Direction of Practical Research at Experimental Schools Immediately after the 1963 Revision of the Course of Study (Music): Focusing on Setagaya Elementary School attached to Tokyo Gakugei University and Kamakura Elementary School attached to Yokohama National University

After the 1958 Course of Study (Music) was announced, the government, local governments, and private organizations searched for model music education. This study sheds light on two Ministry of Education’s experimental schools: Setagaya Elementary School attached to Tokyo Gakugei University and Kamakura Elementary School attached to Yokohama National University. The Ministry of Education would have given research subjects to the experimental schools alongside revisions of the course of study. In addition, the experimental schools would have captured the Course of Study (Music) and research subjects as a practical site and have considered the model and problem of music education. This study clarifies how the Ministry of Education and the experimental schools interpreted music education at that time and how the results of practical research by the experimental schools influenced subsequent music education. The results of practical research at the experimental schools may have affected the 1968 Course of Study (Music) and current music education.三村真弓教授退職記念号 Special Number Commemorating the Retirement of Professor Mayumi Mimur

Dietary Cholic Acid Exacerbates Liver Fibrosis in NASH Model of Sprague–Dawley Rats Fed a High-Fat and High-Cholesterol Diet

Background: Recently, we established a novel rodent model of nonalcoholic steatohepatitis (NASH) with advanced fibrosis induced by a high-fat and high-cholesterol (HFC) diet containing cholic acid (CA), which is known to cause hepatotoxicity. The present study aimed to elucidate the direct impact of dietary CA on the progression of NASH induced by feeding the HFC diet. Methods: Nine-week-old male Sprague–Dawley rats were randomly assigned to receive a normal, HFC, or CA-supplemented (0.1%, 0.5% or 2.0%, w/w) HFC diet for 9 weeks. Results: Histopathological assessment revealed that the supplementation of CA dose-dependently aggravated hepatic steatosis, inflammation, and fibrosis, reaching stage 4 cirrhosis in the 2.0% CA diet group. In contrast, the rats that were fed the HFC diet without any added CA developed mild steatosis and inflammation without fibrosis. The hepatic cholesterol content and mRNA expression involved in inflammatory response and fibrogenesis was higher in a CA dose-dependent manner. The hepatic chenodeoxycholic acid levels were higher in 2.0% CA diet group than in the control, although hepatic levels of total bile acid and CA did not increase dose-dependently with CA intake. Conclusion: Adding CA to the HFC diet altered bile acid metabolism and inflammatory response and triggered the development of fibrosis in the rat liver

Evaluation of the reactivity and receptor competition of HLA-G isoforms toward available antibodies: Implications of structural characteristics of HLA-G isoforms

金沢大学医薬保健研究域薬学系The human leucocyte antigen (HLA)-G, which consists of seven splice variants, is a tolerogenic immune checkpoint molecule. It plays an important role in the protection of the fetus from the maternal immune response by binding to inhibitory receptors, including leukocyte Ig-like receptors (LILRs). Recent studies have also revealed that HLA-G is involved in the progression of cancer cells and the protection from autoimmune diseases. In contrast to its well characterized isoform, HLA-G1, the binding activities of other major HLA-G isoforms, such as HLA-G2, toward available anti-HLA-G antibodies are only partially understood. Here, we investigate the binding specificities of anti-HLA-G antibodies by using surface plasmon resonance. MEM-G9 and G233 showed strong affinities to HLA-G1, with a nM range for their dissociation constants, but did not show affinities to HLA-G2. The disulfide-linker HLA-G1 dimer further exhibited significant avidity effects. On the other hand, 4H84 and MEM-G1, which can be used for the Western blotting of HLA-G isoforms, can bind to native HLA-G2, while MEM-G9 and G233 cannot. These results reveal that HLA-G2 has a partially intrinsically disordered structure. Furthermore, MEM-G1, but not 4H84, competes with the LILRB2 binding of HLA-G2. These results provide novel insight into the functional characterization of HLA-G isoforms and their detection systems. © 2019 by the authors. Licensee MDPI, Basel, Switzerland

The Absence of NOD1 Enhances Killing of Aspergillus fumigatus Through Modulation of Dectin-1 Expression

