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Neurosteroid Binding and Actions on GABAA Receptors. 神经类固醇与 GABAA 受体的结合和作用。
Pub Date : 2024-05-24 eCollection Date: 2024-01-01 DOI: 10.14789/jmj.JMJ24-0002-R
Yusuke Sugasawa

Neurosteroids positively modulate GABAA receptor (GABAAR) channel activity by binding to a transmembrane domain intersubunit site. Using photo-affinity labeling and an ELIC-α1GABAAR chimera, we investigated the impact of mutations within the intersubunit site on neurosteroid binding. These mutations reduce neither photolabeling within the intersubunit site nor competitive prevention of labeling by allopregnanolone. Instead, these mutations change the orientation of neurosteroid photolabeling. The data indicate that mutations at Gln242 or Trp246 that eliminate neurosteroid effects do not eliminate neurosteroid binding within the intersubunit site, but significantly alter the preferred orientation of the neurosteroid within the site. The interactions formed by Gln242 and Trp246 within this pocket play a vital role in determining the orientation of the neurosteroid. We also examined how site-specific binding to three identified neurosteroid-binding sites in the α1β3GABAAR contributes to neurosteroid allosteric modulation. We found that the potentiating neurosteroid, allopregnanolone, but not its inhibitory 3β-epimer epi-allopregnanolone, binds to the canonical β3(+)-α1(-) intersubunit site that mediates receptor activation by neurosteroids. In contrast, both allopregnanolone and epi-allopregnanolone bind to intrasubunit sites in the β3 subunit, promoting receptor desensitization and the α1 subunit promoting effects that vary between neurosteroids. Two neurosteroid analogues with diazirine moieties replacing the 3-hydroxyl bind to all three sites, but do not potentiate GABAAR currents. One is a desensitizing agent, whereas the other is devoid of allosteric activity. Collectively, these data show that differential occupancy and efficacy at three discrete neurosteroid-binding sites determine whether a neurosteroid has potentiating, inhibitory, or competitive antagonist activity on GABAAR.

神经类固醇通过与跨膜结构域亚基间位点结合来积极调节 GABAA 受体(GABAAR)通道活性。通过光亲和标记和 ELIC-α1GABAAR 嵌合体,我们研究了亚基间位点突变对神经类固醇结合的影响。这些突变既没有减少亚基间位点内的光标记,也没有竞争性地阻止异丙孕酮的标记。相反,这些突变改变了神经类固醇光标记的方向。数据表明,Gln242 或 Trp246 的突变消除了类神经甾醇的作用,但并没有消除类神经甾醇在亚基间位点内的结合,而是显著改变了类神经甾醇在该位点内的优先方向。Gln242 和 Trp246 在这个口袋中形成的相互作用在决定神经类固醇的取向方面起着至关重要的作用。我们还研究了与α1β3GABAAR中三个已确定的神经甾体结合位点的位点特异性结合是如何促进神经甾体异位调节的。我们发现,神经类固醇的增强型异丙孕酮(allopregnanolone),而非其抑制型 3β-epimer epi-allopregnanolone,能与介导神经类固醇激活受体的标准 β3(+)-α1(-) 亚基间位点结合。相反,异丙孕酮和表异丙孕酮都与β3亚基的亚基内位点结合,促进受体脱敏,而α1亚基则促进不同神经类固醇的作用。有两种神经类固醇类似物以重氮基取代了 3-羟基,可与所有三个位点结合,但不会增强 GABAAR 电流。其中一种是脱敏剂,而另一种则没有异构活性。总之,这些数据表明,神经类固醇在三个不同的神经类固醇结合位点上的不同占有率和功效决定了神经类固醇对 GABAAR 是否具有增效、抑制或竞争性拮抗剂活性。
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引用次数: 0
Impact of the Aboral Pouch in Roux-en-Y Reconstruction after Laparoscopic Total Gastrectomy for Elderly Patients. 腹腔镜全胃切除术后 Roux-en-Y 重建中口袋对老年患者的影响
Pub Date : 2024-05-24 eCollection Date: 2024-01-01 DOI: 10.14789/jmj.JMJ23-0036-OA
Akira Kubota, Suguru Yamauchi, Yutaro Yoshimoto, Kenki Tsuda, Yukinori Yube, Sanae Kaji, Hajime Orita, Malcolm V Brock, Tetsu Fukunaga

