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慢性腎臓病と脂質異常症の新規発症との関連の検討 : The Japan Specific Health Checkups (J-SHC) study
Get PDFBackground and aims: Dyslipidemias are common among patients with chronic kidney disease (CKD) and are a major risk factor for cardiovascular disease. This study aimed to investigate the association between early-stage CKD and new-onset dyslipidemia for each lipid profile. Methods: This nationwide longitudinal study included data from the Japan Specific Health Checkups (J-SHC) Study. New-onset dyslipidemia was indicated by hypertriglyceridemia (High-TG; ≥150 mg/dL), hyper-LDL cholesterolemia (High-LDL-C; ≥140 mg/dL), or hypo-HDL chelesterolemia (Low-HDL-C; <40 mg/dL) levels according to the guideline of Japan Atherosclerosis Society, or High-TG/HDL-C ratio (≥3.5) which was a good predictor of atherosclerosis. The incidence of new-onset dyslipidemia was compared between participants with and without CKD. Survival curves were used to analyze the incidence of each dyslipidemia. Results: Of 289,462 participants with a median follow-up period of 3 years, the incidence of High-TG, High-LDL-C, Low-HDL-C, and High-TG/HDL-C ratios were 64.4/1000 person-years, 83.1/1000 person-years, 14.5/1000 person-years, and 39.6/1000 person-years, respectively. The adjusted hazard ratios (95% confidence intervals) for High-TG, High-LDL-C, Low-HDL-C, and High-TG/HDL-C ratio were 1.09 (1.05-1.13), 0.99 (0.95-1.04), 1.12 (1.05-1.18), and 1.14 (1.09-1.18), respectively, in CKD participants as compared to non-CKD participants. Decreased eGFR and presence of proteinuria were independently associated with higher risks for new-onset of High-TG, Low-HDL-C, and High-TG/HDL-C ratios. Conclusions: CKD was associated with a higher risk of new-onset High-TG, Low-HDL-C, and High-TG/HDL-C ratios, but not High-LDL-C, in the general population. These CKD-specific lipid abnormalities may explain the residual risk for CKD-related cardiovascular disease.博士（医学）・甲第823号・令和4年3月15日Copyright © 2021 Elsevier B.V. All rights reserved
ヘモグロビン小胞体を用いた一酸化炭素投与の海馬組織への影響
Get PDFCarbon monoxide (CO) is a toxic gas that causes neuropathy. However, CO is endogenously produced in small amounts showing various beneficial effects. We hypothesized that CO-bound haemoglobin-vesicle (HbV) administration would reduce cerebral ischaemia-reperfusion injury without causing neuropathy. Three experiments were conducted. First, rats were exposed to CO inhalation to create a CO-poisoning group, and they were sacrificed on 0, 7, 14, and 21 days after CO exposure. Histopathologically, hippocampal damage was prominent at 14 days. Second, the rats were administered with CO-HbV equivalent to 50 or 25% of circulating blood volume (CO-HbV50 or CO-HbV25 group). Rats were sacrificed 14 days after administration. Third, rats put into haemorrhagic shock by 50% of circulating blood withdrawal were resuscitated using saline, autologous blood, and CO-HbV. They were sacrificed 14 days after resuscitation. Hippocampal damage assessment clarified that almost no necrotic cells were observed in the CO-HbV50 group. Necrotic cells in the CO-HbV25 group were comparable to those found for the control group. In rats resuscitated from haemorrhagic shock, the hippocampal damage in the group using CO-HbV was the mildest. Administration of CO-HbV did not lead to marked hippocampal damage. Furthermore, CO-HbV was effective at preventing cerebral ischaemia-reperfusion injury after haemorrhagic shock.博士（医学）・甲第841号・令和4年6月29日© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
腱板断裂患者の上腕二頭筋腱長頭位置異常の診断における超音波診断の有用性
Get PDFPurpose: This study aimed to determine the role of preoperative shoulder ultrasonography (SUS) in detecting positional abnormalities of the long head of the biceps tendon (LHBT) and predicting subscapularis (SSC) tears in patients with rotator cuff injuries. Methods: A total of 331 patients (365 shoulders) who had undergone arthroscopic shoulder surgery for the treatment of rotator cuff tears were included in the study. Their preoperative SUS and magnetic resonance imaging (MRI) findings were examined retrospectively to assess the presence of LHBT abnormalities at the bicipital groove. Using arthroscopic findings as the standard of reference, the sensitivity, specificity, and diagnostic accuracy of SUS and MRI were calculated for detection of LHBT malposition. Furthermore, the correlation between SSC rupture and preoperative LHBT condition was evaluated by MRI and SUS. Results: LHBT malposition was preoperatively diagnosed with a sensitivity of 92%, specificity of 90%, and accuracy of 91% with SUS, and a sensitivity of 74%, specificity of 84%, and accuracy of 80% with MRI. Preoperative SUS was significantly superior to MRI in terms of sensitivity, specificity, and accuracy (p < 0.001 each). Further, the preoperative SUS LHBT findings could predict well the presence or absence of intraoperative SSC rupture (odds ratio: 1.73, p < 0.001). Conclusion: SUS is a useful diagnostic modality for preoperative detection of LHBT malposition and prediction of SSC tears in patients with rotator cuff tears.博士（医学）・甲第842号・令和4年6月29日© 2022. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.This is a post-peer-review, pre-copyedit version of an article published in Journal of medical ultrasonics. The final authenticated version is available online at: https://doi.org/10.1007/s10396-022-01200-y
