Effect of Hemodialysis on Plasma Glucose Profile and Plasma Level of Liraglutide in Patients with Type 2 Diabetes Mellitus and End-Stage Renal Disease: A Pilot Study

The effect of hemodialysis on the plasma glucose profile and liraglutide level after liraglutide injection was investigated in patients with diabetes and end-stage renal disease (ESRD). Either 0.6 mg or 0.9 mg liraglutide was subcutaneously administered daily to 10 Japanese type 2 diabetic patients with ESRD. Hemodialysis was conducted on days 1 and 3. Plasma liraglutide and glucose concentrations were measured by enzyme-linked immunosorbent assay and a continuous glucose monitoring system, respectively. The safety profile of liraglutide was also assessed. Hemodialysis had no effect on the pharmacokinetic parameters of liraglutide in patients with diabetes and ESRD; the maximum plasma concentration (Cmax), tmax, area under the concentration-time curve (AUC), and CL/f were unaltered. Similarly, hemodialysis did not affect the mean or minimum glucose levels, AUC, or duration of hyperglycemia (>180 mg/dL) and hypoglycemia (<70 mg/dL) following liraglutide administration. However, significant increases in mean amplitude of glycemic excursions (MAGE) and standard deviation (SD) as markers of glucose fluctuation, and the maximum glucose level were observed during hemodialysis. No adverse events, including hypoglycemia, were observed after liraglutide injection, either off-hemodialysis (day 2) or on-hemodialysis (day 3). Liraglutide was well tolerated in patients with type 2 diabetes and ESRD undergoing hemodialysis. The present results suggested that hemodialysis did not affect the pharmacokinetic profile of liraglutide or most glycemic indices, with the exception of MAGE, SD, and the maximum glucose level. These results suggested that it may be possible to use liraglutide during hemodialysis for diabetes with ESRD, without dose adjustment. Trial Registration UMIN Clinical Trials Registry (UMIN-CTR) UMIN000010159.\ud \u

A Retrospective Study of Canine Idiopathic Epilepsy in Referral Centers in Japan

Idiopathic epilepsy (IE) is one of the most common neurologic disorder in dogs. The aim of this study was to describe the clinical data of dogs with IE in Japan and to search for predisposing factors of IE for further investigation. Medical records and clinical information of dogs diagnosed with IE at 2 referral centers between April 2013 and March 2016 were retrospectively reviewed. It was conducted according to the consensus statement published by International Veterinary Epilepsy Task Force. A total of 70 dogs were used with a median (range) weight of 5.15 (1.85–79.85) kg and age at initial epileptic seizure onset of 4.2 (0.3–11.8) years. Fortyfour dogs were male, and 26 were female. Toy Poodles were over-represented in the present study indicating that this breed may be predisposed to IE and would be a candidate for gene study to elucidate the cause of IE in dogs

Comparative evaluation of clinical glycemic control markers treated with imeglimin and its effect on erythrocytes in patients with type 2 diabetes mellitus: study protocol of a single-arm, open-label, prospective, exploratory trial

Background: Imeglimin is a novel type 2 diabetes (T2D) drug that is expected to improve mitochondrial function. In its phase 3 clinical trials in Japanese patients with T2D, the hemoglobin A1c (HbA1c) decrease following imeglimin administration was slow, reaching a plateau after 20–24 weeks of treatment. In general, the erythrocyte lifespan may be a factor when HbA1c shows an abnormal value. Therefore, this study will comparatively evaluate HbA1c and other markers of glycemic control in patients with T2D after imeglimin administration and also examine the effects of imeglimin on erythrocytes.Methods: This single-arm, open-label, prospective, exploratory study is designed to evaluate the divergence between HbA1c and glycoalbumin (GA) or 1,5-anhydroglucitol (1,5-AG) and the glycemic reduction rate in 30 patients with T2D with inadequate glycemic control when imeglimin 2,000 mg is administered for 6 months. In addition, we will examine the effect on erythrocytes, the presumed cause of this divergence. We will measure sustained glycemic variability using flash glucose monitoring and examine the relationship between changes in these indices and HbA1c. Moreover, because prolonged erythrocyte lifespan is a possible cause of falsely high HbA1c levels, erythrocyte lifespan, erythrocyte deformability, and hemoglobin concentration will be evaluated as effects of imeglimin on erythrocytes. Furthermore, if imeglimin has an ameliorative effect on erythrocyte deformability, it may improve peripheral arterial disease; thus, we will also evaluate the toe-brachial pressure index, a measure of this effect.Discussion: In this study, if imeglimin administration results in diverging rates of hypoglycemic effect between HbA1c and GA or 1,5-AG and prolongs erythrocyte lifespan, GA and 1,5-AG, rather than HbA1c, will be considered appropriate measures of the hypoglycemic effect in the early stages of imeglimin administration. If imeglimin improves erythrocyte deformability, it may also be a new treatment strategy for peripheral arterial disease, a chronic complication of T2D.Ethics and dissemination: The study protocol was scientifically and ethically reviewed and approved by the Certified Clinical Research Review Board of Toho University (approval number: THU22002). The study protocol was registered in the Japan Registry of Clinical Trials (jRCT) in December 2022 (jRCTs031220489)