Objectives: The number of elderly people with stomach cancer is increasing; therefore, minimally invasive surgical treatments are required. Elderly patients have multiple comorbidities and are prone to postoperative weight loss, nutritional disorders, Postgastrectomy syndrome (PGS), and decreased quality of life (QOL). Total gastrectomy is particularly associated with these complications, although aboral-pouch creation reportedly improves the condition by compensating for lost reservoir capacity. However, there is no consensus regarding its significance. This study aimed to investigate the impact of the aboral pouch on total gastrectomy outcomes in elderly patients.

Materials and methods: Thirty-six patients who met the eligibility criteria, defined as elderly patients aged ≥75 years, were retrospectively analyzed. The patients had undergone Roux-en-Y reconstructions with an aboral pouch in laparoscopic total gastrectomy procedures performed at Juntendo University from July 2016 to June 2022. The main outcomes were postoperative nutritional status, PGS, and QOL.

Results: The average postoperative period was approximately 1 year (12.0 vs. 13.5 months, P=0.536), for 14 elderly and 22 non-elderly patients, respectively. Elderly patients had more comorbidities (78.5% vs. 40.9%, P=0.041). The outcome of nutritional status demonstrated no differences in weight-loss rate (-5.3% vs. -8.6%, P=0.651) or prognostic nutritional status (-7.9% vs. -5.9%, P=0.243). There was no significant difference in PGS and QOL between elderly and non-elderly patients.

Conclusions: Total gastrectomy with an aboral-pouch creation could be beneficial for elderly 43 patients from the perspective of postoperative nutritional status, PGS, and QOL.

目的:患胃癌的老年人越来越多,因此需要微创手术治疗。老年患者有多种并发症,术后容易出现体重减轻、营养失调、胃切除术后综合征(PGS)和生活质量下降(QOL)。全胃切除术尤其容易引起这些并发症,尽管有报道称口袋的创建可以通过补偿失去的储胃能力来改善这种状况。然而,关于其重要性还没有达成共识。本研究旨在调查口唇袋对老年患者全胃切除术结果的影响:回顾性分析了符合资格标准的 36 例患者,即年龄≥75 岁的老年患者。这些患者于2016年7月至2022年6月在顺天堂大学进行的腹腔镜全胃切除术中接受了带口袋的Roux-en-Y重建术。主要结果为术后营养状况、PGS和QOL:14名老年患者和22名非老年患者的平均术后时间约为1年(12.0个月 vs. 13.5个月,P=0.536)。老年患者合并症较多(78.5% 对 40.9%,P=0.041)。营养状况结果显示,体重减轻率(-5.3% 对 -8.6%,P=0.651)和预后营养状况(-7.9% 对 -5.9%,P=0.243)无差异。老年患者和非老年患者在PGS和QOL方面没有明显差异:结论:从术后营养状况、PGS 和 QOL 的角度来看,43 例老年患者接受全胃切除术并创建口袋可能是有益的。
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引用次数: 0
Activity of a Medical Relief Team from Shizuoka Hospital that was Dispatched to the Noto Peninsula Earthquake in Reiwa 6 (2024). 灵和 6 年(2024 年)能登半岛地震静冈医院医疗救援队的活动。
Pub Date : 2024-05-10 eCollection Date: 2024-01-01 DOI: 10.14789/jmj.JMJ24-0006-OT
Youichi Yanagawa, Ikuto Takeuchi, Yoshiki Nagasawa, Kazuki Horii, Motohiro Ishibashi, Taiki Asaka, Shinya Tada, Misao Sakurai, Harumi Kato, Yoko Nozawa, Akio Kanda, Hiromichi Ohsaka

Objective: The present study aimed to report on the activity of a medical relief team from Juntendo Shizuoka Hospital that was dispatched to the Noto Peninsula Earthquake in Reiwa 6.

