IntroductionGut microbial imbalance (dysbiosis) has been reported in patients with acute Kawasaki disease (KD). However, no studies have analyzed the gut microbiota while focusing on susceptibility to KD. This study aimed to evaluate whether dysbiosis elevates susceptibility to KD by assessing children with a history of KD. MethodsFecal DNA was extracted from 26 children with a history of KD approximately 1 year prior (KD group, 12 boys; median age, 32.5 months; median time from onset, 11.5 months) and 57 age-matched healthy controls (HC group, 35 boys; median age, 36.0 months). 16S rRNA gene analysis was conducted with the Illumina Miseq instrument. Sequence reads were analyzed using QIIME2.ResultsFor alpha diversity, Faith’s phylogenetic diversity was significantly higher in the KD group. Regarding beta diversity, the two groups formed significantly different clusters based on Bray–Curtis dissimilarity. Comparing microbial composition at the genus level, the KD and HC groups were significantly different in the abundance of two genera with abundance over 1% after Benjamini–Hochberg false discovery rate correction for multiple comparisons. Compared with the HC group, the KD group had higher relative abundance of Ruminococcus gnavus group and lower relative abundance of Blautia. Discussion and conclusionRuminococcus gnavus group reportedly includes pro-inflammatory bacteria. In contrast, Blautia suppresses inflammation via butyrate production. In the predictive functional analysis, the proportion of gut microbiota involved in several pathways was lower in the KD group. Therefore, dysbiosis characterized by distinct microbial diversity and decreased abundance of Blautia in parallel with increased abundance of Ruminococcus gnavus group might be a susceptibility factor for KD.
Objective: Reconstruct compound median nerve action currents using magnetoneurography to clarify the physiological characteristics of axonal and volume currents and their relationship to potentials.Methods: The median nerves of both upper arms of five healthy individuals were investigated. The prop-agating magnetic field of the action potential was recorded using magnetoneurography, reconstructed in -to a current, and analyzed. The currents were compared with the potentials recorded from multipolar surface electrodes.Results: Reconstructed currents could be clearly visualized. Axonal currents flowed forward or backward in the axon, arcing away from the depolarization zone, turning about the subcutaneous volume conduc-tor, and returning to the depolarization zone. The zero-crossing latency of the axonal current was approx-imately the same as the peak of its volume current and the negative peak of the surface electrode potential. Volume current waveforms were proportional to the derivative of axonal ones.Conclusions: Magnetoneurography allows the visualization and quantitative evaluation of action cur-rents. The currents in axons and in volume conductors could be clearly discriminated with good quality. Their properties were consistent with previous neurophysiological findings.Significance: Magnetoneurography could be a novel tool for elucidating nerve physiology and pathophysiology.& COPY; 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Background: Gaseous by-products generated by surgical devices - collectively referred to as 'surgical smoke' - present the hazard of transmitting infective viruses from patients to surgical teams. However, insufficient evidence exists to evaluate and mitigate the risks of SARS-CoV-2 transmission via surgical smoke. Aim: To demonstrate the existence and infectivity of human coronavirus RNA in surgical smoke using a model experiment and to evaluate the possibility of lowering transmission risk by filtration through a surgical mask. Methods: Pelleted HeLa-ACE2-TMPRSS2 cells infected with human coronavirus were incised by electric scalpel and ultrasonic scalpel, separately. A vacuum system was used to obtain surgical smoke in the form of hydrosol. Reverse transcription-quantitative polymerase chain reaction was used to analyse samples for the presence of viral RNA, and infectivity was determined through plaque assay. Furthermore, a surgical mask was placed centrally in the vacuum line to evaluate its ability to filter viral RNA present in the surgical smoke. Findings: In this model, 1/10(6) to 1/10(5) of the viral RNA contained in the incision target was detected in the collected surgical smoke. The virus present in the smoke was unable to induce plaque formation in cultured cells. In addition, filtration of surgical smoke through a surgical mask effectively reduced the amount of viral RNA by at least 99.80%. Conclusion: This study demonstrated that surgical smoke may carry human coronavirus, though viral infectivity was considerably reduced. In clinical settings, surgical mask filtration should provide sufficient additional protection against potential coronavirus, including SARS-CoV-2, infection facilitated by surgical smoke. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of The Healthcare Infection Society.
