugawa, Yukihiko Kawasaki

The Journal of pediatrics   230   264 - 265  2021.03  [Refereed]  [International journal]

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

Aya Saitoh, Akihiko Saitoh, Tomohiro Katsuta, Mahito Mine, Hajime Kamiya, Isao Miyairi, Naruhiko Ishiwada, Makoto Oshiro, Ryutaro Kira, Naoki Shimizu, Shigeru Suga, Takeshi Tsugawa, Masashi Fujioka, Chiaki Miyazaki, Ichiro Morioka, Seigo Korematsu, Takashi Nakano, Keiko Tanaka-Taya, Tetsushi Yoshikawa, Satoshi Iwata, Koichi Kusuhara, Hiroshi Azuma, Hiroyuki Moriuchi, Nobuhiko Okabe, Mitsuaki Hosoya, Hiroyuki Tsutsumi, Kenji Okada

Vaccine   38 ( 50 ) 8049 - 8054  2020.11  [Refereed]  [International journal]

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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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Detailed Molecular Interactions of Favipiravir with SARS-CoV-2, SARS-CoV, MERS-CoV, and Influenza Virus Polymerases In Silico.

Mitsuru Sada, Takeshi Saraya, Haruyuki Ishii, Kaori Okayama, Yuriko Hayashi, Takeshi Tsugawa, Atsuyoshi Nishina, Koichi Murakami, Makoto Kuroda, Akihide Ryo, Hirokazu Kimura

Microorganisms   8 ( 10 )  2020.10  [Refereed]  [International journal]

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Favipiravir was initially developed as an antiviral drug against influenza and is currently used in clinical trials against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19). This agent is presumably involved in RNA chain termination during influenza virus replication, although the molecular interactions underlying its potential impact on the coronaviruses including SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) remain unclear. We performed in silico studies to elucidate detailed molecular interactions between favipiravir and the SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza virus RNA-dependent RNA polymerases (RdRp). As a result, no interactions between favipiravir ribofuranosyl-5'-triphosphate (F-RTP), the active form of favipiravir, and the active sites of RdRps (PB1 proteins) from influenza A (H1N1)pdm09 virus were found, yet the agent bound to the tunnel of the replication genome of PB1 protein leading to the inhibition of replicated RNA passage. In contrast, F-RTP bound to the active sites of coronavirus RdRp in the presence of the agent and RdRp. Further, the agent bound to the replicated RNA terminus in the presence of agent, magnesium ions, nucleotide triphosphate, and RdRp proteins. These results suggest that favipiravir exhibits distinct mechanisms of action against influenza virus and various coronaviruses.

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