Design: Narrative report.

Results: The activities conducted on-site in the Noto Peninsula involved multiple deployments of the Juntendo University Shizuoka Hospital Disaster Medical Assistance Team (JS-DMAT). The first deployment from January 2nd to January 6th faced challenges due to damaged infrastructure, particularly roads, affecting mobility. The team focused on hospital medical support, patient transportation, and DMAT headquarters assistance. The second deployment, from January 8th to January 12th, encountered persistently damaged roads, leading to incidents but no significant vehicle damage. The team engaged in screening, zoning, medical examinations, and DMAT headquarters support in evacuation shelters. The third team's planned activities in early February were canceled by Shizuoka Prefecture.Additionally, on January 7, 2024, personnel from Juntendo Shizuoka Hospital participated in the Shizuoka Prefectural DMAT Coordination Headquarters activity, documenting DMAT activities and assessing team members' health. The Ministry of Health, Labour and Welfare's request for the fourth Shizuoka Prefecture DMAT dispatch led to the selection of the second JS-DMAT for deployment.

Conclusion: The activities related to the Noto Peninsula earthquake by JS-DMAT were reported. Lessons from this disaster are being sought to guide future disaster response preparations.

研究目的本研究旨在报告静冈顺天堂医院派遣到能登半岛地震的医疗救援队的活动情况:结果顺天堂大学静冈医院灾害医疗救援队(JS-DMAT)在能登半岛现场开展了多次活动。从 1 月 2 日到 1 月 6 日的第一次部署面临着由于基础设施,特别是道路受损而影响行动的挑战。医疗队的工作重点是医院医疗支援、病人转运和医疗队总部援助。1 月 8 日至 1 月 12 日的第二次部署遇到了道路持续受损的问题,导致了一些事故,但没有造成重大车辆损坏。该小组在疏散掩体中进行了筛查、分区、体检和 DMAT 总部支持。此外,2024 年 1 月 7 日,顺天堂静冈医院的人员参加了静冈县 DMAT 协调总部的活动,记录了 DMAT 的活动情况,并对队员的健康状况进行了评估。根据厚生劳动省提出的第四次派遣静冈县灾害管理队的要求,选择了第二次派遣 JS-DMAT:报告了 JS-DMAT 在能登半岛地震中开展的相关活动。正在从这次灾害中吸取经验教训,以指导今后的救灾准备工作。
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引用次数: 0
Revolutionary Advances of Robotic Surgery in Urology Field. 机器人手术在泌尿外科领域的革命性进展。
Pub Date : 2024-05-10 eCollection Date: 2024-01-01 DOI: 10.14789/jmj.JMJ24-0008-R
Hisamitsu Ide

The advent of robotic surgery has significantly impacted various surgical fields, particularly urology, gynecology, general surgery, and cardiac surgery. While the da Vinci robotic platform has been predominant over the past two decades, recent years have witnessed the emergence of new robotic platforms in Japan, now actively used in clinical practice. Currently, the available systems in Japan, alongside the da Vinci, include the Hinotori, Senhance, Hugo Ras, and Saroa surgical systems. This review focuses on comparing the notable functions of each system in urologic surgery, emphasizing the areas in which they differ from the da Vinci robotic platform. The development of new robotic systems is ongoing, promising not only cost reductions but also the introduction of innovative devices and educational systems. Soft robotics, which constructs robotic devices using soft, adaptable materials, has the potential to become central to the next generation of robotic surgery. Moreover, the collaboration between Artificial Intelligence (AI) and robotic surgery significantly contributes to increasing efficiency, accuracy, and safety in the medical field, with more innovative applications expected in the future.