One of the major life-threatening infections for which severely immunocompromised patients are at risk is invasive aspergillosis (IA). Despite the current treatment options, the increasing antifungal resistance and poor outcome highlight the need for novel therapeutic strategies to improve outcome of patients with IA. In the current study, we investigated whether and how the intracellular pattern recognition receptor NOD1 is involved in host defense against Aspergillus fumigatus. When exploring the role of NOD1 in an experimental mouse model, we found that Nod1(-/-) mice were protected against IA and demonstrated reduced fungal outgrowth in the lungs. We found that macrophages derived from bone marrow of Nod1(-/-) mice were more efficiently inducing reactive oxygen species and cytokines in response to Aspergillus. Most strikingly, these cells were highly potent in killing A. fumigatus compared with wild-type cells. In line, human macrophages in which NOD1 was silenced demonstrated augmented Aspergillus killing and NOD1 stimulation decreased fungal killing. The differentially altered killing capacity of NOD1 silencing versus NOD1 activation was associated with alterations in dectin-1 expression, with activation of NOD1 reducing dectin-1 expression. Furthermore, we were able to demonstrate that Nod1(-/-) mice have elevated dectin-1 expression in the lung and bone marrow, and silencing of NOD1 gene expression in human macrophages increases dectin-1 expression. The enhanced dectin-1 expression may be the mechanism of enhanced fungal killing of Nod1(-/-) cells and human cells in which NOD1 was silenced, since blockade of dectin-1 reversed the augmented killing in these cells. Collectively, our data demonstrate that NOD1 receptor plays an inhibitory role in the host defense against Aspergillus. This provides a rationale to develop novel immunotherapeutic strategies for treatment of aspergillosis that target the NOD1 receptor, to enhance the efficiency of host immune cells to clear the infection by increasing fungal kilMG was supported by the Erasmus lifelong learning program. FV was supported by the E-rare project EURO-CMC. TK was supported by the National Institutes of Health [grant numbers AI101935, AI124346, AR056296, and CA163507]. AC was supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145FEDER-000013), and the Fundação para a Ciência e Tecnologia (FCT) (IF/00735/2014).info:eu-repo/semantics/publishedVersio

Improving Adherence to Daily Weight Orders on an Inpatient Pediatric Unit

Background: Weight is a crucial metric in the optimal care of pediatric patients in the inpatient setting. A patient’s weight is not only necessary for appropriate medication dosing, but is also often an indicator of fluid and nutritional status. As such, having a documented weight is integral to clinical decision making, and failure to obtain daily weight measurements when needed can result in delays in treatment and discharge plans. The importance of daily weight monitoring as well as the challenges surrounding good adherence to daily weight orders has long been recognized. There is currently no formal standardized process for obtaining daily weights on our inpatient pediatric unit, resulting in suboptimal adherence to daily weight orders. Methods: Our primary outcome measure is adherence to daily weight orders on our inpatient unit of Kravis Children’s Hospital 5th Floor, measured as the percentage of all patient-days for which a weight is recorded when there is an active daily weight order in the EMR. Baseline data was established through retrospective chart review of patients admitted to the unit prior to intervention. With the use of process mapping, we created interventions to standardize the method for obtaining weight measurements, to be implemented through standard PDSA cycles; our first intervention established an official time for weight measurements. Biweekly chart audits of all admitted patients were performed to monitor adherence to weight orders as well as identify further opportunities for improvement. We aim to implement 4 adjustments to our current weight measurement process, including further interventions aimed at weight ordering practices, nursing and PCA workflow, as well as continued education and reinforcement for staff. Results: We hypothesize that our intervention will increase adherence to daily weight orders through standardizing and streamlining the workflow to record daily weights. Preliminary baseline data showed that pre-intervention adherence to daily weight orders on Kravis Children’s Hospital 5th Floor was 73.8%. After our first PDSA cycle, preliminary data suggests improved adherence of 79%. There were also days when weights were obtained in the absence of a daily weight order, as well as days when a daily weight order was missing inappropriately. A balancing measure is to determine whether improved adherence to daily weight orders has any unintended or detrimental effects, such as decreased adherence to other types of weight orders at different frequencies (i.e. biweekly). Conclusions: Current adherence to daily weight orders on Kravis Children’s Hospital 5th Floor is inconsistent. Interventions that standardize the process of obtaining weight measurements in accordance with daily weight orders aims to improve adherence. Further directions may include investigating whether improved adherence to daily weight orders results in more clinically appropriate management, as well as identifying needs in standardizing weight ordering practices to only request measurements at frequencies appropriate for the admission diagnosis or clinical situation; minimizing clinically inappropriate daily weight orders may improve daily weight order adherence

