海洋生物抽出物からのC型肝炎ウイルスNS3 helicase阻害剤の探索および作用機序の解析

早大学位記番号:新6601早稲田大

Intravenous infusion route in maternal resuscitation:a scoping review

BACKGROUND: The concept that upper extremities can be used as an infusion route during cardiopulmonary resuscitation in pregnant women is a reasonable recommendation considering the characteristic circulation of pregnant women; however, this method is not based on scientific evidence. OBJECTIVE OF THE REVIEW: We conducted a scoping review to determine whether the infusion route should be established above the diaphragm during cardiopulmonary resuscitation in a pregnant woman. DISCUSSION: We included randomized controlled trials (RCTs) and non-RCTs on the infusion of fluids in pregnant women after 20 weeks of gestation requiring establishment of an infusion route due to cardiac arrest, massive bleeding, intra-abdominal bleeding, cesarean section, severe infection, or thrombosis. In total, 3150 articles from electronic database were extracted, respectively. After title and abstract review, 265 articles were extracted, and 116 articles were extracted by full-text screening, which were included in the final analysis. The 116 articles included 78 studies on infusion for pregnant women. The location of the intravenous infusion route could be confirmed in only 17 studies, all of which used the upper extremity to secure the venous route. CONCLUSION: Pregnant women undergo significant physiological changes that differ from those of normal adults, because of pressure and drainage of the inferior vena cava and pelvic veins by the enlarged uterus. Therefore, despite a lack of evidence, it seems logical to secure the infusion route above the diaphragm when resuscitating a pregnant woman. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12873-021-00546-9

Exo2EgoDVC: Dense Video Captioning of Egocentric Procedural Activities Using Web Instructional Videos

We propose a novel benchmark for cross-view knowledge transfer of dense video captioning, adapting models from web instructional videos with exocentric views to an egocentric view. While dense video captioning (predicting time segments and their captions) is primarily studied with exocentric videos (e.g., YouCook2), benchmarks with egocentric videos are restricted due to data scarcity. To overcome the limited video availability, transferring knowledge from abundant exocentric web videos is demanded as a practical approach. However, learning the correspondence between exocentric and egocentric views is difficult due to their dynamic view changes. The web videos contain mixed views focusing on either human body actions or close-up hand-object interactions, while the egocentric view is constantly shifting as the camera wearer moves. This necessitates the in-depth study of cross-view transfer under complex view changes. In this work, we first create a real-life egocentric dataset (EgoYC2) whose captions are shared with YouCook2, enabling transfer learning between these datasets assuming their ground-truth is accessible. To bridge the view gaps, we propose a view-invariant learning method using adversarial training in both the pre-training and fine-tuning stages. While the pre-training is designed to learn invariant features against the mixed views in the web videos, the view-invariant fine-tuning further mitigates the view gaps between both datasets. We validate our proposed method by studying how effectively it overcomes the view change problem and efficiently transfers the knowledge to the egocentric domain. Our benchmark pushes the study of the cross-view transfer into a new task domain of dense video captioning and will envision methodologies to describe egocentric videos in natural language

Endomucin, a CD34-like sialomucin, marks hematopoietic stem cells throughout development

To detect as yet unidentified cell-surface molecules specific to hematopoietic stem cells (HSCs), a modified signal sequence trap was successfully applied to mouse bone marrow (BM) CD34−c-Kit+Sca-1+Lin− (CD34−KSL) HSCs. One of the identified molecules, Endomucin, is an endothelial sialomucin closely related to CD34. High-level expression of Endomucin was confined to the BM KSL HSCs and progenitor cells, and, importantly, long-term repopulating (LTR)–HSCs were exclusively present in the Endomucin+CD34−KSL population. Notably, in the yolk sac, Endomucin expression separated multipotential hematopoietic cells from committed erythroid progenitors in the cell fraction positive for CD41, an early embryonic hematopoietic marker. Furthermore, developing HSCs in the intraembryonic aorta-gonad-mesonephros (AGM) region were highly enriched in the CD45−CD41+Endomucin+ fraction at day 10.5 of gestation (E10.5) and in the CD45+CD41+Endomucin+ fraction at E11.5. Detailed analyses of these fractions uncovered drastic changes in their BM repopulating capacities as well as in vitro cytokine responsiveness within this narrow time frame. Our findings establish Endomucin as a novel cell-surface marker for LTR-HSCs throughout development and provide a powerful tool in understanding HSC ontogeny

The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset

With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Sierra Leone, Liberia, Guinea and Nigeria. Additionally several cases of Lassa fever have been imported into North America, Europe and Asia making LASV a global threat to public health. Despite this, currently no approved therapeutic or vaccine exists to treat or prevent LASV infections. Here, using a passaged strain of LASV that is uniformly lethal in Hartley guinea pigs, we demonstrate that favipiravir, a broad-spectrum antiviral agent and leading treatment option for influenza, has potent activity against LASV infection. In this model, once daily treatment with favipiravir significantly reduced viral titers in tissue samples and reduced mortality rates when compared with animals receiving vehicle-only or ribavirin, the current standard of care for Lassa fever. Favipiravir remained highly effective against lethal LASV infection when treatments were initiated nine days post-infection, a time when animals were demonstrating advanced signs of disease. These results support the further preclinical evaluation of favipiravir for Lassa fever and other VHFs

Effect of maternal positioning during cardiopulmonary resuscitation: a systematic review and meta-analyses.