机器人手术的出现极大地影响了各个外科领域,尤其是泌尿外科、妇科、普通外科和心脏外科。虽然达芬奇机器人平台在过去二十年中一直占据主导地位,但近年来日本也出现了新的机器人平台,并已积极应用于临床实践。目前,除达芬奇外,日本可用的系统还包括 Hinotori、Senhance、Hugo Ras 和 Saroa 手术系统。本综述重点比较了每种系统在泌尿外科手术中的显著功能,强调了它们与达芬奇机器人平台的不同之处。新型机器人系统的开发仍在继续,不仅有望降低成本,还将引入创新设备和教育系统。软机器人技术利用柔软、可适应的材料构建机器人设备,有可能成为下一代机器人手术的核心。此外,人工智能(AI)与机器人手术之间的合作大大有助于提高医疗领域的效率、准确性和安全性,预计未来还会有更多的创新应用。
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引用次数: 0
Development and Validation of a Machine Learning Model to Predict Post-dispatch Cancellation of Physician-staffed Rapid Car. 开发和验证机器学习模型,以预测派车后取消医生值班的快速车。
Pub Date : 2024-05-10 eCollection Date: 2024-01-01 DOI: 10.14789/jmj.JMJ23-0031-OA
Takaaki Kawasaki, Yohei Hirano, Yutaka Kondo, Shigeru Matsuda, Ken Okamoto

Objectives: This study aimed to develop and validate a machine learning prediction model for post-dispatch cancellation of physician-staffed rapid car.

Materials: Data were extracted from the physician-staffed rapid response car database at our Hospital between April 2017 and March 2019.

Methods: After obtaining 2019 cases, we divided the dataset into a training set for developing the model and a test set for validation using stratified random sampling with an 8 : 2 allocation ratio. We selected random forest as the machine-learning classifier. The outcome was the post-dispatch cancellation of a rapid car. The model was trained using predictor variables, including 18 different reasons for rapid car request, age and gender of a patient, date (month), and distance from the hospital.

Results: This machine learning model predicted the occurrence of post-dispatch cancellation of rapid cars with an accuracy of 75.5% [95% confidence interval (CI): 71.0-79.6], sensitivity of 81.5% (CI: 75.0-86.9), specificity of 70.8% (CI: 64.4-76.6), and an area under the receiver operating characteristic value of 0.83 (CI: 0.79-0.87). The important features were distance from the hospital to the scene, age, suspicion of non-witnessed cardiac arrest, farthest geographic area, and date (months).

Conclusions: We developed a favorable machine learning model to predict post-dispatch cancellation of rapid cars in a local district. This study suggests the potential of machine-learning models in improving the efficiency of dispatching physicians outside hospitals.

研究目的本研究旨在开发并验证一种机器学习预测模型,用于预测派车后取消医生值班快速反应车的情况:数据来源于我院2017年4月至2019年3月期间的医生值班快速反应车数据库:获得2019个病例后,我们将数据集分为用于开发模型的训练集和用于验证的测试集,采用分层随机抽样,分配比例为8:2。我们选择随机森林作为机器学习分类器。结果是调度后取消一辆快速车。该模型使用预测变量进行训练,其中包括 18 种不同的快速用车请求原因、患者的年龄和性别、日期(月)以及与医院的距离:该机器学习模型预测派车后取消快速车的准确率为 75.5%[95%置信区间 (CI):71.0-79.6],灵敏度为 81.5%(CI:75.0-86.9),特异性为 70.8%(CI:64.4-76.6),接收者操作特征值下面积为 0.83(CI:0.79-0.87)。重要特征包括医院到现场的距离、年龄、怀疑非目击者心脏骤停、最远的地理区域和日期(月):我们开发了一个有利的机器学习模型,用于预测当地地区快速车调度后的取消情况。这项研究表明,机器学习模型在提高医院外医生调度效率方面具有潜力。
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引用次数: 0
Designing Future Clinical Trials for Sepsis-associated Disseminated Intravascular Coagulation. 设计针对败血症相关弥散性血管内凝血的未来临床试验。
Pub Date : 2024-04-18 eCollection Date: 2024-01-01 DOI: 10.14789/jmj.JMJ24-0010-P
Cheryl L Maier, Toshiaki Iba

Defining success in a clinical trial is not necessarily a straightforward task, especially when the target population is critically ill patients where few agents have demonstrated effectiveness. This has been the case for trials of anticoagulation in patients with sepsis-associated disseminated intravascular coagulation (DIC), which have generally examined patients with severe sepsis but not specifically DIC. Limitations of existing studies include inadequate anticoagulant doses and delayed initiation of treatment. Furthermore, 28-day mortality has been adopted as the primary endpoint but is affected by a panoply of factors other than anticoagulant therapies and may not be the most relevant measure. Future trials must address several current limitations in order to improve our understanding of the role of anticoagulation in patients with sepsis-associated DIC.