アキレス腱付着部症に対しアキレス腱モーメントアーム長が及ぼす影響
Get PDFInsertional Achilles tendinopathy (IAT) is caused by traction force of the tendon. The effectiveness of the suture bridge technique in correcting it is unknown. We examined the moment arm in patients with IAT before and after surgery using the suture bridge technique, in comparison to that of healthy individuals. We hypothesized that the suture bridge method influences the moment arm length. An IAT group comprising 10 feet belonging to 8 patients requiring surgical treatment for IAT were followed up postoperatively and compared with a control group comprising 15 feet of 15 healthy individuals with no ankle complaints or history of trauma or surgery. The ratio of the moment arm (MA) length/foot length was found to be statistically significant between the control group, the IAT group preoperatively and the IAT group postoperatively (p < 0.01). Despite no significant difference in the force between the control and preoperative IAT groups, a significantly higher force to the Achilles tendon was observed in the IAT group postoperatively compared to the other groups (p < 0.05). This study demonstrates that a long moment arm may be one of the causes of IAT, and the suture bridge technique may reduce the Achilles tendon moment arm.博士（医学）・甲第845号・令和4年9月28日© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
A CASE OF CORONAVIRUS DISEASE 2019 COMPLICATED BY VENTILATORASSOCIATED PNEUMONIA, LUNG ABSCESS, AND STAPHYLOCOCCUS AUREUS BACTEREMIA
Get PDFComplications of healthcare-associated infections have been reported in patients with coronavirus disease 2019 (COVID-19). We encountered a case of ventilator-associated pneumonia and lung abscess, complicated with Staphylococcus aureus bacteremia and multiple abscesses, in a patient with COVID-19. Streptococci and anaerobes were cultured from the sputum, which was considered to be the causative organism of the lung abscess. In the management of severe COVID-19, care should be taken to prevent complications of healthcare-associated infections; when secondary respiratory tract infections are suspected, the presence of lung abscess and anaerobic culture should be considered
組織因子惹起-トロンボモジュリン添加凝固波形解析を用いたプロテインC経路異常を伴う血栓性素因のスクリーニング法
Get PDFObjectives: Absolute or relative protein (P)C pathway abnormalities (PC deficiency, PS deficiency, antiphospholipid syndrome (APS), factor (F)V-abnormality, and high FVIII level) cause thrombophilia. Although screening assays for these thrombophilias are available, one utilizing clot waveform analysis (CWA) remains unknown. We aimed to establish a CWA-based screening assay to distinguish PC pathway abnormality-related thrombophilia. Methods: Samples were reacted with tissue factor (TF)/phospholipids and recombinant thrombomodulin (rTM; optimal 20 nM), followed by CWA measurement. The peak ratio (with/without rTM) of the first derivative curve of clot waveform was calculated. Results: The peak ratio in healthy plasmas (n = 35) was 0.36 ± 0.13; hence, the cutoff value was set to 0.49. The peak ratios in plasmas with PC deficiency, PS deficiency, high-FVIII (spiked 300 IU/dl), and APS were higher than the cutoff values (0.79/0.97/0.50/0.93, respectively). PC-deficient plasma or PS-deficient plasma mixed with normal plasma (25%/50%/75%/100% PC or PS level) showed dose-dependent decreases in the peak ratios (PC deficient: 0.85/0.64/0.44/0.28; PS deficient: 0.69/0.53/0.40/0.25), suggesting that the peak ratio at ≤50% of PC or PS level exceeded the cutoff value. The peak ratio in FV deficiency with FV ≤25% was higher than the cutoff value. FV-deficient plasma spiked with 40 IU/dl rFV-R506Q (FVLeiden ) or rFV-W1920R (FVNara ) showed >90% peak ratios. Conclusions: rTM-mediated TF-triggered CWA might be useful for screening PC pathway abnormality-related thrombophilia.博士（医学）・乙第1527号・令和4年9月28日© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.This is the peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/10.1111/ejh.13777], which has been published in final form at [https://doi.org/10.1111/ejh.13777]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.発行元が定める登録猶予期間終了の後、本文を登録予定（2023.07