BACKGROUND: Although rare, cardiac arrest during pregnancy is the leading cause of maternal death. Recently, its incidence has been increasing worldwide because more pregnant women have risk factors. The provision of early, high-quality cardiopulmonary resuscitation (CPR) plays a major role in the increased likelihood of survival; therefore, it is important for clinicians to know how to manage it. Due to the aortocaval compression caused by the gravid uterus, clinical guidelines often emphasise the importance of maternal positioning during CPR, but there has been little evidence regarding which position is most effective. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and OpenGrey (updated on April 3, 2021). We included clinical trials and observational studies with reported outcomes related to successful resuscitations. RESULTS: We included eight studies from the 1,490 screened. The eight studies were simulation-based, crossover trials that examine the quality of chest compressions. No data were available about the survival rates of mothers or foetuses/neonates. The meta-analyses showed that resuscitation of pregnant women in the 27°-30° left-lateral tilt position resulted in lower quality chest compressions. The difference is an 19% and 9% reduction in correct compression depth rate and correct hand position rate, respectively, compared with resuscitations in the supine position. Inexperienced clinicians find it difficult to perform chest compressions in the left-lateral tilt position. CONCLUSIONS: Given that manual left uterine displacement allows the patient to remain supine, the resuscitation of women in the supine position using manual left uterine displacement should continue to be supported. Further research is needed to fill knowledge gaps regarding the effects of maternal positioning on clinical outcomes, such as survival rates following maternal cardiac arrest

A Case of Granulocyte-Colony Stimulating Factor-Producing Hepatocellular Carcinoma Confirmed by Immunohistochemistry

Granulocyte-colony stimulating factor (G-CSF) is a naturally occurring glycoprotein that stimulates the proliferation and maturation of precursor cells in the bone marrow into fully differentiated neutrophils. Several reports of G-CSF-producing malignant tumors have been published, but scarcely any in the hepatobiliary system, such as in hepatocellular carcinoma (HCC). Here, we encountered a 69-yr-old man with a hepatic tumor who had received right hepatic resection. He showed leukocytosis of 25,450/µL along with elevated serum G-CSF. Histological examination of surgical samples demonstrated immunohistochemical staining for G-CSF, but not for G-CSF receptor. The patient survived without recurrence for four years, but ultimately passed away with multiple bone metastases. In light of the above, clinicians may consider G-CSF-producing HCC when encountering patients with leukocytosis and a hepatic tumor. More cases are needed to clarify the clinical picture of G-CSF-producing HCC

Inhibition of Hepatitis C Virus Replication and Viral Helicase by Ethyl Acetate Extract of the Marine Feather Star Alloeocomatella polycladia

Hepatitis C virus (HCV) is a causative agent of acute and chronic hepatitis, leading to the development of hepatic cirrhosis and hepatocellular carcinoma. We prepared extracts from 61 marine organisms and screened them by an in vitro fluorescence assay targeting the viral helicase (NS3), which plays an important role in HCV replication, to identify effective candidates for anti-HCV agents. An ethyl acetate-soluble fraction of the feather star Alloeocomatella polycladia exhibited the strongest inhibition of NS3 helicase activity, with an IC50 of 11.7 µg/mL. The extract of A. polycladia inhibited interaction between NS3 and RNA but not ATPase of NS3. Furthermore, the replication of the replicons derived from three HCV strains of genotype 1b in cultured cells was suppressed by the extract with an EC50 value of 23 to 44 µg/mL, which is similar to the IC50 value of the NS3 helicase assay. The extract did not induce interferon or inhibit cell growth. These results suggest that the unknown compound(s) included in A. polycladia can inhibit HCV replication by suppressing the helicase activity of HCV NS3. This study may present a new approach toward the development of a novel therapy for chronic hepatitis C

Hepatic Sarcoidosis Mimicking Hilar Cholangiocarcinoma: Case Report and Review of the Literature

Sarcoidosis is a multisystemic granulomatous disease of unknown etiology. Hepatic involvement was reported in about 11% of patients with sarcoidosis. However, cases of sarcoidosis in which the granuloma is solitary and limited in the liver are very rare. A 51-year-old woman with tumors in the liver underwent extended left lobectomy with caudate lobectomy and bile duct resection. The tumor was located between segment 4 and the hilar region. Some daughter nodules were found in the left lobe, which were regarded as intrahepatic metastasis. Our case displayed clinical and radiologically distinct findings, which are very similar to those of hilar cholangiocarcinoma restricted to the liver. This report demonstrates that sarcoidosis can show solitary hepatic involvement in the absence of thoracic lymphadenopathy. In such a case, it is difficult to distinguish the diagnosis from other malignant neoplasms. In conclusion, the diagnosis of hepatic sarcoidosis has to be made through prudent and comprehensive investigations that include a full clinical history of sarcoidosis in other organs. Despite utilizing several detailed diagnostic modalities, the definitive diagnosis of cases of solitary sarcoidosis may remain difficult. In these cases, surgical treatment including liver resection should be considered in order to avoid missing a suitable opportunity for treatment

学生による企画展の報告「写真で見る前身校PartⅡ～キンダイ医学の源流を辿る～」

In this article, we look back on the studentʼs exhibition “Kanazawa Universityʼs Former Schools seen in the photos, Part II : Tracing the origins of modern medicine,” at Kanazawa University (9/11/2020-20/01/2021) and it will be evaluated by the students who actuary participated in this exhibition program. Kawai and Matsunaga introduce this article, presenting the background of the special exhibition by the students at Kanazawa University as a part of the class “Museum Training” and the overview of the class schedule. Furuta discusses Chapter 2, 4, 5, 6, while Ooki discusses Chapter 3. In Chapter 2, Furuta explains the idea of this exhibition, and provides selection and research of the materials in Chapter 3, focuses on the display of the exhibition in Chapter 4, describes on the exhibition devices in Chapter 5, discuses related events in Chapter 6. Finally, Matsunaga, who is another instructor of the class and a curator of Kanazawa University Museum, considers this significance of the special exhibition conducted by the students in the University Museum