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Diagnostic assessment of deep learning algorithms for detection of lymph node metastases in women with breast cancer

Importance Application of deep learning algorithms to whole-slide pathology images can potentially improve diagnostic accuracy and efficiency. Objective Assess the performance of automated deep learning algorithms at detecting metastases in hematoxylin and eosin–stained tissue sections of lymph nodes of women with breast cancer and compare it with pathologists’ diagnoses in a diagnostic setting. Design, Setting, and Participants Researcher challenge competition (CAMELYON16) to develop automated solutions for detecting lymph node metastases (November 2015-November 2016). A training data set of whole-slide images from 2 centers in the Netherlands with (n = 110) and without (n = 160) nodal metastases verified by immunohistochemical staining were provided to challenge participants to build algorithms. Algorithm performance was evaluated in an independent test set of 129 whole-slide images (49 with and 80 without metastases). The same test set of corresponding glass slides was also evaluated by a panel of 11 pathologists with time constraint (WTC) from the Netherlands to ascertain likelihood of nodal metastases for each slide in a flexible 2-hour session, simulating routine pathology workflow, and by 1 pathologist without time constraint (WOTC). Exposures Deep learning algorithms submitted as part of a challenge competition or pathologist interpretation. Main Outcomes and Measures The presence of specific metastatic foci and the absence vs presence of lymph node metastasis in a slide or image using receiver operating characteristic curve analysis. The 11 pathologists participating in the simulation exercise rated their diagnostic confidence as definitely normal, probably normal, equivocal, probably tumor, or definitely tumor. Results The area under the receiver operating characteristic curve (AUC) for the algorithms ranged from 0.556 to 0.994. The top-performing algorithm achieved a lesion-level, true-positive fraction comparable with that of the pathologist WOTC (72.4% [95% CI, 64.3%-80.4%]) at a mean of 0.0125 false-positives per normal whole-slide image. For the whole-slide image classification task, the best algorithm (AUC, 0.994 [95% CI, 0.983-0.999]) performed significantly better than the pathologists WTC in a diagnostic simulation (mean AUC, 0.810 [range, 0.738-0.884]; P < .001). The top 5 algorithms had a mean AUC that was comparable with the pathologist interpreting the slides in the absence of time constraints (mean AUC, 0.960 [range, 0.923-0.994] for the top 5 algorithms vs 0.966 [95% CI, 0.927-0.998] for the pathologist WOTC). Conclusions and Relevance In the setting of a challenge competition, some deep learning algorithms achieved better diagnostic performance than a panel of 11 pathologists participating in a simulation exercise designed to mimic routine pathology workflow; algorithm performance was comparable with an expert pathologist interpreting whole-slide images without time constraints. Whether this approach has clinical utility will require evaluation in a clinical setting

Effects of Musical Activities on Children in Japan with Diverse Cultural or Lingual Backgrounds: Enhancing Children’s Emotional Well-being

Recently, due to an increase in children from diverse cultural and lingual backgrounds in Japan, arts activities that help them to maintain stable emotions and strengthen their sense of self-esteem have become as important as linguistic education. This study aims to clarify the effects of musical activities on foreign children living in Japan. Nine children aged four to eight years attending extracurricular Japanese language classes participated in a music workshop. A questionnaire based on the mood checklist was administered before and after the workshop. The results showed that the positive mood state (pleasantness, relaxation) decreased slightly, and the negative mood state (anxiety) increased, despite eight out of nine children answering, “I really enjoyed myself.” On individual examination, one of the children showed an increase in the positive mood state and a decrease in the negative mood state. Six children registered positive mood changes or maintained the highest score for positive mood or the lowest score for negative mood. The two children did not exhibit any productivity. Based on the results of the mood checklist and the children’s individual situations, most of the children had some positive changes after the workshop. In conclusion, the results suggest that musical activities can positively affect children’s emotions, and percussion performance can contribute to an increased positive mood with a feeling of satisfaction.This research was supported by JSPS KAKENHI Grant Number JP19K0276