骨粗鬆症は特に閉経後の女性に多い骨の疾患である.これまで骨粗鬆症の治療薬は骨量の増加効果に主眼をおいて開発されているが,治療のエンドポイントである骨折リスクの軽減には骨量と骨質を改善し,骨代謝バランスを正常にする有効性の高い治療薬の開発が重要である.近年,様々な漢方製剤の骨維持の有効性が臨床では示されているが,その作用機序については明らかにされていない.本研究では,閉経後の更年期障害の治療で汎用される漢方製剤の中で,温経湯(UKT)に着目し,破骨細胞分化誘導因子であるRANKL刺激による破骨細胞分化への影響を調べ,UKTの作用メカニズムについて明らかにした.我々がスクリーニングした様々な漢方製剤の中で,UKTが最も強い破骨細胞分化阻害効果を示した.UKTは破骨細胞の初期分化に不可欠な転写因子NFATc1を阻害した.またNFATc1の上流シグナルであるNF-κBの核移行を阻害した一方で,NFATc1を阻害するBlimp1-Bcl6シグナルを活性化し,破骨細胞の分化成熟を抑制することを明らかにした.さらに我々は活性型Caspase-3によって,UKTが単核破骨細胞のアポトーシスを誘導することを示した.本研究はUKTがBlimp1-Bcl6およびNF-κBシグナル伝達経路を介して,RANKL誘導による破骨細胞分化を抑制し,単核破骨細胞の細胞死を誘導することを初めて明らかにした研究であり,UKTが閉経後骨粗鬆症の効果的な治療薬となりうる可能性を示した.本稿では,我々の研究成果について概説する.
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新型コロナウイルス感染症（COVID-19）の流行に伴い，COVID-19患者のインシデントも多く発生するようになったが，流行前とはインシデントの種類や要因に異なる傾向があるように感じられた．今回，インシデント報告システムからCOVID-19患者におけるインシデント報告と死亡報告についてまとめ，それらの特徴について考察を加えた．対象期間は2020年3月1日から2021年5月31日までとした．COVID-19患者におけるインシデント報告は計149件であった．問題の種類として処置・手術（33%），チューブ類関係（14%），注射・点滴（10%）が多かった．問題の要因として観察不足（32%），手順の非順守（21%），確認不足（14%）が多かった．COVID-19の病態に由来するインシデントと，COVID-19感染対策に由来すると考えられたインシデントに分けられた．死亡報告は78例の報告があり，80歳以上の高齢者に多かった．
排泄が自立する時期は，幼児の排泄の健康問題が生じやすく，養育者が子どもの対応に困難を抱えることがある．本研究は，幼児の自律的な排泄への移行に伴う幼児の排泄の健康問題や養育者の育児上の困難を予防・早期発見/介入するために，幼児が学ぶプロセスに着眼し，看護介入プログラムを開発することを目的とした．
分化型甲状腺癌は一般に予後良好であるが,進行癌ではしばしば局所再発や遠隔転移をきたし予後不良である.切除不能の進行分化型甲状腺癌の治療としては放射性ヨウ素(131I)内用療法,およびチロシンキナーゼ阻害剤が主であるが,前者は131I治療抵抗例が多く,後者は有害事象の発生率が高いことが問題となる.そこで我々は分化型甲状腺癌細胞とxenograftモデルマウスを用いて分子標的薬レンバチニブと放射線外照射の併用による相乗効果を検討した.レンバチニブと放射線外照射の併用療法は,in vitroにおいて顕著な細胞増殖抑制効果を示し,in vivoにおいてもヌードマウスに移植した腫瘍の増大を有意に抑制しその相乗効果が示唆された.細胞増殖マーカーKi-67を用いた蛍光免疫および免疫組織化学では併用療法群において腫瘍細胞のKi-67発現が低下していた.併用療法による相乗効果のメカニズムとして,アポトーシス誘導,G2/M期における細胞周期の停止,および腫瘍細胞内へのレンバチニブ取り込みの亢進が高い抗腫瘍効果に寄与している可能性が示唆された.レンバチニブと放射線(外照射および131I)の併用療法は,進行分化型甲状腺癌に対する強力かつ忍容性のある新たな治療戦略となることが期待される.