定义临床试验的成功与否并不一定是一项简单的任务,尤其是当目标人群是危重病人时,几乎没有药物能证明其有效性。针对脓毒症相关弥散性血管内凝血(DIC)患者的抗凝试验就属于这种情况。现有研究的局限性包括抗凝剂剂量不足和延迟开始治疗。此外,28 天死亡率被作为主要终点,但它受到抗凝疗法以外的一系列因素的影响,可能不是最相关的衡量标准。未来的试验必须解决目前存在的几个局限性,以提高我们对抗凝在脓毒症相关 DIC 患者中作用的认识。
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引用次数: 0
Stereotaxic Coordinates of Human Hypothalamic Nuclei Used for Region of Interest Analyses in Functional Magnetic Resonance Imaging. 用于功能磁共振成像感兴趣区分析的人类下丘脑核的立体坐标。
Pub Date : 2024-04-18 eCollection Date: 2024-01-01 DOI: 10.14789/jmj.JMJ24-0009-P
Natsuki Omori Rison, Akitoshi Ogawa, Takahiro Osada, Seiki Konishi

The hypothalamus maintains homeostasis by controlling various organs and the central nervous system, but analyzing the human hypothalamic nuclei is challenging. Our previous studies applied areal parcellation to high-resolution functional magnetic resonance imaging (fMRI) data to delineate hypothalamic nuclei boundaries. This article presents stereotaxic coordinates of these nuclei for fMRI analyses, offering guidance on defining regions of interest and appropriate spatial smoothing kernel sizes. The provided coordinates aid future research in nuclear level hypothalamus analyses.

下丘脑通过控制各种器官和中枢神经系统来维持体内平衡,但对人类下丘脑核进行分析具有挑战性。我们之前的研究将areal parcellation应用于高分辨率功能磁共振成像(fMRI)数据,以划分下丘脑核团的边界。本文介绍了用于 fMRI 分析的这些核团的立体坐标,为定义感兴趣区和适当的空间平滑核大小提供了指导。所提供的坐标有助于今后在下丘脑核水平分析方面的研究。
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引用次数: 0
Why is DIC a Rare Diagnosis in the 21st Century? 为什么 DIC 是 21 世纪的罕见诊断?
Pub Date : 2024-03-28 eCollection Date: 2024-01-01 DOI: 10.14789/jmj.JMJ24-0005-P
Jecko Thachil, Toshiaki Iba, Ecaterina Scarlatescu, Jerrold H Levy

Disseminated Intravascular Coagulation (DIC) has been a common diagnosis made by health care givers since the dawn of the 20th century. However, currently, this diagnosis is entertained rarely in clinical settings that can predispose to this complication. The incidence of four common clinical scenarios traditionally associated with DIC, sepsis, trauma, obstetrical disorders, and cancers, are on the increase due to better diagnostics and management strategies, but DIC is rarely diagnosed in these disease categories currently. The authors suggest the rarity of a DIC diagnosis is due to varied understanding of the pathophysiology of this condition. In this perspectives, we would like to present reasons for this change in consideration and encourage caregivers to consider a DIC diagnosis at an early stage based on new criteria to help patients benefit from available treatments.