Influence of the Objective Structural Clinical Examination (OSCE) Before Completion of the Master's Program in Midwifery Education and the Tasks of New Face Midwives
No full text目的：A大学院の助産師課程で修士課程修了前に実施している分娩介助の客観的臨床能力試験(Objective Structured Clinical Examination :以下，修了前OSCE)に関して，修了生が病院就職後に感じた修了前OSCEの影響と助産師1年目の課題を明らかにし，修了前OSCEの中期的な評価を行うこととした。方法：A大学院の修了生で，所属施設および本人から同意の得られた修了後3年以内の臨床助産師10名を対象に半構造化面接を実施した。得られたデータは質的帰納的に分析した。結果：修了前OSCEの影響として7カテゴリー，15サブカテゴリーが抽出され，修了前OSCEの効果が示された一方，修了前OSCEの受験が否定的な体験となったことも明らかになった。助産師1年目の課題には，学生時代には実習の対象とならなかった正常逸脱事例のほか，授乳支援も抽出された。考察：各大学院で行われているカリキュラムや実習内容によって，修士課程修了前に補強すべき内容を検討し修了前OSCEを実施することは，大学院の助産師教育の質担保に寄与しうると考える。Objective : This study aimed to conduct a midterm assessment of the impact of the Objective Structural Clinical Examination (OSCE) carried out before the students completed their master's program in midwifery education (precompletion OSCE) and clarify the tasks of midwives in the first year after graduation. Methods : The participants included 10 clinical midwives who had completed their graduate studies. Semistructured interviews were conducted after obtaining consent from the midwives and their institutions.The data were analyzed qualitatively and inductively.Results : Thus, 7 categories and 15 subcategories were extracted with respect to the impact of precompletion OSCE.The precompletion OSCE had positive effects and some negative outcomes. The tasks of new face midwives included cases that deviated from the normal cases and not the usual target of care when they were midwifery students.In addition，nursing support for breastfeeding was also one of their tasks. Discussion : Enhancing the quality of midwifery education in the master's program is possible by OSCE that includes relevant contents to be reinforced before program completion，despite the differences in the curriculum and practical training conducted in different graduate schools
細胞外増幅活性Natural Killer細胞は膠芽腫由来腫瘍を移植したマウスの全生存期間を延長させる
Get PDFGlioblastoma (GBM) is the leading malignant intracranial tumor and is associated with a poor prognosis. Highly purified, activated natural killer (NK) cells, designated as genuine induced NK cells (GiNKs), represent a promising immunotherapy for GBM. We evaluated the anti-tumor effect of GiNKs in association with the programmed death 1(PD-1)/PD-ligand 1 (PD-L1) immune checkpoint pathway. We determined the level of PD-1 expression, a receptor known to down-regulate the immune response against malignancy, on GiNKs. PD-L1 expression on glioma cell lines (GBM-like cell line U87MG, and GBM cell line T98G) was also determined. To evaluate the anti-tumor activity of GiNKs in vivo, we used a xenograft model of subcutaneously implanted U87MG cells in immunocompromised NOG mice. The GiNKs expressed very low levels of PD-1. Although PD-L1 was expressed on U87MG and T98G cells, the expression levels were highly variable. Our xenograft model revealed that the retro-orbital administration of GiNKs and interleukin-2 (IL-2) prolonged the survival of NOG mice bearing subcutaneous U87MG-derived tumors. PD-1 blocking antibodies did not have an additive effect with GiNKs for prolonging survival. GiNKs may represent a promising cell-based immunotherapy for patients with GBM and are minimally affected by the PD-1/PD-L1 immune evasion axis in GBM.博士（医学）・甲第827号・令和4年3月15日© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)
CRISPR-Cas9を用いてTIM3をノックアウトしたヒトNK細胞の膠芽腫細胞株に対する抗腫瘍効果の検討
Get PDFGlioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults. Natural Killer (NK) cells are potent cytotoxic effector cells against tumor cells inducing GBM cells; therefore, NK cell based- immunotherapy might be a promising target in GBM. T cell immunoglobulin mucin family member 3 (TIM3), a receptor expressed on NK cells, has been suggested as a marker of dysfunctional NK cells. We established TIM3 knockout in NK cells, using the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9). Electroporating of TIM3 exon 2- or exon 5-targeting guide RNA- Cas9 protein complexes (RNPs) inhibited TIM3 expression on NK cells with varying efficacy. T7 endonuclease I mutation detection assays showed that both RNPs disrupted the intended genome sites. The expression of other checkpoint receptors, i.e., programmed cell death 1 (PD1), Lymphocyte-activation gene 3 (LAG3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), and TACTILE (CD96) were unchanged on the TIM3 knockout NK cells. Real time cell growth assays revealed that TIM3 knockout enhanced NK cell-mediated growth inhibition of GBM cells. These results demonstrated that TIM3 knockout enhanced human NK cell mediated cytotoxicity on GBM cells. Future, CRISPR-Cas9 mediated TIM3 knockout in NK cells may prove to be a promising immunotherapeutic alternative in patient with GBM.博士（医学）・甲第828号・令和4年3月15日© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)