Critical role of the MCAM-ETV4 axis triggered by extracellular S100A8/A9 in breast cancer aggressiveness

Metastatic breast cancer is the leading cause of cancer-associated death in women. The progression of this fatal disease is associated with inflammatory responses that promote cancer cell growth and dissemination, eventually leading to a reduction of overall survival. However, the mechanism(s) of the inflammation-boosted cancer progression remains unclear. In this study, we found for the first time that an extracellular cytokine, S100A8/A9, accelerates breast cancer growth and metastasis upon binding to a cell surface receptor, melanoma cell adhesion molecule (MCAM). Our molecular analyses revealed an important role of ETS translocation variant 4 (ETV4), which is significantly activated in the region downstream of MCAM upon S100A8/A9 stimulation, in breast cancer progression in vitro as well as in vivo. The MCAM-mediated activation of ETV4 induced a mobile phenotype called epithelial-mesenchymal transition (EMT) in cells, since we found that ETV4 transcriptionally upregulates ZEB1, a strong EMT inducer, at a very high level. In contrast, downregulation of either MCAM or ETV4 repressed EMT, resulting in greatly weakened tumor growth and lung metastasis. Overall, our results revealed that ETV4 is a novel transcription factor regulated by the S100A8/A9-MCAM axis, which leads to EMT through ZEB1 and thereby to metastasis in breast cancer cells. Thus, therapeutic strategies based on our findings might improve patient outcomes

臨地実習における看護技術経験状況 : 1999年度及び2000年度3年次生の「看護技術の実習経験リスト」からの検討

本学では、学生に対し看護への学習意識の動機づけ、及び経験状況の把握を目的とし、平成11年度に「看護技術の実習経験リスト」を作成し、平成11年度及び平成12年度に臨地実習で活用した。今回、「看護技術の実習経験リスト」に記載された学生の自己評価を基に、平成11年度及び12年度の3年次生を対象として、本学の卒業時における看護技術経験状況の実態を調査した。その結果、観察・計測、食事、清潔、排泄など主に生活援助に関わる項目は経験状況が高く、処置、検査時の介助などの項目は未経験である学生が多い傾向であった。また、見学のみ、未経験の学生が多い技術項目は、患者の状態、治療内容が関与するものが多かった。今後、本学の基礎教育における看護技術教育の充実に向けての取り組みが必要であることが示唆された

研修生参画型院内教育において教育委員に求める能力の検討

研修生参画型院内教育を企画・支援した教育委員の学び・感想より、そのプロセスを明らかにし、教育委員に求める能力を明らかにすることを目的とした。具体的には、本教育方法を担当した教育委員7名に、学び・感想を人10～ 15枚のカードに記入してもらい、K」法により図解化した。その結果、本教育方法のプロセスは、［参画支援要素］と［相互成長促進要素］が循環する「研修生－教育委員の相互成長循環モデル」として表すことができた。教育委員に求める能力として、〈研修生の力を信じる力〉が必要であり、研修生の成長や満足感を知って喜ぶことができ、〈こだわりと決断を使い分けられる力〉〈連携・調整する力〉〈やる気を引き出す力〉が抽出できた