自 20 世纪初以来,弥散性血管内凝血(DIC)一直是医护人员的常见诊断。然而,目前在容易发生这种并发症的临床环境中,这种诊断很少被采用。由于更好的诊断和管理策略,传统上与 DIC 相关的四种常见临床情况(败血症、创伤、产科疾病和癌症)的发病率正在上升,但目前在这些疾病类别中很少诊断出 DIC。作者认为,DIC 诊断罕见的原因是对该病症的病理生理学存在不同的理解。在这篇论文中,我们想介绍这种考虑变化的原因,并鼓励护理人员根据新标准及早考虑 DIC 诊断,以帮助患者从现有治疗中获益。
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引用次数: 0
Long-term Prognosis of Pediatric Ocular Disease. 小儿眼疾的长期预后。
Pub Date : 2024-03-28 eCollection Date: 2024-01-01 DOI: 10.14789/jmj.JMJ23-0040-R
Toshiyuki Yokoyama

Several problems differentiate the treatment of children, especially those with congenital ocular disease, from adults, including the absence of complaints and the complication of systemic diseases. However, the most challenging is the continuing developing anatomical and functional development and immaturity in children. Consequently, the timing of disease onset and treatment can greatly affect the prognosis, and the prognosis cannot be confirmed without long-term follow-up periods. The prognosis for unilateral congenital cataract is very poor. However, some cases achieved good vision with successful refractive correction and amblyopia therapy, suggesting that long-term parental enthusiasm and adherence are important for the visual prognosis. Penetrating keratoplasty is rarely performed in children, and outcomes at our hospital have been extremely poor for congenital corneal opacity over the past 28 years. The visual prognosis is also poor for large limbal dermoids approaching the center of the cornea, which did not respond to preoperative amblyopia therapy. Consequently, early excision, lamellar keratoplasty, wearing of hard contact lenses, and amblyopia therapy were considered necessary. Treatment of pediatric ocular disease should consider the pros and cons, methods, and timing, especially the development of the pediatric eye and the time of onset of the disease.

儿童,尤其是患有先天性眼病的儿童,在治疗上有几个与成人不同的问题,包括没有主诉和并发全身性疾病。然而,最具挑战性的是,儿童的解剖和功能发育仍在继续发展,而且尚未成熟。因此,发病和治疗的时机会对预后产生很大影响,而且如果没有长期随访,预后也无法确定。单侧先天性白内障的预后很差。然而,一些病例通过成功的屈光矫正和弱视治疗获得了良好的视力,这表明家长的长期热情和坚持对视力预后非常重要。穿透性角膜成形术很少在儿童中开展,在过去的 28 年中,我院先天性角膜混浊的治疗效果极差。对于接近角膜中心的大型角膜缘皮样囊肿,术前弱视治疗无效,视觉预后也很差。因此,有必要尽早进行切除术、板层角膜移植术、佩戴硬性隐形眼镜和弱视治疗。小儿眼病的治疗应考虑利弊、方法和时机,尤其是小儿眼球的发育和发病时间。
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引用次数: 0
The Effect of Antiplatelet Therapy on COVID-19. 抗血小板疗法对 COVID-19 的影响
Pub Date : 2024-03-18 eCollection Date: 2024-01-01 DOI: 10.14789/jmj.JMJ24-0004-P
Ecaterina Scarlatescu, Toshiaki Iba

Platelets are one of the major targets of SARS-CoV-2. Activated platelets release prothrombotic substances, express adhesion molecules, and activate coagulation, thereby contributing to the thrombotic tendency in COVID-19. However, the antiplatelet therapy is not recommended in the current international guidelines. We think that the initiation timing and the target severity are the causes of the failure in clinical trials. As shown in the clinical studies that examined the effects of anticoagulants, early initiation in moderate severity is necessary for the success of antithrombotic therapy. Future trials are warranted to study the effects of antiplatelets in such conditions.

血小板是 SARS-CoV-2 的主要攻击目标之一。活化的血小板会释放促血栓形成物质,表达粘附分子,激活凝血功能,从而导致 COVID-19 的血栓形成倾向。然而,目前的国际指南并未推荐抗血小板治疗。我们认为,启动时机和目标严重程度是临床试验失败的原因。正如研究抗凝剂效果的临床研究所示,抗血栓治疗要取得成功,就必须在中度严重程度时尽早开始。今后有必要开展试验,研究抗血小板药物在此类情况下的效果。
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引用次数: 0
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Juntendo Iji Zasshi
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