腸内細菌叢はヒトの腸管内で一定のバランスを保ちながら共存している多種多様な細菌集団である．近年，遺伝子解析技術の進歩に伴い腸内細菌叢の研究が加速しヒトの健康に果たす役割の重要性が明らかとなってきた．特に小児期の腸内細菌叢の乱れ（dysbiosis）はその後の疾患発症のリスクを上昇させるため，dysbiosisの予防や是正は，生涯を通じた健康維持や促進につながる可能性がある．腸内細菌叢の形成に影響を与える様々な因子の中でも，抗菌薬投与が腸内細菌叢に及ぼす負の影響は大きい．そこで筆者らは抗菌薬の長期投与が乳幼児の腸内細菌叢に及ぼす影響を明らかにするため，有熱性尿路感染症の乳幼児を対象とした検討を行った．その結果，治療量のセフェム系抗菌薬の投与は腸内細菌叢の多様性を著明に低下させ，耐性のLactobacillales目が腸内細菌叢のほとんどを占めるようになること，しかし投与中止後1–2か月で多様性は回復すること，その後少量の予防量（0.2 g/日）のST合剤の持続投与を行っても多様性は乱されず，腸内細菌叢に及ぼす影響は小さいことが明らかとなった．そしてST合剤の少量持続投与中，尿路感染症の起因菌が属するEnterobacteriales目の構成割合が抑制されていたことから，ST合剤の少量持続投与は有熱性尿路感染症の再発予防に有効かつ安全な治療であると考えられた．
IgG4-related disease (IgG4-RD) is a systemic inflammatory disease, which includes type 1 autoimmune pancreatitis (AIP). Interleukin-35 (IL-35) exhibits immunosuppressive effects in several autoimmune diseases. However, the expression of IL-35 had not been reported so far in type 1 AIP. We evaluated the association between IL-35 and several cytokines, which mediate the function of Tregs in type 1 AIP. Plasma was collected from patients with type 1 AIP, alcoholic chronic pancreatitis (ACP), and healthy controls (HC) and assayed for cytokine expression. Total mRNA separated from peripheral blood was isolated from naïve Tregs (nTregs) and effector Tregs (eTregs). EBI3 and IL-12p35 gene expressions were tested in these cells by quantitative PCR. In addition, expression of IL-35 subunits in the pancreatic tissues of patients with type 1 AIP and ACP was analyzed by immunohistochemistry. IL-35 was significantly elevated in type 1 AIP (n = 32) plasma compared with ACP (n = 16) and HC (n = 22), but IL-27 was not. We also detected many cells expressing both EBI3 and IL-12p35 in type 1 AIP tissues. Moreover, in peripheral blood lymphocyte, the percentage of nTregs and eTregs of CD4+ T cells in patients with type 1 AIP (n = 14) compared with HC (n = 15) was significantly decreased and increased, respectively. There were no significant differences of gene expression in patients with type 1 AIP and HC. This study identified elevated expression of plasma IL-35 and tissue IL-35 subunits in patients with type 1 AIP. This might lead to inflammation suppression via activated eTregs. IL-35 might be associated with this anti-inflammatory role, especially against the Th2 response through several cytokines and the differentiation of Tregs in type 1 AIP.