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

A contrastive study of japanese and portuguese

Orientador: José Erasmo GruginskiResumo também em japonêsDissertação (mestrado) - Universidade Federal do Paraná. Setor de Ciências Humanas, Letras e Artes. Curso de Pós-Graduação em Letras. Defesa : Curitiba, 1987Inclui referênciasÁrea de concentração : Língua inglesaAbstract : The objective of this dissertation is to examine the common syntactic errors made by Japanese people speaking Portuguese and to compare the linguistic systems of Portuguese and Japanese in relation to those syntactic areas, in an effort to determine whether those errors correspond to differences between the two systems which, in turn, may account for the area of error. Thus this paper is seen as belonging to the field of Contrastive Analysis, not with the purpose of predicting the difficulties speakers may have (which would fall within WARDHAUGH's strong version of the Contrastive Analysis Hypothesis) but aimed at ascertaining whether there is a difference between the systems that can account for the errors alre'ady found (the weak, version of Contrastive Analysis' Hypothesis). To this end, a language sample (in Portuguese) was obtained from 15 native speakers of Japanese through recorded interviews, and this sample was analysed for possible errors in relation to the use of articles, prepositions, verb tenses, verbal and nominal agreement and word order. The linguistic systems of Portuguese and Japanese were then compared in order to determine existing differences. The paper therefore includes a discussion of whether each kind of error could be accounted for by the differences between the two systems. The answer proved to. be positive for the majority of cases, tending to confirm the weak version of Contrastive Analysis Hypothesis. In some cases, however, the errors simply could not be explained by the difference between the systems, and their presence would seem to depend upon other factors which will have to be studied. Finally, this study points to the fact that the expectation that speakers will transfer their habits from one language to another is not well founded, and there is a great deal of data to contradict such a prediction.Resumo : O objetivo desta dissertação é examinar os erros sintáticos mais comuns feitos por falantes de japonês ao se expressarem em português, e comparar os sistemas lingüísticos do português e do japonês, com referência a esses aspectos sintáticos, para ver se a esses erros corresponde uma diferença de sistema que possa explicá-los. Trata-se, nesse caso, de fazer uma análise contrastiva não com o objetivo de prever as dificuldades dos falantes (o que estaria dentro da versão forte da hipótese da Análise Contrastiva, conforme a classificação de WARDHAUGH), mas apenas com o objetivo de verificar se há uma diferença de sistemas que possa dar conta dos erros já encontrados versão fraca da hipótese da Análise Contrastiva) . Para esse fim foi obtida, através de entrevistas gravadas, uma amostra da linguagem de 15 falantes de japonês, e essa amostra foi analisada para verificar se havia erros quanto ao uso do artigo, da preposição, dos tempos verbais} bem como erros de concordância verbal e nominal e ordem das palavras. Foram comparados os sistemas lingüísticos do japonês e do português para ver as possíveis divergências. Discutiu-se, então, para cada tipo de erros, se eles podiam ser explicados pelas diferenças entre os dois sistemas. A resposta foi positiva na grande maioria dos casos, tendendo a confirmar a validade da versão fraca da hipótese da Análise Contrastiva. Em alguns casos, entretanto, os erros simplesmente não podem ser explicados pelas diferenças de sistemas, e sua presença se deve a outros fatores a serem estudados. Por fim, o presente estudo aponta para o fato de que é infundada a expectativa de que os falantes transferiam seus hábitos lingüísticos de uma língua para outra, sendo inúmeros os dados que contradizem essa previsão

The Potential of Bemegride as an Activation Agent in Electroencephalography in Dogs

The present study investigated the potential of bemegride as a pharmacological activation agent that elicits epileptiform discharges (EDs) in interictal electroencephalogram (EEG) recordings in dogs. Four laboratory dogs with idiopathic epilepsy and four without epilepsy were included. The dogs were anesthetized using sevoflurane during EEG recordings. Bemegride was administered intravenously and repeatedly until EDs were enhanced or induced, or until the maximum dose (20 mg/kg) had been administered. Bemegride activated EDs in all dogs with epilepsy. These EDs predominantly occurred in each dog&rsquo;s spontaneous irritative zones, which were identified without the administration of bemegride. EDs occurred after the administration of bemegride in 50% of dogs without epilepsy. The dose required for activation was significantly lower in dogs with epilepsy (median; 7.3 mg/kg) than in those without (median; 19.7 mg/kg) (p = 0.0294). The only suspected adverse effect associated with the administration of bemegride was vomiting in two dogs after awakening from anesthesia. There were no other adverse effects, including seizures. The present results demonstrated the potential of bemegride as a safe and effective pharmacological activation agent of EDs in anesthetized dogs with epilepsy and provided more options for the diagnosis and therapeutic planning of epilepsy, including presurgical evaluations, in dogs